Skin wound healing part I: ancestral and modern medicines for the development of new technologies

The human body, once regarded primarily as a spiritual vessel, is now understood as a highly complex biological system governed by intricate cellular and molecular processes. As civilizations and technologies have evolved, so too have the methodologies, materials, and epistemologies surrounding wound care. From herbal applications in ancient cultures to the development of bioengineered dressings in contemporary medicine, the field of wound healing reflects a continuous trajectory of innovation and adaptation. This review presents a concise overview of wound management practices across diverse cultural contexts, highlighting the contributions of ancestral knowledge systems. It further examines the current landscape of wound dressing technologies, with particular emphasis on soft materials engineered, such as polymers, gels, and foams, to optimize healing outcomes in both acute and chronic wounds. In seeking deeper integration of ancestral knowledge into biomedical innovation, this review explores clinical trials, patent activity, regulatory standards, and epistemological considerations related to medicinal plant applications. By honoring origin and embracing plural knowledge systems, we aim to advance the development of wound care nanotechnologies that are not only scientifically robust but also culturally inclusive, ethically grounded, and accessible across diverse healthcare settings. The second part of this review summarizes tissue engineering in the market and clinical trials, plant-based remedies and pharmacopoeias, medicinal activities of the plants, analyzing skin wound healing from traditional cataplasm to advanced wound dressings within a holistic framework.

GRAPHICAL ABSTRACT

GRAPHICAL ABSTRACT |

1 Introduction

Wound healing is a complex, multi-phase biological process involving hemostasis, inflammation, proliferation, and remodeling. It is triggered by the disruption of tissue integrity due to mechanical, thermal, or chemical trauma, and its progression is influenced by both intrinsic cellular mechanisms and extrinsic environmental factors. The development of wound dressings—materials designed to protect, modulate, and accelerate tissue repair—has evolved in parallel with human civilization, reflecting not only technological advancement but also cultural epistemologies of care.

Historical evidence indicates that wound management practices emerged alongside early human settlements, driven by the need to mitigate infection, restore function, and preserve survival. Archaeobotanical and ethnomedical records reveal that Homo neanderthalensis utilized medicinal herbs for burn treatment as early as 60,000 BCE. In ancient Egypt, castor oil was used to treat wounds and irritated body areas, while fermented bread was observed to have beneficial effects on wounds (Ramírez A. and Dagnino U., 2006). On the other hand, the Hebrews documented the preparation of ointments for wound healing. In India, Sushruta Samhita, an ancient physician and surgeon, described the use of bandages and dressings, detailing their applications, and made important contributions to reconstructive surgery of the ear and nose (van de Vyver et al., 2022). In the Pre-Columbian era, people treated wounds with a mixture of astringent herbs or substances derived from eggs of birds, covering them with feathers or bandages made of skin. The Incas used various substances, such as coca, benzoin balsam, seed oils and copper sulphate to heal wounds (Marino and Gonzales-Portillo, 2000). The Aztecs used obsidian scalpels to open abscesses and phlegmons, applied corn tortilla with mushrooms and sutured wounds with hair (Verano, 1999).

Ancient wound management practices typically involved a three-step process: cleansing the wound, preparing therapeutic plasters, and applying bandages. These early practitioners were among the first to use honey for its healing properties and to develop adhesive dressings. What we now refer to as wound dressings were historically known as plasters—composite mixtures often made from oil, mud or clay, and medicinal herbs, designed to protect and promote tissue repair.

These ancestral systems of wound care were not merely empirical—they were embedded within relational ontologies that viewed healing as a convergence of ecological, spiritual, and communal forces. Materials such as honey, clay, feathers, and plant resins functioned as soft interfaces between body and environment, offering antimicrobial, anti-inflammatory, and regenerative properties long before their biochemical mechanisms were elucidated.

Modern wound dressings have transitioned from passive barriers to bioactive platforms capable of modulating cellular behavior. Innovations in soft materials—including hydrogels, electrospun nanofibers, alginate composites, and stimuli-responsive polymers—enable precise control over moisture retention, drug delivery, and tissue integration. Semmelweis’s aseptic protocols, Lister’s antiseptic techniques, and Winter’s moist wound healing paradigm (Brocke and Barr, 2020) laid the foundation for contemporary design principles in wound care materials (Castellanos-Ramirez and Gonzalez-Villordo, 2014).

However, the epistemological rupture between ancestral knowledge systems and industrial biomedical frameworks remains a critical challenge. The dominant paradigm often marginalizes traditional practices, despite their empirical efficacy and cultural relevance. Integrating ancestral wisdom into the development of soft materials requires not only biochemical validation of bioactive compounds (Laguerre et al., 2007), but also a reorientation of design ethics—toward technologies that are culturally situated, ecologically regenerative, and socially inclusive. The Figure 1 shows clearly the evolution of wound healing over time.

Figure 1

Figure 1. Time line of evaluation of wound healing.

This review proposes a transdisciplinary synthesis of wound healing strategies, bridging ancestral pharmacopoeias with advanced soft material engineering. By examining ancestral methodologies, material properties, modern technologies and epistemological foundations, we aim to articulate a framework for wound care innovation that honors origin, fosters equity, and expands the therapeutic potential of soft materials across diverse sociocultural contexts.

Therefore, this study examines traditional methods as well as the latest technologies for wound healing. It reviews scientific advancements that combine both areas of knowledge, seeking a novel perspective in the field of medicine.

2 Search methodology and study design

A systematic literature search was conducted to identify and analyze scientific publications that explore the integration of ancestral medicinal practices with contemporary technological approaches for wound treatment. The review aimed to bridge ethnobotanical knowledge and biomedical innovation, focusing on the therapeutic use of medicinal plants.

The search was performed across three major scientific databases: PubMed, Scopus and Google Scholar. These platforms were selected for their comprehensive coverage of biomedical, ethnobotanical, and technological research.

The search strategy was structured around two primary thematic axes around the core concept: “wound healing”. This term was consistently used across all searches to anchor the scope of the review. The first axis was “Ancestral Medicine” to capture traditional healing practices, the following keywords were incorporated: cataplasms, poultice, herbs, medicinal plants, ethnobotany, ancestral medicine. The second axis was the “Modern Technological Approaches” to identify contemporary biomedical innovations involving plant-based therapies, the following terms were used: wound dressing, regenerative medicine, nanoencapsulation, dermatological scaffold. Search combinations were refined to ensure that results included references to medicinal plants within the context of modern technologies.

The selection criteria and screening process was as follows: Titles and abstracts of retrieved articles were screened manually to assess relevance. Inclusion criteria focused on studies that explored ancestral medicine through ethnobotanical surveys, traditional formulations, or plant extract preparation or investigated the incorporation of medicinal plants into modern delivery systems, such as encapsulation technologies or bioengineered scaffolds. The selected literature was categorized into two main groups: Group A: Studies emphasizing traditional knowledge, plant-based remedies, and ethnopharmacological practices; Group B: Research focused on the integration of medicinal plants into advanced therapeutic platforms, including nanotechnology and tissue engineering. We selected papers published 25 years ago to date. Conducting the bibliographic search in this manner allowed us to observe how wound healing has been approached from diverse scientific disciplines including ancestral knowledge. This integrative perspective enables us to situate ourselves within a broader understanding of the same topic, enriching it through the plurality of viewpoints and methodological approaches.

3 Classification of skin wounds

There are two main categories of wounds: acute wounds, which occur suddenly and follow a predictable healing trajectory, typically resolving within 4–6 weeks, and chronic wounds which take a long time to heal and make the injury aggravated (Tottoli et al., 2020).

Although chronic wounds are very common, they do not have a normal recovery in the sense that they do not follow an orderly sequence of steps for complete repair, and are usually not treated correctly which translates into morbidity for the patient.

Depending on their etiology (appearance, location and depth) they can be classified as follows:

Arterial: caused by insufficient arterial blood flow.

Venous: related to a deficient venous flow.

Pressure: caused by excessive and prolonged pressure on the blood vessels.

Diabetic: associated with diabetic neuropathy and peripheral vascular disease.

All have common characteristics, such as excessive levels of cytokines, constant exposure to infections, formation of antibiotic-resistant biofilms and cells that do not respond to repetitive stimuli (Larouche et al., 2018).

4 Physiology of skin wounds

These kinds of injuries are the result of a problem at some point in a complex sequence of events, beginning with the wound and ending with wound closure. The healing process for a common wound can be divided into overlapping stages: bleeding and hemostasis, inflammation, proliferation or granular tissue formation, and remodeling or scar formation (Figure 2). (Albahri et al., 2023).

Figure 2

Figure 2. The four main phases of the wound healing process. Image adapted from The Therapeutic Wound Healing Bioactivities of Various Medicinal Plants (Albahri et al., 2023). Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

4.1 Hemostasis - inflammation

The hemostatic reaction occurs immediately after the wound occurs due to adhesion of platelets from nearby blood vessels. Followed by fibrin matrix formation, which acts as a scaffold for cell infiltration (Tottoli et al., 2020). The platelets release growth factors and cytokines, include platelet-derived growth factor (PDGF) and transforming growth factors A1 and 2 (TGF-A1 and TGF-2), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), fibroblast growth factor (FGF), these factors cause the recruitment of inflammatory cells (Sorg and Sorg, 2023).

Initially, neutrophils migrate to the injured area, starting the phagocytosis of the necrotic tissue and the pathogenic antigens. Additionally the neutrophils release pro-inflammatory cytokines as IL-1β, TNF-α, interleukin-6 (IL-6) and interleukin-8 (IL-8), which attract macrophages to the wounded area. Moreover the neutrophils release VEGF (vascular endothelial growth factor) and IGF-1 (insulin growth factor 1) which activate the local proliferation of keratinocytes, fibroblasts and endothelial cells. Macrophages subsequently migrate to the wound bed, continuing the clearance of cellular debris and are actively involved in the secretion of cytokines and growth factors which coordinate the subsequent phases of the wound healing (Gushiken et al., 2021).

4.2 Formation of granulation tissue

In this stage, the growth factors remaining from the previous phase maintain cell proliferation and initiate cell migration, necessary to form granulation tissue and maintain epithelialization of the damaged tissue (Sorg et al., 2017). The granulation tissue consists of a provisional extracellular matrix populated by macrophages, endothelial cells, and fibroblasts. These cells secrete growth factors such as FGF, VEGF, EGF (epidermal growth factor), and TGF-β1 to stimulate the proliferation of fibroblasts, keratinocytes, and endothelial cells (Rodrigues et al., 2019). Fibroblasts produce type III collagen, proteoglycans, and fibronectin. Although Angiogenesis reaches its peak activity during this phase, ensuring oxygen and nutrient supply for matrix synthesis and cell proliferation. VEGF stimulates endothelial cell proliferation and vascular remodeling at the wound site. Re-epithelialization restores the skin’s barrier function. Growth factors stimulate keratinocyte proliferation, differentiation, and migration by downregulating adhesion molecules and disrupting cell–matrix contacts.

4.3 Scar formation

Also called matrix remodeling phase, involves granulation tissue regression, replacement of the provisional extracellular matrix, and apoptosis of transient cells. TGF-β1 induces fibroblast differentiation into contractile myofibroblasts, promoting wound contraction through collagen fiber anchorage (Wilkinson and Hardman, 2020). Concurrently, neovessels formed during the proliferative phase undergo regression to restore pre-injury vascular architecture, a process essential for scar maturation and tissue normalization (Shi et al., 2023). Matrix metalloproteinases (MMPs), secreted by resident cells, degrade provisional matrix components, enabling the synthesis of type I collagen, elastin, and other structural proteins that enhance the mechanical integrity of regenerated skin (Karppinen et al., 2019).

5 Pathophysiology of chronic wounds

The pathophysiology of chronic wounds is characterized by profound alterations in the mechanisms that regulate normal healing (Eming et al., 2014). In particular, an imbalance between pro- and anti-inflammatory mediators sustains leukocyte recruitment and promotes excessive production of reactive oxygen species (ROS) and inflammatory cytokines (Hunt et al., 2024). As a result, this persistent oxidative and inflammatory burden induces cellular damage, apoptosis, and degradation of essential growth factors, thereby maintaining a chronic inflammatory microenvironment (Zhao et al., 2016).

Furthermore, re-epithelialization is markedly delayed due to persistent inflammation and impaired vascularization, which compromise keratinocyte activity (Pastar et al., 2014). Notably, keratinocytes at the wound margins acquire a hyperproliferative yet migration-deficient phenotype, largely attributed to altered expression of adhesion molecules and dysregulated signaling pathways such as β-catenin/c-myc; (Piipponen et al., 2020).

In parallel, angiogenesis is disrupted by an imbalance between pro- and anti-angiogenic factors. This condition reduces neovascularization and blood supply, further limiting oxygen delivery and delaying tissue repair (Li M. et al., 2021).

Likewise, during the remodeling phase, excessive synthesis of matrix metalloproteinases (MMPs) and other proteases promotes degradation of extracellular matrix (ECM) components, cell surface receptors, cytokines, and growth factors. This process is exacerbated by decreased levels of tissue inhibitors of metalloproteinases (TIMPs), establishing a self-sustaining cycle of ECM degradation and impaired structural reorganization (Krishnaswamy et al., 2017).

Beyond intrinsic molecular disruptions, several extrinsic factors further complicate the healing process, contributing to the persistence of chronic wounds.The major factors that affect wound healing are as follows: hypoxia, nutrition, infection, stress, age, sex hormones, chronic diseases, medication, smoking, alcohol, and genetic predisposition (Figure 3).

Figure 3

Figure 3. Common factors that affect the skin wound healing. Image adapted from the Cicatrización de heridas cutáneas: una actualización desde la fisiopatología hasta las terapias actuales (Gushiken el al 2021) Licensee MDPI, Basel, Switzerland.This article is an open access articles distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/4.0/).

Thus, for example, prolonged hypoxia can impair healing by producing ROS and pro-inflammatory cytokines (Darby and Hewitson, 2016);. Nutrition is key to the supply of various nutrients during tissue regeneration. Malnutrition prolongs inflammation and decreases angiogenesis and fibroblast metabolism. Local bacterial infections like Staphylococcus aureus, Pseudomonas aeruginosa, and other Streptococci species are largely responsible for increased chronic inflammation and necrosis due to endotoxin release from bacteria (Gushiken et al., 2021). Biofilm represents the primary lifestyle of bacteria and is associated with numerous human diseases. An increasing amount of scientific and clinical evidence indicates the presence of biofilm in wounds. Metcalf and Bowler (2013) highlights clinical experiences and in vivo evidence linking biofilm to delayed wound healing. They discuss various mechanisms by which biofilm hinders healing, such as impaired epithelialization, granulation tissue formation, and reduced effectiveness of antimicrobial agents and host defenses. Stress negatively impacts healing by altering endocrine hormones, increasing epinephrine, norepinephrine, and cortisol, which reduce immune response and necessary inflammation for healing (Gilliver et al., 2007). Aging (Gushiken et al., 2021) and Sex Hormones (Gilliver et al., 2007) also affect wound healing. Moreover, diseases like diabetes cause chronic inflammation and alter skin microvasculature (Avishai et al., 2017). Some drugs, like corticosteroids and non-steroidal anti-inflammatory drugs NSAIDs, interfere with wound healing by reducing fibroblast proliferation and angiogenesis (Malfait et al., 2010). Chemotherapeutic drugs also negatively impact cellular metabolism and proliferation (Krischak et al., 2007). Smoking impairs wound healing due to compounds like tobacco and nicotine, which reduce erythrocyte proliferation, oxygenation, and blood flow, and increase blood viscosity and infection risk (Beahrs et al., 2019). In addition, alcohol consumption (Gushiken et al., 2021).

6 Treatment of skin wound

When clinically treating a chronic wound, it is recommended to follow the guidelines established by the TIME protocol (Tissue debridement, Infection control, Moisture balance and Edge of Wound) (Powers et al., 2016). Once these general parameters are properly controlled, the wound should be diagnosed and classified in order to use the appropriate treatment for each type of ulcer (Bowers and Franco, 2020).

A chronic wound differs from an acute wound because the healing process is interrupted in one or more stages and it is necessary to identify the barriers that prevent it, and to eliminate them. For that reason, the TIME protocol aims to prepare the wound to accelerate endogenous healing and facilitate the effectiveness of other therapeutic treatments (Schultz et al., 2003).

6.1 Debridement

The process of wound debridement is to remove necrotic tissue and foreign material from the wound and surrounding tissue to improve wound healing. The presence of necrotic tissue or foreign material in a wound prolongs the inflammatory response, and also increases the risk of infection. For that, this stage is essential as the removal of damaged or necrotic tissue, which plays a very important role in wound healing. Currently, there are different types of debridements (Powers et al., 2016) as shown in Table 1.

Table 1

Table 1. Different kinds of Debridements (Powers et al., 2016).

6.2 Infection control

The next stage is infection control. This is a key step since its development directly affects the healing process by increasing the size of the wound, the amount of exuded fluid, stench, pain and tenderness, pus and even the formation of an abscess. It is important at this stage to try to interrupt the progress of the infection (contamination, colonization, expansion of the infection and systemic infection) either by cleaning the wound using saline solution or common water or by resorting to antimicrobial drugs that act directly on the wound area (Powers et al., 2016).

6.3 Moisture balance

Moisture balance is a step that deals exclusively with the various patches or cloths that cover the wound to absorb the substances emanating from it and at the same time keeping it moist. The latter is important because it has been proven that moisture accelerates the healing process significantly (Cordts et al., 1992).

6.4 Edge of wound

Edge of wound is the next and covers everything related to the local and systemic factors that play a role in the re-epithelialization of the wound. This requires a well vascularized system, adequately oxygenated and nourished, in addition to a good control of systemic pathologies such as diabetes mellitus and chronic venous and arterial insufficiencies.

7 Ancestral wound healing

Throughout history and across different cultures of the world each culture has developed specific formulations and preparation methods. In general, different plants are combined based on local availability, the type of wound, and the experience of healers and ancestral knowledge. For example, Salazar-Gomez and Alonso-castro (Salazar-Gómez and Alonso-Castro, 2022) describe the methods of preparation and administration of medicinal plants for wound healing in Latin America. Only 18% of medicinal plants are administered orally. The primary preparation method is infusion (36%), followed by decoction (24%), pulverized plant parts (12%), cataplasm (9%), maceration (7%), decoction (6%), and others. The main plant parts used are leaves (38%), followed by bark (15%), whole plant (13%), aerial parts (11%), latex (8%), roots (7%), and others. This data indicates that medicinal plants used for wound healing in Latin America are predominantly administered topically, with extraction mainly conducted through water infusion of aerial parts. In another context in the world, the people of the Eastern Cape Province, South Africa, still depend largely on traditional herbal medicine for the treatment of wounds. Information collected from the traditional healers, the Sangomas, has revealed that 38 plant species are used for the treatment of wounds in Province. The methods of preparation are in seven categories: plant parts which are applied as a cataplasm (14 species), those applied directly or worn as bandages (ten species), infusions made from fresh or dried material (ten species), and those from which the juice is extracted and applied as dressings or used for washing the wounds (five species). Others are prepared as lotions (five species), ground into powders (four species) or prepared as ointment (two species). It was also observed that some plants were used in more than one method of preparation and it is specified for what type of wound each herb is used (Grierson and Afolayan, 1999).

7.1 Ancestral formulations

The formulations used for wound healing are similar throughout the world. These formulations correspond to the modern classification of dressings, which are liquid solutions (infusions, bath, decoction, lotion and alcoholic extracts), and semi-solid dressings (ointments, poultices and herbs mixed with animal fat, resin, honey, mud or oils).

7.1.1 Liquid solutions: infusion and decoction

Infusions and decoctions are the most common ways to use medicinal plants for wound treatment. A common method involves washing the wound with an aqueous solution of specific plants, which supports the early stages of the wound healing process. For example, L. camara has been used for wound treatment in different parts of Latin America. Numerous studies have demonstrated its antioxidant and anti-inflammatory properties, for instance, Nayak et al. demonstrate that L. camara is effective in healing excision wounds in experimental animals and could be considered as a therapeutic agent for tissue repair processes associated with skin injuries (Nayak et al., 2013).

Traditionally, F. benghalensis is used for wound healing in ayurvedic medicine. The wound-healing efficacy of ethanolic and aqueous extracts of F. benghalensis was evaluated in excision and incision wound models. The study evaluated the wound-healing properties of F. benghalensis extracts in excision and incision models. Both ethanolic and aqueous extracts significantly improved wound healing by accelerating epithelialization, increasing wound contraction, and enhancing tensile strength compared to a placebo (Garg and Paliwal, 2011).

Pharmacological studies conducted in vitro of Calendula officinalis extracts have demonstrated that has antiviral, antigenotoxic, antimicrobial and anti-inflammatory properties (Jiménez-Medina et al., 2006). In suspension or tincture form, it is applied topically to reduce inflammation, control bleeding, and promote the healing of poorly healing wounds.

7.1.2 Semisolid preparations: natural dressings, ointments and cataplasm

Historically, traditional wound healing agents include liquid and semisolid topical formulations, as well as cataplasm and dry dressings. Since ancient times, numerous formulations have been made from the combination of oils, resins, powders, and plant extracts, honey, clay, etc., to create ointments or semi-solid forms that promote wound healing. These formulations can sometimes be applied directly to the skin and, in other cases, as cataplasm (Shah, 2011).

For 4,000 years, honey has been used for its therapeutic properties in wound healing. Honey’s benefits include antimicrobial activity, reducing edema, and promoting granulation tissue formation (Efem, 1988). Ancient Egyptians exploited these properties, and communities in East Africa, such as the Maasai, use honey as a traditional wound-healing salve (Bodeker et al., 1999). The antibacterial activity of honey is due to hydrogen peroxide, a byproduct of the enzymatic reaction between glucose oxidase from bees and glucose in honey. Honey shares critical qualities with glycerol that help preserve skin grafts (Subrahmanyam, 1993). At Mahidol University in Thailand, 13 patients with chronic wounds treated with honey healed completely in 7–38 days, with a significant reduction in micro-organism load. Both topical application and ingestion of honey promote wound healing, as shown in studies with experimental rats and buffaloes.

Oil-based ointments are one of the oldest formulations, made from vegetable and/or animal fats. Oils act as protective barriers for the skin, retain moisture and have high bioavailability with localized effects (Al Musaimi et al., 2024). Components such as free fatty acids (FFAs), phenolic compounds and tocopherols in vegetable oils have antioxidant effects and modulate skin processes including barrier function and inflammation. Vegetable oils contain various compounds such as triglycerides, FFAs, sterols and squalene that influence skin physiology differently. Unsaponifiables in vegetable oils contribute to antioxidant activity and support skin health (Lin et al., 2017). Shea butter is extracted from the seeds of the shea tree (Vitellaria paradoxa) and has historically been used as an indigenous therapy for dermatological conditions and umbilical cord care in sub-Saharan Africa. Shea butter was most often used in combination with other ingredients to produce a medical treatment, the most frequent adjuvant being Elaeis guineensis, the African oil palm (Scarpa and Rosso, 2019).

Ointments made from Centella leaves are used to treat leg ulcers, sores, gangrene, defective scars, fistulas, traumatic and surgical wounds, burns and skin grafts (Polesna et al., 2011). Healing creams made with rosemary (Rosmarinus vulgare) and plantain (Plantago major) and Portulaca oleracea L. showed excellent results in in-vivo studies (Velasquez Ramos, 2020).

In many communities, cataplasm or poultices are used for wound treatment and sometimes herbal leaves are used directly as a wound dressing. For example, all parts of the banana plant have medicinal applications due to their numerous health benefits. Bananas can be particularly effective for treating burns and wounds (Raina et al., 2008). The wax layer on the banana leaf reduces liquid evaporation, and the leaf provides a cooling sensation to the skin. It does not stick to the wound and has a large surface area, making it suitable for covering all parts of the body (Gore and Akolekar, 2003). Additionally, banana leaves are low cost and readily available, making them particularly useful for treating chronic and long-term wounds, as well as large-area wounds or burns (Colwell et al., 1993). In a study of banana leaf applied as a cataplasm on wound healing in rabbits (Al-Mutheffer, 2013) concluded that banana leaf provides a clean, waxy non adherent, water proof, and cheap dress to prevent the wound from the contaminated external environment.

Moreover, Marham-e-ushaq is an ointment used in Iranian traditional medicine to treat various types of wounds. When applied to the wound area, ushaq gum helps eliminate excess discharge, remove corrupted tissues, promote the growth of healthy tissue, and prevent scar formation (Zaheri Abdevand et al., 2020).

7.2 Medicinal plant extracts and their integration into emerging technologies

The literature described the families as having prevalence in ethnopharmacological practices with efficacy in in vitro and in vivo wound healing models, as follows;

• Fabaceae: Rich in flavonoids and alkaloids; known for anti-inflammatory and antimicrobial effects.

• Asteraceae: Contains sesquiterpene lactones and polyphenols; widely used in traditional wound care.

• Euphorbiaceae: Produces diterpenes and phenolic compounds; supports tissue regeneration.

• Lamiaceae: Includes genera such as Lavandula and Salvia, valued for essential oils and wound contraction.

• Apiaceae: Known for terpenoids and coumarins; promotes angiogenesis and collagen synthesis

As detailed before, there has been an increasing number of research articles exploring the use of herbal natural products as beneficial agents in wound healing. The primary advantages of these botanical remedies include their low cost and high availability. Furthermore, there is also the advantage that, in some cases, they may have very few side effects (Sofowora et al., 2013), which encourages further research into this type of medicine.

Plants contain a wide array of bioactive phytochemicals, predominantly from the families of alkaloids, carotenoids, flavonoids, tannins, terpenoids, saponins, and phenolic compounds (Vitale et al., 2022). These substances are known to exert numerous healing effects, either directly or indirectly (Agarwal et al., 2021). Phytocompounds can influence different stages of the wound healing process through various mechanisms. These mechanisms include anti-inflammatory, antimicrobial, and antioxidant activity, as well as stimulation of collagen synthesis, promotion of cell proliferation, and angiogenic effects (Vitale et al., 2022).

Depending on the extraction method and solvent used, different classes of compounds—such as flavonoids, alkaloids, terpenoids, tannins, and saponins—can be isolated, each contributing uniquely to the regenerative process. Below is a detailed description of the main types of extracts employed in wound care formulations and their therapeutic relevance:

Aqueous extracts, obtained through maceration or decoction in water, are traditionally used for their accessibility and safety. Plants such as Centella asiatica and Calendula officinalis yield hydrophilic compounds that promote angiogenesis, reduce inflammation, and accelerate epithelial regeneration. These extracts are commonly incorporated into gels, creams, and hydrocolloid dressings (Sharma et al., 2022))

Ethanolic extracts utilize ethanol as a solvent to isolate polyphenols, flavonoids, and other mid-polarity compounds. Extracts from Curcuma longa (turmeric) and Aloe vera are particularly noted for their antioxidant capacity, antimicrobial activity, and ability to stimulate fibroblast proliferation and collagen synthesis. These are often formulated into bioactive wound dressings and emulsions (Landge, 2024).

Methanolic extracts, derived using methanol, are effective in extracting alkaloids and terpenoids with potent antimicrobial and immunomodulatory effects. Plants such as Azadirachta indica (neem) and Ocimum sanctum (holy basil) have demonstrated efficacy in reducing microbial load and enhancing tissue repair. These extracts are frequently used in nanoparticle-based delivery systems to improve bioavailability and targeted action (Gupta and Pathak, 2016; Sharma et al., 2022).

Essential oils, obtained via steam distillation, contain volatile compounds with antiseptic, analgesic, and anti-inflammatory properties. Oils from Lavandula angustifolia (lavender) and Melaleuca alternifolia (tea tree) are widely used in wound sprays, vapor-phase therapies, and smart dressings due to their rapid absorption and broad-spectrum antimicrobial effects (Mitra et al., 2025).

Hydroalcoholic extracts, which combine water and ethanol, allow for a broader spectrum of phytochemical recovery. Extracts from P. major and Chamomilla recutita (chamomile) are known for their anti-edematous and granulation-promoting properties. These are often integrated into hydrogels and electrospun nanofiber matrices for sustained release and enhanced tissue compatibility (Landge, 2024).

The therapeutic efficacy of plant-based wound healing agents is closely linked to the polarity of the extract and its compatibility with delivery vehicles:

Using both extract types in formulation allows for a broader spectrum of bioactivity. For example, polar extracts (water, ethanol) are ideal for anti-inflammatory and antimicrobial action, but they have limited skin penetration and may exclude lipophilic bioactives, while apolar extracts (hexane, chloroform, oils) may better support tissue regeneration and barrier repair due to their lipid affinity, but they are less compatible with aqueous system and potential cytotoxicity if not purified.

7.3 Benefits of polyherbal formulations

Interestingly, the use of combinations of medicinal plants in wound treatment show a significant reduction in wound closure time and improvement in the quality of the healed wound compared to individual plant use. The application of herbal combinations shows promising potential in wound treatment and management due to the presence of diverse, multitargeted phytoconstituents (Aslam et al., 2016). Unlike synthetic drugs, the topical application of polyherbal formulations for wound treatment has generally not shown any side effects, such as skin irritation, toxicity, erythema, eschar, or edema during acute dermal toxicity and skin irritation tests in animal burn wound models. Topical wound healing drugs can easily enter the systemic circulation due to the loss of the epidermal layer in full-thickness wounds, causing various dysfunctions. However, studies on the adverse effects of herbal wound healing products on systemic functions after skin penetration are scarce. Carefully selected medicinal plants and their combinations have shown potential for positive interactions among phytoconstituents, such as synergism, reinforcement, potentiation, complementation, and mutual enhancement or assistance. The process of selecting plants for combination must be meticulously carried out to avoid incompatibility and counteraction among phytoconstituents, which could lead to undesirable outcomes (Tanimu et al., 2022).

8 Modern approaches: wound dressings

An ideal wound dressing should have the following characteristics: preserving moisture around the wound, enabling gaseous transmission, biocompatibility, biodegradability, nontoxicity, stimulation of growth factors, ease of changing and removing wound dressings, ability to transfer bioactive compounds to wound sites, and wound protection from infections and microbial growth (Rezvani Ghomi et al., 2019). Wound dressings have evolved significantly over the years, transitioning from crude applications of plant herbs, animal fat, and honey to sophisticated tissue-engineered scaffolds (Boateng et al., 2008).

Traditional dressings include cotton wool, natural or synthetic bandages, and gauzes. Unlike topical pharmaceutical formulations, these dressings are dry and do not provide a moist wound environment. They can be used as primary or secondary dressings, or as part of a composite dressing system with each component performing a specific function (Boateng et al., 2008).

In recent times, regenerative medicine and tissue engineering have gained great interest in scientific and technological advances within modern medicine. The objective of bio engineered dressings is to try to mimic the architecture of normal skin by optimizing the wound microenvironment for healing by increasing moisture, through the use of human or animal tissues, replacing the epidermal barrier, providing structural scaffolding, and releasing other factors to stimulate healing (MacNeil, 2007).

Dressings are classified in several ways, depending on their function in the wound (e.g., debridement, antibacterial, occlusive, absorbent, adherence), the type of material used to produce the dressing (e.g., hydrocolloid, alginate, collagen), or the technology used for their fabrication (electrospinning, hydrogel, 3D impression, nanotechnologies).

8.1 Dressings classified based on materials used

In summary, there are five types of patches or dressings commercially available. All of them are bravely described as following:

8.1.1 Hydrocolloid dressings

Hydrocolloid dressings are among the most widely used wound dressings. These dressings, their properties, mechanisms of action, and the range of wounds they treat effectively have been thoroughly reviewed (Boateng et al., 2008; Dhivya et al., 2015). The term “hydrocolloid” refers to a family of wound management products made from colloidal gel-forming agents combined with elastomers and adhesives. Typical gel-forming agents include carboxymethylcellulose, gelatin, and pectin (Dhivya et al., 2015).

They are used for mildly to moderately exuding wounds, such as pressure sores, minor burns, and traumatic injuries, as well as managing leg ulcers (Koksal and Bozkurt, 2003). In their intact state, hydrocolloid dressings are impermeable to water vapor, but upon absorbing wound exudate, they form a gel that covers the wound and gradually becomes more permeable to water and air. Their painless removal makes them particularly useful in pediatric wound care for both acute and chronic wounds where minimizing trauma and discomfort is essential (Thomas, 1992). Recent studies have emphasized their role in reducing dressing change frequency, enhancing patient comfort, and lowering overall wound care costs, especially in outpatient and home-care settings (Jones and San Miguel, 2006). However, hydrocolloids are not recommended for heavily exuding wounds or infected lesions, as their occlusive nature may exacerbate anaerobic bacterial growth.

8.1.2 Alginate dressings

Alginate dressings are produced from the calcium and sodium salts of alginic acid, a polysaccharide composed of mannuronic and guluronic acid units. These dressings are available as freeze-dried porous sheets (foams) or flexible fibers, the latter suitable for packing cavity wounds. Alginates are primarily used due to their ability to form gels upon contact with wound exudates, exhibiting high absorbency through strong hydrophilic gel formation, which limits wound secretions and minimizes bacterial contamination (Heenan, 1988). Alginates rich in mannuronate, such as Sorbsan™ (Maersk, UK), form soft, flexible gels upon hydration, while those rich in guluronic acid, like Kaltostat™ (ConvaTec), form firmer gels. Some alginate dressings, like Sorbsan™ and Tegagen™ (3M Healthcare), contain calcium alginate fibers. When applied to wounds, the ions in the alginate fiber exchange with those in exudate and blood, forming a protective gel film that maintains optimal moisture and temperature for healing. In addition to wound management, calcium alginate fibers have been explored as scaffolds in tissue engineering, due to their slow degradation rate and ability to support cellular infiltration and angiogenesis (Kuo and Ma, 2001; Zhang H. et al., 2021).

Alginate dressings are beneficial for moderate to heavily exuding wounds. They are readily biodegradable and can be rinsed away with saline irrigation, making dressing changes virtually painless and not destructive to granulation tissue. This biodegradability is also exploited in alginate sutures used in surgical wound closures. However, alginate dressings require moisture to function effectively and are not suitable for dry wounds or those covered with hard necrotic tissue, as this can delay healing by dehydrating the wound (Gilchrist and Martin, 1983). This property is especially valuable in pediatric and geriatric wound care, where tissue preservation is critical (Sood et al., 2014). They are contraindicated in dry wounds or necrotic lesions, where insufficient exudate may prevent gel formation and lead to desiccation of the wound bed, potentially delaying healing.

8.1.3 Hydrogel dressings

Hydrogels are hydrophilic, crosslinked three-dimensional polymeric networks capable of absorbing and retaining large volumes of water. Common synthetic polymers used include poly (methacrylates), polyvinylpyrrolidone, and polyethylene glycol, while natural polymers such as alginate, chitosan, and hyaluronic acid are increasingly incorporated for biocompatibility and bioactivity (Chai et al., 2017; Cai et al., 2025). They also possess tunable biodegradability, mechanical properties, injectability, self-healing, and shear-thinning properties, making them advantageous for biomedical research (Chai et al., 2017). Hydrogels can encapsulate synthetic drugs and herbal extracts, providing sustained release and enhancing wound healing. Examples include Theobroma cacao extracts dispersed in Carbopol 940 hydrogels and Pterocarpus marsupium heartwood extract loaded into chitosan nanoparticles and blended into Carbopol 940 hydrogel.

Hydrogels can be applied either as an amorphous gel or as an elastic solid sheet or film. To prepare the sheets, the polymeric components are crosslinked to physically entrap water, allowing them to absorb and retain significant volumes of water upon contact with suppurating wounds.

When applied as a gel, hydrogel dressings usually require a secondary covering, such as gauze, and need to be changed frequently. Hydrogel dressings contain significant amounts of water (70%–90%), limiting their ability to absorb much exudate, making them suitable for mildly to moderately exuding wounds (Martin et al., 2002). Excess fluid accumulation can lead to skin maceration and bacterial proliferation, which produces a foul odor in infected wounds. Additionally, hydrogels have low mechanical strength, making them difficult to handle and potentially affecting patient compliance.

Hydrogels possess many desirable characteristics of an ideal dressing (Cannarozzo et al., 2020).' They are suitable for cleansing dry, sloughy, or necrotic wounds by rehydrating dead tissues and enhancing autolytic debridement. Hydrogel dressings are nonreactive with biological tissue, permeable to metabolites, and nonirritant (Moody, 2006). They promote moist healing, are nonadherent, cool the wound surface, reducing pain, and thus have high patient acceptability. Hydrogels leave no residue, are malleable, and improve wound reepithelization. It has been stated that hydrogels are suitable for use at all four stages of wound healing, except for infected or heavily exuding wounds.

Recent studies have focused on nanocomposite hydrogels incorporating functional materials such as silver, gold, graphene oxide, and titanium nanoparticles to enhance antimicrobial activity, mechanical stability, and controlled drug release, expanding the therapeutic potential of hydrogel-based dressings (Cai et al., 2025).

8.1.4 Foam dressings

Foam dressings are made from porous polyurethane foam or foam film, sometimes with adhesive borders. Some, like Tielle™, include additional wound contact layers to prevent adherence when the wound is dry, and an occlusive polymeric backing layer to minimize fluid loss and bacterial contamination. These dressings maintain a moist environment, provide thermal insulation, and are highly absorbent, with their absorbency controlled by properties such as texture, thickness, and pore size. The open pore structure also allows a high moisture vapor transmission rate (MVTR), making them suitable for partial- or full-thickness wounds with minimal to heavy exudate (Thomson, 2006).

Current researchers developed antimicrobial foam dressings impregnated with silver, iodine, or polyhexamethylene, which enhance infection control in chronic or contaminated wounds. Additionally, smart foam composites integrating biosensors and drug delivery systems are under development to monitor wound status and release therapeutics in response to pH or temperature changes.

A systematic review of clinical trials found foam dressings preferable to gauze for postoperative wounds without closure, in terms of pain reduction, patient satisfaction, and nursing time. They are also suitable for granulating wounds, helping to treat over-granulation, and typically do not require a secondary dressing due to their high absorbency and moisture vapor permeability. However, foam dressings are not suitable for dry epithelializing wounds or dry scars, as they rely on exudates for optimal wound healing. Examples include Lyofoam™ (ConvaTec) and Allevyn™ (Smith and Nephew).

8.1.5 Biological dressings

Biological dressings, also known as bioactive dressings, are made from biomaterials that actively participate in the wound healing process, which are biocompatible, biodegradable, and possess intrinsic biological activity. Their ability to support cell adhesion, migration, and proliferation contributes to accelerated healing and reduced scarring, particularly in chronic or complex wounds.

These include tissue-engineered products derived from natural tissues or artificial sources, often combining polymers such as collagen, hyaluronic acid, chitosan, alginates, and elastin (Ramshaw et al., 1996). These biomaterials are biocompatible, biodegradable, and some play an active role in normal wound healing and new tissue formation, making them attractive choices from a biocompatibility and toxicological perspective.

Collagen, a major structural protein in connective tissue, is vital in the wound healing process, stimulating fibroblast formation and endothelial cell migration. Collagen matrices can be medicated to serve as reservoirs for drug delivery. Hyaluronic acid, a component of the extracellular matrix, has unique physiochemical and biological functions, such as lubrication and involvement in inflammation processes. Crosslinked hyaluronic acid hydrogels and liposomes modified with hyaluronic acid have been developed for drug delivery and wound healing (Luo et al., 2000) and chitosan is known to accelerate granulation during the proliferative stage of wound healing (Ho et al., 2024). Phytochemicals are most naturally combined with bioactive dressings such as curcumin (Curcuma longa), acemannan (Aloe vera), nimbidin (Azadirachta indica), and flavonoids from Calendula officinalis or Centella asiatica have been incorporated into collagen, chitosan, or alginate matrices to stimulate granulation, modulate inflammation, and accelerate epithelialization (Singh et al., 2021).

In summary, the dressings are classified based on the materials used in their production as shown in Table 2.

Table 2

Table 2. Different kinds of dressings.

8.2 Tissue engineering: herbal scaffolds

Tissue engineering (TI) is a part of regenerative medicine, which uses engineering principles combined with life sciences to develop biocompatible three-dimensional porous dressings, commonly named scaffolds. These scaffolds help the healing process by providing a suitable microenvironment for cell growth and functional restoration.

The combination of herbal extracts and biomaterials leverages the advantages of both components to create bioactive scaffolds with enhanced regenerative potential. Biomaterials facilitate the controlled release of the herbal extracts, ensuring their prolonged presence at target sites instead of rapid clearance. Controlled release of extracts also helps mitigate associated side effects (Noreen et al., 2016; Singh et al., 2019).

In most studies, herbal extracts are incorporated into biomaterials to modulate cell behavior, and immune response, and prevent microbial infections. Additionally, the integration of herbal extracts into biomaterials can alter the physicochemical properties of the resulting constructs, such as microstructure, mechanical strength, wettability, swelling ratio, biodegradation, porosity, morphology, and thermal characteristics. Tuning these physicochemical properties is crucial as they significantly impact cytocompatibility and functionality (Gasiorowski et al., 2013; Li J. et al., 2021).

8.2.1 Biomaterial for herbal scaffolds

Biomaterials play an important role in constructing the scaffolds for tissue engineering, which serve as carrier matrices for inductive substances, and provide external support for cell migration, attachment, proliferation and differentiation (Socci et al., 2023). For that reason, the selection of biomaterial and bioactive molecules is crucial for the new tissue formation within the scaffold implanted in the damaged area (Socci et al., 2023). Actually, natural and synthetic polymers have been used for preparing herbal scaffolds, which must present biocompatibility, biodegradability and bioactivity properties. Natural polymers are derived from resources such as polysaccharides (e.g., chitosan, dextran, cellulose), proteins (e.g., collagen, gelatin), and decellularized extracellular matrices (Agarwal et al., 2021). However, they have disadvantages such as low mechanical properties and potential immunogenicity (Agarwal et al., 2021; Sood et al., 2021). On the contrary, synthetic polymers, such as polycaprolactone (PCL), polyvinyl alcohol (PVA), and polylactic acid (PLA), which provide low immunogenicity, defined composition and tunable properties, but require careful synthesis to avoid toxic byproducts (Agarwal et al., 2021; Sood et al., 2021). Strategies such as blending natural and synthetic polymers or incorporating additives (e.g., nanoparticles) can achieve scaffolds with desired properties. Herbal extracts, as bioactive components, are incorporated into these constructs through direct blending, nano-delivery vehicles, or coating procedures (Ghaseminezhad et al., 2020; Kashte et al., 2021; Manne et al., 2021). These extracts interact with biomaterials via hydrophobic interactions, hydrogen bonding, and van der Waals interactions, which alter the physicochemical and mechanical properties of the scaffolds and control the drug release profiles (Gao et al., 2021; Zhang X. et al., 2021).

8.2.2 Herbal scaffolds fabrication

There are currently several manufacturing strategies for the design and construction of scaffolds combined with herbal extracts. The main techniques are the following: Solvent Casting, Lyophilization/Freeze-Drying, Hydrogel Formation, Electrospinning (Figure 4) and 3D Printing. All these methods ensure the development of herbal constructs with desirable morphology, mechanical properties, surface chemistry, and controlled degradation and release rates. The Figure 3 shows the macroscopic and microscopic appearance of scaffolds fabricated by electrospinning techniques.

Figure 4

Figure 4. (A,B): macroscopic appearance of a 2D PCL scaffold fabricated by electrospinning technique. (C,D): microarchitecture of scaffolds observed under scanning electron microscopy, (C): randomly oriented nanofibers, and (D): nanofibers with parallel orientation. Bibliography consulted from the Polymeric Materials, Advances and Applications in Tissue Engineering: A Review (Socci et al., 2023). Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/4.0/).

8.2.2.1 Solvent casting

This is a simple and inexpensive method where the polymer is dissolved in a volatile solvent and cast in a mold. Its disadvantage is that the toxic solvents may cause denaturation of incorporated proteins or pharmaceuticals. However, to prevent the presence of toxic solvents.

The scaffold must be dried under a vacuum desiccator (Agarwal et al., 2021). Daisy et al. reported that this method to fabricate graphene oxide (GO)/polyhydroxybutyrate/alginate nanocomposite films loaded with curcumin and Gymnema sylvestre extract. The materials were initially dissolved separately in chloroform, mixed, and then the solvent was evaporated, depositing the mixture into a Petri dish. For extract loading, the nanocomposite was dispersed in an aqueous solution containing the extracts and dried at 50 °C. (Daisy et al., 2020).

8.2.2.2 Lyophilization/freeze-drying

This is a low-temperature dehydration process that maintains the stability of bioactive components. The characteristic of this method eliminates rinsing steps but requires long processing times. Initially, the solution is frozen at low temperatures between −70 °C and −80 °C. This is followed by a primary drying process where pressure is lowered through a partial vacuum, causing the ice within the material to sublimate directly. Finally, in the secondary drying process, most unfrozen water is removed by desorption. The porosity, pore sizes, and structures of the fabricated scaffolds largely depend on parameters such as the water ratio, viscosity and processing parameters applied to the starting polymer solution. This relatively simple procedure eliminates several rinsing steps and it maintains the stability of bioactive components due to low-temperature processing. However, the long processing time and risk of heterogeneous freezing, affecting scaffold homogeneity, are major limitations (Sutar et al., 2021). For example, this strategy was utilized to fabricate pectin/sodium alginate biopolymeric dressings (Sutar et al., 2021). The solution containing both polymers and glycerol was crosslinked with calcium chloride, frozen and lyophilized. The scaffold was then coated with Croton Oblongifolius extract using a dipping method followed by vacuum drying, achieving a porosity of approximately 90%. In another study, Veerasubramanian et al. incorporated Avena Sativa extract within a Konjac Glucomannan and Keratin polymeric formulation, which was further crosslinked with sodium trimetaphosphate, dispensed onto Teflon molds, and then it was lyophilized. The incorporation of Avena Sativa extract significantly affected the porosity due to pore intercalation by the β-glucan present in the extract (Veerasubramanian et al., 2018). Another study adopted a different strategy to incorporate Cissus Quadrangularis extract into lyophilized scaffolds (Thongtham et al., 2020). First, extract-loaded nanoparticles were prepared using a double emulsion technique with PCL and Polyvinyl Alcohol (PVA), as oil and aqueous phases respectively (Thongtham et al., 2020). These nanoparticles were added to a polymeric formulation containing chitosan, collagen, and hydroxyapatite, which were crosslinked with glutaraldehyde and lyophilized. This strategy significantly prevented initial burst release and prolonged the extract release rate. The resulting scaffolds exhibited an interconnected porous architecture with pore sizes of 90–100 μm.

8.2.2.3 Electrospinning

Electrospinning is a method used to create nanofibers that mimic the fibrous structure of native extracellular matrices in tissues and organs, which has taken on great importance in TE. This equipment includes a collector, syringe pump and high voltage power supply. During the electrospinning process, a high voltage is applied to the polymeric fluid, a potential difference forms between the needle containing the polymer solution and the collecting target, resulting in the formation of a continuous polymer jet that creates the fibers (Socci et al., 2023). Electrospun nanofibers provide mechanical properties, nanomechanical cues and biodegradation characteristics necessary for the new tissue formation. In this procedure, bioactive agents are directly dissolved in the polymer solution for encapsulating hydrophilic or hydrophobic agents. Here, different materials such as natural, synthetic, or blended polymers can be used (Ersanli et al., 2023).

Nanofibrous scaffolds using electrospinning have shown promise in tissue engineering, particularly for loading and delivering herbal extracts. The Figure 5 shows the incorporation of herbal extracts into the polymeric scaffolds with direct and indirect effects (Ersanli et al., 2023). The Direct Effect of Herbal Extracts on Wound Healing corresponds to antimicrobial, antioxidant, anticarcinogenic, and anti-inflammatory activities. The indirect effects, the herbal extracts may enhance the wound healing ability of electrospun nanofibers by altering their physicochemical, hydrophilicity, mechanical properties and morphological characteristics (Ersanli et al., 2023). Thus, nanofibrous PCL combined with Achyranthes aspera obtained by electrospinning presented antibacterial activities and wound healing within 9 days in the rat model (Suryamathi et al., 2022).

Figure 5

Figure 5. Direct and indirect effects of the herbal extracts incorporated into electrospun polymers. Bibliography consulted from the Electrospun Scaffolds as Antimicrobial Herbal Extract Delivery Vehicles for Wound Healing (Ersanli et al., 2023). Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

8.2.2.4 Rapid prototyping

Rapid prototyping (RP) is the rapid manufacture of an object using 3D computational design. There are different kinds of printing techniques, for example,: Stereolithography Apparatus, Fused Deposition Modeling, 3D Printing and Selective Laser Synthesis (SLS) (Moreno Madrid et al., 2019). These methods have become highly suitable for producing 3D scaffolds for tissue engineering. The Figure 6 shows the general procedure of RP of a manufacture of a jaw, which is composed of (a) a computer with software to carry out the design, (b) machinery to carry out the additive process (or printers), and (c) suitable materials (Ng et al., 2019).

Figure 6

Figure 6. Process of design and manufacture of scaffold by 3D printing: (A): Tomographic image of the patient’s skull (B): 3D reconstruction of the skull and the bone defect and surrounding tissue (C): 3D computational model of the bone defect (D): 3D impression of the scaffold and surrounding bone tissue. Bibliography consulted from the Polymeric Materials, Advances and Applications in Tissue Engineering: A Review (Socci et al., 2023). Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/4.0/).

Recent studies have explored the fabrication of 3D-printed herbal scaffolds. For example,Baniasadi et al. (2021) developed scaffolds of TEMPO-oxidized cellulose nanofibrils reinforced Aloe barbadensis Miller bio-hydrogels with good viscoelastic properties, wet stability and porosity. However, the application of 3D printing in herbal scaffolds is still in its early stages and requires further investigation (Agarwal et al., 2021).

9 Nanotechnology-based medicinal plants

Medicinal plants have enormous potential to improve wound healing due to their active components such as flavonoids, essential oils, alkaloids, phenolic compounds, terpenoids, fatty acids, etc (Bahramsoltani et al., 2014). However, they have several disadvantages, including low solubility, low bioavailability and poor stability (Dewi et al., 2022). These limitations hinder the clinical application of herbal medicines, but nanotechnology-based delivery systems offer solutions to overcome these challenges (Farhang Hameed Awlqadr; Noreen, et al., 2025). ​Nanoherbal formulations have the key advantages because they are well absorbed and enter the bloodstream with the active compounds (Awlqadr FarhangH. et al., 2025). For this reason, this advantageous efficacy of nanostructured medicinal plants stimulated the authors to investigate plant-derived nanomaterials for wound healing (Hajialyani et al., 2018). Furthermore, nano-herbal systems allow for the prolonged release of the active biomolecules to the target sites of the body. The approach of precision medicine leads to lower systemic exposure and toxicity, which increases the safety and efficacy of the treatment and, at the same time, minimizes damage to healthy tissues (Farhang Hameed et al., 2025) These systems can reduce the required dosages of the active compounds, which lowers the risk of side effects, and increase the efficacy of therapeutic agents by providing sustained and controlled delivery (Balram et al., 2024). Thus, different nanostructured formulations have been successfully produced to stimulate and accelerate wound healing (Figure 7).

Figure 7

Figure 7. The different nanotechnology to produce nanoformulations from medicinal plants. Image adapted from Natural product-based nanomedicines for wound healing purposes: therapeutic targets and drug delivery systems (Hajialyani M et al 2018). This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).

9.1 Nanoformulations-based medicinal plants

Incorporating natural products into different nanostructures is a promising technique for utilizing medicinal plants in wound healing. Controlled drug delivery systems employ diverse biocompatible carriers, including nanoparticles, nanoemulsions, nanohydrogels, nanofilms, and nanoliposomes (Hajialyani et al., 2018). Besides, these therapeutics into nanoparticles allow controlled delivery to injury sites and can enhance their chemical activity.

When nanoemulsions of essential oils are applied to injured sites, the water content evaporates forming a film with the oil droplets. For instance, nanoemulsification of Eucalyptus globulus enhanced its antibacterial activity due to the presence of eucalyptol, which helps in transdermal and topical drug delivery (Sugumar et al., 2014). Similarly, tragacanth gum nanoemulsions impregnated with Aloe vera extract showed promising results in vitro and in vivo studies (Kianvash et al., 2017). For that reason, the encapsulation of active components of medicinal plants into nanoemulsions has taken attention as controlled drug delivery for topical administration of lipophilic drugs that facilitated their penetration into the superficial skin layers (Hajialyani et al., 2018).

Another group of nanostructures for wound dressing is nanohydrogels, which offer high flexibility, hydrophilicity, mechanical strength, tunable structure, and the ability to absorb wound exudates, permeate oxygen, and prevent dehydration (Engel et al., 2015). These nanohydrogels have porous structures that provide sustained and controlled drug delivery. For example, micro/nanohydrogels of Alginate-gum Arabic possess adhesive properties that permit them to bind to injured tissues and serve as a guide for cell migration, proliferation, and differentiation (Li et al., 2017).

Nanoliposomes are used to improve the efficacy of poorly soluble herbal therapies. They are composed of lipid and/or phospholipid bilayers encapsulating aqueous compartments that enhance bioavailability to provide sustained transdermal delivery and avoid toxicity. In addition, curcumin nanoliposomes entrapped in polyethylene glycol enhanced its anti-inflammatory activity, favored permeation of the dermal layer, and accelerated tissue regeneration (Hajialyani et al., 2018).

9.2 Effect of nanoherbal drugs in wound healing

Researchers examined the potential of two medicinal plants, Plectranthus amboinicus and Hemigraphis colorata, for developing a nano-encapsulated antimicrobial ointment. These botanicals exhibit strong antimicrobial, anti-inflammatory, and antioxidant properties. They demonstrated effectiveness against both Gram-positive and Gram-negative bacteria, as well as various fungal strains. The anti-inflammatory effects contribute to accelerated wound healing, while the antioxidant activity helps neutralize free radicals on the skin (Srinivas Reddy et al., 2008).

Recent research has identified Staphylococcus, Pseudomonas, Escherichia coli, Proteus, and Enterococcus as the most common bacterial species found in chronic wounds, all of which contribute to severe tissue necrosis (Thanganadar Appapalam and Panchamoorthy, 2017). Noble metal nanoparticles, particularly silver nanoparticles (AgNPs), have demonstrated broad-spectrum antimicrobial activity against Gram-positive and Gram-negative bacteria, fungi, protozoa, and viruses (Parra-Ortiz and Malmsten, 2022). Metal nanoparticles can be synthesized and stabilized using plant-based extracts. In particular, the leaf extract of Artemisia haussknechtii has been employed as a green synthesis agent to produce zinc oxide nanoparticles with diameters ranging from 50 to 60 nm (Alavi et al., 2019). These nanoparticles exhibit multiple bioactive properties, including antimicrobial, antibiofilm, antiquorum sensing, and antimotility effects. The extract contains various secondary metabolites such as thymol, linalool, α-terpineol, and myrcenol. ZnO nanoparticles synthesized from this botanical source have demonstrated inhibitory activity against antibiotic-resistant Pseudomonas aeruginosa. On the other hand, nanosized curcumin particles have demonstrated well-regulated and sustained delivery, improved antimicrobial, anti-inflammatory, and angiogenic effects, and enhanced wound healing activity (Momtazi-Borojeni et al., 2018).

9.3 Future of nanoherbal medicine

There are several challenges that hinder the widespread application of nanoparticle technology in herbal medicine. The lack of standardization in herbal sources and insufficient data on inter-species chemical variability pose major obstacles (Awlqadr FarhangHameed et al., 2025). Factors such as geographic origin, seasonal variation, and extraction techniques influence the composition of bioactive compounds in herbal extracts, limiting the reproducibility of nanoherbal formulations. Additionally, concerns regarding nanoparticle toxicity remain significant. Although nanocarriers enhance the delivery of bioactive agents, their small size and large surface area may lead to unintended interactions with biological systems, resulting in bioaccumulation and long-term safety risks (Shah et al., 2024).

Economic and regulatory barriers further complicate the adoption of nanotechnology in herbal medicine. The high cost of synthesizing nanocarriers makes these technologies less accessible in resource-limited settings. Moreover, the absence of standardized regulatory frameworks makes it difficult to approve nanoherbal formulations for clinical use, particularly in pain management. Overcoming these challenges requires rigorous safety evaluations and the establishment of clear regulatory protocols.

Promising solutions lie in the development of improved biomaterials and environmentally friendly nanocarriers. Green synthesis methods, which utilize plant extracts as reducing agents, offer scalable and eco-conscious alternatives. Furthermore, the integration of artificial intelligence and machine learning in nanoherbal formulation and optimization is expected to accelerate progress. To fully realize the potential of nanotechnology in herbal medicine, global collaboration among researchers, policymakers, and industry stakeholders is essential.

10 The challenges of the integration of modern medicine and medicinal plants

10.1 The complexity of standardization

Integrating the timeless wisdom of traditional medicines with modern scientific advancements offers a profound opportunity to enhance healthcare holistically. Ensuring the detection, verification, safety and efficacy of bioactive compounds in herbal medicines to guarantee the quality of both raw materials and finished products is crucial (Laguerre et al., 2007).

To achieve this, utilizing single, rapid, and cost-effective analytical methods is essential. Techniques such as Thin Layer Chromatography (TLC), High-Performance Thin Layer Chromatography (HPTLC), High-Performance Liquid Chromatography (HPLC), Ultraviolet (UV) spectroscopy, and Nuclear Magnetic Resonance (NMR) spectroscopy are vital for qualitative and quantitative analyses. These methods assist in identifying marker molecules and elucidating the structures of biologically active components. UV spectroscopy, infrared spectroscopy, NMR, and mass spectroscopy are particularly valuable in this regard. While spectrophotometric techniques and the use of marker molecules have their advantages and limitations in standardizing herbal formulations, chromatographic techniques like HPLC, HPTLC, and Gas Chromatography (GC) are widely applicable despite challenges related to cost and real-time application limitations (Butt et al., 2018). These methods help identify marker molecules and elucidate the structures of active components, effectively bridging the simplicity and curative capacity of natural formulations with the rigor and efficacy that science offers.

Advancements in genetic analysis, particularly DNA barcoding, have revolutionized the standardization and validation of medicinal herbs. By utilizing small, standardized DNA regions to identify individual bioactives, scientists weave together ancient knowledge with modern technology (Ganie et al., 2015). This approach addresses various issues in taxonomy, molecular phylogenetics, population genetics, and biogeography, ensuring purity and authenticity in herbal products. Techniques like LC-MS and next-generation DNA sequencing are instrumental in detecting adulterants and contaminants, safeguarding the integrity of herbal medicines (Qiu et al., 2017).

Safety aspects of traditional medicines are also of paramount importance. While these medicines are generally considered safe due to their long-term use in various traditions, scientific advancements have shown that some natural products can cause significant adverse effects on the skin, including allergic reactions, rashes, and other dermatological issues. The toxicity of these products is often linked to pollutants, adulterants, and non-authenticated sources. Contaminants such as heavy metals, endotoxins, and aflatoxins present in raw materials pose major safety concerns. Long-term use of traditional medicines can lead to heavy metal intoxication, resulting in serious health problems like lead, mercury, and arsenic poisoning. Notably, out of more than 6,000 Ayurvedic medicines, 35%–40% intentionally contain at least one metal, prepared through specific detoxification processes known as the Shodhana process, involving multiple heating and cooling cycles with the addition of specific herbs and liquid media.

Bridging the ancestral-modern medicine gap for wound management requires a comprehensive approach: characterizing traditional formulations’ chemical constituents and dosages, validating their wound healing potential through rigorous experimentation, superior institute of social science and elucidating the molecular mechanisms underlying their biological activity. This integration honors the simplicity and efficacy of natural remedies while embracing the precision and accountability of scientific methods. Examples like Panchvalkal and Herboheal demonstrate the successful fusion of traditional polyherbal formulations with modern therapeutic standards.

Preclinical and clinical research are vital for substantiating the efficacy and safety of Traditional Wound Healing Medicines. Plant extracts rich in bioactives, such as curcumin and asiaticoside, exhibit significant potential in wound healing and skin regeneration. Ethnopharmacology emphasizes systematic screening of plant constituents, fostering drug development that respects traditional knowledge while meeting modern efficacy standards (Thangapazham et al., 2016).

However, challenges in clinical trials persist. Factors like poor bioavailability, administration difficulties, instability, and safety-related issues limit the progression of natural products to market approval. Most trials focus on topical applications for external wounds, burns, and ulcers. Innovative solutions, like combining bioactives with biomaterials, can enhance delivery to target sites, addressing bioavailability constraints. A robust preclinical and clinical foundation is essential for proposing substantial therapeutic claims for traditional medicines.

10.2 Patenting medicinal herbs

In the context of traditional medicine, patenting a drug manufactured from medicinal herbs might seem unnecessary. However, this is not the case, as humanity has consistently demonstrated over thousands of years a tendency to act as “parasites”—in the sense of taking advantage of others’ efforts. The patent system of each country and international agreements regulating relations between nations tacitly recognize this reality.

A patent protects the inventor from the “parasite”; fundamentally, it safeguards the enormous investment of time, money, and effort required to make a “botanical drug” marketable. Without a patent, any “parasite” could claim before the FDA or a similar authority: “I produce the same drug; it is safe and effective since it has already been approved for someone else…” The parasite invests nothing and merely manufactures the drug painstakingly developed by the original inventor.

Of course, the inventor and investors can choose to lose all the money and time invested in obtaining approval for the drug from regulatory bodies worldwide (yes, approval is needed for global distribution) and donate their invention to humanity—i.e., not patent it. However, finding investors willing to accept this condition is a significant challenge.

It is common to think that there are no intellectual property (IP) rights over herbal medicines and drugs. However, for many years, trade secrets and trademarks have been the primary IP protections for herbal medicines and their derivatives (Boyd, 1996). Currently, due to growing interest in the development of new therapeutic drugs and the desire to protect the knowledge of traditional herbal medicine practiced by indigenous communities, new guidelines and laws on intellectual property are being developed to address these factors.

In particular, China and India are actively pursuing more efficient protection of intellectual property rights for traditional medicines. China seeks ways to protect its single-herb prescriptions called “danfang” and multiple-herb prescriptions called “fufang”, believed to synergize therapeutic effects while minimizing toxicity (Wang and Chan, 2010). India aims to protect its traditional Ayurvedic medicine practices by applying modern drug discovery techniques and defining the most appropriate type of intellectual property protection (Mishra et al., 2021; Singh et al., 2021; Patil and Wadekar, 2021).

In both countries, for inventions involving medicinal herbs, the most appropriate patents are (Patil and Wadekar, 2021):

1. Patents on herbal medicine formulations: They protect the use of new technologies to develop innovative dosage forms achieving significant or synergistic therapeutic effects.

2. Combination patents in herbal medicine: They protect new combinations of herbal medicines for the same indication, provided that:

a. The composition is entirely new or varies the proportions of its components.

b. It reports new indications different from existing ones.

3. Patents on herbal medicine processes: They protect innovation in preparation methods, including:

a. Cultivation, harvesting, drying, and sampling processes.

b. Methods for preparing pharmaceutical formulations.

c. Separation, extraction, and identification of phytochemicals from known herbs.

d. Formulation and standardization of solid or liquid extracts, tinctures, and granulates.

e. Methods to prevent contamination and eliminate harmful substances (e.g., pesticides).

f. Techniques to increase production, reduce costs, improve purity, and minimize side effects of herbal medicines.

4. Patents for a new indication of an herbal drug or medicinal herb.

a. When an herbal drug or medicinal herb demonstrates a new therapeutic effect, a patent can be granted.

b. When a new technology is used to prepare a formulation that shows a significantly new therapeutic effect, a patent can be granted.

Some additional suggestions for Herbal Drug Patents (Wang and Chan, 2010) that may be valuable when seeking a patent are as follows:

1. A patent for a pure chemical drug synthesized after its discovery in a plant can coexist with a patent for the traditional herb prescribed for different therapies.

2. Patents claiming “a composition for treating X disease comprising H (a single herbal ingredient)” are almost always rejected for lack of novelty or inventiveness. This obstacle can be overcome using approaches such as “method of processing,” “product by processing,” “method of administration,” and “new use of the herb.”

3. If a syrup made from a plant’s fruit without seeds or husks was used as a cough medicine, proposing the use of the whole fruit as a sweetening syrup is a patentable idea.

4. Herbal formulations can be patented if the essential herb is specified as an independent claim with additional herbs as dependent claims.

5. If an herbal formulation is used for multiple diseases, separate patents should be filed for each disease to avoid the loss of inventive unity. Each patent must highlight the specific effect, and if the chemical structure of the primary active ingredients is known, the patent will be stronger. However, this last requirement is extremely difficult to meet, so the most successful patents are those protecting herbal compositions and formulations.

In conclusion, it is possible for classical pharmacology and traditional medicine to coexist, offering a range of new therapeutic options to physicians while respecting the customs, legal rights, and economic benefits of communities.

Any herb-derived substance claiming therapeutic properties must be considered as a pharmaceutical drug and subjected to be tested like an antibiotic. This means the substance must meet safety, efficacy, and quality requirements (a process that can be lengthy and costly due to the complexities inherent to herbal products).

10.3 Challenges in demonstrating the clinical efficacy and safety of herbal products

1. Standardization: the complex mixture of compounds in herbal products makes standardization and quality control challenging. A single plant may contain hundreds of bioactive compounds, complicating product standardization and quality assurance. For example, “Hypericum perforatum” (St. John’s Wort) contains dozens of bioactive compounds (Patočka, 2003)

2. Consistency: when a product is submitted for approval (e.g., to the FDA), it must have a defined and stable composition. Achieving these qualities is challenging, as they depend on factors such as geographic origin, climate during growth and harvest, cultivation method, plant maturity, and the stability of compounds that may degrade during extraction or storage.

3. Clinical Evidence: some substances have a long history of traditional use but lack solid clinical data under regulatory standards, such as those required by the FDA.

The FDA has a category for “Botanical Drug Products” to ensure the safety and efficacy of plant-derived products intended for human disease treatment. For Investigational New Drug Applications, the guidelines detail the necessary clinical phases (1, 2 and 3) for commercialization:

Phase 1 and Phase 2:

a. Product description: includes characterization of plant materials, identification of active components, and documentation of prior human use.

b. Chemistry and Manufacturing Controls (CMC): requires information about raw botanical materials, pharmaceutical substances, and products to ensure quality and consistency.

c. Non-clinical evaluation: pharmacology and toxicology studies to assess safety before human trials.

d. Clinical pharmacology and considerations: design of initial clinical studies to evaluate safety and potential efficacy signals.

Phase 3:

a. Regulatory considerations: emphasis on more robust data and stricter quality controls.

b. Product description and CMC: greater detail in product characterization and assurance of batch-to-batch consistency.

c. Non-clinical safety evaluation: additional studies, including reproductive toxicity, genotoxicity, and carcinogenic potential as needed.

Approval of a new drug based on plant compounds poses a significant challenge (Wu et al., 2020) for communities practicing traditional medicine. The FDA guidelines are an invaluable tool in this regard (Dou, 2017). The 2016 version, an update of the first presented in 2004, addresses issues such as environmental evaluation, the use of appropriate placebos in clinical studies, and the importance of standardization in manufacturing to ensure the quality of the final product.

In summary, the guidelines allow therapeutic compounds used by indigenous communities worldwide for centuries to enter the global market, ensuring they meet the regulatory standards required for safe and effective clinical use.

10.4 Ephistemological and ethical challenge

The incorporation of herbal extracts into contemporary wound healing technologies presents not only a pharmacological opportunity but also a profound epistemological and ethical challenge. While the therapeutic efficacy of phytochemicals—such as flavonoids, alkaloids, and terpenoids—is well documented, the origins of this knowledge often lie in ancestral, communal, and orally transmitted knowledge that resist reduction to proprietary frameworks. The development of biomedical applications from these resources must be situated within a broader discourse of epistemic justice, biocultural recognition, and equitable innovation.

Boaventura de Sousa Santos argues for the recognition of epistemologies of the South—knowledge systems rooted in the lived experiences, cosmologies, and relational practices of communities historically marginalized by colonial and capitalist structures (Santos, 2015). In this context, medicinal plant knowledge is not merely empirical but deeply embedded in cultural, ecological, and spiritual frameworks. Its appropriation through scientific research and technological development, without adequate recognition or reciprocity, constitutes a form of epistemicide—the silencing or erasure of alternative ways of knowing.

This concern is echoed in the work of Shiva (2007), who critiques the commodification of biodiversity and traditional knowledge through mechanisms of biopiracy. Shiva emphasizes that the patenting of plant-based compounds—often derived from Indigenous practices—frequently occurs without the consent, participation, or benefit of the communities who have cultivated and preserved this knowledge for generations. Such practices not only violate ethical principles but also undermine the integrity of scientific inquiry by severing knowledge from its cultural and ecological context.

In response to these concerns, international frameworks have sought to establish legal mechanisms for the fair and equitable sharing of benefits arising from the utilization of genetic resources and associated traditional knowledge.

The Convention on Biological Diversity (CBD) (Buck and Hamilton, 2011) is an international treaty adopted at the Earth Summit in Rio de Janeiro in 1992. Its main objective is to promote the conservation of biodiversity, the sustainable use of its components, and the fair and equitable sharing of benefits arising from using genetic resources. The CBD aims to halt the global loss of biodiversity by promoting cooperation among countries and establishing measures to protect ecosystems, species, and genetic resources.

On the other hand, the Nagoya Protocol is a supplementary agreement to the CBD, adopted in 2010 in Nagoya, Japan. This protocol focuses on access to genetic resources and the fair and equitable sharing of benefits arising from their utilization. The Nagoya Protocol provides guidelines to ensure that local communities and indigenous peoples, who possess traditional knowledge related to genetic resources, receive fair compensation when these resources and knowledge are used commercially. It also promotes transparency and compliance with international standards on the access and use of genetic resources.

Together, the CBD and the Nagoya Protocol create a supportive environment for harnessing the potential of medicinal plants and ancestral wisdom. They encourage collaboration between researchers, traditional knowledge holders, and industry, leading to innovative medical technologies that enhance wound healing and overall healthcare. However, its implementation remains uneven, and many communities continue to face challenges in asserting their epistemic and territorial sovereignty within scientific and commercial domains.

11 Discussion

From a technological perspective, the integration of plant extracts into advanced wound care systems—such as hydrogels, nanofibers, and smart bandages—offers promising avenues for regenerative medicine. These innovations must be guided by principles of accessibility, cultural relevance, and social inclusion. Technologies derived from ancestral knowledge should not be confined to elite biomedical markets but designed to serve diverse populations, particularly those historically excluded from healthcare infrastructures. This requires a shift from extractive models of innovation to co-creative frameworks that honor the origin of knowledge and foster reciprocal relationships.

Moreover, the concept of biocultural heritage—which encompasses the interlinked biological and cultural dimensions of traditional practices—must be central to research and development processes. Recognizing biocultural heritage affirms the dignity of knowledge holders and reinforces the ethical imperative to engage with communities not as subjects of study but as co-authors of innovation. This approach aligns with pluriversal methodologies that value relationality, diversity, and rootedness over universality and abstraction.

In this light, the development of wound healing technologies based on medicinal plants becomes more than a scientific endeavor—it becomes a cultural, ethical, and political act. It invites researchers to reconfigure their methodologies, to listen deeply to ancestral voices, and to design systems that nourish both the body and the social fabric. As the metaphor suggests, humanity is a great tree: when its roots—our ancestral wisdom—are respected and nourished, its fruits—our scientific and technological achievements—become more abundant, resilient, and shared.

12 Conclusion

Wound healing remains a multifaceted clinical challenge, shaped by biological complexity, environmental factors, and cultural contexts. Common complications—such as infection, chronic inflammation, delayed epithelialization, and impaired angiogenesis—continue to drive the search for more effective and integrative treatment strategies. In response, modern medicine has developed a range of advanced technologies, including bioactive dressings, herbal scaffolds, nanoencapsulation systems, and tissue-engineered constructs, all aimed at optimizing healing outcomes while minimizing adverse effects.

The evolution of these technologies reflects a growing convergence between soft material engineering, regenerative biology, and ancestral knowledge systems. This review has demonstrated that traditional formulations based on medicinal plants are not merely empirical remedies, but complex therapeutic frameworks with biochemical, symbolic, and relational dimensions. Their integration into contemporary platforms offers promising avenues for developing wound care solutions that are both clinically effective and culturally resonant.

However, this integration presents critical challenges: the standardization of plant extracts, clinical validation, intellectual property rights concerning collective knowledge, and epistemological tensions between biomedical models and ancestral worldviews. Addressing these issues requires not only technical innovation but also ethical frameworks that recognize the legitimacy of diverse knowledge systems and promote epistemic justice.

To develop wound healing technologies with consciousness is to acknowledge that every material, protocol, and therapeutic design carries ontological and social implications. In the context of regenerative medicine, this means creating devices that not only restore tissue integrity but also honor territories, memories, and relationships. The science of the future must be culturally responsive and ethically grounded—capable of regenerating not only skin, but the networks of meaning that sustain life.

Author contributions

APR: Visualization, Funding acquisition, Validation, Conceptualization, Supervision, Writing – original draft. AGR: Visualization, Writing – review and editing, Validation, Writing – original draft, Conceptualization. SK: Visualization, Writing – review and editing. LC: Writing – original draft. KN: Writing – review and editing, Validation. CF: Writing – original draft. NK: Writing – review and editing.

Funding

The author(s) declare that financial support was received for the research and/or publication of this article. This work was funded by PIP 2022 (CONICET) and PIUNT E741 of the Secretariat of Science, Art and Technological Innovation (SCAIT, UNT).

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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The author(s) declare that no Generative AI was used in the creation of this manuscript.

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