Advancements in Metal Ion-Driven Tissue Repair Materials

Over the past few decades, rapid progress in both tissue engineering and regenerative medicine has revolutionized approaches to tissue regeneration and reconstruction. This new era of research aims at combining the use of biomaterials with cellular therapy to restore injured/tissue-depleted organs. However, despite this tremendous success, traditional biomaterials face several limitations: poor mechanical properties, unsuitable degradation rates, low bioactivity etc., which prevent them from completely mimicking natural tissue microenvironments.
To address this issue, researchers have begun integrating various bioactive metal ions such as Ca²⁺, Mg²⁺, Zn²⁺, Si⁴⁺, Cu²⁺, etc., into material designs. Metal ions play important roles in many essential physiological functions that occur throughout our body, ranging from bone formation to vasculature development to immunological function. Incorporation of these ions within scaffold structures, hydrogel networks, or even surface coatings has been shown to induce favorable cellular interactions through enhanced adhesion, proliferation, and growth characteristics; they also possess inherent antimicrobial and anti-inflammatory effects. In addition, the distinct biological activity induced by each individual ion provides an exciting opportunity to develop patient-specific tissue engineering therapies aimed specifically towards cells residing within certain organs/tissues (e.g.: bone, cartilage, and skin). Despite a series of remarkable advancements, numerous challenges remain. How to precisely control the release of metal ions, ensure their biocompatibility, and adapt to the needs of different tissues requires further investigation. While it may not yet seem possible, continued advances will lead us down a path toward future generations of regenerative medical technologies which successfully integrate both material sciences and clinical practice.

The objective of this project is to develop intelligent, tissue-specific biomaterial platforms that synergize precision-engineered ion delivery systems with comprehensive biological validation, thereby advancing personalized therapies. This includes:
1. Advanced material design: Utilizing 3D printing, nanocomposites, and stimuli-responsive systems to achieve tunable ion release kinetics, addressing unique repair demands across diverse tissues. Such as 3D printed calcium phosphate scaffolds incorporating strontium-doped nanomaterials that release osteogenic ions in synchrony with the remodeling phase and dynamic hydrogel systems that regulate chondrocyte metabolism through spatially controlled ionic gradients.
2. Multifunctional integration: Incorporating antibacterial, anti-inflammatory or pro-angiogenic properties into doped ion systems to address complex clinical situations such as chronic wounds or degenerative diseases.
3. Multiscale mechanistic studies: Investigating ion-mediated cellular signaling (e.g., differentiation, angiogenesis) and tissue remodeling through integrated in vitro, in vivo, and computational models.
4. Safety and efficacy frameworks: Establishing standardized protocols for assessing ion toxicity, optimal dosage long-term biocompatibility across tissues, and determining the optimal doses for different types of tissue.
This research aims to unify material science, bioengineering, and clinical insights, ultimately enabling next-generation therapies that adapt to dynamic healing processes while addressing unmet needs in large tissue defects and degenerative conditions.

The present Research Topic is dedicated to the advancement of metal ion-integrated biomaterials for the purposes of tissue engineering and regenerative medicine, with particular emphasis on interdisciplinary innovation. Contributions addressing, but not limited to, the following areas are invited:
1. Design strategies: Novel synthesis methods (e.g., nanocomposites, 3D-printed scaffolds) for controlled metal ion delivery.
2. Mechanistic insights: Roles of ions (Ca²⁺, Mg²⁺, Zn²⁺, Sr²⁺, etc.) in cellular signaling, differentiation, and tissue remodeling.
3. Functional optimization: Balancing ion release kinetics, mechanical stability, and biodegradability for tissue-specific applications.
4. Multifunctionality: Antimicrobial, anti-inflammatory, or angiogenic properties of ion-doped systems.
5. Synergistic Interactions and Safety: How different ions interact, what levels are toxic, and ensuring long-term safety to use over the long haul.
6. Clinical translation: Running preclinical studies to test how well treatments work for regenerating bone, cartilage, skin, or nerve tissues.
We welcome Original Research, Reviews, Methodologies, Perspectives, and Brief Reports that bridge material science, bioengineering, and translational medicine. Submissions integrating computational modeling, advanced characterization (e.g., in situ imaging), or patient-specific approaches are encouraged. High-impact studies addressing unmet clinical needs and scalability will be prioritized.