Research Topic

Bioactive Materials for Angiogenesis During Tissue Repair and Regeneration

About this Research Topic

Blood vessels play a crucial role in the transport and exchange of oxygen, nutrients, growth factors and waste substances during tissue repair and/or regeneration. Following tissue injury or insult, disruption of blood vessels commonly occurs and results in the induction of angiogenesis, the process underpinning the formation of new blood vessels from pre-existing vessels in the physiological environment.

As a well-documented phenomenon, the onset of angiogenesis occurs in response to an array of physico-chemical signals, with a series of molecules (e.g., HIF-1α and MMPs), cells (e.g., endothelial cell (EC)), and signaling pathways (e.g. VEGF) involved in promoting this process. Hence, stimulation of angiogenesis via different approaches is considered one of the most difficult challenges in current tissue engineering approaches, but is necessary in order to succeed in promoting the healing of large, complex tissue defects. Thus, it is imperative that angiogenesis should be entirely considered at both the design and fabrication stages of tissue engineered (TE) constructs.

Current strategies to enhance angiogenesis are often based on transferring genes that encode pro-angiogenic proteins via recombinant DNA technology or embedding angiogenic growth factors into a scaffold structure in order to be released according to defined kinetics. However, both strategies suffer from limitations, including the risk of tumorigenicity. Embedding pro-angiogenic growth factors – which direct physiological angiogenesis - in biomaterial carriers is also complex due to the high temperatures and harsh organic solvents that may be necessary to fabricate these tissue engineered constructs. These processing conditions can involve denaturation of proteins, which thereby lose their function. Hence, new approaches based on modifying and optimizing the inherent physicochemical properties of bioactive materials (e.g. bioactive glass) have recently attracted great interest in promoting angiogenesis without the need for embedding exogenous organic moieties.

Here, we use the term “bioactive” to define any biomaterial with the capability to interact with the biological environment to therapeutically promote (or inhibit in some cases) angiogenesis, including biocompatible polymers containing bioactive species (e.g., proteins), functionalized polymers, bioactive glasses/glass-ceramics, and their composites. Nowadays, angiogenesis-inducing bioactive materials, which are available in different shapes and structures (e.g., membranes, porous scaffolds, fibers), have shown great promise for optimized healing of both hard and soft tissues. In this sense, three-dimensional (3D) moldable structures containing bioactive materials have received a growing reputation as feasible approaches for promoting angiogenesis and accelerating tissue healing following injury or insult.

This Research Topic has the ambition of providing a valuable collection of contributions, and a platform for scientific discussion, focused on biomaterial-driven strategies within the context of angiogenesis. Original research papers and reviews are welcome in this Research Topic, the key topics of which include innovative synthesis approaches, drug and ion delivery systems, structure-function relationships, in vitro interactions, and in vivo outputs of bioactive materials.


Keywords: Biopolymers, Bioactive glasses, Composites, Scaffold, Angiogenesis


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

Blood vessels play a crucial role in the transport and exchange of oxygen, nutrients, growth factors and waste substances during tissue repair and/or regeneration. Following tissue injury or insult, disruption of blood vessels commonly occurs and results in the induction of angiogenesis, the process underpinning the formation of new blood vessels from pre-existing vessels in the physiological environment.

As a well-documented phenomenon, the onset of angiogenesis occurs in response to an array of physico-chemical signals, with a series of molecules (e.g., HIF-1α and MMPs), cells (e.g., endothelial cell (EC)), and signaling pathways (e.g. VEGF) involved in promoting this process. Hence, stimulation of angiogenesis via different approaches is considered one of the most difficult challenges in current tissue engineering approaches, but is necessary in order to succeed in promoting the healing of large, complex tissue defects. Thus, it is imperative that angiogenesis should be entirely considered at both the design and fabrication stages of tissue engineered (TE) constructs.

Current strategies to enhance angiogenesis are often based on transferring genes that encode pro-angiogenic proteins via recombinant DNA technology or embedding angiogenic growth factors into a scaffold structure in order to be released according to defined kinetics. However, both strategies suffer from limitations, including the risk of tumorigenicity. Embedding pro-angiogenic growth factors – which direct physiological angiogenesis - in biomaterial carriers is also complex due to the high temperatures and harsh organic solvents that may be necessary to fabricate these tissue engineered constructs. These processing conditions can involve denaturation of proteins, which thereby lose their function. Hence, new approaches based on modifying and optimizing the inherent physicochemical properties of bioactive materials (e.g. bioactive glass) have recently attracted great interest in promoting angiogenesis without the need for embedding exogenous organic moieties.

Here, we use the term “bioactive” to define any biomaterial with the capability to interact with the biological environment to therapeutically promote (or inhibit in some cases) angiogenesis, including biocompatible polymers containing bioactive species (e.g., proteins), functionalized polymers, bioactive glasses/glass-ceramics, and their composites. Nowadays, angiogenesis-inducing bioactive materials, which are available in different shapes and structures (e.g., membranes, porous scaffolds, fibers), have shown great promise for optimized healing of both hard and soft tissues. In this sense, three-dimensional (3D) moldable structures containing bioactive materials have received a growing reputation as feasible approaches for promoting angiogenesis and accelerating tissue healing following injury or insult.

This Research Topic has the ambition of providing a valuable collection of contributions, and a platform for scientific discussion, focused on biomaterial-driven strategies within the context of angiogenesis. Original research papers and reviews are welcome in this Research Topic, the key topics of which include innovative synthesis approaches, drug and ion delivery systems, structure-function relationships, in vitro interactions, and in vivo outputs of bioactive materials.


Keywords: Biopolymers, Bioactive glasses, Composites, Scaffold, Angiogenesis


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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12 September 2019 Manuscript

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Manuscripts can be submitted to this Research Topic via the following journals:

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Topic Editors

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Submission Deadlines

12 September 2019 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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