Cell Interactions with Vascular Regenerative MAA‐Based Materials in the Context of Wound Healing

Abstract

In diabetic patients the development of chronic non-healing wounds is a common complication. A methacrylic acid-based biomaterial is a vascular regenerative material that enhances diabetic healing without the use of cells or growth factors. The bioactive nature of this material is thought to be associated with its anionic charge or surface chemistry. Contact between the methacrylic acid-based biomaterial and tissue begins with protein (including complement) adsorption and is followed by interaction of the biomaterial with resident and infiltrating cells in the wound bed (e.g., macrophages and endothelial cells). This results in changes to their surface receptors to activate phosphorylation cascades that lead to differential activation of signalling pathways such as those involving osteopontin and sonic hedgehog. These changes modulate the phenotype of the cells in the wound bed, eventually improving vessel formation and wound healing. Understanding the molecular and cellular mechanisms will have broad implications for biomaterials, not just the methacrylic acid-based material, and will facilitate the advancement of regenerative biomaterials for diverse applications.

A Biomimetic Approach toward Enhancing Angiogenesis: Recombinantly Expressed Domain V of Human Perlecan Is a Bioactive Molecule That Promotes Angiogenesis and Vascularization of Implanted Biomaterials

“…Difficulties associated with temporal control of growth factor delivery, as well as the short half‐life requiring delivery of supra‐physiological concentrations, and costs associated with their manufacture, limit the use of this approach as a sole means of promoting tissue vascularization. [ 4a,5 ]…”

Skin wound healing assisted by angiogenic targeted tissue engineering: A comprehensive review of bioengineered approaches

“…This compound showed an increase in angiogenesis without the need for cell or growth factor incorporation. One of the main capabilities of MAA‐based biomaterials is the improvement of angiogenesis and wound healing in either diabetic or nondiabetic individuals 135 …”

Shh pathway in wounds in non-diabetic Shh-Cre-eGFP/Ptch1-LacZ mice treated with MAA beads

“…[31]]. Similar to the early diabetic wound healing experiment [5], large (15 mm  15 mm) full-thickness wounds were made on the backs of mice.…”

“…In addition, gene modifications in Shh and Ptch1 alleles in transgenic mice may have contributed to altered profiles of the studied genes; the interconnections among these genes [reviewed in Ref. [31]] in the context of MAA beads are discussed below.…”