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Review collagen-based biomaterials for wound healing.

ABSTRACT: With its wide distribution in soft and hard connective tissues, collagen is the most abundant of animal proteins. In vitro, natural collagen can be formed into highly organized, three-dimensional scaffolds that are intrinsically biocompatible, biodegradable, nontoxic upon exogenous application, and endowed with high tensile strength. These attributes make collagen the material of choice for wound healing and tissue engineering applications. In this article, we review the structure and molecular interactions of collagen in vivo; the recent use of natural collagen in sponges, injectables, films and membranes, dressings, and skin grafts; and the on-going development of synthetic collagen mimetic peptides as pylons to anchor cytoactive agents in wound beds.

SUBMITTER: Chattopadhyay S

PROVIDER: S-EPMC4203321 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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Review collagen-based biomaterials for wound healing.

Chattopadhyay Sayani S Raines Ronald T RT

Biopolymers 20140801 8

With its wide distribution in soft and hard connective tissues, collagen is the most abundant of animal proteins. In vitro, natural collagen can be formed into highly organized, three-dimensional scaffolds that are intrinsically biocompatible, biodegradable, nontoxic upon exogenous application, and endowed with high tensile strength. These attributes make collagen the material of choice for wound healing and tissue engineering applications. In this article, we review the structure and molecular ...[more]

PMID: 24633807

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Project description:BackgroundStem cell therapies represent a promising tool in regenerative medicine. Considering the drawbacks of direct stem cell injections (e.g. poor cell localisation), extracellular matrix-based biomaterials (e.g. scaffolds and tissue grafts), due to their compositional biofunctionality and cytocompatibility, are under investigation as potential stem cell carriers.MethodsThe present study assessed the potential of three commercially available extracellular matrix-based biomaterials [a collagen/glycosaminoglycan scaffold (Integra™ Matrix Wound Dressing), a decellularised porcine peritoneum (XenoMEM™) and a porcine urinary bladder (MatriStem™)] as human adipose-derived stem cell delivery vehicles.ResultsBoth tissue grafts induced significantly (p < 0.01) higher human adipose-derived stem cell proliferation in vitro over the collagen scaffold, especially when the cells were seeded on the basement membrane side. Human adipose-derived stem cell phenotype and trilineage differentiation potential was preserved in all biomaterials. In a splinted wound healing nude mouse model, in comparison to sham, biomaterials alone and cells alone groups, all biomaterials seeded with human adipose-derived stem cells showed a moderate improvement of wound closure, a significantly (p < 0.05) lower wound gap and scar index and a significantly (p < 0.05) higher proportion of mature collagen deposition and angiogenesis (the highest, p < 0.01, was observed for the cell loaded at the basement membrane XenoMEM™ group). All cell-loaded biomaterial groups retained more cells at the implantation side than the direct injection group, even though they were loaded with half of the cells than the cell injection group.ConclusionsThis study further advocates the use of extracellular matrix-based biomaterials (in particular porcine peritoneum) as human adipose-derived stem cell delivery vehicles. Comparative analysis of a collagen scaffold (Integra™ Matrix Wound Dressing) and two tissue grafts [decellularised porcine peritoneum (XenoMEM™) and porcine urinary bladder (MatriStem™)] as human adipose-derived stem cells carriers.

Project description:Porous collagen-glycosaminoglycan (collagen-GAG) scaffolds have shown promising clinical results for wound healing; however, these scaffolds do not replace the dermal and epidermal layer simultaneously and rely on local endogenous signaling to direct healing. Functionalizing collagen-GAG scaffolds with signaling factors, and/or additional matrix molecules, could help overcome these challenges. An ideal candidate for this is platelet-rich plasma (PRP) as it is a natural reservoir of growth factors, can be activated to form a fibrin gel, and is available intraoperatively. We tested the factors released from PRP (PRPr) and found that at specific concentrations, PRPr enhanced cell proliferation and migration and induced angiogenesis to a greater extent than fetal bovine serum (FBS) controls. This motivated us to develop a strategy to successfully incorporate PRP homogeneously within the pores of the collagen-GAG scaffolds. The composite scaffold released key growth factors for wound healing (FGF, TGFβ) and vascularization (VEGF, PDGF) for up to 14 days. In addition, the composite scaffold had enhanced mechanical properties (when compared to PRP gel alone), while providing a continuous upper surface of extracellular matrix (ECM) for keratinocyte seeding. The levels of the factors released from the composite scaffold were sufficient to sustain proliferation of key cells involved in wound healing, including human endothelial cells, mesenchymal stromal cells, fibroblasts, and keratinocytes; even in the absence of FBS supplementation. In functional in vitro and in vivo vascularization assays, our composite scaffold demonstrated increased angiogenic and vascularization potential, which is known to lead to enhanced wound healing. Upon pro-inflammatory induction, macrophages released lower levels of the pro-inflammatory marker MIP-1α when treated with PRPr; and released higher levels of the anti-inflammatory marker IL1-ra upon both pro- and anti-inflammatory induction when treated with the composite scaffold. Finally, our composite scaffold supported a co-culture system of human fibroblasts and keratinocytes that resulted in an epidermal-like layer, with keratinocytes constrained to the surface of the scaffold; by contrast, keratinocytes were observed infiltrating the PRP-free scaffold. This novel composite scaffold has the potential for rapid translation to the clinic by isolating PRP from a patient intraoperatively and combining it with regulatory approved scaffolds to enhance wound repair.

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Review collagen-based biomaterials for wound healing.

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Review collagen-based biomaterials for wound healing.

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