Designer Collagen-Fibril Biograft Materials for Tunable Molecular Delivery

Rucha V Joshi, Purdue University

Abstract

One of the biggest challenges in tissue engineering currently is the formation of a functional microvascular network as part of an engineered tissue graft. Despite many advances in tissue engineering methods, the field still awaits biograft designs that enable neovascularization at clinically relevant size scales. Critical to the design of such materials are tissue-specific physico-mechanical properties and controlled local therapeutic molecular release. The purpose of the current research is to develop such a multifunctional biograft material from type I collagen polymers. Although collagen-based biomaterials have been applied broadly to tissue engineering and local drug delivery applications, persistent shortcomings remain, including poor mechanical properties, rapid proteolytic degradation, and cursory control over physical properties and molecular release profiles. In large part, this is owing to 1) poor characterization of conventional formulations in terms of their molecular composition and 2) inability to fully capitalize on the inherent self-assembly or polymerization capacity of collagen. Here we address current shortcomings through the development of self-assembling, collagen-fibril biograft materials through integrated tissue engineering and molecular delivery design. More specifically, collagen polymers specified by their intermolecular crosslink composition and self-assembly capacity were used to customize and design materials in terms of 1) collagen fibril microstructure and 2) proteolytic degradability, collectively defining overall local molecular release profiles. Application of the designed collagen biograft materials to control vascular endothelial growth factor (VEGF) release for promoting neovascularization and tissue regeneration was shown using an established in-vivo chicken egg chorioallantoic membrane (CAM) model. Results indicated that the collagen polymers specified by their intermolecular crosslink composition and self-assembly capacity can be used effectively to fashion a broad range of multifunctional collagen-fibril biograft materials with tunable physical and molecular delivery properties in absence of excessive processing and exogenous crosslinking. Further, using heparin affinity-based VEGF retention in collagen constructs, we demonstrated improved and accelerated neovascularization as well as cellularization of the collagen biografts implanted on CAM. These highly porous collagen materials comprise D-banded fibrils, resembling those found in tissues, and maintain their inherent biological signaling properties, thereby providing an ideal platform for integrated tissue engineering and molecular therapy design.

Degree

Ph.D.

Advisors

Voytik-Harbin, Purdue University.

Subject Area

Biomedical engineering

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