Matricellular proteins and biomaterials

Abstract

Biomaterials are essential to modern medicine as components of reconstructive implants, implantable sensors, and vehicles for localized drug delivery. Advances in biomaterials have led to progression from simply making implants that are nontoxic to making implants that are specifically designed to elicit particular functions within the host. The interaction of implants and the extracellular matrix during the foreign body response is a growing area of concern for the field of biomaterials, because it can lead to implant failure. Expression of matricellular proteins is modulated during the foreign body response and these proteins interact with biomaterials. The design of biomaterials to specifically alter the levels of matricellular proteins surrounding implants provides a new avenue for the design and fabrication of biomimetic biomaterials.

Keywords: Biocompatible; Biomaterials; Decellularization; Extracellular matrix; Foreign body response; Matricellular.

Figure 1

Overview of the foreign body response. A. Implantation of biomaterial into soft tissues elicits a unique inflammatory response leading to encapsulation by a largely avascular capsule consisting of dense collagenous matrix. A number of complications are encountered including: 1) FBGC form on the implant surface and can damage the implant; 2) FBGC and macrophages secrete pro-fibrotic factors; 3) blood vessels are generally excluded from the capsule; 4) the lack of vessels and the dense collagen arrangement limit diffusion of small molecules; and 5) fibroblasts can differentiate into myofibroblasts and contract the capsule. B. Representative image of the foreign body response to PDMS disk implanted subcutaneous (SC) in a mouse for 4 wk. Sections were stained with Masson's trichrome to visualize collagen deposition (blue color) in between the implant (*) and muscle fibers (red). Arrowhead and arrow indicate FBGC and blood vessel, respectively. Scale bar = 50 μm.

Figure 2

ECM retention following decellularization. Dermal fibroblasts were cultured for 10 d in the presence of ascorbic acid to induce ECM production. Cultures were analyzed by immunohistochemistry for the deposition of fibronectin (red color in A, B) and TSP2 ( green color in C, D) prior (A, C) or following decellularization (B, D). Nuclei were counterstained with DAPI (blue). Retention of both proteins was observed following decellularization. Scale bar = 100 μm.