Development of Technologies Aiding Large-Tissue Engineering

Abstract

There are many clinical situations in which a large tissue mass is required to replace tissue lost to surgical resection (e.g., mastectomy). It is possible that autologous cell transplantation on biodegradable polymer matrices may provide a new therapy to engineer large tissue which can be used to treat these patients. A number of challenges must be met to engineer a large soft tissue mass. These include the design of (1) a structural framework to maintain a space for tissue development, (2) a space-filling matrix which provides for localization of transplanted cells, and (3) a strategy to enhance vascularization of the forming tissue. In this paper we provide an overview of several technologies which are under development to address these issues. Specifically, support matrices to maintain a space for tissue development have been fabricated from polymers of lactide and glycolide. The ability of these structures to resist compressive forces was regulated by the ratio of lactide to glycolide in the polymer. Smooth muscle cell seeding onto polyglycolide fiber-based matrices has been optimized to allow formation of new tissues in vitro and in vivo. Finally, polymer microsphere drug delivery technology is being developed to release vascular endothelial growth factor (VEGF), a potent angiogenic molecule, at the site of tissue formation. This strategy, which combines several different technologies, may ultimately allow for the engineering of large soft tissues.

Silk based biomaterials to heal critical sized femur defects

“…The advantage of this approach is the combined transplantation of autologous cells, scaffold material, and growth factors stored within the matrix [55,56]. However, harvesting autologous bone is associated with second site morbidity and hampered by insufficient amounts of collected bone substance to fill the entire defect [57].…”

Fibrin Gel-Immobilized VEGF and bFGF Efficiently Stimulate Angiogenesis in the AV Loop Model

“…Sufficient vascularization remains the fundamental limitation for successful implantation of tissue-engineered constructs to any recipient site (26). It is well known that cells cannot survive when located further than 200-500 microns away from a capillary (1,5).…”

Oxygen Tension-Controlled Matrices with Osteogenic and Vasculogenic Cells for Vascularized Bone Regeneration In Vivo

“…20 In vitro prevascularization of bone tissue engineering constructs with endothelial progenitor cells (EPCs) has gained significant attention in this respect. [21][22][23][24][25][26] EPCs, which may be easily isolated from the patient's peripheral blood, demonstrate high proliferative potential for ex vivo expansion, as well as the ability to enhance and accelerate neovascularization in vivo.…”