Biomaterial-based strategies for craniofacial tissue engineering
Kretlow, James D.
Mikos, Antonios G.
Doctor of Philosophy
Damage to or loss of craniofacial tissues, often resulting from neoplasm, trauma, or congenital defects, can have devastating physical and psychosocial effects. The presence of many specialized tissue types integrated within a relatively small volume leads to difficulty in achieving complete functional and aesthetic repair. Tissue engineering offers a promising alternative to conventional therapies by potentially enabling the regeneration of normal native tissues. Initially, a stimulus responsive biomaterial designed for injectable cell delivery applications was investigated with the goal of providing a substrate for osteogenic differentiation of delivered cells. In order to enable faster clinical translation, later efforts focused on novel combinations of regulated materials. Most common approaches using cell delivery for bone tissue engineering involve the harvest and ex vivo expansion of progenitor cell populations over multiple weeks and cell passages. The effect of aging and passage on proliferation and differentiation were analyzed using murine mesenchymal stem cells as a model. These cells lose their ability to proliferate and differentiate with increases in donor age and passages during cell culture. Delivery of uncultured bone marrow mononuclear cells was then investigated, and it was determined that when delivered to porous scaffolds these cells, which can be harvested, isolated, and returned to the body within the setting of a single operation, significantly increased bone regeneration in vivo. Finally, because these techniques of scaffold implantation and cell delivery would likely fail if delivered to an exposed or infected wound, a method of space maintenance was investigated. Space maintainers made of poly(methyl methacrylate) and having tunable porosity and pore interconnectivity were evaluated within a clean/contaminated mandibular defect. Low porosity space maintainers were found to prevent soft tissue collapse or contracture into the bony defect and allowed surrounding soft tissues to penetrate the pores of the implant, enabling healing over 12 weeks. The tissue response and wound healing characteristics of these implant was favorable when compared to solid or high porosity implants. Although optimization and further investigation of these techniques is necessary, in combination these approaches demonstrate one possible and translatable approach towards craniofacial tissue regeneration.