The overall goal of this research project is to integrate tissue engineered cartilage with native tissue. Specifically, we will achieve this goal by creating covalent bonds between a photopolymerizing hydrogel and the cartilage extracellular matrix. Cartilage is an avascular tissue that acts as a cushion and lubricating surface for proper articulating joint function and provides smactural function in numerous other tissues. Cartilage has been the focus of significant tissue engineering research since it lacks the ability to self repair when it is lost due to trauma, disease, or congenital abnormalities. For example, we have investigated photopolymerizing hydrogel scaffolds that may be formed in situ for engineering cartilage using differentiated chondrocytes and bone marrow-derived mesenchyrnal stem cells. Unfortunately, numerous barriers remain for translating this research to a successful clinical application. Integration of tissue-engineered cartilage with the native host tissue remains one of the most significant challenges in translating this research. Lack of integration with the surrounding tissues allows micromotion of the implant to occur, often causing dislocation. Furthermore, the extracellular matrix of the transplanted tissue rarely forms a contiguous network with the host which prevents proper tissue maintenance and ultimately leads to implant failure. Unlike other tissue engineering strategies that focus on improving the scaffold or implantation technique, we have focused on modifying the native cartilage tissue in order to initiate polymerization and scaffold formation. We propose to solve this problem by designing a method to covalently attach a tissue engineering scaffold directly to the strong collagen fibers in native cartilage will improve tissue integration, preventing implant movement while providing a bridge for engineered and native cartilage extracellular matrix to integrate. Furthermore, the technique we have developed, tissue-initiated photopolymerization, allows in situ hydrogel formation to occur without an exogenous photoinitiator, improving biocompatibility. To achieve the goal of designing a novel system for hydrogel integration to cartilage and testing the hypothesis that it will improve matrix integration the following specific aims have been developed:
Specific Aim 1. Development of an efficient and biocompatible method to directly bond a photopolymerizing hydrogel to cartilage tissue. Specifically, collagen fibers will be exposed on the cartilage surface and oxidized to generate a radical and initiate photopolymerization.
Specific Aim 2. Test the hypothesis that covalent attachment of a cell-hydrogel construct to the cartilage surface will improve integration of cartilage engineered from chondrocytes and bone marrow-derived mesenchymal cells and host cartilage matrix both in vitro and in vivo. Tissue integration will be monitored by morphological, biochemical, and mechanical analysis.
| Sharma, Blanka; Williams, Christopher G; Kim, Tae Kyun et al. (2007) Designing zonal organization into tissue-engineered cartilage. Tissue Eng 13:405-14 |
| Wang, Dong-An; Varghese, Shyni; Sharma, Blanka et al. (2007) Multifunctional chondroitin sulphate for cartilage tissue-biomaterial integration. Nat Mater 6:385-92 |
| Sharma, Blanka; Williams, Christopher G; Khan, Mehnaz et al. (2007) In vivo chondrogenesis of mesenchymal stem cells in a photopolymerized hydrogel. Plast Reconstr Surg 119:112-20 |
| Pirouzmanesh, Ashkan; Herretes, Samantha; Reyes, Johann M G et al. (2006) Modified microkeratome-assisted posterior lamellar keratoplasty using a tissue adhesive. Arch Ophthalmol 124:210-4 |
| Reyes, Johann M G; Herretes, Samantha; Pirouzmanesh, Ashkan et al. (2005) A modified chondroitin sulfate aldehyde adhesive for sealing corneal incisions. Invest Ophthalmol Vis Sci 46:1247-50 |
