Evaluation of Hyaleo pre-clinical safety and efficacy for healing large cartilage defects in the knee

PROJECT SUMMARY The goal of this proposal is to evaluate the safety and efficacy of HyaleonTM to heal large defects in the knee in a pre-clinical large animal model. HyaleonTM is an allogeneic neocartilage implant that exhibits biomimetic properties, for example, biomechanical properties on par with native cartilage. It is derived from juvenile rib cartilage and it is engineered specifically to address the healing of large defects, in contrast to current clinical approaches (e.g., microfracture, chondroplasty, and mosaicplasty) which address only small defects. Cell-based treatments are emerging as alternatives to current clinical approaches. However, obtaining sufficient cell numbers, maintaining functionality of the cells, and donor site morbidity are significant obstacles to successful clinical outcomes of cell-based approaches. To address these shortcomings, Cartilage Inc., an all women-run company, developed HyaleonTM using novel, patent-pending platform technologies, Apeira-cellsTM and NeotisTM. Apeira-cellsTM and NeotisTM enable the production of mechanically robust, scaffold-free engineered neocartilage from an abundance of pure, functional cells obtained from a miniscule amount of donor tissue. Unlike current treatments, HyaleonTM produces native-like repair cartilage and is not limited by cell scarcity, donor site morbidity, or poor functionality of cells. HyaleonTM utilizes juvenile costal chondrocytes that are highly passaged (up to passage 9). Costal cartilage is more readily available than healthy articular cartilage, rendering it an attractive alternative cell source for tissue-engineered products. Toward collecting critical pre-clinical data that will contribute to an Investigational New Drug (IND) application to the Food andamp; Drug Administration (FDA), this proposal aims to evaluate the safety and efficacy of HyaleonTM to heal large cartilage defects in vivo. According to FDA guidance documents, due to immunological reactions of human products in animals, pre-clinical studies need to be performed using animal cellular products that are analogous to the intended human clinical products. Thus, Aim 1 focuses on generating an analogous animal cellular product (Hyaleon-MP) using HyaleonTM technology (i.e., Apeira-cellsTM and NeotisTM) for investigation in Aim 2’s pre-clinical animal study. Aim 2 focuses on evaluating the safety and efficacy of Hyaleon-MP to heal large knee articular cartilage defects in the minipig. Completion of this proposal will provide a solid foundation for HyaleonTM as a promising solution for cartilage repair. Next steps include validating the long-term (6-12 months) in vivo safety and efficacy of HyaleonTM in definitive pre-clinical large animal studies, establishing GMP-compliant processes to manufacture HyaleonTM, and creating a GMP-compliant allogeneic cell bank for the production of HyaleonTM. Data generated from these aims will contribute to a submission to the FDA to begin clinical investigation of HyaleonTM as a solution for knee cartilage repair, and ultimately, to the commercialization of HyaleonTM.PROJECT NARRATIVE HyaleonTM is a mechanically robust, allogeneic, biomimetic tissue-engineered scaffold-free neocartilage implant derived from juvenile rib cartilage that can be used for the effective healing of large, as well as small, cartilage defects. With Hyaleonandapos;sTM off-the-shelf, allogeneic approach, patients could be treated with a single surgery, resulting in zero donor site morbidity. This proposal aims to collect safety and efficacy data of HyaleonTM in a pre-clinical animal model, which will contribute toward a submission to the Food andamp; Drug Administration to begin clinical trials for HyaleonTM as a solution for knee cartilage repair.