Biodendrimers are a new class of well-defined modular biopolymers prepared from monomers that are natural metabolites or known to be biocompatible, that can be custom-designed to provide a unique scaffold appropriate for articular cartilage repair. Biodendrimers have several features that make them uniquely attractive for scaffold fabrication: (1) their chemical composition, physical structure, and molecular weight can be precisely controlled; (2) the dendrimer structure permits diverse and extensive functionalization that facilitates covalent intermolecular crosslinking to form a hydrogel; (3) aqueous solutions of biodendrimer can be crosslinked in situ to form a functional and well-integrated hydrogel scaffold using a mild photoinitiated crosslinking reaction; (4) and the mechanical properties of crosslinked biodendrimer hydrogels can be tuned over a wide range of values by varying the functional groups, molecular weight, dendrimer structure, and concentration. In this SBIR proposal, HyperBranch Medical Technology will engineer biodendrimer hydrogel scaffolds for functional in vivo repair of articular cartilage by optimizing a polyester-carbamate biodendrimer hydrogel scaffold, analyzing chondrocytes-scaffold interactions in vitro, and obtaining safety data on the biodendrimer hydrogel scaffold. The specific aims of this proposal are: AIM 1: Synthesize and characterize polyester-carbamate biodendrimer hydrogel scaffolds. AIM 2: Evaluate interactions of the biodendrimer scaffolds with chondrocytes in vitro. AIM 3: Obtain safety data on the biodendrimer hydrogel scaffold formulation necessary for the submission of an Investigational Device Exemption with the FDA, required for human use. Successful completion of these studies in 12 months will lead to Phase II work designed to evaluate the biodendrimer scaffold in an in vivo goat model of articular cartilage and to address issues of GMP manufacturing for ultimate commercialization of this product. The objective at HyperBranch Medical Technology is to commercialize an articular cartilage repair product: (1) with fluid-like properties that can be used as an acellular scaffold (2) that permits injection and filling of an irregularly shaped tissue defect in situ; (3) that polymerizes to form a mechanically functional and well-integrated 3D scaffold in situ by a mild photo- initiated crosslinking procedure; (4) that allows for cellular proliferation and production of cartilaginous extracellular matrix. Successful completion of this research will lead to development and commercialization of a biopolymer cartilage repair product used for the restoration of articular cartilage function. [unreadable] [unreadable] [unreadable]