Development of Hydrogel Spinal Disc Replacement

DESCRIPTION (provided by applicant): The overall goal of Orthonics, Inc. is to develop novel tissue replacements based on biologically relevant design principles. Current methods for resolving intractable spine pain associated with the intervertebral disc include discectomy and fusion of the vertebral bodies. This approach reduces movement and predisposes the patient to future fusions. We are developing a disc replacement that is fabricated from a polyvinyl alcohol hydrogel. Intervertebral disc prostheses of this type must be anchored in some way to the subchondral bone, but current anchor devices are impractical. We propose to obtain fixation of the hydrogel disc in the intervertebral space by creating a surface on the ends of the disc that promotes bone ingrowth. We have adapted surface design strategies that have been successful in promoting bone formation adjacent to dental implants and have developed novel technology for producing hydrogel surfaces with specific microarchitectural features. The purpose of the STTR grant is to verify that these novel hydrogel surfaces are compatible with osteogenesis using in vitro and in vivo models. Phase I will assess feasibility by examining the response of osteoblast-like cells to the surfaces in vitro. This project is based on the hypothesis that osteogenesis occurs on surfaces that have specific microtopographies. Our aims are: (I) To determine the optimal microarchitecture for osteoblast attachment, proliferation, and differentiation on a hydrogel surface in vitro; and (II)To determine in vitro if growth on the micropatterned hydrogel surface identified in Aim I alters osteoblast response to osteogenic factors used to promote bone growth in spine. Orthonics, Inc. will produce hydrogel disks with smooth and rough microtopographies using its proprietary technology. Human osteoblast-like cells (MG63 cell line and normal human NHOst osteoblasts) will be used to assess the effects on attachment, proliferation, and differentiation, and production of autocrine and I paracrine regulators of bone formation and resorption. We will examine differentiation of the osteoblast progenitor 2T3 cell line in the presence of BMP-2, which is an osteoinductive agent used in spine surgery, and determine if growth on the optimal osteogenic surface alters osteoblast response to agents that regulate bone cell physiology (17-beta-estradiol, 1,25(OH)2D3, TGF-beta-1).