Hyaluronic Acid-Based Polymers as Cell Carriers for Tissue-Engineered Repair of Bone and Cartilage

Abstract

Culture-expanded bone marrow-derived mesenchymal progenitor cells differentiate into chondrocytes or osteoblasts when implanted subcutaneously in vivo in combination with an appropriate delivery vehicle. This in vivo implantation technique is used to test new materials as putative delivery vehicles in skeletal tissue-engineering models. HYAFF 11 and ACP sponges, two biomaterials based on hyaluronic acid modified by esterification of the carboxyl groups of the glucuronic acid, were tested as osteogenic or chondrogenic delivery vehicles for rabbit mesenchymal progenitor cells and compared with a well characterized porous calcium phosphate ceramic delivery vehicle. The implant materials were examined by scanning electron microscopy for differences in pore structure or cellular interactions, were quantified for their ability to bind and retain mesenchymal progenitor cells, and were examined histologically for their ability to support osteogenesis and chondrogenesis after subcutaneous implantation into nude mice. The ACP sponge bound the same number of cells as fibronectin-coated ceramic, whereas the HYAFF 11 sponge bound 90% more. When coated with fibronectin, ACP and HYAFF 11 bound, respectively, 100 and 130% more cells than the coated ceramics. HYAFF 11 sponge composites retained their integrity after the 3 or 6-week incubation period in the animals and were processed for histomorphometric analysis. As a result of rapid degradation or resorption in vivo, ACP sponges could not be recovered after implantation and could not be analyzed. HYAFF 11 sponges presented more area available for cell attachment and more available volume for newly formed tissue. Following loading with mesenchymal progenitor cells and implantation, the pore of the sponges contained more bone and cartilage than the pores of ceramic cubes at either time point. Thus, relative to ceramic, HYAFF 11 sponges allow incorporation of twice as many cells and produce a 30% increase in the relative amount of bone and cartilage per unit area. Hence, the hyaluronic acid-based delivery vehicles are superior to porous calcium phosphate ceramic with respect to the number of cells loaded per unit volume of implant, and HYAFF 11 sponges are superior to the ceramics with regard to the amount of bone and cartilage formed. Additionally, hyaluronic acid-based vehicles have the advantage of degradation/resorption characteristics that allow complete replacement of the implant with newly formed tissue.