Evaluation of Osteoconductive Scaffolds in the Canine Femoral Multi-Defect Model

Abstract

Treatment of large segmental bone defects remains an unsolved clinical challenge, despite a wide array of existing bone graft materials. This project was designed to rapidly assess and compare promising biodegradable osteoconductive scaffolds for use in the systematic development of new bone regeneration methodologies that combine scaffolds, sources of osteogenic cells, and bioactive scaffold modifications. Promising biomaterials and scaffold fabrication methods were identified in laboratories at Rutgers, MIT, Integra Life Sciences, and Mayo Clinic. Scaffolds were fabricated from various materials, including poly(L-lactide-co-glycolide) (PLGA), poly(Llactide-co-e-caprolactone) (PLCL), tyrosine-derived polycarbonate (TyrPC), and poly(propylene fumarate) (PPF). Highly porous three-dimensional (3D) scaffolds were fabricated by 3D printing, laser stereolithography, or solvent casting followed by porogen leaching. The canine femoral multi-defect model was used to systematically compare scaffold performance and enable selection of the most promising substrate(s) on which to add cell sourcing options and bioactive surface modifications. Mineralized cancellous allograft (MCA) was used to provide a comparative reference to the current clinical standard for osteoconductive scaffolds. Percent bone volume within the defect was assessed 4 weeks after implantation using both MicroCT and limited histomorphometry. Bone formed at the periphery of all scaffolds with varying levels of radial ingrowth. MCA produced a rapid and advanced stage of bone formation and remodeling throughout the defect in 4 weeks, greatly exceeding the performance of all polymer scaffolds. Two scaffold constructs, TyrPC PL /TCP and PPF4 SLA /HA PLGA Dip , proved to be significantly better than alternative PLGA and PLCL scaffolds, justifying further development. MCA remains the current standard for osteoconductive scaffolds.

Research of the effects of autologous cancellous bone graft and hyaluronic acidon the healing of bone defects experimentally induced in rabbits

“…With fibrotic healing, some clinical complications, such as nonunion and encapsulation, can emerge. To avoid such complications, and to provide regeneration of bone tissue in the region, reconstruction of defects with graft materials is required (21,22). In the defects that are not reconstructed with graft material, the cells of fibrous tissue migrate to the defect region and activate fibrotic healing.…”

Three-Dimensional Printing-based Reconstruction of a Maxillary Bone Defect in a Dog Following Tumor Removal

“…Composite scaffolds are usually printed using synthetic polymers such as polylactic acid (PLA), polyglycolic acid (PGA), polylactic-polyglycolic acid (PLGA), polyethylene glycol (PEG), and PCL, combined with hydroxyapatite (HA) or β-TCP (16)(17)(18). In this case, we used PCL and β-TCP.…”

Present Strategies for Critical Bone Defects Regeneration

“…This study proposed new class of magnetic hydroxyapatites which can be used to develop new magnetic ceramic scaffolds with enhanced regenerative properties for bone regeneration based on hyperthermia [97]. Other common synthetic materials used to form scaffolds for bone healing are polymer materials, such as poly (alpha-hydroxy esters) [98], poly(urethanes) [99], and poly(carbonates) [100]. All of them have been applied within large bone defects, as void filler and as an osteoconductive matrix.…”