Description:
The inability of bone to heal large defects necessitates the use of bone grafts in many traumatic injuries and disease states. Autograft bone exhibits superior healing over other options due to its inherent ability to provide an osteoconductive scaffold, osteoinductive growth factors, and autogenous osteogenic cells. Unfortunately, limited donor site availability and donor site morbidity preclude autograft use in many cases. Bone allograft is an attractive alternative to autograft and non-biologic endoprostheses because of the potential to integrate with the host and subsequently restore normal limb function without the morbidity associated with the harvest of autograft. In order to mitigate a host-allograft immune response and disease transmission, the periosteum is removed. The removal of the periosteum, which serves as a source of osteoprogenitor cells and osteoinductive factors that are critical to natural bone healing, leads to suboptimal clinical performance. Resultantly, the failure rate of segmental bone allografts at 10 years has been documented as high as 60 %.
Brief summary of invention:
The present invention comprises three distinct tissue engineered coatings on cortical bone in order to mimic the biological function of the periosteum. First, chitosan nanofibers were directly electrospun on murine bone allografts and subsequently modified with N,N,N-trimethyl chitosan and heparin polyelectrolyte multilayers using a layer-by-layer deposition technique. Second, N,N,N-trimethyl chitosan and heparin polyelectrolyte multilayers were deposited on murine cortical bone coated with freeze-dried chitosan scaffold. Third, N,N,N-trimethyl chitosan and heparin polyelectrolyte multilayers were directly deposited onto murine cortical bone. These three scaffolds can locally deliver growth factors and stem cells in order to improve host-allograft union. The methods can be expanded for other tissue engineering and regenerative medicine applications.
Figure 1. Scanning electron micrographs of (top row) (A) cortical bone, (B) cortical bone coated with PUA, and (C) cortical bone coated with PUA and a TMC-heparin PEM; (middle row) (D) cortical bone coated with a chitosan freeze-dried (FD) scaffold, (E) the same FD scaffold after ammonium hydroxide neutralization, and (F) after TMC-heparin PEM deposition; (bottom row) (G) cortical bone coated with electrospun chitosan nanofibers (NF), (H) the NF after ammonium hydroxide neutralization, and (I) after TMC-heparin PEM deposition.
Patent status - US and PCT applications pending.
