Large skull defects arise frequently following neurosurgery and craniofacial reconstructive surgery for trauma, cancer resection, and congenital deformity. Concerns over revascularization, aesthetics, and protective strength of the patient's own bone or artificial plating are magnified by the post-surgical need to protect the brain from infection and trauma. Tissue engineered bone replacements have been shown to ossify small skeletal defects with potential utility in fracture repair, but currently, these materials do not effectively address skull defects large enough to require graft or prosthetic augmentation. The primary surgical option, autogenous grafts, extend the patient's deficits to a new site and may resorb or become infected. Non-tissue engineered implanted materials interrupt vasculature between the dura, bone and scalp, and risk infection or extrusion. Limited means of diagnostic assay lead to neurocranial repair problems presenting initially as a failure requiring surgery. Tissue engineering neurocranial prosthetics could overcome these limitations if shown to maintain their shape and protective strength while bone migrates from the host into the implant's center. The investigators propose an animal model that extends current work on poly(propylene fumarate)/beta-tricalcium phosphate (PPF/beta-TCP) photopolymer critical size implants to truly large size neurocranial defects. Specifically, the following three hypotheses will be tested: 1) Control peri-implant morphology, resorption environment, and strength concomitant to upward scaling of implant size to a level clinically useful for neurocranial repair (i.e., longest dimension form 1.5 to 4 cm); 2) Use standard clinical MR and CT to track prosthetic vascular ingrowth and ossification; and 3) Use composite solid/foam PPF/beta-TCP prosthetics, micro-machined with channels that promote vascular ingrowth through the solid core without loss of strength. To address these hypotheses, the investigators propose to determine the optimal design for PPF/beta-TCP composite implants seeded with bone marrow's osteoprogenitor cells and growth factors. They will collect in vitro strength before and during PPF/beta-TCP degradation, in vivo ossification and vascular ingrowth, and explant ex vivo strength and histology data.
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