Treatment options for critical size defects - Comparison of different materials in a calvaria split model in sheep

Abstract

Bone defects of the craniofacial skeleton are often associated with aesthetic and functional impairment as well as loss of protection to intra- and extracranial structures. Solid titanium plates and individually adapted bone cements have been the materials of choice, but may lead to foreign-body reactions and insufficient osseointegration. In contrast, porous scaffolds are thought to exhibit osteoconductive properties to support bone ingrowth. Here, we analyse in critical size defects of the calvaria in sheep whether different bone replacement materials may overcome those remaining challenges. In a critical size defect model, bilateral 20 × 20 × 5-mm craniectomies were performed on either side of the sagittal sinus in 24 adult female blackheaded sheep. Bony defects were randomised to one of five different bone replacement materials (BRMs): titanium scaffold, biodegradable poly(d,l-lactic acid) calcium carbonate scaffold (PDLLA/CC), polyethylene 1 (0.71 mm mean pore size) or 2 (0.515 mm mean pore size) scaffolds and polymethyl methacrylate (PMMA)-based bone cement block. Empty controls (n = 3) served as references. To evaluate bone growth over time, three different fluorochromes were administered at different time points. At 3, 6 and 12 months after surgery, animals were sacrificed and the BRMs and surrounding bone analysed by micro-CT and histomorphometry. The empty control group verified that the calvaria defect in this study was a reliable critical size defect model. Bone formation in vivo was detectable in all BRMs after 12 months by micro-CT and histomorphometric analysis, except for the non-porous PMMA group. A maximum of bone formation was detected in the 12-months group for titanium and PDLLA/CC. Bone formation in PDLLA/CC starts to increase rapidly between 6 and 12 months, as the BRM resorbs over time. Contact between bone and BRM influenced bone formation inside the BRM. Empty controls exhibited bone formation solely at the periphery. Overall, porous BRMs offered bone integration to different extent over 12 months in the tested calvaria defect model. Titanium and PDLLA/CC scaffolds showed remarkable osseointegration properties by micro-CT and histomorphometric analysis. PDLLA/CC scaffolds degraded over time without major residues. Pore size influenced bone ingrowth in polyethylene, emphasising the importance of porous scaffold structure.

Keywords: Bone healing; Calvaria split model; Critical size defect; Osteogenesis; Scaffold.