Plastic Surgery Research Council
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Presenter: Sameer Shakir, BS
Co-Authors: MacIsaac ZM; Naran S; Gilbert JR; Cray JJ; Wang D; Kubala AA; Losee JE; Cooper GM
University of Pittsburgh

BACKGROUND: Repair of complex cranial defects is complicated by the paucity of appropriate donor tissues. BMP2 and TGF≤b1 induce bone formation and potentially improve surgical outcome for cranial defect repair by obviating the need for donor tissue. We hypothesized that combining BMP2 and TGF≤b1 using inkjet-based biopatterning would augment cranial repair within complex calvarial defects.

METHODS: Suturectomies (3?15mm) were performed in 10 day old New Zealand White rabbits (n=16). Acellular dermamatrix (3x15mm) patterned with 4 treatments (vehicle, 350ng BMP2, 200ng TGF≤b1, or 350ng BMP2 + 200ng TGF≤b1) were placed in suturectomy sites and rabbits were euthanized 4 weeks post-surgery. Bone healing was quantified by computerized tomography (CT). Regenerated bone was qualitatively assessed histologically.

RESULTS: Percent healing in control animals (n=8) was -9.7232.29 (SE); BMP2 (n=8) was 52.5617.23; TGF≤b1 (n=8) was 74.3910.25; combination of BMP2 and TGF≤b1 (n=8) was 67.6115.34. One-way ANOVA revealed significant differences between the groups. Bonferonni posthoc analysis revealed significant differences between the control and other groups. No significant differences were detected between BMP2, TGF≤b1 or BMP2 + TGF≤b1 groups. The TGF≤b1 treatment group produced bone that was most similar to native bone in terms of cellularity and matrix density. Pentachrome staining demonstrated cartilage in the BMP2-regenerated bone. This cartilaginous intermediate was not present in other treatment groups.

CONCLUSIONS: Growth factor delivery using inkjet-based biopatterning augmented cranial repair in our model. Total healing in BMP2 and TGF≤b1 treatment groups was not significantly different. In contrast to BMP, TGF≤b1 improved bone formation without producing a cartilaginous intermediate. The lack of a cartilaginous intermediate more closely resembles the ossification pathway native to calvarial bones of the skull. Future work will adapt this therapeutic strategy to the correction of cranial defects within a naturally occurring craniosynostotic rabbit model.

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