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Despite advances in surgical reconstruction of the head and neck region in recent years, several clinical scenarios continue to pose significant reconstructive challenges such as the reconstruction of complex maxillofacial defects affected by chemotherapy, and/or radiation. The common factor which makes these typically post-traumatic or post oncologic defects difficult to treat is the compromised wound bed. Thus, reliable reconstructive methods to re-establish form and function are needed. The current study hence aimed to elucidate the effect of 3D-printed β–tricalcium phosphate scaffolds coated with a bioactive molecule, dipyridamole (DIPY) - an indirect agonist of the adenosine A2A receptor, via different coating techniques to regenerate critically sized mandibular defects in a previously established (irradiated) rabbit model of compromised wound healing. Eighteen New Zealand white rabbits received a total of 36 Gy radiation followed by surgical intervention to induce unilateral, critically sized, 10 mm full-thickness mandibular defects. Animals were divided into one of three groups and defects were (i) left empty - negative control, or filled with either (ii) DIPY 1 coated scaffolds - scaffolds immersed in a mixture of Bovine Type I Collagen and DIPY (1000 µM) (dip coating), or (iii) DIPY 2 coated scaffolds – individual scaffolds were placed into wells of cell culture plate containing the DIPY solution and allowed to dry/precipitate (drop casting). At the study endpoint (8 weeks), rabbits were euthanized, and their mandibles harvested for micro-computed tomographic (μCT), histological, and histomorphometric processing and analysis.Defects left untreated (negative control) demonstrated fracture of the mandible post-surgery, resulting in partial or complete collapse of the defect site. Scaffolds treated with DIPY 2 yielded significantly higher bone formation at 8 weeks relative to DIPY 1 (p=0.031). This was accompanied by increased levels of soft tissue presence in the DIPY 2 group in the intermediary regions of the defect site (p=0.008). No statistical differences were observed in scaffold resorption at the 8-week time point. However, irrespective of the DIPY coating technique, qualitative histological analysis at 8 weeks depicted bone at the periphery of defects treated with a scaffold. In addition, bone growth was observed to have proceeded from the periphery towards the center of the defect through the lattice-like, porous structure of the scaffolds. 3D-printed bioceramic scaffolds not only effectively provide adequate mechanical stability at the defect site, but also serve as a viable carrier of DIPY – to elicit the desired osteogenic response, relative to untreated defects, in this compromised model of wound healing.
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