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Description
Extensive defects of the upper extremity cause significant patient burden, including disability and social stigma. Approximately, 500,000 bone defects are reconstructed annually in the USA alone at a cost of ~$2.5 billion, due to factors including donor site harvest and lengthy operative times. Bone defects >5cm are usually reconstructed with autologous vascularized bone transfer (bone from another region of the patient’s body is harvested to replace the defect), but limitations include donor site morbidity, infection, and delayed healing. These limitations drive innovation of biomaterial applications, but a tissue engineered approach to reconstruction remains elusive. The objective of this study was to assess the efficacy of 3D printed bioactive ceramic (3DPBC) scaffolds augmented with dipyridamole (DIPY), an indirect A2AR agonist known to enhance bone formation, to stimulate bone regeneration of a critical-sized defect of the radius in an in vivo translational model. A 3DPBC scaffold was utilized to repair critical sized long bone defects in-vivo. In this study, 3DPBC scaffolds were fabricated in a two-piece system. Following IACUC approval critical-sized full thickness (~7xm x full thickness) defects were created in the tibia diaphysis in sheep (N=8). The 3DPBC scaffold composed of β tri-calcium phosphate (β-TCP) was placed into the defect site, along with an intramedullary rod and animals were euthanized 24 weeks. The tibia were retrieved, for micro-CT, histological and mechanical analysis. Bone growth was assessed exclusively within scaffold pores and evaluated by microCT and advanced reconstruction software. Biomechanical properties were evaluated utilizing nanoindentation to assess the newly regenerated bone for elastic modulus (E) and hardness (H). Qualitative evaluation of the histological micrographs indicated directional bone ingrowth of bone, with an increase in bone formation toward the native bone morphology. Extensive bone formation with signs that scaffold has significantly resorbed, presenting areas of extensive structural discontinuity resorption was observed at both low and high magnifications. Histological micrographs at high magnification to better appreciate the features of the newly regenerated bone within the scaffold. Furthermore, qualitative evaluation did not yield any exuberant bone growth and the newly regenerated bone was limited to the defect and the scaffold regions. Our previous studies using a smaller preclinical model, rabbit, yielded favorable results, where with the implantation of a custom-fit 3D printed resorbable bioactive ceramic scaffolds into critical size radius defects resulted in bone morphology that remarkably resembled the original bone segment with a haversian cortical shell presenting cortical-like mechanical properties and associated marrow space. The application of this β-TCP scaffold has the potential for successful treatment outcomes while potentially minimizing the amount of surgery and less time spent in hospitals for individuals that would not fully recover from injury though current technology and treatment strategies available. Custom engineered, biocompatible and resorbable, β-TCP scaffolds treated with DIPY demonstrated to have an increased bone regeneration qualitatively and quantitatively. The custom approach and expedited healing has the potential to positively benefit the patient in terms of lowering health care costs and patient's quality of life, as well as returning to form and function.
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