Abstract
This study investigates a comprehensive model of bone regeneration capacity of dypiridamole-loaded 3D-printed bioceramic (DIPY-3DPBC) scaffolds composed of 100% beta-tricalcium phosphate (β –TCP) in an immature rabbit model through the time of facial maturity. The efficacy of this construct was compared to autologous bone graft, the clinical standard of care in pediatric craniofacial reconstruction, with attention paid to volume of regenerated bone by 3D reconstruction, histologic and mechanical properties of regenerated bone, and long-term safety regarding potential craniofacial growth restriction. Additionally, long-term degradation of scaffold constructs was evaluated. At 24 weeks in vivo, DIPY-3DPBC scaffolds demonstrated volumetrically significant osteogenic regeneration of calvarial and alveolar defects comparable to autogenous bone graft with favorable biodegradation of the bioactive ceramic component in vivo. Characterization of regenerated bone reveals osteogenesis of organized, vascularized bone with histologic and mechanical characteristics comparable to native bone. Radiographic and histologic analyses were consistent with patent craniofacial sutures. Lastly, through application of 3D morphometric facial surface analysis, our results support that DIPY-3DPBC scaffolds do not cause premature closure of sutures and preserve normal craniofacial growth. Based on this novel evaluation model, this DIPY-3DPBC scaffold strategy is a promising candidate as a safe, efficacious pediatric bone tissue engineering strategy.
Highlights
This study investigates a comprehensive model of bone regeneration capacity of dypiridamole-loaded 3D-printed bioceramic (DIPY-3DPBC) scaffolds composed of 100% beta-tricalcium phosphate (β –TCP) in an immature rabbit model through the time of facial maturity
Affected patients commonly require bony reconstruction at the time of active facial growth and surgical interventions are designed to restore the craniofacial skeleton while limiting impairment to face and skull development
Autologous bone grafting remains the standard of care for reconstruction of the pediatric craniofacial skeleton[1,5,6,7]
Summary
This study investigates a comprehensive model of bone regeneration capacity of dypiridamole-loaded 3D-printed bioceramic (DIPY-3DPBC) scaffolds composed of 100% beta-tricalcium phosphate (β –TCP) in an immature rabbit model through the time of facial maturity The efficacy of this construct was compared to autologous bone graft, the clinical standard of care in pediatric craniofacial reconstruction, with attention paid to volume of regenerated bone by 3D reconstruction, histologic and mechanical properties of regenerated bone, and long-term safety regarding potential craniofacial growth restriction. An ideal pediatric bone replacement or regenerative therapeutic agent would be biocompatible, patient specific, bioresorbable, lead to the regeneration of mature, vascularized bone and restore form and function of the skeleton without impeding facial development[16,18] Due to these unique considerations, efficacious translation of bone tissue engineering strategies in a pediatric context have been limited and investigation into pediatric skeletal tissue engineering strategies remains in its infancy[20,21]. The scaffolds described in this study comprised of 100% beta-tricalcium phosphate (β -TCP) to provide structure and rigidity to the defect, promote osteocyte migration and osteoconduction within scaffold interstices, and demonstrate better biodegradability compared to other commonly used biomaterials such as hydroxyappetite (HA)[12], leaving uninterrupted regenerated bone
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