Speaker
Description
Pediatric bone tissue engineering presents distinct challenges related to the growing patient including: the need for a construct strategy that preserves growth plates; bone generation that remodels in parallel with skeletal development to prevent long-term growth restrictions; and a degradation profile that aligns with the process of bone generation. Despite the recognized limitations of donor-site pain, resorption of autologous bone grafts and complications associated with alternative bone replacement materials, autologous bone grafts continue to be the standard of care for bony defect repair in the pediatric population. Advancements in additive manufacturing have facilitated precise control over the micro- and macro-architecture of biomaterials, enabling the production of tissue engineering devices (e.g., scaffolds) with enhnaced osteogenic properties that can be tailored to accommodate patient-specific defects. The objective of this long term study was to evaluate bone regeneration in a critically-sized calvarial defect using skeletally, immature Gottingen minipigs (5 weeks old), through facial maturity, treated with dipyridamole-augmented 3D-printed bioceramic (DIPY-3DPBC) scaffolds composed of 100% beta-tricalcium phosphate (β -TCP) versus autologous bone graft using a immature porcine model followed. Subjects were set to heal for 24 months post implantation, followed by quantitative and qualitative assessments of bone regeneration bone were conducted using micro-computer tomography (micro-CT) to evaluate volume of regenerated tissue and bridging, alongside two-dimensional histologic analysis to examine the level of regeneration. Volumetric analysis of calvarial defects treated with DIPY-3DPBC scaffolds demonstrated significantly greater bone regeneration, with ~53 ± 8% of total defect volume occupied by new bone, with approximately 3% (±2.0) scaffold remaining, compared to subjects treated with autologous bone graft (44 ± 4%, p = 0.2). Qualitative analysis of the histological micrographs revealed vascularized and organized lamellar bone, along with patent cranial sutures and no evidence of ectopic bone or excess inflammation. Radiographic and histologic analysis revealed patent craniofacial sutures. 3D facial symmetry analysis found that bony growth centers were preserved with no disruption of craniofacial growth. Given the results of longitudinal scaffold osteogenesis, favorable scaffold resorption, with safety of scaffold agents through skeletal maturity in a preclinical model, this DIPY-3DPBC scaffold strategy may serve as promising candidate for future implementation in clinical trials investigating bone tissue engineering alternatives within the pediatric population.
53381501364
