Repair of critical-size porcine craniofacial bone defects using a collagen-polycaprolactone composite biomaterial

Abstract

Regenerative medicine approaches for massive craniomaxillofacial bone defects face challenges associated with the scale of missing bone, the need for rapid graft-defect integration, and challenges related to inflammation and infection. Mineralized collagen scaffolds have been shown to promote mesenchymal stem cell osteogenesis due to their porous nature and material properties, but are mechanically weak, limiting surgical practicality. Previously, these scaffolds were combined with 3D-printed polycaprolactone mesh to form a scaffold-mesh composite to increase strength and promote bone formation in sub-critical sized porcine ramus defects. Here, we compare the performance of mineralized collagen-polycaprolactone composites to the polycaprolactone mesh in a critical-sized porcine ramus defect model. While there were no differences in overall healing response between groups, our data demonstrated broadly variable metrics of healing regarding new bone infiltration and fibrous tissue formation. Abscesses were present surrounding some implants and polycaprolactone polymer was still present after 9-10 months of implantation. Overall, while there was limited successful healing, with 2 of 22 implants showed substantial levels of bone regeneration, and others demonstrating some form of new bone formation, the results suggest targeted improvements to improve repair of large animal models to more accurately represent craniomaxillofacial bone healing. Notably, strategies to increase osteogenesis throughout the implant, modulate the immune system to support repair, and employ shape-fitting tactics to avoid implant micromotion and resultant fibrosis. Improvements to the mineralized collagen scaffolds involve changes in pore size and shape to increase cell migration and osteogenesis and inclusion or delivery of factors to aid vascular ingrowth and bone regeneration.

Soluble extracts from amnion and chorion membranes improve hMSC osteogenic response in a mineralized collagen scaffold

“…The mechanics of low-density open-cell foams dictates that scaffold micromechanics required to support cell activity yields sub-optimal macroscale mechanical performance [52]. As a result, we have separately reported a reinforcement strategy that incorporates macroscale reinforcement mesh architectures into these scaffolds to support surgical practicality [53, 54]. These meshes do not influence scaffold microarchitecture or negatively affect cell activity in scaffolds and were not included in this study as we focused on modification to scaffold composition.…”

Remote control of the recruitment and capture of endogenous stem cells by ultrasound for in situ repair of bone defects

“…The healing often fails when the large bone defect exceeds host self-repair capacity, especially for those with trauma, congenital anomalies, and tissue resection due to cancer [ [3] , [4] , [5] ]. Conventional surgical reconstructive procedures using autograft or allograft bone tissues may repair the defects to some degree in anatomical and functional outcomes [ 6 , 7 ]. But these treatment options occasionally bring with some considerable risks to the patients [ [8] , [9] , [10] , [11] ].…”