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Bone Fracture-Treatment Method: Fixing 3D-Printed Polycaprolactone Scaffolds with Hydrogel Type Bone-Derived Extracellular Matrix and β-Tricalcium Phosphate as an Osteogenic Promoter.

ABSTRACT: Bone formation and growth are crucial for treating bone fractures. Improving bone-reconstruction methods using autologous bone and synthetic implants can reduce the recovery time. Here, we investigated three treatments using two different materials, a bone-derived decellularized extracellular matrix (bdECM) and β-tricalcium phosphate (β-TCP), individually and in combination, as osteogenic promoter between bone and 3D-printed polycaprolactone scaffold (6-mm diameter) in rat calvarial defects (8-mm critical diameter). The materials were tested with a human pre-osteoblast cell line (MG63) to determine the effects of the osteogenic promoter on bone formation in vitro. A polycaprolactone (PCL) scaffold with a porous structure was placed at the center of the in vivo rat calvarial defects. The gap between the defective bone and PCL scaffold was filled with each material. Animals were sacrificed four weeks post-implantation, and skull samples were preserved for analysis. The preserved samples were scanned by micro-computed tomography and analyzed histologically to examine the clinical benefits of the materials. The bdECM-β-TCP mixture showed faster bone formation and a lower inflammatory response in the rats. Therefore, our results imply that a bdECM-β-TCP mixture is an ideal osteogenic promoter for treating fractures.

SUBMITTER: Yun S

PROVIDER: S-EPMC8396563 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Biodegradable polycaprolactone/β-tricalcium phosphate (PT) composites are desirable candidates for bone tissue engineering applications. A higher β-tricalcium phosphate (TCP) ceramic content improves the mechanical, hydrophilic and osteogenic properties of PT scaffolds in vitro. Using a dynamic degradation reactor, we established a steady in vitro degradation model to investigate the changes in the physio-chemical and biological properties of PT scaffolds during degradation.PT46 and PT37 scaffolds underwent degradation more rapidly than PT scaffolds with lower TCP contents. In vivo studies revealed the rapid degradation of PT (PT46 and PT37) scaffolds disturbed macrophage responses and lead to bone healing failure. Macrophage co-culture assays and a subcutaneous implantation model indicated that the scaffold degradation process dynamically affected macrophage responses, especially polarization. RNA-Seq analysis indicated phagocytosis of the degradation products of PT37 scaffolds induces oxidative stress and inflammatory M1 polarization in macrophages. Overall, this study reveals that the dynamic patterns of biodegradation of degradable bone scaffolds highly orchestrate immune responses and thus determine the success of bone regeneration. Therefore, through evaluation of the biological effects of biomaterials during the entire process of degradation on immune responses and bone regeneration are necessary in order to develop more promising biomaterials for bone regeneration. Graphical abstract Schematic illustration of the mechanisms of scaffold degradation-mediated macrophage polarization and bone healing processes. A) Degradation of typical PT 55 scaffolds mediates sequential macrophage M1-M2 polarization and a matched “slow early-fast afterwards” bone regeneration mode. B) Degradation of typical PT37 scaffolds mediates ROS generation by macrophages, constant M1 polarization and a disordered “fast initially-slow in late stage” bone regeneration mode.Image 1 Highlights • This work found the vital role of bone scaffolds bio-degradation process in bone regenerative determination.• Excessive polycaprolactone/β-TCP scaffolds degradation disturbed sequential macrophages polarization.• Dynamic degradation model provided a way of investigation of degradation process of PCL/β-TCP scaffolds.• Phagocytosis of degradation products (DPs) by macrophages caused oxidative stress and M1 polarization in macrophages.

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Bone Fracture-Treatment Method: Fixing 3D-Printed Polycaprolactone Scaffolds with Hydrogel Type Bone-Derived Extracellular Matrix and β-Tricalcium Phosphate as an Osteogenic Promoter.

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