Biomimetic scaffolds for vascularized bone regeneration in load-bearing bones
Creators: name: Madhavarapu, Shreya
Publisher: name: No Publisher Supplied
Year: 2025

description: Significant bone loss due to trauma, infection, tumor invasion, or degenerative diseases often results in large bone defects that are challenging to treat. Typically, autografts or allografts are used to reconstruct these defects and promote bone regeneration. However, autografts are limited in availability and require additional harvesting surgeries, increasing pain and resulting in donor site morbidity, while allografts carry the risk of disease transmission and immune rejection. Synthetic grafts, particularly metallic and ceramic implants, have been explored as alternatives, but a mismatch in mechanical properties and poor integration with native bone have limited their success. These challenges were addressed by developing biodegradable, 3D-printed scaffolds that mimic trabecular and cortical architectures of native bone. The scaffolds were mineralized to promote osteogenesis, and prevascularized lumens were developed within the cortical osteons to promote angiogenesis. Mechanical testing showed that the compressive yield stress and compressive modulus values of the trabecular portion matched those of native trabecular bone, while the cortical portion demonstrated greater strength. The complete scaffold exhibited mechanical properties superior to trabecular bone but slightly below those of native whole bone. It was hypothesized that when used with existing surgical techniques that use internal or external fixation devices, these scaffolds would be sufficiently strong to allow immediate load bearing. The ability of the scaffolds to support capillary action was studied to develop cell-free scaffolds. The osteogenic and angiogenic capabilities were successfully tested in vitro, followed by in vivo evaluation of the scaffolds in a rabbit critical-sized radial defect load-sharing model. The mineralized, prevascularized scaffolds were implanted with and without the addition of autologous bone marrow, with allografts serving as controls. Progressive bone regeneration was observed through biweekly X-ray images and live CT imaging at 12, 16, and 20 weeks. Scaffolds seeded with bone marrow showed greater new bone infiltration into the scaffold structure. Histological analysis showed mineralized bone tissue growth within the scaffold and the presence of blood vessels. Positive immunostaining for CD31 and vWF further validated vascularization, which was observed in both scaffold groups. In allografts, vascularization was limited to the scaffold-native bone interfaces, with minimal vascularization in the middle portion, demonstrating that the scaffolds were more successful in promoting vascularized bone regeneration compared to the allografts. By combining structural mimicry and biological functionality, these scaffolds address key challenges in bone tissue regeneration, offering a promising bone graft alternative for vascularized bone regeneration and load-bearing applications. Furthermore, this work demonstrates the feasibility of scaffolds that are easily scalable, cell-free, and compatible with existing surgical methods, facilitating seamless translation to clinical applications.