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Multicellularity-interweaved bone regeneration of BMP-2-loaded scaffold with orchestrated kinetics of resorption and osteogenesis
- Niu, Haoyi, Ma, Yifan, Wu, Guangyu, Duan, Bing, Wang, Ying, Yuan, Yuan, Liu, Changsheng
- Biomaterials 2019 v.216 pp. 119216
- X-radiation, bone formation, gadolinium, genes, glass, histology, liver, magnetic resonance imaging, mesenchymal stromal cells, micro-computed tomography, microarray technology, models, osteoclasts, resorption, spleen, tissue repair
- Synchronization of material resorption and new bone formation is vital to achieve harmonious bone regeneration in the treatment of large bone defects. To exposit the resorption/osteogenesis properties in the guided bone repairing, rhBMP-2-loaded trimodal macro/micro/nano-porous bioactive glass scaffolds (TMS-rhBMP-2) were set as substrate model. We penetratingly investigated the particular function of hierarchical structure and incorporated rhBMP-2 in the resorption/osteogenesis, and dissected the cellular interplay throughout the regenerative procedure. The results suggested that rhBMP-2 significantly facilitated osteoclastogenesis-mediated scaffold degradation and strikingly up-regulated mesenchymal stem cells (MSCs)-involved osteogenesis in vitro. Further gene microarray and related proteins expression indicated that in the presence of rhBMP-2, MSCs rather than differentiated MSCs could exert synergistic effects on osteoclastogenesis, osteoclasts maturation and resorptive function; meanwhile, rhBMP-2-induced MSCs osteogenesis was also strengthened by the osteoclasts. In vivo micro-CT, X-ray, kinetic and histological analyses qualitatively and quantitively demonstrated the optimized coupling of bioresorption/osteogenesis and the most rapid regeneration in TMS-rhBMP-2. Consequently, with rhBMP-2 acted as ignitor and MSCs/osteoclasts interaction as booster, a harmonious bone regeneration was obtained. Besides, long-term magnetic resonance imaging (MRI) in virtue of Gd3+ suggested that the degradation products mainly distributed in liver and spleen, verifying the accumulation/discharge profiles and safety application of TMS-rhBMP-2 system in vivo. This study will not merely provide guidance for the design of clinical bone repairing materials, but shed substantial light on the multicell-mediated tissue regeneration.