The reconstruction of severe alveolar bone defects remains a complex and challenging field for clinicians. Three-dimensional-printed scaffolds can adapt precisely to the complicated shape of the bone defects, which is an alternative solution to bone tissue engineering. Our previous study constructed an innovative low-temperature 3D-printed silk fibroin/collagen I/nano-hydroxyapatite (SF/COL-I/nHA) composite scaffold with a stable structure and remarkable biocompatibility. However, the clinical translation of most scaffolds is limited by insufficient angiogenesis and osteogenesis. In this study, we investigated the effects of human umbilical cord mesenchymal-stem-cell-derived exosomes (hUCMSC-Exos) on bone regeneration, especially from the perspective of inducing angiogenesis. HUCMSC-Exos were isolated and characterized. In vitro, the effect of hUCMSC-Exos on the proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) was examined. Moreover, the loading and release of hUCMSC-Exos on 3D-printed SF/COL-I/nHA scaffolds were evaluated. In vivo, hUCMSC-Exos and 3D-printed SF/COL-I/nHA scaffolds were implanted into alveolar bone defects, and bone regeneration and angiogenesis were investigated by micro-CT, HE staining, Masson staining, and immunohistochemical analysis. The results showed that hUCMSC-Exos stimulated HUVEC proliferation, migration, and tube formation in vitro, and the effect increased with increasing exosome concentrations. In vivo, the combination of hUCMSC-Exos and 3D-printed SF/COL-I/nHA scaffolds promoted alveolar bone defect repair by enhancing angiogenesis and osteogenesis. We constructed an elaborate cell-free bone-tissue-engineering system by combining hUCMSC-Exos with 3D-printed SF/COL-I/nHA scaffolds, potentially providing new ideas for treating alveolar bone defects.

One of the most challenging clinical issues continues to be the effective bone regeneration and rebuilding following bone abnormalities. Although osteogenic growth peptide (OGP) has been proven to be effective in promoting osteoblast activity, its clinical application is constrained by abrupt release and easily degradation. We developed a GelMA/HAMA dual network hydrogel loaded with OGP based on a combination of physical chain entanglement and chemical cross-linking effects to produce an efficient long-term sustained release of OGP. The hydrogel polymers were quickly molded under ultraviolet (UV) light and had the suitable physical characteristics, porosity structure and biocompatibility. Significantly, the GelMA/HAMA-OGP hydrogel could promote cell proliferation, adhesion, increase osteogenic-related gene and protein expression in vitro. In conclusion, the OGP sustained-release system based on GelMA/HAMA dual network hydrogel offers a fresh perspective on bone regeneration therapy.

A porous chitosan electret membrane, possessing a three-dimensional porous structure and surface charges, was developed using thermally induced phase separation method and grid-controlled corona charging. Results showed that surface charge release of porous electret membrane could be altered by varying charging voltage. Rat osteoblasts adhered well, and cell proliferation and differentiation were enhanced by porous electret membrane compared to porous uncharged membrane. Furthermore, rabbit calvarial defects model demonstrated that porous electret membrane promoted bone regeneration more significantly than porous uncharged membrane. Therefore, the porous chitosan electret membrane might be a promising material for bone regeneration and bone tissue engineering applications.

Bone metabolism involves complex genetic and cellular processes. While many advances have been made in understanding the molecular mechanisms of osteogenic differentiation, many aspects remain to be fully elucidated. This study investigated the role of CYB5A in promoting osteogenic differentiation of MC3T3-E1 cells and explored the influence of autophagy via the AKT/mTOR/ULK1 signaling pathway. CYB5A expression during osteogenesis was analyzed through bioinformatics, quantitative reverse transcription polymerase chain reaction, and Western blotting. CYB5A was overexpressed or knocked down via plasmid or small interfering RNA transfection, and its effects on cell proliferation, migration, and differentiation were evaluated. Results showed that CYB5A expression increased during differentiation without affecting proliferation. However, CYB5A significantly enhanced cell differentiation by stimulating autophagy, as indicated by an increased ratio of the autophagic marker LC3-II/LC3-I and reduced levels of P62. Mechanistically, CYB5A modulates autophagy by activating ULK1 and reducing active mTOR phosphorylation. Autophagy inhibitors and activators confirmed that the AKT/mTOR/ULK1 pathway mediates CYB5A’s regulatory effects on osteogenesis. This study reveals that CYB5A positively regulates osteogenic differentiation through autophagy, offering insights into bone metabolism mechanisms. These findings suggest that CYB5A is a promising therapeutic target for managing bone metabolic disorders.