Oxygen is essential for cell survival and tissue regeneration. Scaffolds releasing oxygen have been hypothesized as an ideal strategy for bone repair. However, excessive oxygen supply will disturb the redox balance, lead to oxidative stress, and affect bone regeneration. In this study, we synthesized a hydrogel from sodium alginate and loaded it calcium peroxide nanoparticles as an oxygen generating material and vitamin C as a pH regulator and antioxidant. The composite hydrogel, with a pH value close to physiological humoral fluid, could release oxygen to alleviate hypoxia in the bone defect and reduce the side effects of excessive hydrogen peroxide. In in vitro experiments, the composite hydrogel promoted the osteogenic differentiation and ALP and mineralization ability of rat bone marrow mesenchymal stem cells in a hypoxic environment (2% O2). In animal experiments, the composite hydrogel was applied in rat skull defect models. It promoted the healing of bone defects. These results suggest that sodium alginate hydrogel releasing oxygen and vitamin C is suitable for cell survival and tissue regeneration in a hypoxic environment and has good application prospects in bone defect repair.

This study introduces hyaluronic acid-based (HA) hydrogel microspheres loaded with zinc oxide nanoparticles (ZnO-NPs) for the treatment of infectious bone defects. The microspheres were fabricated using a 3D-printing process, with a formulation consisting of 6 wt% HAD (methacrylated HA), 3 wt% AOHA (AMP-conjugated oxidized HA), 1 % BOHA (phenylboric acid-conjugated HA), 0.5 % photoinitiator, and 0.05 % ZnO-NPs. In vitro, the hydrogel microspheres demonstrated significant antibacterial activity against Staphylococcus aureus, with colony counts and biofilm inhibition assays showing a marked reduction in bacterial growth after 12 and 24 h. The release of antimicrobial peptides (AMPs) was enhanced in acidic conditions and in the presence of hyaluronidase. The microspheres also promoted osteogenic differentiation of bone marrow stromal cells (BMSCs), as evidenced by increased expression of osteogenic markers (ALP, OCN, OPN, and COL-1). In vivo, the hydrogel microspheres were tested in a rat skull defect model, showing significant bone regeneration, improved angiogenesis, and an anti-inflammatory response. These results indicate that ABOHA@ZnO hydrogel microspheres provide a promising strategy for treating infectious bone defects by combining antimicrobial, osteogenic.

Increased intracranial pressure after traumatic brain injury (TBI) is an urgent problem in clinical practice. A pliable hydrogel is preferred for cranioplasty applications after TBI since it can protect brain tissue and promote bone healing. Nevertheless, biohydrogels for cranial bone regeneration still face challenges of poor mechanical properties, large swelling ratios, and low osteogenesis activity. Herein, inspired by Hofmeister effects, biopolymer hydrogels composed of protein and polysaccharides were treated with a Hofmeister series including a series of monovalent and divalent anions. Our results reveal that the divalent anion-cross-linked biohydrogels exhibit stronger mechanical properties and lower swelling ratios compared with monovalent-anion treated gels. Intriguingly, the divalent HPO42- anion induced biohybrid hydrogels with excellent mechanical behaviors (3.7 ± 0.58 MPa, 484 ± 76.7 kPa, and 148.3 ± 6.85 kJ/m3), anti-swelling capability (16.7%), and gradual degradation ability, significantly stimulating osteogenic differentiation and in vivo cranial bone regeneration. Overall, this study may provide new insights into the design of biomimetic hydrogels for treating cranial bone defects after TBI.

Although 3D printed scaffolds are widely used in irregularly shaped bone defects, additional steps often need to be introduced when fabricating structures with curvature. In contrast, 4D printing has a unique advantage in the fabrication of scaffolding with a curved structure. Bone defects such as skull is generally curved, so a self-bending scaffold would be more appropriate for the cranial defect site. This paper presents a novel self-bending SAGMA hydrogel was loaded with nano-spherical mineralized collagen, then fabricated by a 4D printing method, which achieves adjustable self-bending through three-step crosslinking. When subjected to UV light irradiation, variations in gradient of photo-crosslinking are induced within the scaffold. This gradient of photo-crosslinking serves as the foundation for the scaffold's self-bending. The scaffold exhibited self-bending after crosslinking with calcium ions and chitosan, respectively, with curvature ranging from 0.05 mm-1 to 0.446 mm-1. In vivo experiments demonstrated the efficacy of the scaffold in enhancing the repair of cranial bone defects and promoting new bone formation in rats, as evidenced by microcomputed tomography and histochemical analysis. Therefore, this self-bending scaffold provides a potentially effective method for the clinical treatment of skull defects with curvature.

Tissue engineering employs the use of bioactive materials to facilitate the filling and acceleration of bone defect healing, thereby introducing novel concepts to the field of in situ bone repair. Some studies have shown that periosteum plays an important role in bone regeneration and repair. In this study, biomimetic periosteum-bone scaffolds were prepared by depositing poly-L-lactic acid (PLLA) electrospun fibers on the surface of the gelatin/chitosan cryogel to mimic the bone and periosteum structure, respectively. To improve the bioactivity of the scaffold, bone morphogenetic protein-2 (BMP-2) was loaded into a loose porous mesh-like cryogel, while platelet-derived growth factor-BB (PDGF-BB) was encapsulated in the core of PLLA nanofibers with core-shell structure. Both of these two growth factors were released locally at the site of bone defect, where they exert a synergistic effect on osteogenesis, thereby greatly accelerating bone healing. The in vitro experiments demonstrated that the biomimetic periosteum-bone scaffolds exhibited favourable biocompatibility and osteogenesis ability. Furthermore, the in vivo experiments indicated that the composite scaffold repaired rat skull defects in a more rapid and effective manner. In conclusion, biomimetic periosteum-bone scaffolds with codelivery of BMP-2 and PDGF-BB shows significant potential for bone regeneration.