Nano artificial periosteum PCL/Ta/ZnO accelerates repair of periosteum via antibacterial, promoting vascularization and osteogenesis.

The periosteum plays a critical role in bone development, shaping, remodeling, and fracture healing due to its abundance of osteoprogenitor cells, osteoblasts, and capillary network. However, the role of periosteum in bone injury healing has been underestimated, thus there is an urgent need to develop a multifunctional artificial periosteum that mimics the natural one. To tackle this issue, electrospinning technology was employed to fabricate an artificial periosteum composed of Poly-ε-caprolactone (PCL) doped with tantalum (Ta) and zinc oxide (ZnO) nanoparticles to enhance its antibacterial, osteogenic, and angiogenic properties. The in vitro cell experiments have demonstrated that the PCL/Ta/ZnO artificial periosteum exhibits excellent biocompatibility and can effectively facilitate osteogenic differentiation of BMSCs as well as angiogenic differentiation of EPCs. Antibacterial experiments have demonstrated the excellent bactericidal effects of PCL/Ta/ZnO artificial periosteum against both S. aureus and E. coli. The subcutaneous infection and critical-sized skull bone defect models have validated its in vivo properties of antibacterial activity, promotion of osteogenesis, and angiogenic potential. The PCL/Ta/ZnO artificial periosteum demonstrates remarkable efficacy in infection control and favorable immunomodulation, thereby achieving rapid vascularized bone repair. In conclusion, the utilization of PCL/Ta/ZnO tissue-engineered periosteum has been demonstrated to exhibit antibacterial properties, pro-vascularization effects, and promotion of osteogenesis at the site of bone defects. This promising approach could potentially offer effective treatment for bone defects.

The bio-functionalized membrane loaded with Ta/WH nanoparticles promote bone regeneration through neurovascular coupling.

Electrospinning technology, as a novel approach, has been extensively applied in the field of tissue engineering. Nanofiber membranes prepared by electrospinning can effectively mimic the structure and function of natural bone matrix, providing an ideal scaffold for attachment, proliferation, and differentiation of bone cells while inducing osteogenic differentiation and new bone formation. However, it lacks bioactivities such as osteoinduction, angiogenesis and the ability to promote nerve regeneration. In the presence of complex critical bone defects, a single component electrospun membrane often fails to suffice for bone repair needs. Based on this, we prepared a biofunctionalized membrane loaded with Tantalum(Ta)/Whitlockite(WH) nanoparticles (poly-ε-caprolactone (PCL)/Ta/WH) in order to promote high-quality bone defect repair through neurovascular coupling effect. According to the results of in vitro and in vivo experiments, the early Mg2+ release of WH can effectively increase the local nerve and vascular density, and synergize with Tantalum nanoparticles (TaNPs) to create a rich nerve-vascular microenvironment. This allows the PCL/Ta/WH membrane to repair bone defects in multiple dimensions and achieve high-quality repair of bone tissue, providing new solutions for the treatment of critical bone defects in clinical.

Fabrication, bacteriostasis and osteointegration properties researches of the additively-manufactured porous tantalum scaffolds loading vancomycin.

Infected bone defects (IBDs) remains a challenging problem for orthopedists. Clinically, routine management for IBDs has two stages: debridement and systematic antibiotics administration to control infection, and secondary grafting to repair bone defects. Whereas the efficacy is not satisfactory, because the overuse of antibiotics may lead to systemic toxicity, and the emergence of drug-resistant bacteria, as well as the secondary surgery would cause additional trauma and economic burden to the patients. Therefore, it is imperative to develop a novel scaffold for one-stage repair of IBDs. In this study, vancomycin (Van) was encapsulated into poly(lactic co-glycolic acid) (PLGA) microspheres through the double emulsion method, which were then loaded into the additively-manufactured porous tantalum (AM-Ta) through gelatin methacryloyl (GelMA) hydrogel to produce the composite Ta/GelMA hydrogel (Gel)/PLGA/vancomycin(Van) scaffolds for repairing IBDs. Physiochemical characterization of the newly-developed scaffold indicated that the releasing duration of Van was over 2 weeks. Biological experiments indicated good biocompatibility of the composite scaffold, as well as bacteriostasis and osteointegration properties, which showed great potential for clinical application. The construction of this novel scaffold would provide new sight into the development of orthopaedic implants, shedding a novel light on the treatment of IBDs.

Tantalum and magnesium nanoparticles enhance the biomimetic properties and osteo-angiogenic effects of PCL membranes.

Segmental bone defects, accompanied by periosteum stripping or injury, usually lead to delayed bone union or nonunion, which have challenged orthopedic surgeons. The periosteum, which provides essential blood supply and initial stem cells for bone tissue, plays an important role in the repair of bone defects. The reconstruction of the destroyed periosteum has attracted the attention of researchers exploring more satisfactory therapies to repair bone defects. However, periosteum-like biomaterials have yet to meet the clinical requirements and resolve this challenging problem. In this study, we manufactured a nanofiber periosteum replacement based on poly-ε-caprolactone (PCL), in which tantalum nanoparticles (TaNPs) and nanoscale magnesium oxide (MgO) were introduced to enhance its osteogenic and angiogenic ability. The results of in vitro experiments indicated that the PCL/Ta/MgO periosteum replacement, with excellent cytocompatibility, promoted the proliferation of both bone marrow mesenchymal stem cells (BMSCs) and endothelial progenitor cells (EPCs). Furthermore, the incorporation of TaNPs and nano-MgO synergistically enhanced the osteogenic differentiation of BMSCs and the angiogenic properties of EPCs. Similarly, the results of in vivo experiments from subcutaneous implantation and critical-sized calvarial defect models showed that the PCL/Ta/MgO periosteum replacement combined the osteogenesis and angiogenesis abilities, promoting vascularized bone formation to repair critical-sized calvarial defects. The results of our study suggest that the strategy of stimulating repairing bone defects can be achieved with the periosteum repaired in situ and that the proposed periosteum replacement can act as a bioactive medium to accelerate bone healing.

The optimization of pepsin processing time to balance the mechanical and biological properties of xenogeneic bone.

Xenogeneic bone showed great prospects to treat large bone defects due to its bionic composition and structure, but the immunogenicity limited its wide applications. Previously, we developed a pepsin treating method to eliminate the immunogenicity of xenogeneic bone. In this study, we further investigated the effect of pepsin processing time on the biological and mechanical properties. The results indicated that increased pepsin treating time impaired the mechanical properties of xenogeneic bone. And MC3T3-E1 cells showed enhanced adhesion ability, as well as increased production of alkaline phosphatase and calcium nodulus production on the xenogeneic bone processed by pepsin for 24 hr (P24), as compared with xenogeneic bone processed by pepsin for 30 hr (P30) and 36 hr (P36). In addition, we found no significant inflammatory responses after implanting different xenogeneic bone into the intermuscular site of rats. These results suggested that xenogeneic bone processed by pepsin for 24 hr may be a preferable choice when using the xenogeneic bone as biomaterials for further researches.