The regeneration of bone tissue is regulated by both osteogenic and angiogenic growth factors which are expressed in a coordinated cascade of events. The aim of this study was to create a dual growth factor-release system that allows for time-controlled release to facilitate bone regeneration. We fabricated core−shell SF/PCL/PVA nanofibrous mats using coaxial electrospinning and layer-by-layer (LBL) techniques, where bone morphogenetic protein 2 (BMP2) was incorporated into the core of the nanofibers and connective tissue growth factor (CTGF) was attached onto the surface. Our study confirmed the sustained release of BMP2 and a rapid release of CTGF. Both in vitro and in vivo experiments demonstrated improvements in bone tissue recovery with the dual-drug release system. In vivo studies showed improvement in bone regeneration by 43% compared with single BMP2 release systems. Time-controlled release enabled by the core−shell nanofiber assembly provides a promising strategy to facilitate bone healing.

Silk fibroin is regarded as a natural fibrous protein with tunable mechanical properties, acceptable biocompatibility, and favorable capability of enhancing attachment, proliferation, and differentiation of chondrocytes. These properties make it suitable for the fabrication of scaffolds and a broad range of silk fibroin-based biomaterials for cartilage regenerative therapy, which can heal functional cartilage without scar tissue. It can be used as a single material for making different kinds of scaffolds or as a composite with other types of biomaterials. Together with some growth factors, silk fibroin scaffolds can form a support for the growth and differentiation of seeding cells, such as chondrogenic lineage cells and mesenchymal stem cells. Recent advancements of silk fibroin in cartilage regeneration are summarized in this review. Furthermore, the manufacturing methods of silk fibroin materials and their applications in the regeneration of cartilage are also discussed.

The treatment of massive bone defects is still a significant challenge for orthopedists. Here we have engineered synthetic porous AuPd alloy nanoparticles (pAuPds) as a hyperthermia agent for in situ bone regeneration through photothermal therapy (PTT). After being swallowed by cells, pAuPds produced a mild localized heat (MLH) (40−43 °C) under the irradiation of a nearinfrared laser, which can greatly accelerate cell proliferation and bone regeneration. Almost 97% of the cranial defect area (8 mm in diameter) was covered by the newly formed bone after 6 weeks of PTT. RNA sequencing analysis was used to obtain insight into the molecular mechanism of the MLH on cell proliferation and bone formation. These results demonstrated that the Wnt signaling pathway was involved in the MLH. This Letter provides a unique strategy with mild heat stimulation and high efficiency for in situ bone regeneration.

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Exosomes are extracellular membranous nanovesicles that mediate local and systemic cell-to-cell communication by transporting functional molecules, such as proteins, into target cells, thereby affecting the behavior of receptor cells. Exosomes originating from adipose-derived mesenchymal stem cells (ADSCs) are considered a multipotent and abundant therapeutic tool for tissue injury. To investigate ADSC-secreted exosomes and their potential function in tissue repair, we isolated exosomes from the supernatants of ADSCs via ultracentrifugation, characterized them via transmission electron microscopy, nanoparticle tracking analysis, and Western blot analysis. Then, we determined their protein profile via proteomic analysis. Results showed that extracellular vesicles, which have an average diameter of 116 nm, exhibit a cup-shaped morphology and express exosomal markers. A total of 1,185 protein groups were identified in the exosomes. Gene Ontology analysis indicated that exosomal proteins are mostly derived from cells mainly involved in protein binding. Protein annotation via the Cluster of Orthologous Groups system indicated that most proteins were involved in general function prediction, posttranslational modification, protein turnover, and chaperoning. Further, pathway analysis revealed that most of the proteins obtained participated in metabolic pathways, focal adhesion, regulation of the actin cytoskeleton, and microbial metabolism. Some tissue repair-related signaling pathways were also discovered. The identified molecules might serve as potential therapeutic targets for future studies.

BackgroundHypoxia in the vicinity of bone defects triggers the osteogenic differentiation of precursor cells and promotes healing. The activation of STAT3 signaling in mesenchymal stem cells (MSCs) has similarly been reported to mediate bone regeneration. However, the interaction between hypoxia and STAT3 signaling in the osteogenic differentiation of precursor cells during bone defect healing is still unknown.MethodsIn this study, we assessed the impact of different durations of CoCl2-induced cellular hypoxia on the osteogenic differentiation of MSCs. Role of STAT3 signaling on hypoxia induced osteogenic differentiation was analyzed both in vitro and in vivo. The interaction between cellular hypoxia and STAT3 signaling in vivo was investigated in a mouse femoral bone defect model.ResultsThe peak osteogenic differentiation and expression of vascular endothelial growth factor (VEGF) occurred after 3 days of hypoxia. Inhibiting STAT3 reversed this effect. Hypoxia enhanced the expression of hypoxia-inducible factor 1-alpha (HIF-1α) and STAT3 phosphorylation in MSCs. Histology and μ-CT results showed that CoCl2 treatment enhanced bone defect healing. Inhibiting STAT3 reduced this effect. Immunohistochemistry results showed that CoCl2 treatment enhanced Hif-1α, ALP and pSTAT3 expression in cells present in the bone defect area and that inhibiting STAT3 reduced this effect.ConclusionsThe in vitro study revealed that the duration of hypoxia is crucial for osteogenic differentiation of precursor cells. The results from both the in vitro and in vivo studies show the role of STAT3 signaling in hypoxia-induced osteogenic differentiation of precursor cells and bone defect healing.

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The search for biodegradable and biocompatible materials applied to the antibacterial field has become a significant topic of interest worldwide. In this study, the electrospinning and electrostatic layer-by-layer self-assembly (LBL) techniques were applied to achieve composite mats with enhanced physical and biological properties. Electrospun silk fibroin (SF) was selected as the substrate, and chitosan (CS) and rectorite (REC) were assembled on the surface of the substrate as positively and negatively charged layers via electrostatic LBL. The morphology, composition and structure of the mats were examined, and the results suggested that LBL modification was successful. In addition, the variation of the bilayer numbers and the component of the outmost layer could affect the morphology and the physical and biological properties of LBL mats. Additionally, the morphology and the water contact angle investigation results of the as-prepared mats indicated that the surface features were changed through the LBL process, resulting in a rougher surface than in pure SF mats. Moreover, the mechanical properties of the SF mats were improved after the LBL process. Furthermore, the antibacterial activity of the LBL self-assembled SF mats against E. coli and S. aureus with a concentration of 10 CFU/mL were 84 and 92%, respectively. The cell-culture experiments demonstrated that the mats maintained superior biocompatibility after the introduction of CS and REC.