Long-lasting, controlled-release, and minimally invasive injectable platforms that provide a stable blood concentration to promote bone regeneration are less well developed. Using hexagonal mesoporous silica (HMS) loaded with dexamethasone (DEX) and poly(lactic-co-glycolic acid) (PLGA), we prepared porous DEX/HMS/PLGA microspheres (PDHP). In contrast to HMS/PLGA microspheres (HP), porous HMS/PLGA microspheres (PHP), DEX/PLGA microspheres (DP), and DEX/HMS/PLGA microspheres (DHP), PDHP showed notable immuno-coordinated osteogenic capabilities and were best at promoting bone mesenchymal stem cell proliferation and osteogenic differentiation. PDHP were combined with methacrylated silk (SilMA) and sodium alginate (SA) to form an injectable photocurable dual-network hydrogel platform that could continuously release the drug for more than 4 months. By adjusting the content of the microspheres in the hydrogel, a zero-order release hydrogel platform was obtained in vitro for 48 days. When the microsphere content was 1%, the hydrogel platform exhibited the best biocompatibility and osteogenic effects. The expression levels of the osteogenic gene alkaline phosphatases, BMP-2 and OPN were 10 to 15 times higher in the 1% group than in the 0% group, respectively. In addition, the 1% microsphere hydrogel strongly stimulated macrophage polarization to the M2 phenotype, establishing an immunological milieu that supports bone regrowth. The aforementioned outcomes were also observed in vivo. The most successful method for correcting cranial bone abnormalities in SD rats was to use a hydrogel called SilMA/SA containing 1% drug-loaded porous microspheres (PDHP/SS). The angiogenic and osteogenic effects of this treatment were also noticeably greater in the PDHP/SS group than in the control and blank groups. In addition, PDHP/SS polarized M2 macrophages and suppressed M1 macrophages in vivo, which reduced the local immune-inflammatory response, promoted angiogenesis, and cooperatively aided in situ bone healing. This work highlights the potential application of an advanced hydrogel platform for long-term, on-demand, controlled release for bone tissue engineering.

Exosomes produced by mesenchymal stem cells (MSCs) have vascular generative properties and are considered new effective candidates for the treatment of bone defects as alternatives to cell therapy. Improving the pro-regenerative function and efficacy of exosomes has been a popular research topic in the field of orthopaedics. We prepared mesoporous bioactive glass (mBG) microspheres via the template method. The ionic products of mBGs used to treat MSCs were extracted, and the effects of exosomes secreted by MSCs on osteoblast (OB) and macrophage (MP) behaviour and bone defect repair were observed in vivo (Micro-CT, H&E, Masson, and immunofluorescence staining for BMP2, COL1, VEGF, CD31, CD163, and iNOS). The mBG spheres were successfully prepared, and the Exo-mBG were isolated and extracted. Compared with those in the blank and Exo-Con groups, the proliferation and osteogenic differentiation of OBs in the Exo-mBG group were significantly greater. For example, on Day 7, OPN gene expression in the Ctrl-Exo group was 3.97 and 2.83 times greater than that in the blank and Exo-mBG groups, respectively. In a cranial defect rat model, Exo-mBG promoted bone tissue healing and angiogenesis, increased M2 macrophage polarisation and inhibited M1 macrophage polarisation, as verified by micro-CT, H&E staining, Masson staining and immunofluorescence staining. These effects may be due to the combination of a higher silicon concentration and a higher calcium-to-phosphorus ratio in the mBG ionic products. This study provides insights for the application of exosomes in cell-free therapy and a new scientific basis and technical approach for the utilisation of MSC-derived exosomes in bone defect repair. Our study demonstrated that exosomes produced by mBG-stimulated MSCs have excellent in vitro and in vivo bone-enabling and immunomodulatory functions and provides insights into the use of exosomes in clinical cell-free therapies.

Recently, biofunctional ions (Mg ²⁺ , Si ⁴⁺ , etc) and graphene derivatives are proved to be promising in stimulating bone formation. In this study, a novel inorganic/organic composite porous scaffold based on silk fibroin (SF), graphene oxide (GO), and calcium magnesium silicate (CMS) was developed for bone repair. The porous scaffolds obtained by lyophilization showed a little difference in pore structure while GO and CMS displayed a good interaction with SF matrix. The addition of CMS with good mineralization potential and sustainedly release ability of biofunctional ions (Ca ²⁺ , Mg ²⁺ and Si ⁴⁺ ) increased the strength of SF scaffolds a little and facilitated the osteogenic differentiation of bone mesenchymal stem cells (BMSCs) by upregulating bone formation-related genes (ALP, COL1, OC and Runx2). The further incorporation of GO in SF scaffolds enhanced the compressive strength and water retention, and also remarkably promoted the osteogenic differentiation of BMSCs. Besides, the angiogenesis of human umbilical vein endothelial cells was significantly promoted by CMS/GO/SF scaffold extract through the upregulation of angiogenesis genes (eNOs and bFGF). Moreover, the osteoclastic formation ability of RAW264.7 cells was suppressed by the released ions from CMS/GO/SF scaffold through the down-regulation of CAK, MMP9 and TRAP. The promoted osteogenesis, angiogenesis and inhibited osteoclastogenesis functions of CMS/GO/SF composite scaffold may enable it as a novel therapy for bone repair and regeneration.

Micropatterned structures on the surface of materials possessing biomimetic properties to mimic the extracellular matrix and induce cellular behaviors have been widely studied. However, it is still a major challenge to obtain internally stable and controllable micropatterned 3D scaffolds for bone repair and regeneration. In this study, 3D scaffolds with regular grating arrays using polycaprolactone (PCL) as a matrix material were prepared by combining 3D printing and soft lithography, and the effects of grating micropatterning on osteogenic differentiation of BMSCs and M1/M2 polarization of macrophages were investigated. The results showed that compared with the planar group and the 30um grating spacing group, PCL with a grating spacing of 20um significantly promoted the osteogenic differentiation of BMSCs, induced the polarization of RAW264.7 cells toward M2 type, and suppressed the expression of M1-type pro-inflammatory genes and markers. In conclusion, we successfully constructed PCL-based three-dimensional scaffolds with stable and controllable micrographs (grating arrays) inside, which possess excellent osteogenic properties and promote the formation of an immune microenvironment conducive to osteogenesis. This study is a step forward to the exploration of bone-filling materials affecting cell behavior, and makes a new contribution to the provision of high-quality materials.

Bioceramic composite polycaprolactone (PCL) scaffolds are widely used in bone defect repair studies. Among them, bioactive glass (BG) is considered an excellent bone-based repair material due to its unique inorganic amorphous structure, bioactivity, and osseointegration properties. However, the dense pores and low specific surface area of ordinary BGs and mesoporous BGs limit the mechanical properties and bioactivity of the overall scaffolds, and it is often necessary to increase the proportion of BGs to offset these shortcomings. Here, we prepared highly active dendritic mesoporous structured bioactive glass (MBG) with a high specific surface area (457.14 m2/g) and pore volume (1.38 cm3/g) by sol-gel method. PCL scaffolds containing different percentages of MBG were prepared by three-dimensional printing technology, and the physicochemical and immunomodulatory osteogenic properties were investigated. The results showed that the low-concentration MBG/ PCL scaffolds with 10% content (10MBG/PCL) possessed the highest compressive strength (about two times that of pure PCL scaffolds) and excellent in vitro immunomodulatory osteogenic properties. Finally, 10MBG/PCL was selected for further exploration to investigate the effects of different fiber diameters (F300, F500, F800) and pore sizes (P200, P500, P800) on the scaffolds performance. Ultimately, we found that the 10MBG/PCL scaffolds with fiber diameter and pore size of 500 μm had high osteogenic potential, significantly induced macrophage polarization toward the M2 phenotype, and downregulated the expression of inflammatory genes and that this group was the most capable of mediating macrophage polarization and thus inducing the osteogenic differentiation of rat bone marrow mesenchymal stem cells (BMSCs) to form an immune microenvironment conducive to osteogenesis. This study is a step forward in the exploration of the performance of BG composite PCL scaffolds and provides a new idea for the development of bone graft materials.

Blockage and infection are common in hospitals, especially with long-term indwelling catheters, due to bacterial adhesion, colonization, and other reasons. A drug-sustained-release antibacterial coating for urinary catheters was described in this paper. Chlorhexidine (CHX) and triclosan (TCS) were encapsulated in poly(lactic-co-glycolic acid) microspheres and mixed with a modified chitosan hydrogel deposited on the surface of silicone rubber. The results showed that drugs can be released continuously more than 35 days. Catechol-modified chitosan (Chi-C) hydrogel was successful synthesized according to FT-IR and UV spectrophotometry, as well as ¹H NMR. Furthermore, the coating with CHX and TCS presented stable antibacterial ability compared to the other groups. The results of CCK-8 revealed that the coating was cytotoxic-free and had a wide range of applications. The findings could provide a new drug sustained-release system and hydrogel-microsphere assembly for urinary catheters. Graphical Abstract