Repairing damage in the craniofacial skeleton is challenging. Craniofacial bones require intramembranous ossification to generate tissue-engineered bone grafts via angiogenesis and osteogenesis. Here, we designed a mineralized collagen delivery system for BMP-2 and vascular endothelial growth factor (VEGF) for implantation into animal models of mandibular defects. BMP-2/VEGF were mixed with mineralized collagen which was implanted into the rabbit mandibular. Animals were divided into (i) controls with no growth factors; (ii) BMP-2 alone; or (iii) BMP-2 and VEGF combined. CT and hisomputed tomography and histological staining were performed to assess bone repair. New bone formation was higher in BMP-2 and BMP-2-VEGF groups in which angiogenesis and osteogenesis were enhanced. This highlights the use of mineralized collagen with BMP-2/VEGF as an effective alternative for bone regeneration.

Biomaterials regulate macrophages and promote regeneration function, which is a new hot pot in tissue engineering and regenerative medicine. The research based on macrophage materials biology has appeared happy future, but related research on regulating macrophages and promoting tissue regeneration is still in its infancy. The surface roughness of biomaterials is one of the important factors affecting macrophage behavior. Previous study also found that the surface roughness of many biomaterials regulating macrophage polarization, but not including mineralized collagen (MC). In this study, we designed and fabricated MC with different roughness and investigated the influence of MC with different roughness on macrophages. In the study, we found that on the rough surface of MC, macrophages exhibited M1 phenotype-amoeboid morphology and high-level secretory of inflammatory factor (tumor necrosis factor-α and interleukin-6), while smoother surface exhibited M2 phenotype. These data will be beneficial to understand the mechanism deeply and enrich biomaterials tissue regeneration theory, provide a new train of thought biomaterials inducing tissue regeneration and repair and guide the optimum design of new biomaterials, development and reasonable applications.

The effective healing of a bone defect is dependent on the careful coordination of inflammatory and bone-forming cells. In the current work, pro-inflammatory M1 and anti-inflammatory M2 macrophages were co-cultured with primary murine bone mesenchymal stem cells (BMSCs), in vitro, to establish the cross-talk among polarized macrophages and BMSCs, and as well as their effects on osteogenesis. Meanwhile, macrophages influence the osteogenesis of BMSCs through paracrine forms such as exosomes. We focused on whether exosomes of macrophages promote osteogenic differentiation. The results indicated that M1 and M2 polarized macrophage exosomes all can promote osteogenesis of BMSCs. Especially, M1 macrophage-derived exosomes promote osteogenesis of BMSCs through microRNA-21a-5p at the early stage of inflammation. This research helps to develop an understanding of the intricate interactions among BMSCs and macrophages, which can help to improve the process of bone healing as well as additional regenerative processes by local sustained release of exosomes.

Photothermal therapy (PTT) has emerged as a promising cancer therapeutic method. In this study, Arg-Gly-Asp (RGD) peptide-conjugated polydopamine-coated gold nanostars (Au@PDA-RGD NPs) were prepared for targeting PTT of hepatocellular carcinoma (HCC). A polydopamine (PDA) shell was coated on the surface of gold nanostars by the oxidative self-polymerization of dopamine (termed as Au@PDA NPs). Au@PDA NPs were further functionalized with polyethylene glycol and RGD peptide to improve biocompatibility as well as selectivity toward the HCC cells. Au@PDA-RGD NPs showed an intense absorption at 822 nm, which makes them suitable for near-infrared-excited PTT. Our results indicated that the Au@PDA-RGD NPs were effective for the PTT therapy of the α_Vβ₃ integrin receptor-overexpressed HepG2 cells in vitro. Further antitumor mechanism studies showed that the Au@PDA-RGD NPs-based PTT induced human liver cancer cells death via the mitochondrial–lysosomal and autophagy pathways. In vivo experiments showed that Au@PDA-RGD NPs had excellent tumor treatment efficiency and negligible side effects. Thus, our study showed that Au@PDA-RGD NPs could offer an excellent nanoplatform for PTT of HCC.

The design of a novel interpenetrating network hydrogel inspired by the microscopic architecture of natural cartilage based on a supramolecular sodium alginate (SA) nanofibril network is reported in this paper. The mechanical strength and toughness of the poly(vinyl alcohol) (PVA) hydrogel were significantly improved after being incorporated with the alginate nanofibril network. The multiple hydrogen bonds between PVA chains and alginate fibers provided an efficient energy dissipation, thus leading to a significant increase in the mechanical strength of the PVA/SA/NaCl hydrogel. The PVA/SA/NaCl hydrogel demonstrated superior water-lubrication and load-bearing performance due to noncovalent interactions compared with pure PVA hydrogels. Moreover, the bioactivity of the PVA/SA/NaCl hydrogel was proved by the MC3T3 cell proliferation and viability assays over 7 days. Therefore, alginate fiber-enhanced hydrogels with high strength and low friction properties are expected to be used as novel biomimetic lubrication materials.

Bone immune responses based on macrophages are critical in the osteogenesis of bone abnormalities. In general, M2 macrophage facilitate the promotion of osteogenesis, as well, M1 macrophage play an important role in early bone healing, as confirmed by previous studies. However, it is not clear how M1 macrophage are involved in the bone immune response. MiR-21a-5p is a highly expressed microRNA in M1 macrophage in contrast to M2. Therefore, the current work sought to ascertain the influence of M1 macrophage on bone healing via exosomal miR-21a-5p and the probable mechanism. We discovered that injecting M1 macrophage exosomes overexpressing miR-21a-5p into bone defect locations enhanced bone regeneration in vivo. Furthermore, by directly targeting GATA2, miR-21a-5p accelerated MC3T3-E1 osteogenic differentiation. Our findings showed that exosomal miR-21a-5p from M1 macrophage may be transported to osteoblasts and target GATA2 to enhance bone defect healing.