Photothermal effective CeO2NPs combined in thermosensitive hydrogels with enhanced antibacterial, antioxidant and vascularization performance to accelerate infected diabetic wound healing.

Chronic diabetic wound healing remains a formidable challenge due to susceptibility to bacterial infection, excessive oxidative stress, and poor angiogenesis. To address these issues, a sodium alginate (SA) based photothermal hydrogel dressing with multifunction was fabricated to facilitate wound treatment. Ceria nanoparticles (CeO2NPs) was synthesized, and their antibacterial performance by near-infrared light triggered photothermal effects was first studied and verified in this work. In addition, to release CeO2NPs to achieve antioxidation and pro-vascularization, thermosensitive gelatin (Gel) was utilized to embed the nanoparticles in advance and then composited in SA hydrogel networks. SA network was finally strengthened by acid soaking to form partially crystalline regions to act as natural crosslinkers. Results showed that the Gel/SA/CeO2 hydrogel displayed temperature-responsive release of CeO2NPs, significant antibacterial and antioxidative activity, as well as the ability to remove without injury and promote infected diabetic wound healing with low cytotoxicity, according to antibacterial investigations, cell studies, and in vivo animal studies. This research offers not only a successful method for quickening the healing of diabetic wounds but also a fresh approach to the general use of CeO2NPs.

An injectable and pH-responsive hyaluronic acid hydrogel as metformin carrier for prevention of breast cancer recurrence.

To achieve the pH-responsive release of metformin in tumor acidic microenvironment, we prepared OHA-Met by covalently grafting metformin (Met) onto oxidized hyaluronic acid (OHA) through imine bonds, and then prepared carboxymethyl chitosan (CMCS)/OHA-Met drug loaded hydrogels. The CMCS/OHA-Met hydrogels showed the in-situ injection performance. At pH = 7.4, the cumulative release rate of metformin from CMCS/OHA-Met20 hydrogel was 42.7 ± 2.6 % in 6 h, and the release tended to balance after 72 h. At pH = 5.5, the release kept constant and the cumulative release rate was 79.3 ± 4.7 % at 6 h, showing good pH-responsive behavior. Metformin induced apoptosis of MCF-7 cells through the caspase 3/PARP pathway. CMCS/OHA-Met20 hydrogel could effectively kill MCF-7 cells, while reducing the cytotoxicity of free metformin to L929 cells. In vivo breast cancer recurrence experiments showed CMCS/OHA-Met20 hydrogel could achieve local injection and pH-responsive smart drug delivery at the tumor resection site, inhibiting breast cancer recurrence. Compared with direct administration, CMCS/OHA-Met20 hydrogel reduced the metformin dosage, frequency of administration and systemic side effects.

Incorporation of NGR1 promotes bone regeneration of injectable HA/nHAp hydrogels by anti-inflammation regulation via a MAPK/ERK signaling pathway.

Suitable bone grafts are commonly required to achieve successful bone regeneration, wherein much effort has been spent to optimize their osteogenesis. Increasing evidence has demonstrated that reducing the levels of TNF-α can enhance bone regeneration at the injury site. Notoginsenoside R1 (NGR1) has been extensively studied in the field of anti-inflammation and regenerative medicine. Nanosized hydroxyapatite (nHAp) possesses excellent biocompatibility and osteoconductivity. In this study, we fabricated a thermoresponsive, injectable hyaluronic acid/nHAp (HA/nHAp) composite hydrogel incorporated with NGR1 to promote bone regeneration. Furthermore, NGR1-HA/nHAp hydrogel could enhance bone regeneration than those of HA and HA/nHAp hydrogels, profited by the underlying osteoblastic mechanism that NGR1 could facilitate activation of the MAPK/ERK signaling pathway and down-regulate the expression of TNF-α, ultimately upregulated expression of osteogenic genes. In summary, the NGR1-HA/nHAp composite hydrogel with controlled inflammation, and excellent osteogenic effect, will have great potential for use in bone regeneration applications.

Liquid Crystal Modified Polylactic Acid Improves Cytocompatibility and M2 Polarization of Macrophages to Promote Osteogenesis.

Liquid crystalline phases (LC phases) are widely present in an organism. The well-aligned domain and liquidity of the LC phases are necessary for various biological functions. How to stabilize the floating LC phases and maintain their superior biology is still under study. In addition, it is unclear whether the exogenous LC state can regulate the immune process and improve osteogenesis. In this work, a series of composite films (PLLA/LC) were prepared using cholesteryl oleyl carbonate (COC), cholesteryl pelargonate (CP), and polylactic acid (PLLA) via a controlled facile one-pot approach. The results showed that the thermo-responsive PLLA/LC films exhibited stable LC phases at human body temperature and the cytocompatibility of the composites was improved significantly after modification by the LC. In addition, the M2 polarization of macrophages (RAW264.7) was enhanced in PLLA/LC films, and the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) was improved as co-cultured with macrophages. The in vivo bone regeneration of the materials was verified by calvarial repair, in which the amount of new bone in the PLLA-30% LC group was greater than that in the PLLA group. This work revealed that the liquid crystal-modified PLLA could promote osteogenesis through immunomodulation.

Sulfated chitosan coated polylactide membrane enhanced osteogenic and vascularization differentiation in MC3T3-E1s and HUVECs co-cultures system.

This study aimed to compare the effects of the two type chitosan derivatives, sulfated chitosan (SCS) and phosphorylated chitosan (PCS), coated on poly(d,l-lactide) (PDLLA) membrane via polydopamine, respectively, on vascularization and osteogenesis in vitro. Mouse preosteoblast cells (MC3T3-E1s) and human umbilical vein endothelial cells (HUVECs) were used as co-cultures system. The effects of two type membranes on calcium deposition, alkaline phosphatase (ALP) activity, vascularization related factors nitric oxide (NO) and angiogenic growth factor vascular endothelial growth factor (VEGF) were assessed. The changes of osteogenic and angiogenic related gene, and protein expression were evaluated too. In fact, SCS modified PDLLA membrane had the highest related gene and protein expression than other PDLLA membranes. Our results demonstrated that the SCS maybe a promising matrix for bone regeneration by co-cultures of ECs and OCs than PCS.