The development of functional materials for osteoporosis is ultimately required for bone remodeling. However, grafts were accompanied by increasing pro-inflammatory cytokines that impaired bone formation. In this work, nano-hydroxyapatite (n-HA)/resveratrol (Res)/chitosan (CS) composite microspheres were designed to create a beneficial microenvironment and help improve the osteogenesis by local sustained release of Res. Study of in vitro release confirmed the feasibility of n-HA/Res/CS microspheres for controlled Res release. Notably, microspheres had anti-inflammatory activity evidenced by the decreased expression of pro-inflammatory cytokines TNF-α, IL-1β and iNOS in RAW264.7 cells in a dose dependent manner. Further, enhanced adhesion and proliferation of BMSCs seeded onto microspheres demonstrated that composite microspheres were conducive to cell growth. The ability to enhance osteo-differentiation was supported by up-regulation of Runx2, ALP, Col-1 and OCN, and substantial mineralization in osteogenic medium. When implanted into bone defects in the osteoporotic rat femoral condyles, enhanced entochondrostosis and bone regeneration suggested that the n-HA/Res/CS composite microspheres were more favorable for impaired fracture healing. The results indicated that optimized n-HA/Res/CS composite microspheres could serve as promising multifunctional fillers for osteoporotic bone defect/fracture treatment.

BackgroundAtezolizumab plus bevacizumab has been proved to have promising antitumor activity and tolerable safety in patients with unresectable hepatocellular carcinoma (HCC). Hepatic arterial infusion chemotherapy (HAIC) also demonstrated high response rates and favorable survival for patients with advanced HCC. This study aimed to explore the preliminary clinical efficacy and safety of atezolizumab plus bevacizumab combined with HAIC for patients with treatment-naive advanced HCC.MethodsBetween October 2020 and September 2021, patients with advanced HCC who initially received atezolizumab plus bevacizumab combined with HAIC of oxaliplatin, fluorouracil, and leucovorin (FOLFOX) from three hospitals in China were reviewed for eligibility. The efficacy was evaluated by tumor response rate and survival, and the safety was evaluated by the frequency of key adverse events (AEs).ResultsIn total, 52 eligible patients with advanced HCC who received triple therapy were included in this study. The objective response rates (ORRs) based on mRECIST and RECIST1.1 criteria were 67.3% and 44.2%, respectively. The median progression-free survival (PFS) of patients was 10.6 months (95% CI, 8.37–13.8), and the overall survival (OS) was not reached. Extrahepatic metastasis was an independent risk factor associated with PFS. All AEs were controlled and no treatment-related deaths occurred.ConclusionAtezolizumab plus bevacizumab combined with HAIC-FOLFOX had a significant therapeutic effect and manageable AEs in patients with advanced HCC, which may be a potential treatment option for advanced HCC.

Vascular grafts must avoid negative inflammatory responses and thrombogenesis to prohibit fibrotic deposition immediately upon implantation and promote the regeneration of small diameter blood vessels (<6 mm inner diameter). Here, polyurethane (PU) elastomers incorporating anti-coagulative and anti-inflammatory Gastrodin were fabricated. The films had inter-connected pores with porosities equal to or greater than 86% and pore sizes ranging from 250 to 400 μm. Incorporation of Gastrodin into PU films resulted in desirable mechanical properties, hydrophilicity, swelling ratios and degradation rates without collapse. The released Gastrodin maintained bioactivity over 21 days as assessed by its anti-oxidative capability. The Gastrodin/PU had better anti-coagulation response (less observable BSA, fibrinogen and platelet adhesion/activation and suppressed clotting in whole blood). Red blood cell compatibility, measured by hemolysis, was greatly improved with 2Gastrodin/PU compared to other Gastrodin/PU groups. Notably, Gastrodin/PU upregulated anti-oxidant factors Nrf2 and HO-1 expression in H 2 O 2 treated HUVECs, correlated with decreasing pro-inflammatory cytokines TNF-α and IL-1β in RAW 264.7 cells. Upon implantation in a subcutaneous pocket, PU was encapsulated by an obvious fibrous capsule, concurrent with a large amount of inflammatory cell infiltration, while Gastrodin/PU induced a thinner fibrous capsule, especially 2Gastrodin/PU. Further, enhanced adhesion and proliferation of HUVECs seeded onto films in vitro demonstrated that 2Gastrodin/PU could help cell recruitment, as evidenced by rapid host cell infiltration and substantial blood vessel formation in vivo . These results indicate that 2Gastrodin/PU has the potential to facilitate blood vessel regeneration, thus providing new insight into the development of clinically effective vascular grafts.

No abstract

No abstract