Hui Zeng

Intra-articular injection of therapeutics is an effective strategy for treating osteoarthritis (OA), but it is hindered by rapid drug diffusion, thereby necessitating high-frequency injections. Hence, the development of a biofunctional hydrogel for improved delivery is required. In this study, we introduce a liposome-anchored teriparatide (PTH (1-34)) incorporated into a gallic acid-grafted gelatin injectable hydrogel (GLP hydrogel). We show that the GLP hydrogel can form in situ and without affecting knee motion after intra-articular injection in mice. We demonstrate controlled, sustained release of PTH (1-34) from the GLP hydrogel. We find that the GLP hydrogel promotes ATDC5 cell proliferation and protects the IL-1β-induced ATDC5 cells from further OA progression by regulating the PI3K/AKT signaling pathway. Further, we show that intra-articular injection of hydrogels into an OA-induced mouse model promotes glycosaminoglycans synthesis and protects the cartilage from degradation, supporting the potential of this biomaterial for OA treatment.

Natural polysaccharide (NPH)-based injectable hydrogels have shown great potential for critical-sized bone defect repair. However, their osteogenic, angiogenic, and mechanical properties are insufficient. Here, MgO nanoparticles (NPs) were incorporated into a newly synthesized water-soluble phosphocreatine-functionalized chitosan (CSMP) water solution to form an injectable hydrogel (CSMP-MgO) via supramolecular combination between phosphate groups in CSMP and magnesium in MgO NPs to circumvent these drawbacks of chitosan-based injectable hydrogels. Water-soluble chitosan deviate CSMP was first synthesized by grafting methacrylic anhydride and phosphocreatine into a chitosan chain in a one-step lyophilization process. The phosphocreatine in this hydrogel not only provides sites to combine with MgO NPs to form supramolecular binding but also serves as the reservoir to control Mg2+ release. As a result, the lyophilized CSMP-MgO hydrogels presented a porous structure with some small holes in the pore wall, and the pore diameters ranged from 50 to 100 μm. The CSMP-MgO injectable hydrogels were restricted from swelling in DI water (lowest swelling ratio was 16.0 ± 1.1 g/g) and presented no brittle failure during compression even at a strain above 85% (maximum compressive strength was 195.0 kPa) versus the control groups (28.0 and 41.3 kPa for CSMP and CSMP-MgO (0.5) hydrogels), with regulated Mg2+ release in a stable and sustained manner. The CSMP-MgO injectable hydrogels promoted in vitro calcium phosphate (hydroxyapatite (HA) and tetracalcium phosphate (TTCP)) deposition in supersaturated calcium phosphate solution and presented no cytotoxicity to MC3T3-E1 cells; the CSMP-MgO hydrogel promoted MC3T3-E1 cell osteogenic differentiation with upregulation of BSP, OPN, and Osterix osteogenic gene expression and mineralization and HUVEC tube formation. Among them, CSMP-MgO (5) presented most of these properties. Moreover, this hydrogel (CSMP-MgO (5)) showed an excellent ability to promote new bone formation in critical-sized calvarial defects in rats. Thus, the CSMP-MgO injectable hydrogel shows great promise for bone regeneration.

Microcystins have been reported to be carcinogenic by animal and cell experimentation, but there are no data on the linkage between serum microcystins and hepatocellular carcinoma (HCC) risk in humans. We conducted a clinical case-control study to investigate the association between serum microcystins and HCC risk after controlling several known risk factors, such as hepatitis B virus, alcohol, and aflatoxin. From December 2013 to May 2016, 214 patients newly diagnosed with HCC along with 214 controls (frequency-matched by age and sex) were recruited from three hospitals in Chongqing, southwest China. Basic information on lifestyle and history of disease was obtained by questionnaire. Blood samples were collected and analyzed for serum microcystin-LR (MC-LR) and aflatoxin-albumin adduct by enzyme-linked immunosorbent assay and for hepatitis B surface antigen status by chemiluminescence assay. Binary logistic regression analyses were performed to assess the independent effects of MC-LR and its joint effects with other factors on HCC risk. The adjusted odds ratio for HCC risk by serum MC-LR was 2.9 (95% confidence interval [CI], 1.5-5.5) in all patients. Notably, a clear relationship between increased MC-LR level (Q2, Q3, and Q4) and HCC risk was observed with elevated adjusted odds ratios (1.3, 2.6, and 4.0, respectively). Positive interactions with the additive model were investigated between MC-LR and hepatitis B virus infection (synergism index = 3.0; 95% CI, 2.0-4.5) and between MC-LR and alcohol (synergism index = 4.0; 95% CI, 1.7-9.5), while a negative interaction was found between MC-LR and aflatoxin (synergism index = 0.4; 95% CI, 0.3-0.7). Additionally, serum MC-LR was significantly associated with tumor differentiation (r = -0.228, P < 0.001). CONCLUSION: We provide evidence that serum MC-LR was an independent risk factor for HCC in humans, with an obvious positive interaction with hepatitis B virus and alcohol but a negative interaction with aflatoxin. (Hepatology 2017;66:1519-1528).