Background
Immune responses and osteogenesis differentiation induced by implants are crucial for bone tissue regeneration. Consideration of only one of those properties is not sufficient. To investigate the synergistic actions, we designed alginate/graphene oxide/sericin/nanohydroxyapatite (Alg/GO/Ser/nHAP) nanocomposite hydrogels with both osteoimmunomodulatory and osteoinductive activities. This study aimed to explore the effect of hydrogel with osteoimmunomodulatory properties on promoting osteogenesis of bone marrow stem cells (BMSCs).
Methods
Alg/GO/Ser/nHAP nanocomposite hydrogel was fabricated and was characterized by SEM, FTIR, XRD, stress-strain, rheology, swelling and degradation. After the impact of sericin on M2 macrophage polarization was identified, the BMSCs viability and adhesion were evaluated by CCK8 assay, live/dead staining, cytoskeleton staining. The cell osteogenic differentiation was observed by ALP/ARS staining, immunofluorescence staining, RT-PCR, and Western blotting, respectively. Rat cranial defect model was used to assess osteoimmunomodulatory effects of scaffolds in vivo by micro‑computed tomographic, histological, and immunohistochemical analyses after 8 weeks of healing.
Results
In vitro experiments revealed that the hydrogel presented desirable mechanical strength, stability, porosity, and biocompatibility. Significantly, sericin and nHAP appeared to exert synergistic effects on bone regeneration. Sericin was observed to inhibit the immune response by inducing macrophage M2-type polarization to create a positive osteoimmune microenvironment, contributing to improving osseointegration at the bone-implant interface to promote osteogenesis. However, the osteogenic differentiation in rat BMSCs was further enhanced by combining nHAP and sericin in the nanocomposite hydrogel. Eventually, the hydrogel was implanted into the rat cranial defect model, assisting in the reduction of local inflammation and efficient bone regeneration.
Conclusion
The nanocomposite hydrogel stimulated bone formation by the synergistic effects of immunomodulation of macrophage polarization by sericin and direct osteogenic induction by nHAP, demonstrating that such a scaffold that modulates the osteoimmune microenvironment to promote osteogenesis is a promising approach for the development of bone tissue engineering implants in the future.
Background
Oxidative stress status may affect bone metabolism and regeneration. However, few studies reported whether oxidative stress could impact the outcomes of hip fractures. This study aimed to explore if superoxide dismutase and glutathione reductase, the critical antioxidant enzymes, correlated with the prognosis of hip fractures.
Methods
Patients with hip fractures were extracted from our database, and those who met the inclusion criteria were analyzed. Propensity score matching was used to reduce the influence of confounding factors, and ROC curves based on matched populations were created to determine the optimal cutoff points of SOD and GR. Then, outcomes between SOD or GR and outcomes of hip fractures were compared.
Results
Out of 301 patients enrolled in this study, 50 patients died within one year. After a 1:1 PSM, the patients with less than 1-year survival had significantly lower SOD (p = 0.026) and GR (p = 0.021) than those who were still alive at one year. Logistics analysis showed that low SOD and low GR may be independent risk factors for 6-month survival, 1-year survival, 6-month free walking ability, and 1-year free walking ability.
Conclusion
SOD and GR may be the independent risk factors for survival and walking abilities of hip fractures.
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