Bone regeneration is still one of the greatest challenges for the treatment of bone defects since no current clinical approach has been proven effective. To develop an alternative biodegradable bone graft material, multiarm polyethylene glycol (PEG) crosslinked hyaluronic acid (HA) hydrogels are synthesized and applied to promote osteogenesis of mesenchymal stem cells (MSCs) with the ultimate goal for bone defect repair. The multiarm PEG‐HA hydrogels provide a significant improvement of alkaline phosphatase (ALP) activity and calcium mineralization of the in vitro encapsulated MSCs under osteogenic condition after 3, 7, and 28 days. In addition, the multiarm PEG‐HA hydrogels also facilitate healing of the cranial bone defects more effectively in a Sprague Dawley rat model after 10 weeks of implantation based on histological evaluations and microcomputed tomography analysis. These promising results set the stage for the development of innovative biodegradable hydrogels to provide a more effective and versatile treatment option for bone regeneration.

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Background: Neuroinflammation, autophagy, NLRP3 inflammasome, and microglia polarizationhave been implicated in spinal cord injury (SCI).Moreover, exosomes, a classic nanovesicles secreted by MSCs, may have a neuroprotective effect on transformation of microglia from the M1 state to the M2 phenotype. However, the effect of MSCs derived exosomes on neuroinflammation is still unclear. Here, we investigated the mechanisms of MSCs derived exosomes mediated NLRP3 inflammasome signaling cascades and its protective effects in SCI. Methods:The SCI model was performed by weight-drop impact in adult male Sprague-Dawley (SD) rats. Control andexosome rats were randomly subjecttoexosomeadminister (20 mg/kg) or placebo via intraperitoneal route 1 h after SCI.Autophagy inhibitor(3-MA) was administered intraperitoneally 20 min before experiment.Neurological function was measured by Basso-Beattie-Bresnahan (BBB) scoring and an open-field test.Neuronal death was measured by HE stainingandNisslstaining.Inducible nitric oxide synthase (iNOS) levels were determined using fluorescent probes. The autophagy and TXNIP and its downstream signaling pathways-mediated polarization of macrophages/microglia was assessed by immunohistochemistry. Results:Exosome significantly downregulated intracellular iNOS and inhibited TXNIP, pyrin domain-containing 3 (NLRP3) inflammasome pathway activation by activating autophagy. Additionally, Exosomepromoted expression of autophagy markers, such as LC3A/B and beclin1,and abrogated the expression of p62. Autophagy inhibitor, 3-MA, blockage of autophagy flux abolished the inhibition of apoptosis and iNOS/TXNIP/NLRP3 inflammasome axisafterSCI. Here, we demonstrated that exosomeadministration in spinal cord markedly reduced tissue loss, attenuate pathological morphology of the injuredregion, and promoted tissue recovery. Moreover. our resultshowed that exosome administration alleviated neuronal cells apoptosis, and inhibited nitric oxide release in microglia.The activation of inflammatoryresponse in neuronal cells facilitates interactions of iNOS‐NLRP3 andTXNIP‐NLRP3and inhibited NLRP3 inflammasome where neuronal cells apoptosis was induced.Further, we found that exosome could suppress macrophages/microglia polarized to M1 phenotype in vivo and in vitro.Taken together, exosome administration exerts protective effects in neuronal cells through inhibiting iNOS production, and exosome administration could inhibit iNOS/TXNIP/NLRP3 inflammasome axis via enhancing autophagy and both in vitro and in vivo. Conclusions:These resultsreveal that exosometreatment alleviatedneuroinflammation and mitigates neuronal apoptosis via autophagy-mediate inhibition of the iNOS/TXNIP/NLRP3 inflammasome axis. Our findings suggest that exosome may be a novel therapeutic target for treating SCI.

Background: The combination of minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) and recombinant human bone morphogenetic protein 2 (rhBMP-2) is widely used for its advantage of rapid recovery and improved bone fusion. However, no previous study has reported the synergistic effect of MIS-TLIF with rhBMP-2 in patients with degenerative lumbar disease (DLD). Objective: To investigate the radiographic and patient-reported outcomes (PROs) in patients with DLD who underwent MIS-TLIF with and without a low dose of rhBMP-2. Methods: We retrospectively reviewed 48 patients treated with MIS-TLIF from 2013 to 2016. The patients were classified into the rhBMP-2 group (n = 25) and non-rhBMP-2 group (n = 23). Fusion-related parameters were measured before and after the operation. Clinical data included the numeric rating scale (NRS) score, Japanese Orthopedic Association (JOA) scores, and the MOS 36-item short form health survey (SF-36) score, which were documented to evaluate the effect of surgery. Results: In the 48 patients who underwent MIS-TLIF, the operated disc was predominantly at the L4/5 and L5/S1 levels. ADH, MDH, and PDH increased significantly in both groups after surgery (P < 0.05). FH improved in the rhBMP-2 group, but not in the non-rhBMP-2 group. There was no obvious improvement in SA in both groups. Furthermore, the SL showed a significant difference in both groups and a significant improvement over the baseline. The LL showed significant improvement in the two groups at the early follow-up (P < 0.05), but the improvement did not persist. Cage subsidence had no significant effect on different subsidence grades. In addition, no differences in cage subsidence were observed in different types of modic change (MC), except for MC 0 in both groups. There was no difference in PROs even though all clinical outcomes improved significantly during the postoperative follow-up period in both groups. Conclusion: MIS-TLIF with the low doses of rhBMP-2 resulted in an improvement in radiographic and clinical results, but not a longer-lasting restoration for radiographic outcomes. Cage subsidence is not associated with the MC. Further, our clinical data demonstrated no difference between both groups.