Osteoarthritis (OA) is a common joint disease characterized by progressive loss of cartilage and reduction in lubricating synovial fluid, which lacks effective treatments currently. Here, we propose a hydrogel-based miRNA delivery strategy to rejuvenate impaired cartilage by creating a regenerative microenvironment to mitigate chondrocyte senescence that mainly contributes to cartilage breakdown during OA development. An aging-related miRNA, miR-29b-5p, was first found to be markedly down-regulated in OA cartilage, and their up-regulation suppressed the expression of matrix metalloproteinases and senescence-associated genes ( P16 INK4a /P21 ) via ten-eleven-translocation enzyme 1 (TET1). An injectable bioactive self-assembling peptide nanofiber hydrogel was applied to deliver agomir-29b-5p, which was functionalized by conjugating a stem cell–homing peptide SKPPGTSS for endogenous synovial stem cell recruitment simultaneously. Sustained miR-29b-5p delivery and recruitment of synovial stem cells and their subsequent differentiation into chondrocytes led to successful cartilage repair and chondrocyte rejuvenation. This strategy enables miRNA-based therapeutic modality to become a viable alternative for surgery in OA treatment.

The regenerative capacity of the peripheral nervous system is closely related to the role that Schwann cells (SCs) play in construction of the basement membrane containing multiple extracellular matrix proteins and secretion of neurotrophic factors, including laminin (LN) and brain-derived neurotrophic factor (BDNF). Here, we developed a self-assembling peptide (SAP) nanofiber hydrogel based on self-assembling backbone Ac-(RADA) 4 -NH 2 (RAD) dual-functionalized with laminin-derived motif IKVAV (IKV) and a BDNF-mimetic peptide epitope RGIDKRHWNSQ (RGI) for peripheral nerve regeneration, with the hydrogel providing a three-dimensional (3D) microenvironment for SCs and neurites. Methods: Circular dichroism (CD), atomic force microscopy (AFM), and scanning electron microscopy (SEM) were used to characterize the secondary structures, microscopic structures, and morphologies of self-assembling nanofiber hydrogels. Then the SC adhesion, myelination and neurotrophin secretion were evaluated on the hydrogels. Finally, the SAP hydrogels were injected into hollow chitosan tubes to bridge a 10-mm-long sciatic nerve defect in rats, and in vivo gene expression at 1 week, axonal regeneration, target muscular re-innervation, and functional recovery at 12 weeks were assessed. Results: The bioactive peptide motifs were covalently linked to the C-terminal of the self-assembling peptide and the functionalized peptides could form well-defined nanofibrous hydrogels capable of providing a 3D microenvironment similar to native extracellular matrix. SCs displayed improved cell adhesion on hydrogels with both IKV and RGI, accompanied by increased cell spreading and elongation relative to other groups. RSCs cultured on hydrogels with IKV and RGI showed enhanced gene expression of NGF, BDNF, CNTF, PMP22 and NRP2, and decreased gene expression of NCAM compared with those cultured on other three groups after a 7-day incubation. Additionally, the secretion of NGF, BDNF, and CNTF of RSCs was significantly improved on dual-functionalized peptide hydrogels after 3 days. At 1 week after implantation, the expressions of neurotrophin and myelin-related genes in the nerve grafts in SAP and Autograft groups were higher than that in Hollow group, and the expression of S100 in groups containing both IKV and RGI was significantly higher than that in groups containing either IKV or RGI hydrogels, suggesting enhanced SC proliferation. The morphometric parameters of the regenerated nerves, their electrophysiological performance, the innervated muscle weight and remodeling of muscle fibers, and motor function showed that RAD/IKV/RGI and RAD/IKV-GG-RGI hydrogels could markedly improve axonal regeneration with enhanced re-myelination and motor functional recovery through the synergetic effect of IKV and RGI functional motifs. Conclusions: We found that the dual-functionalized SAP hydrogels promoted RSC adhesion, my...

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Study Design. Retrospective comparative study. Objective. This study aimed to compare the clinical effects and imaging features of polymethyl methacrylate (PMMA) bone cement with and without mineralized collagen (MC) in percutaneous kyphoplasty (PKP) for osteoporotic vertebral compression fractures (OVCFs). Summary of Background Data. PKP with PMMA is widely performed for OVCF. However, numerous complications have also been reported about the PMMA bone cement. Moreover, PMMA bone cement with and without MC have not been compared with respect to their postoperative efficacy and long-term follow-up. Methods. From July 2016 to July 2017, 105 OVCF patients were randomly divided into two groups based on their PKP treatment: MC-PMMA group and PMMA group. Clinical operation, cement leakage, Oswestry Disability Index, visual analog scale, height of the fractured vertebrae, Cobb angle, refracture of the adjacent vertebra, recompression, and computed tomography values of the injured vertebra were compared between the two groups postoperatively and after 1-year follow-up. Results. Clinical operation showed no differences between the two groups. Visual analog scale scores, Oswestry Disability Index scores, and Cobb angles showed statistically significant differences between the two groups after 1-year follow-up. The height of the vertebral body showed significant difference at 3 days postoperatively and preoperatively in each group and significant difference after 1 year between the two groups. The rate of refracture and leakage of the MC-PMMA group was lower than that of the PMMA group. The computed tomography value of the MC-PMMA group was obviously higher than that of the PMMA group after 1-year follow-up. Conclusion. MC-modified PMMA did not change the beneficial properties of PMMA. This new bone cement has better biocompatibility, can form a stable structure in the vertebral body, and improve the prognosis of patients by reducing pain and reoperation. Level of Evidence: 3

This work suggested a biofabricated SIS scaffold coated with osteogenic ECM-facilitated bone regeneration with ADSCs synergistically.