Even small cartilage defects could finally degenerate to osteoarthritis if left untreated, owing to the poor self-healing ability of articular cartilage. Stem cell transplantation has been well implemented as a common approach in cartilage tissue engineering but has technical complexity and safety concerns. The stem cell homing-based technique emerged as an alternative promising therapy for cartilage repair to overcome traditional limitations. In this study, we constructed a composite hydrogel scaffold by combining an oriented acellular cartilage matrix (ACM) with a bone marrow homing peptide (BMHP)-functionalized self-assembling peptide (SAP). We hypothesized that increased recruitment of endogenous stem cells by the composite scaffold could enhance cartilage regeneration.Methods: To test our hypothesis, in vitro proliferation, attachment and chondrogenic differentiation of rabbit mesenchymal stem cells (MSCs) were tested to confirm the bioactivities of the functionalized peptide hydrogel. The composite scaffold was then implanted into full-thickness cartilage defects on rabbit knee joints for cartilage repair, in comparison with microfracture or other sample groups. Stem cell recruitment was monitored by dual labeling with CD29 and CD90 under confocal microcopy at 1 week after implantation, followed by chondrogenic differentiation examined by qRT-PCR. Repaired tissue of the cartilage defects was evaluated by histological and immunohistochemistry staining, microcomputed tomography (micro-CT) and magnetic resonance imaging (MRI) at 3 and 6 months post-surgery. Macroscopic and histological scoring was done to evaluate the optimal in vivo repair outcomes of this composite scaffold.Results: The functionalized SAP hydrogels could stimulate rabbit MSC proliferation, attachment and chondrogenic differentiation during in vitro culture. At 7 days after implantation, increased recruitment of MSCs based on CD29+ /CD90+ double-positive cells was found in vivo in the composite hydrogel scaffold, as well as upregulation of cartilage-associated genes (aggrecan, Sox9 and type II collagen). After 3 and 6 months post-surgery, the articular cartilage defect in the composite scaffold-treated group was fully covered with cartilage-like tissue with a smooth surface, which was similar to the surrounding native cartilage, according to the results of histological and immunohistochemistry staining, micro-CT and MRI analysis. Macroscopic and histological scoring confirmed that the quality of cartilage repair was significantly improved with implantation of the composite scaffold at each timepoint, in comparison with microfracture or other sample groups.Conclusion: Our findings demonstrated that the composite scaffold could enhance endogenous stem cell homing and chondrogenic differentiation and significantly improve the therapeutic outcome of chondral defects. The present study provides a promising approach for in vivo cartilage repair without cell transplantation. Optimization of this strategy may offer great potential and benefits for cl...

In situ tissue regeneration by homing endogenous reparative cells to the injury site has been extensively researched as a promising alternative strategy to facilitate tissue repair. In this study, a promising scaffolding system DCM-RAD/ SKP, which integrated a decellularized cartilage matrix (DCM)-derived scaffold with a functionalized self-assembly Ac-(RADA) 4 -CONH 2 /Ac-(RA-DA) 4 GGSKPPGTSS-CONH 2 (RAD/SKP) peptide nanofiber hydrogel, was designed for repairing rabbit osteochondral defect. In vitro experiments showed that rabbit bone marrow stem cells migrated into and have higher affinity toward the functional scaffolding system DCM-RAD/SKP than the control scaffolds. One week after in vivo implantation, the functional scaffolding system DCM-RAD/SKP facilitated the recruitment of endogenous mesenchymal stem cells within the defect site. Moreover, gene expression analysis indicated that the DCM-RAD/SKP promoted chondrogenesis of the recruited cells. In vivo results showed that the DCM-RAD/SKP achieved superior hyaline-like cartilage repair and successful subchondral bone reconstruction. By contrast, the control groups mostly led to fibrous tissue repair. These findings indicate that the DCM-RAD/SKP can recruit endogenous stem cells into the site of cartilage injury and promote differentiation of the infiltrating cells into the chondrogenic lineage, holding great potential as a one-step surgery strategy for cartilage repair.

The influence of glucagon-like peptide-1 has been studied in several studies in patients with acute myocardial infarction, but not in patients with non-ST-segment elevation myocardial infarction (NSTEMI). We planned to evaluate the effects of liraglutide on left ventricular function in patients with NSTEMI. A total of 90 patients were randomized 1:1 to receive either liraglutide (0.6 mg for 2 days, 1.2 mg for 2 days, followed by 1.8 mg for 3 days) or placebo for 7 days. Eighty-three patients completed the trial. Transthoracic echocardiography was used to assess left ventricular function. At 3 months, the primary endpoint, the difference in the change in left ventricular ejection fraction between the two groups was +4.7 % (liraglutide vs. placebo 95 % CI +0.7 to +9.2 % P = 0.009) under intention-to-treat analysis. The difference in decrease in serum glycosylated hemoglobin levels was -0.2 % (liraglutide vs. placebo 95 % CI -0.1 to -0.3 %; P < 0.001). Inflammation and oxidative stress improved significantly in the liraglutide group compared to the placebo group. Liraglutide could improve left ventricular function in patients with NSTEMI, making it a potential adjuvant therapy for NSTEMI.

We developed the functionalized self-assembling peptide nanofiber hydrogel RAD/KLT/RGI that was dual-functionalized with VEGF- and BDNF-mimetic peptide epitopes for peripheral nerve regeneration.