Promotion of Hernia Repair with High-Strength, Flexible, and Bioresorbable Silk Fibroin Mesh in a Large Abdominal Hernia Model

The use of synthetic surgical meshes for abdominal hernia repair presents numerous challenges due to insufficient mechanical strength, nonabsorbability, and implant rigidity that leads to complications including chronic inflammatory reactions and adhesions. In this study, a naturally derived, high-strength, flexible, and bioresorbable silk fibroin mesh was developed by knitted textile engineering and biochemical manipulation. The mechanical properties of the mesh were optimized with the trial of different surface coating methods (thermal or chemical treatment) and 12 different knit patterns. Our silk fibroin mesh showed sufficient tensile strength (67.83 N longitudinally and 62.44 N vertically) which afforded the high mechanical strength required for abdominal hernia repair (16 N). Compared to the commonly used commercial nonabsorbable and absorbable synthetic meshes (Prolene mesh and Ultrapro mesh, respectively), the developed silk fibroin mesh showed advantages over other meshes, including lower elongation rate (47.14% longitudinally and 67.15% vertically, <i>p</i> < 0.001), lower stiffness (10–1000 fold lower, <i>p</i> < 0.001), and lower anisotropic behavior (λ = 0.32, <i>p</i> < 0.001). In a rat model of large abdominal hernia repair, our mesh facilitated effective hernia repair with minimal chronic inflammation which gradually decreased from 15 to 60 days postoperation, as well as lower adhesion formation rate and scores compared to control meshes. There was more abundant and organized collagen deposition, together with more pronounced neovascularization in the repaired tissue treated with silk fibroin mesh as compared to that treated with synthetic meshes. Besides, the silk fibroin mesh gradually transferred load-bearing responsibilities to the repaired host tissue as it was bioresorbed after implantation. Its isotropic architecture favored an ease of use during operations. In summary, our findings indicate that the use of knitted silk fibroin mesh provides a safe and effective alternative solution for large abdominal hernia repairs as it overcomes the prevailing limitations associated with synthetic meshes

Platelets promote cartilage repair and chondrocyte proliferation via ADP in a rodent model of osteoarthritis

<p>Osteoarthritis (OA) is the most common age-related degenerative joint disease and platelet-rich plasma (PRP) has been shown to be beneficial in OA. Therefore, in this study, we aimed to investigate the effects of platelets on chondrocytes and the underlying mechanisms. Anabolic and catabolic activity and the proliferation rate of chondrocytes were evaluated after co-culture with platelets. Chondrocyte gene expression was measured by real-time PCR. Chondrocyte protein expression and phosphorylation were measured by western blot. Chondrocytes treated with or without platelets were transplanted into a rat model of OA induced by intra-articular injection of monosodium iodoacetate and the repair of articular cartilage was evaluated macroscopically and histologically. Platelets significantly promoted the proliferation of chondrocytes, while mildly influencing anabolic and catabolic activity. Chondrocytes co-cultured with platelets showed significantly increased production of bone morphogenetic protein 7 (BMP7). The autocrine/paracrine effect of BMP7 was responsible for the increased proliferation of chondrocytes, via the ERK/CDK1/cyclin B1 signaling pathway. Transplantation of platelet-treated chondrocytes showed better cartilage repair in the OA model. Platelet-derived ADP was identified as the major mediator to promote the production of BMP7 and the proliferation of chondrocytes, through the ADP receptor P2Y1. Finally, direct injection of α,β-methyleneadenosine-5′-diphosphate into OA joints also enhanced cartilage repair. This study has identified that platelet-derived ADP, but not ATP, is the key mediator for platelet-promoted chondrocyte proliferation and cartilage repair in osteoarthritis. This finding may provide a key explanation for the therapeutic effect of platelets in OA and help shaping a strategy to improve OA therapy.</p