No abstract

Implanting hydroxyapatite-mineralized tough hydrogel into osteochondral defects of rabbits, osteogenesis spontaneously penetrates into the gel matrix owing to the semi-permeablility of the hydrogel. The gradient layer (around 40 μm thick) contributes quite strong bonding of the gel to bone. This is the first success in realizing the robust osteointegration of tough hydrogels, and the method is simple and feasible for practical use

We have developed a novel method to induce spontaneous hyaline cartilage regeneration in vivo for a large osteochondral defect by implanting a plug made from a double-network hydrogel composed of poly(2-acrylamido-2-methylpropanesulfonic acid) and poly(N,N'-dimethylacrylamide) at the bottom of the defect, leaving the cavity vacant. In cells regenerated in the treated defect, type-2 collagen, Aggrican, and SOX9 mRNAs were highly expressed and the regenerated matrix was rich in proteoglycan and type-2 collagen at 4 weeks. This fact gave a significant modification to the commonly established concept that hyaline cartilage tissue cannot regenerate in vivo. This study prompted an innovative strategy in the field of joint surgery to repair an osteochondral defect using an advanced, high-function hydrogel.

No abstract

Remnant preservation in anatomic double-bundle ACL reconstruction did not significantly improve subjective and functional results in the short-term evaluation, but it significantly improved postoperative knee stability. The degree of initial graft coverage significantly affected postoperative knee stability.

Based on the molecular stent concept, a series of tough double-network hydrogels (St-DN gels) made from the components of proteoglycan aggregates - chondroitin sulfate proteoglycans (1), chondroitin sulfate (2), and sodium hyaluronate (3) - are successfully developed in combination with a neutral biocompatible polymer. This work demonstrates a promising method to create biopolymer-based tough hydrogels for biomedical applications.

No abstract

Obesity, an important risk factor for metabolic syndrome (MetS) and cardiovascular disease, is often complicated by CKD, which further increases cardiovascular risk and causes ESRD. To elucidate the mechanism underlying this relationship, we investigated the role of the endocytic receptor megalin in proximal tubule epithelial cells (PTECs). We studied a high-fat diet (HFD)-induced obesity/MetS model using kidney-specific mosaic megalin knockout (KO) mice. Compared with control littermates fed a normal-fat diet, control littermates fed an HFD for 12 weeks showed autolysosomal dysfunction with autophagy impairment and increased expression of hypertrophy, lipid peroxidation, and senescence markers in PTECs of the S2 segment, peritubular capillary rarefaction with localized interstitial fibrosis, and glomerular hypertrophy with mesangial expansion. These were ameliorated in HFD-fed megalin KO mice, even though these mice had the same levels of obesity, dyslipidemia, and hyperglycemia as HFD-fed control mice. Intravital renal imaging of HFD-fed wild-type mice also demonstrated the accumulation of autofluorescent lipofuscin-like substances in PTECs of the S2 segment, accompanied by focal narrowing of tubular lumens and peritubular capillaries. In cultured PTECs, fatty acid-rich albumin induced the increased expression of genes encoding PDGF-B and monocyte chemoattractant protein-1 via megalin, with large (auto)lysosome formation, compared with fatty acid-depleted albumin. Collectively, the megalin-mediated endocytic handling of glomerular-filtered (lipo)toxic substances appears to be involved primarily in hypertrophic and senescent PTEC injury with autophagy impairment, causing peritubular capillary damage and retrograde glomerular alterations in HFD-induced kidney disease. Megalin could be a therapeutic target for obesity/MetS-related CKD, independently of weight, dyslipidemia, and hyperglycemia modification.