Unlike bone tissue, articular cartilage regeneration has not been very successful and has many challenges ahead. We have previously developed injectable hydrogels using photopolymerizable chitosan (MeGC) that supported growth of chondrocytes. In this study, we demonstrate a biofunctional hydrogel for specific use in cartilage regeneration by conjugating transforming growth factor-β1 (TGF-β1), a well-documented chondrogenic factor, to MeGC hydrogels impregnating type II collagen (Col II), one of the major cartilaginous extracellular matrix (ECM) components.

Poly(lactic-co-glycolic acid) (PLGA) has been widely used as a biomaterial for pharmaceutical and medical applications. However, the decomposition products of PLGA are known to acidify the surrounding tissue of the implanted site, causing an inflammatory response. Previously, we developed PLGA/inorganic nanocomposites and optimized the amounts of inorganic compounds, β-tricalcium phosphate (β-TCP) and magnesium hydroxide [Mg(OH)₂], in terms of osteogenesis of normal human osteoblasts and anti-inflammatory responses of preosteoclastic cells in vitro. In this study, the potential of the optimized PLGA/β-TCP/Mg(OH)₂ nanocomposite (TCP/MH) to promote bone repair through osteoinductive, osteoconductive, and anti-inflammatory abilities was assessed using a bone defect in a rat humeral defect model. PLGA nanocomposites with or without inorganic compounds, PLGA, β-TCP, MH, and TCP/MH were prepared through one-step bulk modification using a twin-screw extruder. The resulting TCP/MH nanocomposite successfully enhanced the bone regeneration rate for allowing complete bone defect healing with significantly suppressed inflammatory responses. Taken together, the organic and inorganic bioactive nanocomposite developed in this study, TCP/MH, is a promising material in orthopedic implantation.

Introduction: Mesenchymal stem cells (MSCs) are widely considered to hold promise for the treatment of intervertebral disc (IVD) degeneration. However, variation in the therapeutic efficacy of MSCs is a major problem and the derivation of MSCs for use in IVD regeneration has not been optimized. Additionally, no data are available on the efficacy of Wharton’s Jelly-derived MSC (WJ-MSC) transplantation in an animal model of IVD degeneration. Methods: This study evaluated the effectiveness of a cross-linked hyaluronic acid (XHA) scaffold loaded with human WJ-MSCs, according to their expression levels of transforming growth factor-β receptor I/activin-like kinase receptor 5 (TβRI/ALK5) and TβRII, for IVD regeneration in a rabbit model. We compared the degree of IVD regeneration between rabbits transplanted with a XHA scaffold loaded with WJ-MSCs highly and lowly expressing TβRI/ALK5 and TβRII (MSC-highTR and MSC-lowTR, respectively) using magnetic resonance imaging (MRI) and histological analysis. Results: At 12 weeks after transplantation, T2-weighted MRI analysis showed significant restoration of the disc water content in rabbits treated with a MSC-highTR-loaded XHA scaffold in comparison to rabbits treated with the scaffold alone or a MSC-lowTR-loaded XHA scaffold. In addition, morphological and histological analyses revealed that IVD regeneration was highest in rabbits transplanted with a MSC-highTR-loaded XHA scaffold. Conclusion: Taken together, our results suggest that a MSC-highTR-loaded XHA scaffold supports IVD regeneration more effectively than a MSC-lowTR-loaded XHA scaffold. This study supports the potential clinical use of MSC-highTR-loaded XHA scaffolds to halt IVD degeneration or to enhance IVD regeneration.

Although drug-eluting stents (DESs) are mainly coated with biodegradable polymers such as PLGA and PLLA, their acidic degradation products can alter the local microenvironment and affect the homeostasis of adjacent tissue. Previously, we developed anti-inflammatory PLGA-based materials including magnesium hydroxide (MH) to relieve the side effects caused by PLGA degradation. However, the underlying molecular mechanism of its protective effects has not yet been clarified. Here, we demonstrated the pathological mechanism of vascular endothelial activation caused by PLGA by-products. The PLGA by-products accumulated in HCAECs through MCT1, followed by oxidative stress and the activation of the MAPK/NF-κB signaling pathway. Finally, the PLGA by-products increased the expression of VCAM-1 as well as the secretion of proinflammatory cytokines. However, the addition of MH particles significantly diminished the activation of this molecular pathway and the expression of inflammation-related factors induced by acidic PLGA degradation products. Furthermore, Mg²⁺ released from MH particles restored endothelial function in both intracellular and extracellular spaces. Taken together, MH particles prevent the accumulation of PLGA degradation products in HCAECs, thereby repressing the associated vascular endothelial activation. These findings on the biochemical mechanisms are expected to provide important clues for addressing the safety issues in nearly all biodegradable polymer-based implants.

Poly(L-lactic acid) (PLLA) is a biocompatible and biodegradable polymer that has received much attention as a biomedical material. However, PLLA also produces by-products that acidify the surrounding tissues during in vivo degradation, which induces inflammatory responses. To overcome these problems, magnesium hydroxide nanoparticles (nano-magnesium hydroxide; nMH) were added to the PLLA matrix as a bioactive filler that can suppress inflammatory responses by neutralizing the acidified environment caused by the degradation of PLLA. Despite the advantages of nMH, the strong cohesion of these nanoparticles toward each other makes it difficult to manufacture a polymer matrix containing homogeneous nanoparticles through thermal processing. Here, we prepared two types of surface-modified nMH with oligolactide (ODLLA) utilizing grafting to (GT) and grafting from (GF) strategies to improve the mechanical and biological characteristics of the organic–inorganic hybrid composite. The incorporation of surface-modified nMH not only enhanced mechanical properties, such as Young's modulus, but also improved homogeneity of magnesium hydroxide particles in the PLLA matrix due to the increase in interfacial interaction. Additionally, the PLLA composites with surface-modified nMH exhibited reduced bulk erosion during hydrolytic degradation with lower cytotoxicity and immunogenicity. Hemocompatibility tests on the PLLA composites with nMH showed a higher albumin to fibrinogen ratio (AFR) and a lower influence of platelet activation, when compared with unmodified control samples. Taken all together, the surface-modified nMH could be seen to successfully improve the physical and biological characteristics of polymer composites. We believe this technology has great potential for the development of hybrid nanocomposites for biomedical devices, including cardiovascular implants.

Human adipose-derived stem cells (hASCs) have a capacity to undergo adipogenic, chondrogenic, and osteogenic differentiation. Recently, hASCs were applied to various fields including cell therapy for tissue regeneration. However, it is hard to predict the direction of differentiation of hASCs in real-time. Matrix metalloproteinases (MMPs) are one family of proteolytic enzymes that plays a pivotal role in regulating the biology of stem cells. MMPs secreted by hASCs are expected to show different expression patterns depending on the differentiation state of hASCs because biological functions exhibit different patterns during the differentiation of stem cells. Here, we investigated proteolytic enzyme activity, especially MMP-2 activity, in hASCs during their differentiation. The activities of proteolytic enzymes and MMP-2 were higher during chondrogenic differentiation than during adipogenic and osteogenic differentiation. During chondrogenic differentiation, mRNA expression of MMP-2 and the level of the active form of MMP-2 were increased, which also correlated with Col II. It is concluded that proteolytic enzyme activity and the level of the active form of MMP-2 were increased during chondrogenic differentiation, which was accelerated in the presence of Col II protein. According to our findings, MMP-2 could be a candidate maker for real-time detection of chondrogenic differentiation of hASCs.