Modular Microgel-Based Bioassembly Scaffold Induced Chondrogenic and Osteogenic Differentiation of BMSCs.

Bioactive scaffolds capable of simultaneously repairing osteochondral defects remain a big challenge due to the heterogeneity of bone and cartilage. Currently modular microgel-based bioassembly scaffolds are emerged as potential solution to this challenge. Here, microgels based on methacrylic anhydride (MA) and dopamine modified gelatin (GelMA-DA) are loaded with chondroitin sulfate (CS) (the obtained microgel named GC Ms) or bioactive glass (BG) (the obtained microgel named GB Ms), respectively. GC Ms and GB Ms show good biocompatibility with BMSCs, which suggested by the adhesion and proliferation of BMSCs on their surfaces. Specially, GC Ms promote chondrogenic differentiation of BMSCs, while GB Ms promote osteogenic differentiation. Furthermore, the injectable GC Ms and GB Ms are assembled integrally by bottom-up in situ cross-linking to obtain modular microgel-based bioassembly scaffold (GC-GB/HM), which show a distinct bilayer structure and good porous properties and swelling properties. Particularly, the results of in vivo and in vitro experiments show that GC-GB/HM can simultaneously regulate the expression levels of chondrogenic- and osteogenesis-related genes and proteins. Therefore, modular microgel-based assembly scaffold in this work with the ability to promote bidirectional differentiation of BMSCs and has great potential for application in the minimally invasive treatment of osteochondral tissue defects.

Functional nano drug delivery system with dual lubrication and immune escape for treating osteoarthritis.

Local drug delivery via inter-articular injection offers a promising scenario to treat the most common joint disease, osteoarthritis (OA), which is closely associated with the increased friction or cartilage degeneration and the inflammatory syndrome of synovium. Therefore, it is quite necessary to improve the retention of drug delivery system within synovial joint, simultaneously restore the lubrication of degraded cartilage and meanwhile alleviate the inflammation. In this study, we propose a hydrophilic coating modified nano-liposome drug carrier (PMPC-Lipo) to achieve these functions. A modified chain transfer agent was utilized to polymerize 2-methacryloyloxyethyl phosphorylcholine (MPC), the obtained polymer, combined with lecithin and cholesterol, formed a liposome (PMPC-Lipo) where poly (MPC) acted as hydrophilic coating. PMPC-Lipo was found to restore the lubrication of mechanically damage cartilage (mimicking OA conditions) to the level like healthy cartilage due to the hydration lubrication. Additionally, due to the presence of poly (MPC), we also found PMPC-Lipo avoid the recognition of macrophage and thus escape from the phagocytosis to prolong its retention in synovial joint. Furthermore, after encapsulating gallic acid (GA) into PMPC-Lipo, the obtained GA-PMPC-Lipo can effectively scavenge reactive oxygen species and restore the imbalance of matrix secretion in inflammatory chondrocytes. Collectively, the proposed GA-PMPC-Lipo may provide a new idea for osteoarthritis treatment by providing both long-term effective drug action and excellent lubrication properties.

Bioactive Phenylboronic Acid-Functionalized Hyaluronic Acid Hydrogels Induce Chondro-Aggregates and Promote Chondrocyte Phenotype.

Hydrogels are extensively investigated as biomimetic extracellular matrix (ECM) scaffolds in tissue engineering. The physiological properties of ECM affect cellular behaviors, which is an inspiration for cell-based therapies. Photocurable hyaluronic acid (HA) hydrogel (AHAMA-PBA) modified with 3-aminophenylboronic acid, sodium periodate, and methacrylic anhydride simultaneously is constructed in this study. Chondrocytes are then cultured on the surface of the hydrogels to evaluate the effect of the physicochemical properties of the hydrogels on modulating cellular behaviors. Cell viability assays demonstrate that the hydrogel is non-toxic to chondrocytes. The existence of phenylboronic acid (PBA) moieties enhances the interaction of chondrocytes and hydrogel, promoting cell adhesion and aggregation through filopodia. RT-PCR indicates that the gene expression levels of type II collagen, Aggrecan, and Sox9 are significantly up-regulated in chondrocytes cultured on hydrogels. Moreover, the mechanical properties of the hydrogels have a significant effect on the cell phenotype, with soft gels (≈2 kPa) promoting chondrocytes to exhibit a hyaline phenotype. Overall, PBA-functionalized HA hydrogel with low stiffness exhibits the best effect on promoting the chondrocyte phenotype, which is a promising biomaterial for cartilage regeneration.

Thermosensitive Injectable Gradient Hydrogel-Induced Bidirectional Differentiation of BMSCs.

Osteochondral defects threaten the quality of life of patients to a great extent. To simulate gradient changes in osteochondral tissue, a gradient-mixing injection device consisting of a controller and injection pumps is design. Bioactive glass (BG) and gellan gum (GG) are used to prepare thermosensitive injectable gradient hydrogels (B0.5 G, B1 G) with an upper critical solution temperature (UCST) range of 37.7-40.2 °C using this device for the first time. The mechanical properties of gradient hydrogels are significantly better than those of pure GG hydrogels. The gradients in the composition, structure, and morphology of gradient hydrogels are confirmed via physicochemical characterization. Cytocompatibility tests show that hydrogels, especially B0.5 G gradient hydrogels, promote the proliferation of bone marrow mesenchymal stem cells (BMSCs). Most importantly, qRT-PCR shows that the different components in B0.5 G gradient hydrogels simultaneously induce the osteogenic and chondrogenic differentiation of BMSCs. Experimental injection in porcine osteochondral defects indicates that the B0.5 G gradient hydrogel seamlessly fills irregular osteochondral defects in a less invasive manner by controlling the temperature to avoid cellular and tissue damage arising from crosslinkers or other conditions. These results show that thermosensitive injectable B0.5 G gradient hydrogels have the potential for less invasive integrated osteochondral repair.