Thermosensitive hydrogel for cartilage regeneration via synergistic delivery of SDF-1α like polypeptides and kartogenin.

Regeneration of injured articular cartilage is limited by low early-stage recruitment of stem cells and insufficient chondrogenic differentiation. Hydrogels are widely used to repair cartilage because they have excellent mechanical and biological properties. In this study, a dual drug-loaded thermosensitive hydroxypropyl chitin hydrogel (HPCH) system was prepared to release stromal-derived factor-1α-like polypeptides (SDFP) and kartogenin (KGN) for stem-cell recruitment and chondrogenic differentiation. The hydrogel had a network structure that promoted cell growth and nutrient exchange. Moreover, it was temperature sensitive and suitable for filling irregular defects. The system showed good biocompatibility in vitro and promoted stem-cell recruitment and chondrogenic differentiation. Furthermore, it reduced chondrocyte catabolism under inflammatory conditions. Animal experiments demonstrated that the dual-drug hydrogel systems can promote the regeneration of articular cartilage in rats. This study confirmed that an HPCH system loaded with KGN and SDFP could effectively repair articular cartilage defects and represents a viable treatment strategy.

3D printed magnesium-doped ß-TCP gyroid scaffold with osteogenesis, angiogenesis, immunomodulation properties and bone regeneration capability in vivo.

Bioceramics have been used in orthopedic surgery for several years. Magnesium (Mg) is an essential element in bone tissue and plays an important role in bone metabolism. Mg-doped bioceramics has attracted the attention of researchers recently. However, the optimal doping amount of Mg in ß-TCP and the immunomodulatory property of Mg-doped ß-TCP (Mg-TCP) have not been determined yet. In this study, ß-TCP scaffolds doped with different contents of magnesium oxide (0 wt%, 1 wt%, 3 wt%, and 5 wt%) with gyroid structure were printed by digital light processing (DLP) method, and the physicochemical and biological functions were then investigated. Mg-doping improved the physicochemical properties of the ß-TCP scaffolds. In vitro experiments confirmed that the doping of Mg in ß-TCP scaffolds promoted the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and angiogenic differentiation of endothelial progenitor cells (EPCs), where the 5Mg-TCP has the optimal properties when using the "one cell type" method. It was also found that all Mg-TCP facilitated the polarization of RAW264.7 cells to the M2 phenotype, especially the 3Mg-TCP. However, 3Mg-TCP displayed the optimal osteogenic and angiogenic potential when using a "multiple cell type" method, which referred to culturing the BMSCs or EPCs in the macrophage-conditioned medium. Finally, the in vivo experiments were conducted and the results confirmed that the 3Mg-TCP scaffolds possessed the satisfying bone defect repair capability both after 6 and 12 weeks of implantation. This study suggests that 3Mg-TCP scaffolds provide the optimal biological performance and thus have the potential for clinical translation.

Three-dimensional printing of gyroid-structured composite bioceramic scaffolds with tuneable degradability.

Customisation of bioactivity and degradability of porous bioceramic scaffolds is a formidable challenge in the field of regenerative medicine. In this study, we developed gyroid-structured ternary composite scaffolds (biphasic calcium phosphate (BCP) and 45S5 bioglass® (BG)) using digital light processing 3D printing technology based on material and structural design. Additionally, the mechanical strength, bioactivity, degradability, and biocompatibility of the composite ceramic scaffolds were evaluated. The results revealed that BG reacted with BCP to generate major active crystalline phases of CaSiO3 and Na3Ca6(PO4)5. These active crystalline phases accelerated the exchange rate of Si4+, Ca2+, and PO43- with HCO3- in simulated body fluids and resulted in the rapid formation of carbonated hydroxyapatite (CHA), analogous to the formation of natural bone tissue. Interestingly, the precipitated CHA showed petal- and needle-like morphologies, which provided a large surface area to promote cell adhesion and proliferation. Furthermore, an increase in the BG content improved the degradability of ternary composite scaffolds after soaking in Tris-HCl solution. The tuneable degradability increased by three times at 30 wt% BG and sharply increased by 6.8 times at 40 wt% BG. This study provides a promising strategy to design scaffolds with improved bioactivity and tuneable degradability to assist a diverse population suffering from orthopedic conditions.