Repairing damaged articular cartilage is challenging due to the limited regenerative capacity of hyaline cartilage. In this study, we fabricated a bilayered poly (lactic-co-glycolic acid) (PLGA) scaffold with small (200–300 μm) and large (200–500 μm) pores by salt leaching to stimulate chondrocyte differentiation, cartilage formation, and endochondral ossification. The scaffold surface was treated with tyramine to promote scaffold integration into native tissue. Porcine chondrocytes retained a round shape during differentiation when grown on the small pore size scaffold, and had a fibroblast-like morphology during transdifferentiation in the large pore size scaffold after five days of culture. Tyramine-treated scaffolds with mixed pore sizes seeded with chondrocytes were pressed into three-mm porcine osteochondral defects; tyramine treatment enhanced the adhesion of the small pore size scaffold to osteochondral tissue and increased glycosaminoglycan and collagen type II (Col II) contents, while reducing collagen type X (Col X) production in the cartilage layer. Col X content was higher for scaffolds with a large pore size, which was accompanied by the enhanced generation of subchondral bone. Thus, chondrocytes seeded in tyramine-treated bilayered scaffolds with small and large pores in the upper and lower parts, respectively, can promote osteochondral regeneration and integration for articular cartilage repair.

Continuous passive motion (CPM) is widely used after total knee replacement. In this study, we investigated the effect of CPM combined with cell-based construct-transplantation in osteochondral tissue engineering. We created osteochondral defects (3 mm in diameter and 3 mm in depth) in the medial femoral condyle of 36 knees and randomized them into three groups: ED (empty defect), EPC/PLGA (endothelial progenitor cells (EPCs) seeded in the poly lactic-co-glycolic acid (PLGA) scaffold), or EPC/PLGA/CPM (EPC/PLGA scaffold complemented with CPM starting one day after transplantation). We investigated the effects of CPM and the EPC/PLGA constructs on tissue restoration in weight-bearing sites by histological observation and micro-computed tomography (micro-CT) evaluation 4 and 12 weeks after implantation. After CPM, the EPC/PLGA construct exhibited early osteochondral regeneration and prevention of subchondral bone overgrowth and cartilage degeneration. CPM did not alter the microenvironment created by the construct; it up-regulated the expression of the extracellular matrix components (glycosaminoglycan and collagen), down-regulated bone formation, and induced the biosynthesis of lubricin, which appeared in the EPC/PLGA/CPM group after 12 weeks. CPM can provide promoting signals during osteochondral tissue engineering and achieve a synergistic effect when combined with EPC/PLGA transplantation, so it should be considered a non-invasive treatment to be adopted in clinical practices.

The success of many endosseous implants in orthopaedic and dental applications depends on the surface characteristics, as they affect osseous integration. Previous investigations indicated that a novel large-grit sand-blasted and acid-etched (SLA) titanium (denoted as SLAffinity-Ti) implant had better bone integration than that of a comparably shaped implant with a plasma-sprayed titanium surface. The purpose of the present investigation was to create a SLAffinity surface on pedicle screws and trauma screws and to compare it with the surfaces of a sand-blasted-only implant and commercial implants in terms of bone integration. The cortical bone and spine of twelve minipigs were implanted with 3 and 4 implants, respectively, and the bone integration was evaluated using micro-computed tomography (micro-CT), mechanical tests (pull-out strength and stripping torque), and histological analysis (toluidine blue and hematoxylin and eosin staining) one and three months after implantation. The micro-CT images showed that the gap between the bone and implant was consistently higher in the sand-blasted-only and commercial groups compared to that in the SLAffinity group 1 and 3 months after implantation. Moreover, the bone volume of implant inserted into bone and the percentage of implant inside bone tissue were greater in the SLAffinity screws 1 and 3 months after implantation, as compared to the sand-blasted and commercial screws. In the mechanical tests, the removal torque and pull-out strength (p < 0.05) were higher in the SLAffinity group at 1 and 3 months. The histological results were consistent with mechanical testing, showing that the SLAffinity group had the most mineralized matrix, the most bone formation around the screws, and the most bone cells in bone tissue. These findings indicate that a SLAffinity surface can effectively enhance the holding strength and integration of pedicle screws and cortical screws, promoting early healing and improving outcomes, compared to sand-blasted-only and commercial implants.

Repairing damaged articular cartilage is particularly challenging because of the limited ability of cartilage to perform self-repair. Intra-articular injections of N-acetylglucosamine (GlcNAc) comprise a method of repairing full-thickness articular cartilage defects in the rabbit knee joint model. To date, the effects of administration of GlcNAc and hyaluronic acid (HA) have been investigated only in the context of osteoarthritis treatment. Therefore, we evaluated the therapeutic effects of using cell-free porous poly lactic-co-glycolic acid (PLGA) graft implants and intra-articular injections of GlcNAc or HA in a rabbit model of osteochondral regeneration to investigate whether they have the potential for inducing osteochondral regeneration when used alone or simultaneously. Twenty-four rabbits were randomized into one of four groups: the scaffold-only group (PLGA), the scaffold with intra-articular injections of GlcNAc (PLGA+G) group, twice per week for four weeks; the scaffold with intra-articular injections of HA group (PLGA+HA) group, once per week for three weeks; and the scaffold with intra-articular injections of GlcNAc and HA (PLGA+G+HA) group, once per week for three weeks. Knees were evaluated at 4 and 12 weeks after surgery. At the end of testing, only the PLGA+G+HA group exhibited significant bone reconstruction, chondrocyte clustering, and good interactions with adjacent surfaces at 4 weeks. Additionally, the PLGA+G+HA group demonstrated essentially original hyaline cartilage structures that appeared to have sound chondrocyte orientation, considerable glycosaminoglycan levels, and reconstruction of the bone structure at 12 weeks. Moreover, the PLGA+G+HA group showed organized osteochondral integration and significantly higher bone volume per tissue volume and trabecular thickness. However, there were no significant differences between the PLGA+G and PLGA+HA groups except for gap formation on subchondral bone in the PLGA+G group. This study demonstrated that PLGA implantation combined with intra-articular injections of GlcNAc and HA allowed for cartilage and bone regeneration and significantly promoted osteochondral regeneration in rabbits without supplementation of exogenous growth factors. And the combination of this two supplements with PLGA scaffold could also prolong injection interval and better performance than either of them alone for the reconstruction of osteochondral tissue in the knee joints of rabbits.