RESUMO
Background: Osteochondral regeneration has long been recognized as a complex and challenging project in the field of tissue engineering. In particular, reconstructing the osteochondral interface is crucial for determining the effectiveness of the repair. Although several artificial layered or gradient scaffolds have been developed recently to simulate the natural interface, the functions of this unique structure have still not been fully replicated. In this paper, we utilized laser micro-patterning technology (LMPT) to modify the natural osteochondral "plugs" for use as grafts and aimed to directly apply the functional interface unit to repair osteochondral defects in a goat model. Methods: For in vitro evaluations, the optimal combination of LMPT parameters was confirmed through mechanical testing, finite element analysis, and comparing decellularization efficiency. The structural and biological properties of the laser micro-patterned osteochondral implants (LMP-OI) were verified by measuring the permeability of the interface and assessing the recellularization processes. In the goat model for osteochondral regeneration, a conical frustum-shaped defect was specifically created in the weight-bearing area of femoral condyles using a customized trephine with a variable diameter. This unreported defect shape enabled the implant to properly self-fix as expected. Results: The micro-patterning with the suitable pore density and morphology increased the permeability of the LMP-OIs, accelerated decellularization, maintained mechanical stability, and provided two relative independent microenvironments for subsequent recellularization. The LMP-OIs with goat's autologous bone marrow stromal cells in the cartilage layer have securely integrated into the osteochondral defects. At 6 and 12 months after implantation, both imaging and histological assessments showed a significant improvement in the healing of the cartilage and subchondral bone. Conclusion: With the natural interface unit and zonal recellularization, the LMP-OI is an ideal scaffold to repair osteochondral defects especially in large animals. The translational potential of this article: These findings suggest that such a modified xenogeneic osteochondral implant could potentially be explored in clinical translation for treatment of osteochondral injuries. Furthermore, trimming a conical frustum shape to the defect region, especially for large-sized defects, may be an effective way to achieve self-fixing for the implant.
RESUMO
BACKGROUND: The repair of large bone defects remains challenging for orthopaedic surgeons. Bone grafting remains the method of choice; such grafts fill spaces and enhance bone repair. Therapeutic agents also aid bone healing. The objective of this study is to develop a composite bioactive scaffold composed of polylactide-coglycolide (PLGA) and tricalcium phosphate (TCP) (the basic carrier) incorporating osteogenic, bioactive magnesium metal powder (Mg). METHOD: Porous PLGA/TCP scaffolds incorporating Mg were fabricated using a low-temperature rapid-prototyping process. We term the PLGA/TCP/Mg porous scaffold (hereafter, PPS). PLGA/TCP lacking Mg served as the control material when evaluating the efficacy of PPS. A total of 36 New Zealand white rabbits were randomly divided into blank, PLGA/TCP (P/T) and PPS group, with 12 rabbits in each group. We established bone defects 15 mm in length in rabbit radii to evaluate the in vivo osteogenic potential of the bioactive scaffold in terms of the direct controlled release of osteogenic Mg ion during in vivo scaffold degradation. Radiographs of the operated radii were taken immediately after implantation and then at 2, 4, 8 and 12 weeks. Micro-computed tomography of new bone formation and remaining scaffold and histological analysis were performed at 4, 8, 12 weeks after operation. RESULTS: X-ray imaging performed at weeks 4, 8 and 12 post-surgery revealed more newly formed bone within defects implanted with PPS and PLGA/TCP scaffolds than blank group (p < 0.05). And micro-computed tomography performed at weeks 4 and 8 after surgery revealed more newly formed bone within defects implanted with PPS scaffolds than PLGA/TCP scaffolds (p < 0.05). Histologically, the PPS group had more newly mineralized bone than controls (p < 0.05). The increases in new bone areas (total implant regions) in the PPS and PLGA/TCP groups were 19.42% and 5.67% at week 4 and 48.23% and 28.93% at week 8, respectively. The percentages of remaining scaffold material in total implant regions in the PPS and PLGA/TCP groups were 53.30% and 7.65% at week 8 and 20.52% and 2.70% at week 12, respectively. CONCLUSION: Our new PPS composite scaffold may be an excellent orthopaedic substitute; it exhibits good biocompatibility and may potentially have clinical utility. TRANSLATIONAL POTENTIAL OF THIS ARTICLE: Magnesium and beta-tricalcium phosphate had osteoinduction. It is significant to print a novel bone composite scaffold with osteoinduction to repair segmental bone defects. This study evaluated efficacy of PPS in the rabbit radius segmental bone defect model. The results showed that the novel scaffold with good biocompatibility may be an excellent graft and potentially have clinical utility.
RESUMO
In older adults, the prevalence of osteoarthritis (OA) increases directly with age and is the most common cause of chronic disability. It is necessary to recognize that OA is a degenerative disease that strongly correlates with age, and often promotes elevated levels of cartilage injury. Chondrocytes undergo an age-dependent decline in proliferative and synthetic capacity. It is thought that cellular senescence may play a significant role in the pathology of OA, with chondrocytes exhibiting a variety of senescence-associated phenotypes. In this review, we discuss cellular senescence and its relationship with OA. More importantly, we introduce novel strategies for the modulation of cellular senescence, including the use of sirtuin 6, mammalian target of rapamycin, N-acetyl-l-cysteine, proteoglycan-4 and senolytic, which may help to delay senescence and improve cartilage regeneration in the aging population.
