Mesenchymal Stem Cells in Oriented PLGA/ACECM Composite Scaffolds Enhance Structure-Specific Regeneration of Hyaline Cartilage in a Rabbit Model

Abstract

Articular cartilage lacks a blood supply and nerves. Hence, articular cartilage regeneration remains a major challenge in orthopedics. Decellularized extracellular matrix- (ECM-) based strategies have recently received particular attention. The structure of native cartilage exhibits complex zonal heterogeneity. Specifically, the development of a tissue-engineered scaffold mimicking the aligned structure of native cartilage would be of great utility in terms of cartilage regeneration. Previously, we fabricated oriented PLGA/ACECM (natural, nanofibrous, articular cartilage ECM) composite scaffolds. In vitro, we found that the scaffolds not only guided seeded cells to proliferate in an aligned manner but also exhibited high biomechanical strength. To detect whether oriented cartilage regeneration was possible in vivo, we used mesenchymal stem cell (MSC)/scaffold constructs to repair cartilage defects. The results showed that cartilage defects could be completely regenerated. Histologically, these became filled with hyaline cartilage and subchondral bone. Moreover, the aligned structure of cartilage was regenerated and was similar to that of native tissue. In conclusion, the MSC/scaffold constructs enhanced the structure-specific regeneration of hyaline cartilage in a rabbit model and may be a promising treatment strategy for the repair of human cartilage defects.

MSC-derived exosomes promote proliferation and inhibit apoptosis of chondrocytes via lncRNA-KLF3-AS1/miR-206/GIT1 axis in osteoarthritis

“…Chondrocytes were isolated from the knee joint of C57BL/6 mice. Briefly, the articular cartilage tissue from the right knee joint of the hindlegs of OA mice was cut into small pieces (< 1 mm [3]) and incubated with 0.2% trypsin at 37°C for 30 min. Following removal of the trypsin solution, the tissue was treated with 2 ml 0.2% Type II collagenase at 37°C for 2 h. Released cells were cultured in Dulbecco's modified Eagle's medium (DMEM; Gibco) supplemented with 10% FBS, penicillin (100 U/ml) and streptomycin (100 g/ml).…”

“…Mesenchymal stem cell (MSC) therapies have demonstrated efficacy in cartilage repair in both animal studies [3] and human clinical trials [4]. The efficacy of MSC-based therapies, which was previously predicated on the chondrogenic potential of MSC, has been increasingly attributed to the paracrine secretion, particularly exosomes.…”

3D Bone Biomimetic Scaffolds for Basic and Translational Studies with Mesenchymal Stem Cells

“…Bone ECM itself has been employed after specific manipulations such as decellularization, demineralization, or deproteination [ 39 ]. The resulting modified ECM offered the advantage of displaying, simultaneously, many different chemical and physical instructive signals for the host cells, preserved osteoconductive and osteoinductive properties [ 61 , 62 , 63 ], and showed promising results also for potential exploitation in cartilage regeneration [ 64 , 65 ]. As our specific focus is on cell–biomaterial interaction, we will mention, as an example the work by Bourgine and colleagues, which tested the in vivo bone regeneration capacity of engineered and devitalized hypertrophic cartilage templates obtained in a two-step protocol: chondrogenic differentiation of hMSCs followed by genetically induced cell apoptosis [ 66 ].…”

Periodontal Tissues, Maxillary Jaw Bone, and Tooth Regeneration Approaches: From Animal Models Analyses to Clinical Applications

“…However, the combination with stem cells, such as bone-marrow derived stromal cells, may be of interest to improve clinical outcomes [ 42 ]. Such strategies have already been evaluated and are already used clinically in orthopedic surgery, with functionalization based on multipotent mesenchymal stem cells [ 43 ]. However, it is of importance to describe the significant impact of the surgical technique used for membrane placement on regeneration related outcomes.…”