Osteoarthritis (OA) is the most common age-related degenerative joint disease mainly characterized by the destruction of articular cartilage. Owing to its native avascular property, intrinsic repair of articular cartilage is very limited. Thus, a chondrogenic microenvironment in the joint is essential to the preservation of healthy chondrocytes and OA treatment. Recently, cartilage progenitor cells (CPCs)-based therapy is emerging as a promising strategy to repair degenerated and damaged articular cartilage. In this study, injectable hypoxia-preconditioned three-dimensional (3D) cultured CPCs-laden gelatin methacryloyl (GelMA) microspheres (CGMs) were constructed and characterized. Compared to normoxia-pretreated 3D CPCs and two-dimensional (2D) cultured CPCs, hypoxia-preconditioned 3D cultured CPCs exhibited enhanced cartilage extracellular matrix (ECM) secretion and greater chondrogenic ability. In addition, hypoxia-preconditioned 3D cultured CPCs more effectively maintained cartilage matrix metabolism balance and attenuated articular cartilage degeneration in subacute and chronic rat OA models. Mechanistically, our results demonstrated hypoxia-preconditioned 3D cultured CPCs exerted chondro-protective effects by inhibiting inflammation and oxidative stress via NRF2/HO-1 pathway in vitro and in vivo. Together, through the 3D culture of CPCs using GelMA microspheres (GMs) under hypoxia environment, our results proposed an efficient articular cartilage regeneration strategy for OA treatment and could provide inspiration for other stem cells-based therapies. 

Injectable hypoxia-preconditioned cartilage progenitor cells-laden GelMA microspheres system for enhanced osteoarthritis treatment

miR-140-5p protects cartilage progenitor/stem cells from fate changes in knee osteoarthritis.

Hypoxia-mimicking scaffolds with controlled release of DMOG and PTHrP to promote cartilage regeneration via the HIF-1α/YAP signaling pathway.

With the help of biomaterials, cartilage stem/progenitor cells (CSPCs) derived from cartilage tissue present a promising choice for cartilage regeneration. In our previous study, we investigated whether CSPCs could be ideal seeding cells for cartilage tissue regeneration. Biomaterials are fabricated to accelerate tissue regeneration, providing a suitable environment for cell attachment, proliferation, and differentiation. Among the biomaterials used in cartilage regeneration medicine, alginate and collagen are classified as natural biomaterials and are characterized by high biocompatibility, bioactivity, and non-toxic degradation products. However, it is unclear which material would have a competitive advantage in CSPC-based cartilage regeneration in vivo. In the present study, we employed alginate and type Ⅰ collagen as substrates for CSPCs and chondrocytes, which was made control group, to explore a more suitable biomaterials for CSPCs to fabricate tissue-engineered cartilage, in vivo. Hematoxylin and eosin (HE) staining, Safranin O, immunohistochemical assay, and quantitative real-time polymerase chain reaction (qRT-PCR) were used to evaluate the tissue-engineered cartilage in vivo. Compared with the alginate group, collagen enhanced the expression of cartilage-specific genes, such as ACAN, SOX9, and COLII, more markedly. Furthermore, the marker genes of expression, dedifferentiation, and hypertrophy, COLI and COLX, were downregulated in the collagen group. The results demonstrated that collagen as a substrate was superior to alginate in increasing the accumulation of cartilage-like ECM for CSPCs in vivo. In summary, compared with alginate, collagen hydrogel is an effective biomaterial for CSPC-based cartilage regeneration.

Comparative study of alginate and type I collagen as biomaterials for cartilage stem/progenitor cells to construct tissue-engineered cartilage in vivo

YY1/miR-140-5p/Jagged1/Notch axis mediates cartilage progenitor/stem cells fate reprogramming in knee osteoarthritis.

Purpose To determine the effects of cartilage progenitor cells, bone marrow mesenchymal stem cells and chondrocytes on cartilage repair as seed cells. Methods Porcine cartilage progenitor cells (CPCs), bone marrow mesenchymal stem cells (BMSCs) and chondrocytes (CCs) were obtained from the femoropatellar joints of young pigs, and seeded in agarose gel as a graft. During the 28-day culture, proliferation ability was measured by MTT assay, and gene expression of Collagen I, Collagen II, Aggrecan and SOX 9 were measured by qPCR. Qualitative and quantitative analysis of collagen, glycosaminoglycan and DNA were appraised by immunohistochemical staining and biochemical assay, and integration strength was analyzed by push-out tests. Results After 28-day culture, proliferation ability of CPCs and BMSCs was higher than CCs. Collagen, glycosaminoglycan, DNA content and chondrocyte-related genes expression in the cartilage progenitor cells seeded gel were significantly higher than the other two gels. Integration strength in the cartilage progenitor cells seeded gel was also higher compared with the other two gels. Conclusion Compared with CCs and BMSCs, CPCs in vitro have dominance in the ability of cell proliferation and differentiation as seed cells in tissue engineering.

Effects of Cartilage Progenitor Cells, Bone Marrow Mesenchymal Stem Cells and Chondrocytes on Cartilage Repair as Seed Cells: An in vitro Study

Objective: To design a new draining method for hemithyroidectomy at the lower side of the neck. Methods: Hemithyroidectomies of 235 cases were performed with the new drain incision at the lower side of the neck between December 1998 and July 2003. Results: All the draining operative procedures were performed smoothly, and produced a cosmeticulous scar. The mean amount drained was 20 ml (minimum 5 ml, maximum 80 ml) and no patients developed wound infection. Conclusion: The drain incision for hemithyroidectomy placed at the lower side of the neck results in a cosmeticulous scar which is easily covered by the collar and was safe and effective. We thereby recommend the use of this drain incision for hemithyroidectomy.

Clinical use of a drain incision placed below and laterial to the thyroidectomy incision

Peroneal Artery “Terminal” Perforator Pedicled Flap for Surrounding Soft Tissue Defects: A Retrospective Cohort Study

Efficacy analysis of three kinds of surgery for trigger thumb

A two-stage surgery for completely degloving injury of multiple fingers: A retrospective cohort study

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