Cell-Free HA-MA/PLGA Scaffolds with Radially Oriented Pores for In Situ Inductive Regeneration of Full Thickness Cartilage Defects

2016 ◽  
Vol 16 (11) ◽  
pp. 1632-1642 ◽  
Author(s):  
Yuankun Dai ◽  
Zhenzhen Gao ◽  
Lie Ma ◽  
Dongan Wang ◽  
Changyou Gao
Keyword(s):  
Cartilage Defects ◽  
Full Thickness

Cell-free macro-porous fibrin scaffolds for in situ inductive regeneration of full-thickness cartilage defects

2016 ◽  
Vol 4 (25) ◽  
pp. 4410-4419 ◽  
Author(s):  
Yuankun Dai ◽  
Gang Liu ◽  
Lie Ma ◽  
Dongan Wang ◽  
Changyou Gao
Keyword(s):  
Growth Factors ◽  
Cartilage Regeneration ◽  
Cartilage Defects ◽  
Full Thickness ◽  
Fibrin Scaffold

Macro-porous fibrin scaffold was fabricated and used to induce cartilage regenerationin situwithout pre-loaded cells or growth factors.

Donor Cell Fate in Particulated Juvenile Allograft Cartilage for the Repair of Articular Cartilage Defects

2020 ◽  
Vol 48 (13) ◽  
pp. 3224-3232
Author(s):  
Changgui Zhang ◽  
Yunong Ao ◽  
Jin Cao ◽  
Liu Yang ◽  
Xiaojun Duan
Keyword(s):  
In Situ Hybridization ◽  
Cartilage Defects ◽  
Control Group ◽  
Full Thickness ◽  
Positive Signal ◽  
Sry Gene ◽  
The Difference ◽  
Articular Cartilage Defects ◽  
Experimental Group

Background: Particulated juvenile allograft cartilage (PJAC) has demonstrated good clinical efficacy in repairing articular cartilage defects, but the related repair mechanism after transplant and the biological characteristics of the transplanted cells are still unclear. Purpose: To study the efficacy of PJAC in repairing full-thickness cartilage defects and the specific fate of donor cells to provide experimental evidence for its clinical application. Study Design: Controlled laboratory study. Methods: Twenty female Guizhou minipigs were randomly divided into an experimental group and a control group. An 8-mm cylindrical full-thickness cartilage defect was created in the femoral trochlea of 1 knee in all minipigs. The experimental group received transplant of PJAC from 5 male juvenile Guizhou minipigs (PJAC group; n = 10) and the control group received autologous cartilage chips (ACC group; n = 10). Follow-up assessments were conducted at 1 month and 3 months to track the transplanted cells by the male-specific sex-determining region Y-linked (SRY) gene; tissue sections were hybridized in situ, and O’Driscoll histological scoring was performed according to hematoxylin and eosin staining, safranin O and fast green staining, and toluidine blue O staining, as well as immunohistochemical evaluation of aggrecan and Sry-type HMG-box 9 (SOX9). Results: All 20 Guizhou minipigs were followed; no infection or incision healing disorder occurred after the operation. By SRY in situ hybridization, the SRY signal of the transplanted cells was positive in the repaired tissue of the defect, and the SRY positive signal could still be detected in repaired tissue at 3 months postoperatively. The average number of positive cells was 68.6 ± 11.91 at 1 month and 32.6 ± 3.03 at 3 months (confocal microscope: ×400), and the difference was statistically significant. The O’Driscoll histological scores were 14 ± 0.71 in the ACC group and 9.8 ± 0.84 in the PJAC group at 1 month, and 18 ± 1.20 in the ACC group and 17.4 ± 1.14 in the PJAC group at 3 months. The scores were statistically significant between the ACC group and PJAC group at 1 month. The positive rates of SOX9 in the PJAC and ACC groups at 1 month were 67.6% ± 3.78% and 63.4% ± 5.30%, respectively, and the difference was not statistically significant ( P > .05). The positive rates of SOX9 in the PJAC and ACC groups at 3 months were 68.8% ± 2.69% and 17.1% ± 1.26%, respectively, and the difference was statistically significant ( P < .05). The positive rates of aggrecan in the PJAC and ACC groups at 1 month were 40.5% ± 2.78% and 42.4% ± 0.54% respectively, and the difference was not statistically significant ( P > .05). The positive rates of aggrecan in the PJAC and ACC groups at 3 months were 40.8% ± 1.50% and 30.1% ± 2.44%, respectively, and the difference was not statistically significant ( P > .05). Conclusion: An animal model was established with Guizhou minipigs, and the cartilage defect was repaired with PJAC from male minipigs. The SRY gene positive signal could be detected from the repaired tissue by in situ hybridization, indicating that the transplanted cells survived at least 3 months. The key genes of cartilage formation, SOX9 and aggrecan, were expressed at 1 month and 3 months, and SOX9 expression was stronger in the PJAC group than the ACC group at 3 months. Clinical Relevance: This study suggests that it is feasible to study the biological characteristics of transplanted cells in the cartilage region by the sex-determining gene.

scholarly journals Allogeneic Umbilical Cord Blood–Derived Mesenchymal Stem Cell Implantation Versus Microfracture for Large, Full-Thickness Cartilage Defects in Older Patients: A Multicenter Randomized Clinical Trial and Extended 5-Year Clinical Follow-up

2021 ◽  
Vol 9 (1) ◽  
pp. 232596712097305
Author(s):  
Hong-Chul Lim ◽  
Yong-Beom Park ◽  
Chul-Won Ha ◽  
Brian J. Cole ◽  
Beom-Koo Lee ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Adverse Events ◽  
Cartilage Repair ◽  
Older Patients ◽  
Cartilage Defects ◽  
Full Thickness ◽  
Phase 3 ◽  
Randomized Controlled ◽  
Cartilage Restoration

Background: There is currently no optimal method for cartilage restoration in large, full-thickness cartilage defects in older patients. Purpose: To determine whether implantation of a composite of allogeneic umbilical cord blood–derived mesenchymal stem cells and 4% hyaluronate (UCB-MSC-HA) will result in reliable cartilage restoration in patients with large, full-thickness cartilage defects and whether any clinical improvements can be maintained up to 5 years postoperatively. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: A randomized controlled phase 3 clinical trial was conducted for 48 weeks, and the participants then underwent extended 5-year observational follow-up. Enrolled were patients with large, full-thickness cartilage defects (International Cartilage Repair Society [ICRS] grade 4) in a single compartment of the knee joint, as confirmed by arthroscopy. The defect was treated either with UCB-MSC-HA implantation through mini-arthrotomy or with microfracture. The primary outcome was proportion of participants who improved by ≥1 grade on the ICRS Macroscopic Cartilage Repair Assessment (blinded evaluation) at 48-week arthroscopy. Secondary outcomes included histologic assessment; changes in pain visual analog scale (VAS) score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and International Knee Documentation Committee (IKDC) score from baseline; and adverse events. Results: Among 114 randomized participants (mean age, 55.9 years; 67% female; body mass index, 26.2 kg/m2), 89 completed the phase 3 clinical trial and 73 were enrolled in the 5-year follow-up study. The mean defect size was 4.9 cm2 in the UCB-MSC-HA group and 4.0 cm2 in the microfracture group ( P = .051). At 48 weeks, improvement by ≥1 ICRS grade was seen in 97.7% of the UCB-MSC-HA group versus 71.7% of the microfracture group ( P = .001); the overall histologic assessment score was also superior in the UCB-MSC-HA group ( P = .036). Improvement in VAS pain, WOMAC, and IKDC scores were not significantly different between the groups at 48 weeks, however the clinical results were significantly better in the UCB-MSC-HA group at 3- to 5-year follow-up ( P < .05). There were no differences between the groups in adverse events. Conclusion: In older patients with symptomatic, large, full-thickness cartilage defects with or without osteoarthritis, UCB-MSC-HA implantation resulted in improved cartilage grade at second-look arthroscopy and provided more improvement in pain and function up to 5 years compared with microfracture. Registration: NCT01041001, NCT01626677 (ClinicalTrials.gov identifier).

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