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

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

Marine Drugs ◽  
2019 ◽  
Vol 17 (4) ◽  
pp. 236 ◽  
Author(s):  
Lu ◽  
Chang ◽  
Tsai ◽  
Chen ◽  
Chen ◽  
...  

Platelet-rich plasma (PRP) is rich in growth factors and has commonly been utilized in the repair and regeneration of damaged articular cartilage. However, the major drawbacks of direct PRP injection are unstable biological fixation and fast or burst release of growth factors. Fucoidan is a heparinoid compound that can bind growth factors to control their release rate. Furthermore, fucoidan can reduce arthritis through suppressing inflammatory responses and thus it has been reported to prevent the progression of osteoarthritis, promote bone regeneration and accelerate healing of cartilage injury. Injectable hydrogels can be used to deliver cells and growth factors for an alternative, less invasive treatment of cartilage defects. In this study, hyaluronic acid (HA) and fucoidan (FD) was blended with gelatin (GLT) and the GLT/HA/FD hybrid was further cross-linked with genipin (GP) to prepare injectable GP-GLT/HA/FD hydrogels. The gelation rate was affected by the GP, GLT, HA and FD concentrations, as well as the pH values. The addition of HA and FD to GLT networks improved the mechanical strength of the hydrogels and facilitated the sustained release of PRP growth factors. The GP-GLT/HA/FD hydrogel showed adequate injectability, shape-persistent property and strong adhesive ability, and was more resistant to enzymatic degradation. The PRP-loaded GP-GLT/HA/FD hydrogel promoted cartilage regeneration in rabbits, which may lead to an advanced PRP therapy for enhancing cartilage repair.


2021 ◽  
Author(s):  
Guo Song ◽  
Kumar Gurung ◽  
ShouYong Fu ◽  
GuangWen Jin ◽  
Longhao Jin

Abstract BackgroundAutologous bone marrow buffy coat transplantation possesses obvious advantages in the therapy of large cartilage defects and osteoarthritis. However, there is no definite research on the specific effective components of bone marrow buffy coat and its mechanism of cartilage regeneration. Moreover, as the crucial cartilage regenerative cell in bone marrow buffy coat, mesenchymal stem cells(MSCs) are difficult to fix onto the damaged cartilage area without damaging the subchondral bone. We assessed the effect of using hyaluronic acid(HA) as a liquid scaffold mixed with autologous bone marrow buffy coat to fix cartilage defect.Methods and MaterialsWe extracted the bone marrow from the anterior superior iliac crest of the white New Zealand rabbit, centrifuged to obtain a buffy coat, and analyzed the components of buffy coat by ELISA. Buffy coat+HA group, MSC+HA group, MSC+TGF-β+HA group were cultured in vitro and observed by staining. In addition, we made damage to the femoral condyle of rabbits, and divided them into groups: HA group, buffy coat group, buffy coat with HA group. Each group was assessed for cartilage regeneration by visual observation, histological and immunohistochemical analysis at 4 weeks and 8 weeks, and biochemical analysis at 8 weeks postoperatively. One-way ANOVA and LSD were used for statistic analysis.ResultsBuffy coat have a variety of growth factors, inflammatory factors and anti-inflammatory factors that stimulate the MSCs’ regeneration. Buffy coat can differentiate into cartilage without TGF-β stimulation in vitro. The cartilage regeneration ability of buffy coat and buffy coat+HA is strong, and the combination of buffy coat and liquid scaffold HA can make cartilage formation ability more stable in vivo.ConclusionMSC, multiple growth factors and cytokines in buffy coat synergistically promote cartilage regeneration. Liquid scaffold HA enhances the effect of buffy coat on cartilage attachment and regeneration of cartilage defects.


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

2018 ◽  
Vol 27 (3) ◽  
pp. 950-961 ◽  
Author(s):  
Juan Manuel Domínguez Pérez ◽  
José Andrés Fernández-Sarmiento ◽  
Daniel Aguilar García ◽  
María del Mar Granados Machuca ◽  
Juan Morgaz Rodríguez ◽  
...  

2020 ◽  
Author(s):  
Guo Song ◽  
Kumar Gurung ◽  
Shouyong Fu ◽  
Guangwen Jin ◽  
Longhao Jin

Abstract BackgroundAutologous bone marrow buffy coat transplantation possesses obvious advantages in the therapy of large cartilage defects and osteoarthritis. However, there is no definite research on the specific effective components of bone marrow buffy coat and its mechanism of cartilage regeneration. Moreover, as the crucial cartilage regenerative cell in bone marrow buffy coat, mesenchymal stem cells(MSCs) are difficult to fix onto the damaged cartilage area without damaging the subchondral bone. We assessed the effect of using hyaluronic acid(HA) as a liquid scaffold mixed with autologous bone marrow buffy coat to fix cartilage defect.Methods and MaterialsWe extracted the bone marrow from the anterior superior iliac crest of the white New Zealand rabbit, centrifuged to obtain a buffy coat, and analyzed the components of buffy coat by ELISA. Buffy coat+HA group, MSC+HA group, MSC+TGF-β+HA group were cultured in vitro and observed by staining. In addition, we made damage to the femoral condyle of rabbits, and divided them into groups: HA group, buffy coat group, buffy coat with HA group. Each group was assessed for cartilage regeneration by visual observation, histological and immunohistochemical analysis at 4 weeks and 8 weeks, and biochemical analysis at 8 weeks postoperatively. One-way ANOVA and LSD were used for statistic analysis.ResultsBuffy coat have a variety of growth factors, inflammatory factors and anti-inflammatory factors that stimulate the MSCs’ regeneration. Buffy coat can differentiate into cartilage without TGF-β stimulation in vitro. The cartilage regeneration ability of buffy coat and buffy coat+HA is strong, and the combination of buffy coat and liquid scaffold HA can make cartilage formation ability more stable in vivo.ConclusionMSC, multiple growth factors and cytokines in buffy coat synergistically promote cartilage regeneration. Liquid scaffold HA enhances the effect of buffy coat on cartilage attachment and regeneration of cartilage defects.


2020 ◽  
Vol 48 (13) ◽  
pp. 3224-3232
Author(s):  
Changgui Zhang ◽  
Yunong Ao ◽  
Jin Cao ◽  
Liu Yang ◽  
Xiaojun Duan

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.


Author(s):  
Vikas V. Gaikwad ◽  
Abasaheb B. Patil ◽  
Madhuri V. Gaikwad

Scaffolds are used for drug delivery in tissue engineering as this system is a highly porous structure to allow tissue growth.  Although several tissues in the body can regenerate, other tissue such as heart muscles and nerves lack regeneration in adults. However, these can be regenerated by supplying the cells generated using tissue engineering from outside. For instance, in many heart diseases, there is need for heart valve transplantation and unfortunately, within 10 years of initial valve replacement, 50–60% of patients will experience prosthesis associated problems requiring reoperation. This could be avoided by transplantation of heart muscle cells that can regenerate. Delivery of these cells to the respective tissues is not an easy task and this could be done with the help of scaffolds. In situ gel forming scaffolds can also be used for the bone and cartilage regeneration. They can be injected anywhere and can take the shape of a tissue defect, avoiding the need for patient specific scaffold prefabrication and they also have other advantages. Scaffolds are prepared by biodegradable material that result in minimal immune and inflammatory response. Some of the very important issues regarding scaffolds as drug delivery systems is reviewed in this article.


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