scholarly journals Second Generation Needling Techniques for the Treatment of Chondral Defects in Animal Model

Joints ◽  
2017 ◽  
Vol 05 (01) ◽  
pp. 027-033 ◽  
Author(s):  
Pietro Zedde ◽  
Sebastiano Cudoni ◽  
Lucia Manunta ◽  
Eraldo Passino ◽  
Gerolamo Masala ◽  
...  

Purpose To compare the macroscopic, histological, and immunohistochemical characteristics of the repair tissue of chondral defects treated with microfracture and nanofracture in an ovine model. Methods Full-thickness chondral lesions were created in the medial femoral condyle of both knees in four adult sheep and were treated with microfracture on one side and with nanofracture on the contralateral side. Chondral repair was assessed after 12 months by macroscopic, histological, and immunohistochemical analyses. Results Histological cartilage repair significantly improved in the samples treated with nanofracture for cellular morphological characteristics and cartilage architecture. The immunohistochemical analysis showed a significantly higher immunoreactivity to type II collagen in the defects treated with nanofracture. Conclusion Nanofracture provided better repair tissue than microfracture, with a more satisfactory cartilage architecture renovation and tissue having greater type II collagen content. Clinical Relevance Mesenchymal stem cell stimulation is the most frequently used primary cartilage repair procedure. Nanofracture represents a novel technique to stimulate bone marrow that results into a successful repair of chondral defects.

Cartilage ◽  
2019 ◽  
pp. 194760351989075 ◽  
Author(s):  
Aswin Beck ◽  
David Wood ◽  
Christopher J. Vertullo ◽  
Jay Ebert ◽  
Greg Janes ◽  
...  

Objective To compare the histological and immunohistochemical characteristics of matrix-assisted chondrocyte implantation (MACI) grafts between patients with revision surgery and patients with total joint arthroplasty. Methods Biopsies of MACI grafts from patients with revision and total joint arthroplasty. The graft tissue characteristics and subchondral bone were examined by qualitative histology, ICRS (International Cartilage Repair Society) II scoring and semiquantitative immunohistochemistry using antibodies specific to type I and type II collagen. Results A total of 31 biopsies were available, 10 undergoing total knee arthroplasty (TKA) and 21 patients undergoing revision surgery. Patients in the clinically failed group were significantly older (46.3 years) than patients in the revision group (36.6 years) ( P = 0.007). Histologically, the predominant tissue in both groups was of fibrocartilaginous nature, although a higher percentage of specimens in the revision group contained a hyaline-like repair tissue. The percentages of type I collagen (52.9% and 61.0%) and type II collagen (66.3% and 42.2%) were not significantly different between clinically failed and revised MACI, respectively. The talar dome contained the best and patella the worst repair tissue. Subchondral bone pathology was present in all clinically failed patients and consisted of bone marrow lesions, including edema, necrosis and fibrosis, intralesional osteophyte formation, subchondral bone plate elevation, intralesional osteophyte formation, subchondral bone cyst formation, or combinations thereof. Conclusions MACI grafts in patients with revision and total joint arthroplasty were predominantly fibrocartilage in repair type, did not differ in composition and were histologically dissimilar to healthy cartilage. Clinically failed cases showed evidence of osteochondral unit failure, rather than merely cartilage repair tissue failure. The role of the subchondral bone in relation to pain and failure and the pathogenesis warrants further investigation.


2017 ◽  
Vol 45 (7) ◽  
pp. 1490-1496 ◽  
Author(s):  
Bjørn Borsøe Christensen ◽  
Morten Lykke Olesen ◽  
Martin Lind ◽  
Casper Bindzus Foldager

Background: Repair of chondral injuries by use of cartilage chips has recently demonstrated clinical feasibility. Purpose: To investigate in vivo cartilage repair outcome of autologous cartilage chips compared with marrow stimulation in full-thickness cartilage defects in a minipig model. Study Design: Controlled laboratory study. Methods: Six Göttingen minipigs received two 6-mm chondral defects in the medial and lateral trochlea of each knee. The two treatment groups were (1) autologous cartilage chips embedded in fibrin glue (ACC) (n = 12) and (2) marrow stimulation (MST) (n = 12). The animals were euthanized after 6 months, and the composition of repair tissue was quantitatively determined using histomorphometry. Semiquantitative evaluation was performed by means of the International Cartilage Repair Society (ICRS) II score. Collagen type II staining was used to further evaluate the repair tissue composition. Results: Significantly more hyaline cartilage was found in the ACC (17.1%) compared with MST (2.9%) group ( P < .01). Furthermore, the ACC group had significantly less fibrous tissue (23.8%) compared with the MST group (41.1%) ( P < .01). No significant difference in fibrocartilage content was found (54.7% for ACC vs 50.8% for MST). The ACC group had significantly higher ICRS II scores for tissue morphological characteristics, matrix staining, cell morphological characteristics, surface assessment, mid/deep assessment, and overall assessment ( P < .05). The ACC-treated defects had significantly more collagen type II staining (54.5%) compared with the MST-treated defects (28.1%) ( P < .05). Conclusion: ACC transplant resulted in improved quality of cartilage repair tissue compared with MST at 6 months postoperatively. Clinical Relevance: Further studies are needed to investigate ACC as a possible alternative first-line treatment for focal cartilage injuries in the knee.


Cartilage ◽  
2010 ◽  
Vol 1 (2) ◽  
pp. 87-95 ◽  
Author(s):  
C. Wayne McIlwraith ◽  
David D. Frisbie

The therapeutic value of microfracture has been demonstrated in clinical patients. The rationale is that focal penetration of the dense subchondral plate exposes cartilage defects to the benefits of cellular and growth factor influx in addition to improving anchorage of the new tissue to the underlying subchondral bone and, to some extent, the surrounding cartilage. While functional outcomes have been reported, there is a paucity of data on the histological, biochemical, and molecular changes in human patients. This paper reviews 4 basic science studies of microfracture using an equine chondral defect model that gave some insight into possible mechanisms of action and also how the microfracture response could be augmented. In study I, microfracture of full-thickness chondral defects in exercised horses significantly increased the repair tissue volume in the defects at both 4 and 12 months. No adverse effects were seen. In study II, an investigation of the healing of full-thickness chondral defects during the first 8 weeks with or without microfracture demonstrated that microfracture significantly increased type II collagen expression as early as 8 weeks after treatment compared to controls; aggrecan expression was progressively increased during the first 8 weeks but was not significantly enhanced by microfracture. In study III, it was demonstrated that removal of the calcified cartilage layer provided optimal amount and attachment of repair tissue, emphasizing that careful removal of calcified layer is critical during debridement prior to microfracture. Study IV assessed the ability of IL-1ra/IGF-1 combination gene therapy to further modulate repair of microfractured chondral defects. The repair tissue in gene therapy–treated joints demonstrated increased proteoglycan and type II collagen content compared to microfracture alone.


Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1999
Author(s):  
Jade Perry ◽  
Anke J. Roelofs ◽  
Claire Mennan ◽  
Helen S. McCarthy ◽  
Alison Richmond ◽  
...  

Human umbilical cord (hUC)- or bone marrow (hBM)-derived mesenchymal stromal cells (MSCs) were evaluated as an allogeneic source of cells for cartilage repair. We aimed to determine if they could enhance healing of chondral defects with or without the recruitment of endogenous cells. hMSCs were applied into a focal joint surface injury in knees of adult mice expressing tdTomato fluorescent protein in cells descending from Gdf5-expressing embryonic joint interzone cells. Three experimental groups were used: (i) hUC-MSCs, (ii) hBM-MSCs and (iii) PBS (vehicle) without cells. Cartilage repair was assessed after 8 weeks and tdTomato-expressing cells were detected by immunostaining. Plasma levels of pro-inflammatory mediators and other markers were measured by electrochemiluminescence. Both hUC-MSC (n = 14, p = 0.009) and hBM-MSC (n = 13, p = 0.006) treatment groups had significantly improved cartilage repair compared to controls (n = 18). While hMSCs were not detectable in the repair tissue at 8 weeks post-implantation, increased endogenous Gdf5-lineage cells were detected in repair tissue of hUC-MSC-treated mice. This xenogeneic study indicates that hMSCs enhance intrinsic cartilage repair mechanisms in mice. Hence, hMSCs, particularly the more proliferative hUC-MSCs, could represent an attractive allogeneic cell population for treating patients with chondral defects and perhaps prevent the onset and progression of osteoarthritis.


2018 ◽  
Vol 46 (10) ◽  
pp. 2384-2393 ◽  
Author(s):  
Kazunori Shimomura ◽  
Yukihiko Yasui ◽  
Kota Koizumi ◽  
Ryota Chijimatsu ◽  
David A. Hart ◽  
...  

Background: Articular cartilage has limited healing capacity, owing in part to poor vascularity and innervation. Once injured, it cannot be repaired, typically leading to high risk for developing osteoarthritis. Thus, cell-based and/or tissue-engineered approaches have been investigated; however, no approach has yet achieved safety and regenerative repair capacity via a simple implantation procedure. Purpose: To assess the safety and efficacy of using a scaffold-free tissue-engineered construct (TEC) derived from autologous synovial membrane mesenchymal stem cells (MSCs) for effective cartilage repair. Study Design: Case series; Level of evidence, 4. Methods: Five patients with symptomatic knee chondral lesions (1.5-3.0 cm2) on the medial femoral condyle, lateral femoral condyle, or femoral groove were included. Synovial MSCs were isolated from arthroscopic biopsy specimens and cultured to develop a TEC that matched the lesion size. The TECs were then implanted into chondral defects without fixation and assessed up to 24 months postoperatively. The primary outcome was the safety of the procedure. Secondary outcomes were self-assessed clinical scores, arthroscopy, tissue biopsy, and magnetic resonance image–based estimation of morphologic and compositional quality of the repair tissue. Results: No adverse events were recorded, and self-assessed clinical scores for pain, symptoms, activities of daily living, sports activity, and quality of life were significantly improved at 24 months after surgery. Secure defect filling was confirmed by second-look arthroscopy and magnetic resonance imaging in all cases. Histology of biopsy specimens indicated repair tissue approaching the composition and structure of hyaline cartilage. Conclusion: Autologous scaffold-free TEC derived from synovial MSCs may be used for regenerative cartilage repair via a sutureless and simple implantation procedure. Registration: 000008266 (UMIN Clinical Trials Registry number).


Cartilage ◽  
2019 ◽  
pp. 194760351986531 ◽  
Author(s):  
Morten Lykke Olesen ◽  
Bjørn Borsøe Christensen ◽  
Casper Bindzus Foldager ◽  
Kris Chadwick Hede ◽  
Natasja Leth Jørgensen ◽  
...  

Background Repair of chondral injuries using cartilage chips has recently demonstrated clinical feasibility. Autologous platelet-rich plasma (PRP) is a potential promising technique for improving healing response during cartilage repair. Purpose To assess the cartilage repair tissue quality after autologous cartilage chips treatment (CC) with and without repeated local injections of PRP for the treatment of full-thickness focal chondral defects of the knee. Materials and Methods Two full-thickness chondral defects (Ø = 6 mm) were created in the medial and lateral trochlea facets of each knee in 6 skeletally mature Göttingen minipigs. The 2 treatment groups were (1) CC with 1 weekly PRP injection for 3 weeks ( n = 12) and (2) CC alone ( n = 12). The animals were euthanized after 6 months. Samples of whole blood and PRP were analyzed for concentrations of platelets and nucleated cells. The composition of the cartilage repair tissue was assessed using gross appearance assessment, histomorphometry, and semiquantitative scoring (ICRS II). Results Histological evaluation demonstrated no significant difference in the content of hyaline cartilage (CC + PRP: 18.7% vs. CC: 19.6%), fibrocartilage (CC + PRP: 48.1% vs. CC: 51.8%), or fibrous tissue (CC + PRP: 22.7% vs. CC: 21.8%) between the treatment groups. Macroscopic evaluation did not demonstrate any difference between groups. Conclusions PRP injections after CC in the treatment of full-thickness cartilage injuries demonstrated no beneficial effects in terms of macroscopic and histologic composition of cartilage repair tissue.


2008 ◽  
Vol 19 (5) ◽  
pp. 1253-1262 ◽  
Author(s):  
Goetz H. Welsch ◽  
Tallal C. Mamisch ◽  
Sebastian Quirbach ◽  
Lukas Zak ◽  
Stefan Marlovits ◽  
...  

2017 ◽  
Vol 46 (3) ◽  
pp. 713-727 ◽  
Author(s):  
Chin-Chean Wong ◽  
Chih-Hwa Chen ◽  
Li-Hsuan Chiu ◽  
Yang-Hwei Tsuang ◽  
Meng-Yi Bai ◽  
...  

Background: Insufficient cell numbers still present a challenge for articular cartilage repair. Converting heterotopic auricular chondrocytes by extracellular matrix may be the solution. Hypothesis: Specific extracellular matrix may convert the phenotype of auricular chondrocytes toward articular cartilage for repair. Study Design: Controlled laboratory study. Methods: For in vitro study, rabbit auricular chondrocytes were cultured in monolayer for several passages until reaching status of dedifferentiation. Later, they were transferred to chondrogenic type II collagen (Col II)–coated plates for further cell conversion. Articular chondrogenic profiles, such as glycosaminoglycan deposition, articular chondrogenic gene, and protein expression, were evaluated after 14-day cultivation. Furthermore, 3-dimensional constructs were fabricated using Col II hydrogel-associated auricular chondrocytes, and their histological and biomechanical properties were analyzed. For in vivo study, focal osteochondral defects were created in the rabbit knee joints, and auricular Col II constructs were implanted for repair. Results: The auricular chondrocytes converted by a 2-step protocol expressed specific profiles of chondrogenic molecules associated with articular chondrocytes. The histological and biomechanical features of converted auricular chondrocytes became similar to those of articular chondrocytes when cultivated with Col II 3-dimensional scaffolds. In an in vivo animal model of osteochondral defects, the treated group (auricular Col II) showed better cartilage repair than did the control groups (sham, auricular cells, and Col II). Histological analyses revealed that cartilage repair was achieved in the treated groups with abundant type II collagen and glycosaminoglycans syntheses rather than elastin expression. Conclusion: The study confirmed the feasibility of applying heterotopic chondrocytes for cartilage repair via extracellular matrix–induced cell conversion. Clinical Relevance: This study proposes a feasible methodology to convert heterotopic auricular chondrocytes for articular cartilage repair, which may serve as potential alternative sources for cartilage repair.


2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Jeong-Eun Huh ◽  
Yeon-Cheol Park ◽  
Byung-Kwan Seo ◽  
Jae-Dong Lee ◽  
Yong-Hyeon Baek ◽  
...  

We sought to determine the cartilage repair capacity of WIN-34B in the collagenase-induced osteoarthritis rabbit model and in progenitor cells from subchondral bone. The cartilage protective effect of WIN-34B was measured by clinical and histological scores, cartilage area, and proteoglycan and collagen contents in the collagenase-induced osteoarthritis rabbit model. The efficacy of chondrogenic differentiation of WIN-34B was assessed by expression of CD105, CD73, type II collagen, and aggrecanin vivoand was analyzed by the surface markers of progenitor cells, the mRNA levels of chondrogenic marker genes, and the level of proteoglycan, GAG, and type II collagenin vitro. Oral administration of WIN-34B significantly increased cartilage area, and this was associated with the recovery of proteoglycan and collagen content. Moreover, WIN-34B at 200 mg/kg significantly increased the expression of CD105, CD73, type II collagen, and aggrecan compared to the vehicle group. WIN-34B markedly enhanced the chondrogenic differentiation of CD105 and type II collagen in the progenitor cells from subchondral bone. Also, we confirmed that treatment with WIN-34B strongly increased the number of SH-2(CD105) cells and expression type II collagen in subchondral progenitor cells. Moreover, WIN-34B significantly increased proteoglycan, as measured by alcian blue staining; the mRNA level of type IIα1 collagen, cartilage link protein, and aggrecan; and the inhibition of cartilage matrix molecules, such as GAG and type II collagen, in IL-1β-treated progenitor cells. These findings suggest that WIN-34B could be a potential candidate for effective anti-osteoarthritic therapy with cartilage repair as well as cartilage protection via enhancement of chondrogenic differentiation in the collagenase-induced osteoarthritis rabbit model and progenitor cells from subchondral bone.


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