Cartilage repair on magnesium scaffolds used as a subchondral bone replacement

Background: Ultrapurified alginate (UPAL) gel implantation has been demonstrated as effective in cartilage repair for osteochondral defects; however, cell transplantation within UPAL gels would be required to treat larger defects. Hypothesis: The combination of UPAL gel and bone marrow aspirate concentrate (BMAC) would enhance cartilage repair and subchondral bone repair for large osteochondral defects. Study Design: Controlled laboratory study. Methods: A total of 104 osteochondral defects (1 defect per knee) of 52 rabbits were randomly divided into 4 groups (26 defects per group): defects without any treatment (Defect group), defects treated using UPAL gel alone (UPAL group), defects treated using UPAL gel containing allogenic bone marrow mesenchymal stromal cells (UPAL-MSC group), and defects treated using UPAL gel containing BMAC (UPAL-BMAC group). At 4 and 16 weeks postoperatively, macroscopic and histologic evaluations and measurements of repaired subchondral bone volumes of reparative tissues were performed. Collagen orientation and mechanical properties of the reparative tissue were assessed at 16 weeks. Results: The defects in the UPAL-BMAC group were repaired with hyaline-like cartilage with well-organized collagen structures. The histologic scores at 4 weeks were significantly higher in the UPAL-BMAC group (16.9 ± 2.0) than in the Defect group (4.7 ± 1.9; P < .05), the UPAL group (10.0 ± 3.3; P < .05), and the UPAL-MSC group (12.2 ± 2.9; P < .05). At 16 weeks, the score in the UPAL-BMAC group (24.4 ± 1.7) was significantly higher than those in the Defect group (9.0 ± 3.7; P < .05), the UPAL group (14.2 ± 3.9; P < .05), and the UPAL-MSC group (16.3 ± 3.6; P < .05). At 4 and 16 weeks, the macroscopic evaluations were significantly superior in the UPAL-BMAC group compared with the other groups, and the values of repaired subchondral bone volumes in the UPAL-BMAC group were significantly higher than those in the Defect and UPAL groups. The mechanical properties of the reparative tissues were significantly better in the UPAL-BMAC group than in the other groups. Conclusion: The implantation of UPAL gel containing BMAC-enhanced hyaline-like cartilage repair and subchondral bone repair of osteochondral defects in a rabbit knee model. Clinical Relevance: These data support the potential clinical application of 1-step treatment for large osteochondral defects using biomaterial implantation with cell transplantation.

Download Full-text

Intra-Articular Injection of Umbilical Cord Mesenchymal Stem Cells Loaded With Graphene Oxide Granular Lubrication Ameliorates Inflammatory Responses and Osteoporosis of the Subchondral Bone in Rabbits of Modified Papain-Induced Osteoarthritis

Frontiers in Endocrinology ◽

10.3389/fendo.2021.822294 ◽

2022 ◽

Vol 12 ◽

Author(s):

Aifeng Liu ◽

Jixin Chen ◽

Juntao Zhang ◽

Chao Zhang ◽

Qinxin Zhou ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Graphene Oxide ◽

Animal Models ◽

Cartilage Repair ◽

Subchondral Bone ◽

Inflammatory Responses ◽

Micro Ct ◽

Tnf Α ◽

Femoral Condyles

AimThis study is to investigate the effects of umbilical cord mesenchymal stem cells (UCMSCs) loaded with the graphene oxide (GO) granular lubrication on ameliorating inflammatory responses and osteoporosis of the subchondral bone in knee osteoarthritis (KOA) animal models.MethodsThe KOA animal models were established using modified papain joint injection. 24 male New Zealand rabbits were classified into the blank control group, GO group, UCMSCs group, and GO + UCMSCs group, respectively. The concentration in serum and articular fluid nitric oxide (NO), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), type II collagen (COL-II), and glycosaminoglycan (GAG) was detected using ELISA, followed by the dissection of femoral condyles and staining of HE and Micro-CT for observation via the microscope.ResultsGO granular lubrication and UCMSCs repaired the KOA animal models. NO, IL-6, TNF-α, GAG, and COL-II showed optimal improvement performance in the GO + UCMSCs group, with statistical significance in contrast to the blank group (P <0.01). Whereas, there was a great difference in levels of inflammatory factors in serum and joint fluid. Micro-CT scan results revealed the greatest efficacy of the GO + UCMSCs group in improving joint surface damage and subchondral bone osteoporosis. HE staining pathology for femoral condyles revealed that the cartilage repair effect in GO + UCMSCs, UCMSCs, GO, and blank groups were graded down.ConclusionUCMSCs loaded with graphene oxide granular lubrication can promote the secretion of chondrocytes, reduce the level of joint inflammation, ameliorate osteoporosis of the subchondral bone, and facilitate cartilage repair.

Download Full-text

An Injectable Hydrogel Scaffold With Kartogenin-Encapsulated Nanoparticles for Porcine Cartilage Regeneration: A 12-Month Follow-up Study

The American Journal of Sports Medicine ◽

10.1177/0363546520957346 ◽

2020 ◽

Vol 48 (13) ◽

pp. 3233-3244

Author(s):

Wenqiang Yan ◽

Xingquan Xu ◽

Qian Xu ◽

Ziying Sun ◽

Zhongyang Lv ◽

...

Keyword(s):

Cartilage Repair ◽

Subchondral Bone ◽

Therapeutic Efficacy ◽

Tissue Repair ◽

Porcine Model ◽

Hyaline Cartilage ◽

Plga Nanoparticles ◽

Full Thickness ◽

Subchondral Bone Tissue

Background: Treatment of cartilage lesions is clinically challenging. A previous study demonstrated that a hyaluronic acid hydrogel ( m-HA) with kartogenin (KGN)-loaded PLGA nanoparticles ( m-HA+KGN treatment) achieved superior cartilage repair in a rabbit model. However, large animals serve as a bridge to translate animal outcomes into the clinic. Hypotheses: (1) m-HA+KGN treatment could facilitate hyaline cartilage and subchondral bone tissue repair in a porcine model. (2) Defect size and type (full-thickness chondral vs osteochondral) influence the therapeutic efficacy of m-HA+KGN treatment. Study Design: Controlled laboratory study. Methods: 48 minipigs were randomized into 3 treatment groups: m-HA hydrogel with KGN-loaded PLGA nanoparticles ( m-HA+KGN treatment), m-HA hydrogel ( m-HA treatment), and untreated (blank treatment). Full-thickness chondral (6.5 mm or 8.5 mm in diameter) or osteochondral (6.5 mm or 8.5 mm in diameter; 5-mm depth) defects were prepared in the medial femoral condyle. At 6 and 12 months postoperatively, defect repair was assessed by macroscopic appearance, magnetic resonance imaging (MRI), micro–computed tomography (µCT), and histologic and biomechanical tests. Results: The m-HA+KGN group exhibited superior gross and histological healing after evaluation at 6 and 12 months postoperatively. Improved quality of the repaired cartilage demonstrated by MRI and better subchondral bone reconstruction assessed by µCT were observed in the m-HA+KGN group. The m-HA+KGN group showed more hyaline-like cartilage exhibited by histological staining in terms of extracellular matrix, cartilage lacuna, and type II collagen. The biomechanical properties were improved in the m-HA+KGN group. With m-HA+KGN treatment, defects with a diameter of 6.5 mm or full-thickness chondral-type defects possessed significantly higher ICRS macroscopic and histological scores compared with diameter 8.5 mm or osteochondral-type defects. Conclusion: (1) m-HA+KGN treatment facilitated hyaline cartilage and subchondral bone tissue repair in a porcine model at the 12-month follow-up. (2) m-HA+KGN treatment demonstrated better therapeutic efficacy in defects with a diameter of 6.5 mm or full-thickness chondral-type defects. Clinical Relevance: This study verified the efficacy of this innovative KGN release system on cartilage repair. The KGN release system can be injected into defect sites arthroscopically. This convenient and minimally invasive operation holds important prospects for clinical application.

Download Full-text

Interspecies comparison of subchondral bone properties important for cartilage repair

Journal of Orthopaedic Research® ◽

10.1002/jor.22740 ◽

2014 ◽

Vol 33 (1) ◽

pp. 63-70 ◽

Cited By ~ 26

Author(s):

Anik Chevrier ◽

Ahou S. M. Kouao ◽

Genevieve Picard ◽

Mark B. Hurtig ◽

Michael D. Buschmann

Keyword(s):

Cartilage Repair ◽

Subchondral Bone ◽

Interspecies Comparison ◽

Bone Properties

Download Full-text

Age-Dependent Subchondral Bone Remodeling and Cartilage Repair in a Minipig Defect Model

Tissue Engineering Part C Methods ◽

10.1089/ten.tec.2017.0109 ◽

2017 ◽

Vol 23 (11) ◽

pp. 745-753 ◽

Cited By ~ 12

Author(s):

Christian G. Pfeifer ◽

Matthew B. Fisher ◽

Vishal Saxena ◽

Minwook Kim ◽

Elizabeth A. Henning ◽

...

Keyword(s):

Bone Remodeling ◽

Cartilage Repair ◽

Subchondral Bone ◽

Defect Model ◽

Age Dependent ◽

And Cartilage

Download Full-text

Fresh Allograft Replacement for Osteochondral Lesions of the Talus

Foot & Ankle Orthopaedics ◽

10.1177/2473011418s00137 ◽

2018 ◽

Vol 3 (3) ◽

pp. 2473011418S0013

Author(s):

Samuel Adams ◽

Nicholas Allen ◽

James Nunley ◽

Mark Easley

Keyword(s):

Surface Roughness ◽

Cartilage Repair ◽

Subchondral Bone ◽

Bone Destruction ◽

Osteochondral Allograft ◽

Osteochondral Lesions ◽

Normal Cartilage ◽

Allograft Transplantation ◽

Fresh Osteochondral Allograft ◽

Osteochondral Allografts

Category: Basic Sciences/Biologics Introduction/Purpose: Large osteochondral lesion of the talus (OLT) can be difficult to treat. Although many treatment options exist, fresh osteochondral allograft transplantation has demonstrated promise as the primary treatment for OLTs with substantial cartilage and bone involvement as well as a secondary treatment option after failure of other cartilage repair techniques. Fresh osteochondral allografts are size-matched from organ donors and, in theory, have healthy articular cartilage and bone. However, the quality of allograft cartilage and bone has never been examined with respect to the OLT cartilage and bone being replaced. The purpose of this study was to perform a matched comparison of the cartilage and bone from patients OLTs to the fresh osteochondral allograft replacement. Methods: Discarded intact osteochondral specimens were collected from 8 patients undergoing surgery for an OLT. The specimens included the excised OLT and a portion of the fresh allograft replacement that the same patient received at the time of surgery. Histologic analysis was performed. The safranin-o histology was then scored using the International Cartilage Repair Society (ICRS) histopathology grading and staging system. In this system the grade determines cartilage and bone destruction on a scale of 0 to 6.5, the stage determines the percentage of involvement in the specimen on a scale of 0 to 4, and the total score is the grade multiplied by the stage. The surface roughness was also compared between the OLT and allograft cartilage using ImageJ software (NIH). Paired t-tests were performed on the ICRS grade, stage, and total score, and surface roughness comparing the OLTs and allografts. Significance was set at p<0.05. Results: Gross histological inspection of the samples demonstrated cartilage erosion and subchondral bone destruction in the OLTs. In constrast, the osteochondral allografts demonstrated intact cartilage surface and normal subchondral bone in the allografts (Figure 1). The ICRS grade, stage, and total score were significantly higher in the implanted allografts compared to the resected OLTs (Figure 2); indicating better cartilage and bone morphology for the allografts compared to the OLTs. In fact, the mean grade and stage for the allograft samples were both less than a score of 1 which corresponds to healthy cartilage and bone with less than 10% surface fibrillations. Moreover, the surface roughness of the allograft cartilage was significantly smoother than the OLT cartilage. Conclusion: This is the first study to demonstrate that the use of fresh allograft transplantation for the treatment of OLTs replaces the damaged cartilage and bone with normal or near normal cartilage and bone. The replacement of damaged cartilage and subchondral bone with normal or near normal cartilage and bone may be the reason for improved pain relief and functional outcomes after fresh allograft transplantation for OLTs.

Download Full-text

Cartilage Protective and Chondrogenic Capacity of WIN-34B, a New Herbal Agent, in the Collagenase-Induced Osteoarthritis Rabbit Model and in Progenitor Cells from Subchondral Bone

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/527561 ◽

2013 ◽

Vol 2013 ◽

pp. 1-12 ◽

Cited By ~ 3

Author(s):

Jeong-Eun Huh ◽

Yeon-Cheol Park ◽

Byung-Kwan Seo ◽

Jae-Dong Lee ◽

Yong-Hyeon Baek ◽

...

Keyword(s):

Progenitor Cells ◽

Cartilage Repair ◽

Subchondral Bone ◽

Chondrogenic Differentiation ◽

Rabbit Model ◽

Type Ii Collagen ◽

Blue Staining ◽

Vehicle Group ◽

Potential Candidate ◽

Type Ii

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.

Download Full-text

Morphological Assessment of MACI Grafts in Patients with Revision Surgery and Total Joint Arthroplasty

Cartilage ◽

10.1177/1947603519890754 ◽

2019 ◽

pp. 194760351989075 ◽

Cited By ~ 3

Author(s):

Aswin Beck ◽

David Wood ◽

Christopher J. Vertullo ◽

Jay Ebert ◽

Greg Janes ◽

...

Keyword(s):

Cartilage Repair ◽

Subchondral Bone ◽

Revision Surgery ◽

Total Joint Arthroplasty ◽

Type Ii Collagen ◽

Joint Arthroplasty ◽

Type I ◽

Type Ii ◽

Osteophyte Formation ◽

Repair Tissue

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.

Download Full-text

The Effect of Single vs Serial Platelet-Rich Plasma Injections in Osteochondral Lesions Treated With Microfracture: An In Vivo Rabbit Model

The American Journal of Sports Medicine ◽

10.1177/03635465211052512 ◽

2021 ◽

pp. 036354652110525

Author(s):

Youichi Yasui ◽

John F. Dankert ◽

Ichiro Tonogai ◽

Nathaniel P. Mercer ◽

Margaret B. Goodale ◽

...

Keyword(s):

Bone Remodeling ◽

Cartilage Repair ◽

Subchondral Bone ◽

Inflammatory Cytokine ◽

Platelet Rich Plasma ◽

Cytokine Expression ◽

Osteochondral Lesions ◽

Micro Ct ◽

Cartilaginous Tissue ◽

Expression Levels

Background: Biological adjuvants are used after a musculoskeletal injury to improve healing, decrease inflammation, and restore joint homeostasis. Work on 1 such adjuvant, platelet-rich plasma (PRP), has suggested a positive effect when introduced during cartilage repair. However, it remains unknown whether healing osteochondral injuries benefit from serial PRP injections. Purpose: To evaluate the effects of serial PRP injections versus a single PRP injection on reparative cartilaginous tissue, subchondral bone remodeling, and the expression of inflammatory cytokines in joint synovium. Study Design: Controlled laboratory study. Methods: A total of 48 New Zealand White rabbits were randomly assigned to receive 1 (1P), 2 (2P), or 3 (3P) PRP injections. Cylindrical full-thickness cartilage defects (2.9 × 2.9 mm) with microdrillings (0.6-mm diameter) were created on the medial condyles of both knees. PRP was injected into the right knee after closure (groups 1P, 2P, and 3P), at 2 weeks after surgery (groups 2P and 3P), and at 4 weeks after surgery (group 3P). The left knees did not receive any PRP injections. A total of 6 rabbits in each group were euthanized at 3, 6, and 12 weeks postoperatively. Cartilage repair tissue was assessed using the Goebel macroscopic and modified International Cartilage Regeneration & Joint Preservation Society (ICRS) histological scoring systems. Subchondral bone remodeling was evaluated by micro–computed tomography analysis (micro-CT). Inflammatory cytokine levels were assessed by quantitative polymerase chain reaction. Results: No significant differences were found for the mean macroscopic score between the PRP groups at 12 weeks (control, 6.1 ± 3.3; group 1P, 3.4 ± 2.7; group 2P, 4.2 ± 2.9; group 3P, 0.7 ± 1.5). All PRP groups had a significantly higher mean modified ICRS histological score compared with the control group, but no significant difference was found among the PRP groups. No significant differences were seen in outcomes for the tested micro-CT parameters or cytokine expression levels. Conclusion: Serial PRP injections conferred no apparent advantage over single injections according to evaluations of the macroscopic and histological appearance of the cartilaginous tissue, subchondral bone healing, and inflammatory cytokine expression levels in the synovium. Clinical Relevance: The use of PRP as a biological adjuvant to bone marrow stimulation for osteochondral lesions has the potential to enhance the quality of regenerative cartilaginous tissue. We recommend only a single PRP injection if the use of PRP is indicated by the operating surgeon as an adjuvant therapy for osteochondral lesions.

Download Full-text

Bone Marrow Progenitor Cells Isolated from Young Rabbit Trochlea Are More Numerous and Exhibit Greater Clonogenic, Chondrogenic, and Osteogenic Potential than Cells Isolated from Condyles

Cartilage ◽

10.1177/1947603517693044 ◽

2017 ◽

Vol 9 (4) ◽

pp. 378-390 ◽

Cited By ~ 3

Author(s):

Garima Dwivedi ◽

Anik Chevrier ◽

Caroline D. Hoemann ◽

Michael D. Buschmann

Keyword(s):

Bone Marrow ◽

Progenitor Cells ◽

Cartilage Repair ◽

Subchondral Bone ◽

Biological Properties ◽

Biological Characteristics ◽

Cell Yield ◽

Young Rabbit ◽

Bone Marrow Progenitor

Objective. Bone marrow stimulation procedures initiate repair by fracturing or drilling subchondral bone at base of cartilaginous defect. Earlier studies have shown that defect location and animal age affect cartilage repair outcome, suggesting a strong influence of structural and biological characteristics of subchondral bone. Here, we analyzed comprehensive biological characteristics of bone marrow progenitor cells (BMPCs) in subchondral bone of young and old rabbit condyle and trochlea. We tested the hypothesis that in vitro biological properties of BMPCs are influenced by location, age of donor and method of their isolation. Design. In vitro biological properties, including cell yield, colony-forming unit fibroblasts (CFU-f), surface marker expression, and differentiation potential were determined. Comparisons were carried out between trochlea versus condyle and epiphyseal versus metaphyseal bone using old ( N = 5) and young animal knees ( N = 8) to generate collagenase and explant-derived BMPC cultures. Results. CFU-f, cell yield, expression of stem cell markers, and osteogenic differentiation were significantly superior for younger animals. Trochlear subchondral bone yielded the most progenitors with the highest clonogenic potential and cartilaginous matrix expression. Trochlear collagenase-derived BMPCs had higher clonogenic capacity than explant-derived ones. Epiphyseal cells generated a larger chondrogenic pellet mass than metaphyseal-derived BMPCs. All older pellet cultures and one non-responder young rabbit failed to accumulate glycosaminoglycans (GAGs). Conclusion. Taken together, these results suggest that properties intrinsic to subchondral progenitors could significantly influence cartilage repair potential, and could partly explain variability in cartilage repair outcomes using same cartilage repair approach.

Download Full-text