Overlapping Allografts Provide Superior and More Reliable Surface Topography Matching Than Oblong Allografts: A Computer-Simulated Model Study

2021 ◽  
pp. 036354652110030
Author(s):  
Hailey P. Huddleston ◽  
Atsushi Urita ◽  
William M. Cregar ◽  
Theodore M. Wolfson ◽  
Brian J. Cole ◽  
...  

Background: Osteochondral allograft transplantation is 1 treatment option for focal articular cartilage defects of the knee. Large irregular defects, which can be treated using an oblong allograft or multiple overlapping allografts, increase the procedure’s technical complexity and may provide suboptimal cartilage and subchondral surface matching between donor grafts and recipient sites. Purpose: To quantify and compare cartilage and subchondral surface topography mismatch and cartilage step-off for oblong and overlapping allografts using a 3-dimensional simulation model. Study Design: Controlled laboratory study. Methods: Human cadaveric medial femoral hemicondyles (n = 12) underwent computed tomography and were segmented into cartilage and bone components using 3-dimensional reconstruction and modeling software. Segments were then exported into point-cloud models. Modeled defect sizes of 17 × 30 mm were created on each recipient hemicondyle. There were 2 types of donor allografts from each condyle utilized: overlapping and oblong. Grafts were virtually harvested and implanted to optimally align with the defect to provide minimal cartilage surface topography mismatch. Least mean squares distances were used to measure cartilage and subchondral surface topography mismatch and cartilage step-off. Results: Cartilage and subchondral topography mismatch for the overlapping allograft group was 0.27 ± 0.02 mm and 0.80 ± 0.19 mm, respectively. In comparison, the oblong allograft group had significantly increased cartilage (0.62 ± 0.43 mm; P < .001) and subchondral (1.49 ± 1.10 mm; P < .001) mismatch. Cartilage step-off was also found to be significantly increased in the oblong group compared with the overlapping group ( P < .001). In addition, overlapping allografts more reliably provided a significantly higher percentage of clinically acceptable (0.5- and 1-mm thresholds) cartilage surface topography matching (overlapping: 100% for both 0.5 and 1 mm; oblong: 90% for 1 mm and 56% for 0.5 mm; P < .001) and cartilage step-off (overlapping: 100% for both 0.5 and 1 mm; oblong: 86% for 1 mm and 12% for 0.5 mm; P < .001). Conclusion: This computer simulation study demonstrated improved topography matching and decreased cartilage step-off with overlapping osteochondral allografts compared with oblong osteochondral allografts when using grafts from donors that were not matched to the recipient condyle by size or radius of curvature. These findings suggest that overlapping allografts may be superior in treating large, irregular osteochondral defects involving the femoral condyles with regard to technique. Clinical Relevance: This study suggests that overlapping allografts may provide superior articular cartilage surface topography matching compared with oblong allografts and do so in a more reliable fashion. Surgeons may consider overlapping allografts over oblong allografts because of the increased ease of topography matching during placement.

2009 ◽  
Vol 18 (5-6) ◽  
pp. 505-512 ◽  
Author(s):  
Jung Yoon Bae ◽  
Kazuaki Matsumura ◽  
Shigeyuki Wakitani ◽  
Amu Kawaguchi ◽  
Sadami Tsutsumi ◽  
...  

A fresh osteochondral allograft is one of the most effective treatments for cartilage defects of the knee. Despite the clinical success, fresh osteochondral allografts have great limitations in relation to the short storage time that cartilage tissues can be well-preserved. Fresh osteochondral grafts are generally stored in culture medium at 4°C. While the viability of articular cartilage stored in culture medium is significantly diminished within 1 week, appropriate serology testing to minimize the chances for the disease transmission requires a minimum of 2 weeks. (–)-Epigallocatechin-3- O-gallate (EGCG) has differential effects on the proliferation of cancer and normal cells, thus a cytotoxic effect on various cancer cells, but a cytopreservative effect on normal cells. Therefore, a storage solution containing EGCG might extend the storage duration of articular cartilages. Rabbit osteochondral allografts were performed with osteochondral grafts stored at 4°C in culture medium containing EGCG for 2 weeks and then the clinical effects were examined with macroscopic and histological assessment after 4 weeks. The cartilaginous structure of an osteochondral graft stored with EGCG was well-preserved with high cell viability and glycosaminoglycan (GAG) content of the extracellular matrix (ECM). After an osteochondral allograft, the implanted osteochondral grafts stored with EGCG also provided a significantly better retention of the articular cartilage with viability and metabolic activity. These data suggest that EGCG can be an effective storage agent that allows long-term preservation of articular cartilage under cold storage conditions.


Author(s):  
Wenli Dai ◽  
Muyang Sun ◽  
Xi Leng ◽  
Xiaoqing Hu ◽  
Yingfang Ao

Despite considerable progress for the regenerative medicine, repair of full-thickness articular cartilage defects and osteochondral interface remains challenging. This low efficiency is largely due to the difficulties in recapitulating the stratified zonal architecture of articular cartilage and engineering complex gradients for bone-soft tissue interface. This has led to increased interest in three-dimensional (3D) printing technologies in the field of musculoskeletal tissue engineering. Printable and biocompatible hydrogels are attractive materials for 3D printing applications because they not only own high tunability and complexity, but also offer favorable biomimetic environments for live cells, such as porous structure, high water content, and bioactive molecule incorporation. However, conventional hydrogels are usually mechanically weak and brittle, which cannot reach the mechanical requirements for repair of articular cartilage defects and osteochondral interface. Therefore, the development of elastic and high-strength hydrogels for 3D printing in the repairment of cartilage defects and osteochondral interface is crucial. In this review, we summarized the recent progress in elastic and high-strength hydrogels for 3D printing and categorized them into six groups, namely ion bonds interactions, nanocomposites integrated in hydrogels, supramolecular guest–host interactions, hydrogen bonds interactions, dynamic covalent bonds interactions, and hydrophobic interactions. These 3D printed elastic and high-strength hydrogels may provide new insights for the treatment of osteochondral and cartilage diseases.


Cartilage ◽  
2020 ◽  
pp. 194760352096707
Author(s):  
Kezhou Wu ◽  
Leila Laouar ◽  
Janet A. W. Elliott ◽  
Nadr M. Jomha

Objective Successful preservation of articular cartilage will increase the availability of osteochondral allografts to treat articular cartilage defects. We compared the effects of 2 methods for storing cartilage tissues using 10-mm diameter osteochondral dowels or femoral condyles at −196°C: (a) storage with a surrounding vitrification solution versus (b) storage without a surrounding vitrification solution. We investigated the effects of 2 additives (chondroitin sulfate and ascorbic acid) for vitrification of articular cartilage. Design Healthy porcine stifle joints ( n = 11) from sexually mature pigs were collected from a slaughterhouse within 6 hours after slaughtering. Dimethyl sulfoxide, ethylene glycol, and propylene glycol were permeated into porcine articular cartilage using an optimized 7-hour 3-step cryoprotectant permeation protocol. Chondrocyte viability was assessed by a cell membrane integrity stain and chondrocyte metabolic function was assessed by alamarBlue assay. Femoral condyles after vitrification were assessed by gross morphology for cartilage fractures. Results There were no differences in the chondrocyte viability (~70%) of 10-mm osteochondral dowels after vitrification with or without the surrounding vitrification solution. Chondrocyte viability in porcine femoral condyles was significantly higher after vitrification without the surrounding vitrification solution (~70%) compared to those with the surrounding vitrification solution (8% to 36%). Moreover, articular cartilage fractures were not seen in femoral condyles vitrified without surrounding vitrification solution compared to fractures seen in condyles with surrounding vitrification solution. Conclusions Vitrification of femoral condyle allografts can be achieved by our optimized approach. Removing the surrounding vitrification solution is advantageous for vitrification outcomes of large size osteochondral allografts.


2020 ◽  
Vol 8 (7_suppl6) ◽  
pp. 2325967120S0045
Author(s):  
Hailey Huddleston ◽  
Adam Yanke ◽  
Nozomu Inoue

Objectives: When performing a patellar osteochondral allograft, the patellar allograft is harvested from a similar anatomic location as the defect. This approach assumes that graft will have similar topography to the patellar defect. However, to our knowledge, no prior study has investigated the topography of the patella and what intrinsic factors of the graft and the recipient affect mismatch of the chondral and osseous layers between the graft and defect. Methods: Three-dimensional (3D) computed tomography (CT) models of the patella were created and exported into point-cloud models using a 3D reconstruction program (Mimics, Materialise Inc., Leuven, Belgium). Circular articular cartilage and subchondral bone defect models were created in each model of the recipient patella (diameter=18mm) at 3 locations: medial, distal, and lateral. Articular cartilage and subchondral bone graft models were created on all possible locations on the articular cartilage surface models of the donor patellae. 3D surface topographies of the articular cartilage surface and resulting subchondral bone surfaces were compared between graft and defect models. The graft models were virtually placed on the surface of the defect model. Least distances, defined as the shortest distance from the point in question to the corresponding point in space, where a perfect congruent match would equal a least distance of 0.00mm for given data points on the simulated articular cartilage surface, were calculated. A mean value of the least distances was calculated for each position of the graft model and for the subchondral bone surface, simultaneously. The graft model was then rotated 360° around the axis perpendicular to the articular cartilage surface in 1° increments, and the least distance of articular cartilage surface and least distance of subchondral bone surface were calculated at each rotating angle. This procedure was repeated for all points in the articular surface model of the donor patella. The 3D model creation and geometry matching were performed using a custom-written program coded by in Microsoft Visual C++ with Microsoft Foundation Class programming environment (Microsoft Corp., Redmond, WA). Multivariate linear regression analysis was conducted in SPSS (v26, IBM, Armonk, NY). Results: Chondral and osseous mismatch between the graft and defect were analyzed. ANOVA analysis on the multivariate linear regressions found significant predictors of cartilage mismatch for medial (p=0.002), lateral (p=0.022), and central (p=0.001) defects when testing 5 variables. However, no predicting variables were identified for osseous mismatch for medial (p=0.099), lateral (p=0.703), and central (p=0.641) defects. Differences in tibia width (p=0.005), bone width (p=0.004), and medial cartilage length (p=0.003) were predictive of mismatch in medial defects. When evaluating lateral defects, no variables were found to significantly effect mismatch, However, in this lateral defect group, the collinearity assumption of the regression was violated, as the VIF for bone width and lateral length were over 10. For the central group, difference in bone width (p=0.037), difference in percent of patella that was medial facet (p=0.001), and difference in tibial width (p=0.006) were predictive of mismatch. Conclusions: Differences between graft and recipient tibia width, bone width, and size of the medial or lateral facet are significant predictors of mismatch in patella allograft selection.


2012 ◽  
Vol 94 (21) ◽  
pp. 1984-1995 ◽  
Author(s):  
Andrea L. Pallante ◽  
Simon Görtz ◽  
Albert C. Chen ◽  
Robert M. Healey ◽  
Derek C. Chase ◽  
...  

2021 ◽  
Vol 14 (4) ◽  
pp. 315
Author(s):  
Anne-Mari Mustonen ◽  
Petteri Nieminen

Osteoarthritis (OA) is a chronic joint disease characterized by inflammation, gradual destruction of articular cartilage, joint pain, and functional limitations that eventually lead to disability. Join tissues, including synovium and articular cartilage, release extracellular vesicles (EVs) that have been proposed to sustain joint homeostasis as well as to contribute to OA pathogenesis. EVs transport biologically active molecules, and OA can be characterized by altered EV counts and composition in synovial fluid. Of EV cargo, specific non-coding RNAs could have future potential as diagnostic biomarkers for early OA. EVs may contribute to the propagation of inflammation and cartilage destruction by transporting and enhancing the production of inflammatory mediators and cartilage-degrading proteinases. In addition to inducing OA-related gene expression patterns in synoviocytes and articular chondrocytes, EVs can induce anti-OA effects, including increased extracellular matrix deposition and cartilage protection. Especially mesenchymal stem cell-derived EVs can alleviate intra-articular inflammation and relieve OA pain. In addition, surgically- or chemically-induced cartilage defects have been repaired with EV therapies in animal models. While human clinical trials are still in the future, the potential of actual cures to OA by EV products is very promising.


2020 ◽  
Vol 33 (12) ◽  
pp. 1187-1200
Author(s):  
Jacob G. Calcei ◽  
Taylor Ray ◽  
Seth L. Sherman ◽  
Jack Farr

AbstractLarge, focal articular cartilage defects of the knee (> 4 cm2) can be a source of significant morbidity and often require surgical intervention. Patient- and lesion-specific factors must be identified when evaluating a patient with an articular cartilage defect. In the management of large cartilage defects, the two classically utilized cartilage restoration procedures are osteochondral allograft (OCA) transplantation and cell therapy, or autologous chondrocyte implantation (ACI). Alternative techniques that are available or currently in clinical trials include a hyaluronan-based scaffold plus bone marrow aspirate concentrate, a third-generation autologous chondrocyte implant, and an aragonite-based scaffold. In this review, we will focus on OCA and ACI as the mainstay in management of large chondral and osteochondral defects of the knee. We will discuss the techniques and associated clinical outcomes for each, while including a brief mention of alternative treatments. Overall, cartilage restoration techniques have yielded favorable clinical outcomes and can be successfully employed to treat these challenging large focal lesions.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1052.1-1052
Author(s):  
S. Eldridge ◽  
A. Barawi ◽  
H. Wang ◽  
A. Roelofs ◽  
M. Kaneva ◽  
...  

Background:Cartilage defects in the joints are reported in 61% of all arthroscopies1&2. The size of the cartilage repair market is estimated to be $2.195 million by 20253. Cartilage defects can evolve into osteoarthritis, in which abnormal load results in cartilage breakdown, joint pain and reduced mobility. Osteoarthritis is the leading cause of permanent disability and absenteeism and affects up to 1/3 of the people over 60yrs. In western countries osteoarthritis costs 1.5-2% of the GDP4. Joint replacement with a prosthesis restores some degree of independence but in up to 20% of patients it does not meet expectations 5 and has a limited life span. There is no pharmacological intervention that arrests or reverts the course of osteoarthritis, despite the desperate need.We previously published that agrin plays an important role in cartilage homeostasis6. The addition of agrin to chondrocytes in vivo resulted in enhanced cartilage formation, suggesting a potential role for agrin in cartilage repair.Objectives:Investigate the potential of agrin for use in cartilage repair.Methods:Critical size osteochondral defects were generated in mice and sheep and injected intraarticularly with type I collagen gel containing agrin or vehicle. Animals were monitored for 8 weeks or 6 months respectively. MicroCT, histological analysis, qPCR, linage tracking, reporter assays, chondrogenesis assay, immunohistochemistry were performed.Results:A single intraarticular administration of agrin induced regeneration of critical-size osteochondral defects in mice, restoring the tissue architecture and bone-cartilage interface. Agrin stem cells to the site of injury and, through simultaneous activation of CREB and suppression of canonical WNT signalling, induced GDF5 expression and differentiation into stable articular chondrocytes, forming stable articular cartilage. In sheep, agrin treatment resulted in regeneration of bone and cartilage, which promoted increased ambulatory activity.Conclusion:Agrin orchestrates repair morphogenesis at the joint surface by modulating multiple signalling pathways, supporting the therapeutic use of agrin for joint surface regeneration.References:[1]Curl, W. W. et al. Cartilage injuries: a review of 31,516 knee arthroscopies. Arthrosc. J. Arthrosc. Relat. Surg. Off. Publ. Arthrosc. Assoc. N. Am. Int. Arthrosc. Assoc. 13, 456–460 (1997).[2]Hjelle, K., Solheim, E., Strand, T., Muri, R. & Brittberg, M. Articular cartilage defects in 1,000 knee arthroscopies. Arthrosc. J. Arthrosc. Relat. Surg. Off. Publ. Arthrosc. Assoc. N. Am. Int. Arthrosc. Assoc. 18, 730–734 (2002).[3]Cartilage Repair Market Size, Share, Industry Analysis 2018-2025 | AMR. Allied Market Research https://www.alliedmarketresearch.com/cartilage-repair-market.[4]Hiligsmann, M. et al. Health economics in the field of osteoarthritis: an expert’s consensus paper from the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO). Semin. Arthritis Rheum. 43, 303–313 (2013).[5]Dieppe, P., Lim, K. & Lohmander, S. Who should have knee joint replacement surgery for osteoarthritis? Int. J. Rheum. Dis. 14, 175–180 (2011).[6]Eldridge, S., et al. Agrin mediates chondrocyte homeostasis and requires both LRP4 and α-dystroglycan to enhance cartilage formation in vitro and in vivo. Annals of the rheumatic diseases 75 (6), 1228-1235 (2016).Acknowledgements:We thank the technical staff in the ARM Lab and Staff at the University of Aberdeen’s Animal Facility and Microscopy and Histology Facility for support. Funding: We gratefully acknowledge funding support of this work by the MRC (MR/L022893/1, MR/N010973/1,and MR/P026362/1), Versus Arthritis (19667, 21515, 20886, and 21621), Rosetrees Trust (A1205), the Medical College of St Bartholomew’s Hospital Trust, and the William Harvey Research Foundation.Disclosure of Interests:Suzanne Eldridge: None declared, Aida Barawi: None declared, Hui Wang: None declared, Anke Roelofs: None declared, Magdalena Kaneva: None declared, Zeyu Guan: None declared, Helen Lydon: None declared, Bethan Thomas: None declared, Anne-Sophie Thorup: None declared, Beatriz F Fernandez: None declared, Sara Caxaria: None declared, Danielle Strachan: None declared, Ahmed Ali: None declared, Kanatheepan Shanmuganathan: None declared, Costantino Pitzalis: None declared, James Whiteford: None declared, Fran Henson: None declared, Andrew McCaskie: None declared, Cosimo De Bari: None declared, Francesco Dell’Accio Consultant of: F.D. has received consultancy fees from Samumed and UCB.


2021 ◽  
Vol 9 (10_suppl5) ◽  
pp. 2325967121S0031
Author(s):  
Mithun Neral ◽  
Karan Patel ◽  
Michael Getty ◽  
Nabeel Salka ◽  
John Grant

Objectives: Recent research has shown that implanting a patellar osteochondral allograft with a non-matched surface morphology (i.e., Wiberg classification) does not create increased chondral surface deviation or circumferential step-off in the donor plug compared to the native patella. While much of the research on patellar osteochondral allografts has been focused on chondral surface matching, little has been done to determine if the subchondral bone alignment at the donor:native interface plays a role in graft healing, local force distribution, and long term success of the allograft transplant. Previous work in our lab demonstrated that even when the patellar cartilage surface was well matched, notable differences in subchondral bone alignment were observed. The purpose of this study was therefore to use surface contour mapping of subchondral bone to determine if differences in Wiberg classification play a role in the ability of donor patellar osteochondral allograft subchondral bone to align with the native patellar subchondral bone when treating osteochondral defects of the patellar apex. The hypothesis was that patellar surface morphology would have an effect on subchondral bone surface height deviation and circumferential step-off when performing osteochondral allograft transplants of the patellar apex. Methods: Sixty fresh frozen human patellae were acquired from a national donor procurement company. Twenty (10 Wiberg I and 10 Wiberg II/III) patellae were designated as the recipient and then nano-CT scanned. Each recipient was size-matched (within ±2mm tibial width) to both a Wiberg I and a Wiberg II/III patellar donor. A 16mm circular osteochondral “defect” centered on the central ridge of the patella was then created in the recipient patella. A randomly-ordered donor Wiberg I or Wiberg II/III plug was harvested from a homologous location and transplanted into the recipient. The recipient was then nano-CT scanner, digitally reconstructed, and superimposed on the initial nano-CT scan of the native recipient patella. After careful atraumatic removal of the first donor plug, the process was repeated using the other allograft plug. MATLAB was used to determine the root mean square (RMS) surface height deviation between the native and donor subchondral bone surfaces. Dragonfly 3D imaging software was used to measure the RMS subchondral bone step-off height at 3° increments around the circumference of the graft. Surface height deviation and circumferential step-off height were analyzed for the whole surface and by quadrant to determine if there were local differences. ANOVA was used to compare surface deviation and step-off heights between matched and unmatched grafts. Sidak’s multiple comparison test was used to complete sub-analysis between patellar graft quadrants. Comparisons were made between matched and unmatched grafts in terms of the RMS surface height deviation and step-off, as well as in the percentage of measurements that were more than 0.5mm, 1mm, and 2mm proud or sunken relative to the native surface. Results: There were no significant differences in RMS subchondral bone surface height deviation between matched and unmatched Wiberg plugs as a whole or by quadrant (RMS range = 0.69 to 0.97mm, p = 0.45 – 1.0). There was a significant difference in RMS circumferential step-off height between matched (1.14 ± 0.52mm) and unmatched (1.38 ± 0.49mm) Wiberg plugs ( p=0.015). The majority of these increased step-off measurements occurred in the lateral quadrant with lateral quadrant RMS step-off of 0.89 ± 0.43mm in matched grafts and 1.60 ± 0.78mm in unmatched grafts ( p=0.007). There was also a significant difference in the percent of step-off measurements greater than 2mm sunken in the lateral quadrant between matched and unmatched grafts (5.17 ± 20.87% matched, 24.5 ± 36.39% unmatched, p=0.028). There were no significant differences between matched and unmatched grafts for any other comparison using 0.5, 1, or 2mm cut-offs for circumferential step-off or surface height deviation. Combining all allografts, the respective proportion of surface deviation and circumferential step-off height measurements that were above the stated thresholds were as follows: 31% and 34% for a 0.5mm threshold, 15% and 21% for a 1mm threshold, and 2% and 8% for a 2mm threshold. Conclusions: While unmatched Wiberg patella osteochondral allograft implantation did not result in significantly different subchondral bone surface height deviations, there were significant differences in circumferential subchondral bone step-off heights. The majority of step-off height differences between Wiberg matched and unmatched osteochondral allografts occurred in the lateral quadrant. In comparison to previous data evaluating differences in the cartilage surface match in these patellar OCA transplants, the deviations and step-off heights in the subchondral bone identified in the current study were approximately 0.5mm greater than the differences in the cartilage surface. These findings therefore suggest there is greater variability in the alignment of the subchondral bone in these patellar osteochondral allografts than there is in the cartilage surface. Further investigation using finite element analysis modeling will help determine the implications of subchondral bone surface deviation and circumferential step-off on local cartilage:bone compression and shear force distribution. These studies may shed light on the mechanisms of failure in patellar osteochondral transplants and may help to better understand the contribution of subchondral bone alignment in OCA healing and long-term outcome.


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