Scientific Developments and Clinical Applications Utilizing Chondrons and Chondrocytes with Matrix for Cartilage Repair

Cartilage ◽  
2020 ◽  
pp. 194760352096888 ◽  
Author(s):  
Sarav S. Shah ◽  
Kai Mithoefer
Keyword(s):  
Extracellular Matrix ◽  
Articular Cartilage ◽  
Cartilage Repair ◽  
Basic Science ◽  
Matrix Theory ◽  
Operative Management ◽  
Clinical Applications ◽  
Osteochondral Allograft ◽  
Cartilage Defects ◽  
Comprehensive Overview

Injuries to articular cartilage of the knee are increasingly common. The operative management of these focal chondral lesions continues to be problematic for the treating orthopedic surgeon secondary to the limited regenerative capacity of articular cartilage. The pericellular matrix (PCM) is a specialized, thin layer of the extracellular matrix that immediately surrounds chondrocytes forming a unit together called the chondron. The advancements in our knowledge base with regard to the PCM/chondrons as well as interterritorial matrix has permeated and led to advancements in product development in conjunction with minced cartilage, marrow stimulation, osteochondral allograft, and autologous chondrocyte implantation (ACI). This review intends to summarize recent progress in chondrocytes with matrix research, with an emphasis on the role the PCM/extracellular matrix (ECM) plays for favorable chondrogenic gene expression, as a barrier/filtration unit, and in osteoarthritis. The bulk of the review describes cutting-edge and evolving clinical developments and discuss these developments in light of underlying basic science applications. Clinical applications of chondrocytes with matrix science include Reveille Cartilage Processor, Cartiform, and ACI with Spherox (which was recently recommended for the treatment of grade III or IV articular cartilage defects over 2 cm2 by the National Institute of Health and Care Excellence [NICE] in the United Kingdom). The current article presents a comprehensive overview of both the basic science and clinical results of these next-generation cartilage repair techniques by focusing specifically on the scientific evolution in each category as it pertains with underlying chondrocytes with matrix theory.

scholarly journals Microfracture Versus Drilling of Articular Cartilage Defects: A Systematic Review of the Basic Science Evidence

2020 ◽  
Vol 8 (8) ◽  
pp. 232596712094531 ◽  
Author(s):  
Matthew J. Kraeutler ◽  
Gianna M. Aliberti ◽  
Anthony J. Scillia ◽  
Eric C. McCarty ◽  
Mary K. Mulcahey
Keyword(s):  
Systematic Review ◽  
Articular Cartilage ◽  
Cartilage Repair ◽  
Basic Science ◽  
Science Studies ◽  
Cartilage Regeneration ◽  
Cartilage Defects ◽  
Repair Tissue ◽  
Marrow Stimulation

Background: Microfracture (MFx) is one of the most common techniques used for the treatment of articular cartilage defects, although recently there has been a trend toward the use of drilling rather than MFx for the treatment of these defects. Purpose: To perform a systematic review of basic science studies to determine the effect of microfracture versus drilling for articular cartilage repair. Study Design: Systematic review. Methods: A systematic review was performed by searching PubMed, the Cochrane Library, and EMBASE to identify basic science studies comparing outcomes of MFx versus drilling. The search phrase used was microfracture AND (drilling OR microdrilling). Inclusion criteria were basic science studies that directly compared the effect of MFx versus drilling on subchondral bone, bone marrow stimulation, and cartilage regeneration. Results: A total of 7 studies met the inclusion criteria and were included in this systematic review. Of these, 4 studies were performed in rabbits, 1 study in sheep, and 2 studies in humans. All of the included studies investigated cartilage repair in the knee. In the animal studies, microfracture produced fractured and compacted bone and led to increased osteocyte necrosis compared with drilling. Deep drilling (6 mm) was superior to both shallow drilling (2 mm) and MFx in terms of increased subchondral hematoma with greater access to marrow stroma, improved cartilage repair, and increased mineralized bone. However, the overall quality of cartilage repair tissue was poor regardless of marrow stimulation technique. In 2 studies that investigated repair tissue after MFx and/or drilling in human patients with osteoarthritis and cartilage defects, the investigators found that cartilage repair tissue did not achieve the quality of normal hyaline articular cartilage. Conclusion: In the limited basic science studies that are available, deep drilling of cartilage defects in the knee resulted in improved biological features compared with MFx, including less damage to the subchondral bone and greater access to marrow stroma. Regardless of marrow stimulation technique, the overall quality of cartilage regeneration was poor and did not achieve the characteristics of native hyaline cartilage. Overall, there is a general lack of basic science literature comparing microfracture versus drilling for focal chondral defects.

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 ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Surface Topography ◽  
Osteochondral Allograft ◽  
Cartilage Defects ◽  
Radius Of Curvature ◽  
Cartilage Surface ◽  
3 Dimensional ◽  
Cloud Models ◽  
And Cartilage ◽  
Osteochondral Allografts

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.

scholarly journals Returning to Work After Articular Cartilage Repair Intervention: A Systematic Review

2020 ◽  
Vol 8 (3) ◽  
pp. 232596712090552 ◽  
Author(s):  
Puwapong Nimkingratana ◽  
Mats Brittberg
Keyword(s):  
Systematic Review ◽  
Articular Cartilage ◽  
General Population ◽  
Return To Work ◽  
Cartilage Repair ◽  
Rate Of Return ◽  
Osteochondral Allograft ◽  
Articular Cartilage Repair ◽  
Surgical Interventions ◽  
Returning To Work

Background: The process of returning to work after cartilage treatment has not been studied in depth, even though a better understanding of potential outcomes could lead to significant benefits for the general population. Purpose: To determine which surgical interventions are most effective in helping patients return to work after cartilage repair and to identify factors that affect the ability to return to work. Study Design: Systematic review; Level of evidence, 4. Methods: This systematic review followed PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines in analyzing reports on articular cartilage treatment and return to work published from January 1966 (when the first system of classifying articular cartilage injuries based on the mechanism of injuries and type of lesions was developed) to January 2019. General surgical information and available clinical scores were used to assess outcomes. Results: Only 5 studies describing 283 patients were found to be relevant to our objectives and were therefore included in the analysis. Autologous chondrocyte implantation (ACI) and osteochondral allografts were the only 2 procedures for which information was included regarding patient return to work rates. The mean (overall) return-to-work time after a cartilage repair operation was 4.80 ± 3.02 months. ACI was the most common procedure (3 studies; 227 patients). Return to work after ACI or ACI with high tibial osteotomy (HTO) occurred in almost 100% of cases, whereas the rate of return to work was 51.78% for patients who underwent osteochondral allograft ( P < .01); further, patients who had ACI or ACI+HTO returned to work sooner compared with patients who underwent osteochondral allograft. The Knee injury and Osteoarthritis Outcome Score (KOOS) and Single Assessment Numerical Evaluation (SANE) scores were significantly higher in patients who fully returned to work. No significant difference was found in rates of return to work after ACI related to sex, area of the lesion, or size of the defect. Conclusion: The vast majority of published results on articular cartilage repair do not include data on return to work. Although available data on articular cartilage repair in the general population reveal a high rate of return to work, including those patients treated with ACI, the data do not stratify patients by the type and demand of work. No randomized studies have examined return-to-work rates. Hence, authors should include these data in future studies. A refined definition of work intensity, rather than just return to work, may provide a clearer picture of the relative effectiveness of different surgical interventions. To that end, the authors propose a return to work prognostic score called the Prognostic Cartilage Repair Return to Work Score, or PROCART-RTW score.

Facilitating In Vivo Articular Cartilage Repair by Tissue-Engineered Cartilage Grafts Produced From Auricular Chondrocytes

2017 ◽  
Vol 46 (3) ◽  
pp. 713-727 ◽  
Author(s):  
Chin-Chean Wong ◽  
Chih-Hwa Chen ◽  
Li-Hsuan Chiu ◽  
Yang-Hwei Tsuang ◽  
Meng-Yi Bai ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Articular Cartilage ◽  
Cartilage Repair ◽  
Articular Chondrocytes ◽  
Type Ii Collagen ◽  
Type Ii ◽  
Articular Cartilage Repair ◽  
3 Dimensional ◽  
Cell Conversion

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.

scholarly journals Beneficial Storage Effects of Epigallocatechin-3-O-Gallate on the Articular Cartilage of Rabbit Osteochondral Allografts

2009 ◽  
Vol 18 (5-6) ◽  
pp. 505-512 ◽  
Author(s):  
Jung Yoon Bae ◽  
Kazuaki Matsumura ◽  
Shigeyuki Wakitani ◽  
Amu Kawaguchi ◽  
Sadami Tsutsumi ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Disease Transmission ◽  
Culture Medium ◽  
Clinical Success ◽  
Osteochondral Allograft ◽  
Cartilage Defects ◽  
Clinical Effects ◽  
Normal Cells ◽  
Osteochondral Grafts ◽  
Osteochondral Allografts

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.

Cell-derived decellularized extracellular matrix scaffolds for articular cartilage repair

2020 ◽  
pp. 039139882095386
Author(s):  
Wenrun Zhu ◽  
Lu Cao ◽  
Chunfeng Song ◽  
Zhiying Pang ◽  
Haochen Jiang ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Extracellular Matrix ◽  
Articular Cartilage ◽  
Cartilage Repair ◽  
Cell Attachment ◽  
Tissue Growth ◽  
Bioactive Molecules ◽  
Cartilage Tissue ◽  
Articular Cartilage Repair ◽  
Decellularized Extracellular Matrix

Articular cartilage repair remains a great clinical challenge. Tissue engineering approaches based on decellularized extracellular matrix (dECM) scaffolds show promise for facilitating articular cartilage repair. Traditional regenerative approaches currently used in clinical practice, such as microfracture, mosaicplasty, and autologous chondrocyte implantation, can improve cartilage repair and show therapeutic effect to some degree; however, the long-term curative effect is suboptimal. As dECM prepared by proper decellularization procedures is a biodegradable material, which provides space for regeneration tissue growth, possesses low immunogenicity, and retains most of its bioactive molecules that maintain tissue homeostasis and facilitate tissue repair, dECM scaffolds may provide a biomimetic microenvironment promoting cell attachment, proliferation, and chondrogenic differentiation. Currently, cell-derived dECM scaffolds have become a research hotspot in the field of cartilage tissue engineering, as ECM derived from cells cultured in vitro has many advantages compared with native cartilage ECM. This review describes cell types used to secrete ECM, methods of inducing cells to secrete cartilage-like ECM and decellularization methods to prepare cell-derived dECM. The potential mechanism of dECM scaffolds on cartilage repair, methods for improving the mechanical strength of cell-derived dECM scaffolds, and future perspectives on cell-derived dECM scaffolds are also discussed in this review.

Costal Chondrocyte–Derived Pellet-Type Autologous Chondrocyte Implantation for Treatment of Articular Cartilage Defect

2020 ◽  
Vol 48 (5) ◽  
pp. 1236-1245 ◽  
Author(s):  
Kyoung-Ho Yoon ◽  
Jae-Young Park ◽  
Jin-Yeon Lee ◽  
EunAh Lee ◽  
Jungsun Lee ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Magnetic Resonance ◽  
Cartilage Repair ◽  
Therapeutic Option ◽  
Cartilage Defects ◽  
Resonance Imaging ◽  
Defect Filling ◽  
Costal Chondrocyte ◽  
Autologous Chondrocyte

Background: Because articular chondrocyte-based autologous chondrocyte implantations (ACIs) have restrictively restored articular cartilage defects, alternative cell sources as a new therapeutic option for cartilage repair have been introduced. Purpose: To assess whether implantation of a costal chondrocyte–derived pellet-type (CCP) ACI allows safe, functional, and structural restoration of full-thickness cartilage defects in the knee. Study Design: Case series; Level of evidence, 4. Methods: In this first-in-human study, 7 patients with symptomatic, full-thickness cartilage lesions were enrolled. The chondrocytes isolated from the patients’ costal cartilage were expanded, followed by 3-dimensional pellet culture to prepare the CCP-ACI. Implantation of the pellets was performed via minimal arthrotomy and secured with a fibrin sealant. Clinical scores, including the International Knee Documentation Committee (IKDC) subjective, Lysholm, and Tegner activity scores, were estimated preoperatively and at 1, 2, and 5 years postoperatively. High-resolution magnetic resonance imaging was also performed to evaluate cartilage repair as well as to calculate the MOCART (magnetic resonance observation of cartilage repair tissue) score. Results: The costal chondrocytes of all patients formed homogeneous-sized pellets, which showed the characteristics of the hyaline cartilaginous tissue with lacunae-occupied chondrocytes surrounded by glycosaminoglycan and type II collagen-rich extracellular matrix. There were no treatment-related serious adverse events during the 5-year follow-up period. Significant improvements were seen in all clinical scores from preoperative baseline to the 5-year follow-up (IKDC subjective score, 34.67 to 75.86; Lysholm score, 34.00 to 85.33; Tegner activity score, 1.17 to 4.67; and MOCART score, 28.33 to 83.33). Two patients had complete defect filling on magnetic resonance imaging evaluation at 1 year. Moreover, at 5 years postoperatively, complete defect filling was observed in 4 patients, and hypertrophy or incomplete defect filling (50%-100%) was observed in 2 patients. Conclusion: The overall results of this clinical study suggest that CCP-ACI can emerge as a promising therapeutic option for articular cartilage repair with good clinical outcomes and structural regeneration and with stable results at midterm follow-up. Registration: NCT03517046 ( ClinicalTrials.gov identifier)

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