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Repair and tissue engineering techniques for articular cartilage.

ABSTRACT: Chondral and osteochondral lesions due to injury or other pathology commonly result in the development of osteoarthritis, eventually leading to progressive total joint destruction. Although current progress suggests that biologic agents can delay the advancement of deterioration, such drugs are incapable of promoting tissue restoration. The limited ability of articular cartilage to regenerate renders joint arthroplasty an unavoidable surgical intervention. This Review describes current, widely used clinical repair techniques for resurfacing articular cartilage defects; short-term and long-term clinical outcomes of these techniques are discussed. Also reviewed is a developmental pipeline of acellular and cellular regenerative products and techniques that could revolutionize joint care over the next decade by promoting the development of functional articular cartilage. Acellular products typically consist of collagen or hyaluronic-acid-based materials, whereas cellular techniques use either primary cells or stem cells, with or without scaffolds. Central to these efforts is the prominent role that tissue engineering has in translating biological technology into clinical products; therefore, concomitant regulatory processes are also discussed.

SUBMITTER: Makris EA

PROVIDER: S-EPMC4629810 | biostudies-other | 2015 Jan

REPOSITORIES: biostudies-other

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Repair and tissue engineering techniques for articular cartilage.

Makris Eleftherios A EA Gomoll Andreas H AH Malizos Konstantinos N KN Hu Jerry C JC Athanasiou Kyriacos A KA

Nature reviews. Rheumatology 20140923 1

Chondral and osteochondral lesions due to injury or other pathology commonly result in the development of osteoarthritis, eventually leading to progressive total joint destruction. Although current progress suggests that biologic agents can delay the advancement of deterioration, such drugs are incapable of promoting tissue restoration. The limited ability of articular cartilage to regenerate renders joint arthroplasty an unavoidable surgical intervention. This Review describes current, widely u ...[more]

PMID: 25247412

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Project description:Articular cartilage is integral to the mechanical function of many joints in the body. When injured, cartilage lacks the capacity to self-heal, and thus, therapies and replacements have been developed in recent decades to treat damaged cartilage. Given that the primary function of articular cartilage is mechanical in nature, rigorous physical evaluation of cartilage tissues undergoing treatment and cartilage constructs intended for replacement is an absolute necessity. With the large number of groups developing cartilage tissue engineering strategies, however, a variety of mechanical testing protocols have been reported in the literature. This lack of consensus in testing methods makes comparison between studies difficult at times, and can lead to misinterpretation of data relative to native tissue. Therefore, the purpose of this study was to systematically review mechanical testing of articular cartilage and cartilage repair constructs over the past 10 years (January 2009-December 2018), to highlight the most common testing configurations, and to identify key testing parameters. For the most common tests, key parameters identified in this systematic review were validated by characterizing both cartilage tissue and hydrogels commonly used in cartilage tissue engineering. Our findings show that compression testing was the most common test performed (80.2%; 158/197), followed by evaluation of frictional properties (18.8%; 37/197). Upon further review of those studies performing compression testing, the various modes (ramp, stress relaxation, creep, dynamic) and testing configurations (unconfined, confined, in situ) are described and systematically reviewed for parameters, including strain rate, equilibrium time, and maximum strain. This systematic analysis revealed considerable variability in testing methods. Our validation testing studies showed that such variations in testing criteria could have large implications on reported outcome parameters (e.g., modulus) and the interpretation of findings from these studies. This analysis is carried out for all common testing methods, followed by a discussion of less common trends and directions in the mechanical evaluation of cartilage tissues and constructs. Overall, this work may serve as a guide for cartilage tissue engineers seeking to rigorously evaluate the physical properties of their novel treatment strategies. Impact Statement Articular cartilage tissue engineering has made significant strides with regard to treatments and replacements for injured tissue. The evaluation of these approaches typically involves mechanical testing, yet the plethora of testing techniques makes comparisons between studies difficult, and often leads to misinterpretation of data compared with native tissue. This study serves as a guide for the mechanical testing of cartilage tissues and constructs, highlighting recent trends in test conditions and validating these common procedures. Cartilage tissue engineers, especially those unfamiliar with mechanical testing protocols, will benefit from this study in their quest to physically evaluate novel treatment and regeneration approaches.

Project description:BackgroundFull-thickness articular cartilage lesions that reach to the subchondral bone yet are restricted to the chondral compartment usually fill with a fibrocartilage-like repair tissue which is structurally and biomechanically compromised relative to normal articular cartilage. The objective of this study was to evaluate transcriptional differences between chondrocytes of normal articular cartilage and repair tissue cells four months post-microfracture.MethodsBilateral one-cm2 full-thickness defects were made in the articular surface of both distal femurs of four adult horses followed by subchondral microfracture. Four months postoperatively, repair tissue from the lesion site and grossly normal articular cartilage from within the same femorotibial joint were collected. Total RNA was isolated from the tissue samples, linearly amplified, and applied to a 9,413-probe set equine-specific cDNA microarray. Eight paired comparisons matched by limb and horse were made with a dye-swap experimental design with validation by histological analyses and quantitative real-time polymerase chain reaction (RT-qPCR).ResultsStatistical analyses revealed 3,327 (35.3%) differentially expressed probe sets. Expression of biomarkers typically associated with normal articular cartilage and fibrocartilage repair tissue corroborate earlier studies. Other changes in gene expression previously unassociated with cartilage repair were also revealed and validated by RT-qPCR.ConclusionThe magnitude of divergence in transcriptional profiles between normal chondrocytes and the cells that populate repair tissue reveal substantial functional differences between these two cell populations. At the four-month postoperative time point, the relative deficiency within repair tissue of gene transcripts which typically define articular cartilage indicate that while cells occupying the lesion might be of mesenchymal origin, they have not recapitulated differentiation to the chondrogenic phenotype of normal articular chondrocytes.

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Repair and tissue engineering techniques for articular cartilage.

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Repair and tissue engineering techniques for articular cartilage.

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