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A range of surgical techniques have been developed for the repair or regeneration of lesioned cartilage in the human knee and a corresponding array of scoring systems have been created to assess their outcomes. The published literature displays a wide range of opinions regarding the factors that influence the success of surgical cartilage repair and which parameters are the most useful for measuring the quality of the repair at follow-up. Our objective was to provide some clarity to the field by collating items that were agreed upon by a panel of experts to be important in these areas. A modified, three-round Delphi consensus study was carried out consisting of one idea-generating focus-group and two subsequent, self-completed questionnaire rounds. In each round, items were assessed for their importance and level of consensus against pre-determined threshold levels. In total, 31 items reached consensus, including a hierarchy of tissues in the joint based on their importance in cartilage repair, markers of repair cartilage quality and the implications of environmental and patient-related factors. Items were stratified into those that can be employed for predicting the success of cartilage repair and those that could be used for assessing the structural quality of the resulting repair cartilage. Items that did not reach consensus represent areas where dissent remains and could, therefore, be used to guide future clinical and fundamental scientific research.

Objective Autologous chondrocyte implantation was the first cell-based therapy that used a tissue engineering process to repair cartilage defects. Recently improved approaches and tissue-engineered cell constructs have been developed for growing patient populations. We developed a chondrocyte construct using a collagen gel and sponge scaffold and physicochemical stimuli, implanted with a surgical adhesive. We conducted a proof-of-concept study of these improvements using a cartilage defect model in miniature swine. Design We implanted the autologous chondrocyte constructs into full-thickness chondral defects in the femoral condyle, compared those results with empty and acellular scaffold controls, and compared implantation techniques with adhesive alone and with partial adhesive with suture. Two weeks after the creation of the defects and implantation of the cellular or acellular constructs, we arthroscopically confirmed that the implanted constructs remained at the chondral defects. We evaluated the regenerated tissue macro- and microscopically 6 months after the cell constructs were implanted. The tissues were stained with Safranin-O and evaluated using Sellers’ histology grading system. Results The defects implanted with processed cell constructs and acellular scaffolds were filled with chondrocyte-like round cells and with nearly normal tissue architecture that were significantly greater degree compared to empty defect control. Even with the adhesive alone and with suture alone, the cell construct was composed of the dense cartilaginous matrix that was found in the implantation using both the sutures and the adhesive. Conclusion Implantation of cell constructs promoted regeneration and integration of articular cartilage at chondral defects in swine by 6 months.

Herein we review the state-of-the-art in tissue engineering for repair of articular cartilage. First, we describe the molecular, cellular, and histologic structure and function of endogenous cartilage, focusing on chondrocytes, collagens, extracellular matrix, and proteoglycans. We then explore in vitro cell culture on scaffolds, discussing the difficulties involved in maintaining or obtaining a chondrocytic phenotype. Next, we discuss the diverse compounds and designs used for these scaffolds, including natural and synthetic biomaterials and porous, fibrous, and multilayer architectures. We then report on the mechanical properties of different cell-loaded scaffolds, and the success of these scaffolds following in vivo implantation in small animals, in terms of generating tissue that structurally and functionally resembles native tissue. Last, we highlight future trends in this field. We conclude that despite major technical advances made over the past 15 years, and continually improving results in cartilage repair experiments in animals, the development of clinically useful implants for regeneration of articular cartilage remains a challenge.

Objective The limits of the microfracture (MFX) treatment in terms of lesion size and long-term tissue functionality makes it necessary to investigate different alternatives to repair focal cartilage lesions. The present study aims at evaluating the efficacy of a minimally invasive approach against the conventional MFX to repair a chondral defect in rabbits. An injectable scaffold of BMP-2 pre-encapsulated in PLGA microspheres dispersed in a Pluronic F-127 solution is proposed as support of cells and controlled delivery system for the growth factor. Design MFX was compared versus the injectable system seeded with mesenchymal stem cells (MSCs), both without BMP-2 and under controlled release of BMP-2 at 2 different doses (3 and 12 µg/scaffold). The different treatments were evaluated on a 4-mm diameter chondral defect model using 9 experimental groups of 4 rabbits (8 knees) each, throughout 24 weeks. Results Histologically, all the treated groups, except MFX treated, responded significantly better than the control group (nontreated defect). Although no significant differences were found between the treated groups, only BMP(12), MSC-BMP(12), and MFX-BMP(3) groups showed nonsignificant differences when compared with the normal cartilage. Conclusions The hydrogel system proposed to control the release rate of the BMP-2 was safe, easily injectable, and also provided good support for cells. Treatments with MSCs or BMP-2 repaired efficiently the chondral lesion created in rabbits, being less invasive than MFX treatment.

The application of multilayered monolithic scaffolds to repair osteochondral defects has become a hot research topic due to the advantage of simulating native osteochondral physiological structure. However, it was difficult to promote proliferation and migration of different kinds of cells in the corresponding layers under the same culture condition. Besides, the methods utilized in previous researches to construct tissue-engineered osteochondral construct were time-consuming, laborious, complicated, costly and difficult to ensure the quality and integration of multilayered construction. Inspired by the application of titanium mesh cage (TMC) for bone graft in spinal fusion surgery, we attempt to 3D print an integrated tri-layered scaffold with Titanium-Mesh-Cage base which could be filled with autogenous cancellous bone for bone graft to the osteochondral defect. Finally, the results of repairing cartilage defects of knee with this scaffold in goat model were evaluated. The results of in-vivo experiments suggested that utilizing the integrated tri-layered scaffold with Titanium-Mesh-Cage base to repair osteochondral defect was a convenient, cost-effective and time-saving procedures, which could achieve a satisfactory repair result as good as that of Mosaicplasty.

Cartilage tissue engineering has rapidly developed in recent decades, exhibiting promising potential to regenerate and repair cartilage. However, the origin of a large amount of a suitable seed cell source is the major bottleneck for the further clinical application of cartilage tissue engineering. The use of a monoculture of passaged chondrocytes or mesenchymal stem cells results in undesired outcomes, such as fibrocartilage formation and hypertrophy. In the last two decades, co-cultures of chondrocytes and a variety of mesenchymal stem cells have been intensively investigated in vitro and in vivo, shedding light on the perspective of co-culture in cartilage tissue engineering.We summarize the recent literature on the application of heterologous cell co-culture systems in cartilage tissue engineering and compare the differences between direct and indirect co-culture systems as well as discuss the underlying mechanisms.Co-culture system is proven to address many issues encountered by monocultures in cartilage tissue engineering, including reducing the number of chondrocytes needed and alleviating the dedifferentiation of chondrocytes. With the further development and knowledge of biomaterials, cartilage tissue engineering that combines the co-culture system and advanced biomaterials is expected to solve the difficult problem regarding the regeneration of functional cartilage.

Background We used multimodal compositional magnetic resonance imaging (MRI) techniques, combined with clinical outcomes, to differentiate the alternations of composition in repair cartilage with allogeneic human adipose-derived mesenchymal progenitor cells (haMPCs) in knee osteoarthritis (KOA) patients. Methods Eighteen patients participated a phase I/IIa clinical trial. All patients were divided randomly into three groups with intra-articular injections of haMPCs: the low-dose (1.0 × 107 cells), mid-dose (2.0 × 107), and high-dose (5.0 × 107) groups with six patients each. Compositional MRI examinations and clinical evaluations were performed at different time points. Results Significant differences were observed in quantitative T1rho, T2, T2star, R2star, and ADC measurements in patients of three dose groups, suggesting a possible compositional changes of cartilage with the treatment of allogeneic haMPCs. Also significant reduction in WOMAC and SF-36 scores showed the symptoms might be alleviated to some extent with this new treatment. As regards sensibilities of multi-parametric mappings to detect compositional or structural changes of cartilage, T1rho mapping was most sensitive to differentiate difference between three dose groups. Conclusions These results showed that multi-compositional MRI sequences might be an effective tool to evaluate the promotion of the repair of cartilage with allogeneic haMPCs by providing information of compositional alterations of cartilage. Trial registration Clinicaltrials, NCT02641860. Registered 3 December 2015.

Owing to own nature of articular cartilage, it almost has no self-healing ability once damaged. Despite lots of restore technologies having been raised in the past decades, no repair technology has smoothly substituted for damaged cartilage using regenerated cartilage tissue. The approach of tissue engineering opens a door to successfully repairing articular cartilage defects. For instance, grafting of isolated chondrocytes has huge clinical potential for restoration of cartilage tissue and cure of chondral injury. In this paper, SD rats are used as subjects in the experiments, and they are classified into three groups: natural repair (group A), hyaluronic acid repair (group B), and polysaccharide biocomposites repair (hyaluronic acid hydrogel containing chondrocytes, group C). Through the observation of effects of repairing articular cartilage defects, we concluded that cartilage repair effect of polysaccharide biocomposites was the best at every time point, and then the second best was hyaluronic acid repair; both of them were better than natural repair. Polysaccharide biocomposites have good biodegradability and high histocompatibility and promote chondrocytes survival, reproduction, and spliting. Moreover, polysaccharide biocomposites could not only provide the porous network structure but also carry chondrocytes. Consequently hyaluronic acid-based polysaccharide biocomposites are considered to be an ideal biological material for repairing articular cartilage.

Articular cartilage injuries occur frequently and are quite common in clinical practice [1]. However, articular cartilage does not usually heal spontaneously due to its avascular and aneural surroundings, and it has a relatively unique matrix organization. Therefore, a variety of approaches have been tested to improve cartilage healing over the past few decades [2, 3].

Objective: The aim of this study was to determine if the noninvasive or minimally invasive and nondestructive imaging techniques of quantitative T2-mapping or multiphoton microscopy (MPM) respectively, could detect differences in cartilage collagen orientation similar to polarized light microscopy (PLM). It was hypothesized that MRI, MPM, and PLM would all detect quantitative differences between repair and normal cartilage tissue. Methods: Osteochondral defects in the medial femoral condyle were created and repaired in 5 mature goats. Postmortem, MRI with T2-mapping and histology were performed. T2 maps were generated and a mean T2 value was calculated for each region of interest. Histologic slides were assessed using MPM with measurements of autocorrelation ellipticity, and by PLM with application of a validated scoring method. Collagen orientation using each of the 3 modalities (T2-mapping, MPM, and PLM) was measured in the center of the repair tissue and compared to remote, normal cartilage. Results: MRI, MPM, and PLM were able to detect a significant difference between repair and normal cartilage ( n = 5). The average T2 value was longer for repair tissue (41.43 ± 9.81 ms) compared with normal cartilage (27.12 ± 14.22 ms; P = 0.04); MPM autocorrelation ellipticity was higher in fibrous tissue (3.75 ± 1.17) compared with normal cartilage (2.24 ± 0.51; P = 0.01); the average PLM score for repair tissue was lower (1.6 ± 1.02) than the score for remote normal cartilage (4.4 ± 0.42; P = 0.002). The strongest correlation among the methods was between MRI and PLM ( r = −0.76; P = 0.01), followed by MPM and PLM ( r = −0.58; P = 0.08), with the weakest correlation shown between MRI and MPM ( r = 0.35; P = 0.31). Conclusion: All 3 imaging methods quantitatively measured differences in collagen orientation between repair and normal cartilage, but at very different levels of resolution. PLM is destructive to tissue and requires euthanasia, but because MPM can be used arthroscopically, both T2-mapping and MPM can be performed in vivo, offering nondestructive means to assess collagen orientation that could be used to obtain longitudinal data in cartilage repair studies.

The protocol for delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) was adapted for the evaluation of transplanted osteochondral allograft cartilage. Eight patients with focal grade 4 cartilage defects of the femoral condyle were treated with single cylindrical osteochondral allografts. At 1 and 2 years, dGEMRIC image sequences were acquired and regions of interest (ROIs) were drawn in repair and native control cartilage. Mean T1 values of region of interest were used to calculate established dGEMRIC metrics. The correlation was measured between the ΔR1 and R1 -Post metrics for repair and native cartilage. T1 times were measured in deep and superficial zones of cartilage. A strong correlation was identified between full-thickness, deep, and superficial ΔR1 and R1 -Post values for native cartilage and repair cartilage for all years (range: 0.893-1.0). The mean T1 times and ΔR1 rate between deep and superficial regions of articular cartilage were statistically different for all regions of the distal femora analyzed at 1 year and 2 years after osteochondral allograft transplantation (P

Healthy cartilage is a highly robust tissue, and is resilient against the stringent mechanical and biological contraints imposed upon it. Cartilage defects are common features of joint diseases, but current treatments can rarely restore the full function of native cartilage. Recent studies have provided new perspectives for cartilage engineering using mesenchymal stem cells (MSCs). However, the sequential events occurring during chondrogenesis must be fully understood before we are able to reproduce faithfully the complex molecular events that lead to MSC differentiation and long-term maintenance of cartilage characteristics. Here, we focus on the potential of MSCs to repair cartilage with an emphasis on the factors that are known to be required in inducing chondrogenesis.

Disorders affecting cartilage touch almost the whole population and are one of the leading causes of invalidity in adults. To repair cartilage, therapeutic approaches initially focused on the implantation of autologous chondrocytes, but this technique proved unsatisfactory because of the limited number of chondrocytes obtained at harvest. The discovery that several adult human tissues contain mesenchymal stem cells (MSCs) capable of differentiating into chondrocytes raised the possibility of injecting MSCs to repair cartilages. The important data published recently on the factors controlling chondrocyte commitment must be thoroughly considered to make further progress towards this therapeutic approach. The potential application of MSC therapy provides new hope for the development of innovative treatments for the repair of cartilage disorders.

Background: The purpose of this research was to evaluate whether the macroscopic assessment of repair cartilage quality of talar osteochondral defects in a goat model using the ICRS score is in correspondence with histological assessment using the O’Driscoll histology score. Methods: 32 caprine samples with six mm osteochondral defects treated with microfracture were analyzed six months postoperatively using high-resolution digital images. Two observers independently scored the defects using the ICRS (0-12 points). Histological analysis was performed by one expert histologist using the O’Driscoll Score (0-24 points) on 5 μm slices stained with Masson Goldner and Safranin O. Total ICRS and O’Driscoll scores as well as sub items were compared using a Spearman correlation coefficient (p0.05). Conclusion: This animal study suggests that isolated macroscopic ICRS assessment of cartilage repair tissue does not correlate well with histological assessment. Possible explanations may be limitations of surface assessment compared to analysis deeper into the tissue and the necessity of more elaborate macroscopic assessment including hypertrophy, colour, lesion size, location and degenerative status of the joint. Techniques that are more accurate, precise and reliable, such as histology, dGEMERIC and T2 mapping MRI, contrast enhanced CT or optical coherence tomography (OCT), should be considered as alternatives or at least as complimentary methods.

Magnetic resonance imaging (MRI) has been used for morphological joint imaging, allowing visualization of abnormalities in cartilage, ligaments, bone, and other anatomical features. Quantitative MRI sequences provide noninvasive or minimally invasive means to assess proteoglycan and collagen integrity. These sequences vary in sensitivity to macromolecular content and differences between native and repair cartilage. When these standard MR sequences are used to image repaired cartilage, the presence of implanted metallic objects interferes and causes artifacts in the images affecting the clinical outcomes. Different types of artifacts, pulse sequences currently used, and emerging techniques to minimize these artifacts are discussed.

Cartilage tissue engineering has primarily focused on the generation of grafts to repair cartilage defects due to traumatic injury and disease. However engineered cartilage tissues have also a strong scientific value as advanced 3D culture models. Here we first describe key aspects of embryonic chondrogenesis and possible cell sources/culture systems for in vitro cartilage generation. We then review how a tissue engineering approach has been and could be further exploited to investigate different aspects of cartilage development and degeneration. The generated knowledge is expected to inform new cartilage regeneration strategies, beyond a classical tissue engineering paradigm.

Tracheal circumferential defects involving more than half of the tracheal wall still represent an unsolved problem. Several studies have developed different methods to help repair cartilage and improve healing but a suitable tracheal reconstruction or replacement has not been achieved yet. Novel bioengineering technologies seem to be the new answer to this serious problem. This chapter briefly describes the fundamentals of the anatomical and physiological tracheal functions and provides a review of trachea tissue engineering. Then it describes the project and development by means of electrospinning of a biodegradable tubular tracheal scaffold with an in vitro and in vivo preliminary experimental approach.

The aim of this work is to view different processes used for repair cartilage defect, and their suitability for laser based manufacturing. Many of human tissues can be equated to composite structure. Combination of a regular interconnected pore structure, materials¿ mechanical properties and hydrogel¿s lubrication characteristic can bring implant¿s structure closer to the form that can be founded in natural cartilage. Laser can be used for a wide variety of materials to manufacture complicated three dimensional structures. For this reason it was chosen for closer analysis. Research papers in official databases, medical science books and patents were used as research material.

The increasing spectrum of different cartilage repair strategies requires the introduction of adequate nondestructive methods to analyse their outcome in-vivo, i.e. arthroscopically. The validity of non-destructive quantitative ultrasound biomicroscopy (UBM) was investigated in knee joints of five miniature pigs. After 12 weeks, six 5-mm defects, treated with different cartilage repair approaches, provided tissues with different structural qualities. Healthy articular cartilage from each contralateral unoperated knee joint served as a control. The reflected and backscattered ultrasound signals were processed to estimate the integrated reflection coefficient (IRC) and apparent integrated backscatter (AIB) parameters. The cartilage repair tissues were additionally assessed biomechanically by cyclic indentation, histomorphologically and immunohistochemically. UBM allowed high-resolution visualisation of the structure of the joint surface and subchondral bone plate, as well as determination of the cartilage thickness and demonstrated distinct differences between healthy cartilage and the different repair cartilage tissues with significant higher IRC values and a steeper negative slope of the depth-dependent backscatter amplitude AIB slope for healthy cartilage. Multimodal analyses revealed associations between IRC and the indentation stiffness. Furthermore, AIB slope and AIB at the cartilage-bone boundary (AIB dC ) were associated with the quality of the repair matrices and the subchondral bone plate, respectively. This ex-vivo pilot study confirms that UBM can provide detailed imaging of articular cartilage and the subchondral bone interface also in repaired cartilage defects, and furthermore, contributes in certain aspects to a basal functional characterization of various forms of cartilage repair tissues. UBM could be further established to be applied arthroscopically in-vivo.

Damaged cartilage has a limited power of regeneration. Although present surgical approaches are often effective, they can’t restore articular cartilage to its normal structure. Cartilage regeneration can be stimulated by gene transfer using vectors. Early studies show how gene therapy is a promising but feasible tool to repair cartilage damage.

Articular cartilage is often damaged due to trauma or degenerative diseases, resulting in severe pain and disability. Most clinical approaches have been shown to have limited capacity to treat cartilage lesions. Tissue engineering (TE) has been proposed as an alternative strategy to repair cartilage. Cartilage defects often penetrate to the subchondral bone, or full-thickness defects are also produced in some therapeutic procedures. Therefore, in TE strategies one should also consider the need for a simultaneous regeneration of both cartilage and subchondral bone in situations where osteochondral defects are present, or to provide an enhanced support for the cartilage hybrid construct. In this review, different concepts related to TE in osteochondral regeneration will be discussed. The focus is on the need to produce new biphasic scaffolds that will provide differentiated and adequate conditions for guiding the growth of the two tissues, satisfying their different biological and functional requirements. Copyright © 2007 John Wiley & Sons, Ltd.

Cartilage functions as a low-friction, wear-resistant, load-bearing tissue. During a normal gait cycle, one cartilage surface rolls and slides against another, all the while being loaded and unloaded. The durability of the tissue also makes for an impressive material to study. However, when cartilage is damaged or diseased, the tissue has little capacity to repair itself. The goal of cell-based repair strategies to replace damaged or diseased tissue requires that the functional biomechanical properties of normal (developing or mature), diseased, and repair cartilage be restored. This chapter addresses some of the major methods used to assess the biomechanical properties of native and tissue-engineered cartilage. First, the traditional methods of testing by compression, tension, shear, and indentation are reviewed. Next, additional methods to evaluate interfacial mechanics and lubrication are described. Thus, a variety of mechanical tests may be used to assess functional properties for normal, diseased, and tissue-engineered cartilage.

There is now over 10 years experience with autologous chondrocyte implantation (ACI) for the management of full-thickness chondral injuries in the knee. This article briefly reviews the surgical procedure, the time lines of graft maturation, and patient rehabilitation in the context of postoperative magnetic resonance imaging (MRI) assessment. The normal and abnormal appearances of ACI repair cartilage on MR images are described, with an emphasis on the MR appearances of the complications that may occur after this procedure, and the usefulness of MR imaging for the surgeon.

Qualitative magnetic resonance imaging of repair cartilage after micro fracturing procedure: Evaluation using dGEMRIC and T2 mapping A. Watanabe, C. Boesch, S.E. Anderson, W. Brehm, Y. Wada, P. Mainil-Varlet; Department Of Radiology, Teikyo University Chiba Medical Center, Ichihara, Japan, Department Of Clinical Research, Unit For Mr Spectroscopy And Methodology, University of Bern, Bern, Switzerland, Department Of Diagnostic, Interventional And Pediatric Radiology, University of Bern, Bern, Switzerland, University Of Bern, Institute of Pathology, Bern, Switzerland, Orthopedic Surgery, Teikyo University Chiba Medical Center, Ichihara, Japan, Cro, Allevia AG, Bern, Switzerland

Wounds penetrating articular cartilage to bone heal with cartilage described variably as either fibrous or hyaline. In the present study, such repair cartilage was induced in the rabbit for biochemical comparison with normal articular cartilage. The main collagen in the repair tissue after three weeks was type I. By six to eight weeks, type II had become predominant and continued to be enriched up to one year; but type I still persisted as a significant constituent of the repair tissue even after a year, so the repair cartilage never fully resembled normal articular cartilage. From radiochemical analysis, type II was determined to be the major collagen synthesized by the repair tissue after three to four weeks. After six months, the repair cartilage contained more collagen and less hexosamine than control cartilage, suggesting that the fibrous texture that often developed was due to a loss of proteoglycans rather than to a change in the type of collagen. Clinical Relevance: Procedures capable of inducing the differentiation of authentic articular cartilage to resurface degenerated human joints would be invaluable. Surgical methods, such as drilling through to subchondral bone, are often attempted. It is not known, however, whether the cartilage that forms is true articular cartilage or, for example, fibrocartilage. The present experimental study in rabbits compared the properties of such repair cartilage with those of normal articular cartilage.