Normal Hyaline Cartilage Research Articles

Advances in viscosupplementation and tribosupplementation for early-stage osteoarthritis therapy.

Joint kinematic instability, arising from congenital or acquired musculoskeletal pathoanatomy or from imbalances in anabolism and catabolism induced by pathophysiological factors, leads to deterioration of the composition, structure and function of cartilage and, ultimately, progression to osteoarthritis (OA). Alongside articular cartilage degeneration, synovial fluid lubricity decreases in OA owing to a reduction in the concentration and molecular weight of hyaluronic acid and surface-active mucinous glycoproteins that form a lubricating film over the articulating joint surfaces. Minimizing friction between articulating joint surfaces by lubrication is fundamental for decreasing hyaline cartilage wear and for maintaining the function of synovial joints. Augmentation with highly viscous supplements (that is, viscosupplementation) offers one approach to re-establishing the rheological and tribological properties of synovial fluid in OA. However, this approach has varied clinical outcomes owing to limited intra-articular residence time and ineffective mechanisms of chondroprotection. This Review discusses normal hyaline cartilage function and lubrication and examines the advantages and disadvantages of various strategies for restoring normal joint lubrication. These strategies include contemporary viscosupplements thatcontain antioxidants, anti-inflammatory drugs or platelet-rich plasma and new synthetic synovial fluid additives and cartilage matrix enhancers. Advanced biomimetic tribosupplements offer promise for mitigating cartilage wear, restoring joint function and, ultimately, improving patient care.

Laser Ablation Facilitates Implantation of Dynamic Self-Regenerating Cartilage for Articular Cartilage Regeneration.

This study investigated a novel strategy for improving regenerative cartilage outcomes. It combines fractional laser treatment with the implantation of neocartilage generated from autologous dynamic Self-Regenerating Cartilage (dSRC). dSRC was generated in vitro from harvested autologous swine chondrocytes. Culture was performed for 2, 4, 8, 10, and 12 weeks to study matrix maturation. Matrix formation and implant integration were also studied in vitro in swine cartilage discs using dSRC or cultured chondrocytes injected into CO2 laser-ablated or mechanically punched holes. Cartilage discs were cultured for up to 8 weeks, harvested, and evaluated histologically and immunohistochemically. The dSRC matrix was injectable by week 2, and matrices grew larger and more solid with time, generating a contiguous neocartilage matrix by week 8. Hypercellular density in dSRC at week 2 decreased over time and approached that of native cartilage by week 8. All dSRC groups exhibited high glycosaminoglycan (GAG) production, and immunohistochemical staining confirmed that the matrix was typical of normal hyaline cartilage, being rich in collagen type II. After 8 weeks in cartilage lesions in vitro, dSRC constructs generated a contiguous cartilage matrix, while isolated cultured chondrocytes exhibited only a sparse pericellular matrix. dSRC-treated lesions exhibited high GAG production compared to those treated with isolated chondrocytes. Isolated dSRC exhibits hyaline cartilage formation, matures over time, and generates contiguous articular cartilage matrix in fractional laser-created microenvironments in vitro, being well integrated with native cartilage.

Exploring the Mechanism of Microfracture in the Treatment of Porcine Full-Thickness Cartilage Defect

Background: Microfracture has the most extensive clinical application because of its advantages of a single operation, unified process, and low operation cost. Because research on the repair mechanism of microfractures in the treatment of cartilage defects is not in-depth, this study aimed to elucidate the mechanism. Purpose: To identify the characteristic cell subsets at different repair stages after microfracture, systematically analyze the repair process of the defect area after microfracture, and investigate the mechanism of fibrocartilage repair. Study Design: Descriptive laboratory study. Methods: Full-thickness articular cartilage defects and microfractures was established in the right knee of Bama miniature pigs. Single-cell transcriptional assays were used to identify the characteristics of cells isolated from healthy articular cartilage and regenerated tissues. Results: Microfractures induced mature fibrous repair in the full-thickness cartilage defect six months after surgery, while early stages of repair occurred within six weeks. Based on single-cell sequencing results, eight subsets and specific marker genes were identified. Two processes may occur after microfracture: normal hyaline cartilage regeneration and abnormal fibrocartilage repair. Regulatory chondrocytes, proliferative chondrocytes and cartilage progenitor cells (CPCs) may play important roles in the normal regeneration process. During abnormal repair, CPCs and skeletal stem cells may have different functions, and macrophages and endothelial cells may play important regulatory roles in the formation of fibrochondrocytes. Conclusions: Using single-cell transcriptome sequencing, this study investigated the tissue regeneration process and identified key cell subsets after microfracture. Clinical Relevance: These results provide future targets for optimizing the repair effect of microfracture.

Poster 196: Articular Chondrocytes in Hip Femoroacetabular Impingement Present a Less Catabolic Phenotype than Late Stage of Disease

Objectives:Pathophysiologic mechanisms during osteoarthritis (OA) have been primarily identified using tissues harvested from end stage of disease. However, it is likely that the disease-initiating molecular changes have already occurred in early-stage diseased joints. Femoroacetabular impingement (FAI) has an etiologic role in up to 50% of hip osteoarthritis (OA) and offers a unique opportunity to study molecular changes during early stage OA. Cartilage samples from the impingement zone of FAI patients express catabolic inflammatory molecules. Previously, we have confirmed that DNA methyltransferase 3B (DNMT3B) regulates post-natal articular cartilage homeostasis and 4 aminobutyrate aminotransferase (ABAT) is a downstream target for DNMT3B and attenuates catabolic gene expression. The purpose of the present study is to examine the catabolic state of ACs during progression of disease in hip FAI, specifically, to investigate the catabolic phenotype and to assess the expression levels of DNMT3B and ABAT during early (FAI) and late stage disease (OA-FAI).Methods:Full-thickness cartilage samples were collected from the anterolateral head-neck junction (impingement zone) of 11 patients. 5 patients underwent hip preservation surgery for symptomatic cam FAI (early stage OA- FAI) and 6 patients underwent total hip replacement for advanced OA secondary to cam FAI (late stage FAI-OA). As a non-disease (ND) group, 4 healthy samples were procured from hip joint cadavers. A liberator was used to harvest full thickness tissue samples for cartilage explant cultures. The cartilage tissues were washed several times using antibiotics and incubated at 37 °C and 5% CO2 for 24h. Subsequently, the explants were cultured in unstimulated conditions (no-treatment), under anabolic (TGFβ) and catabolic stimulus (IL-1β) for 48h. After culture, sections were stained with safranin O and fast green for histological analysis and cartilage degeneration was graded based on the Mankin score. RNA was isolated from explants, gene expression was analyzed via qPCR for the following specific markers: GADPH (housekeeping gene), DNMT3B, ABAT, MMP-13, and Type X collagen (COL10A1) (Figure-1). Comparisons among three groups were performed using one-way analysis of variance followed by the post hoc Bonferroni correction test.Results:Histological Mankin-scores are shown in Figure-2. Cartilage samples without treatment in ND group showed normal hyaline cartilage. However, reduction in safranin-O staining with significant increase of Mankin-score was observed under catabolic stimulus of IL-1β (Figure-2A). Contrary, in early FAI and late FAI-OA group, degenerative changes including superficial irregularities with some clefts, cell cloning, and reduced staining was observed in unstimulated conditions and became more pronounced when treated with IL-1β (Figure-2A and B). Degenerative changes were alleviated by anabolic stimulus with TGFβ1 (Figure-2B). qPCR revealed that compared to ND group, the expression levels of ABAT, MMP-13 and COL10A1 were increase in the early-FAI and late FAI-OA confirming a catabolic phenotype. Contrary, expression of DNMT3B gradually declined as the disease progressed showing significant differences between early-FAI and late FAI-OA (Figure-3B). Remarkably, although histological findings were similar between early and late stage FAI, catabolic molecule expression varied between early and late stage of disease suggesting a more catabolic phenotype state for late stage of disease.Conclusions:This current study provides initial data regarding the catabolic state of human ACs in early and late stage of hip FAI disease and characterized a catabolic phenotype of ACs from impingement zone in FAI. Importantly, although histological findings were similar between early and late stage FAI, catabolic molecule expression varied suggesting a less catabolic phenotype for early stage of disease. Most interestingly, the expression of DNMT3B gradually decrease as the disease progresses, and ABAT expression increase. Identification of these changes of methylation profiles during disease progression can distinguish pre- and early disease states from end diseased state and could provide a potential intervention to stop the OA progression in the near future. Future interventional therapies will confirm if ACs from early stage of disease can be rescued to a normal phenotype.

Review of Quantitative Knee Articular Cartilage MR Imaging.

Osteoarthritis (OA) is one of the most prevalent disorders in today’s society, resulting in significant socio-economic costs and morbidity. MRI is widely used as a non-invasive imaging tool for OA of the knee. However, conventional knee MRI has limitations to detect subtle early cartilage degeneration before morphological changes are visually apparent. Novel MRI pulse sequences for cartilage assessment have recently received increased attention due to newly developed compositional MRI techniques, including: T2 mapping, T1rho mapping, delayed gadolinium-enhanced MRI of cartilage (dGEMRIC), sodium MRI, diffusion-weighted imaging (DWI)/ diffusion tensor imaging (DTI), ultrashort TE (uTE), and glycosaminoglycan specific chemical exchange saturation transfer (gagCEST) imaging. In this article, we will first review these quantitative assessments. Then, we will discuss the variations of quantitative values of knee articular cartilage with cartilage layer (depth)- and angle (regional)-dependent approaches. Multiple MRI sequence techniques can discern qualitative differences in knee cartilage. Normal articular hyaline cartilage has a zonal variation in T2 relaxation times with increasing T2 values from the subchondral bone to the articular surface. T1rho values were also higher in the superficial layer than in the deep layer in most locations in the medial and lateral femoral condyles, including the weight-bearing portion. Magic angle effect on T2 mapping is clearly observed in the both medial and lateral femoral condyles, especially within the deep layers. One of the limitations for clinical use of these compositional assessments is a long scan time. Recent new approaches with compressed sensing (CS) and MR fingerprinting (MRF) have potential to provide accurate and fast quantitative cartilage assessments.

Particulated Autologous Chondral−Platelet-Rich Plasma Matrix Implantation (PACI) for Treatment of Full-Thickness Cartilage Osteochondral Defects

Articular hyaline cartilage injuries can occur as a result of either traumatic of progressive degeneration. When the articular cartilage in a joint is damaged, it can cause joint pain and dysfunction, predisposing patients for the development of early-onset osteoarthritis. There are many restoration procedures available to treat these injuries, such as bone marrow−stimulation techniques, osteoarticular auto/allograft transplants, and autologous chondrocyte implantation. Each of these techniques has its own limitations, which led researchers to explore new regenerative and repair techniques to produce normal hyaline cartilage. The purpose of this Technical Note is to describe in detail the particulated autologous chondral−platelet-rich plasma matrix implantation (PACI) technique that could be used as a single-stage cartilage restoration procedure for treatment of full-thickness cartilage and osteochondral defects.

Endogenous Repair and Regeneration of Injured Articular Cartilage: A Challenging but Promising Therapeutic Strategy

Articular cartilage (AC) has a very limited intrinsic repair capacity after injury or disease. Although exogenous cell-based regenerative approaches have obtained acceptable outcomes, they are usually associated with complicated procedures, donor-site morbidities and cell differentiation during ex vivo expansion. In recent years, endogenous regenerative strategy by recruiting resident mesenchymal stem/progenitor cells (MSPCs) into the injured sites, as a promising alternative, has gained considerable attention. It takes full advantage of body’s own regenerative potential to repair and regenerate injured tissue while avoiding exogenous regenerative approach-associated limitations. Like most tissues, there are also multiple stem-cell niches in AC and its surrounding tissues. These MSPCs have the potential to migrate into injured sites to produce replacement cells under appropriate stimuli. Traditional microfracture procedure employs the concept of MSPCs recruitment usually fails to regenerate normal hyaline cartilage. The reasons for this failure might be attributed to an inadequate number of recruiting cells and adverse local tissue microenvironment after cartilage injury. A strategy that effectively improves local matrix microenvironment and recruits resident MSPCs may enhance the success of endogenous AC regeneration (EACR). In this review, we focused on the reasons why AC cannot regenerate itself in spite of potential self-repair capacity and summarized the latest developments of the three key components in the field of EACR. In addition, we discussed the challenges facing in the present EACR strategy. This review will provide an increasing understanding of EACR and attract more researchers to participate in this promising research arena.

Cartilage Extracellular Matrix Scaffold With Kartogenin-Encapsulated PLGA Microspheres for Cartilage Regeneration.

Repair of articular cartilage defects is a challenging aspect of clinical treatment. Kartogenin (KGN), a small molecular compound, can induce the differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) into chondrocytes. Here, we constructed a scaffold based on chondrocyte extracellular matrix (CECM) and poly(lactic-co-glycolic acid) (PLGA) microspheres (MP), which can slowly release KGN, thus enhancing its efficiency. Cell adhesion, live/dead staining, and CCK-8 results indicated that the PLGA(KGN)/CECM scaffold exhibited good biocompatibility. Histological staining and quantitative analysis demonstrated the ability of the PLGA(KGN)/CECM composite scaffold to promote the differentiation of BMSCs. Macroscopic observations, histological tests, and specific marker analysis showed that the regenerated tissues possessed characteristics similar to those of normal hyaline cartilage in a rabbit model. Use of the PLGA(KGN)/CECM scaffold may mimic the regenerative microenvironment, thereby promoting chondrogenic differentiation of BMSCs in vitro and in vivo. Therefore, this innovative composite scaffold may represent a promising approach for acellular cartilage tissue engineering.

Cartilage regeneration with human dental pulp stem cells - a systematic review

Background & Aim Background there is a high prevalence of patients with symptomatic cartilage lesions and it rises as a socioeconomic issue with a considerable economic problem. Despite the numerous techniques available today, complete healing of damaged or defective cartilage and the consistent reproduction of normal hyaline cartilage is not possible. Choice of harvesting site is motivated by MSCs abilities to modulate immunologic and inflammatory response. Recently, dental pulp has been shown to contain a stem cell niche and these dental pulp stem cells (DPSCs) maintain their self-renewal capacity due to the active environment in the dental pulp of deciduous teeth. Aim the aim of this study was to review the current literature on the potential and limitations of cell-based therapies in cartilage regeneration using dental pulp derived mesenchymal stem cells. Methods, Results & Conclusion Methods an customized electronic search of scientific articles was conducted using PubMed/ MEDLINE and EMBASE databases from their inception to December 2018. Inclusion criteria were applied and the manuscripts that described usage chondral treatment with dental pulp stem cells were elected for complete evaluation. The articles were classified according to scaffold used, experimental model, features of chondrogenic differentiation, local of the defect, cartilage evaluation and results. After application of eligibility criteria, a total of 9 studies were selected and fully analyzed. Results a variety of animal models were used in the studies analyzed in this systematic review, including mice, rat, rabbit and miniature pig. It was evidenced tissue engineering for articular cartilage defects and safety of using human DPSCs to repair cartilage defects. There are six studies that created local defects to receive scaffold and test for DPSCs efficacy. Two studies focused on preclinical models for cartilage tissue engineering. Conclusion once presented and ongoing studies confirm positive results of DPSCs for articular cartilage treatment, new boundaries of stem cell therapy are open for cartilage tissue bioengineering and subsequent clinical trials should be performed.

Systematic Review of Human Dental Pulp Stem Cells for Cartilage Regeneration.

Background: Symptomatic cartilage lesions and early osteoarthritis produce significant clinical and economic burdens. Cartilage repair can improve the symptoms and delay arthroplasty. The complete healing of damaged cartilage with the consistent reproduction of normal hyaline cartilage has not yet been achieved. The choice of harvesting site might influence the cells' abilities to modulate immunologic and inflammatory responses. Recently, dental pulp has been shown to contain a stem cell niche consisting of dental pulp stem cells (DPSCs) that maintain their self-renewal capacity due to the active environment in the dental pulp of deciduous teeth. Objective: The aim of this study was to critically review the current literature on the potential and limitations of the use of dental pulp-derived mesenchymal stem cells in cell-based therapies for cartilage regeneration. Methods: An electronic, customized search of scientific articles was conducted using the PubMed/MEDLINE and EMBASE databases from their inception to December 2018. The inclusion criteria were applied, and the articles that described the use of DPSC in cartilage treatment were selected for complete evaluation. The articles were classified according to the scaffold used, experimental model, chondrogenic differentiation features, defect location, cartilage evaluation, and results. After the application of the eligibility criteria, a total of nine studies were selected and fully analyzed. Results: A variety of animal models were used, including mice, rats, rabbits, and miniature pigs, to evaluate the quality and safety of human DPSCs in the repair of cartilage defects. Among the articles, two studies focused on preclinical models of cartilage tissue engineering. Five studies implanted DPSCs in other animal sites. Conclusion: The use of DPSCs is a potential new stem cell therapy for articular cartilage repair. The preclinical evidence discussed in this article provides a solid foundation for future clinical trials. Impact statement Osteoarthritis presents an ever-increasing clinical and socioeconomic burden. While cartilage repair has the potential to improve symptoms and delay joint replacement, complete regeneration of hyaline cartilage has been an elusive goal. Dental pulp has been shown to contain a niche that protects dental pulp stem cells (DPSCs) from the cumulative effects of genetic and environmental factors and maintains their self-renewal capacity due to the active environment. Transplantation and preclinical trials have demonstrated the strong potential of regenerative tissue-engineering protocols using DPSCs.

Mesenchymal Stem Cell Therapy in Osteoarthritis and Regenerative Medicine.

Mesenchymal Stem Cell Therapy in Osteoarthritis and Regenerative Medicine.

A single integrated osteochondral in situ composite scaffold with a multi-layered functional structure.

This work focuses on the optimization design of a functional biomimetic scaffold for the repair of osteochondral defects and includes the study of single integrated osteochondral tissue engineering scaffolds with a multi-layered functional structure. Rabbit model experiments were used to evaluate the repair of osteochondral defects. The results revealed that good integration was achieved both at the interfaces between the scaffold material and the host tissue and between the newly formed subchondral bone and cartilage. The highest total histological score of 24.2 (based on the modified O'Driscoll scoring system at 12 weeks post-operation) was achieved for osteochondral repair. The completely repaired cylindrical full-thickness defects for the rabbit animal model reached 5 mm in diameter. The thickness of the regenerated cartilage was almost in line with that of the surrounding normal cartilage, the number and arrangement of cells in the superficial area of cartilage were very close to those of normal hyaline cartilage, and there were clear cartilage lacunas in the regenerated cartilage. The hybrid-use of growth factors and LIPUS stimulation exhibited good potential in enhancing vascularization and the formation of new bone and cartilage, providing better conditions for the overall osteochondral repair.

Role of the Biomimetic Scaffolds in the Regeneration of Articular Tissue in Deep Osteochondral Defects in a Rabbit Model

The ability of damaged articular cartilage to recover with normal hyaline cartilage is limited. Our aim was to study the mechanism of in vivo cartilage repair in case of severe osteochondral lesions using a three-dimensional matrix implanted without any preseeded cells in the osteochondral defect in a rabbit model. According to the ICRS scores from macroscopic observations of the femoral condyles, the average scores in the scaffold groups were higher than those in the control groups at every time (P[0.001). Histological examination of the ostheochondral defects, revealed regeneration of new tissue with hyaline-like cartilage features only in matrix groups. At twelve weeks from implantation, complete filling of the defect with hyaline cartilage with a tendency of mineralization and the absence of implant material is observed. The superficial area of the defect is completely covered with hyaline-like cartilage. The scaffold used leaded to the regeneration of articular tissue with an ordered histoarchitecture.

Investigating cellulose derived glycosaminoglycan mimetic scaffolds for cartilage tissue engineering applications.

Articular cartilage has a limited capacity to heal and, currently, no treatment exists that can restore normal hyaline cartilage. Creating tissue engineering scaffolds that more closely mimic the native extracellular matrix may be an attractive approach. Glycosaminoglycans, which are present in native cartilage tissue, provide signalling and structural cues to cells. This study evaluated the use of a glycosaminoglycan mimetic, derived from cellulose, as a potential scaffold for cartilage repair applications. Fully sulfated sodium cellulose sulfate (NaCS) was initially evaluated in soluble form as an additive to cell culture media. Human mesenchymal stem cell (MSC) chondrogenesis in pellet culture was enhanced with 0.01% NaCS added to induction media as demonstrated by significantly higher gene expression for type II collagen and aggrecan. NaCS was combined with gelatine to form fibrous scaffolds using the electrospinning technique. Scaffolds were characterized for fibre morphology, overall hydrolytic stability, protein/growth factor interaction and for supporting MSC chondrogenesis in vitro. Scaffolds immersed in phosphate buffered saline for up to 56days had no changes in swelling and no dissolution of NaCS as compared to day 0. Increasing concentrations of the model protein lysozyme and transforming growth factor-β3 were detected on scaffolds with increasing concentrations of NaCS (p<0.05). MSC chondrogenesis was enhanced on the scaffold with the lowest NaCS concentration as seen with the highest collagen type II production, collagen type II immunostaining, and expression of cartilage-specific genes. These studies demonstrate the feasibility of cellulose sulfate as a scaffolding material for cartilage tissue engineering. Copyright © 2016 John Wiley & Sons, Ltd.

Hyaline Articular Matrix Formed by Dynamic Self-Regenerating Cartilage and Hydrogels.

Injuries to the articular cartilage surface are challenging to repair because cartilage possesses a limited capacity for self-repair. The outcomes of current clinical procedures aimed to address these injuries are inconsistent and unsatisfactory. We have developed a novel method for generating hyaline articular cartilage to improve the outcome of joint surface repair. A suspension of 10(7) swine chondrocytes was cultured under reciprocating motion for 14 days. The resulting dynamic self-regenerating cartilage (dSRC) was placed in a cartilage ring and capped with fibrin and collagen gel. A control group consisted of chondrocytes encapsulated in fibrin gel. Constructs were implanted subcutaneously in nude mice and harvested after 6 weeks. Gross, histological, immunohistochemical, biochemical, and biomechanical analyses were performed. In swine patellar groove, dSRC was implanted into osteochondral defects capped with collagen gel and compared to defects filled with osteochondral plugs, collagen gel, or left empty after 6 weeks. In mice, the fibrin- and collagen-capped dSRC constructs showed enhanced contiguous cartilage matrix formation over the control of cells encapsulated in fibrin gel. Biochemically, the fibrin and collagen gel dSRC groups were statistically improved in glycosaminoglycan and hydroxyproline content compared to the control. There was no statistical difference in the biomechanical data between the dSRC groups and the control. The swine model also showed contiguous cartilage matrix in the dSRC group but not in the collagen gel and empty defects. These data demonstrate the survivability and successful matrix formation of dSRC under the mechanical forces experienced by normal hyaline cartilage in the knee joint. The results from this study demonstrate that dSRC capped with hydrogels successfully engineers contiguous articular cartilage matrix in both nonload-bearing and load-bearing environments.

Identification of genes required for the spontaneous repair of partial-thickness cartilage defects in immature rats

ABSTRACTPurpose: Our previous study showed that partial-thickness articular cartilage defects (PTCDs) created in immature rats spontaneously healed to resemble normal hyaline cartilage, but that of mature rats did not. To identify molecules involved in the spontaneous cartilage repair observed in this model, gene expression was compared between PTCD and sham-operated cartilage of immature and mature rats. Materials and Methods: Six sets of gene comparisons were made at 12, 24, and 48 hours after the creation of PTCDs in immature and mature rats using microarrays. All the genes upregulated in immature cartilage at 12 hours were selected for further analysis if their expression pattern was not irregular such that diminished at 24 hours and re-upregulated at 48 hours. Relationships among genes selected through the above steps were analyzed using Ingenuity Pathway Analysis (IPA) software. After deriving networks, important molecules were further narrowed down by location within a network. Genes were regarded as central if they had relationships with more than 10 molecules in a network. Protein localization in tissues was confirmed by immunohistochemistry. Results: Five networks were identified. Their functional annotations were gene expression, cell cycle, growth and proliferation, and cell signaling. Transforming growth factor-beta (TGF-β) was centrally located in the network with the highest IPA score and mothers against decapentaplegic homolog-3 (Smad3) were centrally located in the second highest ranking network. Phosphorylated Smad3 was detected in the nuclei of chondrocytes in immature cartilage. Conclusions: Our data suggest the possible importance of Smad3 in the TGF-β signaling in the spontaneous healing of PTCDs in immature rats.

Cartilage tissue engineering: Role of mesenchymal stem cells along with growth factors & scaffolds.

Articular cartilage injury poses a major challenge for both the patient and orthopaedician. Articular cartilage defects once formed do not regenerate spontaneously, rather replaced by fibrocartilage which is weaker in mechanical competence than the normal hyaline cartilage. Mesenchymal stem cells (MSCs) along with different growth factors and scaffolds are currently incorporated in tissue engineering to overcome the deficiencies associated with currently available surgical methods and to facilitate cartilage healing. MSCs, being readily available with a potential to differentiate into chondrocytes which are enhanced by the application of different growth factors, are considered for effective repair of articular cartilage after injury. However, therapeutic application of MSCs and growth factors for cartilage repair remains in its infancy, with no comparative clinical study to that of the other surgical techniques. The present review covers the role of MSCs, growth factors and scaffolds for the repair of articular cartilage injury.

Cartilage Resurfacing: Unresolved Enigma. Commentary on an article by L.R. Goodrich, DVM, PhD, et al.: "Addition of Mesenchymal Stem Cells to Autologous Platelet-Enhanced Fibrin Scaffolds in Chondral Defects. Does It Enhance Repair?".

Full-thickness cartilage defects present a substantial clinical challenge. People are remaining active longer, and orthopaedic surgeons need techniques that effectively produce repair tissue that can withstand the test of time. The challenge is to find a way to achieve filling of cartilage defects with sufficiently cartilage-like tissue that is able to withstand repetitive loads without degeneration and loss of function. To date, efforts have failed to achieve good long-term results, at least in part because of the inability to recapitulate the type-II-collagen and aggrecan content of normal hyaline cartilage. Recent efforts have focused on cellular therapies—using chondrocytes or mesenchymal stem cells—as the basis for regeneration of repair tissue and for gene therapy approaches to enhance healing. Chondrocytes are ideally suited for the production of hyaline cartilage but challenging to obtain without donor site morbidity or the potential for inciting an immune response to allogenic cells. Bone-marrow-derived mesenchymal stem cells (BMDMSCs) provide an appealing alternative cell source with the potential to differentiate into chondrocytes following implantation and ease of collection with acceptable morbidity. Platelet-rich plasma has also gained recent attention as a readily available source of anabolic growth factors and cytokines with the potential to drive chondrogenesis. The paper by Goodrich et al. describes the use of culture-expanded BMDMSCs combined with platelet-rich plasma in the form of an autologous platelet-enhanced fibrin (APEF) scaffold to enhance cartilage …

Endogenous Cartilage Repair by Recruitment of Stem Cells.

Articular cartilage has a very limited capacity for repair after injury. The adult body has a pool of stem cells that are mobilized during injury or disease. These cells exist inside niches in bone marrow, muscle, adipose tissue, synovium, and other connective tissues. A method that mobilizes this endogenous pool of stem cells will provide a less costly and less invasive alternative if these cells successfully regenerate defective cartilage. Traditional microfracture procedures employ the concept of bone marrow stimulation to regenerate cartilage. However, the regenerated tissue usually is fibrous cartilage, which has very poor mechanical properties compared to those of normal hyaline cartilage. A method that directs the migration of a large number of autologous mesenchymal stem cells toward injury sites, retains these cells around the defects, and induces chondrogenic differentiation that would enhance success of endogenous cartilage repair. This review briefly summarizes chemokines and growth factors that induce recruitment, proliferation, and differentiation of endogenous progenitor cells, endogenous cell sources for regenerating cartilage, scaffolds for delivery of bioactive factors, and bioadhesive materials that are necessary to bring about endogenous cartilage repair.

Knee Articular Cartilage Repair and Restoration Techniques: A Review of the Literature.

Context:Isolated chondral and osteochondral defects of the knee are a difficult clinical challenge, particularly in younger patients for whom alternatives such as partial or total knee arthroplasty are rarely advised. Numerous surgical techniques have been developed to address focal cartilage defects. Cartilage treatment strategies are characterized as palliation (eg, chondroplasty and debridement), repair (eg, drilling and microfracture [MF]), or restoration (eg, autologous chondrocyte implantation [ACI], osteochondral autograft [OAT], and osteochondral allograft [OCA]).Evidence Acquisition:PubMed was searched for treatment articles using the keywords knee, articular cartilage, and osteochondral defect, with a focus on articles published in the past 5 years.Study Design:Clinical review.Level of Evidence:Level 4.Results:In general, smaller lesions (<2 cm2) are best treated with MF or OAT. Furthermore, OAT shows trends toward greater longevity and durability as well as improved outcomes in high-demand patients. Intermediate-size lesions (2-4 cm2) have shown fairly equivalent treatment results using either OAT or ACI options. For larger lesions (>4 cm2), ACI or OCA have shown the best results, with OCA being an option for large osteochondritis dissecans lesions and posttraumatic defects.Conclusion:These techniques may improve patient outcomes, though no single technique can reproduce normal hyaline cartilage.