Current Tissue Engineering (Discontinued) - Volume 4, Issue 2, 2015

Background: Chronic overuse or acute injury to the knee has been determined to be a major cause of knee osteoarthritis (OA). Studies have indicated an increased incidence of osteoarthritis in athletes, with or without a history of significant knee injury. Method: This review examines the relationship between physical activity and the onset of articular cartilage damage, which may progress to OA. The contact forces and stresses sustained by the knee joint during dynamic movement in sports is summarized, followed by exploring the potential correlation between these contact loads and impact injury of articular cartilage. Finally, potential modalities to prevent the progression of OA of mechanically injured cartilage are discussed. The articles regarding OA, contact forces and stresses in dynamic movements, and prevention modalities of OA were identified in PubMed databases. Results: Increases in physical demand on the body can have adverse effects on knee joint health, especially during high contact stresses in sports. This was shown by various studies recording changes in knee joint biomarkers, cartilage deformation rates, and cartilage volume after exposing knee joints to a variety of stresses including long distance running or short-term high impact exercises. The data of joint contact force and stress previously reported have indicated a high risk of cartilage injury in high impact sports. Some potential modalities may be able to prevent OA development after performing high impact sport actives. Conclusion: Changes in knee cartilage due to overuse or injury can lead to OA later on in life. Identifying the forces involved at the onset of articular cartilage damage would allow physicians to pinpoint the early stage of articular cartilage damage and provide proper preventive treatments to avoid OA development.

Background: Notochordal cells (NCs) from the central nucleus pulposus (NP) region of the intervertebral discs (IVD) in the spine have an important function in IVD development, as well as in maintaining disc homeostasis. Indeed, the disappearance of NCs, which occurs early in life in humans, is associated with the earliest stages of disc degeneration, suggesting a link between the two events. Given the vital role NCs play in the IVD, a more complete knowledge of NC behavior and function, as well as how NCs may be employed in the development of new treatment methods for IVD degeneration, is necessary. The purpose of this paper is to provide an overview of NCs, including their phenotypic expression, their loss and consequences thereof in the disc, and possible strategies to use NCs in disc regeneration and repair. Methods: Background information regarding the phenotypic expression and role of NCs in the IVD is reviewed. An overview of the current knowledge on possible factors contributing to NC cell loss is presented, along with resulting consequences of the shift in cell population in the NP. Finally, the current research on methods to employ NCs in regenerative treatment strategies is provided. Results: Notochordal NP cells have a particular phenotype that is unique from aged or degenerated NP cells which is important for IVD development and maintenance. Thus, the disappearance of NCs has detrimental effects on the health and function of the IVD. Numerous factors may contribute to change in NC activity and/or viability, including microenvironmental conditions such as hypoxia, hyperosmolarity, and mechanical loading. Research is ongoing in determining how the positive effects of NCs can be harnessed into new strategies for IVD restoration, including use of NCs in cell transplantation as a cell source, via co-culture of NCs with other cells, or through the use of NC conditioned media. Conclusion: Given the important role NCs play in the health and functionality of the IVD, as well as the positive effects of NCs on other cells, notochordal cells show great potential in the development of new cellular based strategies to prevent and/or treat disc degeneration.

Osteoarthritis (OA) is a debilitating and painful orthopedic joint disease, affecting over 20 million people in the United States and is characterized by the degeneration of cartilage at the articulating surfaces of bones and inflammation of joint capsule. While the field of orthopedic research has progressed immensely in the previous decades, understanding of suitable targets for therapeutic techniques for treating or preventing OA is severely lacking in current clinical methods. Genetic regulation of the catabolic enzymes and anabolic proteins that characterize OA begins in the cytosol of the chondrocyte by short non-coding microRNAs (miRNAs). Proper regulation of miRNAs has shown to be critical to maintain healthy cartilage. In this review, we outline the various miRNAs that have the potential to act as targets or therapies for OA and its symptoms. We conclude with a brief discussion the current and potential methods of delivering miRNA to joint tissues via intra-articular injection, and the challenges of miRNA therapeutics translating clinically.

Introduction: Currently used methods of articular cartilage repair, other than transplantation of autologous chondrocytes, include transplantation of allogeneic cartilage, non-viable cartilage preparations and various matrices in combination with in vitro cultured chondrocytes or pluripotent stem cells. Methods: The material for this paper was derived from the review of scientific literature and that of our own laboratory experience. Conclusion: To date, non-viable particulate cartilage preparations show the most promise in as much as their application results in healing of isolated articular cartilage defects. The experience with bioengineering of cartilage demonstrates that despite numerous efforts various techniques based on in vitro cultivation of isolated chondrocytes have not resulted in the formation of structurally and functionally sound cartilage. The experience gained to date indicates that to produce normal cartilage chondrocytes must act in concert with biologic matrices and substrates.

Background: The present study evaluates the benefits of associating bone marrow-derived mesenchymal stem cells (MSCs) with pharmacologically active microcarriers (PAMs) on cartilage healing in horses. Methods: This experimental study was carried out on ten standardbred horses with an induced cartilaginous lesion on the articulation of the fetlocks and with a follow-up of two months. Autologous MSCs, isolated from the bone marrow, were associated with either platelet-rich plasma (PRP), PAMs (functionalized with fibronectin and releasing or not TGF (Transforming Growth Factor)-β3) and injected into the joint 5 days after the creation of the lesion. A postoperative rehabilitation protocol was followed with a clinical and radiological follow-up. Two months after the injection, computed tomodensitometry (CT), magnetic resonance imaging (MRI) and histological examinations were performed on ex vivo samples of the joints. Results: MSCs associated with PAMs releasing TGF-β3 significantly improved cartilage repair as assessed by histological analyses for tidemark presence and glycosaminoglycans content (p<0.05), while no effect of the treatment was evident at macroscopic examinations. In addition, the MSCs combined with PAM-TGFβ3 ameliorated these histological results when compared to MSCs with PAMs. These observations were supported by UTE (ultrashort time echo) sequences in the MRI images (p<0.0001). Conclusion: A significant improvement in cartilage repair was detected based on histologic and UTE-MRI analyses in joints treated with MSCs associated with PAM-TGFβ3. The association of equine MSCs with PAMs releasing TGF-β3 could be a novel therapeutic strategy for cartilage repair in athletic horses.

Background: Articular cartilage plays a critical biomechanical function in physiological activities of joints, owing to the unique biochemical structures of the tissue. In osteoarthritis, cartilage irreversibly loses its integrity in extracellular matrix organization followed by enzymatic degradation, leading to the deterioration in joint function. Often surgical interventions with implantation of autologous chondrocytes or engineered cartilage tissue, a promising alternative, are necessary to restore cartilage function. Therefore, non-invasively assessing and monitoring the outcomes of repair surgeries is an important issue for cartilage regeneration. Quantitative MRI methods show great promise in assessing the extent of the repair and elucidating information on the biochemical composition of the repair cartilage. Methods: PubMed and Web of Science searches were run on queries related to MR imaging of healthy, diseased and regenerated cartilage in human, animal and in vitro studies. The results were synthesized to highlight key themes in current technologies and future directions. Results: Three imaging techniques emerged as the most widely studied: T2 imaging, gadolinium enhanced T1 (T1Gd) imaging and diffusion imaging. T2 imaging can be used to determine if the zonal architecture of cartilage has been replicated by the repair tissue, T1Gd is widely utilized to quantify the amount of proteoglycans in the repair tissue, and diffusion imaging can quantify the direction and magnitude of the mobility of water molecules through the cartilage. Conclusion: Quantitative MRI shows great promise as a non-invasive measure of regenerated cartilage health. Studies are more successful when they combine multiple modalities to achieve a multi-parametric view of cartilage properties. Taken together, T2, T1Gd and diffusion imaging have great potential to accurately assess the success of cartilage regeneration and repair.

Background: Restoration of human cartilage structures and function using materials highly similar to human native tissues remains to be a major challenge in bioengineering and orthopedics fields. The chondrogenic potential and quality of cellular components used in cartilage repair and tissue engineering have a profound impact on the function of cartilage constructs. Many types of somatic stem cells have been shown as potential sources to obtain the cellular components suitable for cartilage regeneration. Although mesenchymal stem cells derived from bone marrow and adipose tissues have long been known for and favored in chondrogenic applications, later discoveries indicate that perichondrial progenitor cells (PPCs) existing in cartilage perichondrium may provide greater capacity and advantages in cartilage repair and tissue engineering. The primary focus of this review article is to discuss human cartilage composition, clinical conditions requiring cartilage repair, the anatomical location and characteristics of PPCs, as well as their potential value in tissue engineering and regenerative medicine. Areas covered: A literature survey on the progenitors of chondrocytes using NCBI-PubMed and Google Scholar was performed in 2014 and 2015. The information and experimental results gathered from preceding studies were summarized and presented in this review article. Conclusion: Recent advances in stem cell biology and regenerative medicine provide hope for new strategies to treat cartilage lesions. PPCs have been considered a potential source for the cellular component suitable for cartilage repair and tissue engineering. Emerging evidence has suggested that these cells play critical roles in cartilage regeneration in vivo, and that they could be an ideal cellular material for cartilage reconstruction and tissue engineering due to their proliferative capacity and strong propensity for chondrogenic differentiation. We believe that further studies and characterization in human PPCs and their chondrogenic differentiated derivatives will provide important information that could assist the development of better regeneration and tissue engineering approaches to treat cartilage disease and injury.

Background: There exists a range of surgical and non-surgical approaches to the treatment of both acute and chronic tendon injuries. Despite surgical advances in the management of acute tears and increasing treatment options for tendinopathies, strategies frequently are unsuccessful, due to impaired mechanical properties of the treated tendon and/or a deficiency in progenitor cell activities. Methods: Here, we review the emerging concepts and scientific evidence which provide a rationale for tissue engineering and regeneration strategies as well as discuss the clinical translation of recent innovations. Results: Biologic therapies for treatment of tendon injuries include the utilization of scaffolds as well as gene, growth factor, and cell delivery. These treatment modalities aim to provide mechanical durability or augment the biologic healing potential of the repaired tissue. Conclusion: There is an urgent need for effective therapeutic strategies to augment intrinsic and/or surgical repair. Such approaches can benefit both tendinopathies and tendon tears which, due to their severity, appear to be irreversible or irreparable.