Science.gov

Sample records for osteochondritis

  1. Osteochondral autografts.

    PubMed

    Patil, Shantanu; Tapasvi, Sachin R

    2015-12-01

    The healing potential for articular cartilage lesions is limited due to many physiological, local and mechanical factors. Spontaneous healing of partial- and full-thickness lesions is slow, and subsequent tissue response is usually not durable. In symptomatic, and high-demand, patients, a definitive treatment modality must be offered which allows for a sustained recovery with minimal debilitation. Injuries, which damage the subchondral bone, heal with the formation of fibrocartilage. This tissue fails long-term survival because of its inability to withstand the variable cyclic loads and compression forces that it is subjected to. While regeneration of the damaged cartilage by an entirely new articular surface is a goal beyond current available techniques, repair of the osteochondral defects with normal hyaline cartilage is possible by various options. Osteochondral defects that are larger then 2 cm are best treated by osteochondral autograft technique. The short-term outcomes of the present series show excellent results. PMID:26381671

  2. Role of Fresh Osteochondral Allografts for Large Talar Osteochondral Lesions.

    PubMed

    Gross, Christopher E; Adams, Samuel B; Easley, Mark E; Nunley, James A

    2016-01-01

    Osteochondral lesions of the talus, large or small, present a challenge to the treating orthopaedic surgeon. These cartilage and bony defects can cause substantial pain and functional disability. Surgical treatment of small lesions of the talus has been thoroughly explored and includes retrograde drilling, arthroscopic débridement and marrow stimulation, osteochondral autografting from cartilage/bone unit harvested from the ipsilateral knee (mosaicplasty), and autologous chondrocyte implantation. Although each of these reparative, replacement, or regenerative techniques has various degrees of success, they may be insufficient for the treatment of large osteochondral lesions of the talus. Large-volume osteochondral lesions of the talus (>1.5 cm in diameter or area >150 mm) often involve sizable portions of the weight-bearing section of the talar dome, medially or laterally. To properly treat these osteochondral lesions of the talus, a fresh structural osteochondral allograft is a viable treatment option. PMID:26589459

  3. How I Manage Osteochondritis Dissecans.

    ERIC Educational Resources Information Center

    DiStefano, Vincent J.

    1986-01-01

    Osteochondritis dissecans, a lesion found most often on the femur at the knee joint, occurs most frequently in active adolescents. This article describes treatment for preadolescents, adolescents, and adults. Osteochondritus dissecans of the patella is also presented. (MT)

  4. Osteochondral Lesions of Major Joints

    PubMed Central

    Durur-Subasi, Irmak; Durur-Karakaya, Afak; Yildirim, Omer Selim

    2015-01-01

    This paper provides information about osteochondral lesions (OCL) and example cases of OCL occurring in major joints, some of which are rarely seen. This simple tutorial is presented in question and answer format. PMID:26180500

  5. Osteochondritis dissecans of the talus

    PubMed Central

    ZANON, GIACOMO; DI VICO, GIOVANNI; MARULLO, MATTEO

    2014-01-01

    Osteochondritis dissecans (OCD) is an acquired idiopathic lesion of subchondral bone that can produce delamination and sequestration with or without articular cartilage involvement and instability. The cause of OCD is still debated: the most recognized etiology is the occurrence of repetitive micro-traumas associated with vascular impairment, causing progressive ankle pain and dysfunction in skeletally immature and young adult patients. Ankle OCD is classically located in the medial part of the talus, while lateral and posterior involvement is less frequent. Diagnosis of OCD, based on MRI findings, is quite straightforward; MRI examination can also be very useful for dating the defect and obtaining information about the associated bone bruise. Osteochondritis dissecans, if not recognized and treated appropriately, may lead to secondary osteoarthritis with pain and functional limitation. Surgical treatment is mandatory especially in young patients with unstable cartilage fragments. There are various surgical options: fixation, microfracture, or substitution using autologous chondrocyte implantation techniques. PMID:25606554

  6. Osteochondral tissue engineering: current strategies and challenges.

    PubMed

    Nukavarapu, Syam P; Dorcemus, Deborah L

    2013-01-01

    Osteochondral defect management and repair remain a significant challenge in orthopedic surgery. Osteochondral defects contain damage to both the articular cartilage as well as the underlying subchondral bone. In order to repair an osteochondral defect the needs of the bone, cartilage and the bone-cartilage interface must be taken into account. Current clinical treatments for the repair of osteochondral defects have only been palliative, not curative. Tissue engineering has emerged as a potential alternative as it can be effectively used to regenerate bone, cartilage and the bone-cartilage interface. Several scaffold strategies, such as single phase, layered, and recently graded structures have been developed and evaluated for osteochondral defect repair. Also, as a potential cell source, tissue specific cells and progenitor cells are widely studied in cell culture models, as well with the osteochondral scaffolds in vitro and in vivo. Novel factor strategies being developed, including single factor, multi-factor, or controlled factor release in a graded fashion, not only assist bone and cartilage regeneration, but also establish osteochondral interface formation. The field of tissue engineering has made great strides, however further research needs to be carried out to make this strategy a clinical reality. In this review, we summarize current tissue engineering strategies, including scaffold design, bioreactor use, as well as cell and factor based approaches and recent developments for osteochondral defect repair. In addition, we discuss various challenges that need to be addressed in years to come. PMID:23174560

  7. Concomitant Osteochondral Autograft Transplantation and Fixation of Osteochondral Fragment for Treatment of a Massive Osteochondritis Dissecans: A Report of 8-Year Follow-up Results

    PubMed Central

    Lee, Byung Ill

    2015-01-01

    Numerous procedures exist to treat osteochondritis dissecans (OCD); however, it remains a topic of debate which procedure is most ideal. When restoring a massive osteochondral defect, the use of only one procedure may not always allow complete filling of the defect. This case report presents a massive OCD with displaced osteochondral fragment and loose body in the knee joint that occupied almost all of the weight bearing area of the medial femoral condyle and was treated with concomitant osteochondral autograft transplantation and fixation of displaced osteochondral fragment. To our knowledge, this is a rare report on OCD treated with concomitant osteochondral autograft transplantation and fixation of displaced osteochondral fragment. At 8 years after surgery, the clinical outcome was excellent, and radiographs revealed congruence of the medial femoral condyle. The patient returned to sports activities. In massive and complex OCD lesions, individual techniques have limitations. Two or more techniques are needed to increase the rate of success. PMID:26672950

  8. Osteochondritis dissecans of the elbow.

    PubMed

    Nissen, Carl W

    2014-04-01

    Osteochondritis dissecans affects the elbow of many young, skeletally immature athletes. The incidence of OCD in the elbow is second to its occurrence in the knee and similar to the incidence in the ankle. Young, athletically active individuals are at increased risk for developing this problem. There is a predilection for those involved in overhead-dominant sports and sports that require the arm to be a weight-bearing limb. The diagnosis is occurring earlier because of an increased awareness of the entity and the increased use of advanced imaging techniques, primarily magnetic resonance imaging. This earlier diagnosis has led to an increase in treatment ideas and modalities and ultimately improved care and outcomes. PMID:24698041

  9. Arthroscopic Osteochondral Grafting for Radiocarpal Joint Defects

    PubMed Central

    Ho, Pak-cheong; Tse, Wing-Iim; Wong, Clar Wing-Yee; Chow, Esther Ching-San

    2013-01-01

    Background Focal chondral lesion is a common cause of chronic wrist pain. The best treatment remains unknown. We have developed a technique of arthroscopic transplantation of an osteochondral autograft from the knee joint to the distal radius with satisfactory clinical results. Materials and Methods Between December 2006 and December 2010, four patients (average age 31 years) with posttraumatic osteochondral lesions over the dorsal lunate fossa were treated with arthroscopic osteochondral grafting. Pre- and postoperative motion, grip strength, wrist functional performance score, pain score, and return to work status were charted. Postoperative computed tomography (CT) scan, magnetic resonance imaging (MRI), and second-look arthroscopy were performed to assess graft incorporation. Description of Technique With the arthroscope in the 3-4 portal, synovitis over the dorsal lunate fossa was débrided to uncover the underlying osteochondral lesion. We employed the 6-mm trephine of the Osteoarticular Transfer System (OATS) to remove the osteochondral defect. Osteochondral graft was harvested from the lateral femoral condyle and delivered into the wrist joint arthroscopically. Results In all cases, grafts incorporation was completed by 3-4 months postoperative. All patients showed improvement in the wrist performance score (preoperative 27.5, postoperative 39 out of 40) with no pain on final follow-up at average 48.5 months (range 24-68 months). Grip strength improved from 62.6 to 98.2% of the contralateral side. Motion improved from 115.5 to 131.3°. X-ray images showed preserved joint space. Patient satisfaction was high with no complication. Conclusion An arthroscopic-assisted transfer of an osteochondral graft is a viable treatment option for chondral defects of the distal radius. PMID:24436819

  10. Strategies for osteochondral repair: Focus on scaffolds

    PubMed Central

    Seo, Seog-Jin; Mahapatra, Chinmaya; Singh, Rajendra K; Knowles, Jonathan C

    2014-01-01

    Interest in osteochondral repair has been increasing with the growing number of sports-related injuries, accident traumas, and congenital diseases and disorders. Although therapeutic interventions are entering an advanced stage, current surgical procedures are still in their infancy. Unlike other tissues, the osteochondral zone shows a high level of gradient and interfacial tissue organization between bone and cartilage, and thus has unique characteristics related to the ability to resist mechanical compression and restoration. Among the possible therapies, tissue engineering of osteochondral tissues has shown considerable promise where multiple approaches of utilizing cells, scaffolds, and signaling molecules have been pursued. This review focuses particularly on the importance of scaffold design and its role in the success of osteochondral tissue engineering. Biphasic and gradient composition with proper pore configurations are the basic design consideration for scaffolds. Surface modification is an essential technique to improve the scaffold function associated with cell regulation or delivery of signaling molecules. The use of functional scaffolds with a controllable delivery strategy of multiple signaling molecules is also considered a promising therapeutic approach. In this review, we updated the recent advances in scaffolding approaches for osteochondral tissue engineering. PMID:25343021

  11. Osteochondral Allografts in the Ankle Joint

    PubMed Central

    Vannini, Francesca; Buda, Roberto; Ruffilli, Alberto; Cavallo, Marco; Giannini, Sandro

    2013-01-01

    Purpose: The aim of this systematic review is to report about the clinical use of partial and total fresh osteochondral allograft in the ankle joint. The state of the art of allografts with regard to basic science, procurement and storage methods, immunogenicity, generally accepted indications and contraindications, and the rationale of the allografting procedure have been described. Methods: All studies published in PubMed from 2000 to January 2012 addressing fresh osteochondral allograft procedures in the ankle joint were identified, including those that fulfilled the following criteria: (a) level I-IV evidence addressing the areas of interest outlined above; (b) measures of functional, clinical, or imaging outcome; and (c) outcome related to ankle cartilage lesions or ankle arthritis treated by allografts. Results: The analysis showed a progressively increasing number of articles from 2000. The number of selected articles was 14; 9 of those focused on limited dimension allografts (plugs, partial) and 5 on bipolar fresh osteochondral allografts. The evaluation of evidence level showed 14 case series and no randomized studies. Conclusions: Fresh osteochondral allografts are now a versatile and suitable option for the treatment of different degrees of osteochondral disease in the ankle joint and may even be used as total joint replacement. Fresh osteochondral allografts used for total joint replacement are still experimental and might be considered as a salvage procedure in otherwise unsolvable situations. A proper selection of the patients is therefore a key point. Moreover, the patients should be adequately informed about the possible risks, benefits, and alternatives to the allograft procedure. PMID:26069666

  12. Bipolar fresh osteochondral allograft of the shoulder

    PubMed Central

    GIANNINI, SANDRO; SEBASTIANI, ELISA; SHEHU, ALBA; BALDASSARRI, MATTEO; MARALDI, SUSANNA; VANNINI, FRANCESCA

    2013-01-01

    Purpose to describe an original technique and preliminary results of bipolar fresh osteochondral allograft implantation for the treatment of end-stage glenohumeral osteoarthritis. Methods three patients underwent bipolar fresh osteochondral allograft implantation to the shoulder. Clinical and radiographical evaluations were carried out periodically through to final follow-up. Results constant Score increased from 38.3 ± 2.9 pre-operatively to 78.7 ± 16.2 at 12 months, 72.3 ±15.3 at 24 months, and 59.3 ± 22.0 at 34 months. Arthritis and partial reabsorption of the implanted surfaces were evident radiographically. Conclusions the clinical results obtained in these patients seem to support the applicability of bipolar fresh osteochondral allograft implantation in the shoulder in subjects with severe post-traumatic arthritis and intact rotator cuff. The development of arthritis of the implanted surfaces, while not impacting the clinical result, is a cause of concern. Level of evidence level IV, therapeutic case series. PMID:25606526

  13. Recent progress in interfacial tissue engineering approaches for osteochondral defects.

    PubMed

    Castro, Nathan J; Hacking, S Adam; Zhang, Lijie Grace

    2012-08-01

    This review provides a brief synopsis of the anatomy and physiology of the osteochondral interface, scaffold-based and non-scaffold based approaches for engineering both tissues independently as well as recent developments in the manufacture of gradient constructs. Novel manufacturing techniques and nanotechnology will be discussed with potential application in osteochondral interfacial tissue engineering. PMID:22677924

  14. Multiphasic construct studied in an ectopic osteochondral defect model

    PubMed Central

    Jeon, June E.; Vaquette, Cédryck; Theodoropoulos, Christina; Klein, Travis J.; Hutmacher, Dietmar W.

    2014-01-01

    In vivo osteochondral defect models predominantly consist of small animals, such as rabbits. Although they have an advantage of low cost and manageability, their joints are smaller and more easily healed compared with larger animals or humans. We hypothesized that osteochondral cores from large animals can be implanted subcutaneously in rats to create an ectopic osteochondral defect model for routine and high-throughput screening of multiphasic scaffold designs and/or tissue-engineered constructs (TECs). Bovine osteochondral plugs with 4 mm diameter osteochondral defect were fitted with novel multiphasic osteochondral grafts composed of chondrocyte-seeded alginate gels and osteoblast-seeded polycaprolactone scaffolds, prior to being implanted in rats subcutaneously with bone morphogenic protein-7. After 12 weeks of in vivo implantation, histological and micro-computed tomography analyses demonstrated that TECs are susceptible to mineralization. Additionally, there was limited bone formation in the scaffold. These results suggest that the current model requires optimization to facilitate robust bone regeneration and vascular infiltration into the defect site. Taken together, this study provides a proof-of-concept for a high-throughput osteochondral defect model. With further optimization, the presented hybrid in vivo model may address the growing need for a cost-effective way to screen osteochondral repair strategies before moving to large animal preclinical trials. PMID:24694896

  15. Dysplasia Epiphysealis Hemimelica Treated with Osteochondral Allograft: A Case Report

    PubMed Central

    Anthony, Chris A.; Wolf, Brian R.

    2015-01-01

    Background Dysplasia epiphysealis hemimelica (DEH), or Trevor's disease, is a developmental disorder of the pediatric skeleton characterized by asymmetric osteochondral overgrowth. Methods We present the case of a five year old boy with a two year history of right knee pain and evidence of DEH on imaging who underwent initial arthroscopic resection of his lesion with subsequent recurrence. The patient then underwent osteochondral allograft revision surgery and was asymptomatic at two year follow-up with a congruent joint surface. Results To our knowledge, this is the first reported case of a DEH lesion treated with osteochondral allograft and also the youngest reported case of osteochondral allograft placement in the literature. Conclusions Osteochondral allograft may be a viable option in DEH and other deformities of the pediatric knee. Level of Evidence Level V PMID:26361443

  16. Rabbit Trochlear Model of Osteochondral Allograft Transplantation

    PubMed Central

    To, Nhat; Curtiss, Shane; Neu, Corey P; Salgado, Christopher J; Jamali, Amir A

    2011-01-01

    Allografting and autografting of osteochondral tissues is a promising strategy to treat articular cartilage lesions in damaged joints. We developed a new model of fresh osteochondral allografting using the entire rabbit trochlea. The objective of the current study was to demonstrate that this model would achieve reproducible graft–host healing and maintain normal articular cartilage histologic, immunolocalization, and biochemical characteristics after transplantation under diverse storage and transplantation conditions. New Zealand white (n = 8) and Dutch belted (n = 8) rabbits underwent a 2-stage transplantation operation using osteochondral grafts that had been stored for 2 or 4 wk. Trochlear grafts harvested from the left knee were transplanted to the right knee as either autografts or allografts. Grafts were fixed with 22-gauge steel wire or 3-0 nylon suture. Rabbits were euthanized for evaluation at 1, 2, 4, 6, and 12 wk after transplantation. All grafts that remained in vivo for at least 4 wk demonstrated 100% interface healing by microCT. Trabecular bridging was present at the host–graft interface starting at 2 wk after transplantation, with no significant difference in cartilage histology between the various groups. The combined histology scores indicated minimal evidence of osteoarthritis. Immunostaining revealed that superficial zone protein was localized at the surface of all transplants. The rabbit trochlear model met our criteria for a successful model in regard to the ease of the procedure, low rate of surgical complications, relatively large articular cartilage surface area, and amount of host–graft bone interface available for analysis. PMID:22330350

  17. Fresh osteochondral allografts in the knee: only a salvage procedure?

    PubMed Central

    Scotti, Celeste; Lane, John G.; Peretti, Giuseppe M.

    2015-01-01

    The role of fresh allogeneic osteochondral allograft transplantation (OCA) in the cartilage repair algorithm has been long debated and this procedure is primarily considered as a salvage procedure, to be used when other, simple, techniques have failed. Gracitelli et al. in a retrospective comparison of patients who received OCA as primary treatment or as a salvage procedure, demonstrates that the outcome of this procedure is minimally influenced by a previous failed treatment and that OCA represents an effective solution for both primary and revision surgery of chondral and osteochondral lesions of the knee. In particular, optimal indications for OCA seem to be revision of previously failed bone marrow stimulation techniques with an impaired subchondral bone plate and primary treatment of large osteochondral defects. PMID:26261835

  18. Surgical treatment for osteochondritis dessicans of the knee.

    PubMed

    Winthrop, Zachary; Pinkowsky, Gregory; Hennrikus, William

    2015-12-01

    Osteochondritis dissecans (OCD) of the knee is a disease of the subchondral bone with secondary injury to the overlying articular cartilage. OCD lesions are generally categorized as juvenile-growth plates open-or adult-growth plates closed. This maturity-based classification scheme has a prognostic value in that many juvenile OCD lesions will heal with conservative care while most symptomatic adult OCD lesions need surgical intervention. OCD can result in pain, knee joint effusions, loose body formation, and arthritis. Short-term treatment goals include pain and symptom resolution while the long-term goal is to minimize arthritis. Surgical options include debridement, drilling, microfracture, reduction and fixation, autograft osteochondral transplantation, autologous chondrocyte implantation, and allograft osteochondreal transplantation. PMID:26409885

  19. Diagnosing, planning and evaluating osteochondral ankle defects with imaging modalities.

    PubMed

    van Bergen, Christiaan Ja; Gerards, Rogier M; Opdam, Kim Tm; Terra, Maaike P; Kerkhoffs, Gino Mmj

    2015-12-18

    This current concepts review outlines the role of different imaging modalities in the diagnosis, preoperative planning, and follow-up of osteochondral ankle defects. An osteochondral ankle defect involves the articular cartilage and subchondral bone (usually of the talus) and is mostly caused by an ankle supination trauma. Conventional radiographs are useful as an initial imaging tool in the diagnostic process, but have only moderate sensitivity for the detection of osteochondral defects. Computed tomography (CT) and magnetic resonance imaging (MRI) are more accurate imaging modalities. Recently, ultrasonography and single photon emission CT have been described for the evaluation of osteochondral talar defects. CT is the most valuable modality for assessing the exact location and size of bony lesions. Cartilage and subchondral bone damage can be visualized using MRI, but the defect size tends to be overestimated due to bone edema. CT with the ankle in full plantar flexion has been shown a reliable tool for preoperative planning of the surgical approach. Postoperative imaging is useful for objective assessment of repair tissue or degenerative changes of the ankle joint. Plain radiography, CT and MRI have been used in outcome studies, and different scoring systems are available. PMID:26716090

  20. Diagnosing, planning and evaluating osteochondral ankle defects with imaging modalities

    PubMed Central

    van Bergen, Christiaan JA; Gerards, Rogier M; Opdam, Kim TM; Terra, Maaike P; Kerkhoffs, Gino MMJ

    2015-01-01

    This current concepts review outlines the role of different imaging modalities in the diagnosis, preoperative planning, and follow-up of osteochondral ankle defects. An osteochondral ankle defect involves the articular cartilage and subchondral bone (usually of the talus) and is mostly caused by an ankle supination trauma. Conventional radiographs are useful as an initial imaging tool in the diagnostic process, but have only moderate sensitivity for the detection of osteochondral defects. Computed tomography (CT) and magnetic resonance imaging (MRI) are more accurate imaging modalities. Recently, ultrasonography and single photon emission CT have been described for the evaluation of osteochondral talar defects. CT is the most valuable modality for assessing the exact location and size of bony lesions. Cartilage and subchondral bone damage can be visualized using MRI, but the defect size tends to be overestimated due to bone edema. CT with the ankle in full plantar flexion has been shown a reliable tool for preoperative planning of the surgical approach. Postoperative imaging is useful for objective assessment of repair tissue or degenerative changes of the ankle joint. Plain radiography, CT and MRI have been used in outcome studies, and different scoring systems are available. PMID:26716090

  1. Osteochondral Lesion of the Bilateral Femoral Heads in a Young Athletic Patient

    PubMed Central

    Lee, Jung Eun; Park, Ji Seon; Cho, Yoon Je; Yoon, So Hee; Park, So Young; Jin, Wook; Lee, Kyung Ryeol

    2014-01-01

    Osteochondral lesions of the femoral head are uncommon and few studies have reported their imaging findings. Since joints are at risk of early degeneration after osteochondral damage, timely recognition is important. Osteochondral lesions of femoral head may often be necessary to differentiate from avascular necrosis. Here, we report a case of osteochondral lesions on bilateral femoral heads. This lesion manifested as subchondral cysts in initial radiographs, which led to further evaluation by computed tomography arthrography and magnetic resonance imaging, which revealed overlying cartilage defects. PMID:25469091

  2. Review of the biomechanics and biotribology of osteochondral grafts used for surgical interventions in the knee

    PubMed Central

    Bowland, Philippa; Ingham, E; Jennings, Louise; Fisher, John

    2015-01-01

    A review of research undertaken to evaluate the biomechanical stability and biotribological behaviour of osteochondral grafts in the knee joint and a brief discussion of areas requiring further improvement in future studies are presented. The review takes into consideration osteochondral autografts, allografts, tissue engineered constructs and synthetic and biological scaffolds. PMID:26614801

  3. Osteochondral mosaicplasty along with osteochondroplasty of the femoral head in femoroacetabular impingement: a case report.

    PubMed

    Güngör, Harun R; K?ter, Esat; Ök, Nusret; Çatak, Adem

    2015-08-01

    Although femoroacetabular impingement (FAI) syndrome is included in the etiology of lesions involving the acetabular labrum and acetabular cartilage, it is one of many possible reasons behind osteochondral lesions in the femoral head. Herein, we present clinical findings and outcomes of two cases with osteochondral defects and cam type impingement of femoral head. Both cases underwent autologous osteochondral mosaicplasty along with femoral osteochondroplasty following controlled hip dislocation. Harris hip scores improved significantly postoperatively and magnetic resonance imaging showed an adequate graft union and formation of a healthy chondral surface at the final assessment. Autologous osteochondral mosaicplasty of parafoveal region defects and femoral neck osteochondroplasty combination may be an effective treatment method for young patients with FAI syndrome. In addition, we believe that cam type impingement may also have a role in the etiology of parafoveal osteochondral lesions. PMID:26514225

  4. Diagnosis of Knee Osteochondral Lesions With Ultrasound Imaging.

    PubMed

    Penttilä, Pekko; Liukkonen, Jukka; Joukainen, Antti; Virén, Tuomas; Jurvelin, Jukka S; Töyräs, Juha; Kröger, Heikki

    2015-10-01

    Evaluation of articular cartilage and subchondral bone is essential in the diagnosis of joint diseases and injuries. Interobserver and intraobserver reproducibilities of arthroscopic grading are only poor to moderate. Thus, for quantitative and objective evaluation of cartilage and subchondral bone, ultrasound arthroscopy (UA) has been introduced to clarify this dilemma. Assessment of the clinical feasibility of high-frequency ultrasonography (US) during 6 knee arthroscopies was conducted, and the surgical technique is presented. US imaging was conducted with a flexible 9-MHz US catheter inserted into the joint through conventional portals. US and arthroscopy videos were synchronously recorded, and US parameters for cartilage and subchondral bone characteristics were measured. Arthroscopy and US imaging were combined to perform cartilage grading. UA produced quantitative data on lesion size, as well as cartilage quality, and showed subchondral bone changes. Visualization of an osteochondritis dissecans lesion not detected by conventional arthroscopy and US-guided retrograde drilling were possible with UA. To conclude, UA proved to be clinically feasible and aided in the diagnosis when assessing knee osteochondral lesions. PMID:26697300

  5. Diagnosis of Knee Osteochondral Lesions With Ultrasound Imaging

    PubMed Central

    Penttilä, Pekko; Liukkonen, Jukka; Joukainen, Antti; Virén, Tuomas; Jurvelin, Jukka S.; Töyräs, Juha; Kröger, Heikki

    2015-01-01

    Evaluation of articular cartilage and subchondral bone is essential in the diagnosis of joint diseases and injuries. Interobserver and intraobserver reproducibilities of arthroscopic grading are only poor to moderate. Thus, for quantitative and objective evaluation of cartilage and subchondral bone, ultrasound arthroscopy (UA) has been introduced to clarify this dilemma. Assessment of the clinical feasibility of high-frequency ultrasonography (US) during 6 knee arthroscopies was conducted, and the surgical technique is presented. US imaging was conducted with a flexible 9-MHz US catheter inserted into the joint through conventional portals. US and arthroscopy videos were synchronously recorded, and US parameters for cartilage and subchondral bone characteristics were measured. Arthroscopy and US imaging were combined to perform cartilage grading. UA produced quantitative data on lesion size, as well as cartilage quality, and showed subchondral bone changes. Visualization of an osteochondritis dissecans lesion not detected by conventional arthroscopy and US-guided retrograde drilling were possible with UA. To conclude, UA proved to be clinically feasible and aided in the diagnosis when assessing knee osteochondral lesions. PMID:26697300

  6. Osteochondral tissue engineering: scaffolds, stem cells and applications

    PubMed Central

    Nooeaid, Patcharakamon; Salih, Vehid; Beier, Justus P; Boccaccini, Aldo R

    2012-01-01

    Osteochondral tissue engineering has shown an increasing development to provide suitable strategies for the regeneration of damaged cartilage and underlying subchondral bone tissue. For reasons of the limitation in the capacity of articular cartilage to self-repair, it is essential to develop approaches based on suitable scaffolds made of appropriate engineered biomaterials. The combination of biodegradable polymers and bioactive ceramics in a variety of composite structures is promising in this area, whereby the fabrication methods, associated cells and signalling factors determine the success of the strategies. The objective of this review is to present and discuss approaches being proposed in osteochondral tissue engineering, which are focused on the application of various materials forming bilayered composite scaffolds, including polymers and ceramics, discussing the variety of scaffold designs and fabrication methods being developed. Additionally, cell sources and biological protein incorporation methods are discussed, addressing their interaction with scaffolds and highlighting the potential for creating a new generation of bilayered composite scaffolds that can mimic the native interfacial tissue properties, and are able to adapt to the biological environment. PMID:22452848

  7. Elbow arthroscopy: capitellar osteochondritis dissecans and radiocapitellar plica.

    PubMed

    Ahmad, Christopher S; Vitale, Mark A; ElAttrache, Neil S

    2011-01-01

    The combination of excessive radiocapitellar compressive forces and the limited vascularity of the capitellum are responsible for the development of osteochondritis dissecans. Repetitive compressive forces are generated by throwing or racket swinging motions or from constant axial compressive loads on the elbow, which are common in athletes such as gymnasts. Symptoms include activity-associated pain and stiffness. Physical examination findings show tenderness over the radiocapitellar joint and, commonly, loss of extension. Plain radiographs may show flattening and sclerosis of the capitellum, lucencies, and possibly intra-articular loose bodies. MRI can detect bone edema early in the disease process and further delineate the extent of the injury. The management of osteochondritis dissecans lesions is primarily based on the demands of the patient, the size and location of the lesion, and the status and stability of the overlying cartilage. Possible treatments include transarticular drilling; removing detached fragments or loose bodies, followed by drilling; and mosaicplasty.?Radiocapitellar plica can cause chondromalacic changes on the radial head and capitellum, with symptoms including painful clicking and effusions. Arthroscopic plica resection is indicated when nonsurgical treatment fails. PMID:21553772

  8. Integrating biologically inspired nanomaterials and table-top stereolithography for 3D printed biomimetic osteochondral scaffolds

    NASA Astrophysics Data System (ADS)

    Castro, Nathan J.; O'Brien, Joseph; Zhang, Lijie Grace

    2015-08-01

    The osteochondral interface of an arthritic joint is notoriously difficult to regenerate due to its extremely poor regenerative capacity and complex stratified architecture. Native osteochondral tissue extracellular matrix is composed of numerous nanoscale organic and inorganic constituents. Although various tissue engineering strategies exist in addressing osteochondral defects, limitations persist with regards to tissue scaffolding which exhibit biomimetic cues at the nano to micro scale. In an effort to address this, the current work focused on 3D printing biomimetic nanocomposite scaffolds for improved osteochondral tissue regeneration. For this purpose, two biologically-inspired nanomaterials have been synthesized consisting of (1) osteoconductive nanocrystalline hydroxyapatite (nHA) (primary inorganic component of bone) and (2) core-shell poly(lactic-co-glycolic) acid (PLGA) nanospheres encapsulated with chondrogenic transforming growth-factor ?1 (TGF-?1) for sustained delivery. Then, a novel table-top stereolithography 3D printer and the nano-ink (i.e., nHA + nanosphere + hydrogel) were employed to fabricate a porous and highly interconnected osteochondral scaffold with hierarchical nano-to-micro structure and spatiotemporal bioactive factor gradients. Our results showed that human bone marrow-derived mesenchymal stem cell adhesion, proliferation, and osteochondral differentiation were greatly improved in the biomimetic graded 3D printed osteochondral construct in vitro. The current work served to illustrate the efficacy of the nano-ink and current 3D printing technology for efficient fabrication of a novel nanocomposite hydrogel scaffold. In addition, tissue-specific growth factors illustrated a synergistic effect leading to increased cell adhesion and directed stem cell differentiation.

  9. Integrating biologically inspired nanomaterials and table-top stereolithography for 3D printed biomimetic osteochondral scaffolds.

    PubMed

    Castro, Nathan J; O'Brien, Joseph; Zhang, Lijie Grace

    2015-09-01

    The osteochondral interface of an arthritic joint is notoriously difficult to regenerate due to its extremely poor regenerative capacity and complex stratified architecture. Native osteochondral tissue extracellular matrix is composed of numerous nanoscale organic and inorganic constituents. Although various tissue engineering strategies exist in addressing osteochondral defects, limitations persist with regards to tissue scaffolding which exhibit biomimetic cues at the nano to micro scale. In an effort to address this, the current work focused on 3D printing biomimetic nanocomposite scaffolds for improved osteochondral tissue regeneration. For this purpose, two biologically-inspired nanomaterials have been synthesized consisting of (1) osteoconductive nanocrystalline hydroxyapatite (nHA) (primary inorganic component of bone) and (2) core-shell poly(lactic-co-glycolic) acid (PLGA) nanospheres encapsulated with chondrogenic transforming growth-factor ?1 (TGF-?1) for sustained delivery. Then, a novel table-top stereolithography 3D printer and the nano-ink (i.e., nHA + nanosphere + hydrogel) were employed to fabricate a porous and highly interconnected osteochondral scaffold with hierarchical nano-to-micro structure and spatiotemporal bioactive factor gradients. Our results showed that human bone marrow-derived mesenchymal stem cell adhesion, proliferation, and osteochondral differentiation were greatly improved in the biomimetic graded 3D printed osteochondral construct in vitro. The current work served to illustrate the efficacy of the nano-ink and current 3D printing technology for efficient fabrication of a novel nanocomposite hydrogel scaffold. In addition, tissue-specific growth factors illustrated a synergistic effect leading to increased cell adhesion and directed stem cell differentiation. PMID:26234364

  10. Current strategies in multiphasic scaffold design for osteochondral tissue engineering: A review.

    PubMed

    Yousefi, Azizeh-Mitra; Hoque, Md Enamul; Prasad, Rangabhatala G S V; Uth, Nicholas

    2015-07-01

    The repair of osteochondral defects requires a tissue engineering approach that aims at mimicking the physiological properties and structure of two different tissues (cartilage and bone) using specifically designed scaffold-cell constructs. Biphasic and triphasic approaches utilize two or three different architectures, materials, or composites to produce a multilayered construct. This article gives an overview of some of the current strategies in multiphasic/gradient-based scaffold architectures and compositions for tissue engineering of osteochondral defects. In addition, the application of finite element analysis (FEA) in scaffold design and simulation of in vitro and in vivo cell growth outcomes has been briefly covered. FEA-based approaches can potentially be coupled with computer-assisted fabrication systems for controlled deposition and additive manufacturing of the simulated patterns. Finally, a summary of the existing challenges associated with the repair of osteochondral defects as well as some recommendations for future directions have been brought up in the concluding section of this article. PMID:25345589

  11. Acute Osteochondral Fractures in the Lower Extremities - Approach to Identification and Treatment

    PubMed Central

    Pedersen, M.E; DaCambra, M.P; Jibri, Z; Dhillon, S; Jen, H; Jomha, N.M

    2015-01-01

    Chondral and osteochondral fractures of the lower extremities are important injuries because they can cause pain and dysfunction and often lead to osteoarthritis. These injuries can be misdiagnosed initially which may impact on the healing potential and result in poor long-term outcome. This comprehensive review focuses on current pitfalls in diagnosing acute osteochondral lesions, potential investigative techniques to minimize diagnostic errors as well as surgical treatment options. Acute osteochondral fractures are frequently missed and can be identified more accurately with specific imaging techniques. A number of different methods can be used to fix these fractures but attention to early diagnosis is required to limit progression to osteoarthritis. These fractures are common with joint injuries and early diagnosis and treatment should lead to improved long term outcomes. PMID:26587063

  12. Hierarchical Structure of Articular Bone-Cartilage Interface and Its Potential Application for Osteochondral Tissue Engineering

    NASA Astrophysics Data System (ADS)

    Bian, Weiguo; Qin, Lian; Li, Dichen; Wang, Jin; Jin, Zhongmin

    2010-09-01

    The artificial biodegradable osteochondral construct is one of mostly promising lifetime substitute in the joint replacement. And the complex hierarchical structure of natural joint is important in developing the osteochondral construct. However, the architecture features of the interface between cartilage and bone, in particular those at the micro-and nano-structural level, remain poorly understood. This paper investigates these structural data of the cartilage-bone interface by micro computerized tomography (?CT) and Scanning Electron Microscope (SEM). The result of ?CT shows that important bone parameters and the density of articular cartilage are all related to the position in the hierarchical structure. The conjunctions of bone and cartilage were defined by SEM. All of the study results would be useful for the design of osteochondral construct further manufactured by nano-tech. A three-dimensional model with gradient porous structure is constructed in the environment of Pro/ENGINEERING software.

  13. Viral Inactivation of Human Osteochondral Grafts with Methylene Blue and Light

    PubMed Central

    Zhao, Zhixing; Call, Gazell M.; Gao, Jizong; Yao, Jian Q.

    2014-01-01

    Objective: Cartilage injury is one of the most common disorders of synovial joints. Fresh osteochondral allografts are becoming a standard treatment; however, they are supply constrained with a potential risk of disease transmission. There are no known virucidal processes available for osteochondral allografts and most methods presently available are detrimental to cartilage. Methylene blue light treatment has been shown to be successful in the literature for viral inactivation of fresh frozen plasma. The purpose of this study was to determine the capacity of methylene blue light treatment to inactivate a panel of clinically relevant viruses inoculated onto osteochondral allografts. Design: Osteochondral grafts recovered from human cadaveric knees were inoculated with one of the following viruses: bovine viral diarrhea virus (BVDV), hepatitis A virus (HAV), human immunodeficiency virus type 1 (HIV-1), porcine parvovirus (PPV), and pseudorabies virus (PrV). The samples were processed through a methylene blue light treatment, which consisted of an initial soak in nonilluminated circulating methylene blue at ambient temperature, followed by light exposure with circulating methylene blue at cool temperatures. The final titer was compared with the recovery control for the viral log reduction. Results: HIV-1, BVDV, and PrV were reduced to nondetectable levels while HAV and PPV were reduced by 3.1 and 5.6 logs, respectively. Conclusions: The methylene blue light treatment was effective in reducing (a) enveloped DNA and RNA viruses to nondetectable levels and (b) nonenveloped DNA and RNA viruses of inoculated human osteochondral grafts by 3.1 to 5.6 logs. This study demonstrates the first practical method for significantly reducing viral load in osteochondral implants. PMID:26069682

  14. Osteochondritis Dissecans Involving the Trochlear Groove Treated With Retrograde Drilling

    PubMed Central

    Kaji, Yoshio; Nakamura, Osamu; Yamaguchi, Konosuke; Yamamoto, Tetsuji

    2015-01-01

    Abstract Osteochondritis dissecans (OCD) occurs frequently in the humeral capitellum of the upper extremity, whereas OCD involving the trochlear groove (trochlear groove OCD) is rarely reported. A standard treatment for trochlear groove OCD has therefore not been determined, although several methods have been tried. The case of a 14-year-old male gymnast with bilateral trochlear groove OCD is presented. Retrograde drilling from the lateral condyle of the humerus was applied for the OCD lesion of the left elbow, since it was larger in size than that in the right elbow and was symptomatic. Conversely, since the right lesion was small and asymptomatic, it was managed conservatively. After treatment, consolidation of the OCD lesions was observed in both elbows. However, the time to healing was shorter in the left elbow treated surgically than in the right elbow managed conservatively. In conclusion, retrograde drilling is a very simple and minimally invasive treatment. This case suggests that retrograde drilling for trochlear groove OCD may be a useful procedure that may accelerate the healing process for OCD lesions. PMID:26356703

  15. The Augmentation of a Collagen/Glycosaminoglycan Biphasic Osteochondral Scaffold with Platelet-Rich Plasma and Concentrated Bone Marrow Aspirate for Osteochondral Defect Repair in Sheep

    PubMed Central

    Henson, Frances; Skelton, Carrie; Herrera, Emilio; Brooks, Roger; Fortier, Lisa A.; Rushton, Neil

    2012-01-01

    Objective: This study investigates the combination of platelet-rich plasma (PRP) or concentrated bone marrow aspirate (CBMA) with a biphasic collagen/glycosaminoglycan (GAG) osteochondral scaffold for the treatment of osteochondral defects in sheep. Design: Acute osteochondral defects were created in the medial femoral condyle (MFC) and the lateral trochlea sulcus (LTS) of 24 sheep (n = 6). Defects were left empty or filled with a 6 × 6-mm scaffold, either on its own or in combination with PRP or CBMA. Outcome measures at 6 months included mechanical testing, International Cartilage Repair Society (ICRS) repair score, modified O’Driscoll histology score, qualitative histology, and immunohistochemistry for type I, II, and VI collagen. Results: No differences in mechanical properties, ICRS repair score, or modified O’Driscoll score were detected between the 4 groups. However, qualitative assessments of the histological architecture, Safranin O content, and collagen immunohistochemistry indicated that in the PRP/scaffold groups, there was a more hyaline cartilage–like tissue repair. In addition, the addition of CBMA and PRP to the scaffold reduced cyst formation in the subchondral bone of healed lesions. Conclusion: There was more hyaline cartilage–like tissue formed in the PRP/scaffold group and less subchondral cystic lesion formation in the CBMA and PRP/scaffold groups, although there were no quantitative differences in the repair tissue formed. PMID:26069645

  16. Osteochondral defects of the upper extremity treated with particulated juvenile cartilage transfer.

    PubMed

    Dunn, John C; Kusnezov, Nicholas; Orr, Justin; Mitchell, Justin S

    2015-12-01

    We present the novel use of particulated juvenile cartilage transfer in the upper extremity. Our patient is an active duty solider with an osteochondral defect (OCD) of the capitellum that he sustained after an improvised explosive devise injury to his left elbow. PMID:26568723

  17. Biofabrication of osteochondral tissue equivalents by printing topologically defined, cell-laden hydrogel scaffolds.

    PubMed

    Fedorovich, Natalja E; Schuurman, Wouter; Wijnberg, Hans M; Prins, Henk-Jan; van Weeren, P René; Malda, Jos; Alblas, Jacqueline; Dhert, Wouter J A

    2012-01-01

    Osteochondral defects are prone to induce osteoarthritic degenerative changes. Many tissue-engineering approaches that aim to generate osteochondral implants suffer from poor tissue formation and compromised integration. This illustrates the need for further improvement of heterogeneous tissue constructs. Engineering of these structures is expected to profit from strategies addressing the complexity of tissue organization and the simultaneous use of multiple cell types. Moreover, this enables the investigation of the effects of three-dimensional (3D) organization and architecture on tissue function. In the present study, we characterize the use of a 3D fiber deposition (3DF) technique for the fabrication of cell-laden, heterogeneous hydrogel constructs for potential use as osteochondral grafts. Changing fiber spacing or angle of fiber deposition yielded scaffolds of varying porosity and elastic modulus. We encapsulated and printed fluorescently labeled human chondrocytes and osteogenic progenitors in alginate hydrogel yielding scaffolds of 1×2?cm with different parts for both cell types. Cell viability remained high throughout the printing process, and cells remained in their compartment of the printed scaffold for the whole culture period. Moreover, distinctive tissue formation was observed, both in vitro after 3 weeks and in vivo (6 weeks subcutaneously in immunodeficient mice), at different locations within one construct. These results demonstrate the possibility of manufacturing viable centimeter-scaled structured tissues by the 3DF technique, which could potentially be used for the repair of osteochondral defects. PMID:21854293

  18. Treatment of juvenile osteochondritis dissecans of the talus: current concepts review

    PubMed Central

    VANNINI, FRANCESCA; CAVALLO, MARCO; BALDASSARRI, MATTEO; CASTAGNINI, FRANCESCO; OLIVIERI, ALESSANDRA; FERRANTI, ENRICO; BUDA, ROBERTO; GIANNINI, SANDRO

    2014-01-01

    Juvenile osteochondritis dissecans of the talus (JODT) affects the subchondral bone primarily and, in a skeletally immature population, articular cartilage secondarily. It probably consists of aseptic bone necrosis whose spontaneous healing is impaired by microtraumas, resulting in an osteochondral injury and, in some cases, in osteoarthritis. In many cases the clinical presentation is asymptomatic. Mild chronic pain is frequent, sometimes accompanied by swelling, stiffness or locking. Few data are currently available on this topic and, moreover, most existing data were obtained from mixed groups and populations; it is therefore difficult to outline a scheme for the treatment of JODT. However, the most suitable treatment in the first stages of the disease is conservative. The presence of a loose body is an indication for surgical fixation, drilling or regenerative procedures, depending on the presence/extent of subchondral bone sclerosis and the surgeon’s experience. Drilling has been shown to promote the healing of lesions with minimal surgical trauma. Microfractures, since they induce fibrocartilage repair, are to be considered only for small injuries. Mosaicplasty and osteochondral autograft transplantation may cause donor site morbidity and are techniques little reported in JODT. Regenerative techniques and fresh allografts give good results in osteochondral lesions, but further studies are required to describe the results that can be obtained in JODT alone. PMID:25750908

  19. Treatment of juvenile osteochondritis dissecans of the talus: current concepts review.

    PubMed

    Vannini, Francesca; Cavallo, Marco; Baldassarri, Matteo; Castagnini, Francesco; Olivieri, Alessandra; Ferranti, Enrico; Buda, Roberto; Giannini, Sandro

    2014-01-01

    Juvenile osteochondritis dissecans of the talus (JODT) affects the subchondral bone primarily and, in a skeletally immature population, articular cartilage secondarily. It probably consists of aseptic bone necrosis whose spontaneous healing is impaired by microtraumas, resulting in an osteochondral injury and, in some cases, in osteoarthritis. In many cases the clinical presentation is asymptomatic. Mild chronic pain is frequent, sometimes accompanied by swelling, stiffness or locking. Few data are currently available on this topic and, moreover, most existing data were obtained from mixed groups and populations; it is therefore difficult to outline a scheme for the treatment of JODT. However, the most suitable treatment in the first stages of the disease is conservative. The presence of a loose body is an indication for surgical fixation, drilling or regenerative procedures, depending on the presence/extent of subchondral bone sclerosis and the surgeon's experience. Drilling has been shown to promote the healing of lesions with minimal surgical trauma. Microfractures, since they induce fibrocartilage repair, are to be considered only for small injuries. Mosaicplasty and osteochondral autograft transplantation may cause donor site morbidity and are techniques little reported in JODT. Regenerative techniques and fresh allografts give good results in osteochondral lesions, but further studies are required to describe the results that can be obtained in JODT alone. PMID:25750908

  20. Immunogenicity of unprocessed and photooxidized bovine and human osteochondral grafts in collagen-sensitive mice

    PubMed Central

    Kawalec-Carroll, Jill S; Hetherington, Vincent J; Dockery, Douglas S; Shive, Carey; Targoni, Oleg S; Lehmann, Paul V; Nadler, Daniel; Prins, Dustin

    2006-01-01

    Background Autologous and allogeneic osteochondral grafts have been used to repair damaged or diseased cartilage. There are drawbacks to both of these methods, however. Another possible source for osteochondral grafting is photooxidized xenograft scaffolds. The purpose of this study was to evaluate the adaptive immune response to unprocessed and photooxidized xenogeneic osteochondral grafts in a collagen-sensitive mouse model. Methods Unprocessed and photooxidized bovine and human osteochondral grafts were used. The grafts were implanted subcutaneously in collagen-sensitive DBA/1LacJ mice for four or twelve weeks. ELISPOT assays were conducted with spleen cells to evaluate the number of collagen-specific T cells that produce IL-2, IL-4, IL-5 or IFN-?. Serum was collected and ELISA assays were performed to determine the titers of collagen-specific and total IgG, IgG1, IgG2a, or IgM antibodies. Histology was conducted on the retrieved osteochondral grafts. Results Results indicated that, with respect to adaptive T cell immunity, the photooxidized bovine grafts, unprocessed human grafts and photooxidized human grafts did not induce a significant response to collagen. The unprocessed bovine grafts, however, were slightly more immunogenic, inducing a weak immune response. With respect to antibody production, the bovine grafts were less immunogenic than the human grafts. Bovine collagen-specific IgG antibodies were not induced by these grafts, but production of IgM after twelve weeks was observed with both the unprocessed and photooxidized bovine grafts. In contrast, photooxidized human osteochondral grafts induced IgG1 and IgG2a antibodies, while the unprocessed human grafts did not. Pre-existing human collagen-specific IgM antibodies were present in all mice, including sham-operated negative controls that did not receive an implant. Histological analysis revealed some degree of fibrous encapsulation and inflammatory infiltrations in both bovine and human implants, whether unprocessed or photooxidized. Conclusion Both bovine and human cartilage grafts showed weak, but clear immunogenicity in the DBA/1LacJ mice, indicating that immunogenic collagen was still contained in the grafts, even after cleaning and photooxidation. The process of photooxidation is still important in osteochondral grafting, since it stabilizes the surface of the cartilage by cross-linking the collagen fibers, and allows for immediate load bearing and joint resurfacing. PMID:16545115

  1. Development of Novel Three-Dimensional Printed Scaffolds for Osteochondral Regeneration

    PubMed Central

    Holmes, Benjamin; Zhu, Wei; Li, Jiaoyan; Lee, James D.

    2015-01-01

    As modern medicine advances, various methodologies are being explored and developed in order to treat severe osteochondral defects in joints. However, it is still very challenging to cure the osteochondral defects due to their poor inherent regenerative capacity, complex stratified architecture, and disparate biomechanical properties. The objective of this study is to create novel three-dimensional (3D) printed osteochondral scaffolds with both excellent interfacial mechanical properties and biocompatibility for facilitating human bone marrow mesenchymal stem cell (MSC) growth and chondrogenic differentiation. For this purpose, we designed and 3D printed a series of innovative bi-phasic 3D models that mimic the osteochondral region of articulate joints. Our mechanical testing results showed that our bi-phasic scaffolds with key structures have enhanced mechanical characteristics in compression (a maximum Young's modulus of 31?MPa) and shear (a maximum fracture strength of 5768?N/mm2) when compared with homogenous designs. These results are also correlated with numerical simulation. In order to improve their biocompatibility, the scaffolds' surfaces were further modified with acetylated collagen (one of the main components in osteochondral extracellular matrix). MSC proliferation results demonstrated that incorporation of a collagen, along with biomimetically designed micro-features, can greatly enhance MSC growth after 5 days in vitro. Two weeks' chondrogenic differentiation results showed that our novel scaffolds (dubbed “key” scaffolds), both with and without surface collagen modification, displayed enhanced chondrogenesis (e.g., 130%, 114%, and 236% increases in glycosaminoglycan, type II collagen deposition, and total protein content on collagen-modified key scaffolds when compared with homogeneous controls). PMID:25088966

  2. Two Patients with Osteochondral Injury of the Weight-Bearing Portion of the Lateral Femoral Condyle Associated with Lateral Dislocation of the Patella

    PubMed Central

    Inoue, Hiroaki; Atsumi, Satoru; Ichimaru, Shohei; Fujiwara, Hiroyoshi; Kubo, Toshikazu

    2014-01-01

    Complications of patellar dislocation include osteochondral injury of the lateral femoral condyle and patella. Most cases of osteochondral injury occur in the anterior region, which is the non-weight-bearing portion of the lateral femoral condyle. We describe two patients with osteochondral injury of the weight-bearing surface of the lateral femoral condyle associated with lateral dislocation of the patella. The patients were 18- and 11-year-old females. Osteochondral injury occurred on the weight-bearing surface distal to the lateral femoral condyle. The presence of a free osteochondral fragment and osteochondral injury of the lateral femoral condyle was confirmed on MRI and reconstruction CT scan. Treatment consisted of osteochondral fragment fixation or microfracture, as well as patellar stabilization. Osteochondral injury was present in the weight-bearing portion of the lateral femoral condyle in both patients, suggesting that the injury was caused by friction between the patella and lateral femoral condyle when the patella was dislocated or reduced at about 90° flexion of the knee joint. These findings indicate that patellar dislocation may occur and osteochondral injury may extend to the weight-bearing portion of the femur even in deep flexion, when the patella is stabilized on the bones of the femoral groove. PMID:25506015

  3. Stem Cell-Based Microphysiological Osteochondral System to Model Tissue Response to Interleukin-1?

    PubMed Central

    2015-01-01

    Osteoarthritis (OA) is a chronic degenerative disease of the articular joint that involves both bone and cartilage degenerative changes. An engineered osteochondral tissue within physiological conditions will be of significant utility in understanding the pathogenesis of OA and testing the efficacy of potential disease-modifying OA drugs (DMOADs). In this study, a multichamber bioreactor was fabricated and fitted into a microfluidic base. When the osteochondral construct is inserted, two chambers are formed on either side of the construct (top, chondral; bottom, osseous) that is supplied by different medium streams. These medium conduits are critical to create tissue-specific microenvironments in which chondral and osseous tissues will develop and mature. Human bone marrow stem cell (hBMSCs)-derived constructs were fabricated in situ and cultured within the bioreactor and induced to undergo spatially defined chondrogenic and osteogenic differentiation for 4 weeks in tissue-specific media. We observed tissue specific gene expression and matrix production as well as a basophilic interface suggesting a developing tidemark. Introduction of interleukin-1? (IL-1?) to either the chondral or osseous medium stream induced stronger degradative responses locally as well as in the opposing tissue type. For example, IL-1? treatment of the osseous compartment resulted in a strong catabolic response in the chondral layer as indicated by increased matrix metalloproteinase (MMP) expression and activity, and tissue-specific gene expression. This induction was greater than that seen with IL-1? application to the chondral component directly, indicative of active biochemical communication between the two tissue layers and supporting the osteochondral nature of OA. The microtissue culture system developed here offers novel capabilities for investigating the physiology of osteochondral tissue and pathogenic mechanisms of OA and serving as a high-throughput platform to test potential DMOADS. PMID:24830762

  4. Evaluation of novel in situ synthesized nano-hydroxyapatite/collagen/alginate hydrogels for osteochondral tissue engineering.

    PubMed

    Zheng, Li; Jiang, Xianfang; Chen, Xuening; Fan, Hongsong; Zhang, Xingdong

    2014-12-01

    Collagen hydrogel has been widely used for osteochondral repair, but its mechanical properties cannot meet the requirements of clinical application. Previous studies have shown that the addition of either polysaccharide or inorganic particles could reinforce the polymer matrix. However, their synergic effects on collagen-based hydrogel have seldom been studied, and the potential application of triple-phased composite gel in osteochondral regeneration has not been reported. In this study, nano-hydroxyapatite (nano-HA) reinforced collagen-alginate hydrogel (nHCA) was prepared by the in situ synthesis of nano-HA in collagen gel followed by the addition of alginate and Ca(2+). The properties of triple-phased nHCA hydrogel were studied and compared with pure collagen and biphasic gels, and the triple-phased composite of collagen-alginate-HA gels showed a superiority in not only mechanical but also biological features, as evidenced by the enhanced tensile and compressive modulus, higher cell viability, faster cell proliferation and upregulated hyaline cartilage markers. In addition, it was found that the synthesis process could also affect the properties of the triple-phased composite, compared to blend-mixing HCA. The in situ-synthesized nHCA hydrogel showed an enhanced tensile modulus, as well as enhanced biological features compared with HCA. Our study demonstrated that the nHCA composite hydrogel holds promise in osteochondral regeneration. The addition of alginate and nano-HA contribute to the increase in both mechanical and biological properties. This study may provide a valuable reference for the design of an appropriate composite scaffold for osteochondral tissue engineering. PMID:25358331

  5. Percutaneous CT-Guided Treatment of Osteochondritis Dissecans of the Sacroiliac Joint

    SciTech Connect

    Becce, Fabio; Mouhsine, Elyazid; Mosimann, Pascal John; Anaye, Anass; Letovanec, Igor; Theumann, Nicolas

    2012-08-15

    Osteochondritis dissecans (OCD) is a joint disorder that affects the articular cartilage and subchondral bone, most commonly at the knee. OCD of the sacroiliac joint is extremely rare. Management of OCD remains controversial, and surgery is often needed, especially when conservative treatment fails. We present a rare case of OCD involving the left sacroiliac joint successfully treated by percutaneous computed tomography-guided retrograde drilling and debridement.

  6. Traumatic Osteochondral Injury of the Femoral Head Treated by Mosaicplasty: A Report of Two Cases

    PubMed Central

    Shindle, Michael K.; Buly, Robert L.; Kelly, Bryan T.; Lorich, Dean G.

    2010-01-01

    The increased risk of symptomatic progression towards osteoarthritis after chondral damage has led to the development of multiple treatment options for cartilage repair. These procedures have evolved from arthroscopic lavage and debridement, to marrow stimulation techniques, and more recently, to osteochondral autograft and allograft transplants, and autogenous chondrocyte implantation. The success of mosaicplasty procedures in the knee has led to its application to other surfaces, including the talus, tibial plateau, patella, and humeral capitellum. In this report, we present two cases of a chondral defect to the femoral head after a traumatic hip dislocation, treated with an osteochondral autograft (OATS) from the ipsilateral knee, and the inferior femoral head, respectively, combined with a surgical dislocation of the hip. At greater than 1 year and greater than 5 years of follow-up, MRI studies have demonstrated good autograft incorporation with maintenance of articular surface conformity, and both patients clinically continue to have no pain and full active range of motion of their respective hips. In our opinion, treatment of osteochondral defects in the femoral head surface using a surgical dislocation combined with an OATS procedure is a promising approach, as full exposure of the femoral head can be obtained while preserving its vasculature, thus enabling adequate restoration of the articular cartilage surface. PMID:21886541

  7. A novel, visible light-induced, rapidly cross-linkable gelatin scaffold for osteochondral tissue engineering

    PubMed Central

    Mazaki, Tetsuro; Shiozaki, Yasuyuki; Yamane, Kentaro; Yoshida, Aki; Nakamura, Mariko; Yoshida, Yasuhiro; Zhou, Di; Kitajima, Takashi; Tanaka, Masato; Ito, Yoshihiro; Ozaki, Toshifumi; Matsukawa, Akihiro

    2014-01-01

    Osteochondral injuries remain difficult to repair. We developed a novel photo-cross-linkable furfurylamine-conjugated gelatin (gelatin-FA). Gelatin-FA was rapidly cross-linked by visible light with Rose Bengal, a light sensitizer, and was kept gelled for 3 weeks submerged in saline at 37°C. When bone marrow-derived stromal cells (BMSCs) were suspended in gelatin-FA with 0.05% Rose Bengal, approximately 87% of the cells were viable in the hydrogel at 24?h after photo-cross-linking, and the chondrogenic differentiation of BMSCs was maintained for up to 3 weeks. BMP4 fusion protein with a collagen binding domain (CBD) was retained in the hydrogels at higher levels than unmodified BMP4. Gelatin-FA was subsequently employed as a scaffold for BMSCs and CBD-BMP4 in a rabbit osteochondral defect model. In both cases, the defect was repaired with articular cartilage-like tissue and regenerated subchondral bone. This novel, photo-cross-linkable gelatin appears to be a promising scaffold for the treatment of osteochondral injury. PMID:24662725

  8. Knee salvage procedures: The indications, techniques and outcomes of large osteochondral allografts

    PubMed Central

    Chui, Karen; Jeys, Lee; Snow, Martyn

    2015-01-01

    The overall incidence of osteochondral defect in the general population is estimated to be 15 to 30 per 100000 people. These lesions can become symptomatic causing pain, swelling and decreased function of the knee, and may eventually progress to osteoarthritis. In the young and active population, partial or total knee arthroplasty (TKA) is rarely the treatment of choice due to risk of early failure. Osteochondral allograft transplantation has been demonstrated to be a safe and effective treatment of large osteochondral and chondral defects of the knee in appropriately selected patients. The treatment reduces pain, improves function and is a viable limb salvage procedure for patients, especially young and active patients for whom TKA is not recommended. Either large dowels generated with commercially available equipment or free hand shell allografts can be implanted in more posterior lesions. Current recommendations for fresh allografts stored at 4C advise implantation within 21-28 d of procurement for optimum chondrocyte viability, following screening and testing protocols. Higher rates of successful allograft transplantation are observed in younger patients, unipolar lesions, normal or corrected malalignment, and defects that are treated within 12 mo of symptom onset. Patients with bipolar lesions, uncorrectable malalignment, advanced osteoarthritis, and those over 40 tend to have less favourable outcomes. PMID:25893177

  9. Development and characterisation of a decellularised bovine osteochondral biomaterial for cartilage repair.

    PubMed

    Fermor, Hazel L; Russell, Serena L; Williams, Sophie; Fisher, John; Ingham, Eileen

    2015-05-01

    It is proposed that an acellular natural osteochondral scaffold will provide a successful repair material for the early intervention treatment of cartilage lesions, to prevent or slow the progression of cartilage deterioration to osteoarthritis. Here, we investigated the efficacy of methods for the decellularisation of bovine osteochondral plugs. The plugs were subject to four freeze/thaw cycles followed by two cycles of washes in hypotonic solution and low concentration (0.1% w/v) sodium dodecyl sulphate with protease inhibitors. Plugs were treated with nuclease (DNase and RNase) treatment followed by sterilization in peracetic acid. Full tissue decellularisation was achieved as confirmed by histological analysis and DNA quantification, however the resultant acellular matrix had reduced glycosaminoglycan content which led to an increased percent deformation of cartilage. Furthermore, the acellular scaffold was not reproducibly biocompatible. Additional terminal washes were included in the process to improve biocompatibility, however, this led to visible structural damage to the cartilage. This damage was found to be minimised by reducing the cut edge to cartilage area ratio through decellularisation of larger cuts of osteochondral tissue. PMID:25893393

  10. Juvenile Osteochondritis Dissecans in a 13-year-old male athlete: A case report

    PubMed Central

    D’Angelo, Kevin; Kim, Peter; Murnaghan, M. Lucas

    2014-01-01

    Objective: To present the clinical management of juvenile osteochondritis dissecans (OCD) of the knee and highlight the importance of a timely diagnosis to optimize the time needed for less invasive, non-operative therapy. Clinical Features: A 13-year-old provincial level male soccer player presenting with recurrent anterior knee pain despite ongoing manual therapy. Intervention and Outcome: A multidisciplinary, non-operative treatment approach was utilized to promote natural healing of the osteochondral lesion. The plan of management consisted of patient education, activity modification, manual therapy, passive modalities and rehabilitation, while being overseen by an orthopaedic surgeon. Conclusions: Considering the serious consequences of misdiagnosing osteochondritis dissecans, such as the potential for future joint instability and accelerated joint degeneration, a high degree of suspicion should be considered with young individuals presenting with nonspecific, recurrent knee pain. A narrative review of the literature is provided to allow practitioners to apply current best practices to appropriately manage juvenile OCD and become more cognizant of the common knee differential diagnoses in the young athletic population. PMID:25550663

  11. Technical Report: Correlation Between the Repair of Cartilage and Subchondral Bone in an Osteochondral Defect Using Bilayered, Biodegradable Hydrogel Composites.

    PubMed

    Lu, Steven; Lam, Johnny; Trachtenberg, Jordan E; Lee, Esther J; Seyednejad, Hajar; van den Beucken, Jeroen J J P; Tabata, Yasuhiko; Kasper, F Kurtis; Scott, David W; Wong, Mark E; Jansen, John A; Mikos, Antonios G

    2015-12-01

    The present work investigated correlations between cartilage and subchondral bone repair, facilitated by a growth factor-delivering scaffold, in a rabbit osteochondral defect model. Histological scoring indices and microcomputed tomography morphological parameters were used to evaluate cartilage and bone repair, respectively, at 6 and 12 weeks. Correlation analysis revealed significant associations between specific cartilage indices and subchondral bone parameters that varied with location in the defect (cortical vs. trabecular region), time point (6 vs. 12 weeks), and experimental group (insulin-like growth factor-1 only, bone morphogenetic protein-2 only, or both growth factors). In particular, significant correlations consistently existed between cartilage surface regularity and bone quantity parameters. Overall, correlation analysis between cartilage and bone repair provided a fuller understanding of osteochondral repair and can help drive informed studies for future osteochondral regeneration strategies. PMID:26177155

  12. Design and characterization of a tissue-engineered bilayer scaffold for osteochondral tissue repair.

    PubMed

    Giannoni, Paolo; Lazzarini, Erica; Ceseracciu, Luca; Barone, Alberto C; Quarto, Rodolfo; Scaglione, Silvia

    2015-10-01

    Treatment of full-thickness cartilage defects relies on osteochondral bilayer grafts, which mimic the microenvironment and structure of the two affected tissues: articular cartilage and subchondral bone. However, the integrity and stability of the grafts are hampered by the presence of a weak interphase, generated by the layering processes of scaffold manufacturing. We describe here the design and development of a bilayer monolithic osteochondral graft, avoiding delamination of the two distinct layers but preserving the cues for selective generation of cartilage and bone. A highly porous polycaprolactone-based graft was obtained by combining solvent casting/particulate leaching techniques. Pore structure and interconnections were designed to favour in vivo vascularization only at the bony layer. Hydroxyapatite granules were added as bioactive signals at the site of bone regeneration. Unconfined compressive tests displayed optimal elastic properties and low residual deformation of the graft after unloading (< 3%). The structural integrity of the graft was successfully validated by tension fracture tests, revealing high resistance to delamination, since fractures were never displayed at the interface of the layers (n?=?8). Ectopic implantation of grafts in nude mice, after seeding with bovine trabecular bone-derived mesenchymal stem cells and bovine articular chondrocytes, resulted in thick areas of mature bone surrounding ceramic granules within the bony layer, and a cartilaginous alcianophilic matrix in the chondral layer. Vascularization was mostly observed in the bony layer, with a statistically significant higher blood vessel density and mean area. Thus, the easily generated osteochondral scaffolds, since they are mechanically and biologically functional, are suitable for tissue-engineering applications for cartilage repair. Copyright © 2012 John Wiley & Sons, Ltd. PMID:23172816

  13. Osteochondral lesion of the talus in a recreational athlete: a case report

    PubMed Central

    deGraauw, Chris

    1999-01-01

    A 23-year-old recreational male athlete presented with intermittent pain of three weeks duration, localized to the left ankle. Pain was aggravated by walking, although his symptoms had not affected the patient’s jogging activity which was performed three times per week. Past history revealed an inversion sprain of the left ankle, sustained fifteen months previously. Examination showed mild swelling anterior to the ankle mortise joint while other tests including range of motion, strength and motion palpation of specific joints of the ankle were noted to be unremarkable. Radiographic findings revealed a defect in the medial aspect of the talus. An orthopaedic referral was made for further evaluation. Tomography revealed a Grade III osteochondral lesion of the talus. It was determined that follow-up views be taken in three months to demonstrate if the lesion was progressing or healing. Within the three month period, activity modifications and modalities for pain control were indicated. Surgery was considered a reasonable option should conservative measures fail. The present case illustrates an osteochondral lesion of the talus, a condition which has not previously been reported in the chiropractic literature. A review of the pertinent orthopaedic literature has indicated an average delay of three years in diagnosing the existence of this lesion. Although considered rare, the diagnostic frequency of the condition appears to be on the rise due to increased awareness and the use of bone and CT scans. The osteochondral lesion of the talus deserves particular consideration by practitioners working with athletes due to its higher incidence within this group. This diagnosis should be considered in patients presenting with chronic ankle pain particularly when a history of an inversion sprain exists. The purpose of this report is to increase awareness of this condition, and review diagnosis and management strategies. ImagesFigure 1Figure 2

  14. A review of arthroscopic classification systems for osteochondritis dissecans of the knee.

    PubMed

    Jacobs, John C; Archibald-Seiffer, Noah; Grimm, Nathan L; Carey, James L; Shea, Kevin G

    2015-01-01

    Multiple systems for classifying osteochondritis dissecans (OCD) of the knee have been reported. These existing classification systems have some similar characteristics, such as stable lesion/intact articular cartilage and presence of a loose body. However, variations are found in the number of stages and specific lesion characteristics assessed. Currently, no system has been universally accepted. A future classification system should be developed that reconciles the discrepancies among the current systems and provides a clear, consistent, and reliable method for classifying OCD lesions of the knee during arthroscopy. PMID:25435042

  15. Osteochondral repair by a novel interconnecting collagen-hydroxyapatite substitute: a large-animal study.

    PubMed

    Sosio, Corrado; Di Giancamillo, Alessia; Deponti, Daniela; Gervaso, Francesca; Scalera, Francesca; Melato, Marco; Campagnol, Marino; Boschetti, Federica; Nonis, Alessandro; Domeneghini, Cinzia; Sannino, Alessandro; Peretti, Giuseppe Michele

    2015-02-01

    A novel three-dimensional bicomponent substitute made of collagen type I and hydroxyapatite was tested for the repair of osteochondral lesions in a swine model. This scaffold was assembled by a newly developed method that guarantees the strict integration between the organic and the inorganic parts, mimicking the biological tissue between the chondral and the osseous phase. Thirty-six osteochondral lesions were created in the trochlea of six pigs; in each pig, two lesions were treated with scaffolds seeded with autologous chondrocytes (cell+group), two lesions were treated with unseeded scaffolds (cell- group), and the two remaining lesions were left untreated (untreated group). After 3 months, the animals were sacrificed and the newly formed tissue was analyzed to evaluate the degree of maturation. The International Cartilage Repair Society (ICRS) macroscopic assessment showed significantly higher scores in the cell- and untreated groups when compared with the cell+ group. Histological evaluation showed the presence of repaired tissue, with fibroblast-like and hyaline-like areas in all groups; however, with respect to the other groups, the cell- group showed significantly higher values in the ICRS II histological scores for "cell morphology" and for the "surface/superficial assessment." While the scaffold seeded with autologous chondrocytes promoted the formation of a reparative tissue with high cellularity but low glycosaminoglycans (GAG) production, on the contrary, the reparative tissue observed with the unseeded scaffold presented lower cellularity but higher and uniform GAG distribution. Finally, in the lesions treated with scaffolds, the immunohistochemical analysis showed the presence of collagen type II in the peripheral part of the defect, indicating tissue maturation due to the migration of local cells from the surroundings. This study showed that the novel osteochondral scaffold was easy to handle for surgical implantation and was stable within the site of lesion; at the end of the experimental time, all implants were well integrated with the surrounding tissue and no signs of synovitis were observed. The quality of the reparative tissue seemed to be superior for the lesions treated with the unseeded scaffolds, indicating the promising potential of this novel biomaterial for use in a one-stage procedure for osteochondral repair. PMID:25316498

  16. Advancements in Orthopedic Intervention: Retrograde Drilling and Bone Grafting of Osteochondral Lesions of the Knee Using Magnetic Resonance Imaging Guidance

    SciTech Connect

    Seebauer, Christian J.; Bail, Hermann J.; Rump, Jens C. Walter, Thula Teichgraeber, Ulf K. M.

    2010-12-15

    Computer-assisted surgery is currently a novel challenge for surgeons and interventional radiologists. Magnetic resonance imaging (MRI)-guided procedures are still evolving. In this experimental study, we describe and assess an innovative passive-navigation method for MRI-guided treatment of osteochondritis dissecans of the knee. A navigation principle using a passive-navigation device was evaluated in six cadaveric knee joint specimens for potential applicability in retrograde drilling and bone grafting of osteochondral lesions using MRI guidance. Feasibility and accuracy were evaluated in an open MRI scanner (1.0 T Philips Panorama HFO MRI System). Interactive MRI navigation allowed precise drilling and bone grafting of osteochondral lesions of the knee. All lesions were hit with an accuracy of 1.86 mm in the coronal plane and 1.4 mm the sagittal plane. Targeting of all lesions was possible with a single drilling. MRI allowed excellent assessment of correct positioning of the cancellous bone cylinder during bone grafting. The navigation device and anatomic structures could be clearly identified and distinguished throughout the entire drilling procedure. MRI-assisted navigation method using a passive navigation device is feasible for the treatment of osteochondral lesions of the knee under MRI guidance and allows precise and safe drilling without exposure to ionizing radiation. This method may be a viable alternative to other navigation principles, especially for pediatric and adolescent patients. This MRI-navigated method is also potentially applicable in many other MRI-guided interventions.

  17. Wnt/?-catenin signaling of cartilage canal and osteochondral junction chondrocytes and full thickness cartilage in early equine osteochondrosis.

    PubMed

    Kinsley, Marc A; Semevolos, Stacy A; Duesterdieck-Zellmer, Katja F

    2015-10-01

    The objective of this study was to elucidate gene and protein expression of Wnt signaling molecules in chondrocytes of foals having early osteochondrosis (OC) versus normal controls. The hypothesis was that increased expression of components of Wnt signaling pathway in osteochondral junction (OCJ) and cartilage canal (CC) chondrocytes would be found in early OC when compared to controls. Paraffin-embedded osteochondral samples (7 OC, 8 normal) and cDNA from whole cartilage (7 OC, 10 normal) and chondrocytes surrounding cartilage canals and osteochondral junctions captured with laser capture microdissection (4 OC, 6 normal) were obtained from femoropatellar joints of 17 immature horses. Equine-specific Wnt signaling molecule mRNA expression levels were evaluated by two-step real-time qPCR. Spatial tissue protein expression of ?-catenin, Wnt-11, Wnt-4, and Dkk-1 was determined by immunohistochemistry. There was significantly decreased Wnt-11 and increased ?-catenin, Wnt-5b, Dkk-1, Lrp6, Wif-1, Axin1, and SC-PEP gene expression in early OC cartilage canal chondrocytes compared to controls. There was also significantly increased ?-catenin gene expression in early OC osteochondral junction chondrocytes compared to controls. Based on this study, abundant gene expression differences in OC chondrocytes surrounding cartilage canals suggest pathways associated with catabolism and inhibition of chondrocyte maturation are targeted in early OC pathogenesis. PMID:25676127

  18. The effect of interface microstructure on interfacial shear strength for osteochondral scaffolds based on biomimetic design and 3D printing.

    PubMed

    Zhang, Weijie; Lian, Qin; Li, Dichen; Wang, Kunzheng; Hao, Dingjun; Bian, Weiguo; Jin, Zhongmin

    2015-01-01

    Interface integration between chondral phase and osseous phase is crucial in engineered osteochondral scaffolds. However, the integration was poorly understood and commonly failed to meet the need of osteochondral scaffolds. In this paper, a biphasic polyethylene glycol (PEG)/?-tricalcium phosphate (?-TCP) scaffold with enhanced interfacial integration was developed. The chondral phase was a PEG hydrogel. The osseous phase was a ?-TCP ceramic scaffold. The PEG hydrogel was directly cured on the ceramic interface layer by layer to fabricate osteochondral scaffolds by 3D printing technology. Meanwhile, a series of interface structure were designed with different interface pore area percentages (0/10/20/30/40/50/60%), and interfacial shear test was applied for interface structure optimization (n=6 samples/group). The interfacial shear strength of 30% pore area group was nearly three folds improved compared with that of 0% pore area percentage group, and more than fifty folds improved compared with that of traditional integration (5.91±0.59 kPa). In conclusion, the biomimetic PEG/?-TCP scaffolds with interface structure enhanced integration show promising potential application for osteochondral tissue engineering. PMID:25491954

  19. Stem cell- and scaffold-based tissue engineering approaches to osteochondral regenerative medicine

    PubMed Central

    Sundelacruz, Sarah; Kaplan, David L.

    2009-01-01

    In osteochondral tissue engineering, cell recruitment, proliferation, differentiation, and patterning are critical for forming biologically and structurally viable constructs for repair of damaged or diseased tissue. However, since constructs prepared ex vivo lack the multitude of cues present in the in vivo microenvironment, cells often need to be supplied with external biological and physical stimuli to coax them towards targeted tissue functions. To determine which stimuli to present to cells, bioengineering strategies can benefit significantly from endogenous examples of skeletogenesis. As an example of developmental skeletogenesis, the developing limb bud serves as an excellent model system in which to study how an osteochondral structures form from undifferentiated precursor cells. Alongside skeletal formation during embryogenesis, bone also possesses innate regenerative capacity, displaying remarkable ability to heal after damage. Bone fracture healing shares many features with bone development, driving the hypothesis that the regenerative process generally recapitulates development. Similarities and differences between the two modes of bone formation may offer insight into the special requirements for healing damaged or diseased bone. Thus, endogenous fracture healing, as an example of regenerative skeletogenesis, may also inform bioengineering strategies. In this review, we summarize the key cellular events involving stem and progenitor cells in developmental and regenerative skeletogenesis, and discuss in parallel the corresponding cell- and scaffold-based strategies that tissue engineers employ to recapitulate these events in vitro. PMID:19508851

  20. Repair of articular cartilage in rabbit osteochondral defects promoted by extracorporeal shock wave therapy

    NASA Astrophysics Data System (ADS)

    Chu, C.-H.; Yen, Y.-S.; Chen, P.-L.; Wen, C.-Y.

    2015-03-01

    This study investigated the stimulative effect of extracorporeal shock wave therapy (ESWT) on the articular cartilage regeneration in the rabbit osteochondral defect model for the first time. An osteochondral defect, 3 mm in diameter and 3 mm in depth, was drilled in the patellar groove at the distal end of each femur in 24 mature New Zealand rabbits. The right patellar defects received 500 impulses of shock waves of (at 14 kV) at 1 week after surgery and were designated as the experimental samples; the left patellar defects served as control. At 4, 8, and 12 weeks after ESWT, cartilage repair was evaluated macroscopically and histologically using a semiquantitative grading scale. The total scores of the macroscopic evaluation at 4, 8, and 12 weeks in the experimental group were superior to those in the control group (statistical significance level ). As to the total scores of the histologic evaluation, the experimental group showed a tendency toward a better recovery than the control group at 4 weeks (). At 8 and 12 weeks the differences between the experimental and control groups became mild and had no significance on statistical analysis. These findings suggested that regeneration of articular cartilage defects might be promoted by ESWT, especially at the early stage. The easy and safe ESWT is potentially viable for clinical application.

  1. Growth Factor Gradients via Microsphere Delivery in Biopolymer Scaffolds for Osteochondral Tissue Engineering

    PubMed Central

    Wang, Xiaoqin; Wenk, Esther; Zhang, Xiaohui; Meinel, Lorenz; Vunjak-Novakovic, Gordana; Kaplan, David L.

    2009-01-01

    Temporally and spatially controlled delivery of growth factors in polymeric scaffolds is crucial for engineering composite tissue structures, such as osteochondral constructs. In the present study, microsphere-mediated growth factor delivery in polymer scaffolds and its impact on osteochondral differentiation of human bone marrow-derived mesenchymal stem cells (hMSCs) was evaluated. Two growth factors, bone morphogenetic protein 2 (rhBMP-2) and insulin-like growth factor I (rhIGF-I), were incorporated as a single concentration gradient or reverse gradient combining two factors in the scaffolds. To assess the gradient making system and the delivery efficiency of polylactic-co-glycolic acid (PLGA) and silk fibroin microspheres, initially an alginate gel was fabricated into a cylinder shape with microspheres incorporated as gradients. Compared to PLGA microspheres, silk microspheres were more efficient in delivering rhBMP-2, probably due to sustained release of the growth factor, while less efficient in delivering rhIGF-I, likely due to loading efficiency. The growth factor gradients formed were shallow, inducing non-gradient trends in hMSC osteochondral differentiation. Aqueous-derived silk porous scaffolds were used to incorporate silk microspheres using the same gradient process. Both growth factors formed deep and linear concentration gradients in the scaffold, as shown by enzyme-linked immunosorbent assay (ELISA). After seeding with hMSCs and culturing for 5 weeks in a medium containing osteogenic and chondrogenic components, hMSCs exhibited osteogenic and chondrogenic differentiation along the concentration gradients of rhBMP-2 in the single gradient of rhBMP-2 and reverse gradient of rhBMP-2/rhIGF-I, but not the rhIGF-I gradient system, confirming that silk microspheres were more efficient in delivering rhBMP-2 than rhIGF-I for hMSCs osteochondrogenesis. This novel silk microsphere/scaffold system offers a new option for the delivery of multiple growth factors with spatial control in a 3D culture environment for both understanding natural tissue growth process and in vitro engineering complex tissue constructs. PMID:19071168

  2. Utility of computed tomography arthrograms in evaluating osteochondral allograft transplants of the distal femur.

    PubMed

    Cook, Cpt Jay B; Shaha, Cpt James S; Rowles, Cdr Douglas R; Tokish, Col John M; Shaha, Steve H; Bottoni, Craig R

    2015-01-01

    Postsurgical evaluation of osteochondral allograft transplant surgery (OATS) of the distal femur most commonly utilizes radiographs or magnetic resonance imaging. This article proposes the utilization of computed tomography (CT) arthrography as an additional option, which allows clear assessment of articular congruity and osseous integration. A retrospective review was performed of 18 patients who underwent an OATS for distal femoral chondral lesions and obtained CT arthrograms postoperatively. CT arthrograms were evaluated for osseous integration and articular congruity. The average age and follow-up were 30.9 years and 4.3 years, respectively. Only 60% of patients were able to remain in the military postoperatively. The articular cartilage was smooth in eight (44.4%); complete bony integration was noted in eight (44.4%) patients. Neither articular congruity nor bony integration was associated with duty status at final follow-up. Although it allows excellent evaluation, similar to other modalities, CT arthrogram does not appear predictive of functional outcome. PMID:25988692

  3. Bioglass®/chitosan-polycaprolactone bilayered composite scaffolds intended for osteochondral tissue engineering.

    PubMed

    Yao, Qingqing; Nooeaid, Patcharakamon; Detsch, Rainer; Roether, Judith A; Dong, Yanming; Goudouri, Ourania-Menti; Schubert, Dirk W; Boccaccini, Aldo R

    2014-12-01

    Polymer-coated 45S5 Bioglass(®) (BG)/chitosan-polycaprolactone (BG/CS-PCL) bilayered composite scaffolds were prepared via foam replication and freeze-drying techniques for application in osteochondral tissue engineering. The CS-PCL coated and uncoated BG scaffolds were characterized by X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM). The mechanical properties of the coated scaffolds were significantly improved in comparison to uncoated scaffolds. The bioactivity and biodegradation behavior of scaffolds were studied in simulated body fluid (SBF) for up to 28 days. The interface between the BG scaffold and the polymer coating layer was observed by SEM and a suitable interpenetration of the polymer into the scaffold struts was found. The effects of coated and uncoated BG scaffolds on MG-63 osteoblast-like cells were evaluated by cell viability, adhesion and proliferation. PMID:24677705

  4. Hemi resurfacing of the humeral head for an osteochondral lesion affecting the entire head surface.

    PubMed

    Howard, Anthony; Smith, Matthew; Hughes, Peter; Bale, Stephen

    2009-08-01

    An osteochondral lesion of the entire articular surface of the humeral head has not previously been reported. We report the case of a 73-year-old woman with a huge osteochrondal lesion which affected virtually the whole articular surface of the humeral head, caused by an unusal mechanism of injury. Clinical examination revealed a stiff, weak, painful shoulder. Radiographs were unremarkable and an ultrasound scan suggested a supraspinatus tear with retraction. At arthroscopy the lesion was identified but the lesion was to large for arthroscopic removal. A humeral head hemi-resurfacing as a treatment for this lesion produced excellent results, the patient returned to her pre-injury level of function with no pain. PMID:19774825

  5. Use of fresh osteochondral glenoid allograft to treat posteroinferior bone loss in chronic posterior shoulder instability.

    PubMed

    Petrera, Massimo; Veillette, Christian J; Taylor, Drew W; Park, Sam S; Theodoropoulos, John S

    2013-02-01

    We report our experience with the use of fresh glenoid osteochondral allograft in the treatment of a chronic posttraumatic posterior subluxation of the shoulder associated with glenoid bone loss in a 54-year-old recreational football player. Based on the pathoanatomy of the lesion and availability of a bone bank providing fresh allograft, we opted for an open anatomic reconstruction using a fresh glenoid allograft. A posterior approach was used; the prepared allograft was placed in the appropriate anatomic position and fixed with 2 small fragment screws with washers. At 2-year follow-up, the clinical outcome is excellent. This procedure may represent an effective option for the treatment of chronic posterior shoulder instability due to glenoid bone loss. However, the long-term efficacy and the progression of glenohumeral osteoarthritis need to be evaluated. PMID:23431551

  6. The contribution of bone and cartilage to the near-infrared spectrum of osteochondral tissue

    PubMed Central

    McGoverin, Cushla M.; Lewis, Karl; Yang, Xu; Bostrom, Mathias P. G.; Pleshko, Nancy

    2014-01-01

    Near-infrared (NIR) spectroscopy has been utilized to assess hyaline cartilage quality in human and animal osteochondral tissues. However, due to the lack of NIR signal from bone phosphate, and the relatively deep penetration depth of the radiation, the separate contributions of cartilage and bone to the spectral signatures have not been well defined. The objectives of the current study were 1) to improve the understanding of the contributions of bone and cartilage to NIR spectra acquired from osteochondral tissue, and 2) to assess the ability of this non-destructive method to predict cartilage thickness and modified Mankin grade of human tibial plateau articular cartilage. NIR spectra were acquired from samples of bovine bone and cartilage with varying thicknesses, and from twenty-two tibial plateaus harvested from patients undergoing knee replacement surgery. Spectra were recorded from regions of the tibial plateaus with varying degrees of degradation, and the cartilage thickness and modified Mankin grade of these regions were assessed histologically. Spectra from bone and cartilage samples of known thicknesses were investigated to identify spectral regions that were distinct for these two tissues. Univariate and multivariate linear regression methods were used to correlate modified Mankin grade and cartilage thickness with NIR spectral changes. The ratio of the NIR absorbances associated with water at 5270 and 7085 cm?1 were the best differentiator of cartilage and bone spectra. NIR prediction models for thickness and Mankin grade calculated using partial least squares regression were more accurate than univariate-based prediction models, with root mean square errors of cross validation of 0.42 mm (thickness) and 1.3 (modified Mankin grade), respectively. We conclude that NIR spectroscopy may be used to simultaneously assess articular cartilage thickness and modified Mankin grade, based in part on differences in spectral contributions from bone and cartilage. PMID:25197817

  7. Repair of articular osteochondral defects of the knee joint using a composite lamellar scaffold

    PubMed Central

    Lv, Y. M.; Yu, Q. S.

    2015-01-01

    Objectives The major problem with repair of an articular cartilage injury is the extensive difference in the structure and function of regenerated, compared with normal cartilage. Our work investigates the feasibility of repairing articular osteochondral defects in the canine knee joint using a composite lamellar scaffold of nano-ß-tricalcium phosphate (ß-TCP)/collagen (col) I and II with bone marrow stromal stem cells (BMSCs) and assesses its biological compatibility. Methods The bone–cartilage scaffold was prepared as a laminated composite, using hydroxyapatite nanoparticles (nano-HAP)/collagen I/copolymer of polylactic acid–hydroxyacetic acid as the bony scaffold, and sodium hyaluronate/poly(lactic-co-glycolic acid) as the cartilaginous scaffold. Ten-to 12-month-old hybrid canines were randomly divided into an experimental group and a control group. BMSCs were obtained from the iliac crest of each animal, and only those of the third generation were used in experiments. An articular osteochondral defect was created in the right knee of dogs in both groups. Those in the experimental group were treated by implanting the composites consisting of the lamellar scaffold of ß-TCP/col I/col II/BMSCs. Those in the control group were left untreated. Results After 12 weeks of implantation, defects in the experimental group were filled with white semi-translucent tissue, protruding slightly over the peripheral cartilage surface. After 24 weeks, the defect space in the experimental group was filled with new cartilage tissues, finely integrated into surrounding normal cartilage. The lamellar scaffold of ß-TCP/col I/col II was gradually degraded and absorbed, while new cartilage tissue formed. In the control group, the defects were not repaired. Conclusion This method can be used as a suitable scaffold material for the tissue-engineered repair of articular cartilage defects. Cite this article: Bone Joint Res 2015;4:56–64 PMID:25837672

  8. Immunologic testing of xeno-derived osteochondral grafts using peripheral blood mononuclear cells from healthy human donors

    PubMed Central

    Hetherington, Vincent J; Kawalec, Jill S; Dockery, Douglas S; Targoni, Oleg S; Lehmann, Paul V; Nadler, Daniel

    2005-01-01

    Background One means of treating osteoarthritis is with autologous or allogeneic osteochondral grafts. The purpose of this study was to evaluate the innate immunological response in humans toward xeno-derived osteochondral grafts that have been partially or entirely treated by the photooxidation process. Methods The antigens tested included bovine, porcine, ovine and equine osteochondral samples that have been treated in successive steps of photooxidation. ELISPOT assays were used to evaluate the production of IL-1, IL-4, IL-6, IL-10, IL-12 and TNF-? by human monocytes in response to the antigens. Results Results indicated vigorous production of IL-1, IL-6, IL-10 and TNF-? in response to untreated bovine, porcine and equine specimens. This indicates that these samples are perceived as foreign, or stimulatory, by the human monocytes. There was no induction of IL-4 or IL-12, which is required for Th2 and Th1 immunity, respectively. In contrast, the processed bovine, porcine and equine samples did not induce significant activation of cells of the innate immune system. This occurred after the first step in processing (after cleaning in increasing strengths of ethanol). This suggests that the processing steps dramatically, if not completely, negated the immunostimulatory properties of the test sample. The results for the ovine samples indicate a reverse response. Conclusion The findings of the study suggest that photooxidized bovine, porcine or equine samples have the potential to be used as an osteochondral graft. Although the first step in processing reduced the immunological response, photooxidation is still necessary to retain the structure and mechanical integrity of the cartilage, which would allow for immediate joint resurfacing. PMID:15987525

  9. Arthroscopic Treatment of Chondral and Osteochondral Defects in the Ankle Using the Autologous Matrix-Induced Chondrogenesis Technique

    PubMed Central

    Piontek, Tomasz; B?kowski, Pawe?; Ciemniewska-Gorzela, Kinga; Naczk, Jakub

    2015-01-01

    One of the greatest challenges nowadays facing orthopaedic surgeons around the world is the problem of articular cartilage defects and their treatment. The autologous matrix-induced chondrogenesis technique is based on 2 elements—drilling into bones and matrix application. The purpose of this article is to present the surgical technique of arthroscopic treatment of chondral or osteochondral defects in the ankle using the autologous matrix-induced chondrogenesis technique. PMID:26697305

  10. The combined effects of continuous passive motion treatment and acellular PLGA implants on osteochondral regeneration in the rabbit.

    PubMed

    Chang, Nai-Jen; Lin, Chih-Chan; Li, Chien-Feng; Wang, Dong-An; Issariyaku, Nontapot; Yeh, Ming-Long

    2012-04-01

    We investigated the active role of clinical rehabilitation in osteochondral regeneration using continuous passive motion (CPM) treatment together with acellular PLGA implants. CPM treatment was performed and compared with immobilization (Imm) treatment and intermittent active motion (IAM) treatment upon full-thickness osteochondral defects either with or without an PLGA implant in the PI (PLGA-implanted) and ED (empty defect) models. The PI and ED tests were performed in 38 rabbits for 4 and 12 weeks. At the end of testing, the PI-CPM group had the best regeneration with nearly normal articular surfaces and no joint contracture or inflammatory reaction. In contrast, degenerated joints, abrasion cartilage surfaces and synovitis were observed in the Imm and IAM groups. The achieved bone volume/tissue volume (BV/TV) ratio, which was measured using micro-CT, was significantly higher in the CPM group compared with the Imm and IAM groups; in particular, the performance of the PI-CPM group exceeds that of the ED-CPM group. The thickness of the trabecular (subchondral) bone was visibly increased in all of the groups from 4 through 12 weeks of testing. However, a histological analysis revealed differences in cartilage regeneration. At week 4, compared with the ED samples, all of the PI groups exhibited better collagen alignment and higher GAG content in the core of their repaired tissues, particularly in the PI-CPM group. At week 12, sound osteochondral repair and hyaline cartilaginous regeneration was observed in the PI-CPM group, and this was marked by type II collagen expression, osteocyte maturation, and trabecular boney deposition. In contrast, the PI-Imm and PI-IAM groups exhibited fibrocartilaginous tissues that had modest GAG content. In summary, this study demonstrates that early CPM treatment together with acellular PLGA implantation has significant positive effects on osteochondral regeneration in rabbit knee joint models. PMID:22264523

  11. Osteochondritis dissecans of the lateral femoral condyle in a patient affected by osteogenesis imperfecta: a case report.

    PubMed

    Persiani, Pietro; Di Domenica, Marica; Martini, Lorena; Ranaldi, Filippo M; Zambrano, Anna; Celli, Mauro; Villani, Ciro

    2015-11-01

    Osteochondritis dissecans is a very uncommon phenomenon in osteogenesis imperfecta (OI). A 14-year-old boy, affected by OI and followed in our Center for Congenital Osteodystrophies, had a knee trauma and MRI indicated a hollowed area of 2.5×1.5?cm in the lateral femoral condyle, which was classified as grade III. The patient underwent surgery, performed as a one-step surgical treatment: the osteochondral fragment was removed, curettage of lesion's bottom was performed, and a biphasic scaffold was used to fill the defect, implanted with a press-fit technique. MRI at 12 and 24 months after surgery showed scaffold integration. At the final follow-up, the patient did not feel any pain or articular limitations. It is difficult to provide a guideline on osteochondritis dissecans in patients affected by OI because of the lack of literature reports on this rare disorder in a rare disease. According to our experience, in these patients, osteosynthesis of the bone fragment and the use of autograft are not recommended because of the patient's bone weakness and osteoporosis. Moreover, compared with two-step surgery, one-step surgery is preferred to reduce the risk related to anesthesia, often observed to be higher in these patients. PMID:25919806

  12. Comparative study of depth-dependent characteristics of equine and human osteochondral tissue from the medial and lateral femoral condyles.

    PubMed

    Malda, J; Benders, K E M; Klein, T J; de Grauw, J C; Kik, M J L; Hutmacher, D W; Saris, D B F; van Weeren, P R; Dhert, W J A

    2012-10-01

    Articular cartilage defects are common after joint injuries. When left untreated, the biomechanical protective function of cartilage is gradually lost, making the joint more susceptible to further damage, causing progressive loss of joint function and eventually osteoarthritis (OA). In the process of translating promising tissue-engineering cartilage repair approaches from bench to bedside, pre-clinical animal models including mice, rabbits, goats, and horses, are widely used. The equine species is becoming an increasingly popular model for the in vivo evaluation of regenerative orthopaedic approaches. As there is also an increasing body of evidence suggesting that successful lasting tissue reconstruction requires an implant that mimics natural tissue organization, it is imperative that depth-dependent characteristics of equine osteochondral tissue are known, to assess to what extent they resemble those in humans. Therefore, osteochondral cores (4-8 mm) were obtained from the medial and lateral femoral condyles of equine and human donors. Cores were processed for histology and for biochemical quantification of DNA, glycosaminoglycan (GAG) and collagen content. Equine and human osteochondral tissues possess similar geometrical (thickness) and organizational (GAG, collagen and DNA distribution with depth) features. These comparable trends further underscore the validity of the equine model for the evaluation of regenerative approaches for articular cartilage. PMID:22781206

  13. Development of a Large Animal Model of Osteochondritis Dissecans of the Knee

    PubMed Central

    Pfeifer, Christian G.; Kinsella, Stuart D.; Milby, Andrew H.; Fisher, Matthew B.; Belkin, Nicole S.; Mauck, Robert L.; Carey, James L.

    2015-01-01

    Background: Treatment of osteochondritis dissecans (OCD) of the knee is challenging, and evidence for stage-dependent treatment options is lacking. Basic science approaches utilizing animal models have provided insight into the etiology of OCD but have yet to produce a reliable and reproducible large animal model of the disease on which to test new surgical strategies. Purpose/Hypotheses: The purpose of this study was to develop an animal model featuring an OCD-like lesion in terms of size, location, and International Cartilage Repair Society (ICRS) grading. The hypothesis was that surgical creation of an osteochondral defect followed by placement of a barrier between parent bone and progeny fragment would generate a reproducible OCD-like lesion. Study Design: Controlled laboratory study. Methods: Bilateral osteochondral lesions were created in the medial femoral condyles of 9 Yucatan minipigs. After lesion creation, a biodegradable membrane was interposed between the progeny and parent bone. Five different treatment groups were evaluated at 2 weeks: a control with no membrane (ctrl group; n = 4), a slowly degrading nanofibrous poly(?-caprolactone) membrane (PCL group; n = 4), a fenestrated PCL membrane with 1.5-mm holes covering 25% of surface area (fenPCL group; n = 4), a collagen membrane (Bio-Gide) (CM group; n = 3), and a fenestrated CM (fenCM group; n = 3). Five unperturbed lateral condyles (1 from each treatment group) served as sham controls. After euthanasia on day 14, the lesion was evaluated by gross inspection, fluoroscopy, micro–computed tomography (micro-CT), and histology. To quantify changes between groups, a scoring system based on gross appearance (0-2), fluoroscopy (0-2), and micro-CT (0-6) was established. Micro-CT was used to quantify bone volume per total volume (BV/TV) in a defined region surrounding and inclusive of the defect. Results: The no scaffold group showed healing of the subchondral bone at 2 weeks, with continuity of subchondral bone elements. Conversely, condyles treated with PCL or CM showed substantial remodeling, with loss of bone in both the progeny fragment and surrounding parent bone. When these membranes were fenestrated (fenPCL and fenCM groups), bone loss was less severe. Histological analysis showed no integration in the cartilage layer in any treatment group, while fibrous tissue formed between the parent and progeny fragments. Micro-CT showed significant differences in mean BV/TV between the PCL (27.4% ± 2.3%) and the sham (47.7% ± 1.4%) or no scaffold (54.9% ± 15.1%) groups (P < .01 and P < .05, respectively). In addition, a significant difference in bone loss was evident between the PCL and fenPCL groups (mean BV/TV, 46.6% ± 15.2%; P < .05), as well as between the PCL and fenCM (mean BV/TV, 50.9% ± 3.5%) and fenPCL groups (P < .01). Grading by 6 blinded reviewers using an OCD scoring system with 3 subcategories showed a significant difference between control and PCL groups. Conclusion: This study successfully developed a large animal model of OCD-like lesions in the knee joint of Yucatan minipigs. The lesions generated matched characteristics of an ICRS grade 3 OCD lesion in humans. These findings set the stage for ongoing model refinement as well as exploration of novel interventional therapies to restore function and bone and cartilage patency in individuals affected by this rare but significant disease. Clinical Relevance: This developed model will serve as a platform on which to further investigate the natural course as well as emerging treatment options for OCD. PMID:26535380

  14. Peripheral Blood Mononuclear Cells Enhance Cartilage Repair in in vivo Osteochondral Defect Model

    PubMed Central

    Hopper, Niina; Wardale, John; Brooks, Roger; Power, Jonathan; Rushton, Neil; Henson, Frances

    2015-01-01

    This study characterized peripheral blood mononuclear cells (PBMC) in terms of their potential in cartilage repair and investigated their ability to improve the healing in a pre-clinical large animal model. Human PBMCs were isolated with gradient centrifugation and adherent PBMC’s were evaluated for their ability to differentiate into adipogenic, chondrogenic and osteogenic lineages and also for their expression of musculoskeletal genes. The phenotype of the PBMCs was evaluated using Stro-1, CD34, CD44, CD45, CD90, CD106, CD105, CD146 and CD166 cell surface markers. Osteochondral defects were created in the medial femoral condyle (MFC) of 24 Welsh mountain sheep and evaluated at a six month time point. Four cell treatment groups were evaluated in combination with collagen-GAG-scaffold: (1) MSC alone; (2) MSCs and PBMCs at a ratio of 20:1; (3) MSCs and PBMC at a ratio of 2:1 and (4) PBMCs alone. Samples from the surgical site were evaluated for mechanical properties, ICRS score and histological repair. Fresh PBMC samples were 90% positive for hematopoietic cell surface markers and negative for the MSC antibody panel (<1%, p = 0.006). However, the adherent PBMC population expressed mesenchymal stem cell markers in hypoxic culture and lacked CD34/45 positive cells (<0.2%). This finding demonstrated that the adherent cells had acquired an MSC-like phenotype and transformed in hypoxia from their original hematopoietic lineage. Four key genes in muskuloskeletal biology were significantly upregulated in adherent PBMCs by hypoxia: BMP2 4.2-fold (p = 0.0007), BMP6 10.7-fold (p = 0.0004), GDF5 2.0-fold (p = 0.002) and COL1 5.0-fold (p = 0.046). The monolayer multilineage analysis confirmed the trilineage mesenchymal potential of the adherent PBMCs. PBMC cell therapy was equally good as bone marrow MSC therapy for defects in the ovine large animal model. Our results show that PBMCs support cartilage healing and oxygen tension of the environment was found to have a key effect on the derivation of a novel adherent cell population with an MSC-like phenotype. This study presents a novel and easily attainable point-of-care cell therapy with PBMCs to treat osteochondral defects in the knee avoiding any cell manipulations outside the surgical room. PMID:26252391

  15. Refixation of Osteochondral Fractures by an Ultrasound-Activated Pin System – An Ovine In Vivo Examination Using CT and Scanning Electron Microscope

    PubMed Central

    H, Neumann; A.P, Schulz; S, Breer; A, Unger; B, Kienast

    2015-01-01

    Background: Osteochondral injuries, if not treated appropriately, often lead to severe osteoarthritis of the affected joint. Without refixation of the osteochondral fragment, human cartilage only repairs these defects imperfectly. All existing refixation systems for chondral defects have disadvantages, for instance bad MRI quality in the postoperative follow-up or low anchoring forces. To address the problem of reduced stability in resorbable implants, ultrasound-activated pins were developed. By ultrasound-activated melting of the tip of these implants a higher anchoring is assumed. Aim of the study was to investigate, if ultrasound-activated pins can provide a secure refixation of osteochondral fractures comparing to conventional screw and conventional, resorbable pin osteosynthesis. CT scans and scanning electron microscopy should proovegood refixation results with no further tissue damage by the melting of the ultrasound-activated pins in comparison to conventional osteosynthesis. Methods: Femoral osteochondral fragments in sheep were refixated with ultrasound-activated pins (SonicPin™), Ethipins® and screws (Asnis™). The quality of the refixated fragments was examined after three month of full weight bearing by CT scans and scanning electron microscopy of the cartilage surface. Results: The CT examination found almost no statistically significant difference in the quality of refixation between the three different implants used. Concerning the CT morphology, ultrasound-activated pins demonstrated at least the same quality in refixation of osteochondral fragments as conventional resorbable pins or screws. The scanning electron microscopy showed no major surface damage by the three implants, especially any postulated cartilage damage induced by the heat of the ultrasound-activated pin. The screws protruded above the cartilage surface, which may affect the opposingtibial surface. Conclusion: Using CT scans and scanning electron microscopy, the SonicPin™, the Ethipin® and screws were at least equivalent in refixation quality of osteochondral fragments. PMID:25674184

  16. Osteogenesis and chondrogenesis of biomimetic integrated porous PVA/gel/V-n-HA/pa6 scaffolds and BMSCs construct in repair of articular osteochondral defect.

    PubMed

    Li, Xiang; Li, Yubao; Zuo, Yi; Qu, Dan; Liu, Yiming; Chen, Tao; Jiang, Nan; Li, Hui; Li, Jihua

    2015-10-01

    A novel bi-layered osteochondral scaffold, including of PVA/Gel/V layer for the cartilage and n-HA/PA6 layer for the subchondral bone, has been proposed to evaluate the potential of the engineered of osteochondral grafts in repairing articular osteochondral defects in rabbits. The two different layers of the scaffolds were seeded with allogenic bone marrow-derived stem cells (BMSCs), which were chondrogenically and osteogenically induced respectively. The critical-size osteochondral defects were created in the knees of adult rabbits. The defects were treated with cell-bi-layered constructs (Group A), bi-layered constructs (Group B) and untreated group C as control group. The adhesion, proliferation and differentiation of BMSCs were demonstrated by immunohistochemical staining and scanning electron microscopy (SEM) in vitro. Cell survival was tracked via fluorescent labeling in vivo. Overall, the porous PVA/Gel/V-n-HA/PA6 scaffold was compatible and had no negative effects on the BMSCs in vitro culture. The cell-bi-layered scaffolds showed superior repair results as compared to the control group using gross examination and histological assessment. With BMSCs implantation, the two different layers of the composite biomimetic scaffolds provided a suitable environment for cells to form respective tissue. Simultaneously, the RT-PCR results confirmed the expression of specific extracellular matrix (ECM) markers for cartilaginous or osteoid tissue. This investigation showed that the porous PVA/Gel/V-n-HA/PA6 scaffold is a potential matrix for treatment of osteochondral defects, and the method of using chondrogenically and osteogenically differentiated BMSCs as seed cells on each layer might be a promising strategy in repair of articular osteochondral defect due to enhanced chondrogenesis and osteogenesis. PMID:25772000

  17. A new approach to scaffold fixation by magnetic forces: Application to large osteochondral defects.

    PubMed

    Russo, Alessandro; Shelyakova, Tatiana; Casino, Daniela; Lopomo, Nicola; Strazzari, Alessandro; Ortolani, Alessandro; Visani, Andrea; Dediu, Valentin; Marcacci, Maurilio

    2012-11-01

    Scaffold fixation represents one of the most serious challenges in osteochondral defect surgery. Indeed, the fixation should firmly hold the scaffold in the implanted position as well as it should guaranty stable bone/scaffold interface for efficient tissue regeneration. Nonetheless successful results have been achieved for small defect repair, the fixation remains really problematic for large defects, i.e. defects with areas exceeding 2cm(2). This paper advances an innovative magnetic fixation approach based on application of magnetic scaffolds. Finite element modeling was exploited to investigate the fixation efficiency. We considered three magnetic configurations: (1) external permanent magnet ring placed around the leg near the joint; (2) four small permanent magnet pins implanted in the bone underlying the scaffold; (3) four similarly implanted stainless steel pins which magnetization was induced by the external magnet. It was found that for most appropriate magnetic materials and optimized magnet-scaffold positioning all the considered configurations provide a sufficient scaffold fixation. In addition to fixation, we analyzed the pressure induced by magnetic forces at the bone/scaffold interface. Such pressure is known to influence significantly the bone regeneration and could be used for magneto-mechanical stimulation. PMID:22381395

  18. Arthroscopic treatment of osteochondral lesions of the talus: microfracture and drilling versus debridement.

    PubMed

    Backus, Jonathon D; Viens, Nicholas A; Nunley, James A

    2012-01-01

    Operative treatment of osteochondral lesions of the talus (OLTs) is frequently based on lesion size, stability, and surgeon preference. The purpose of this study was to determine if one arthroscopic treatment is superior to another for improving pain in patients with OLTs. Sixty-two patients treated by a single surgeon from 1999 to 2009 had sufficient medical records to be reviewed. Demographics, mechanism of injury, type of operation, lesion characteristics, and pain scores were analyzed. Thirty-one males and 31 females (mean age 32) were included; 54.1% of the lesions were on the medial talar dome and 72.3% were posttraumatic. Seventeen patients underwent arthroscopic debridement and 45 underwent arthroscopic drilling or microfracture. Visual analog scale pain scores were documented in 33 patients, demonstrating a statistically significant decrease at 6 months for debridement (p = .006) and drilling and microfracture (p = .0003) procedures. Neither procedure was superior to the other in pain reduction. No demographic variables were identified that influenced these postoperative pain scores. These results support that most OLTs are posttraumatic lesions caused by inversion or twisting and often occur on the medial talus. Arthroscopic interventions were effective for decreasing pain in both surgical groups. PMID:23327846

  19. Osteochondritis dissecans (OCD), an endoplasmic reticulum storage disease?: a morphological and molecular study of OCD fragments.

    PubMed

    Skagen, P S; Horn, T; Kruse, H A; Staergaard, B; Rapport, M M; Nicolaisen, T

    2011-12-01

    Osteochondritis dissecans (OCD) fragments, cartilage and blood from four patients were used for morphological and molecular analysis. Controls included articular cartilage and blood samples from healthy individuals. Light microscopy and transmission electron microscopy (TEM) showed abnormalities in chondrocytes and extracellular matrix of cartilage from OCD patients. Abnormal type II collagen heterofibrils in "bundles" and chondrocytes with abnormal accumulation of matrix proteins in distended rough endoplasmic reticulum were typical findings. Further, Von Kossa staining and TEM showed empty lacunae close to mineralized "islands" in the cartilage and hypertrophic chondrocytes containing accumulated matrix proteins. Immunostaining revealed: (1) that types I, II, VI and X collagens and aggrecans were deposited intracellulary and (2) co-localization within the islands of types I, II, X collagens and aggrecan indicating that hypertrophic chondrocytes express a phenotype of bone cells during endochondral ossification. Types I, VI and X collagens were also present across the entire dissecates suggesting that chondrocytes were dedifferentiated. DNA sequencings were non-conclusive, only single nucleotide polymorphism was found within the COL2A1 gene for one patient. We suggest that OCD lesions are caused by an alteration in chondrocyte matrix synthesis causing an endoplasmic reticulum storage disease phenotype, which disturbs or abrupts endochondral ossification. PMID:20561273

  20. Neurovascular invasion at the osteochondral junction and in osteophytes in osteoarthritis

    PubMed Central

    Suri, Sunita; Gill, Sarah E; de Camin, Sally Massena; Wilson, Deborah; McWilliams, Daniel F; Walsh, David A

    2007-01-01

    Background Normal adult articular cartilage is thought to be avascular and aneural. Objective To describe neurovascular structures at the osteochondral junction and in osteophytes in tibiofemoral osteoarthritis (OA) displaying a range of severity of cartilage changes. Methods Articular surfaces were obtained from 40 patients at total knee joint replacement surgery for tibiofemoral OA (TKR) and seven patients post mortem (PM). Antibodies directed against CD34 (vascular endothelium), protein gene product 9.5 (pan?neuronal marker), substance P and calcitonin gene?related peptide (sensory nerves) and C?flanking peptide of neuropeptide Y (sympathetic nerves) were used to localise blood vessels and nerves by immunohistochemistry. Severity of OA cartilage changes was graded histologically. Results TKR and PM samples displayed a range of OA cartilage changes including tidemark breaching by vascular channels. Sympathetic and sensory nerves were both present within vascular channels in the articular cartilage, in both mild and severe OA. Perivascular and free nerve fibres, and nerve trunks were observed within the subchondral bone marrow and within the marrow cavities of osteophytes. Sensory and sympathetic nerves displayed similar distributions in each region studied. Conclusion Vascularisation and the associated innervation of articular cartilage may contribute to tibiofemoral pain in OA across a wide range of structural disease severity. PMID:17446239

  1. Acute hyperextension/valgus trauma to the elbow in top-level adult male water polo goalkeepers: a cause of osteochondritis disecans of the capitellum?

    PubMed

    Rod, Eduard; Ivkovic, Alan; Boric, Igor; Jankovic, Sasa; Radic, Andrej; Hudetz, Damir

    2013-09-01

    We report on 2 cases of hyperextension/valgus elbow injuries in two adult male national team water polo goalkeepers. Both were healthy and had never sustained any major injuries of the elbow. Mechanism and type of injury in both of them was identical. Different medical treatment protocols of these injuries possibly have led to different outcomes, with one of them developing osteochondritis dissecans (OCD). Inadequate medical treatment of acute impact elbow injuries could lead to osteochondritis disecans of the elbow in top-level adult male water polo goalkeepers. PMID:24060018

  2. Displaced osteochondral fracture of the lateral femoral condyle associated with an acute anterior cruciate ligament avulsion fracture: a corollary of "the lateral femoral notch sign".

    PubMed

    Sharma, Gaurav; Naik, V Anand; Pankaj, Amite

    2012-08-01

    Anterior cruciate ligament (ACL) rupture is usually accompanied by bone contusions resulting from impact of tibia on femur. The injury sometimes becomes manifest as a depression on the lateral femoral condyle giving rise to "lateral femoral notch" sign. The authors describe a rare case of impaction of the tibia and femur resulting in an osteochondral fracture rather than the usual bone contusion, which frequently occurs with ACL rupture. Open reduction and internal fixation of both the ACL avulsion fracture and the osteochondral fracture from the lateral femoral condyle were done, and the patient had a good outcome at 1-year follow-up. Level of evidence V. PMID:22113226

  3. Chondrogenic differentiation of human bone marrow-derived mesenchymal stem cells in a simulated osteochondral environment is hydrogel dependent.

    PubMed

    de Vries-van Melle, M L; Tihaya, M S; Kops, N; Koevoet, W J L M; Murphy, J M; Verhaar, J A N; Alini, M; Eglin, D; van Osch, G J V M

    2014-01-01

    Hydrogels pose interesting features for cartilage regeneration strategies, such as the option for injectability and in situ gelation resulting in optimal filling of defects. We aimed to study different hydrogels for their capability to support chondrogenesis of human bone marrow-derived mesenchymal stem cells (hBMSCs). hBMSCs were encapsulated in alginate, alginate with hyaluronic acid (alginate/HA), fibrin or thermoresponsive HA grafted with poly(N-isopropyl acrylamide) side-chains (HA-pNIPAM). Glycosaminoglycan production and cartilage-related gene expression were significantly higher in hBMSC-alginate and hBMSC-fibrin constructs than in the other constructs. Supplementation of alginate with HA was not beneficial. hBMSC-alginate, hBMSC-fibrin and hBMSC-HA-pNIPAM constructs were placed in simulated defects in osteochondral biopsies and cultured in vitro for 28 d. Biopsies containing hBMSC-alginate and hBMSC-fibrin were implanted subcutaneously in nude mice for 12 weeks. hBMSC-alginate constructs had significantly higher cartilage-related gene expression after 28 d of culture as well as significantly more safranin-O positive repair tissue after 12 weeks in vivo than hBMSC-fibrin constructs. Although initial experiments with hBMSC-hydrogel constructs suggested comparable results of hBMSC-alginate, hBMSC-fibrin and hBMSC-HA-pNIPAM constructs, culture in the osteochondral biopsy model in vitro as well as in vivo revealed differences, suggests that chondrogenesis of hBMSCs in an osteochondral environment is hydrogel-dependent. PMID:24488855

  4. Cartilage Repair and Subchondral Bone Migration Using 3D Printing Osteochondral Composites: A One-Year-Period Study in Rabbit Trochlea

    PubMed Central

    Li, Dichen; Wang, Kunzheng; Hao, Dingjun; Bian, Weiguo; He, Jiankang; Jin, Zhongmin

    2014-01-01

    Increasing evidences show that subchondral bone may play a significant role in the repair or progression of cartilage damage in situ. However, the exact change of subchondral bone during osteochondral repair is still poorly understood. In this paper, biphasic osteochondral composite scaffolds were fabricated by 3D printing technology using PEG hydrogel and ?-TCP ceramic and then implanted in rabbit trochlea within a critical size defect model. Animals were euthanized at 1, 2, 4, 8, 16, 24, and 52 weeks after implantation. Histological results showed that hyaline-like cartilage formed along with white smooth surface and invisible margin at 24 weeks postoperatively, typical tidemark formation at 52 weeks. The repaired subchondral bone formed from 16 to 52 weeks in a “flow like” manner from surrounding bone to the defect center gradually. Statistical analysis illustrated that both subchondral bone volume and migration area percentage were highly correlated with the gross appearance Wayne score of repaired cartilage. Therefore, subchondral bone migration is related to cartilage repair for critical size osteochondral defects. Furthermore, the subchondral bone remodeling proceeds in a “flow like” manner and repaired cartilage with tidemark implies that the biphasic PEG/?-TCP composites fabricated by 3D printing provides a feasible strategy for osteochondral tissue engineering application. PMID:25177697

  5. Cartilage repair of experimentally 11 induced osteochondral defects in New Zealand White rabbits.

    PubMed

    Aulin, C; Jensen-Waern, M; Ekman, S; Hägglund, M; Engstrand, T; Hilborn, J; Hedenqvist, P

    2013-01-01

    Articular cartilage has a limited capacity for self-repair in adult humans, and methods used to stimulate regeneration often result in re-growth of fibrous cartilage, which has lower durability. No current treatment option can provide complete repair. The possibility of growth factor delivery into the joint for cartilage regeneration after injury would be an attractive treatment option. A full thickness osteochondral defect of 4 mm in diameter and 2 mm deep was created by mechanical drilling in the medial femoral condyle in 20 female adult New Zealand White rabbits. In an attempt to improve regeneration a hyaluronic hydrogel system, with or without bone morphogenetic protein-2 (BMP-2) was delivered intraarticularly. The contralateral joint defect was treated with saline as control. Throughout the study, rabbits were clinically examined and after 12 (n = 6) or 24 (n = 9) weeks, the rabbits were euthanized and the joints evaluated by histology. The defects healed with fibrocartilage like tissue, and the filling of the defects ranged from less than 25% to complete. The healing of the defects varied both inter- and intra-group wise. Treatment with hyaluronan gel with or without BMP-2 had no effect on cartilage regeneration compared with controls. Instead, severe ectopic bone formation was found in seven joints treated with BMP-2. In conclusion, the present study shows that neither treatment with hyaluronic gel alone, nor in combination with BMP-2, improves the healing of an induced cartilage defect in rabbits. It further shows that BMP-2 can induce ectopic bone formation, which severely affects the functionality of the joint. PMID:23467490

  6. Association between intraarticular cytokine levels and clinical parameters of osteochondritis dissecans in the ankle

    PubMed Central

    2014-01-01

    Background Reliable data about in vivo regulation of cytokines in osteochondritis dissecans (OCD) of the ankle are still missing. Disease-specific regulation patterns were hypothesized. Methods 28 patients with a mean age of 30.7?±?14.8 years undergoing an arthroscopy of the ankle because of OCD were prospectively included in a clinical trial. Lavage fluids were analyzed by ELISA for levels of aggrecan, BMP-2, BMP-7, IGF-1, IGF-1R, bFGF, endoglin, MMP-13, and IL-1?. Additionally, clinical parameters and scores (FFI, CFSS, AOFAS) were evaluated and supplemented by the Kellgren Lawrence Score (KLS) for conventional X-rays and the Ankle Osteoarthritis Scoring System (AOSS) for MRI. Results Grading of OCD lesions statistically significant increased with age and was higher in case of previously performed operations (p?

  7. Evaluation of chitosan-GP hydrogel biocompatibility in osteochondral defects: an experimental approach

    PubMed Central

    2014-01-01

    Background Articular cartilage, because of its avascular nature, has little capacity for spontaneous healing, and tissue engineering approaches, employing different biomaterials and cells, are under development. Among the investigated biomaterials are the chitosan-based hydrogels. Although thoroughly studied in other mammalian species, studies are scarce in equines. So, the aim of the present study was to investigate the biocompatibility of chitosan-GP in horse joints submitted to high mechanical loads. Results An osteochondral defect was created by arthroscopy in the medial surface of lateral trochlea of talus of left or right leg, randomly selected, from six healthy geldings. The defect was filled up with chitosan-GP. The contralateral joint received an identical defect with no implant. The chondral fragment removed to produce the defect was collected, processed and used as the “Initial” sample (normal cartilage) for histology, immunohistochemistry, and metabolic labelling of PGs. After 180 days, the repair tissues were collected, and also analyzed. At the end of the experiment (180 days after lesion), the total number of cells per field in repair tissues was equal to control, and macrophages and polymorphonuclear cells were not detected, suggesting that no significant inflammation was present. These cells were able to synthesize type II collagen and proteoglycans (PGs). Nevertheless, the cell population in these tissues, both in presence of chitosan-GP and in untreated controls, were heterogeneous, with a lower proportion of type II collagen-positives cells and some with a fibroblastic aspect. Moreover, the PGs synthesized in repair tissues formed in presence or absence of chitosan-GP were similar to those of normal cartilage. However, the chitosan-GP treated tissue had an disorganized appearance, and blood vessels were present. Conclusions Implanted chitosan-GP did not evoke an important inflammatory reaction, and permitted cell growth. These cells were able to synthesize type II collagen and PGs similar to those synthesized in normal cartilage and in healing tissue without implant, indicating its chondrocyte nature. PMID:25160583

  8. Expression of colony-stimulating factor 1 is associated with occurrence of osteochondral change in pigmented villonodular synovitis.

    PubMed

    Ota, Takehiro; Urakawa, Hiroshi; Kozawa, Eiji; Ikuta, Kunihiro; Hamada, Shunsuke; Tsukushi, Satoshi; Shimoyama, Yoshie; Ishiguro, Naoki; Nishida, Yoshihiro

    2015-07-01

    Pigmented villonodular synovitis (PVNS) is a benign, translocation-derived neoplasm. Because of its high local recurrence rate after surgery and occurrence of osteochondral destruction, a novel therapeutic target is required. The present study aimed to evaluate the significance of protein expression possibly associated with the pathogenesis during the clinical course of PVNS. In 40 cases of PVNS, positivity of colony-stimulated factor 1 (CSF1), its receptor (CSF1R), and receptor activator of nuclear factor kappa-B ligand (RANKL) were immunohistochemically determined. The relationship between the positivity and clinical outcomes was investigated. High positivity of CSF1 staining intensity was associated with an increased incidence of osteochondral lesions (bone erosion and osteoarthritis) (p = 0.009), but not with the rate of local recurrence. Positivity of CSF1R and RANKL staining was not associated with any clinical variables. The number of giant cells was not correlated with positivity of any of the three proteins, or with the clinical outcome. Focusing on knee cases, CSF1 positivity was also associated with the incidence of osteochondal change (p = 0.02). CSF1R positivity was high in cases which had local recurrence, but not significantly so (p = 0.129). Determination of CSF1 and CSF1R expression may be useful as a prognosticator of the clinical course and/or outcomes of PVNS. PMID:25854167

  9. Composite scaffolds for osteochondral repair obtained by combination of additive manufacturing, leaching processes and hMSC-CM functionalization.

    PubMed

    Díaz Lantada, Andrés; Alarcón Iniesta, Hernán; García-Ruíz, Josefa Predestinación

    2016-02-01

    Articular repair is a relevant and challenging area for the emerging fields of tissue engineering and biofabrication. The need of significant gradients of properties, for the promotion of osteochondral repair, has led to the development of several families of composite biomaterials and scaffolds, using different effective approaches, although a perfect solution has not yet been found. In this study we present the design, modeling, rapid manufacturing and in vitro testing of a composite scaffold aimed at osteochondral repair. The presented composite scaffold stands out for having a functional gradient of density and stiffness in the bony phase, obtained in titanium by means of computer-aided design combined with additive manufacture using selective laser sintering. The chondral phase is obtained by sugar leaching, using a PDMS matrix and sugar as porogen, and is joined to the bony phase during the polymerization of PDMS, therefore avoiding the use of supporting adhesives or additional intermediate layers. The mechanical performance of the construct is biomimetic and the stiffness values of the bony and chondral phases can be tuned to the desired applications, by means of controlled modifications of different parameters. A human mesenchymal stem cell (h-MSC) conditioned medium (CM) is used for improving scaffold response. Cell culture results provide relevant information regarding the viability of the composite scaffolds used. PMID:26652367

  10. Ectopic osteochondral formation of biomimetic porous PVA-n-HA/PA6 bilayered scaffold and BMSCs construct in rabbit.

    PubMed

    Qu, Dan; Li, Jihua; Li, Yubao; Khadka, Ashish; Zuo, Yi; Wang, Hang; Liu, Yiming; Cheng, Lin

    2011-01-01

    In this work, the novel poly vinyl alcohol/gelatin-nano-hydroxyapatite/polyamide6 (PVA-n-HA/PA6) bilayered scaffold with biomimetic properties for articular cartilage and subchondral bone is developed. Furthermore, when these osteochondral scaffolds were seeded with induced bone mesenchymal stem cells (BMSCs) and implanted at ectopic sites, showed the potential for an engineered cartilage tissue and the corresponding subchondral bone. BMSCs were expanded in vitro and induced to chondrogenic or osteogenic potential by culturing in suitable media for 14 days. Subsequently, these induced cells were seeded into PVA-n-HA/PA6 separately, and the constructs were implanted into the rabbit muscle pouch for upto 12 weeks. Ectopic neocartilage formation in the PVA layer and reconstitution of the subchondral bone which remained confined within the n-HA/PA6 layer with the alteration of the cellular phenotype were identified with Masson's trichrome stain. Simultaneously, the RT-PCR results confirmed the expression of specific extracellular matrix (ECM) markers for cartilaginous tissue, such as collagen type II (Col-II), or alternatively, markers for osteoid tissue, such as collagen type I (Col-I) at the corresponding layers. During ectopic implantation, the underlying subchondral bone layer was completely integrated with the cartilage layer. The result from the ectopic osteochondral scaffolds implantation suggests that PVA-n-HA/PA6 with induced BMSCs is a possible substitute with potential in cartilage repair strategies. PMID:20967773

  11. Advancement of the Subchondral Bone Plate in Translational Models of Osteochondral Repair: Implications for Tissue Engineering Approaches.

    PubMed

    Orth, Patrick; Madry, Henning

    2015-12-01

    Subchondral bone plate advancement is of increasing relevance for translational models of osteochondral repair in tissue engineering (TE). Especially for therapeutic TE approaches, a basic scientific knowledge of its chronological sequence, possible etiopathogenesis, and clinical implications are indispensable. This review summarizes the knowledge on this topic gained from a total of 31 translational investigations, including 1009 small and large animals. Experimental data indicate that the advancement of the subchondral bone plate frequently occurs during the spontaneous repair of osteochondral defects and following established articular cartilage repair approaches for chondral lesions such as marrow stimulation and TE-based strategies such as autologous chondrocyte implantation. Importantly, this subchondral bone reaction proceeds in a defined chronological and spatial pattern, reflecting both endochondral ossification and intramembranous bone formation. Subchondral bone plate advancement arises earlier in small animals and defects, but is more pronounced at the long term in large animals. Possible etiopathologies comprise a disturbed subchondral bone/articular cartilage crosstalk and altered biomechanical conditions or neovascularization. Of note, no significant correlation was found so far between subchondral bone plate advancement and articular cartilage repair. This evidence from translational animal models adverts to an increasing awareness of this previously underestimated pathology. Future research will shed more light on the advancement of the subchondral bone plate in TE models of cartilage repair. PMID:26066580

  12. An anti-inflammatory cell-free collagen/resveratrol scaffold for repairing osteochondral defects in rabbits.

    PubMed

    Wang, Wei; Sun, Liang; Zhang, Pengfei; Song, Junfei; Liu, Wenguang

    2014-12-01

    Inflammatory factor overexpression is the major cause of cartilage and osteochondral damage. Resveratrol (Res) is known for its anti-inflammatory, antioxidant and immunmodulatory properties. However, these effects are hampered by its water insolubility and rapid metabolism in vivo. To optimize its therapeutic efficacy in this study, Res was grafted to polyacrylic acid (PAA, 1000Da) to obtain a macromolecular drug, PAA-Res, which was then incorporated into atelocollagen (Coll) hydrogels to fabricate anti-inflammatory cell-free (Coll/Res) scaffolds with improved mechanical strengths. The Coll/Res scaffolds demonstrated the ability to capture diphenylpicrylhydrazyl free radicals. Both pure Coll and Coll/Res scaffolds could maintain their original shape for 6weeks in phosphate buffered saline. The scaffolds were degraded by collagenase over several days, and the degradation rate was slowed down by Res loading. The Coll and Coll/Res scaffolds with excellent cytocompatibility were shown to promote the proliferation and maintain the normal phenotype of the seeded chondrocytes and bone marrow stromal stem cells (BMSCs). In addition, the Coll/Res scaffold exhibited the capacity to protect the chondrocytes and BMSCs against reactive oxygen species. The acellular Coll/Res scaffolds were transplanted into the rabbit osteochondral defects. After implantation for 2, 4 and 6weeks, the samples were retrieved for quantitative real-time polymerase chain reaction, and the inflammatory related genes interleukin-1?, matrix metalloproteinases-13, COX-2 and bone and cartilage related genes SOX-9, aggrecan, Coll II and Coll I were determined. Compared with the untreated defects, the inflammatory related genes were down-regulated and those bone and cartilage related genes were up-regulated by filling the defect with an anti-inflammatory scaffold. After 12weeks, the osteochondral defects were completely repaired by the Coll/Res scaffold, and the neo-cartilage integrated well with its surrounding tissue and subchondral bone. Immunohistochemical and glycosaminoglycan staining confirmed the distribution of Coll II and glycosaminoglycans in the regenerated cartilage. The anti-inflammatory acellular Coll/Res scaffolds are convenient to administer in vivo, holding a greater potential for future clinical applications. PMID:25169257

  13. Late-diagnosed large osteochondral fracture of the lateral femoral condyle in an adolescent: a case report.

    PubMed

    Enea, Davide; Busilacchi, Alberto; Cecconi, Stefano; Gigante, Antonio

    2013-07-01

    In this case report, we describe a large osteochondral fracture of the anterolateral femoral condyle in an adolescent athlete while dancing. At 3 months after the misdiagnosed injury, the condylar defect was covered by a layer of disorganized fibrous tissue rich in blood vessels. To achieve good repair, an accurate curettage of the fractured surfaces, a precise reduction, and a stable internal fixation of the fragments were performed. Two poly-L-lactic acid bioabsorbable screws were used to obtain appropriate compression. At the 2-year follow-up, the patient was asymptomatic and had resumed her previous dancing activity. An MRI scan showed no interruptions of the cartilage layer at the boundary with the healthy tissue, but cartilage thinning and extensive subchondral remodeling were detected. PMID:23511583

  14. Knee Osteochondritis Dissecans Treated by the AO Hook Fixation System: A Four Year Follow-Up of an Alternative Technique

    PubMed Central

    Pengas, Ioannis P; Assiotis, Angelos; Kokkinakis, Michail; Khan, Wasim S; Meyers, Paul; Arbuthnot, James; Mcnicholas, Michael J

    2014-01-01

    Surgical fixation is recommended for stable osteochondritis dissecans (OCD) lesions that have failed nonoperative management and for all unstable lesions. In this study we set out to describe and evaluate an alternative method of surgical fixation for such lesions. Five knees with unstable OCD lesions in four male adolescent patients with open physes were treated with the AO Hook Fixation System. The outcome was evaluated both clinically and with three separate outcome systems (IKDC 2000, KOOS, Lysholm) at one and a mean four year follow-up. We demonstrated excellent clinical results in all patients. At four years, all scoring systems demonstrated statistically significant improvement when compared to the preoperative status. Our study suggests that the AO Hook Fixation System is an alternative method of surgical intervention with comparable medium term results with other existing modes of fixation and the added biomechanical advantage of the absence of distracting forces during hardware removal. PMID:25067976

  15. Pulsed electromagnetic fields after arthroscopic treatment for osteochondral defects of the talus: double-blind randomized controlled multicenter trial

    PubMed Central

    van Bergen, Christiaan JA; Blankevoort, Leendert; de Haan, Rob J; Sierevelt, Inger N; Meuffels, Duncan E; d'Hooghe, Pieter RN; Krips, Rover; van Damme, Geert; van Dijk, C Niek

    2009-01-01

    Background Osteochondral talar defects usually affect athletic patients. The primary surgical treatment consists of arthroscopic debridement and microfracturing. Although this is mostly successful, early sport resumption is difficult to achieve, and it can take up to one year to obtain clinical improvement. Pulsed electromagnetic fields (PEMFs) may be effective for talar defects after arthroscopic treatment by promoting tissue healing, suppressing inflammation, and relieving pain. We hypothesize that PEMF-treatment compared to sham-treatment after arthroscopy will lead to earlier resumption of sports, and aim at 25% increase in patients that resume sports. Methods/Design A prospective, double-blind, randomized, placebo-controlled trial (RCT) will be conducted in five centers throughout the Netherlands and Belgium. 68 patients will be randomized to either active PEMF-treatment or sham-treatment for 60 days, four hours daily. They will be followed-up for one year. The combined primary outcome measures are (a) the percentage of patients that resume and maintain sports, and (b) the time to resumption of sports, defined by the Ankle Activity Score. Secondary outcome measures include resumption of work, subjective and objective scoring systems (American Orthopaedic Foot and Ankle Society – Ankle-Hindfoot Scale, Foot Ankle Outcome Score, Numeric Rating Scales of pain and satisfaction, EuroQol-5D), and computed tomography. Time to resumption of sports will be analyzed using Kaplan-Meier curves and log-rank tests. Discussion This trial will provide level-1 evidence on the effectiveness of PEMFs in the management of osteochondral ankle lesions after arthroscopy. Trial registration Netherlands Trial Register (NTR1636) PMID:19591674

  16. Long-term results after operative treatment of osteochondritis dissecans of the knee joint—30 year results

    PubMed Central

    Wurth, A.; Eysel, P.; König, D. P.

    2007-01-01

    Osteochondritis dissecans (OD) mostly appears at the knee joint on the weight-bearing part of the medial femoral condyle. A multi-factorial event is most likely responsible for the triggering of OD. The aim of this retrospective study was to carry out long-term assessment of the results of operative treatment. Between 1959 and 1976, 148 patients were treated for OD by an open technique. For this purpose, a total number of 38 patients were analysed after approximately 30 years. Twenty-six patients were evaluated clinically by means of standardised questionnaires and also radiologically; 12 patients were analysed only by questionnaire. In order to verify the clinical findings and the subjective assessment, radiographs were done and analysed according the Kannus score. The Brückl score was used to evaluate the results of the OD. Twenty-four knee joints were analysed by radiographs. Sixty percent of the operated joints showed poor results in the analysis according to Kannus. Only four patients showed an excellent result by using the clinical scoring system. Nevertheless, we were able to prove a markedly higher rate of osteoarthrosis. The causal explanation for this lies in the patient selection. Most of the patients were above average age, and the OD was discovered quite late, and thus the disease had already progressed to a higher degree. In 74% of all cases, an extirpation of the osteochondral fragment was performed, whereas today there are several operative options. In our view, therefore, the need arises to conduct further follow-up examinations with comparative time spans, as well as to conduct a parallel analysis of corresponding control groups in order to evaluate the aetiology of the increased rate of osteoarthrosis. PMID:18350293

  17. Evaluation of Cartilage Repair by Mesenchymal Stem Cells Seeded on a PEOT/PBT Scaffold in an Osteochondral Defect.

    PubMed

    Barron, V; Merghani, K; Shaw, G; Coleman, C M; Hayes, J S; Ansboro, S; Manian, A; O'Malley, G; Connolly, E; Nandakumar, A; van Blitterswijk, C A; Habibovic, P; Moroni, L; Shannon, F; Murphy, J M; Barry, F

    2015-09-01

    The main objective of this study was to evaluate the effectiveness of a mesenchymal stem cell (MSC)-seeded polyethylene-oxide-terephthalate/polybutylene-terephthalate (PEOT/PBT) scaffold for cartilage tissue repair in an osteochondral defect using a rabbit model. Material characterisation using scanning electron microscopy indicated that the scaffold had a 3D architecture characteristic of the additive manufacturing fabrication method, with a strut diameter of 296 ± 52 ?m and a pore size of 512 ± 22 ?m × 476 ± 25 ?m × 180 ± 30 ?m. In vitro optimisation revealed that the scaffold did not generate an adverse cell response, optimal cell loading conditions were achieved using 50 ?g/ml fibronectin and a cell seeding density of 25 × 10(6) cells/ml and glycosaminoglycan (GAG) accumulation after 28 days culture in the presence of TGF?3 indicated positive chondrogenesis. Cell-seeded scaffolds were implanted in osteochondral defects for 12 weeks, with cell-free scaffolds and empty defects employed as controls. On examination of toluidine blue staining for chondrogenesis and GAG accumulation, both the empty defect and the cell-seeded scaffold appeared to promote repair. However, the empty defect and the cell-free scaffold stained positive for collagen type I or fibrocartilage, while the cell-seeded scaffold stained positive for collagen type II indicative of hyaline cartilage and was statistically better than the cell-free scaffold in the blinded histological evaluation. In summary, MSCs in combination with a 3D PEOT/PBT scaffold created a reparative environment for cartilage repair. PMID:25589372

  18. Functional evaluation of patients treated with osteochondral allograft transplantation for post-traumatic ankle arthritis: one year follow-up.

    PubMed

    Berti, L; Vannini, F; Lullini, G; Caravaggi, P; Leardini, A; Giannini, S

    2013-09-01

    Severe post-traumatic ankle arthritis poses a reconstructive challenge in active patients. Whereas traditional surgical treatments, i.e. arthrodesis and arthroplasty, provide good pain relief, arthrodesis is associated to functional and psychological limitations, and arthroplasty is prone to failure in the active patient. More recently the use of bipolar fresh osteochondral allografts transplantation has been proposed as a promising alternative to the traditional treatments. Preliminary short- and long-term clinical outcomes for this procedure have been reported, but no functional evaluations have been performed to date. The clinical and functional outcomes of a series of 10 patients who underwent allograft transplantation at a mean follow-up of 14 months are reported. Clinical evaluation was performed with the AOFAS score, functional assessment by state-of-the-art gait analysis. The clinical score significantly improved from a median of 54 (range 12-65) pre-op to 76.5 (range 61-86) post-op (p=0.002). No significant changes were observed for the spatial-temporal parameters, but motion at the hip and knee joints during early stance, and the range of motion of the ankle joint in the frontal plane (control: 13.8°±2.9°; pre-op: 10.4°±3.1°, post-op: 12.9°±4.2°; p=0.02) showed significant improvements. EMG signals revealed a good recovery in activation of the biceps femoris. This study showed that osteochondral allograft transplantation improves gait patterns. Although re-evaluation at longer follow-ups is required, this technique may represent the right choice for patients who want to delay the need for more invasive joint reconstruction procedures. PMID:23711988

  19. Combined osteochondral fracture of the posterolateral tibial plateau and Segond fracture with anterior cruciate ligament injury in a skeletally immature patient.

    PubMed

    Tei, Katsumasa; Kubo, Seiji; Matsumoto, Tomoyuki; Matsushita, Takehiko; Matsumoto, Akio; Kurosaka, Masahiro; Kuroda, Ryosuke

    2012-02-01

    A case of a 14-year-old boy with a rare injury--an osteochondral fracture of the posterolateral tibial plateau associated with the anterior cruciate ligament (ACL) rapture, and Segond fracture characterized by an avulsion fracture of the lateral tibial plateau--is reported. This case was noteworthy because it involved a rare combination of ACL injuries. This injury was thought to be caused by the impaction between the posterior aspect of the lateral tibial plateau and the lateral femoral condyle during internal rotational displacement of the knee joint at the time of injury, because the osteochondral fracture of the posterolateral tibial plateau matched the site where the bone bruise was observed. PMID:21559846

  20. Bioprinting of a mechanically enhanced three-dimensional dual cell-laden construct for osteochondral tissue engineering using a multi-head tissue/organ building system

    NASA Astrophysics Data System (ADS)

    Shim, Jin-Hyung; Lee, Jung-Seob; Kim, Jong Young; Cho, Dong-Woo

    2012-08-01

    The aim of this study was to build a mechanically enhanced three-dimensional (3D) bioprinted construct containing two different cell types for osteochondral tissue regeneration. Recently, the production of 3D cell-laden structures using various scaffold-free cell printing technologies has opened up new possibilities. However, ideal 3D complex tissues or organs have not yet been printed because gel-state hydrogels have been used as the principal material and are unable to maintain the desired 3D structure due to their poor mechanical strength. In this study, thermoplastic biomaterial polycaprolactone (PCL), which shows relatively high mechanical properties as compared with hydrogel, was used as a framework for enhancing the mechanical stability of the bioprinted construct. Two different alginate solutions were then infused into the previously prepared framework consisting of PCL to create the 3D construct for osteochondral printing. For this work, a multi-head tissue/organ building system (MtoBS), which was particularly designed to dispense thermoplastic biomaterial and hydrogel having completely different rheology properties, was newly developed and used to bioprint osteochondral tissue. It was confirmed that the line width, position and volume control of PCL and alginate solutions were adjustable in the MtoBS. Most importantly, dual cell-laden 3D constructs consisting of osteoblasts and chondrocytes were successfully fabricated. Further, the separately dispensed osteoblasts and chondrocytes not only retained their initial position and viability, but also proliferated up to 7 days after being dispensed.

  1. A Missense Mutation in the Aggrecan C-type Lectin Domain Disrupts Extracellular Matrix Interactions and Causes Dominant Familial Osteochondritis Dissecans

    PubMed Central

    Stattin, Eva-Lena; Wiklund, Fredrik; Lindblom, Karin; Önnerfjord, Patrik; Jonsson, Björn-Anders; Tegner, Yelverton; Sasaki, Takako; Struglics, André; Lohmander, Stefan; Dahl, Niklas; Heinegĺrd, Dick; Aspberg, Anders

    2010-01-01

    Osteochondritis dissecans is a disorder in which fragments of articular cartilage and subchondral bone dislodge from the joint surface. We analyzed a five-generation family in which affected members had autosomal-dominant familial osteochondritis dissecans. A genome-wide linkage analysis identified aggrecan (ACAN) as a prime candidate gene for the disorder. Sequence analysis of ACAN revealed heterozygosity for a missense mutation (c.6907G > A) in affected individuals, resulting in a p.V2303M amino acid substitution in the aggrecan G3 domain C-type lectin, which mediates interactions with other proteins in the cartilage extracellular matrix. Binding studies with recombinant mutated and wild-type G3 proteins showed loss of fibulin-1, fibulin-2, and tenascin-R interactions for the V2303M protein. Mass spectrometric analyses of aggrecan purified from patient cartilage verified that V2303M aggrecan is produced and present in the tissue. Our results provide a molecular mechanism for the etiology of familial osteochondritis dissecans and show the importance of the aggrecan C-type lectin interactions for cartilage function in vivo. PMID:20137779

  2. Combination therapy with intra-articular injection of mesenchymal stem cells and articulated joint distraction for repair of a chronic osteochondral defect in the rabbit.

    PubMed

    Harada, Yohei; Nakasa, Tomoyuki; Mahmoud, Elhussein Elbadry; Kamei, Goki; Adachi, Nobuo; Deie, Masataka; Ochi, Mitsuo

    2015-10-01

    The present study investigated intra-articular injection of bone-marrow-derived mesenchymal stem cells (MSCs) combined with articulated joint distraction as treatment for osteochondral defects. Large osteochondral defects were created in the weight-bearing area of the medial femoral condyle in rabbit knees. Four weeks after defect creation, rabbits were divided into six groups: control group, MSC group, distraction group, distraction?+?MSC group, temporary distraction group, and temporary distraction?+?MSC group. Groups with MSC received intra-articular injection of MSCs. Groups with distraction underwent articulated distraction arthroplasty. Groups with temporary distraction discontinued the distraction after 4 weeks. The rabbits were euthanized at 4, 8, and 12 weeks after treatment except temporary distraction groups which were euthanized at only 12 weeks. Histological scores in the distraction?+?MSC group were significantly better than in the control, MSC group or distraction group at 4 and 8 weeks, but showed no further improvement. At 12 weeks, the temporary distraction?+?MSC group showed the best results, demonstrating hyaline cartilage repair with regeneration of the osteochondral junction. In conclusion, joint distraction with intra-articular injection of MSCs promotes early cartilage repair, and compressive loading of the repair tissue after temporary distraction stimulates articular cartilage regeneration. PMID:26174695

  3. Hyaluronic Acid (800?kDa) Supplementation of University of Wisconsin Solution Improves Viability of Osteochondral Grafts and Reduces Matrix Metalloproteinase Expression during Cold Preservation

    PubMed Central

    Yamada, Takuya; Uchida, Kentaro; Onuma, Kenji; Inoue, Gen; Aikawa, Jun; Takano, Shotaro; Sekiguchi, Hiroyuki; Fujimaki, Hisako; Miyagi, Masayuki; Takaso, Masashi

    2015-01-01

    Osteochondral allografting is a promising option for the treatment of large cartilage defects. However, because the cell viability of osteochondral tissues (OCTs) gradually reduces during storage at 4°C, methods for maintaining the cell viability of fresh OCTs are needed to improve transplantation outcomes. Here, we evaluated whether the supplementation of preservation solution with one of three different molecular weight forms of hyaluronic acid (HA) improved the viability of rat OCTs during long-term cold storage. The supplementation of University of Wisconsin (UW) solution with 800?kDa significantly improved the cell viability of OCT after 14 days at 4°C compared to nonsupplemented UW solution. In contrast, UW solution supplemented with either 1900 or 6000?kDa HA did not markedly improve the cell viability of the OCT. Real-time PCR analysis revealed that the levels of matrix metalloproteinases 2, 3, and 9 were significantly decreased in OCT stored in UW solution supplemented with 800?kDa HA. Although further studies in human OCT are warranted, these findings demonstrate that the use of 800?kDa HA in place of serum may be a suitable approach for the long-term preservation of osteochondral allografts designated for the repair of large cartilage defects in the clinical setting. PMID:26199955

  4. Influence of Intra-Articular Administration of Trichostatin A on Autologous Osteochondral Transplantation in a Rabbit Model

    PubMed Central

    Hou, Huacheng; Zheng, Ke; Wang, Guanghu; Ikegawa, Shiro; Zheng, Minghao; Gao, Xiang; Qin, Jinzhong; Teng, Huajian; Jiang, Qing

    2015-01-01

    Autologous osteochondral transplantation (AOT) is a method for articular cartilage repair. However, several disadvantages of this method have been reported, such as transplanted cartilage degeneration and the lack of a connection between the grafted and adjacent cartilage tissues. To evaluate the effect of intra-articular administration of trichostatin A (TSA) on AOT, we conducted a case control study in a rabbit model. International Cartilage Repair Society (ICRS) macroscopic scores, the modified O'Driscoll histology scores, and real-time PCR were utilized to evaluate the results. At 4 weeks, both macroscopic and histological assessments showed that there was no significant difference between the TSA and control groups. However, the mean macroscopic and histological scores for the TSA-treated group were significantly higher than the scores for the control group at 12 weeks. TSA was shown to directly reduce collagen type II (COL2), aggrecan, matrix metalloproteinase (MMP), and a disintegrin and metalloproteinase domain with thrombospondin motifs 5 (ADAMTS-5) expression and to simultaneously repress the upregulation of MMP-3, MMP-9, and MMP-13 levels induced by interleukin 1? (IL-1?) in chondrocytes. In conclusion, TSA protects AOT grafts from degeneration, which may provide a benefit in the repair of articular cartilage injury. PMID:25866784

  5. Xenoimplantation of an Extracellular-Matrix-Derived, Biphasic, Cell-Scaffold Construct for Repairing a Large Femoral-Head High-Load-Bearing Osteochondral Defect in a Canine Model

    PubMed Central

    Qiang, Yang; Yanhong, Zhao; Jiang, Peng; Shibi, Lu; Quanyi, Guo; Xinlong, Ma; Qun, Xia; Baoshan, Xu; Bin, Zhao; Aiyuan, Wang; Li, Zhang; Wengjing, Xu; Chao, Zeng

    2014-01-01

    This study was aimed to develop an ECM-derived biphasic scaffold and to investigate its regeneration potential loaded with BM-MSCs in repair of large, high-load-bearing osteochondral defects of the canine femoral head. The scaffolds were fabricated using cartilage and bone ECM as a cartilage and bone layer, respectively. Osteochondral constructs were fabricated using induced BM-MSCs and the scaffold. Osteochondral defects (11?mm diameter × 10?mm depth) were created on femoral heads of canine and treated with the constructs. The repaired tissue was evaluated for gross morphology, radiography, histological, biomechanics at 3 and 6 months after implantation. Radiography revealed that femoral heads slightly collapsed at 3 months and severely collapsed at 6 months. Histology revealed that some defects in femoral heads were repaired, but with fibrous tissue or fibrocartilage, and femoral heads with different degrees of collapse. The bone volume fraction was lower for subchondral bone than normal femoral bone at 3 and 6 months. Rigidity was lower in repaired subchondral bone than normal femoral bone at 6 months. The ECM-derived, biphasic scaffold combined with induced BM-MSCs did not successfully repair large, high-load-bearing osteochondral defects of the canine femoral head. However, the experience can help improve the technique of scaffold fabrication and vascularization. PMID:24737955

  6. Biomaterials/scaffolds. Design of bioactive, multiphasic PCL/collagen type I and type II-PCL-TCP/collagen composite scaffolds for functional tissue engineering of osteochondral repair tissue by using electrospinning and FDM techniques.

    PubMed

    Schumann, Detlef; Ekaputra, Andrew K; Lam, Christopher X F; Hutmacher, Dietmar W

    2007-01-01

    Current clinical therapies for traumatic or chronic injuries involving osteochondral tissue result in temporary pain reduction and filling of the defect but with biomechanically inferior repair tissue. Tissue engineering of osteochondral repair tissue using autologous cells and bioactive biomaterials has the potential to overcome the current limitations and results in native-like repair tissue with good integration capabilities. For this reason, we applied two modem biomaterial design techniques, namely, electrospinning and fused deposition modeling (FDM), to produce bioactive poly(epsilon-caprolactone)/collagen (PCL/Col) type I and type II-PCL-tri-calcium phosphate (TCP)/Col composites for precursor cell-based osteochondral repair. The application of these two design techniques (electrospinning and FDM) allowed us to specifically produce the a suitable three-dimensional (3D) environment for the cells to grow into a particular tissue (cartilage and bone) in vitro prior to in vivo implantation. We hypothesize that our new designed biomaterials, seeded with autologous bone marrow-derived precursor cells, in combination with bioreactor-stimulated cell-culture techniques can be used to produce clinically relevant osteochondral repair tissue. PMID:18085205

  7. Controlled Release Strategies for Bone, Cartilage, and Osteochondral Engineering—Part II: Challenges on the Evolution from Single to Multiple Bioactive Factor Delivery

    PubMed Central

    Santo, Vítor E.; Mano, Joăo F.; Reis, Rui L.

    2013-01-01

    The development of controlled release systems for the regeneration of bone, cartilage, and osteochondral interface is one of the hot topics in the field of tissue engineering and regenerative medicine. However, the majority of the developed systems consider only the release of a single growth factor, which is a limiting step for the success of the therapy. More recent studies have been focused on the design and tailoring of appropriate combinations of bioactive factors to match the desired goals regarding tissue regeneration. In fact, considering the complexity of extracellular matrix and the diversity of growth factors and cytokines involved in each biological response, it is expected that an appropriate combination of bioactive factors could lead to more successful outcomes in tissue regeneration. In this review, the evolution on the development of dual and multiple bioactive factor release systems for bone, cartilage, and osteochondral interface is overviewed, specifically the relevance of parameters such as dosage and spatiotemporal distribution of bioactive factors. A comprehensive collection of studies focused on the delivery of bioactive factors is also presented while highlighting the increasing impact of platelet-rich plasma as an autologous source of multiple growth factors. PMID:23249320

  8. Controlled Release Strategies for Bone, Cartilage, and Osteochondral Engineering—Part I: Recapitulation of Native Tissue Healing and Variables for the Design of Delivery Systems

    PubMed Central

    Santo, Vítor E.; Mano, Joăo F.; Reis, Rui L.

    2013-01-01

    The potential of growth factors to stimulate tissue healing through the enhancement of cell proliferation, migration, and differentiation is undeniable. However, critical parameters on the design of adequate carriers, such as uncontrolled spatiotemporal presence of bioactive factors, inadequate release profiles, and supraphysiological dosages of growth factors, have impaired the translation of these systems onto clinical practice. This review describes the healing cascades for bone, cartilage, and osteochondral interface, highlighting the role of specific growth factors for triggering the reactions leading to tissue regeneration. Critical criteria on the design of carriers for controlled release of bioactive factors are also reported, focusing on the need to provide a spatiotemporal control over the delivery and presentation of these molecules. PMID:23268651

  9. Intra-articular administration of hyaluronic acid increases the volume of the hyaline cartilage regenerated in a large osteochondral defect by implantation of a double-network gel.

    PubMed

    Fukui, Takaaki; Kitamura, Nobuto; Kurokawa, Takayuki; Yokota, Masashi; Kondo, Eiji; Gong, Jian Ping; Yasuda, Kazunori

    2014-04-01

    Implantation of PAMPS/PDMAAm double-network (DN) gel can induce hyaline cartilage regeneration in the osteochondral defect. However, it is a problem that the volume of the regenerated cartilage tissue is gradually reduced at 12 weeks. This study investigated whether intra-articular administration of hyaluronic acid (HA) increases the volume of the cartilage regenerated with the DN gel at 12 weeks. A total of 48 rabbits were used in this study. A cylindrical osteochondral defect created in the bilateral femoral trochlea was treated with DN gel (Group DN) or left without any implantation (Group C). In both Groups, we injected 1.0 mL of HA in the left knee, and 1.0 mL of saline solution in the right knee. Quantitative histological evaluations were performed at 2, 4, and 12 weeks, and PCR analysis was performed at 2 and 4 weeks after surgery. In Group DN, the proteoglycan-rich area was significantly greater in the HA-injected knees than in the saline-injected knees at 12 weeks (P = 0.0247), and expression of type 2 collagen, aggrecan, and Sox9 mRNAs was significantly greater in the HA-injected knees than in the saline-injected knees at 2 weeks (P = 0.0475, P = 0.0257, P = 0.0222, respectively). The intra-articular administration of HA significantly enhanced these gene expression at 2 weeks and significantly increased the volume of the hyaline cartilage regenerated by implantation of a DN gel at 12 weeks. This information is important to develop an additional method to increase the volume of the hyaline cartilage tissue in a potential cartilage regeneration strategy using the DN gel. PMID:24394983

  10. Osteochondritis Dissecans (OCD)

    MedlinePLUS

    ... in sports. It affects athletes, especially gymnasts and baseball players. The adult form occurs in mature bone, ... sports with repetitive motions, such as pitching in baseball. Adults are more likely to need surgery and ...

  11. Evaluation of Early Osteochondral Defect Repair in a Rabbit Model Utilizing Fourier Transform–Infrared Imaging Spectroscopy, Magnetic Resonance Imaging, and Quantitative T2 Mapping

    PubMed Central

    Kim, Minwook; Foo, Li F.; Uggen, Christopher; Lyman, Steven; Ryaby, James T.; Moynihan, Daniel P.; Grande, Daniel Anthony; Potter, Hollis G.

    2010-01-01

    Context Evaluation of the morphology and matrix composition of repair cartilage is a critical step toward understanding the natural history of cartilage repair and efficacy of potential therapeutics. In the current study, short-term articular cartilage repair (3 and 6 weeks) was evaluated in a rabbit osteochondral defect model treated with thrombin peptide (TP-508) using magnetic resonance imaging (MRI), quantitative T2 mapping, and Fourier transform–infrared imaging spectroscopy (FT-IRIS). Methods Three-mm-diameter osteochondral defects were made in the rabbit trochlear groove and filled with either TP-508 plus poly-lactoglycolidic acid microspheres or poly-lactoglycolidic acid microspheres alone (placebo). Repair tissue and adjacent normal cartilage were evaluated at 3 and 6 weeks postdefect creation. Intact knees were evaluated by magnetic resonance imaging for repair morphology, and with quantitative T2 mapping to assess collagen orientation. Histological sections were evaluated by FT-IRIS for parameters that reflect collagen quantity and quality, as well as proteoglycan (PG) content. Results and Conclusion There was no significant difference in volume of repair tissue at either time point. At 6 weeks, placebo repair tissue demonstrated longer T2 values (p?

  12. Platelet-rich plasma increases transforming growth factor-beta1 expression at graft-host interface following autologous osteochondral transplantation in a rabbit model

    PubMed Central

    Boakye, Lorraine A; Ross, Keir A; Pinski, John M; Smyth, Niall A; Haleem, Amgad M; Hannon, Charles P; Fortier, Lisa A; Kennedy, John G

    2015-01-01

    AIM: To explore the effect of platelet-rich plasma on protein expression patterns of transforming growth factor-beta1 (TGF-?1) in cartilage following autologous osteochondral transplantation (AOT) in a rabbit knee cartilage defect model. METHODS: Twelve New Zealand white rabbits received bilateral AOT. In each rabbit, one knee was randomized to receive an autologous platelet rich plasma (PRP) injection and the contralateral knee received saline injection. Rabbits were euthanized at 3, 6 and 12 wk post-operatively. Articular cartilage sections were stained with TGF-?1 antibody. Histological regions of interest (ROI) (left, right and center of the autologous grafts interfaces) were evaluated using MetaMorph. Percentage of chondrocytes positive for TGF-?1 was then assessed. RESULTS: Percentage of chondrocytes positive for TGF-?1 was higher in PRP treated knees for selected ROIs (left; P = 0.03, center; P = 0.05) compared to control and was also higher in the PRP group at each post-operative time point (P = 6.6 × 10-4, 3.1 × 10-4 and 7.3 × 10-3 for 3, 6 and 12 wk, respectively). TGF-?1 expression was higher in chondrocytes of PRP-treated knees (36% ± 29% vs 15% ± 18%) (P = 1.8 × 10-6) overall for each post-operative time point and ROI. CONCLUSION: Articular cartilage of rabbits treated with AOT and PRP exhibit increased TGF-?1 expression compared to those treated with AOT and saline. Our findings suggest that adjunctive PRP may increase TGF-?1 expression, which may play a role in the chondrogenic effect of PRP in vivo. PMID:26716092

  13. Repair of an osteochondral defect by sustained delivery of BMP-2 or TGF?1 from a bilayered alginate-PLGA scaffold.

    PubMed

    Reyes, R; Delgado, A; Sánchez, E; Fernández, A; Hernández, A; Evora, C

    2014-07-01

    Regeneration of cartilage defects can be accelerated by localized delivery of appropriate growth factors (GFs) from scaffolds. In the present study we analysed the in vitro and in vivo release rates and delivery efficacies of transforming growth factor-?1 (TGF?1) and bone morphogenetic protein-2 (BMP-2) from a bilayered system, applied for osteochondral defect repair in a rabbit model. A bone-orientated, porous PLGA cylinder was overlaid with GF containing PLGA microspheres, dispersed in an alginate matrix. Four microsphere formulations were incorporated: (a) blank ones; (b) microspheres containing 50 ng TGF?1; (c) microspheres containing 2.5 µg BMP-2; and (d) microspheres containing 5 µg BMP-2. Release kinetics and tissue distributions were determined using iodinated ((125) I) GFs. Bioactivity of in vitro released BMP-2 and TGF?1 was confirmed in cell-based assays. In vivo release profiles indicated good GF release control. 20% of BMP-2 and 15% of TGF?1 were released during the first day. Virtually the total dose was delivered at the end of week 6. Significant histological differences were observed between untreated and GF-treated specimens, there being especially relevant short-term outcomes with 50 ng TGF?1 and 5 µg BMP-2. Although the evaluation scores for the newly formed cartilage did not differ significantly, 5 µg BMP-2 gave rise to higher quality cartilage with improved surface regularity, tissue integration and increased collagen-type II and aggrecan immunoreactivity 2 weeks post-implantation. Hence, the bilayered system controlled GF release rates and led to preserved cartilage integrity from 12 weeks up to at least 24 weeks. PMID:22733683

  14. Improved quality of cartilage repair by bone marrow mesenchymal stem cells for treatment of an osteochondral defect in a cynomolgus macaque model

    PubMed Central

    Araki, Susumu; Imai, Shinji; Ishigaki, Hirohito; Mimura, Tomohiro; Nishizawa, Kazuya; Ueba, Hiroaki; Kumagai, Kousuke; Kubo, Mitsuhiko; Mori, Kanji; Ogasawara, Kazumasa; Matsusue, Yoshitaka

    2015-01-01

    Background and purpose Integration of repaired cartilage with surrounding native cartilage is a major challenge for successful tissue-engineering strategies of cartilage repair. We investigated whether incorporation of mesenchymal stem cells (MSCs) into the collagen scaffold improves integration and repair of cartilage defects in a cynomolgus macaque model. Methods Cynomolgus macaque bone marrow-derived MSCs were isolated and incorporated into type-I collagen gel. Full-thickness osteochondral defects (3 mm in diameter, 5 mm in depth) were created in the patellar groove of 36 knees of 18 macaques and were either left untreated (null group, n = 12), had collagen gel alone inserted (gel group, n = 12), or had collagen gel incorporating MSCs inserted (MSC group, n = 12). After 6, 12, and 24 weeks, the cartilage integration and tissue response were evaluated macroscopically and histologically (4 null, 4 gel, and 4 MSC knees at each time point). Results The gel group showed most cartilage-rich reparative tissue covering the defect, owing to formation of excessive cartilage extruding though the insufficient subchondral bone. Despite the fact that a lower amount of new cartilage was produced, the MSC group had better-quality cartilage with regular surface, seamless integration with neighboring naďve cartilage, and reconstruction of trabecular subchondral bone. Interpretation Even with intensive investigation, MSC-based cell therapy has not yet been established in experimental cartilage repair. Our model using cynomolgus macaques had optimized conditions, and the method using MSCs is superior to other experimental settings, allowing the possibility that the procedure might be introduced to future clinical practice. PMID:25175660

  15. Influence of the gel thickness on in vivo hyaline cartilage regeneration induced by double-network gel implanted at the bottom of a large osteochondral defect: Short-term results

    PubMed Central

    2013-01-01

    Background A double-network (DN) gel, which is composed of poly(2-acrylamido-2-methylpropanesulfonic acid) and poly(N,N’-dimethyl acrylamide), can induce hyaline cartilage regeneration in vivo in a large osteochondral defect. The purpose of this study was to clarify the influence of the thickness of the implanted DN gel on the induction ability of hyaline cartilage regeneration. Methods Thirty-eight mature rabbits were used in this study. We created an osteochondral defect having a diameter of 4.3-mm in the patellofemoral joint. The knees were randomly divided into 4 groups (Group I: 0.5-mm thick gel, Group II: 1.0-mm thick gel, Group III: 5.0-mm thick gel, and Group IV: untreated control). Animals in each group were further divided into 3 sub-groups depending on the gel implant position (2.0-, 3.0-, or 4.0-mm depth from the articular surface) in the defect. The regenerated tissues were evaluated with the Wayne’s gross and histological grading scales and real time PCR analysis of the cartilage marker genes at 4 weeks. Results According to the total Wayne’s score, when the depth of the final vacant space was set at 2.0 mm, the scores in Groups I, II, and III were significantly greater than that Group IV (p?

  16. Continuous multilayered composite hydrogel as osteochondral substitute.

    PubMed

    Leone, G; Volpato, M D; Nelli, N; Lamponi, S; Boanini, E; Bigi, A; Magnani, A

    2015-08-01

    Cartilage is a highly organized avascular soft tissue that assembles from nano-to macro-scale to produce a complex structural network. To mimic cartilage tissue, we developed a stable multilayered composite material, characterized by a tailored gradient of mechanical properties. The optimized procedure implies chemical crosslinking of each layer directly onto the previous one and ensures a drastic reduction of the material discontinuities and brittleness. The multilayered composite was characterized by infrared spectroscopy, differential scanning calorimetry, thermogravimetry, and scanning electron microscopy in order to compare its physico-chemical characteristics with those of cartilage tissue. The rheological behavior of the multilayered composite was similar to that of human cartilage. Finally its cytocompatibility toward chondrocytes and osteoblasts was evaluated. PMID:25504681

  17. Osteochondral Interface Tissue Engineering using Macroscopic Gradients of Physicochemical Signals

    E-print Network

    Dormer, Nathan Henry

    2011-04-25

    The field of tissue engineering has continually been described as "cells, signals, and scaffolds." The current thesis work describes the evaluation of a continuously-graded microsphere-based scaffold technology for the ...

  18. Joint mice in the fetlock joint--osteochondritis dissecans.

    PubMed

    Sřnnichsen, H V; Kristoffersen, J; Falk-Rřnne, J

    1982-11-01

    Joint mice in the horse is a wellknown condition, but during the last years diagnosed with increasing frequency. Ethiology and prognosis thus become of major interest. 53 cases of mice in the fetlock are examined and divided in 3 groups on the basis of localization and appearance. On one group characterised by a localization in the plantar aspect of the joint and clearly separated from the tuberosites of the first phalanx histological investigations were carried out resulting in the statement that the mice can be the result of osteochondrosis. Surgical intervention in cases with clinical symptoms offers a fairly good prognosis, but it is underlined that the osteochondrotic defect can be restored by filling fibrocartilage. PMID:7177803

  19. Cartilage defect repair by osteochondral allografts : role of tissue surfaces and interfaces

    E-print Network

    Pallante, Andrea L.

    2012-01-01

    remodeling capacity to sustain cartilage structure, matrixstructure may help to elucidate mechanisms of subchondral bone remodeling,structure were used to categorize and differentiate allografts with different pathological states of bone remodeling.

  20. Experimentally induced cartilaginous fractures (osteochondritis dissecans) in foals fed low-copper diets.

    PubMed

    Bridges, C H; Harris, E D

    1988-07-15

    Four Thoroughbred foals were weaned from their dams when they were 1 day old and were fed a liquid milk-replacer diet containing approximately 1.7 micrograms of copper/g from plastic buckets for 4 to 7 months. They were kept in stalls with fiberglass walls and asphalt floors covered with rubber pads. Serum copper and zinc concentrations were determined 3 times/week by atomic absorption spectrophotometry, and liver copper and zinc concentrations were determined similarly after acid digestion of tissues taken at necropsy. The amount of soluble collagen in articular cartilage and aortic tissue was determined after necropsy. Clinical signs of illness, particularly evidence of lameness, were monitored daily. The foals were weighed weekly, and growth rate was monitored by measurement of height at the withers. Packed cell volumes and total and differential WBC counts were measured each time blood was drawn for copper and zinc concentration determinations. The foals were examined by necropsy at the end of the experiment, and the tissues were examined histologically. The foals developed intermittent, but nondebilitating, diarrhea with the onset of low serum copper concentrations. Considering the totally liquid diet, the foals grew well. Serum copper concentrations decreased to less than 0.1 micrograms/ml in 13 to 16 weeks. Lameness was evident 2 to 6 weeks after serum copper concentrations decreased to their lowest value (less than 0.1 micrograms/ml). All foals developed stilted gaits and ultimately walked on the front of their hooves. Major hematologic changes and alterations of hair color were not evident. Soluble collagen of articular cartilage and aortic tissue increased from 340 to 600% greater than that of control foals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3403350

  1. Decellularized Cartilage May Be a Chondroinductive Material for Osteochondral Tissue Engineering

    E-print Network

    Sutherland, Amanda J.; Beck, Emily C.; Detamore, Michael S.; Dennis, S. Connor; Converse, Gabriel L.; Hopkins, Richard A.; Berkland, Cory

    2015-05-12

    . Evaluation of an extracellular matrix-derived acellular biphasic scaffold/cell construct in the repair of a large articular high-load-bearing osteochon- dral defect in a canine model. Chinese medical journal. 2011; 124(23):3930–8. PMID: 22340321 20. Garrigues... NW, Little D, Sanchez-Adams J, Ruch DS, Guilak F. Electrospun cartilage-derived matrix scaffolds for cartilage tissue engineering. Journal of Biomedical Materials Research Part A. 2014; 102 (11):3998–4008. doi: 10.1002/jbm.a.35068 PMID: 24375991 21...

  2. Osteochondral Tissue Engineering for the TMJ Condyle Using a Novel Gradient Scaffold

    E-print Network

    Singh, Milind

    2008-10-22

    and built that allowed controlled positioning of the microspheres along the axis of the cylindrical molds. In Chapter 7, an attempt was made to mimic the mechanical properties of the interfacial region. Using microspheres encapsulating nano-phase filler... materials (i.e., nano-phase CaCO 3 or TiO 2 ), initial steps were taken toward the development of stiffness gradient scaffolds that may allow functional regeneration of interfacial tissues, in general. In Chapter 8, a novel cytocompatible technique...

  3. Decellularized Cartilage May Be a Chondroinductive Material for Osteochondral Tissue Engineering

    PubMed Central

    Sutherland, Amanda J.; Beck, Emily C.; Dennis, S. Connor; Converse, Gabriel L.; Hopkins, Richard A.; Berkland, Cory J.; Detamore, Michael S.

    2015-01-01

    Extracellular matrix (ECM)-based materials are attractive for regenerative medicine in their ability to potentially aid in stem cell recruitment, infiltration, and differentiation without added biological factors. In musculoskeletal tissue engineering, demineralized bone matrix is widely used, but recently cartilage matrix has been attracting attention as a potentially chondroinductive material. The aim of this study was thus to establish a chemical decellularization method for use with articular cartilage to quantify removal of cells and analyze the cartilage biochemical content at various stages during the decellularization process, which included a physically devitalization step. To study the cellular response to the cartilage matrix, rat bone marrow-derived mesenchymal stem cells (rBMSCs) were cultured in cell pellets containing cells only (control), chondrogenic differentiation medium (TGF-?), chemically decellularized cartilage particles (DCC), or physically devitalized cartilage particles (DVC). The chemical decellularization process removed the vast majority of DNA and about half of the glycosaminoglycans (GAG) within the matrix, but had no significant effect on the amount of hydroxyproline. Most notably, the DCC group significantly outperformed TGF-? in chondroinduction of rBMSCs, with collagen II gene expression an order of magnitude or more higher. While DVC did not exhibit a chondrogenic response to the extent that DCC did, DVC had a greater down regulation of collagen I, collagen X and Runx2. A new protocol has been introduced for cartilage devitalization and decellularization in the current study, with evidence of chondroinductivity. Such bioactivity along with providing the ‘raw material’ building blocks of regenerating cartilage may suggest a promising role for DCC in biomaterials that rely on recruiting endogenous cell recruitment and differentiation for cartilage regeneration. PMID:25965981

  4. Correction of infraorbital and malar deficiency using costal osteochondral graft along with orthognathic surgery in Crouzon syndrome.

    PubMed

    Song, Hyunsuk; Park, Myong Chul; Lee, Il Jae; Park, Dong Ha

    2014-09-01

    In syndromic craniosynostosis, such as Crouzon syndrome, midfacial hypoplasia can cause exophthalmos and concave facial profile. Though midfacial hypoplasia in Crouzon syndrome patients can be treated with midface advancement, known as a Le Fort II or Le Fort III osteotomy, such method can change nasal appearance and frequently fails to achieve class I occlusion after surgery. This report presents a case of an aesthetically and functionally successful midfacial augmentation using rib and cartilage graft along with orthognathic surgery (Le fort I and bilateral sagittal split ramus osteotomy) for patients with Crouzon syndrome. The patient was a 21-year-old male with Crouzon syndrome, who had undergone augmentation rhinoplasty 2 years ago. His main issues were midfacial retrusion and mild anterior open bite and cross bite and, furthermore, did not want any change in his nasal appearance. To augment midfacial volume, rib bone graft was inserted on the inferior orbital rim and costal cartilage graft was done on the zygomatic area. The costal osteocartilage was fixed with titanium screws. Additionally, Le Fort I osteotomy and bilateral sagittal split ramus osteotomy were done to treat the anterior open bite and cross bite. The maxillary segment was advanced 2 mm and posteriorly impacted 2.5 mm. Then, 5 mm of mandibular setback was done and the maxillomandibular segment was rotated clockwise. Finally, genioplasty with 5-mm advancement was done to compensate for the chin retrusion after performing the mandibular setback. The operation took 425 minutes and estimated blood loss was 500 mL. After 6 months since surgery, the patient had convex facial profile and class I occlusion. For the patient with mild midface hypoplasia, good nasal profile, and malocclusion, rib bone graft along with Le Fort I and bilateral sagittal ramus osteotomy can be a good surgical modality. PMID:25153066

  5. A novel osteochondral composite consisting of a self-assembling peptide hydrogel and 3D printed polycaprolactone scaffold : potential for articular cartilage repair

    E-print Network

    Saatchi, Sanaz, 1980-

    2004-01-01

    Degenerative diseases, such as osteoarthritis, and traumatic injuries are both prominent causes of cartilage defects. Due to its avascular nature, adult human cartilage displays limited capacity for regeneration. Current ...

  6. Osteochondral tissue engineering using a biphasic collagen/GAG scaffold containing rhFGF18 or BMP7 in an ovine model

    E-print Network

    Getgood, Alan; Henson, Frances; Skelton, Carrie; Brooks, Roger; Guehring, Hans; Fortier, Lisa A.; Rushton, Neil

    2014-09-26

    statistically significant improvement in the modified O’Driscoll score was observed in the rhFGF18 treated group (mean 16.83, 95% CI 13.65-20.61) compared to the empty defects (mean 9, 95% CI 4.88-13.12) (p?=?0.039) in the MFC. Excellent tissue fill, lateral...

  7. Overview of cartilage biology and new trends in cartilage stimulation.

    PubMed

    Triche, Rachel; Mandelbaum, Bert R

    2013-03-01

    This article reviews the basics of articular cartilage biology, which provide a necessary foundation for understanding the evolving field of articular cartilage injury and repair. The currently popular treatment options for osteochondral injury (microfracture, osteochondral autograft transfer system, osteochondral allograft, autologous chondrocyte implantation, and the use of scaffolds with autologous chondrocyte implantation) document the significant advances made in this area in the past 2 decades. Integration of newly available information and technology derived from advances in molecular biology and tissue engineering holds even greater promise for continued advances in optimal management of this challenging problem. PMID:23465945

  8. Chondrocyte death in injured articular cartilage – in vitro evaluation of chondroprotective strategies using confocal laser scanning microscopy 

    E-print Network

    Amin, Anish Kiritkumar

    2011-07-05

    A reproducible in vitro model of mechanically injured (scalpel cut) articular cartilage was developed in this work utilising bovine and human osteochondral tissue. Using fluorescence-mode confocal laser scanning microscopy ...

  9. Success Rates and Immunologic Responses of Autogenic, Allogenic, and Xenogenic Treatments

    E-print Network

    Athanasiou, Kyriacos

    , including osteochondral plug transplantation, chondrocyte implantation, and microfracture, are the most allogenic chondrocytes exhibit a tolerable immunogenic response. Additionally, these repair techniques, controversy and uncertainty remain with respect to the best available treatment option. Organ transplantation

  10. Chondral fracture of the lateral femoral condyle in children with different treatment methods.

    PubMed

    Song, Kwang Soon; Min, Byung Woo; Bae, Ki Cheor; Cho, Chul Hyun; Lee, Si Wook

    2016-01-01

    Adolescents are predisposed to chondral injuries of the knee; however, the incidence of traumatic chondral and osteochondral fractures and their role in the development of joint degeneration are not fully elucidated. Several methods are described for the treatment of chondral or osteochondral fractures of the knee. In our literature review, we could not find any report on the management of chondral fractures with autologous bone pegs or headless screws. We report three cases of traumatic cartilage fractures of the lateral femoral condyle in adolescents who were treated with three different methods. We also present their follow-up outcomes. PMID:26439672

  11. Arthroscopic Distal Clavicular Autograft for Treating Shoulder Instability With Glenoid Bone Loss

    PubMed Central

    Tokish, John M.; Fitzpatrick, Kelly; Cook, Jay B.; Mallon, William J.

    2014-01-01

    Glenoid bone loss is a significant risk factor for failure after arthroscopic shoulder stabilization. Multiple options are available to reconstruct this bone loss, including coracoid transfer, iliac crest bone graft, and osteoarticular allograft. Each technique has strengths and weaknesses. Coracoid grafts are limited to anterior augmentation and, along with iliac crest, do not provide an osteochondral reconstruction. Osteochondral allografts do provide a cartilage source but are challenged by the potential for graft rejection, infection, cost, and availability. We describe the use of a distal clavicular osteochondral autograft for bony augmentation in cases of glenohumeral instability with significant bone loss. This graft has the advantages of being readily available and cost-effective, it provides an autologous osteochondral transplant with minimal donor-site morbidity, and it can be used in both anterior and posterior bone loss cases. The rationale and technical aspects of arthroscopic performance will be discussed. Clinical studies are warranted to determine the outcomes of the use of the distal clavicle as a graft in shoulder instability. PMID:25264509

  12. 2 1 Regenerative surgery (MeMo) fective site. Considering the fact that tissue engineering can be regarded as the

    E-print Network

    Bielefeld, Universität

    plastic), the transplantation of autologous osteochondral cylinders (OCT), and eventually the replacement loading in the transplantation site. From the medical point of view it is crucial to provide implantable all with an appropriate stress-strain behaviour that can tolerate expected in vivo loads. To avoid

  13. Clinics in diagnostic imaging (163). Transient lateral patellar dislocation with trochlear dysplasia

    PubMed Central

    Zhang, Junwei; Lee, Chin Hwee

    2015-01-01

    A 14-year-old girl presented with left knee pain and swelling after an injury. Magnetic resonance (MR) imaging showed a transient lateral patellar dislocation with patellar osteochondral fracture, medial patellofemoral ligament tear and underlying femoral trochlear dysplasia. Open reduction and internal fixation of the osteochondral fracture, plication of the medial patellar retinaculum and lateral release were performed. As lateral patellar dislocation is often clinically unsuspected, an understanding of its characteristic imaging features is important in making the diagnosis. Knowledge of the various predisposing factors for patellar instability may also influence the choice of surgical management. We also discuss signs of acute injury and chronic instability observed on MR imaging, and the imaging features of anatomical variants that predispose an individual to lateral patellar dislocation. Treatment options and postsurgical imaging appearances are also briefly described. PMID:26512145

  14. The pediatric knee: current concepts in sports medicine.

    PubMed

    Beck, Nicholas A; Patel, Neeraj M; Ganley, Theodore J

    2014-01-01

    As the popularity and intensity of children's athletics have increased, so has the risk for knee injuries. Fractures of the tibial eminence may be treated operatively or nonoperatively depending on fracture classification, but arthrofibrosis is a potentially significant complication. Anterior cruciate ligament rupture presents treatment challenges as regards the optimal timing and method of reconstruction. A number of novel reconstructive techniques have been developed to minimize risks to the physes in this population. Recent studies have focused on the prognosis, surgical indications, and operative techniques for osteochondritis dissecans in children. A number of authors have also sought to better-define the optimal diagnostic testing and management of patellar dislocation. In this review, we provide an update on current concepts for tibial eminence fractures, anterior cruciate ligament injuries, osteochondritis dissecans of the knee, and patellar dislocation in young athletes. PMID:24045503

  15. Receptor tyrosine kinase inhibition causes simultaneous bone loss and excess bone formation within growing bone in rats

    SciTech Connect

    Nurmio, Mirja; Joki, Henna; Kallio, Jenny; Maeaettae, Jorma A.; Vaeaenaenen, H. Kalervo; Toppari, Jorma; Jahnukainen, Kirsi; Laitala-Leinonen, Tiina

    2011-08-01

    During postnatal skeletal growth, adaptation to mechanical loading leads to cellular activities at the growth plate. It has recently become evident that bone forming and bone resorbing cells are affected by the receptor tyrosine kinase (RTK) inhibitor imatinib mesylate (STI571, Gleevec (registered)) . Imatinib targets PDGF, ABL-related gene, c-Abl, c-Kit and c-Fms receptors, many of which have multiple functions in the bone microenvironment. We therefore studied the effects of imatinib in growing bone. Young rats were exposed to imatinib (150 mg/kg on postnatal days 5-7, or 100 mg/kg on postnatal days 5-13), and the effects of RTK inhibition on bone physiology were studied after 8 and 70 days (3-day treatment), or after 14 days (9-day treatment). X-ray imaging, computer tomography, histomorphometry, RNA analysis and immunohistochemistry were used to evaluate bone modeling and remodeling in vivo. Imatinib treatment eliminated osteoclasts from the metaphyseal osteochondral junction at 8 and 14 days. This led to a resorption arrest at the growth plate, but also increased bone apposition by osteoblasts, thus resulting in local osteopetrosis at the osteochondral junction. The impaired bone remodelation observed on day 8 remained significant until adulthood. Within the same bone, increased osteoclast activity, leading to bone loss, was observed at distal bone trabeculae on days 8 and 14. Peripheral quantitative computer tomography (pQCT) and micro-CT analysis confirmed that, at the osteochondral junction, imatinib shifted the balance from bone resorption towards bone formation, thereby altering bone modeling. At distal trabecular bone, in turn, the balance was turned towards bone resorption, leading to bone loss. - Research Highlights: > 3-Day imatinib treatment. > Causes growth plate anomalies in young rats. > Causes biomechanical changes and significant bone loss at distal trabecular bone. > Results in loss of osteoclasts at osteochondral junction.

  16. Biomaterials for Tissue Engineering

    PubMed Central

    Lee, Esther J.; Kasper, F. Kurtis; Mikos, Antonios G.

    2013-01-01

    Biomaterials serve as an integral component of tissue engineering. They are designed to provide architectural framework reminiscent of native extracellular matrix in order to encourage cell growth and eventual tissue regeneration. Bone and cartilage represent two distinct tissues with varying compositional and mechanical properties. Despite these differences, both meet at the osteochondral interface. This article presents an overview of current biomaterials employed in bone and cartilage applications, discusses some design considerations, and alludes to future prospects within this field of research. PMID:23820768

  17. CARTILAGE-ON-CARTILAGE VS. METAL-ON-CARTILAGE IMPACT CHARACTERISTICS AND RESPONSES

    PubMed Central

    Heiner, Anneliese D.; Smith, Abigail D.; Goetz, Jessica E.; Goreham-Voss, Curtis M.; Judd, Kyle T.; McKinley, Todd O.; Martin, James A.

    2013-01-01

    A common in vitro model for studying acute mechanical damage in cartilage is to impact an isolated osteochondral or cartilage specimen with a metallic impactor. The mechanics of a cartilage-on-cartilage (COC) impact, as encountered in vivo, are likely different than those of a metal-on-cartilage (MOC) impact. The hypothesis of this study was that impacted in vitro COC and MOC specimens would differ in their impact behavior, mechanical properties, chondrocyte viability, cell metabolism, and histologic structural damage. Osteochondral specimens were impacted with either an osteochondral plug or a metallic cylinder at the same delivered impact energy per unit area, and processed after 14 days in culture. The COC impacts resulted in about half of the impact maximum stress and a quarter of the impact maximum stress rate of change, as compared to the MOC impacts. The impacted COC specimens had smaller changes in mechanical properties, smaller decreases in chondrocyte viability, higher total proteoglycan content, and less histologic structural damage, as compared to the impacted MOC specimens. If metal-on-cartilage impact conditions are to be used for modeling of articular injuries and post-traumatic osteoarthritis, the differences between COC and MOC impacts must be kept in mind. PMID:23335281

  18. Up-to-date Review and Cases Report on Chondral Defects of Knee Treated by ACI Technique: Clinical-instrumental and Histological Results.

    PubMed

    Dell'Osso, Giacomo; Ghilardi, Marco; Bottai, Vanna; Bugelli, Giulia; Guido, Giulio; Giannotti, Stefano

    2015-05-01

    The limited regenerative potential of a full thickness defect of the knee joint cartilage has certainly conditioned the development of therapeutic strategies that take into account all the aspects of the healing process. The most common treatments to repair chondral and osteochondral lesions are bone marrow stimulation, osteochondral autograft transplantation, autologous matrix-induced chondrogenesis, and autologous chondrocyte implantation. We like to emphasize the difference between a chondral and an osteochondral lesion because the difference is sometimes lost in the literature. In the context of treatment of injuries of the knee joint cartilage, the second-generation autologous chondrocyte transplant is a consolidated surgical method alternative to other techniques. Our experience with the transplantation of chondrocytes has had exceptional clinical results. We report 2 complete cases of a group of 22 in knee and ankle. These 2 cases had histological and instrumental evaluation. We cannot express conclusions, but can only make considerations, stating that, with the clinical functional result being equal, we obtained an excellent macroscopic result in both cases of second look. Autologous chondrocyte implantation (ACI) is a multiple surgical procedure with expensive chondrocyte culture, but even with this limitation, we think that it must be the choice in treating chondral lesions, especially in young patients. PMID:26055026

  19. One-step bone marrow-derived cell transplantation in talarosteochondral lesions: mid-term results

    PubMed Central

    BUDA, ROBERTO; VANNINI, FRANCESCA; CAVALLO, MARCO; BALDASSARRI, MATTEO; NATALI, SIMONE; CASTAGNINI, FRANCESCO; GIANNINI, SANDRO

    2013-01-01

    Purpose to verify the capability of scaffold-supported bone marrow-derived cells to be used in the repair of osteochondral lesions of the talus. Methods using a device to concentrate bone marrow-derived cells, a scaffold (collagen powder or hyaluronic acid membrane) for cell support and platelet gel, a one-step arthroscopic technique was developed for cartilage repair. In a prospective clinical study, we investigated the ability of this technique to repair talar osteochondral lesions in 64 patients. The mean follow-up was 53 months. Clinical results were evaluated using the American Orthopaedic Foot and Ankle Society (AOFAS) scale score. We also considered the influence of scaffold type, lesion area, previous surgery, and lesion depth. Results the mean preoperative AOFAS scale score was 65.2 ± 13.9. The clinical results peaked at 24 months, before declining gradually to settle at a score of around 80 at the maximum follow-up of 72 months. Conclusions the use of bone marrow-derived cells supported by scaffolds to repair osteochondral lesions of the talus resulted in significant clinical improvement, which was maintained over time. Level of Evidence level IV, therapeutic case series. PMID:25606518

  20. Diagnostic accuracy of ultrasound for assessment of hemophilic arthropathy: MRI correlation.

    PubMed

    Doria, Andrea S; Keshava, Shyamkumar N; Mohanta, Arun; Jarrin, Jose; Blanchette, Victor; Srivastava, Alok; Moineddin, Rahim; Kavitha, M L; Hilliard, Pamela; Poonnoose, Pradeep; Gibikote, Sridhar

    2015-03-01

    OBJECTIVE. The purpose of this article is to assess the reliability of interpretation of ultrasound findings according to data blinding in maturing hemophilic joints and to determine the diagnostic accuracy of ultrasound compared with MRI for assessing joint components. SUBJECTS AND METHODS. Ankles (n = 34) or knees (n = 25) of boys with hemophilia or von Willebrand disease (median age, 13 years; range, 5-17 years) were imaged by ultrasound, MRI, and radiography in two centers (Toronto, Canada, and Vellore, India). Ultrasound scans were performed by two operators (one blinded and one unblinded to MRI data) and were reviewed by four reviewers who were unblinded to corresponding MRI findings according to a proposed 0- to 14-item scale that matches 14 of 17 items of the corresponding MRI scale. MRI examinations were independently reviewed by two readers. RESULTS. When data were acquired by radiologists, ultrasound was highly reliable for assessing soft-tissue changes (intraclass correlation coefficient [ICC], 0.98 for ankles and 0.97 for knees) and substantially to highly reliable for assessing osteochondral changes (ICC, 0.61 for ankles and 0.89 for knees). Ultrasound was highly sensitive (> 92%) for assessing synovial hypertrophy and hemosiderin in both ankles and knees but had borderline sensitivity for detecting small amounts of fluid in ankles (70%) in contrast to knees (93%) and variable sensitivity for evaluating osteochondral abnormalities (sensitivity range, 86-100% for ankles and 12-100% for knees). CONCLUSION. If it is performed by experienced radiologists using a standardized protocol, ultrasound is highly reliable for assessing soft-tissue abnormalities of ankles and knees and substantially to highly reliable for assessing osteochondral changes in these joints. PMID:25714320

  1. Impaction fracture of the medial femoral condyle.

    PubMed

    Mabry, Lance M; Ross, Michael D; Abbott, Jessica L

    2013-01-01

    The patient was a 20-year-old man who sustained a noncontact left knee hyperextension injury while playing soccer. In reviewing left knee radiographs that had previously been interpreted as normal, the physical therapist noted an abnormally deep depression of the medial condylopatellar sulcus, which was concerning for a possible impacted osteochondral fracture. After discussing the radiographic findings with a radiologist, the physical therapist ordered magnetic resonance imaging, which revealed a focal indentation of the anterior portion of the medial femoral condyle with adjacent bone marrow edema that was consistent with an impaction fracture of the medial femoral condyle. PMID:23812292

  2. Extra-articular Synovial Chondromatosis Eroding and Penetrating the Acromion

    PubMed Central

    El Rassi, George; Matta, Jihad; Hijjawi, Ayman; Khair, Ousama Abou; Fahs, Sara

    2015-01-01

    Synovial chondromatosis of the shoulder is an uncommon disorder. It usually affects the glenohumeral joint and is characterized by metaplasia of the synovium leading to the formation of osteochondral loose bodies. Few cases of extra-articular subacromial synovial chondromatosis involving the rotator cuff tendon have been reported in the literature. The treatment of previously reported cases consisted of open bursectomy and removal of loose bodies. We report a case of subacromial synovial chondromatosis without rotator cuff involvement but with severe erosion and fracture of the acromion. Treatment consisted of shoulder arthroscopy to remove all loose bodies, total bursectomy, and debridement of the acromion. Potential benefits of arthroscopy were also evaluated.

  3. Cartilage Repair With or Without Meniscal Transplantation and Osteotomy for Lateral Compartment Chondral Defects of the Knee

    PubMed Central

    Harris, Joshua D.; Hussey, Kristen; Saltzman, Bryan M.; McCormick, Frank M.; Wilson, Hillary; Abrams, Geoffrey D.; Cole, Brian J.

    2014-01-01

    Background: Treatment decision making for chondral defects in the knee is multifactorial. Articular cartilage pathology, malalignment, and meniscal deficiency must all be addressed to optimize surgical outcomes. Purpose: To determine whether significant clinical improvements in validated clinical outcome scores are observed at minimum 2-year follow-up after articular cartilage repair of focal articular cartilage defects of the lateral compartment of the knee with or without concurrent distal femoral osteotomy and lateral meniscus transplant. Study Design: Case series; Level of evidence, 4. Methods: Symptomatic adults who underwent surgical treatment (microfracture, autologous chondrocyte implantation [ACI], osteochondral autograft or allograft) of full-thickness lateral compartment chondral defects of the knee with or without a postmeniscectomy compartment or valgus malalignment by a single surgeon with minimum 2-year follow-up were analyzed. Validated patient-reported and surgeon-measured outcomes were collected pre- and postsurgery. Pre- and postoperative outcomes were compared via Student t tests. Results: Thirty-five subjects (mean age, 29.6 ± 10.5 years) were analyzed. Patients had been symptomatic for 2.51 ± 3.52 years prior to surgery and had undergone 2.11 ± 1.18 surgeries prior to study enrollment, with a mean duration of follow-up of 3.65 ± 1.71 years. The mean defect size was 4.42 ± 2.06 cm2. Surgeries included ACI (n = 18), osteochondral allograft (n = 14), osteochondral autograft (n = 2), and microfracture (n = 1). There were 18 subjects who underwent concomitant surgery (14 lateral meniscus transplant, 3 distal femoral osteotomy, and 1 combined). Statistically significant (P < .05) and clinically meaningful improvements were observed at final follow-up in Lysholm, subjective International Knee Documentation Committee (IKDS), Knee Injury and Osteoarthritis Outcome Score (KOOS) subscales, Short Form–12 (SF-12) scores, and patient satisfaction. At follow-up, patients undergoing isolated articular cartilage surgery had a significantly higher KOOS quality of life subscore than did those undergoing articular cartilage surgery and lateral meniscus transplant (P = .039). Otherwise, there were no significant postoperative differences between the isolated and combined surgery groups in any outcome score. Five patients underwent 6 reoperations (1 revision osteochondral allograft, 5 chondroplasties). No patient was converted to knee arthroplasty. Conclusion: In patients with lateral compartment focal chondral defects with or without lateral meniscal deficiency and valgus malalignment, surgical cartilage repair and correction of concomitant pathology can significantly improve clinical outcomes at 2-year follow-up with no significant differences between isolated and combined surgery and a low rate of complications and reoperations. PMID:26535271

  4. Magnetic Resonance Arthrography of the Wrist and Elbow.

    PubMed

    LiMarzi, Gary M; O'Dell, M Cody; Scherer, Kurt; Pettis, Christopher; Wasyliw, Christopher W; Bancroft, Laura W

    2015-08-01

    Magnetic resonance (MR) arthrography of the wrist and elbow is useful for detecting a variety of intra-articular pathologies. MR dictations should address whether intrinsic ligament tears of the wrist are partial-thickness or full-thickness, and involve the dorsal, membranous, and/or volar components of the ligaments. With regard to elbow soft tissue pathology, partial-thickness tears of the anterior band of the ulnar collateral ligament in overhead-throwing athletes are well evaluated with MR arthrography. MR arthrography also is helpful in staging osteochondritis dissecans of the capitellum, caused by repetitive valgus impaction injury in adolescent or young adult baseball pitchers. PMID:26216774

  5. Combined autologous chondrocyte implantation (ACI) with supra-condylar femoral varus osteotomy, following lateral growth-plate damage in an adolescent knee: 8-year follow-up

    PubMed Central

    2011-01-01

    We report the 8-year clinical and radiographic outcome of an adolescent patient with a large osteochondral defect of the lateral femoral condyle, and ipsilateral genu valgum secondary to an epiphyseal injury, managed with autologous chondrocyte implantation (ACI) and supracondylar re-alignment femoral osteotomy. Long-term clinical success was achieved using this method, illustrating the effective use of re-alignment osteotomy in correcting mal-alignment of the knee, protecting the ACI graft site and providing the optimum environment for cartilage repair and regeneration. This is the first report of the combined use of ACI and femoral osteotomy for such a case. PMID:21418566

  6. 3D Printing and Biofabrication for Load Bearing Tissue Engineering.

    PubMed

    Jeong, Claire G; Atala, Anthony

    2015-01-01

    Cell-based direct biofabrication and 3D bioprinting is becoming a dominant technological platform and is suggested as a new paradigm for twenty-first century tissue engineering. These techniques may be our next step in surpassing the hurdles and limitations of conventional scaffold-based tissue engineering, and may offer the industrial potential of tissue engineered products especially for load bearing tissues. Here we present a topically focused review regarding the fundamental concepts, state of the art, and perspectives of this new technology and field of biofabrication and 3D bioprinting, specifically focused on tissue engineering of load bearing tissues such as bone, cartilage, osteochondral and dental tissue engineering. PMID:26545741

  7. A new pathological classification of lumbar disc protrusion and its clinical significance.

    PubMed

    Ma, Xin-long

    2015-02-01

    Lumbar disc protrusion is common. Its clinical manifestations and treatments are closely related to the pathological changes; however, the pathological classification of lumbar disc protrusion is controversial. This article introduces a new pathological classification comprising four types of lumbar disc protrusion according to intraoperative findings. The damage-herniation type is probably caused by injury and is characterized by soft herniation, the capsule can easily be cut and the broken disc tissue blocks overflow or is easily removed. The broken disc substances should be completely removed; satisfactory results can be achieved by minimally invasive endoscopic surgery. The degeneration-protrusion type is characterized by hard and tough protrusions and the pathological process by degeneration and proliferative reaction. The nerve should be decompressed and relaxed with minimally invasive removal of the posterior wall; the bulged or protruded disc often need not be excised. The posterior vertebral osteochondrosis with disc protrusion type is characterized by deformity of the posterior vertebral body, osteochondral nodules and intervertebral disc protrusion. The herniated and fragmented disc tissue should be removed with partially protruding osteochondral nodules. Intervertebral disc cyst is of uncertain pathogenesis and is characterized by a cyst that communicates with the disc. Resection of the cyst under microscopic or endoscopic control can achieve good results; and whether the affected disc needs to be simultaneously resected is controversial. The new pathological classification proposed here is will aid better understanding of pathological changes and pathogenesis of lumbar disc protrusion and provides a reference for diagnosis and treatment. PMID:25708029

  8. Guided differentiation of bone marrow stromal cells on co-cultured cartilage and bone scaffolds.

    PubMed

    Lee, Paul; Tran, Katelyn; Zhou, Gan; Bedi, Asheesh; Shelke, Namdev B; Yu, Xiaojun; Kumbar, Sangamesh G

    2015-09-23

    Focal chondral defects that result from traumatic injuries to the knee remain one of the most common causes of disability in patients. Current solutions for healing focal cartilage defects are mainly limited by the production of inferior cartilage-like tissue and subsequent delamination due to incomplete healing of the subchondral bone. In this experiment a polymeric osteochondral implant for guiding autologous bone marrow stem cells (BMSCs) to populate the scaffold to create distinctive bone and cartilage tissue is used. The cartilage component presents bioactive aligned nanofibers containing chondroitin sulfate and hyaluronic acid while the bone component includes hydroxyapatite to promote chondrogenic and osteogenic differentiation of the rat BMSCs in vitro. The different cartilage and bone components resulted in the elevated expression of osteogenic markers such as bone sialoprotein, runt related transcription factor 2, and bone morphogenetic protein 2 in the deeper bone layer and chondrogenic markers such as collagen type II and aggrecan in the cartilage layer. Through immunofluorescence imaging, the alignment of the secreted collagen type II fibrils and aggrecan was visualized and quantified on the cartilage component of the scaffold. These current studies show that the biodegradable biphasic osteochondral implant may be effective in promoting more hyaline-like tissue to fill in chondral defects of the knee. PMID:26292727

  9. Fabrication and in vitro evaluation of an articular cartilage extracellular matrix-hydroxyapatite bilayered scaffold with low permeability for interface tissue engineering

    PubMed Central

    2014-01-01

    Background Osteochondral interface regeneration is challenging for functional and integrated cartilage repair. Various layered scaffolds have been used to reconstruct the complex interface, yet the influence of the permeability of the layered structure on cartilage defect healing remains largely unknown. Methods We designed and fabricated a novel bilayered scaffold using articular cartilage extracellular matrix (ACECM) and hydroxyapatite (HAp), involving a porous, oriented upper layer and a dense, mineralised lower layer. By optimising the HAp/ACECM ratio, differing pore sizes and porosities were obtained simultaneously in the two layers. To evaluate the effects of permeability on cell behaviour, rabbit chondrocytes were seeded. Results Morphological observations demonstrated that a gradual interfacial region was formed with pore sizes varying from 128.2?±?20.3 to 21.2?±?3.1 ?m. The permeability of the bilayered scaffold decreased with increasing compressive strain and HAp content. Mechanical tests indicated that the interface was stable to bearing compressive and shear loads. Accordingly, the optimum HAp/ACECM ratio (7 w/v%) in the layer to mimic native calcified cartilage was found. Chondrocytes could not penetrate the interface and resided only in the upper layer, where they showed high cellularity and abundant matrix deposition. Conclusions Our findings suggest that a bilayered scaffold with low permeability, rather than complete isolation, represents a promising candidate for osteochondral interface tissue engineering. PMID:24950704

  10. Engineering physiologically stiff and stratified human cartilage by fusing condensed mesenchymal stem cells.

    PubMed

    Bhumiratana, Sarindr; Vunjak-Novakovic, Gordana

    2015-08-01

    For a long time, clinically sized and mechanically functional cartilage could be engineered from young animal chondrocytes, but not from adult human mesenchymal stem cells that are of primary clinical interest. The approaches developed for primary chondrocytes were not successful when used with human mesenchymal cells. The method discussed here was designed to employ a mechanism similar to pre-cartilaginous condensation and fusion of mesenchymal stem cells at a precisely defined time. The formation of cartilage was initiated by press-molding the mesenchymal bodies onto the surface of a bone substrate. By image-guided fabrication of the bone substrate and the molds, the osteochondral constructs were engineered in anatomically precise shapes and sizes. After 5 weeks of cultivation, the cartilage layer assumed physiologically stratified histomorphology, and contained lubricin at the surface, proteoglycans and type II collagen in the bulk phase, collagen type X at the interface with the bone substrate, and collagen type I within the bone phase. For the first time, the Young's modulus and the friction coefficient of human cartilage engineered from mesenchymal stem cells reached physiological levels for adult human cartilage. We propose that this method can be effective for generating human osteochondral tissue constructs. PMID:25828645

  11. Effects of Freeze–Thaw Cycle with and without Proteolysis Inhibitors and Cryopreservant on the Biochemical and Biomechanical Properties of Articular Cartilage

    PubMed Central

    Hirviniemi, Mikko; Tiitu, Virpi; Jurvelin, Jukka S.; Töyräs, Juha; Lammi, Mikko J.

    2014-01-01

    Objective: We investigated the effects of freeze-thawing on the properties of articular cartilage. Design: The reproducibility of repeated biomechanical assay of the same osteochondral sample was first verified with 11 patellar plugs from 3 animals. Then, 4 osteochondral samples from 15 bovine patellae were divided into 4 groups. The reference samples were immersed in phosphate-buffered saline (PBS) containing proteolysis inhibitors and biomechanically tested before storage for further analyses. Samples of group 1 were biomechanically tested before and after freeze-thawing in PBS in the absence and those of group 2 in the presence of inhibitors. Samples of the group 3 were biomechanically tested in PBS-containing inhibitors, but frozen in 30% dimethyl sulfoxide/PBS and subsequently tested in PBS supplemented with the inhibitors. Glycosaminoglycan contents of the samples and immersion solutions were analyzed, and proteoglycan structures examined with SDS-agarose gel electrophoresis. Results: Freeze-thawing decreased slightly dynamic moduli in all 3 groups. The glycosaminoglycan contents and proteoglycan structures of the cartilage were similar in all experimental groups. Occasionally, the diffused proteoglycans were partly degraded in group 1. Digital densitometry revealed similar staining intensities for the glycosaminoglycans in all groups. Use of cryopreservant had no marked effect on the glycosaminoglycan loss during freeze-thawing. Conclusion: The freeze-thawed cartilage samples appear suitable for the biochemical and biomechanical studies. PMID:26069689

  12. Patella Dislocation with Vertical Axis Rotation: The “Dorsal Fin” Patella

    PubMed Central

    Gamble, David; Carrothers, Andrew D.; Khanduja, Vikas

    2015-01-01

    A 44-year-old woman presented following minor trauma to her right knee. While dancing she externally rotated around a planted foot and felt sudden pain in her right knee. She presented with her knee locked in extension with a “dorsal fin” appearance of the soft tissues tented over the patella. This was diagnosed as a rare case of an intraarticular patella dislocation, which was rotated 90 degrees about the vertical axis. Closed reduction in the emergency room was unsuccessful but was achieved in theatre under general anaesthetic with muscle relaxation. Postreduction arthroscopy demonstrated that no osteochondral or soft tissue damage to the knee had been sustained. In patients presenting with a knee locked in extension with tenting of skin over the patella (the “dorsal fin” appearance), intra-articular patella dislocation should be suspected. Attempts to reduce vertical patella dislocations under sedation with excessive force or repeatedly without success should be avoided to prevent unnecessary damage to the patellofemoral joint. In this clinical situation we recommend closed reduction under general anaesthetic followed by immediate knee arthroscopy under the same anaesthetic to ensure that there is no chondral damage to the patella or femoral trochlea and to rule out an osteochondral fracture. PMID:25883819

  13. Subchondral bone and cartilage disease: a rediscovered functional unit.

    PubMed

    Imhof, H; Sulzbacher, I; Grampp, S; Czerny, C; Youssefzadeh, S; Kainberger, F

    2000-10-01

    The role of subchondral bone in the pathogenesis of cartilage damage has likely been underestimated. Subchondral bone is not only an important shock absorber, but it may also be important for cartilage metabolism. Contrary to many drawings and published reports, the subchondral region is highly vascularized and vulnerable. Its terminal vessels have, in part, direct contact with the deepest hyaline cartilage layer. The perfusion of these vessels accounts for more than 50% of the glucose, oxygen, and water requirements of cartilage. Bony structure, local metabolism, hemodynamics, and vascularization of the subchondral region differ within a single joint and from one joint to another. Owing to these differences, repetitive, chronic overloading or perfusion abnormalities may result in no pathological reaction at all in one joint, while in another joint, these same conditions may lead to osteonecrosis, osteochondritis dissecans, or degenerative changes. According to this common etiological root, similar pathological reactions beginning with marrow edema and necrosis and followed by bone and cartilage fractures, joint deformity, and insufficient healing processes are found in osteonecrosis, osteochondritis dissecans, and degenerative disease as well. PMID:11041152

  14. Outcome of combined autologous chondrocyte implantation and anterior cruciate ligament reconstruction

    PubMed Central

    Dhinsa, Baljinder S; Nawaz, Syed Z; Gallagher, Kieran R; Skinner, John; Briggs, Tim; Bentley, George

    2015-01-01

    Background: Instability of the knee joint, after anterior cruciate ligament (ACL) injury, is contraindication to osteochondral defect repair. This prospective study is to investigate the role of combined autologous chondrocyte implantation (ACI) with ACL reconstruction. Materials and Methods: Three independent groups of patients with previous ACL injuries undergoing ACI were identified and prospectively followed up. The first group had ACI in combination with ACL reconstruction (combined group); the 2nd group consisted of individuals who had an ACI procedure having had a previously successful ACL reconstruction (ACL first group); and the third group included patients who had an ACI procedure to a clinically stable knee with documented nonreconstructed ACL disruption (No ACL group). Their outcomes were assessed using the modified cincinnati rating system, the Bentley functional (BF) rating system (BF) and a visual analog scale (VAS). Results: At a mean followup of 64.24 months for the ACL first group, 63 months for combined group and 78.33 months for the No ACL group; 60% of ACL first patients, 72.73% of combined group and 83.33% of the No ACL group felt their outcome was better following surgery. There was no significant difference demonstrated in BF and VAS between the combined and ACL first groups. Results revealed a significant affect of osteochondral defect size on outcome measures. Conclusion: The study confirms that ACI in combination with ACL reconstruction is a viable option with similar outcomes as those patients who have had the procedures staged. PMID:26015603

  15. Current Concepts of Articular Cartilage Restoration Techniques in the Knee

    PubMed Central

    Camp, Christopher L.; Stuart, Michael J.; Krych, Aaron J.

    2014-01-01

    Context: Articular cartilage injuries are common in patients presenting to surgeons with primary complaints of knee pain or mechanical symptoms. Treatment options include comprehensive nonoperative management, palliative surgery, joint preservation operations, and arthroplasty. Evidence Acquisition: A MEDLINE search on articular cartilage restoration techniques of the knee was conducted to identify outcome studies published from 1993 to 2013. Special emphasis was given to Level 1 and 2 published studies. Study Design: Clinical review. Level of Evidence: Level 3. Results: Current surgical options with documented outcomes in treating chondral injuries in the knee include the following: microfracture, osteochondral autograft transfer, osteochondral allograft transplant, and autologous chondrocyte transplantation. Generally, results are favorable regarding patient satisfaction and return to sport when proper treatment algorithms and surgical techniques are followed, with 52% to 96% of patients demonstrating good to excellent clinical outcomes and 66% to 91% returning to sport at preinjury levels. Conclusion: Clinical, functional, and radiographic outcomes may be improved in the majority of patients with articular cartilage restoration surgery; however, some patients may not fully return to their preinjury activity levels postoperatively. In active and athletic patient populations, biological techniques that restore the articular surface may be options that provide symptom relief and return patients to their prior levels of function. PMID:24790697

  16. Feet injuries in rock climbers

    PubMed Central

    Schöffl, Volker; Küpper, Thomas

    2013-01-01

    While injuries of the upper extremity are widely discussed in rock climbers, reports about the lower extremity are rare. Nevertheless almost 50 percent of acute injuries involve the leg and feet. Acute injuries are either caused by ground falls or rock hit trauma during a fall. Most frequently strains, contusions and fractures of the calcaneus and talus. More rare injuries, as e.g., osteochondral lesions of the talus demand a highly specialized care and case presentations with combined iliac crest graft and matrix associated autologous chondrocyte transplantation are given in this review. The chronic use of tight climbing shoes leads to overstrain injuries also. As the tight fit of the shoes changes the biomechanics of the foot an increased stress load is applied to the fore-foot. Thus chronic conditions as subungual hematoma, callosity and pain resolve. Also a high incidence of hallux valgus and hallux rigidus is described. PMID:24147257

  17. Common medial elbow injuries in the adolescent athlete.

    PubMed

    Leahy, Ian; Schorpion, Melissa; Ganley, Theodore

    2015-01-01

    Recently there has been increased year-round sports participation among children and adolescents with limited to no rest periods. This has led to increases in pediatric repetitive stress injuries, once considered a rarity. Whether in the throwing athlete or in the athlete that experiences repetitive axial loading; increased medial tension and overload syndromes can lead to stress reactions and fractures. This occurs in the developing athlete due to the bone being weaker than the surrounding tendons and ligaments. The medial elbow is a high stress area and is susceptible to many conditions including apophysitis , avulsion fractures and ulnar collateral ligament disruption. Valgus stress can cause injury to the medial elbow which can lead to increased lateral compression, Panner's disease and osteochondral lesions of the capitellum and olecranon. The purpose of this manuscript is to review common elbow disorders in the adolescent population, outline management and highlight important features of rehabilitation. PMID:25840494

  18. Effect of bone loss in anterior shoulder instability.

    PubMed

    Garcia, Grant H; Liu, Joseph N; Dines, David M; Dines, Joshua S

    2015-06-18

    Anterior shoulder instability with bone loss can be a difficult problem to treat. It usually involves a component of either glenoid deficiency or a Hill-Sachs lesion. Recent data shows that soft tissue procedures alone are typically not adequate to provide stability to the shoulder. As such, numerous surgical procedures have been described to directly address these bony deficits. For glenoid defects, coracoid transfer and iliac crest bone block procedures are popular and effective. For humeral head defects, both remplissage and osteochondral allografts have decreased the rates of recurrent instability. Our review provides an overview of current literature addressing these treatment options and others for addressing bone loss complicating anterior glenohumeral instability. PMID:26085984

  19. Effects of solvent dehydration on creep resistance of poly(vinyl alcohol) hydrogel.

    PubMed

    Choi, Jeeyoung; Bodugoz-Senturk, Hatice; Kung, Hsiang J; Malhi, Arnaz S; Muratoglu, Orhun K

    2007-02-01

    As a synthetic replacement material for osteochondral defect repair, poly(vinyl alcohol) (PVA) hydrogels offer a great potential due to their high water content and strong mechanical integrity. To survive the high stress environment in the joint space, high creep resistance becomes one of the key requirements for hydrogel implants. We hypothesized that reducing the equilibrium water content (EWC) of hydrogels would improve their creep resistance. We investigated the effect of dehydration of PVA theta-gels in various solvent/solution media followed by rehydration in saline solution. Decreasing EWC increased the creep resistance of PVA theta-gels. The most effective medium was isopropyl alcohol for reducing the EWC and increasing the creep resistance of PVA theta-gels. PMID:17070904

  20. Serological survey for antibody to Encephalitozoon cuniculi in horses in the USA.

    PubMed

    Cray, Carolyn; Perritt, Emily; Hughes, Cynthia; Belgrave, Rodney L

    2014-07-01

    Encephalitozoon cuniculi is an obligate intracellular microsporidian parasite that can result in clinical and subclinical infection in many species. In the present study, a serological survey was conducted using samples from 105 horses in the state of New Jersey; 49 of the samples were obtained from clinically abnormal animals. Five or 4.8% of 105 serum samples were found to demonstrate reactivity by ELISA with titers of 1:64 to 1:1,024. One of the samples was obtained from a clinically normal horse. Clinical signs and diagnoses from the other animals included lameness, colic, osteochondritis dissecans, and fever. All clinical issues were resolved with hospitalization and treatment without the institution of E. cuniculi-focused therapy. This is the first report on the detection of E. cuniculi antibodies in horses in the USA. PMID:24802871

  1. Glenohumeral Joint Preservation: A Review of Management Options for Young, Active Patients with Osteoarthritis

    PubMed Central

    van der Meijden, Olivier A.; Gaskill, Trevor R.; Millett, Peter J.

    2012-01-01

    The management of osteoarthritis of the shoulder in young, active patients is a challenge, and the optimal treatment has yet to be completely established. Many of these patients wish to maintain a high level of activity, and arthroplasty may not be a practical treatment option. It is these patients who may be excellent candidates for joint-preservation procedures in an effort to avoid or delay joint replacement. Several palliative and restorative techniques are currently optional. Joint debridement has shown good results and a combination of arthroscopic debridement with a capsular release, humeral osteoplasty, and transcapsular axillary nerve decompression seems promising when humeral osteophytes are present. Currently, microfracture seems the most studied reparative treatment modality available. Other techniques, such as autologous chondrocyte implantation and osteochondral transfers, have reportedly shown potential but are currently mainly still investigational procedures. This paper gives an overview of the currently available joint preserving surgical techniques for glenohumeral osteoarthritis. PMID:22536514

  2. 3D Bioprinting of Cartilage for Orthopedic Surgeons: Reading between the Lines

    PubMed Central

    Di Bella, Claudia; Fosang, Amanda; Donati, Davide M.; Wallace, Gordon G.; Choong, Peter F. M.

    2015-01-01

    Chondral and osteochondral lesions represent one of the most challenging and frustrating scenarios for the orthopedic surgeon and for the patient. The lack of therapeutic strategies capable to reconstitute the function and structure of hyaline cartilage and to halt the progression toward osteoarthritis has brought clinicians and scientists together, to investigate the potential role of tissue engineering as a viable alternative to current treatment modalities. In particular, the role of bioprinting is emerging as an innovative technology that allows for the creation of organized 3D tissue constructs via a “layer-by-layer” deposition process. This process also has the capability to combine cells and biomaterials in an ordered and predetermined way. Here, we review the recent advances in cartilage bioprinting and we identify the current challenges and the directions for future developments in cartilage regeneration. PMID:26322314

  3. Progressive paralyzing sciatica revealing a pelvic pseudoaneurysm a year after hip surgery in a 12yo boy.

    PubMed

    Boulouis, Grégoire; Shotar, Eimad; Dangouloff-Ros, Volodia; Janklevicz, Pierre-Henri; Boddaert, Nathalie; Naggara, Olivier; Brunelle, Francis

    2016-01-01

    Identifying extra spinal causes of a lumbar radiculopathy or polyneuropathy can be a tricky diagnosis challenge, especially in children. Among them, traumatic or iatrogenic pseudoaneurysms of iliac arteries have been seldom reported, in adults' series. The authors report an unusual case of progressive paralyzing left sciatica and lumbar plexopathy in a 12 years old boy, 12 months after a pelvic osteotomy for bilateral hip luxation secondary to osteochondritis dissecans. Spine MRI and pelvic CT angiography revealed a giant internal iliac artery pseudoaneurysm, enclosed in a chronic hematoma. The patient was successfully treated with endovascular coil embolization, and subsequent surgical hematoma evacuation. However, three months after treatment, neurological recovery was incomplete. This case highlights the importance of a rapid and extensive diagnosis work up of all causes of lower limb radiculopathies in children, including pelvic arteries lesions especially after pelvic surgery to avoid therapeutic delays that may jeopardize the chances of neurological recovery. PMID:26545958

  4. Skeletal tissue regeneration: where can hydrogels play a role?

    PubMed

    Moreira Teixeira, Liliana S; Patterson, Jennifer; Luyten, Frank P

    2014-09-01

    The emerging field of tissue engineering reveals promising approaches for the repair and regeneration of skeletal tissues including the articular cartilage, bone, and the entire joint. Amongst the myriad of biomaterials available to support this strategy, hydrogels are highly tissue mimicking substitutes and thus of great potential for the regeneration of functional tissues. This review comprises an overview of the novel and most promising hydrogels for articular cartilage, osteochondral and bone defect repair. Chondro- and osteo-conductive and -instructive hydrogels are presented, highlighting successful combinations with inductive signals and cell sources. Moreover, advantages, drawbacks, and future perspectives of the role of hydrogels in skeletal regeneration are addressed, pointing out the current state of this rising approach. PMID:24968789

  5. Biodegradable microcarriers as cell delivery vehicle for in vivo transplantation and magnetic resonance monitoring.

    PubMed

    Lovati, A B; Vianello, E; Talň, G; Recordati, C; Bonizzi, L; Galliera, E; Broggini, M; Moretti, M

    2011-01-01

    Microcarrier culture systems offer an attractive method for cell amplification and as delivery vehicle. At the same time, super paramagnetic iron oxide (SPIO) nanoparticles represent a unique in vivo tracking system, already approved for clinical use. In our study, we tested the combination of clinically approved microcarriers and SPIO nanoparticles for cell-construct delivery and subsequent tracking after implantation. In order to mimic better a clinical setting, biodegradable macroporous microcarriers were employed as an alternative approach to expand human primary chondrocytes in a dynamic culture system for subsequent direct transplantation. In addition, cellseeded microcarriers were labeled with SPIO nanoparticles to evaluate the benefits of cell-constructs tracking with magnetic resonance. In vivo subcutaneous implants were monitored for up to 3 weeks and orthotopic implantation was simulated and monitored in ex vivo osteochondral defects. PMID:22051172

  6. Multi-scale mechanical response of freeze-dried collagen scaffolds for tissue engineering applications

    E-print Network

    Offeddu, Giovanni S.; Ashworth, Jennifer C.; Cameron, Ruth E.; Oyen, Michelle L.

    2014-11-11

    ., Dorcemus, D., 2012. Osteochondral tissue engineering: current strategies and challenges. Biotechnol. Adv. 31, 706. ASTM Standaqrd E112. (Accessed 2014). O’Brien, F.J., et al., 2004. Influence of freezing rate on pore structure in freeze-dried collagen... j o u r n a l o f t h e m e c h a n i c a l b e h a v i o r o f b i o m e d i c a l m a t e r i a l s 4 2 ( 2 0 1 5 ) 1 9 – 2 5E-mail address: mlo29@cam.ac.uk (M.L. Oyen).clinical problems such as osteoarthritis (Nukavaparu and Dorcemus, 2012; Ahmed...

  7. Imaging of sports ligamentous injuries of the elbow.

    PubMed

    Beltran, Luis S; Bencardino, Jenny T; Beltran, Javier

    2013-11-01

    Ligamentous injuries of the elbow are common in sports. The diagnosis is usually based on a combination of the assessment of the mechanism of injury during the sporting activity and physical examination. Imaging with radiographs and MR imaging has an important diagnostic role, particularly when the clinical presentation is unclear and to evaluate for other important potential associated injuries such as myotendinous injuries, fractures, dislocations, and osteochondral lesions. Treatment includes conservative and surgical measures depending on the severity of the instability and associated injuries. We provide a detailed review of sports-related injuries of the medial and lateral collateral ligament complexes of the elbow with an emphasis on imaging manifestations of disease and a discussion of the anatomy, biomechanics, and treatment options. PMID:24327410

  8. Gene Modification of Mesenchymal Stem Cells and Articular Chondrocytes to Enhance Chondrogenesis

    PubMed Central

    2014-01-01

    Current cell based treatment for articular cartilage and osteochondral defects are hampered by issues such as cellular dedifferentiation and hypertrophy of the resident or transplanted cells. The reduced expression of chondrogenic signalling molecules and transcription factors is a major contributing factor to changes in cell phenotype. Gene modification of chondrocytes may be one approach to redirect cells to their primary phenotype and recent advances in nonviral and viral gene delivery technologies have enabled the expression of these lost factors at high efficiency and specificity to regain chondrocyte function. This review focuses on the various candidate genes that encode signalling molecules and transcription factors that are specific for the enhancement of the chondrogenic phenotype and also how epigenetic regulators of chondrogenesis in the form of microRNA may also play an important role. PMID:24963479

  9. Gene Therapy for Cartilage Repair

    PubMed Central

    Madry, Henning; Orth, Patrick; Cucchiarini, Magali

    2011-01-01

    The concept of using gene transfer strategies for cartilage repair originates from the idea of transferring genes encoding therapeutic factors into the repair tissue, resulting in a temporarily and spatially defined delivery of therapeutic molecules to sites of cartilage damage. This review focuses on the potential benefits of using gene therapy approaches for the repair of articular cartilage and meniscal fibrocartilage, including articular cartilage defects resulting from acute trauma, osteochondritis dissecans, osteonecrosis, and osteoarthritis. Possible applications for meniscal repair comprise meniscal lesions, meniscal sutures, and meniscal transplantation. Recent studies in both small and large animal models have demonstrated the applicability of gene-based approaches for cartilage repair. Chondrogenic pathways were stimulated in the repair tissue and in osteoarthritic cartilage using genes for polypeptide growth factors and transcription factors. Although encouraging data have been generated, a successful translation of gene therapy for cartilage repair will require an ongoing combined effort of orthopedic surgeons and of basic scientists. PMID:26069580

  10. Hip Arthroscopy for Synovial Chondromatosis: Tips and Tricks

    PubMed Central

    Rath, Ehud; Amar, Eyal; Doron, Ran; Matsuda, Dean K.

    2014-01-01

    Hip arthroscopy is an important diagnostic and therapeutic tool in the management of synovial chondromatosis. Removal of osteochondral fragments (OCFs) from the central and peripheral compartments is crucial for the relief of mechanical symptoms and subsequent joint destruction. Direct access to the central compartment is often limited because of the ball-and-socket morphology and limitation of traction. We present our surgical technique for removing OCFs and a new method for the removal of a large loose body using a nitinol stone retrieval basket. The technique facilitates removal of difficult-to-access fragments from the central compartment. Moreover, this technique allows removal of far-medial OCFs from the peripheral compartment. PMID:25685679

  11. [Articular cartilage regeneration using stem cells].

    PubMed

    Kanamoto, Takashi; Nakamura, Norimasa; Nakata, Ken; Yoshikawa, Hideki

    2008-12-01

    Articular cartilage plays pivotal roles in securing smooth joint kinematics and act as a shock absorber, however, it has minimal healing potential. Chondral injury could lead to the development of osteoarthritis (OA) and therefore is a major clinical concern. There have been marrow stimulating technique and osteochondral transplantation explored to promote cartilage repair. In addition, autologous chondrocyte implantation (ACI) has been developed by Peterson and Brittberg and more than 20,000 cases underwent the procedure all over the world. Recent progress in stem cell research has raised the potential application of stem cell therapy to cartilage repair. In this review, potential application of bone marrow or synovial-derived mesenchymal cells to promote cartilage repair would be discussed. PMID:19043188

  12. Chordoma of the thoracic vertebrae in a Bengal tiger (Panthera tigris tigris)

    PubMed Central

    KURAMOCHI, Mizuki; IZAWA, Takeshi; HORI, Mayuka; KUSUDA, Kayo; SHIMIZU, Junichiro; ISERI, Toshie; AKIYOSHI, Hideo; OHASHI, Fumihito; KUWAMURA, Mitsuru; YAMATE, Jyoji

    2015-01-01

    A 19-year-old female Bengal tiger (Panthera tigris tigris) was presented with hind limb weakness, ataxia and respiratory distress. Computed tomography revealed a mass between the left side of the T7 vertebra and the base of the left 7th rib. The tiger then died, and necropsy was performed. Grossly, the vertebral mass was 6 × 5.7 × 3 cm, and invaded the adjacent vertebral bone and compressed the T7 spinal cord. Histologically, the mass was composed of large, clear, vacuolated and polygonal cells with osteochondral matrix. Cellular and nuclear atypia were moderate. The vacuolated cells stained positively for cytokeratin and vimentin and negatively for S-100. Based on these findings, the present case was diagnosed as a vertebral chordoma; the first report in a tiger. PMID:25766770

  13. The effect of a gelatin ?-tricalcium phosphate sponge loaded with mesenchymal stem cells (MSC), bone morphogenic protein-2, and platelet-rich plasma (PRP) on equine articular cartilage defect

    PubMed Central

    Tsuzuki, Nao; Seo, Jong-pil; Yamada, Kazutaka; Haneda, Shingo; Furuoka, Hidefumi; Tabata, Yasuhiko; Sasaki, Naoki

    2013-01-01

    We evaluated the curative efficacy of a gelatin ?-tricalcium phosphate (?-TCP) sponge loaded with mesenchymal stem cells (MSC), bone morphogenic protein-2 (BMP-2), and platelet-rich plasma (PRP) by insertion into an experimentally induced osteochondral defect. A hole of 10 mm diameter and depth was drilled in the bilateral medial femoral condyles of 7 thoroughbred horses, and into each either a loaded sponge (treatment) or a saline-infused ?-TCP sponge (control) was inserted. After 16 weeks, defects were examined by computed tomography, macroscopic analyses, and histological analyses. The median subchondral bone density and macroscopic subscores for joint healing were significantly higher in the treatment legs (P < 0.05). Although there was no significant difference in total histological scores between groups, hyaline cartilaginous tissue was observed across a wider area in the treatment group. Equine joint healing can be enhanced by inserting a BMP-2-, MSC-, and PRP-impregnated ?-TCP sponge at the lesion site. PMID:24155448

  14. Chordoma of the thoracic vertebrae in a Bengal tiger (Panthera tigris tigris).

    PubMed

    Kuramochi, Mizuki; Izawa, Takeshi; Hori, Mayuka; Kusuda, Kayo; Shimizu, Junichiro; Iseri, Toshie; Akiyoshi, Hideo; Ohashi, Fumihito; Kuwamura, Mitsuru; Yamate, Jyoji

    2015-07-01

    A 19-year-old female Bengal tiger (Panthera tigris tigris) was presented with hind limb weakness, ataxia and respiratory distress. Computed tomography revealed a mass between the left side of the T7 vertebra and the base of the left 7th rib. The tiger then died, and necropsy was performed. Grossly, the vertebral mass was 6 × 5.7 × 3 cm, and invaded the adjacent vertebral bone and compressed the T7 spinal cord. Histologically, the mass was composed of large, clear, vacuolated and polygonal cells with osteochondral matrix. Cellular and nuclear atypia were moderate. The vacuolated cells stained positively for cytokeratin and vimentin and negatively for S-100. Based on these findings, the present case was diagnosed as a vertebral chordoma; the first report in a tiger. PMID:25766770

  15. Effect of bone loss in anterior shoulder instability

    PubMed Central

    Garcia, Grant H; Liu, Joseph N; Dines, David M; Dines, Joshua S

    2015-01-01

    Anterior shoulder instability with bone loss can be a difficult problem to treat. It usually involves a component of either glenoid deficiency or a Hill-Sachs lesion. Recent data shows that soft tissue procedures alone are typically not adequate to provide stability to the shoulder. As such, numerous surgical procedures have been described to directly address these bony deficits. For glenoid defects, coracoid transfer and iliac crest bone block procedures are popular and effective. For humeral head defects, both remplissage and osteochondral allografts have decreased the rates of recurrent instability. Our review provides an overview of current literature addressing these treatment options and others for addressing bone loss complicating anterior glenohumeral instability. PMID:26085984

  16. Subchondral Bone Regenerative Effect of Two Different Biomaterials in the Same Patient

    PubMed Central

    Giannini, Sandro

    2013-01-01

    This case report aims at highlighting the different effects on subchondral bone regeneration of two different biomaterials in the same patient, in addition to bone marrow derived cell transplantation (BMDCT) in ankle. A 15-year-old boy underwent a first BMDCT on a hyaluronate membrane to treat a deep osteochondral lesion (8?mm). The procedure failed: subchondral bone was still present at MRI. Two years after the first operation, the same procedure was performed on a collagen membrane with DBM filling the defect. After one year, AOFAS score was 100 points, and MRI showed a complete filling of the defect. The T2 mapping MRI after one year showed chondral tissue with values in the range of hyaline cartilage. In this case, DBM and the collagen membrane were demonstrated to be good biomaterials to restore subchondral bone: this is a critical step towards the regeneration of a healthy hyaline cartilage. PMID:23936705

  17. Bone-Induced Chondroinduction in Sheep Jamshidi Biopsy Defects with and without Treatment by Subchondral Chitosan-Blood Implant

    PubMed Central

    Bell, Angela D.; Lascau-Coman, Viorica; Sun, Jun; Chen, Gaoping; Lowerison, Mark W.; Hurtig, Mark B.

    2013-01-01

    Objective: Delivery of chitosan to subchondral bone is a novel approach for augmented marrow stimulation. We evaluated the effect of 3 presolidified chitosan-blood implant formulations on osteochondral repair progression compared with untreated defects. Design: In N = 5 adult sheep, six 2-mm diameter Jamshidi biopsy holes were created bilaterally in the medial femoral condyle and treated with presolidified chitosan-blood implant with fluorescent chitosan tracer (10 kDa, 40 kDa, or 150k Da chitosan, left knee) or left to bleed (untreated, right knee). Implant residency and osteochondral repair were assessed at 1 day (N = 1), 3 weeks (N = 2), or 3 months (N = 2) postoperative using fluorescence microscopy, histomorphometry, stereology, and micro–computed tomography. Results: Chitosan implants were retained in 89% of treated Jamshidi holes up to 3 weeks postoperative. At 3 weeks, biopsy sites were variably covered by cartilage flow, and most bone holes contained cartilage flow fragments and heterogeneous granulation tissues with sparse leukocytes, stromal cells, and occasional adipocytes (volume density 1% to 3%). After 3 months of repair, most Jamshidi bone holes were deeper, remodeling at the edges, filled with angiogenic granulation tissue, and lined with variably sized chondrogenic foci fused to bone trabeculae or actively repairing bone plate. The 150-kDa chitosan implant elicited more subchondral cartilage formation compared with 40-kDa chitosan-treated and control defects (P < 0.05, N = 4). Treated defects contained more mineralized repair tissue than control defects at 3 months (P < 0.05, N = 12). Conclusion: Bone plate–induced chondroinduction is an articular cartilage repair mechanism. Jamshidi biopsy repair takes longer than 3 months and can be influenced by subchondral chitosan-blood implant. PMID:26069656

  18. Arthroscopic Assessment of Intra-Articular Lesion after Surgery for Rotational Ankle Fracture

    PubMed Central

    Cha, Seung-Do; Gwak, Heui-Chul; Ha, Dong-Jun; Kim, Jong-Yup; Kim, Ui-Cheol; Jang, Yue-Chan

    2015-01-01

    Background The purpose of this study was to report findings of exploratory arthroscopic assessment performed in conjunction with removal of internal fixation device placed in the initial surgery for rotational ankle fracture. Methods A total of 53 patients (33 male, 20 female) who underwent surgery for rotational ankle fracture between November 2002 and February 2008 were retrospectively reviewed. All patients gave consent to the exploratory arthroscopic surgery for the removal of internal fixation devices placed in the initial surgery. Lauge-Hansen classification system of ankle fractures was assessed for all patients. Intra-articular lesions (osteochondral lesion, loose body, and fibrosis) were evaluated via ankle arthroscopy. Comparative analysis was then performed between radiological classification of ankle fracture/patient's symptoms and arthroscopic findings. Results Lauge-Hansen classification system of ankle fractures included supination-external rotation type (n = 35), pronation-external rotation type (n = 9), and pronation-abduction type (n = 9). A total of 33 patients exhibited symptoms of pain or discomfort while walking whereas 20 exhibited no symptoms. Arthroscopic findings included abnormal findings around the syndesmosis area (n = 35), intra-articular fibrosis (n = 51), osteochondral lesions of the talus (n = 33), loose bodies (n = 6), synovitis (n = 13), and anterior bony impingement syndrome (n = 3). Intra-articular fibrosis was seen in 31 of symptomatic patients (93.9%). Pain or discomfort with activity caused by soft tissue impingement with meniscus-like intra-articular fibrosis were found in 19 patients. There was statistical significance (p = 0.02) between symptoms (pain and discomfort) and the findings of meniscus-like fibrosis compared to the group without any symptom. Conclusions Arthroscopic examination combined with treatment of intra-articular fibrosis arising from ankle fracture surgery may help improve surgical outcomes. PMID:26640633

  19. Rho/ROCK and MEK/ERK activation by transforming growth factor-alpha induces articular cartilage degradation.

    PubMed

    Appleton, C Thomas G; Usmani, Shirine E; Mort, John S; Beier, Frank

    2010-01-01

    Identification and characterization of therapeutic targets for joint conditions, such as osteoarthritis (OA), is exceedingly important for addressing the increasing burden of disease. Transforming growth factor-alpha (TGFalpha) is upregulated by articular chondrocytes in experimentally induced and human OA. To test the potential involvement of TGFalpha, which is an activator of epidermal growth factor receptor (EGFR) signaling, in joint degeneration and to identify signaling mechanisms mediating articular chondrocyte responses to TGFalpha, rat chondrocytes and osteochondral explants were treated with TGFalpha and various inhibitors of intracellular signaling pathways. Stimulation of EGFR signaling in articular chondrocytes by TGFalpha resulted in the activation of RhoA/ROCK (Rho kinase), MEK (MAPK/ERK kinase)/ERK (extracellular-signal-regulated kinase), PI3K (phosphoinositide 3-kinase) and p38 MAPK (mitogen-activated protein kinase) pathways. Modification of the chondrocyte actin cytoskeleton was stimulated by TGFalpha, but inhibition of only Rho or ROCK activation prevented morphological changes. TGFalpha suppressed expression of anabolic genes including Sox9, type II collagen and aggrecan, which were rescued only by inhibiting MEK/ERK activation. Furthermore, catabolic factor upregulation by TGFalpha was prevented by ROCK and p38 MAPK inhibition, including matrix metalloproteinase-13 and tumor necrosis factor-alpha, which are well known to contribute to cartilage digestion in OA. To assess the ability of TGFalpha to stimulate degradation of mature articular cartilage, type II collagen and aggrecan cleavage fragments were analyzed in rat osteochondral explants exposed to exogenous TGFalpha. Normal articular cartilage contained low levels of both cleavage fragments, but high levels were observed in the cartilage treated with TGFalpha. Selective inhibition of MEK/ERK and Rho/ROCK activation greatly reduced or completely prevented excess type II collagen and aggrecan degradation in response to TGFalpha. These data suggest that TGFalpha is a strong stimulator of cartilage degradation and that Rho/ROCK and MEK/ERK signaling have critical roles in mediating these effects. PMID:19823173

  20. Iron Administration before Stem Cell Harvest Enables MR Imaging Tracking after Transplantation

    PubMed Central

    Khurana, Aman; Chapelin, Fanny; Beck, Graham; Lenkov, Olga D.; Donig, Jessica; Nejadnik, Hossein; Messing, Solomon; Derugin, Nikita; Chan, Ray Chun-Fai; Gaur, Amitabh; Sennino, Barbara; McDonald, Donald M.; Kempen, Paul J.; Tikhomirov, Grigory A.; Rao, Jianghong

    2013-01-01

    Purpose: To determine whether intravenous ferumoxytol can be used to effectively label mesenchymal stem cells (MSCs) in vivo and can be used for tracking of stem cell transplants. Materials and Methods: This study was approved by the institutional animal care and use committee. Sprague-Dawley rats (6–8 weeks old) were injected with ferumoxytol 48 hours prior to extraction of MSCs from bone marrow. Ferumoxytol uptake by these MSCs was evaluated with fluorescence, confocal, and electron microscopy and compared with results of traditional ex vivo–labeling procedures. The in vivo–labeled cells were subsequently transplanted in osteochondral defects of 14 knees of seven athymic rats and were evaluated with magnetic resonance (MR) imaging up to 4 weeks after transplantation. T2 relaxation times of in vivo–labeled MSC transplants and unlabeled control transplants were compared by using t tests. MR data were correlated with histopathologic results. Results: In vivo–labeled MSCs demonstrated significantly higher ferumoxytol uptake compared with ex vivo–labeled cells. With electron microscopy, iron oxide nanoparticles were localized in secondary lysosomes. In vivo–labeled cells demonstrated significant T2 shortening effects in vitro and in vivo when they were compared with unlabeled control cells (T2 in vivo, 15.4 vs 24.4 msec; P < .05) and could be tracked in osteochondral defects for 4 weeks. Histologic examination confirmed the presence of iron in labeled transplants and defect remodeling. Conclusion: Intravenous ferumoxytol can be used to effectively label MSCs in vivo and can be used for tracking of stem cell transplants with MR imaging. This method eliminates risks of contamination and biologic alteration of MSCs associated with ex vivo–labeling procedures. © RSNA, 2013 Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.13130858/-/DC1 PMID:23850832

  1. Arthroscopic treatment of glenoid fractures.

    PubMed

    Bauer, Thomas; Abadie, Olivier; Hardy, Philippe

    2006-05-01

    The patient was placed in the lateral decubitus position. The arthroscope was introduced through the posterior approach. The probe hook was introduced through a working cannula through the anterosuperior portal performed in an inside-out technique. The mobilization possibilities of the osteochondral fragments were then assessed. The use of a shaver was always necessary to clean the fracture site and evacuate clots. A nonabsorbable suture was passed through the labrum and the capsule tissue of the displaced articular fragment in its superior edge. The first suture was used as a traction stitch and allowed replacing the fragment in its original position and maintaining it during the placement of others sutures. A hole was made in the anterosuperior edge of the nonfractured glenoid and then a long drill was passed backward according to the transglenoid suture technique of Caspari or Morgan. Stitches were passed through the glenoid to the infraspinatus fossa. When articular congruity was judged satisfactory, the stitches were tied on the fascia of the infraspinatus muscle. The patients were immobilized in a sling for 3 weeks. PMID:16651173

  2. Viability of human articular chondrocytes harvested postmortem: changes with time and temperature of in vitro culture conditions.

    PubMed

    Alibegovi?, Armin; Balažic, Jože; Petrovi?, Danijel; Hribar, Gorazd; Blagus, Rok; Drobni?, Matej

    2014-03-01

    Different studies of long-term chondrocytes viability have shown a gradual reduction as a function of time and ambient temperature. The aim of our in vitro study was to establish chondrocyte postmortem viability curves for 4°C, 11°C, 23°C, 35°C during 63 days after the donors' death. Osteochondral cylinders were procured from the knees of 16 male donors (20-47 years), stored in preservation media that was not changed, and analyzed in 3-day intervals using a confocal laser scanning microscope. A significant influence of time on viability was found from Day 9 (p = 0.0029) and onwards (p < 0.0001). The lowest overall chondrocyte viability was at 35°C, followed by 4°C (p < 0.0001). The conditions used in this in vitro analysis suggest that similar viabilities may occur while in situ in the decedent. Further studies of chondrocyte viability from individuals with known postmortem intervals may show premise to help evaluate time since death in the late postmortem interval. PMID:24502347

  3. The optimal combination of cartilage source and apparatus for long-term in vitro chondrocyte viability analysis.

    PubMed

    Alibegovi?, Armin; Balažic, Jože; Petrovi?, Danijel; Velikonja, Nevenka Kregar; Blagus, Rok; Suput, Dušan; Drobni?, Matej

    2012-11-01

    Most studies of long-term chondrocytes survival were for tissue banks. They showed a gradual reduction in the viable chondrocytes percentage as a function of time and ambient temperature, but the samples were harvested under optimal conditions. The aim of our study was to determine the most reliable combination of cartilage source and assay for the in vitro postmortem chondrocyte viability analysis in the conditions that imitate a dead body. Osteochondral cylinders were procured from femoral condyles and talar trochleas of three male donors and stored in the cell culture media at 4 ± 2°C and 23 ± 2°C. The samples were analyzed by a cell viability analyzer and a confocal laser scanning microscope (CLSM) initially 24-36 h after death and then in 4-week intervals. The results reconfirmed the significant influence of time (p = 0.0002), but not of the temperature (p = 0.237). The largest reproducibility was presented for the knee joint and the CLSM. PMID:22621167

  4. In vitro assessment of biomaterial-induced remodeling of subchondral and cancellous bone for the early intervention of joint degeneration with focus on the spinal disc

    NASA Astrophysics Data System (ADS)

    McCanless, Jonathan D.

    Osteoarthritis-associated pain of the spinal disc, knee, and hip derives from degeneration of cartilagenous tissues in these joints. Traditional therapies have focused on these cartilage (and disc specific nucleus pulposus) changes as a means of treatment through tissue grafting, regenerative synthetic implants, non-regenerative space filling implants, arthroplasty, and arthrodesis. Although such approaches may seem apparent upon initial consideration of joint degeneration, tissue pathology has shown changes in the underlying bone and vascular bed precede the onset of cartilaginous changes. It is hypothesized that these changes precedent joint degeneration and as such may provide a route for early prevention. The current work proposes an injectable biomaterial-based therapy within these subchondral and cancellous bone regions as a means of preventing or reversing osteoarthritis. Two human concentrated platelet releasate-containing alginate hydrogel/beta-tricalcium phosphate composites have been developed for this potential biomaterial application. The undertaking of assessing these materials through bench-, in vitro, and ex vivo work is described herein. These studies showed the capability of the biomaterials to initiate a wound healing response in monocytes, angiogenic and differentiation behavior in immature endothelial cells, and early osteochondral differentiation in mesenchymal stem cells. These cellular activities are associated with fracture healing and endochondral bone formation, demonstrating the potential of the biomaterials to induce osseous and vascular tissue remodeling underlying osteoarthritic joints as a novel therapy for a disease with rapidly growing healthcare costs.

  5. Development of an Equine Groove Model to Induce Metacarpophalangeal Osteoarthritis: A Pilot Study on 6 Horses

    PubMed Central

    Maninchedda, Ugo; Lepage, Olivier M.; Gangl, Monika; Hilairet, Sandrine; Remandet, Bernard; Meot, Francoise; Penarier, Geraldine; Segard, Emilie; Cortez, Pierre; Jorgensen, Christian; Steinberg, Régis

    2015-01-01

    The aim of this work was to develop an equine metacarpophalangeal joint model that induces osteoarthritis that is not primarily mediated by instability or inflammation. The study involved six Standardbred horses. Standardized cartilage surface damage or “grooves” were created arthroscopically on the distal dorsal aspect of the lateral and medial metacarpal condyles of a randomly chosen limb. The contralateral limb was sham operated. After 2 weeks of stall rest, horses were trotted 30 minutes every other day for 8 weeks, then evaluated for lameness and radiographed. Synovial fluid was analyzed for cytology and biomarkers. At 10 weeks post-surgery, horses were euthanized for macroscopic and histologic joint evaluation. Arthroscopic grooving allowed precise and identical damage to the cartilage of all animals. Under the controlled exercise regime, this osteoarthritis groove model displayed significant radiographic, macroscopic, and microscopic degenerative and reactive changes. Histology demonstrated consistent surgically induced grooves limited to non-calcified cartilage and accompanied by secondary adjacent cartilage lesions, chondrocyte necrosis, chondrocyte clusters, cartilage matrix softening, fissuring, mild subchondral bone inflammation, edema, and osteoblastic margination. Synovial fluid biochemistry and cytology demonstrated significantly elevated total protein without an increase in prostaglandin E2, neutrophils, or chondrocytes. This equine metacarpophalangeal groove model demonstrated that standardized non-calcified cartilage damage accompanied by exercise triggered altered osteochondral morphology and cartilage degeneration with minimal or inefficient repair and little inflammatory response. This model, if validated, would allow for assessment of disease processes and the effects of therapy. PMID:25680102

  6. Intraosseous infiltration of platelet-rich plasma for severe knee osteoarthritis.

    PubMed

    Sánchez, Mikel; Fiz, Nicolás; Guadilla, Jorge; Padilla, Sabino; Anitua, Eduardo; Sánchez, Pello; Delgado, Diego

    2014-12-01

    We describe a new technique of platelet-rich plasma (PRP) infiltration for the treatment of severe knee osteoarthritis. PRP intra-articular infiltration is a promising treatment for knee osteoarthritis, but it still has some limitations in high-degree osteoarthritis. Diagnosis of osteoarthritis is based on clinical and radiographic findings, and patients with grade III or IV knee tibiofemoral osteoarthritis based on the Ahlbäck scale are considered candidates for this technique. The technique consists of performing intraosseous infiltration of PRP into the subchondral bone, which acts on this tissue and consequently on cartilage-bone communication. Although the intraosseous injection hinders the conventional knee intra-articular infiltration, it allows an extension of the range of action of the PRP, which acts directly on the subchondral bone, which is involved in the progression of osteoarthritis. Thus this technique involves a new administration of PRP that can delay knee arthroplasty; moreover, it can be applied for not only severe osteoarthritis but also other pathologies in which the subchondral bone is critical in the etiology, such as necrosis and osteochondral lesions. PMID:25685680

  7. Intraosseous Infiltration of Platelet-Rich Plasma for Severe Knee Osteoarthritis

    PubMed Central

    Sánchez, Mikel; Fiz, Nicolás; Guadilla, Jorge; Padilla, Sabino; Anitua, Eduardo; Sánchez, Pello; Delgado, Diego

    2014-01-01

    We describe a new technique of platelet-rich plasma (PRP) infiltration for the treatment of severe knee osteoarthritis. PRP intra-articular infiltration is a promising treatment for knee osteoarthritis, but it still has some limitations in high-degree osteoarthritis. Diagnosis of osteoarthritis is based on clinical and radiographic findings, and patients with grade III or IV knee tibiofemoral osteoarthritis based on the Ahlbäck scale are considered candidates for this technique. The technique consists of performing intraosseous infiltration of PRP into the subchondral bone, which acts on this tissue and consequently on cartilage-bone communication. Although the intraosseous injection hinders the conventional knee intra-articular infiltration, it allows an extension of the range of action of the PRP, which acts directly on the subchondral bone, which is involved in the progression of osteoarthritis. Thus this technique involves a new administration of PRP that can delay knee arthroplasty; moreover, it can be applied for not only severe osteoarthritis but also other pathologies in which the subchondral bone is critical in the etiology, such as necrosis and osteochondral lesions. PMID:25685680

  8. Development and evaluation of a device for simultaneous uniaxial compression and optical imaging of cartilage samples in vitro

    NASA Astrophysics Data System (ADS)

    Steinert, Marian; Kratz, Marita; Jaedicke, Volker; Hofmann, Martin R.; Jones, David B.

    2014-10-01

    In this paper, we present a system that allows imaging of cartilage tissue via optical coherence tomography (OCT) during controlled uniaxial unconfined compression of cylindrical osteochondral cores in vitro. We describe the system design and conduct a static and dynamic performance analysis. While reference measurements yield a full scale maximum deviation of 0.14% in displacement, force can be measured with a full scale standard deviation of 1.4%. The dynamic performance evaluation indicates a high accuracy in force controlled mode up to 25 Hz, but it also reveals a strong effect of variance of sample mechanical properties on the tracking performance under displacement control. In order to counterbalance these disturbances, an adaptive feed forward approach was applied which finally resulted in an improved displacement tracking accuracy up to 3 Hz. A built-in imaging probe allows on-line monitoring of the sample via OCT while being loaded in the cultivation chamber. We show that cartilage topology and defects in the tissue can be observed and demonstrate the visualization of the compression process during static mechanical loading.

  9. In vivo telemetric determination of shear and axial loads on a regenerative cartilage scaffold following ligament disruption.

    PubMed

    Szivek, John A; Heden, Gregory J; Geffre, Christopher P; Wenger, Karl H; Ruth, John T

    2014-10-01

    Recent interest in repair of chondral and osteochondral cartilage defects to prevent osteoarthritis caused by ligament disruption has led to the research and development of biomimetic scaffolds combined with cell-based regeneration techniques. Current clinical focal defect repair strategies have had limited success. New scaffold-based approaches may provide solutions that can repair extensive damage and prevent osteoarthritis. This study utilized a novel scaffold design that accommodated strain gauges for shear and axial load monitoring in the canine stifle joint through implantable telemetry technology. Loading changes induced by ligament disruption are widely implicated in the development of injury-related osteoarthritis. Seeding the scaffold end with progenitor cells resulted in higher shear stress than without cell seeding and histology showed significantly more bone and cartilage formation. Biomechanically, the effect of transecting the anterior cruciate ligament was a significant reduction in braking load in shear, but no change axially, and conversely a significant reduction in push-off load axially, but no change in shear. This is the first study to report shear loads measured directly in knee joint tissue. Further, advances of these measurement techniques are critical to developing improved regeneration strategies and personalizing reliable rehabilitation protocols. PMID:24678004

  10. A zebrafish model of Poikiloderma with Neutropenia recapitulates the human syndrome hallmarks and traces back neutropenia to the myeloid progenitor.

    PubMed

    Colombo, Elisa A; Carra, Silvia; Fontana, Laura; Bresciani, Erica; Cotelli, Franco; Larizza, Lidia

    2015-01-01

    Poikiloderma with Neutropenia (PN) is an autosomal recessive genodermatosis characterized by early-onset poikiloderma, pachyonychia, hyperkeratosis, bone anomalies and neutropenia, predisposing to myelodysplasia. The causative C16orf57/USB1 gene encodes a conserved phosphodiesterase that regulates the stability of spliceosomal U6-RNA. The involvement of USB1 in splicing has not yet allowed to unveil the pathogenesis of PN and how the gene defects impact on skin and bone tissues besides than on the haematological compartment. We established a zebrafish model of PN using a morpholino-knockdown approach with two different splicing morpholinos. Both usb1-depleted embryos displayed developmental abnormalities recapitulating the signs of the human syndrome. Besides the pigmentation and osteochondral defects, usb1-knockdown caused defects in circulation, manifested by a reduced number of circulating cells. The overall morphant phenotype was also obtained by co-injecting sub-phenotypic dosages of the two morpholinos and could be rescued by human USB1 RNA. Integrated in situ and real-time expression analyses of stage-specific markers highlighted defects of primitive haematopoiesis and traced back the dramatic reduction in neutrophil myeloperoxidase to the myeloid progenitors showing down-regulated pu.1 expression. Our vertebrate model of PN demonstrates the intrinsic requirement of usb1 in haematopoiesis and highlights PN as a disorder of myeloid progenitors associated with bone marrow dysfunction. PMID:26522474

  11. Interactions between structural and chemical biomimetism in synthetic stem cell niches.

    PubMed

    Nava, Michele M; Raimondi, Manuela T; Credi, Caterina; De Marco, Carmela; Turri, Stefano; Cerullo, Giulio; Osellame, Roberto

    2015-02-01

    Advancements in understanding stem cell functions and differentiation are of key importance for the clinical success of stem-cell-based therapies. 3D structural niches fabricated by two-photon polymerization are a powerful platform for controlling stem cell growth and differentiation. In this paper, we investigate the possibility of further controlling stem cell fate by tuning the mechanical properties of such niches through coating with thin layers of biomimetic hyaluronan-based and gelatin-based hydrogels. We first assess the biocompatibility of chemical coatings and then study the interactions between structural and chemical biomimetism on the response of MSCs in terms of proliferation and differentiation. We observed a clear effect of the hydrogel coating on otherwise identical 3D scaffolds. In particular, in gelatin-coated niches we observed a stronger metabolic activity and commitment toward the osteo-chondral lineage with respect to hyaluronan-coated niches. Conversely, a reduction in the homing effect was observed in all the coated niches, especially in gelatin-coated niches. This study demonstrates the feasibility of controlling independently different mechanical cues, in bioengineered stem cell niches, i.e. the 3D scaffold geometry and the surface stiffness. This will allow, on the one hand, understanding their specific role in stem cell proliferation and differentiation and, on the other hand, finely tuning their synergistic effect. PMID:25594262

  12. Development and evaluation of a device for simultaneous uniaxial compression and optical imaging of cartilage samples in vitro

    SciTech Connect

    Steinert, Marian; Kratz, Marita; Jones, David B.; Jaedicke, Volker; Hofmann, Martin R.

    2014-10-15

    In this paper, we present a system that allows imaging of cartilage tissue via optical coherence tomography (OCT) during controlled uniaxial unconfined compression of cylindrical osteochondral cores in vitro. We describe the system design and conduct a static and dynamic performance analysis. While reference measurements yield a full scale maximum deviation of 0.14% in displacement, force can be measured with a full scale standard deviation of 1.4%. The dynamic performance evaluation indicates a high accuracy in force controlled mode up to 25 Hz, but it also reveals a strong effect of variance of sample mechanical properties on the tracking performance under displacement control. In order to counterbalance these disturbances, an adaptive feed forward approach was applied which finally resulted in an improved displacement tracking accuracy up to 3 Hz. A built-in imaging probe allows on-line monitoring of the sample via OCT while being loaded in the cultivation chamber. We show that cartilage topology and defects in the tissue can be observed and demonstrate the visualization of the compression process during static mechanical loading.

  13. Articular Cartilage Injury and Potential Remedies.

    PubMed

    Chubinskaya, Susanna; Haudenschild, Dominik; Gasser, Seth; Stannard, James; Krettek, Christian; Borrelli, Joseph

    2015-12-01

    Osteoarthritis affects millions of people worldwide, is associated with joint stiffness and pain, and often causes significant disability and loss of productivity. Osteoarthritis is believed to occur as a result of ordinary "wear and tear" on joints during the course of normal activities of daily living. Posttraumatic osteoarthritis is a particular subset of osteoarthritis that occurs after a joint injury. Developing clinically relevant animal models will allow investigators to delineate the causes of posttraumatic osteoarthritis and develop means to slow or prevent its development after joint injury. Chondroprotectant compounds, which attack the degenerative pathways at a variety of steps, are being developed in an effort to prevent posttraumatic osteoarthritis and offer great promise. Often times, cartilage degradation after joint injury occurs despite our best efforts. When this happens, there are several evolving techniques that offer at least short-term relief from the effects of posttraumatic osteoarthritis. Occasionally, these traumatic lesions are so large that dramatic steps must be taken in an attempt to restore articular congruity and joint stability. Fresh osteochondral allografts have been used in these settings and offer the possibility of joint preservation. For patients presenting with neglected displaced intra-articular fractures that have healed, intra-articular osteotomy techniques are being developed in an effort to restore joint congruity and function. This article reviews the results of a newly developed animal model of posttraumatic osteoarthritis, several promising chondroprotectant compounds, and also cartilage techniques that are used when degenerative cartilage lesions develop after joint injury. PMID:26584267

  14. Current Concepts for Patellar Dislocation

    PubMed Central

    Petri, Maximilian; Ettinger, Max; Stuebig, Timo; Brand, Stephan; Krettek, Christian; Jagodzinski, Michael; Omar, Mohamed

    2015-01-01

    Context: Patellar dislocation usually occurs to the lateral side, leading to ruptures of the Medial Patellofemoral Ligament (MPFL) in about 90% of the cases. Even though several prognostic factors are identified for patellofemoral instability after patellar dislocation so far, the appropriate therapy remains a controversial issue. Evidence Acquisition: Authors searched the Medline library for studies on both surgical and conservative treatment for patellar dislocation and patellofemoral instability. Additionally, the reference list of each article was searched for additional studies. Results: A thorough analysis of the anatomical risk factors with a particular focus on patella alta, increased Tibial Tuberosity-Trochlear Groove (TT-TG) distance, trochlear dysplasia as well as torsional abnormalities should be performed early after the first dislocation to allow adequate patient counseling. Summarizing the results of all published randomized clinical trials and comparing surgical and conservative treatment after the first-time patellar dislocation until today indicated no significant evident difference for children, adolescents, and adults. Therefore, nonoperative treatment was indicated after a first-time patellar dislocation in the vast majority of patients. Conclusions: Surgical treatment for patellar dislocation is indicated primarily in case of relevant concomitant injuries such as osteochondral fractures, and secondarily for recurrent dislocations. PMID:26566512

  15. GROSS AND HISTOPATHOLOGIC CORRELATION OF LOW-FIELD MAGNETIC RESONANCE IMAGING FINDINGS IN THE STIFLE OF ASYMPTOMATIC HORSES.

    PubMed

    Santos, Marcos P; Gutierrez-Nibeyro, Santiago D; McKnight, Alexia L; Singh, Kuldeep

    2015-01-01

    With the recent introduction of a 0.25T rotating MRI system, clinical evaluation of the equine stifle joint is now possible in the average equine athlete. A recent publication described common abnormalities of horses with stifle lameness detected with a low-field MRI system; however, postmortem corroboration of the lesions detected was not possible. Therefore, our objective was to compare postmortem findings with low-field MRI findings in equine cadaver stifle joints. Ten fresh cadaver stifle joints from horses without clinical signs of stifle disease were evaluated using low-field MRI, gross dissection, and histopathology. In eight stifles, either the lateral or medial cranial meniscotibial ligament had an irregular shape, fiber separation, or moderate abnormal signal intensity (SI) on all sequences. In five stifles, the medial femoral condyle had articular cartilage fibrillation with or without an osteochondral defect over the weight bearing surface of the medial femoral condyle. All stifles had abnormal SI on all sequences within the patellar ligaments that corresponded with adipose tissue infiltrating between the collagen bundles. Other abnormalities identified included articular cartilage fibrillation of the tibial condyles in three stifles, and articular cartilage fibrillation with chondral defects in the patella in three stifles. All abnormalities detected with low-field MRI were corroborated by gross dissection. Findings from the current study supported the use of low-field MRI for detection of stifle joint lesions in horses and demonstrated that some stifle joint pathologies may be subclinical in horses. PMID:25545132

  16. Tailoring chemical and physical properties of fibrous scaffolds from block copolyesters containing ether and thio-ether linkages for skeletal differentiation of human mesenchymal stromal cells.

    PubMed

    Chen, Honglin; Gigli, Matteo; Gualandi, Chiara; Truckenmüller, Roman; van Blitterswijk, Clemens; Lotti, Nadia; Munari, Andrea; Focarete, Maria Letizia; Moroni, Lorenzo

    2016-01-01

    Bioactive scaffolds for tissue engineering call for demands on new materials which can enhance traditional biocompatibility requirements previously considered for clinical implantation. The current commercially available thermoplastic materials, such as poly(lactic acid) (PLA), poly(glycolic acid) (PGA), poly(?-caprolactone) (PCL) and their copolymers, have been used to fabricate scaffolds for regenerative medicine. However, these polymers have limitations including lacking of broadly tuning mechanical and degradable properties, and activation of specific cell-scaffold interactions, which limit their further application in tissue engineering. In the present study, electrospun scaffolds were successfully fabricated from a new class of block poly(butylene succinate)-based (PBS-based) copolyesters containing either butylene thiodiglycolate (BTDG) or butylene diglycolate (BDG) sequences. The polyesters displayed tunable mechanical properties and hydrolysis rate depending on the molecular architecture and on the kind of heteroatom introduced along the polymer backbone. To investigate their potential for skeletal regeneration, human mesenchymal stromal cells (hMSCs) were cultured on the scaffolds in basic, osteogenic and chondrogenic media. Our results demonstrated that PBS-based copolyesters containing thio-ether linkages (i.e. BTDG segments) were more favorable for chondrogenesis of hMSCs than those containing ether linkages (i.e. BDG sequences). In contrast, PBS-based copolyesters containing ether linkages showed enhanced mineralization. Therefore, these new functional scaffolds might hold potential for osteochondral tissue engineering applications. PMID:26546918

  17. Hip Microfracture

    PubMed Central

    McGill, Kevin C.; Bush-Joseph, Charles A.; Nho, Shane J.

    2010-01-01

    Microfracture is a marrow-stimulating technique used in the hip to treat cartilage defects associated with femoro-acetabular impingement, instability, or traumatic hip injury. These defects have a low probability of healing spontaneously and therefore often require surgical intervention. Originally adapted from the knee, microfracture is part of a spectrum of cartilage repair options that include palliative procedures such as debridement and lavage, reparative procedures such as marrow-stimulating techniques (abrasion arthroplasty and microfracture), and restorative procedures such as autologous chondrocyte implantation and osteochondral allograft/autografts. The basic indications for microfracture of the hip include focal and contained lesions typically less than 4 cm in diameter, full-thickness (Outerbridge grade IV) defects in weightbearing areas, unstable lesions with intact subchondral bone, and focal lesions without evidence of surrounding chondromalacia. Although not extensively studied in the hip, there are some small clinical series with promising early outcomes. Although the widespread use of microfracture in the hip is hindered by difficulties in identifying lesions on preoperative imaging and instrumentation to circumvent the femoral head, this technique continues to gain acceptance as an initial treatment for small, focal cartilage defects. PMID:26069544

  18. Chondrogenesis of Infrapatellar Fat Pad Derived Adipose Stem Cells in 3D Printed Chitosan Scaffold

    PubMed Central

    Ye, Ken; Felimban, Raed; Traianedes, Kathy; Moulton, Simon E.; Wallace, Gordon G.; Chung, Johnson; Quigley, Anita; Choong, Peter F. M.; Myers, Damian E.

    2014-01-01

    Infrapatellar fat pad adipose stem cells (IPFP-ASCs) have been shown to harbor chondrogenic potential. When combined with 3D polymeric structures, the stem cells provide a source of stem cells to engineer 3D tissues for cartilage repair. In this study, we have shown human IPFP-ASCs seeded onto 3D printed chitosan scaffolds can undergo chondrogenesis using TGF?3 and BMP6. By week 4, a pearlescent, cartilage-like matrix had formed that penetrated the top layers of the chitosan scaffold forming a ‘cap’ on the scaffold. Chondrocytic morphology showed typical cells encased in extracellular matrix which stained positively with toluidine blue. Immunohistochemistry demonstrated positive staining for collagen type II and cartilage proteoglycans, as well as collagen type I. Real time PCR analysis showed up-regulation of collagen type II, aggrecan and SOX9 genes when IPFP-ASCs were stimulated by TGF?3 and BMP6. Thus, IPFP-ASCs can successfully undergo chondrogenesis using TGF?3 and BMP6 and the cartilage-like tissue that forms on the surface of 3D-printed chitosan scaffold may prove useful as an osteochondral graft. PMID:24918443

  19. Alignment, segmentation and 3-D reconstruction of serial sections based on automated algorithm

    NASA Astrophysics Data System (ADS)

    Bian, Weiguo; Tang, Shaojie; Xu, Qiong; Lian, Qin; Wang, Jin; Li, Dichen

    2012-12-01

    A well-defined three-dimensional (3-D) reconstruction of bone-cartilage transitional structures is crucial for the osteochondral restoration. This paper presents an accurate, computationally efficient and fully-automated algorithm for the alignment and segmentation of two-dimensional (2-D) serial to construct the 3-D model of bone-cartilage transitional structures. Entire system includes the following five components: (1) image harvest, (2) image registration, (3) image segmentation, (4) 3-D reconstruction and visualization, and (5) evaluation. A computer program was developed in the environment of Matlab for the automatic alignment and segmentation of serial sections. Automatic alignment algorithm based on the position's cross-correlation of the anatomical characteristic feature points of two sequential sections. A method combining an automatic segmentation and an image threshold processing was applied to capture the regions and structures of interest. SEM micrograph and 3-D model reconstructed directly in digital microscope were used to evaluate the reliability and accuracy of this strategy. The morphology of 3-D model constructed by serial sections is consistent with the results of SEM micrograph and 3-D model of digital microscope.

  20. A novel synthesized sulfonamido-based gallic acid--LDQN-C: effects on chondrocytes growth and phenotype maintenance.

    PubMed

    Lu, Zhenhui; Wei, Shixiu; Wu, Huayu; Lin, Xiao; Lin, Cuiwu; Liu, Buming; Zheng, Li; Zhao, Jinmin

    2014-12-01

    Chondrocyte based therapy is promising to treat symptomatic chondral and osteochondral lesions. Growth factors to accelerate the proliferation and retain the phenotype of chondrocytes in vitro are imperative. However, the high cost and rapid degradation of growth factors limited their further application. Therefore, it is significant to find substitutes that can preserve chondrocytes phenotype and ensure sufficient cells for cytotherapy. Antioxidant and anti-inflammatory agents or their derivatives that have effect on arthritis may be an alternative. In this study, we synthesized sulfonamido-based gallate - LDQN-C and investigated its effect on rat articular chondrocytes through examination of the cell proliferation, morphology, viability, glycosaminoglycans (GAGs) synthesis and cartilage specific gene expression. Results showed that LDQN-C could enhance secretion and synthesis of cartilage extracellular matrix (ECM) by up-regulating expression levels of aggrecan, collagen II and Sox9 genes compared to the GA treated group and control group. Expression of collagen type II was effectively up-regulated while collagen I was down-regulated, which demonstrated that the inhibition of chondrocytes dedifferentiation by LDQN-C. Range of 1.36×10(-9)M to 1.36×10(-7)M is recommended dose of LDQN-C, among which the most profound response was observed with 1.36×10(-8)M. GA at concentration of 0.125?g/mL was compared. This study might provide a basis for the development of a novel agent for the treatment of articular cartilage defect. PMID:25305720

  1. Magnetic Resonance Imaging of Ferumoxide-Labeled Mesenchymal Stem Cells in Cartilage Defects: In Vitro and In Vivo Investigations

    PubMed Central

    Henning, Tobias D.; Gawande, Rakhee; Khurana, Aman; Tavri, Sidhartha; Mandrussow, Lydia; Golovko, Daniel; Horvai, Andrew; Sennino, Barbara; McDonald, Donald; Meier, Reinhard; Wendland, Michael; Derugin, Nikita; Link, Thomas M.; Daldrup-Link, Heike E.

    2013-01-01

    The purpose of this study was to (1) compare three different techniques for ferumoxide labeling of mesenchymal stem cells (MSCs), (2) evaluate if ferumoxide labeling allows in vivo tracking of matrix-associated stem cell implants (MASIs) in an animal model, and (3) compare the magnetic resonance imaging (MRI) characteristics of ferumoxide-labeled viable and apoptotic MSCs. MSCs labeled with ferumoxide by simple incubation, protamine transfection, or Lipofectin transfection were evaluated with MRI and histopathology. Ferumoxide-labeled and unlabeled viable and apoptotic MSCs in osteochondral defects of rat knee joints were evaluated over 12 weeks with MRI. Signal to noise ratios (SNRs) of viable and apoptotic labeled MASIs were tested for significant differences using t-tests. A simple incubation labeling protocol demonstrated the best compromise between significant magnetic resonance signal effects and preserved cell viability and potential for immediate clinical translation. Labeled viable and apoptotic MASIs did not show significant differences in SNR. Labeled viable but not apoptotic MSCs demonstrated an increasing area of T2 signal loss over time, which correlated to stem cell proliferation at the transplantation site. Histopathology confirmed successful engraftment of viable MSCs. The engraftment of iron oxide–labeled MASIs by simple incubation can be monitored over several weeks with MRI. Viable and apoptotic MASIs can be distinguished via imaging signs of cell proliferation at the transplantation site. PMID:22554484

  2. Current concepts: tissue engineering and regenerative medicine applications in the ankle joint

    PubMed Central

    Correia, S. I.; Pereira, H.; Silva-Correia, J.; Van Dijk, C. N.; Espregueira-Mendes, J.; Oliveira, J. M.; Reis, R. L.

    2014-01-01

    Tissue engineering and regenerative medicine (TERM) has caused a revolution in present and future trends of medicine and surgery. In different tissues, advanced TERM approaches bring new therapeutic possibilities in general population as well as in young patients and high-level athletes, improving restoration of biological functions and rehabilitation. The mainstream components required to obtain a functional regeneration of tissues may include biodegradable scaffolds, drugs or growth factors and different cell types (either autologous or heterologous) that can be cultured in bioreactor systems (in vitro) prior to implantation into the patient. Particularly in the ankle, which is subject to many different injuries (e.g. acute, chronic, traumatic and degenerative), there is still no definitive and feasible answer to ‘conventional’ methods. This review aims to provide current concepts of TERM applications to ankle injuries under preclinical and/or clinical research applied to skin, tendon, bone and cartilage problems. A particular attention has been given to biomaterial design and scaffold processing with potential use in osteochondral ankle lesions. PMID:24352667

  3. Normal Skeletal Maturation and Imaging Pitfalls in the Pediatric Shoulder.

    PubMed

    Zember, Jonathan S; Rosenberg, Zehava S; Kwong, Steven; Kothary, Shefali P; Bedoya, Maria A

    2015-01-01

    A growing number of magnetic resonance (MR) imaging studies of the shoulder are being performed as a result of greater and earlier participation of children and adolescents in competitive sports such as softball and baseball. However, scant information is available regarding the MR imaging features of the normal sequential development of the shoulder. The authors discuss the radiographic and MR imaging appearances of the normal musculoskeletal maturation patterns of the shoulder, with emphasis on (a) development of secondary ossification centers of the glenoid (including the subcoracoid and peripheral glenoid ossification centers); (b) development of preossification and secondary ossification centers of the humeral head and the variable appearance and number of the secondary ossification centers of the distal acromion, with emphasis on the formation of the os acromiale; (c) development of the growth plates, glenoid bone plates, glenoid bare area, and proximal humeral metaphyseal stripe; and (d) marrow signal alterations in the distal humerus, acromion, and clavicle. In addition, the authors discuss various imaging interpretation pitfalls inherent to the normal skeletal maturation of the shoulder, examining clues that may help distinguish normal development from true disease (eg, osteochondral lesions, labral tears, abscesses, fractures, infection, tendon disease, acromioclavicular widening, and os acromiale). Familiarity with the timing, location, and appearance of maturation patterns in the pediatric shoulder is crucial for correct image interpretation. PMID:26172355

  4. Management and prevention of acute and chronic lateral ankle instability in athletic patient populations

    PubMed Central

    McCriskin, Brendan J; Cameron, Kenneth L; Orr, Justin D; Waterman, Brian R

    2015-01-01

    Acute and chronic lateral ankle instability are common in high-demand patient populations. If not managed appropriately, patients may experience recurrent instability, chronic pain, osteochondral lesions of the talus, premature osteoarthritis, and other significant long-term disability. Certain populations, including young athletes, military personnel and those involved in frequent running, jumping, and cutting motions, are at increased risk. Proposed risk factors include prior ankle sprain, elevated body weight or body mass index, female gender, neuromuscular deficits, postural imbalance, foot/ankle malalignment, and exposure to at-risk athletic activity. Prompt, accurate diagnosis is crucial, and evidence-based, functional rehabilitation regimens have a proven track record in returning active patients to work and sport. When patients fail to improve with physical therapy and external bracing, multiple surgical techniques have been described with reliable results, including both anatomic and non-anatomic reconstructive methods. Anatomic repair of the lateral ligamentous complex remains the gold standard for recurrent ankle instability, and it effectively restores native ankle anatomy and joint kinematics while preserving physiologic ankle and subtalar motion. Further preventative measures may minimize the risk of ankle instability in athletic cohorts, including prophylactic bracing and combined neuromuscular and proprioceptive training programs. These interventions have demonstrated benefit in patients at heightened risk for lateral ankle sprain and allow active cohorts to return to full activity without adversely affecting athletic performance. PMID:25793157

  5. Subchondral bone in osteoarthritis: insight into risk factors and microstructural changes

    PubMed Central

    2013-01-01

    Osteoarthritis (OA) is a major cause of disability in the adult population. As a progressive degenerative joint disorder, OA is characterized by cartilage damage, changes in the subchondral bone, osteophyte formation, muscle weakness, and inflammation of the synovium tissue and tendon. Although OA has long been viewed as a primary disorder of articular cartilage, subchondral bone is attracting increasing attention. It is commonly reported to play a vital role in the pathogenesis of OA. Subchondral bone sclerosis, together with progressive cartilage degradation, is widely considered as a hallmark of OA. Despite the increase in bone volume fraction, subchondral bone is hypomineralized, due to abnormal bone remodeling. Some histopathological changes in the subchondral bone have also been detected, including microdamage, bone marrow edema-like lesions and bone cysts. This review summarizes basic features of the osteochondral junction, which comprises subchondral bone and articular cartilage. Importantly, we discuss risk factors influencing subchondral bone integrity. We also focus on the microarchitectural and histopathological changes of subchondral bone in OA, and provide an overview of their potential contribution to the progression of OA. A hypothetical model for the pathogenesis of OA is proposed. PMID:24321104

  6. Permeation of dimethyl sulfoxide into articular cartilage at subzero temperatures*

    PubMed Central

    Zhang, Shao-zhi; Yu, Xiao-yi; Chen, Guang-ming

    2012-01-01

    Osteochondral allografting has been proved to be a useful method to treat diseased or damaged areas of joint surfaces. Operational long-term stocks of grafts which supply a buffer between procurement and utilization would contribute to the commercialization or industrialization of this technology. Vitrification has been thought to be a promising method for successful preservation of articular cartilage (AC), but high concentration cryoprotectants (CPAs) are used which may cause high cellular toxicity. An effective way to reduce CPA toxicity is to increase CPA concentration gradually while the temperature is lowered. Understanding the mechanism of CPA permeation at subzero temperatures is important for designing the cryopreservation protocol. In this research, the permeation of dimethyl sulfoxide (Me2SO) in ovine AC at subzero temperatures was studied experimentally. Pretreated AC discs were exposed in Me2SO solutions for different time (0, 5, 15, 30, 50, 80, and 120 min) at three temperature levels (?10, ?20, and ?30 °C). The Me2SO concentration within the tissue was determined by ultraviolet (UV) spectrophotometry. The diffusion coefficients were estimated to be 0.85×10?6, 0.48×10?6, and 0.27×10?6 cm2/s at ?10, ?20, and ?30 °C, respectively, and the corresponding activation energy was 29.23 kJ/mol. Numerical simulation was performed to compare two Me2SO addition protocols, and the results demonstrated that the total loading duration could be effectively reduced with the knowledge of permeation kinetics. PMID:22374614

  7. Nutraceutical therapies for degenerative joint diseases: a critical review.

    PubMed

    Goggs, Robert; Vaughan-Thomas, Anne; Clegg, Peter D; Carter, Stuart D; Innes, John F; Mobasheri, Ali; Shakibaei, Mehdi; Schwab, Wolfgang; Bondy, Carolyn A

    2005-01-01

    There is growing recognition of the importance of nutritional factors in the maintenance of bone and joint health, and that nutritional imbalance combined with endocrine abnormalities may be involved in the pathogenesis of osteoarthritis (OA) and osteochondritis dissecans (OCD). Despite this, dietary programs have played a secondary role in the management of these connective tissue disorders. Articular cartilage is critically dependent upon the regular provision of nutrients (glucose and amino acids), vitamins (particularly vitamin C), and essential trace elements (zinc, magnesium, and copper). Therefore, dietary supplementation programs and nutraceuticals used in conjunction with non-steroidal, anti-inflammatory drugs (NSAIDs) may offer significant benefits to patients with joint disorders, such as OA and OCD. This article examines the available clinical evidence for the efficacy of nutraceuticals, antioxidant vitamin C, polyphenols, essential fatty acids, and mineral cofactors in the treatment of OA and related joint disorders in humans and veterinary species. This article also attempts to clarify the current state of knowledge. It also highlights the need for additional targeted research to elucidate the changes in nutritional status and potential alterations to the expression of plasma membrane transport systems in synovial structures in pathophysiological states, so that current therapy and future treatments may be better focused. PMID:16048146

  8. An amphiphilic degradable polymer/hydroxyapatite composite with enhanced handling characteristics promotes osteogenic gene expression in bone marrow stromal cells

    PubMed Central

    Kutikov, Artem B.; Song, Jie

    2013-01-01

    Electrospun polymer/hydroxyapatite (HA) composites combining biodegradability with osteoconductivity are attractive for skeletal tissue engineering applications. However, most biodegradable polymers such as PLA are hydrophobic and do not blend with adequate interfacial adhesion with HA, compromising the structural homogeneity, mechanical integrity, and biological performance of the composite. To overcome this challenge, we incorporated a hydrophilic polyethylene glycol (PEG) block to poly(D,L-lactic acid) to improve the adhesion of the degradable polymer with HA. The amphiphilic triblock copolymer PLA-PEG-PLA (PELA) improved the stability of HA-PELA suspension at 25 wt% HA content, which was readily electrospun into HA-PELA composite scaffolds with uniform fiber dimensions. HA-PELA was highly extensible (failure strain >200% vs. <40% for HA-PLA), superhydrophilic (~0° water contact angle vs. >100° for HA-PLA), and exhibited an 8-fold storage modulus increase (unlike deterioration for HA-PLA) upon hydration, owing to the favorable interaction between HA and PEG. HA-PELA also better promoted osteochondral lineage commitment of bone marrow stromal cells in unstimulated culture and supported far more potent osteogenesis upon induction than HA-PLA. We demonstrate that the chemical incorporation of PEG is an effective strategy to improve the performance of degradable polymer/HA composites for bone tissue engineering applications. PMID:23791675

  9. Bioinspired nanofibers support chondrogenesis for articular cartilage repair

    PubMed Central

    Coburn, Jeannine M.; Gibson, Matthew; Monagle, Sean; Patterson, Zachary; Elisseeff, Jennifer H.

    2012-01-01

    Articular cartilage repair remains a significant and growing clinical challenge with the aging population. The native extracellular matrix (ECM) of articular cartilage is a 3D structure composed of proteinaceous fibers and a hydrogel ground substance that together provide the physical and biological cues to instruct cell behavior. Here we present fibrous scaffolds composed of poly(vinyl alcohol) and the biological cue chondroitin sulfate with fiber dimensions on the nanoscale for application to articular cartilage repair. The unique, low-density nature of the described nanofiber scaffolds allows for immediate cell infiltration for optimal tissue repair. The capacity for the scaffolds to facilitate cartilage-like tissue formation was evaluated in vitro. Compared with pellet cultures, the nanofiber scaffolds enhance chondrogenic differentiation of mesenchymal stems cells as indicated by increased ECM production and cartilage specific gene expression while also permitting cell proliferation. When implanted into rat osteochondral defects, acellular nanofiber scaffolds supported enhanced chondrogenesis marked by proteoglycan production minimally apparent in defects left empty. Furthermore, inclusion of chondroitin sulfate into the fibers enhanced cartilage-specific type II collagen synthesis in vitro and in vivo. By mimicking physical and biological cues of native ECM, the nanofiber scaffolds enhanced cartilaginous tissue formation, suggesting their potential utility for articular cartilage repair. PMID:22665791

  10. Knee cartilage defect: marrow stimulating techniques.

    PubMed

    Mirza, M Zain; Swenson, Richard D; Lynch, Scott A

    2015-12-01

    Painful chondral defects of the knee are very difficult problems. The incidence of these lesions in the general population is not known since there is likely a high rate of asymptomatic lesions. The rate of lesions found during arthroscopic exam is highly variable, with reports ranging from 11 to 72 % Aroen (Aroen Am J Sports Med 32: 211-5, 2004); Curl(Arthroscopy13: 456-60, 1997); Figueroa(Arthroscopy 23(3):312-5, 2007;); Hjelle(Arthroscopy 18: 730-4, 2002). Examples of current attempts at cartilage restoration include marrow stimulating techniques, ostochondral autografts, osteochondral allografts, and autologous chondrocyte transplantation. Current research in marrow stimulating techniques has been focused on enhancing and guiding the biology of microfracture and other traditional techniques. Modern advances in stem cell biology and biotechnology have provided many avenues for exploration. The purpose of this work is to review current techniques in marrow stimulating techniques as it relates to chondral damage of the knee. PMID:26411978

  11. Direct Human Cartilage Repair Using Three-Dimensional Bioprinting Technology

    PubMed Central

    Cui, Xiaofeng; Breitenkamp, Kurt; Finn, M.G.; Lotz, Martin

    2012-01-01

    Current cartilage tissue engineering strategies cannot as yet fabricate new tissue that is indistinguishable from native cartilage with respect to zonal organization, extracellular matrix composition, and mechanical properties. Integration of implants with surrounding native tissues is crucial for long-term stability and enhanced functionality. In this study, we developed a bioprinting system with simultaneous photopolymerization capable for three-dimensional (3D) cartilage tissue engineering. Poly(ethylene glycol) dimethacrylate (PEGDMA) with human chondrocytes were printed to repair defects in osteochondral plugs (3D biopaper) in layer-by-layer assembly. Compressive modulus of printed PEGDMA was 395.73±80.40?kPa, which was close to the range of the properties of native human articular cartilage. Printed human chondrocytes maintained the initially deposited positions due to simultaneous photopolymerization of surrounded biomaterial scaffold, which is ideal in precise cell distribution for anatomic cartilage engineering. Viability of printed human chondrocytes increased 26% in simultaneous polymerization than polymerized after printing. Printed cartilage implant attached firmly with surrounding tissue and greater proteoglycan deposition was observed at the interface of implant and native cartilage in Safranin-O staining. This is consistent with the enhanced interface failure strength during the culture assessed by push-out testing. Printed cartilage in 3D biopaper had elevated glycosaminoglycan (GAG) content comparing to that without biopaper when normalized to DNA. These observations were consistent with gene expression results. This study indicates the importance of direct cartilage repair and promising anatomic cartilage engineering using 3D bioprinting technology. PMID:22394017

  12. Mesenchymal stem cells as a potent cell source for articular cartilage regeneration

    PubMed Central

    Baghaban Eslaminejad, Mohamadreza; Malakooty Poor, Elham

    2014-01-01

    Since articular cartilage possesses only a weak capacity for repair, its regeneration potential is considered one of the most important challenges for orthopedic surgeons. The treatment options, such as marrow stimulation techniques, fail to induce a repair tissue with the same functional and mechanical properties of native hyaline cartilage. Osteochondral transplantation is considered an effective treatment option but is associated with some disadvantages, including donor-site morbidity, tissue supply limitation, unsuitable mechanical properties and thickness of the obtained tissue. Although autologous chondrocyte implantation results in reasonable repair, it requires a two-step surgical procedure. Moreover, chondrocytes expanded in culture gradually undergo dedifferentiation, so lose morphological features and specialized functions. In the search for alternative cells, scientists have found mesenchymal stem cells (MSCs) to be an appropriate cellular material for articular cartilage repair. These cells were originally isolated from bone marrow samples and further investigations have revealed the presence of the cells in many other tissues. Furthermore, chondrogenic differentiation is an inherent property of MSCs noticed at the time of the cell discovery. MSCs are known to exhibit homing potential to the damaged site at which they differentiate into the tissue cells or secrete a wide spectrum of bioactive factors with regenerative properties. Moreover, these cells possess a considerable immunomodulatory potential that make them the general donor for therapeutic applications. All of these topics will be discussed in this review. PMID:25126383

  13. Mosaic arthroplasty of the medial femoral condyle in horses - An experimental study.

    PubMed

    Bodó, Gábor; Vásárhelyi, Gábor; Hangody, László; Módis, László

    2014-06-01

    One Arabian and 5 Hungarian half-bred horses were used to study the macroscopic and microscopic survival of autologous osteochondral grafts in the weight-bearing surface of the medial femoral condyle (MFC). Grafts were harvested from the cranial surface of the medial femoral trochlea (MFT) under arthroscopic control. Three of them were transplanted into the weight-bearing surface of the contralateral MFC using an arthrotomy approach. Three months later this transplantation procedure was repeated on the opposite stifle joints in the same animals, but at that time transplantation was performed arthroscopically. Follow-up arthroscopy was carried out 12 months after the first operations, and biopsies were taken from both the recipient and the donor sites for histological examination. During follow-up arthroscopy, the transplanted areas looked congruent and smooth. Microscopically, the characteristics of hyaline cartilage were present in 5 out of the 10 biopsies examined; however, in the other half of biopsies glycosaminoglycan (GAG) loss and change in the architecture of the transplanted cartilage was observed. In a 16-year-old horse, all grafts broke during harvesting, and thus transplantation was not performed. No radiological signs of osteoarthritic changes were detected 9 to 12 months after the operations in the donor and recipient joints. Clinically, no lameness or effusion was present three months after the transplantations. PMID:24334083

  14. Flexor Digitorum Accessorius Longus: Importance of Posterior Ankle Endoscopy

    PubMed Central

    Batista, Jorge Pablo; del Vecchio, Jorge Javier; Golanó, Pau; Vega, Jordi

    2015-01-01

    Endoscopy for the posterior region of the ankle through two portals is becoming more widespread for the treatment of a large number of conditions which used to be treated with open surgery years ago. The tendon of the flexor hallucis longus (FHL) travels along an osteofibrous tunnel between the posterolateral and posteromedial tubercles of the talus. Chronic inflammation of this tendon may lead to painful stenosing tenosynovitis. The aim of this report is to describe two cases depicting an accessory tendon which is an anatomical variation of the flexor hallucis longus in patients with posterior friction syndrome due to posterior ankle impingement and associated with a posteromedial osteochondral lesion of the talus. The anatomical variation (FDAL) described was a finding during an endoscopy of the posterior region of the ankle, and we have spared it by sectioning the superior flexor retinaculum only. The accessory flexor digitorum longus is an anatomical variation and should be taken into account when performing an arthroscopy of the posterior region of the ankle. We recommend this treatment on this type of injury although we admit this does not make a definite conclusion. PMID:26060592

  15. Talar injuries--the orthopaedic challenge.

    PubMed

    Lesi?, Aleksandar R; Zagorac, Slavisa G; Bumbasirevi?, Marko Z

    2012-01-01

    Injuries of the talus represents an important part of the foot and ankle trauma. Since talar bone connect the lower limb and foot, the sequelas of its trauma could have significant influence on the function of the whole lower limb and gait. The specific vascularization of the talus results in delayed union and even in the avascular necrosis. The diagnosis of the fractures of the talus can be made on the x-rays, but sometimes real picture of the fracture pattern can be seen only in the CT scans. Ocult fractures such as osteochondral fractures and avascular necrosis can be exactly detected on MRI in aim not to be overlookded as the ankle sprain diagnosis. The precise reduction and stable internal fixation is mandatory in the treatment to enable the anatomical position of the talonavicular, talocrural and subtalar joint and to make possible early motion and rehabilitation, without weight bearing. On the other hand, crushed fractures, open fractures and the Hawkins III-IV fractures with the dislocations of the talar body sometimes needs salvage procedures like Blair or tibio-talar or tibio-calcaneal fusion. PMID:22924299

  16. Stem cell regulatory function mediated by expression of a novel mouse Oct4 pseudogene

    SciTech Connect

    Lin, Huey; Shabbir, Arsalan; Molnar, Merced; Lee, Techung . E-mail: chunglee@buffalo.edu

    2007-03-30

    Multiple pseudogenes have been proposed for embryonic stem (ES) cell-specific genes, and their abundance suggests that some of these potential pseudogenes may be functional. ES cell-specific expression of Oct4 regulates stem cell pluripotency and self-renewing state. Although Oct4 expression has been reported in adult tissues during gene reprogramming, the detected Oct4 signal might be contributed by Oct4 pseudogenes. Among the multiple Oct4 transcripts characterized here is a {approx}1 kb clone derived from P19 embryonal carcinoma stem cells, which shares a {approx}87% sequence homology with the parent Oct4 gene, and has the potential of encoding an 80-amino acid product (designated as Oct4P1). Adenoviral expression of Oct4P1 in mesenchymal stem cells promotes their proliferation and inhibits their osteochondral differentiation. These dual effects of Oct4P1 are reminiscent of the stem cell regulatory function of the parent Oct4, and suggest that Oct4P1 may be a functional pseudogene or a novel Oct4-related gene with a unique function in stem cells.

  17. Stem cell origin differently affects bone tissue engineering strategies

    PubMed Central

    Mattioli-Belmonte, Monica; Teti, Gabriella; Salvatore, Viviana; Focaroli, Stefano; Orciani, Monia; Dicarlo, Manuela; Fini, Milena; Orsini, Giovanna; Di Primio, Roberto; Falconi, Mirella

    2015-01-01

    Bone tissue engineering approaches are encouraging for the improvement of conventional bone grafting technique drawbacks. Thanks to their self-renewal and multi-lineage differentiation ability, stem cells are one of the major actors in tissue engineering approaches, and among these adult mesenchymal stem cells (MSCs) hold a great promise for regenerative medicine strategies. Bone marrow MSCs (BM-MSCs) are the first- identified and well-recognized stem cell population used in bone tissue engineering. Nevertheless, several factors hamper BM-MSC clinical application and subsequently, new stem cell sources have been investigated for these purposes. The fruitful selection and combination of tissue engineered scaffold, progenitor cells, and physiologic signaling molecules allowed the surgeon to reconstruct the missing natural tissue. On the basis of these considerations, we analyzed the capability of two different scaffolds, planned for osteochondral tissue regeneration, to modulate differentiation of adult stem cells of dissimilar local sources (i.e., periodontal ligament, maxillary periosteum) as well as adipose-derived stem cells (ASCs), in view of possible craniofacial tissue engineering strategies. We demonstrated that cells are differently committed toward the osteoblastic phenotype and therefore, taking into account their specific features, they could be intriguing cell sources in different stem cell-based bone/periodontal tissue regeneration approaches. PMID:26441682

  18. Directing chondrogenic differentiation of mesenchymal stem cells with a solid-supported chitosan thermogel for cartilage tissue engineering.

    PubMed

    Huang, Hongjie; Zhang, Xin; Hu, Xiaoqing; Dai, Linghui; Zhu, Jingxian; Man, Zhentao; Chen, Haifeng; Zhou, Chunyan; Ao, Yingfang

    2014-06-01

    Hydrogels are attractive for cartilage tissue engineering because of their high plasticity and similarity with the native cartilage matrix. However, one critical drawback of hydrogels for osteochondral repair is their inadequate mechanical strength. To address this limitation, we constructed a solid-supported thermogel comprising a chitosan hydrogel system and demineralized bone matrix. Scanning electron microscopy, the equilibrium scanning ratio, the biodegradation rate, biomechanical tests, biochemical assays, metabolic activity tests, immunostaining and cartilage-specific gene expression analysis were used to evaluate the solid-supported thermogel. Compared with pure hydrogel or demineralized matrix, the hybrid biomaterial showed superior porosity, equilibrium swelling and degradation rate. The hybrid scaffolds exhibited an increased mechanical strength: 75% and 30% higher compared with pure hydrogels and demineralized matrix, respectively. After three days culture, bone-derived mesenchymal stem cells (BMSCs) maintained viability above 90% in all three materials; however, the cell retention of the hybrid scaffolds was more efficient and uniform than the other materials. Matrix production and chondrogenic differentiation of BMSCs in the hybrid scaffolds were superior to its precursors, based on glycosaminoglycan quantification and hyaline cartilage marker expression after three weeks in culture. Its easy preparation, favourable biophysical properties and chondrogenic capacity indicated that this solid-supported thermogel could be an attractive biomaterial framework for cartilage tissue engineering. PMID:24770944

  19. High Density Infill in Cracks and Protrusions from the Articular Calcified Cartilage in Osteoarthritis in Standardbred Horse Carpal Bones

    PubMed Central

    Laverty, Sheila; Lacourt, Mathieu; Gao, Chan; Henderson, Janet E.; Boyde, Alan

    2015-01-01

    We studied changes in articular calcified cartilage (ACC) and subchondral bone (SCB) in the third carpal bones (C3) of Standardbred racehorses with naturally-occurring repetitive loading-induced osteoarthritis (OA). Two osteochondral cores were harvested from dorsal sites from each of 15 post-mortem C3 and classified as control or as showing early or advanced OA changes from visual inspection. We re-examined X-ray micro-computed tomography (µCT) image sets for the presence of high-density mineral infill (HDMI) in ACC cracks and possible high-density mineralized protrusions (HDMP) from the ACC mineralizing (tidemark) front (MF) into hyaline articular cartilage (HAC). We hypothesized and we show that 20-µm µCT resolution in 10-mm diameter samples is sufficient to detect HDMI and HDMP: these are lost upon tissue decalcification for routine paraffin wax histology owing to their predominant mineral content. The findings show that µCT is sufficient to discover HDMI and HDMP, which were seen in 2/10 controls, 6/9 early OA and 8/10 advanced OA cases. This is the first report of HDMI and HDMP in the equine carpus and in the Standardbred breed and the first to rely solely on µCT. HDMP are a candidate cause for mechanical tissue destruction in OA. PMID:25927581

  20. The Healing Effect of Adipose-Derived Mesenchymal Stem Cells in Full-thickness Femoral Articular Cartilage Defects of Rabbit

    PubMed Central

    Mehrabani, D.; Babazadeh, M.; Tanideh, N.; Zare, S.; Hoseinzadeh, S.; Torabinejad, S.; Koohi-Hosseinabadi, O.

    2015-01-01

    Background: Articular cartilage defect can lead to degradation of subchondral bone and osteoarthritis (OA). Objective: To determine the healing effect of transplantation of adipose-derived mesenchymal stem cells (Ad-MSCs) in full-thickness femoral articular cartilage defects in rabbit. Methods: 12 rabbits were equally divided into cell-treated and control groups. In cell-treated group, 2×106 cells of third passage suspended in 1 mL of DMEM was injected into articular defect. The control group just received 1 mL of DMEM. Dulbecco’s modified Eagles medium (DMEM) supplemented with 10% fetal bovine serum (FBS), 1% penicillin and streptomycin and 2 mM L-glutamine were used for cell culture. To induce cartilage defect, 4 mm articular cartilage full-thickness defect was created in the knee. For histological evaluation in each group (H&E, safranin-O and toluidine blue), 3 rabbits were sacrificed 4 weeks and 3 animals, 8 weeks after cell transplantation. Results: In cell therapy group post-transplantation, no abnormal gross findings were noticed. Neo-formed tissues in cell-treated groups were translucent with a smooth and intact surface and less irregularity. In cell-treated group after 8 weeks post-transplantation, the overall healing score of experimental knees were superior when compared to other groups. Conclusion: We showed that Ad-MSCs, as an available and non-invasive produced source of cells, could be safely administered in knee osteochondral defects. PMID:26576262

  1. Popliteomeniscal fascicle tear: diagnosis and operative technique.

    PubMed

    Shin, Hong-Kwan; Lee, Hee-Sung; Lee, Young-Kuk; Bae, Ki-Cheor; Cho, Chul-Hyun; Lee, Kyung-Jae

    2012-09-01

    The occurrence and the consistency of the popliteomeniscal fascicle between the popliteus tendon and the lateral meniscus have been the subject of debate. It is difficult to diagnose and treat popliteomeniscal fascicle tears. Furthermore, popliteomeniscal fascicle tears are difficult to identify with arthroscopy. This article describes the diagnostic factors for popliteomeniscal fascicle tears and the safe, effective operative techniques that can be used for their treatment. We suggest that popliteomeniscal fascicle tears are diagnosed when the following 3 conditions are confirmed: (1) existence of mechanical symptoms such as pain, locking, and giving way in the lateral compartment of the knee; (2) identification of hypermobility of the lateral meniscus through arthroscopic probing; and (3) occurrence of an osteochondral lesion in the posterior area of the lateral femoral condyle. In the case of popliteomeniscal fascicle tears, the tear area can be repaired with a suture hook and polydioxanone with an all-inside technique. If the joint space is narrowing because of soft-tissue tightness, it can be repaired with a zone-specific cannula through an inside-out technique. PMID:23766962

  2. [Risk factors of suppurative complications in case of thoracic injury].

    PubMed

    Danielian, Sh N; Abakumov, M M; Vil'k, A P; Saprin, A A; Tatarinova, E V

    2015-01-01

    It was performed retrospective analysis of 463 cases of suppurative thoracic complications after injury (232) and closed thoracic trauma (231) for 20-year period. Incidence of purulent complications was 3.2% and 1.6% in case of injury and closed thoracic trauma respectively including pleural empyema in 1.5 and 1.3%, pulmonary abscess in 0.3 and 0.4%, mediastinitis in 0.35 and 0.12%, pericarditis in 1.5 and 0.26%, osteomyelitis in 0.4 and 0.18% respectively. Factors preceding suppurative complications in case of injuries and closed trauma have been considered as predictors. Multivariant regression analysis established significant risk factors of suppurative thoracic complications. Clotted hemothorax, mediastinal hemorrhage, heart injury, late appeal for medical assistance and mechanical ventilation over 5 days were identified irrespective of character of trauma. In case of thoracic injury there were damage of osteochondrous frame, hollow thoracic and abdominal organs, gunshot wound of lung, delirium and injuries severity over 20 scores according to ISS scale. Pulmonary bleeding, sternal fracture and Glasgow Coma Scale rate<12 scores were identified as risk factors in case of closed trauma. PMID:26271559

  3. Direct human cartilage repair using three-dimensional bioprinting technology.

    PubMed

    Cui, Xiaofeng; Breitenkamp, Kurt; Finn, M G; Lotz, Martin; D'Lima, Darryl D

    2012-06-01

    Current cartilage tissue engineering strategies cannot as yet fabricate new tissue that is indistinguishable from native cartilage with respect to zonal organization, extracellular matrix composition, and mechanical properties. Integration of implants with surrounding native tissues is crucial for long-term stability and enhanced functionality. In this study, we developed a bioprinting system with simultaneous photopolymerization capable for three-dimensional (3D) cartilage tissue engineering. Poly(ethylene glycol) dimethacrylate (PEGDMA) with human chondrocytes were printed to repair defects in osteochondral plugs (3D biopaper) in layer-by-layer assembly. Compressive modulus of printed PEGDMA was 395.73±80.40?kPa, which was close to the range of the properties of native human articular cartilage. Printed human chondrocytes maintained the initially deposited positions due to simultaneous photopolymerization of surrounded biomaterial scaffold, which is ideal in precise cell distribution for anatomic cartilage engineering. Viability of printed human chondrocytes increased 26% in simultaneous polymerization than polymerized after printing. Printed cartilage implant attached firmly with surrounding tissue and greater proteoglycan deposition was observed at the interface of implant and native cartilage in Safranin-O staining. This is consistent with the enhanced interface failure strength during the culture assessed by push-out testing. Printed cartilage in 3D biopaper had elevated glycosaminoglycan (GAG) content comparing to that without biopaper when normalized to DNA. These observations were consistent with gene expression results. This study indicates the importance of direct cartilage repair and promising anatomic cartilage engineering using 3D bioprinting technology. PMID:22394017

  4. Customized biomimetic scaffolds created by indirect three-dimensional printing for tissue engineering.

    PubMed

    Lee, Ju-Yeon; Choi, Bogyu; Wu, Benjamin; Lee, Min

    2013-12-01

    Three-dimensional printing (3DP) is a rapid prototyping technique that can create complex 3D structures by inkjet printing of a liquid binder onto powder biomaterials for tissue engineering scaffolds. Direct fabrication of scaffolds from 3DP, however, imposes a limitation on material choices by manufacturing processes. In this study, we report an indirect 3DP approach wherein a positive replica of desired shapes was printed using gelatin particles, and the final scaffold was directly produced from the printed mold. To create patient-specific scaffolds that match precisely to a patient's external contours, we integrated our indirect 3DP technique with imaging technologies and successfully created custom scaffolds mimicking human mandibular condyle using polycaprolactone and chitosan for potential osteochondral tissue engineering. To test the ability of the technique to precisely control the internal morphology of the scaffolds, we created orthogonal interconnected channels within the scaffolds using computer-aided-design models. Because very few biomaterials are truly osteoinductive, we modified inert 3D printed materials with bioactive apatite coating. The feasibility of these scaffolds to support cell growth was investigated using bone marrow stromal cells (BMSC). The BMSCs showed good viability in the scaffolds, and the apatite coating further enhanced cellular spreading and proliferation. This technique may be valuable for complex scaffold fabrication. PMID:24060622

  5. Multiscale Biofabrication of Articular Cartilage: Bioinspired and Biomimetic Approaches.

    PubMed

    Tatman, Philip David; Gerull, William; Sweeney-Easter, Sean; Davis, Jeffrey Isaac; Gee, Albert O; Kim, Deok-Ho

    2015-12-01

    Articular cartilage is the load-bearing tissue found inside all articulating joints of the body. It vastly reduces friction and allows for smooth gliding between contacting surfaces. The structure of articular cartilage matrix and cellular composition is zonal and is important for its mechanical properties. When cartilage becomes injured through trauma or disease, it has poor intrinsic healing capabilities. The spectrum of cartilage injury ranges from isolated areas of the joint to diffuse breakdown and the clinical appearance of osteoarthritis. Current clinical treatment options remain limited in their ability to restore cartilage to its normal functional state. This review focuses on the evolution of biomaterial scaffolds that have been used for functional cartilage tissue engineering. In particular, we highlight recent developments in multiscale biofabrication approaches attempting to recapitulate the complex 3D matrix of native articular cartilage tissue. Additionally, we focus on the application of these methods to engineering each zone of cartilage and engineering full-thickness osteochondral tissues for improved clinical implantation. These methods have shown the potential to control individual cell-to-scaffold interactions and drive progenitor cell differentiation into a chondrocyte lineage. The use of these bioinspired nanoengineered scaffolds hold promise for recreation of structure and function on the whole tissue level and may represent exciting new developments for future clinical applications for cartilage injury and restoration. PMID:26200439

  6. A zebrafish model of Poikiloderma with Neutropenia recapitulates the human syndrome hallmarks and traces back neutropenia to the myeloid progenitor

    PubMed Central

    Colombo, Elisa A.; Carra, Silvia; Fontana, Laura; Bresciani, Erica; Cotelli, Franco; Larizza, Lidia

    2015-01-01

    Poikiloderma with Neutropenia (PN) is an autosomal recessive genodermatosis characterized by early-onset poikiloderma, pachyonychia, hyperkeratosis, bone anomalies and neutropenia, predisposing to myelodysplasia. The causative C16orf57/USB1 gene encodes a conserved phosphodiesterase that regulates the stability of spliceosomal U6-RNA. The involvement of USB1 in splicing has not yet allowed to unveil the pathogenesis of PN and how the gene defects impact on skin and bone tissues besides than on the haematological compartment. We established a zebrafish model of PN using a morpholino-knockdown approach with two different splicing morpholinos. Both usb1-depleted embryos displayed developmental abnormalities recapitulating the signs of the human syndrome. Besides the pigmentation and osteochondral defects, usb1-knockdown caused defects in circulation, manifested by a reduced number of circulating cells. The overall morphant phenotype was also obtained by co-injecting sub-phenotypic dosages of the two morpholinos and could be rescued by human USB1 RNA. Integrated in situ and real-time expression analyses of stage-specific markers highlighted defects of primitive haematopoiesis and traced back the dramatic reduction in neutrophil myeloperoxidase to the myeloid progenitors showing down-regulated pu.1 expression. Our vertebrate model of PN demonstrates the intrinsic requirement of usb1 in haematopoiesis and highlights PN as a disorder of myeloid progenitors associated with bone marrow dysfunction. PMID:26522474

  7. In vivo cell tracking by bioluminescence imaging after transplantation of bioengineered cell sheets to the knee joint.

    PubMed

    Takaku, Yuko; Murai, Kunihiko; Ukai, Taku; Ito, Satoshi; Kokubo, Mami; Satoh, Masaaki; Kobayashi, Eiji; Yamato, Masayuki; Okano, Teruo; Takeuchi, Mamoru; Mochida, Joji; Sato, Masato

    2014-02-01

    In our previous studies, we have demonstrated effective regeneration of cartilage through the creation and application of layered cell sheets that combine both chondrocytes and synovial cells. In this study, we were able to demonstrate that cells derived from cell sheets can survive for long periods after transplantation into rat knee joints having osteochondral defects. We established a method for generating cell sheets from firefly luciferase-expressing chondrocytes obtained from transgenic Lewis rats, and carried out allogenic transplantation of these cell sheets into wild-type Lewis rats. We then administered luciferin and monitored the survival of the transplanted cells by using bioluminescence imaging (BLI). Our data showed that the transplanted cells survived and could be detected for more than 21 months, which was longer than expected. Furthermore, the BLI data showed that the transplanted cells remained in the knee joint and did not migrate to other parts of the body, thus confirming the safety of the cell sheets. In this study, we monitored the duration of survival of cell sheets composed of only chondrocytes, only synovial cells, or both chondrocytes and synovial cells, and found that all three types of cell sheets survived for an extended period of time. PMID:24360579

  8. Inorganic-organic hydrogel scaffolds for tissue engineering

    NASA Astrophysics Data System (ADS)

    Bailey, Brennan Margaret

    Analogous to the extracellular matrix (ECM) of natural tissues, properties of a tissue engineering scaffold direct cell behavior and thus regenerated tissue properties. These include both physical properties (e.g. morphology and modulus) and chemical properties (e.g. hydrophobicity, hydration and bioactivity). Notably, recent studies suggest that scaffold properties (e.g. modulus) may be as potent as growth factors in terms of directing stem cell fate. Thus, 3D scaffolds possessing specific properties modified for optimal cell regeneration have the potential to regenerate native-like tissues. Photopolymerizable poly(ethylene glycol) diacrylate (PEG-DA)-based hydrogels are frequently used as scaffolds for tissue engineering. They are ideal for controlled studies of cell-material interactions due to their poor protein adsorption in the absence of adhesive ligands thereby making them "biological blank slates". However, their range of physical and chemical properties is limited. Thus, hydrogel scaffolds which maintain the benefits of PEG-DA but possess a broader set of tunable properties would allow the establishment of predictive relationships between scaffold properties, cell behavior and regenerated tissue properties. Towards this goal, this work describes a series of unique hybrid inorganic-organic hydrogel scaffolds prepared using different solvents and also in the form of continuous gradients. Properties relevant to tissue regeneration were investigated including: swelling, morphology, modulus, degradation rates, bioactivity, cytocompatibility, and protein adhesion. These scaffolds were based on the incorporation of hydrophobic, bioactive and osteoinductive methacrylated star polydimethylsiloxane (PDMSstar-MA) ["inorganic component"] into hydrophilic PEG-DA ["organic component"]. The following parameters were varied: molecular weight (Mn) of PEG-DA (Mn = 3k & 6k g/mol) and PDMSstar-MA (Mn = 1.8k, 7k, 14k), ratio of PDMSstar-MA to PEG-DA (0:100 to 20:80), total macromer concentration (5 to 20 wt%) and utilizing either water or dichloromethane (DCM) fabrication solvent. The use of DCM produced solvent induced phase separation (SIPS) resulting in scaffolds with macroporous morphologies, enhanced modulus and a more homogenous distribution of the PDMSstar-MA component throughout. These hybrid hydrogel scaffolds were prepared in the form of continuous gradients such that a single scaffold contains spatially varied chemical and physical properties. Thus, cell-material interaction studies may be conducted more rapidly at different "zones" defined along the gradient. These gradients are also expected to benefit the regeneration of the osteochondral interface, an interfacial tissue that gradually transitions in tissue type. The final aspect of this work was focused on enhancing the osteogenic potential of PDMS via functionalization with amine and phosphonate. Both amine and phosphonate moieties have demonstrated bioactivity. Thus, it was expected that these properties will be enhanced for amine and phosphonate functionalized PDMS. The subsequent incorporation of these PDMS-based macromers into the previously described PEG-DA scaffold system is expected to be valuable for osteochondral tissue regeneration.

  9. Chondrogenesis of mesenchymal stem cells in a novel hyaluronate-collagen-tricalcium phosphate scaffolds for knee repair.

    PubMed

    Meng, F G; Zhang, Z Q; Huang, G X; Chen, W S; Zhang, Z J; He, A S; Liao, W M

    2016-01-01

    Scaffolds are expected to play a key role in the induction of chondrogenesis of mesenchymal stem cells (MSCs) for cartilage tissue regeneration. Here, we report the development of a novel tricalcium phosphate-collagen-hyaluronate (TCP-COL-HA) scaffold that can function as a stem cell carrier to induce chondrogenesis and promote cartilage repair, and the investigation of chondroinductive properties of scaffolds containing varying amounts of TCP, COL and HA. TCP-COL-HA scaffolds, as well as TCP-COL scaffolds at two different TCP/COL ratios (50:50 and 25:75), were evaluated for their ability to induce cartilage regeneration from rabbit mesenchymal stem cells (rMSCs) in vitro and in vivo. Chondrogenic differentiation was evaluated by sulphated glycosaminoglycan quantification, collagen type II immunohistochemistry, and qRT-PCR. Mechanical strength was evaluated by the compression test. The results showed that the TCP-COL-HA scaffolds enhanced rMSC chondrogenesis to a greater degree than did the TCP-COL scaffolds; for the latter, the scaffold with the lower TCP/COL ratio (25:75) was superior in terms of promoting rMSC chondrogenesis. Similar results were obtained in an ectopic implantation model in nude mice. In a critical-size rabbit osteochondral defect-repair model, rMSCs seeded on TCP-COL-HA scaffolds showed greater cartilage regeneration and integration into surrounding tissue than the TCP-COL groups, in which cartilage repair was more efficient at the 25:75 than at the 50:50 ratio. These results indicate that the addition of HA and different TCP/COL ratios can affect the chondroinductive capacity of scaffolds, and suggest that the TCP-COL-HA scaffold can serve as an effective cell carrier for cartilage regeneration. PMID:26728500

  10. Bioactive glass in tissue engineering

    PubMed Central

    Rahaman, Mohamed N.; Day, Delbert E.; Bal, B. Sonny; Fu, Qiang; Jung, Steven B.; Bonewald, Lynda F.; Tomsia, Antoni P.

    2011-01-01

    This review focuses on recent advances in the development and use of bioactive glass for tissue engineering applications. Despite its inherent brittleness, bioactive glass has several appealing characteristics as a scaffold material for bone tissue engineering. New bioactive glasses based on borate and borosilicate compositions have shown the ability to enhance new bone formation when compared to silicate bioactive glass. Borate-based bioactive glasses also have controllable degradation rates, so the degradation of the bioactive glass implant can be more closely matched to the rate of new bone formation. Bioactive glasses can be doped with trace quantities of elements such as Cu, Zn and Sr, which are known to be beneficial for healthy bone growth. In addition to the new bioactive glasses, recent advances in biomaterials processing have resulted in the creation of scaffold architectures with a range of mechanical properties suitable for the substitution of loaded as well as non-loaded bone. While bioactive glass has been extensively investigated for bone repair, there has been relatively little research on the application of bioactive glass to the repair of soft tissues. However, recent work has shown the ability of bioactive glass to promote angiogenesis, which is critical to numerous applications in tissue regeneration, such as neovascularization for bone regeneration and the healing of soft tissue wounds. Bioactive glass has also been shown to enhance neocartilage formation during in vitro culture of chondrocyte-seeded hydrogels, and to serve as a subchondral substrate for tissue-engineered osteochondral constructs. Methods used to manipulate the structure and performance of bioactive glass in these tissue engineering applications are analyzed. PMID:21421084

  11. Comparison of subjective lameness evaluation, force platforms and an inertial-sensor system to identify mild lameness in an equine osteoarthritis model.

    PubMed

    Donnell, J R; Frisbie, D D; King, M R; Goodrich, L R; Haussler, K K

    2015-11-01

    When mild lameness exists, agreement between clinicians is often controversial due to its subjective nature. The goal of the study was to compare subjective and objective methods to identify the presence of mild lameness using an established model of osteoarthritis (OA) in which OA was induced by creating a unilateral carpal osteochondral fragment (OCF) in the middle carpal joint of 16 horses. Subjective lameness evaluations (blinded and unblinded), force platforms (FP), and an inertial-sensor system (ISS) were used to detect forelimb lameness at four time points. Limbs identified as lame by each method were compared as well as compared with the OCF limb at each time point. Spearman correlations were calculated between all outcome parameters. Independent of time, blinded subjective evaluation (54%) and the ISS (60%) identified a higher percentage of horses as lame in the OCF limb compared to FP (40%). Blinded subjective evaluation and the ISS agreed which forelimb was lame more often (50%) compared with blinded subjective evaluation and the FP (38%). Induction of mild lameness within the OCF limb was supported by an increase in the frequency of horses considered lame by both subjective evaluations the ISS and a decrease (3.6%) in mean (among all horses) peak vertical force from baseline to post OCF induction. The percentage of horses identified as lame in the OCF limb, independent of time, was highest with the ISS (60%) followed by blinded subjective evaluation (51%) and the FP (42%). It was concluded that the best agreement was between subjective evaluation and the inertial-sensor system. PMID:26361749

  12. A Novel Synthesized Sulfonamido-Based Gallate—JEZ-C as Potential Therapeutic Agents for Osteoarthritis

    PubMed Central

    Lin, Xiao; Lin, Cuiwu; Liu, Buming; Zheng, Li; Zhao, Jinmin

    2015-01-01

    Gallic acid (GA) and its derivatives are anti-inflammatory agents reported to have an effect on osteoarthritis (OA). However, GA has much weaker anti-oxidant effects and inferior bioactivity compared with its derivatives. We modified GA with the introduction of sulfonamide to synthesize a novel compound named JEZ-C and analyzed its anti-arthritis and chondro-protective effects. Comparison of JEZ-C with its sources i.e. GA and Sulfamethoxazole (SMZ) was also performed. Results showed that JEZ-C could effectively inhibit the IL-1-mediated induction of MMP-1 and MMP-13 and could induce the expression of TIMP-1, which demonstrated its ability to reduce the progression of OA. JEZ-C can also exert chondro-protective effects by promoting cell proliferation and maintaining the phenotype of articular chondrocytes, as evidenced by improved cell growth, enhanced synthesis of cartilage specific markers such as aggrecan, collagen II and Sox9. Meanwhile, expression of the collagen I gene was effectively downregulated, revealing the inhibition of chondrocytes dedifferentiation by JEZ-C. Hypertrophy that may lead to chondrocyte ossification was also undetectable in JEZ-C groups. The recommended dose of JEZ-C ranges from 6.25×10-7 ?g/ml to 6.25×10-5 ?g/ml, among which the most profound response was observed with 6.25×10-6 ?g/ml. In contrast, its source products of GA and SMZ have a weak effect not only in the inhibition of OA but also in the bioactivity of chondrocytes, which indicated the significance of this modification. This study revealed JEZ-C as a promising novel agent in the treatment of chondral and osteochondral lesions. PMID:26107568

  13. Mild degenerative changes of hip cartilage in elderly patients: an available sample representative of early osteoarthritis

    PubMed Central

    Wei, Bo; Gu, Qiangrong; Li, Dong; Yan, Junwei; Guo, Yang; Mao, Fengyong; Xu, Yan; Zang, Fengchao; Wang, Liming

    2014-01-01

    This study investigated the cellular and molecular changes which occur in cartilage from adults with femoral neck fracture (FNF) and osteoarthritis (OA), and explored the similarities in hip cartilage obtained from elderly patients and patients with early OA. Femoral heads were retrieved from 23 female patients undergoing total hip arthroplasty (THA). This group included 7 healthy patients with FNF (hFNF), 8 elderly adults with FNF (eFNF), and 8 elderly patients with hip OA (OA). After high-field MRI T2 mapping, osteochondral plugs were harvested from the weight-bearing area of femoral heads for subsequent macroscopic, histologic, and immunochemical evaluation. Additionally, the contents of cartilage matrix were analyzed, and gene expression was detected. The surface of cartilage from hFNF and eFNF patients appeared smooth, regular, and elastic, whereas it showed irregularities, thinning, and defects in OA patients. Elevated T2 values and decreased accumulation of glycosaminoglycans (GAGs) were detected in cartilage from eFNF patients. Furthermore, type I collagen accumulation was slightly increased and type X collagen concentration was obviously elevated in eFNF patients; however, type II collagen distribution and the contents and anisotropy of collagen fibrils in eFNF patients showed no significant changes. Consistent with histology and immunohistochemical results, aggrecan was downregulated and type X collagen was upregulated, while collagens types I and II showed no significant changes in eFNF patients. The cellular and molecular characteristics of hip cartilage in eFNF patients who showed no symptoms of OA were similar to those in patients with mild OA. Thus, eFNF cartilage can serve as a comparative specimen for use in studies investigating early OA. PMID:25400727

  14. Identification of cold-temperature-regulated genes in Flavobacterium psychrophilum.

    PubMed

    Hesami, Shohreh; Metcalf, Devon S; Lumsden, John S; Macinnes, Janet I

    2011-03-01

    Flavobacterium psychrophilum is the etiological agent of bacterial coldwater disease (BCWD) and rainbow trout fry syndrome (RTFS). It causes disease primarily in fresh water-reared salmonids, but other fish species can also be affected. A diverse array of clinical conditions is associated with BCWD, including tail rot (peduncle disease), necrotic myositis, and cephalic osteochondritis. Degradation of connective and muscular tissues by extracellular proteases is common to all of these presentations. There are no effective vaccines to prevent BCWD or RTFS, and antibiotics are often used to prevent and control disease. To identify virulence factors that might permit development of an efficacious vaccine, cDNA suppression subtractive hybridization (SSH) was used to identify cold-regulated genes in a virulent strain of F. psychrophilum. Genes predicted to encode a two-component system sensor histidine kinase (LytS), an ATP-dependent RNA helicase, a multidrug ABC transporter permease/ATPase, an outer membrane protein/protective antigen OMA87, an M43 cytophagalysin zinc-dependent metalloprotease, a hypothetical protein, and four housekeeping genes were upregulated at 8°C versus the level of expression at 20°C. Because no F. psychrophilum gene was known to be suitable as an internal standard in reverse transcription-quantitative real-time PCR (RT-qPCR) experiments, the expression stability of nine commonly used reference genes was evaluated at 8°C and 20°C. Expression of the 16S rRNA was equivalent at both temperatures, and this gene was used in RT-qPCR experiments to verify the SSH findings. With the exception of the ATCC 49513 strain, similar patterns of gene expression were obtained with 11 other representative strains of F. psychrophilum. PMID:21216906

  15. Microsphere-Based Scaffolds Carrying Opposing Gradients of Chondroitin Sulfate and Tricalcium Phosphate

    PubMed Central

    Gupta, Vineet; Mohan, Neethu; Berkland, Cory J.; Detamore, Michael S.

    2015-01-01

    Extracellular matrix (ECM) components, such as chondroitin sulfate (CS) and tricalcium phosphate, serve as raw materials, and thus spatial patterning of these raw materials may be leveraged to mimic the smooth transition of physical, chemical, and mechanical properties at the bone-cartilage interface. We hypothesized that encapsulation of opposing gradients of these raw materials in high molecular weight poly(d,l-lactic-co-glycolic acid) (PLGA) microsphere-based scaffolds would enhance differentiation of rat bone marrow–derived stromal cells. The raw material encapsulation altered the microstructure of the microspheres and also influenced the cellular morphology that depended on the type of material encapsulated. Moreover, the mechanical properties of the raw material encapsulating microsphere-based scaffolds initially relied on the composition of the scaffolds and later on were primarily governed by the degradation of the polymer phase and newly synthesized ECM by the seeded cells. Furthermore, raw materials had a mitogenic effect on the seeded cells and led to increased glycosaminoglycan (GAG), collagen, and calcium content. Interestingly, the initial effects of raw material encapsulation on a per-cell basis might have been overshadowed by medium-regulated environment that appeared to favor osteogenesis. However, it is to be noted that in vivo, differentiation of the cells would be governed by the surrounding native environment. Thus, the results of this study demonstrated the potential of the raw materials in facilitating neo-tissue synthesis in microsphere-based scaffolds and perhaps in combination with bioactive signals, these raw materials may be able to achieve intricate cell differentiation profiles required for regenerating the osteochondral interface. PMID:26191526

  16. Bone fatigue and its implications for injuries in racehorses.

    PubMed

    Martig, S; Chen, W; Lee, P V S; Whitton, R C

    2014-07-01

    Musculoskeletal injuries are a common cause of lost training days and wastage in racehorses. Many bone injuries are a consequence of repeated high loading during fast work, resulting in chronic damage accumulation and material fatigue of bone. The highest joint loads occur in the fetlock, which is also the most common site of subchondral bone injury in racehorses. Microcracks in the subchondral bone at sites where intra-articular fractures and palmar osteochondral disease occur are similar to the fatigue damage detected experimentally after repeated loading of bone. Fatigue is a process that has undergone much study in material science in order to avoid catastrophic failure of engineering structures. The term 'fatigue life' refers to the numbers of cycles of loading that can be sustained before failure occurs. Fatigue life decreases exponentially with increasing load. This is important in horses as loads within the limb increase with increasing speed. Bone adapts to increased loading by modelling to maintain the strains within the bone at a safe level. Bone also repairs fatigued matrix through remodelling. Fatigue injuries develop when microdamage accumulates faster than remodelling can repair. Remodelling of the equine metacarpus is reduced during race training and accelerated during rest periods. The first phase of remodelling is bone resorption, which weakens the bone through increased porosity. A bone that is porous following a rest period may fail earlier than a fully adapted bone. Maximising bone adaptation is an important part of training young racehorses. However, even well-adapted bones accumulate microdamage and require ongoing remodelling. If remodelling inhibition at the extremes of training is unavoidable then the duration of exposure to high-speed work needs to be limited and appropriate rest periods instituted. Further research is warranted to elucidate the effect of fast-speed work and rest on bone damage accumulation and repair. PMID:24528139

  17. State of the Art: MR Imaging after Knee Cartilage Repair Surgery.

    PubMed

    Guermazi, Ali; Roemer, Frank W; Alizai, Hamza; Winalski, Carl S; Welsch, Goetz; Brittberg, Mats; Trattnig, Siegfried

    2015-10-01

    Cartilage injuries are common, especially in athletes. Because these injuries frequently affect young patients, and they have the potential to progress to osteoarthritis, treatment to alleviate symptoms and delay joint degeneration is warranted. A number of surgical techniques are available to treat focal chondral defects, including marrow stimulation, osteochondral auto- and allografting, and autologous chondrocyte implantation. Although arthroscopy is considered the standard of reference for the evaluation of cartilage before and after repair, it is invasive with associated morbidity and cannot adequately depict the deep cartilage layer and underlying bone. Magnetic resonance (MR) imaging provides unparalleled noninvasive assessment of the repair site and all other joint tissues. MR observation of cartilage repair tissue is a well-established semiquantitative scoring system for repair tissue that has primarily been used in clinical research studies. The cartilage repair osteoarthritis knee score (CROAKS) optimizes comprehensive morphologic assessment of the knee joint after cartilage repair. Furthermore, quantitative, compositional MR imaging measurements (eg, T2, T2*, T1?), delayed gadolinium-enhanced MR imaging of cartilage (dGEMRIC), and sodium imaging are available for biochemical assessment. These quantitative MR imaging techniques help assess collagen content and orientation, water content, and glycosaminoglycan and/or proteoglycan content both in the repair tissue as it matures and in the "native" cartilage. In this review, the authors discuss the principles of state-of-the-art morphologic and compositional MR imaging techniques for imaging of cartilage repair and their application to longitudinal studies. (©) RSNA, 2015 Online supplemental material is available for this article. PMID:26402492

  18. Optical clearing of articular cartilage: a comparison of clearing agents

    NASA Astrophysics Data System (ADS)

    Bykov, Alexander; Hautala, Tapio; Kinnunen, Matti; Popov, Alexey; Karhula, Sakari; Saarakkala, Simo; Nieminen, Miika T.; Tuchin, Valery

    2015-07-01

    Optical clearing technique was applied to the problem of OCT imaging of articular cartilage and subchondral bone. We show that optical clearing significantly enhances visualization of articular cartilage and cartilage-bone interface. The effect of different clearing agents was analyzed. For the clearing, iohexol solution and propylene glycol (PG) were used. Clearing was performed in vitro at room temperature by immersion method. Cylindrical osteochondral samples (d=4.8mm) were drilled from bovine lateral femur and stored in phosphate-buffered saline at -20°C until clearing. Monitoring of clearing process was performed using high-speed spectral-domain OCT system providing axial resolution of 5.8?m at 930nm. Total duration of experiment was 90-100min to ensure saturation of clearing. We have shown that iohexol solution and PG are capable to optically clear articular cartilage enabling reliable characterization of cartilagebone interface with OCT. Being a low osmolarity agent, iohexol provides minimal changes to the thickness of cartilage sample. Clearing saturation time for the cartilage sample with the thickness of 0.9 mm measured with OCT is of 50 min. However, less than 15 min is enough to reliably detect the rear cartilage boundary. Alternatively, PG significantly (60%) reduces the cartilage thickness enabling better visualization of subchondral bone. It was observed that PG has higher clearing rate. The clearing saturation time is of 30 min, however less than 5 min is enough to detect cartilage-bone interface. We conclude that iohexol solution is superior for OCT imaging of cartilage and cartilage-bone interface, while PG suits better for subhondral bone visualization.

  19. A Novel Synthesized Sulfonamido-Based Gallate-JEZ-C as Potential Therapeutic Agents for Osteoarthritis.

    PubMed

    Wei, Shixiu; Lu, Zhenhui; Zou, Yunfeng; Lin, Xiao; Lin, Cuiwu; Liu, Buming; Zheng, Li; Zhao, Jinmin

    2015-01-01

    Gallic acid (GA) and its derivatives are anti-inflammatory agents reported to have an effect on osteoarthritis (OA). However, GA has much weaker anti-oxidant effects and inferior bioactivity compared with its derivatives. We modified GA with the introduction of sulfonamide to synthesize a novel compound named JEZ-C and analyzed its anti-arthritis and chondro-protective effects. Comparison of JEZ-C with its sources i.e. GA and Sulfamethoxazole (SMZ) was also performed. Results showed that JEZ-C could effectively inhibit the IL-1-mediated induction of MMP-1 and MMP-13 and could induce the expression of TIMP-1, which demonstrated its ability to reduce the progression of OA. JEZ-C can also exert chondro-protective effects by promoting cell proliferation and maintaining the phenotype of articular chondrocytes, as evidenced by improved cell growth, enhanced synthesis of cartilage specific markers such as aggrecan, collagen II and Sox9. Meanwhile, expression of the collagen I gene was effectively downregulated, revealing the inhibition of chondrocytes dedifferentiation by JEZ-C. Hypertrophy that may lead to chondrocyte ossification was also undetectable in JEZ-C groups. The recommended dose of JEZ-C ranges from 6.25×10-7 ?g/ml to 6.25×10-5 ?g/ml, among which the most profound response was observed with 6.25×10-6 ?g/ml. In contrast, its source products of GA and SMZ have a weak effect not only in the inhibition of OA but also in the bioactivity of chondrocytes, which indicated the significance of this modification. This study revealed JEZ-C as a promising novel agent in the treatment of chondral and osteochondral lesions. PMID:26107568

  20. Development and characterization of an acellular porcine cartilage bone matrix for use in tissue engineering.

    PubMed

    Kheir, Ehab; Stapleton, Thomas; Shaw, David; Jin, Zhongmin; Fisher, John; Ingham, Eileen

    2011-11-01

    The aim of this study was to develop a technique to decellularize a porcine cartilage bone construct with view to using this as a biological scaffold for cartilage substitution. The decellularization protocol applied freeze/thaw cycles; this was followed by cyclic incubation in hypotonic tris buffer and 0.1% (w/v) sodium dodecyl sulfate in hypotonic buffer plus protease inhibitors. Nucleases (RNase and DNase) were used to digest nucleic acids followed by disinfection using 0.1% (v/v) peracetic acid. Histological analysis confirmed the absence of visible cells within the decellularized tissue. DNA analysis revealed the near-complete removal of genomic DNA from the decellularized tissues. The decellularization process had minimal effect on the collagen content of the cartilage. However, there was a significant reduction in the glycosaminoglycan content in the decellularized tissues. There was no evidence of the expression of the major xenogeneic epitope, galactose-?-1,3-galactose. Biomechanical indentation testing of decellularized tissues showed a significant change in comparison to the fresh cartilage. This was presumed to be caused by the reduction in the glycosaminoglycan content. Biocompatibility of the acellular scaffold was determined using contact cytotoxicity assays and a galactosyltransferase knockout mouse model. Decellularized porcine cartilage tissue was found to exhibit favorable compatibility in both in vitro and in vivo tests. In conclusion, this study has generated data on the production of an acellular cartilage bone matrix scaffold for use in osteochondral defect repair. To our knowledge, this is the first study that has successfully removed whole cells and ?-gal from xenogeneic cartilage and bone tissue. PMID:21858917

  1. Stem Cell Therapies for Knee Cartilage Repair: The Current Status of Preclinical and Clinical Studies

    PubMed Central

    Anderson, John A.; Little, Dianne; Toth, Alison P.; Moorman, Claude T.; Tucker, Bradford S.; Ciccotti, Michael G.; Guilak, Farshid

    2014-01-01

    Background Articular cartilage damage of the knee is common, causing significant morbidity worldwide. Many adult tissues contain cells that are able to differentiate into multiple cell types, including chondrocytes. These stem cells have gained significant attention over the past decade and may become frontline management for cartilage defects in the very near future. Purpose The role of stem cells in the treatment of knee osteochondral defects was reviewed. Recent animal and clinical studies were reviewed to determine the benefits and potential outcomes of using stem cells for cartilage defects. Study Design Literature review. Methods A PubMed search was undertaken. The key phrase “stem cells and knee” was used. The search included reviews and original articles over an unlimited time period. From this search, articles outlining animal and clinical trials were selected. A search of current clinical trials in progress was performed on the clinicaltrials.gov website, and “stem cells and knee” was used as the search phrase. Results Stem cells have been used in many recent in vitro and animal studies. A number of cell-based approaches for cartilage repair have progressed from preclinical animal studies into clinical trials. Conclusion The use of stem cells for the treatment of cartilage defects is increasing in animal and clinical studies. Methods of delivery of stem cells to the knee’s cartilage vary from direct injection to implantation with scaffolds. While these approaches are highly promising, there is currently limited evidence of a direct clinical benefit, and further research is required to assess the overall outcome of stem cell therapies for knee cartilage repair. PMID:24220016

  2. Loss of Tbx1 induces bone phenotypes similar to cleidocranial dysplasia.

    PubMed

    Funato, Noriko; Nakamura, Masataka; Richardson, James A; Srivastava, Deepak; Yanagisawa, Hiromi

    2015-01-15

    T-box transcription factor, TBX1, is the major candidate gene for 22q11.2 deletion syndrome (DiGeorge/ Velo-cardio-facial syndrome) characterized by facial defects, thymus hypoplasia, cardiovascular anomalies and cleft palates. Here, we report that the loss of Tbx1 in mouse (Tbx1(-/-)) results in skeletal abnormalities similar to those of cleidocranial dysplasia (CCD) in humans, which is an autosomal-dominant skeletal disease caused by mutations in RUNX2. Tbx1(-/-) mice display short stature, absence of hyoid bone, failed closure of fontanelle, bifid xiphoid process and hypoplasia of clavicle and zygomatic arch. A cell-type-specific deletion of Tbx1 in osteochondro-progenitor (Tbx1(OPKO)) or mesodermal (Tbx1(MKO)) lineage partially recapitulates the Tbx1(-/-) bone phenotypes. Although Tbx1 expression has not been previously reported in neural crest, inactivation of Tbx1 in the neural crest lineage (Tbx1(NCKO)) leads to an absence of the body of hyoid bone and postnatal lethality, indicating an unanticipated role of Tbx1 in neural crest development. Indeed, Tbx1 is expressed in the neural crest-derived hyoid bone primordium, in addition to mesoderm-derived osteochondral progenitors. Ablation of Tbx1 affected Runx2 expression in calvarial bones and overexpression of Tbx1 induced Runx2 expression in vitro. Taken together, our current studies reveal that Tbx1 is required for mesoderm- and neural crest-derived osteoblast differentiation and normal skeletal development. TBX1 mutation could lead to CCD-like bone phenotypes in human. PMID:25209980

  3. Molecular changes after shockwave therapy in osteoarthritic knee in rats

    NASA Astrophysics Data System (ADS)

    Wang, C.-J.; Sun, Y.-C.; Wu, C.-T.; Weng, L.-H.; Wang, F.-S.

    2013-10-01

    This study investigated the molecular changes of DKK-1, MMP13, Wnt-5a and \\upbeta-catenin after extracorporeal shockwave therapy (ESWT) in anterior cruciate ligament transected (ACLT) osteoarthritic (OA) knee in rats. 27 male Spraque-Dawley rats were divided into three groups. Group I was the control one and received sham knee arthrotomy but no ACLT or ESWT. Group II underwent ACLT, but no ESWT. Group III underwent ACLT and received ESWT. The animals were killed at 12 weeks, and the harvested knee specimens were subjected to histopathological examination and immunohistochemical analysis. Radiographs of the knees were obtained at 0 and 12 weeks. At 12 weeks, radiographs of group II showed more arthritic changes with formation of osteochondral fragments, whereas very subtle arthritis was noted in groups I and III. In histopathological examination, group II showed a significant increase of Mankin score and a decrease of subchondral bone as compared to groups I and III. Group III showed a significant decrease of Mankin score and an increase of subchondral bone, with the data comparable to group I. In immunohistochemical analysis, group II showed significant increases of DKK-1 and MMP13 and decreases of Wnt-5a and \\upbeta-catenin in articular cartilage and subchondral bone as compared to groups I and III. Group III showed significant decreases of DKK-1 and MMP13 and increases of Wnt-5a and \\upbeta-catenin, with the data comparable to group I. In conclusion, the application of ESWT causes molecular changes that are consistent with the improvement in subchondral bone remodeling and chondroprotective effect in ACLT OA knees in rats.

  4. Cartilage Repair With Autologous Bone Marrow Mesenchymal Stem Cell Transplantation

    PubMed Central

    Yamasaki, Shinya; Mera, Hisashi; Itokazu, Maki; Hashimoto, Yusuke

    2014-01-01

    Clinical trials of various procedures, including bone marrow stimulation, mosaicplasty, and autologous chondrocyte implantation, have been explored to treat articular cartilage defects. However, all of them have some demerits. We focused on autologous culture-expanded bone marrow mesenchymal stem cells (BMSC), which can proliferate without losing their capacity for differentiation. First, we transplanted BMSC into the defective articular cartilage of rabbit and succeeded in regenerating osteochondral tissue. We then applied this transplantation in humans. Our previous reports showed that treatment with BMSC relieves the clinical symptoms of chondral defects in the knee and elbow joint. We investigated the efficacy of BMSC for osteoarthritic knee treated with high tibial osteotomy, by comparing 12 BMSC-transplanted patients with 12 cell-free patients. At 16-month follow-up, although the difference in clinical improvement between both groups was not significant, the arthroscopic and histological grading score was better in the cell-transplanted group. At the over 10-year follow-up, Hospital for Special Surgery knee scores improved to 76 and 73 in the BMSC-transplanted and cell-free groups, respectively, which were better than preoperative scores. Additionally, neither tumors nor infections were observed in all patients, and in the clinical study, we have never observed hypertrophy of repaired tissue, thereby guaranteeing the clinical safety of this therapy. Although we have never observed calcification above the tidemark in rabbit model and human histologically, the repair cartilage was not completely hyaline cartilage. To elucidate the optimum conditions for cell therapy, other stem cells, culture conditions, growth factors, and gene transfection methods should be explored. PMID:26069698

  5. Talar Fractures and Dislocations: A Radiologist's Guide to Timely Diagnosis and Classification.

    PubMed

    Melenevsky, Yulia; Mackey, Robert A; Abrahams, R Brad; Thomson, Norman B

    2015-01-01

    The talus, the second largest tarsal bone, has distinctive imaging characteristics and injury patterns. The predominantly extraosseous vascular supply of the talus predisposes it to significant injury in the setting of trauma. In addition, the lack of muscular attachments and absence of a secondary blood supply can lead to subsequent osteonecrosis. Although talar fractures account for less than 1% of all fractures, they commonly result from high-energy trauma and may lead to complications and long-term morbidity if not recognized and managed appropriately. While initial evaluation is with foot and ankle radiographs, computed tomography (CT) is often performed to evaluate the extent of the fracture, displacement, comminution, intra-articular extension, and associated injuries. Talar fractures are divided by anatomic region: head, neck, and body. Talar head fractures can be treated conservatively if nondisplaced, warranting careful radiographic and CT evaluation to assess rotation, displacement, and extension into the neck. The modified Hawkins-Canale classification of talar neck fractures is most commonly used due to its simplicity, usefulness in guiding treatment, and prognostic value, as it correlates associated malalignment with risk of subsequent osteonecrosis. Isolated talar body fractures may be more common than previously thought. The Sneppen classification further divides talar body fractures into osteochondral talar dome, lateral and posterior process, and shear and crush comminuted central body fractures. Crush comminuted central body fractures carry a poor prognosis due to nonanatomic reduction, bone loss, and subsequent osteonecrosis. Lateral process fractures can be radiographically occult and require a higher index of suspicion for successful diagnosis. Subtalar dislocations are often accompanied by fractures, necessitating postreduction CT. Familiarity with the unique talar anatomy and injury patterns is essential for radiologists to facilitate appropriate and timely management. PMID:25969933

  6. Cartilage Strain Distributions Are Different Under the Same Load in the Central and Peripheral Tibial Plateau Regions.

    PubMed

    Briant, Paul; Bevill, Scott; Andriacchi, Thomas

    2015-12-01

    There is increasing evidence that the regional spatial variations in the biological and mechanical properties of articular cartilage are an important consideration in the pathogenesis of knee osteoarthritis (OA) following kinematic changes at the knee due to joint destabilizing events (such as an anterior cruciate ligament (ACL) injury). Thus, given the sensitivity of chondrocytes to the mechanical environment, understanding the internal mechanical strains in knee articular cartilage under macroscopic loads is an important element in understanding knee OA. The purpose of this study was to test the hypothesis that cartilage from the central and peripheral regions of the tibial plateau has different internal strain distributions under the same applied load. The internal matrix strain distribution for each specimen was measured on osteochondral blocks from the tibial plateau of mature ovine stifle joints. Each specimen was loaded cyclically for 20?min, after which the specimen was cryofixed in its deformed position and freeze fractured. The internal matrix was viewed in a scanning electron microscope (SEM) and internal strains were measured by quantifying the deformation of the collagen fiber network. The peak surface tensile strain, maximum principal strain, and maximum shear strain were compared between the regions. The results demonstrated significantly different internal mechanical strain distributions between the central and peripheral regions of tibial plateau articular cartilage under both the same applied load and same applied nominal strain. These differences in the above strain measures were due to differences in the deformation patterns of the collagen network between the central and peripheral regions. Taken together with previous studies demonstrating differences in the biochemical response of chondrocytes from the central and peripheral regions of the tibial plateau to mechanical load, the differences in collagen network deformation observed in this study help to provide a fundamental basis for understanding the association between altered knee joint kinematics and premature knee OA. PMID:26501505

  7. Comparison of optical coherence tomography and histopathology in quantitative assessment of goat talus articular cartilage

    PubMed Central

    Cernohorsky, Paul; Kok, Aimee C; de Bruin, Daniel Martijn; Brandt, Martin J; Faber, Dirk J; Tuijthof, Gabrielle J; Kerkhoffs, Gino M; Strackee, Simon D; van Leeuwen, Ton G

    2015-01-01

    Background and purpose Optical coherence tomography (OCT) is a light-based imaging technique suitable for depiction of thin tissue layers such as articular cartilage. Quantification of results and direct comparison with a reference standard is needed to confirm the role of OCT in cartilage evaluation. Materials and methods Goat talus articular cartilage repair was assessed quantitatively with OCT and compared with histopathology using semi-automated analysis software. Osteochondral defects were created centrally in goat tali with subsequent healing over 24 weeks. After sacrifice, the tali were analyzed using OCT and processed into histopathology slides. Cartilage thickness, repair tissue area, and surface roughness were measured. Also, light attenuation coefficient measurements were performed to assess differences in the properties of healthy tissue and repair tissue. Results Intra-class correlation coefficients for resemblance between the 2 techniques were 0.95 (p < 0.001) for thickness, 0.73 (p = 0.002) for repair tissue area, and 0.63 (p = 0.015) for surface roughness. Light attenuation differed significantly between healthy cartilage (8.2 (SD 3.9) mm-1) and repair tissue (2.8 (SD 1.5) mm-1) (p < 0.001). Interpretation Compared to histopathology as the standard reference method, OCT is a reproducible technique in quantitative analysis of goat talus articular cartilage, especially when assessing cartilage thickness and to a lesser extent when measuring repair tissue area and surface roughness. Moreover, differences in local light attenuation suggest measurable variation in tissue structure, enhancing the clinical applicability of quantitative measurements from cartilage OCT images. PMID:25350610

  8. Of Mice, Men and Elephants: The Relation between Articular Cartilage Thickness and Body Mass

    PubMed Central

    Malda, Jos; de Grauw, Janny C.; Benders, Kim E. M.; Kik, Marja J. L.; van de Lest, Chris H. A.; Creemers, Laura B.; Dhert, Wouter J. A.; van Weeren, P. René

    2013-01-01

    Mammalian articular cartilage serves diverse functions, including shock absorption, force transmission and enabling low-friction joint motion. These challenging requirements are met by the tissue’s thickness combined with its highly specific extracellular matrix, consisting of a glycosaminoglycan-interspersed collagen fiber network that provides a unique combination of resilience and high compressive and shear resistance. It is unknown how this critical tissue deals with the challenges posed by increases in body mass. For this study, osteochondral cores were harvested post-mortem from the central sites of both medial and lateral femoral condyles of 58 different mammalian species ranging from 25 g (mouse) to 4000 kg (African elephant). Joint size and cartilage thickness were measured and biochemical composition (glycosaminoclycan, collagen and DNA content) and collagen cross-links densities were analyzed. Here, we show that cartilage thickness at the femoral condyle in the mammalian species investigated varies between 90 µm and 3000 µm and bears a negative allometric relationship to body mass, unlike the isometric scaling of the skeleton. Cellular density (as determined by DNA content) decreases with increasing body mass, but gross biochemical composition is remarkably constant. This however need not affect life-long performance of the tissue in heavier mammals, due to relatively constant static compressive stresses, the zonal organization of the tissue and additional compensation by joint congruence, posture and activity pattern of larger mammals. These findings provide insight in the scaling of articular cartilage thickness with body weight, as well as in cartilage biochemical composition and cellularity across mammalian species. They underscore the need for the use of appropriate in vivo models in translational research aiming at human applications. PMID:23437402

  9. ADAMTS-4 activity in synovial fluid as a biomarker of inflammation and effusion

    PubMed Central

    Roberts, S.; Evans, H.; Wright, K.; van Niekerk, L.; Caterson, B.; Richardson, J.B.; Kumar, K.H.S.; Kuiper, J.H.

    2015-01-01

    Summary Objective To evaluate the potential of ADAMTS-4 (aggrecanase -1) activity in synovial fluid (SF) as a biomarker of knee injury and joint disease. Design We have measured ADAMTS-4 activity in the synovial fluid of 170 orthopaedic patients with different degrees of joint pathology, using a commercial ADAMTS-4 fluorescence resonance energy transfer (FRET) substrate assay. Patients were classified at arthroscopy as (i) macroscopically normal, (ii) with an injury of the meniscus, anterior cruciate ligament or chondral/osteochondral defects or (iii) with osteoarthritis, and the influence of independent factors (age, patient group, effusion and synovial inflammation) on ADAMTS-4 activity levels was assessed. Results In most patients (106/170) ADAMTS-4 activity was undetectable; ADAMTS-4 ranged from 0 to 2.8 ng/mL in synovial fluid from patients with an injury, 0–4.1 ng/mL in osteoarthritic patients and 4.0–12.3 ng/mL in patients with large effusions. Four independent variables each significantly influenced ADAMTS-4 activity in synovial fluid (all P < 0.001): age (concordance = 0.69), presence of osteoarthritis (OA) (concordance = 0.66), level of effusion (concordance = 0.78) and inflammation (concordance = 0.68). Not only did effusion influence the amount of ADAMTS-4 activity most strongly, but it also did this in an ordered manner (P < 0.001). Conclusions The main finding of this study is that ADAMTS-4 levels in synovial fluid are most strongly correlated with inflammation and severity of effusion in the knee. Further study is required to determine if it could provide a useful tool to aid clinical diagnoses, indicate treatment, to monitor progression of joint degeneration or OA or alternatively the success of treatment. PMID:26003949

  10. Design and Validation of a Compressive Tissue Stimulator with High-Throughput Capacity and Real-Time Modulus Measurement Capability

    PubMed Central

    Salvetti, David J.; Pino, Christopher J.; Manuel, Steven G.; Dallmeyer, Ian; Rangarajan, Sanjeet V.; Meyer, Tobias; Kotov, Misha

    2012-01-01

    Mechanical stimulation has been shown to impact the properties of engineered hyaline cartilage constructs and is relevant for engineering of cartilage and osteochondral tissues. Most mechanical stimulators developed to date emphasize precision over adaptability to standard tissue culture equipment and protocols. The realization of mechanical characteristics in engineered constructs approaching native cartilage requires the optimization of complex variables (type of stimulus, regimen, and bimolecular signals). We have proposed and validated a stimulator design that focuses on high construct capacity, compatibility with tissue culture plastic ware, and regimen adaptability to maximize throughput. This design utilizes thin force sensors in lieu of a load cell and a linear encoder to verify position. The implementation of an individual force sensor for each sample enables the measurement of Young's modulus while stimulating the sample. Removable and interchangeable Teflon plungers mounted using neodymium magnets contact each sample. Variations in plunger height and design can vary the strain and force type on individual samples. This allows for the evaluation of a myriad of culture conditions and regimens simultaneously. The system was validated using contact accuracy, and Young's modulus measurements range as key parameters. Contact accuracy for the system was excellent within 1.16% error of the construct height in comparison to measurements made with a micrometer. Biomaterials ranging from bioceramics (cancellous bone, 123?MPa) to soft gels (1% agarose, 20?KPa) can be measured without any modification to the device. The accuracy of measurements in conjunction with the wide range of moduli tested demonstrate the unique characteristics of the device and the feasibility of using this device in mapping real-time changes to Young's modulus of tissue constructs (cartilage, bone) through the developmental phases in ex vivo culture conditions. PMID:21988089

  11. Investigation of Localized Delivery of Diclofenac Sodium from Poly(D,L-Lactic Acid-co-Glycolic Acid)/Poly(Ethylene Glycol) Scaffolds Using an In Vitro Osteoblast Inflammation Model

    PubMed Central

    Sidney, Laura E.; Heathman, Thomas R.J.; Britchford, Emily R.; Abed, Arif; Rahman, Cheryl V.

    2015-01-01

    Nonunion fractures and large bone defects are significant targets for osteochondral tissue engineering strategies. A major hurdle in the use of these therapies is the foreign body response of the host. Herein, we report the development of a bone tissue engineering scaffold with the ability to release anti-inflammatory drugs, in the hope of evading this response. Porous, sintered scaffolds composed of poly(D,L-lactic acid-co-glycolic acid) (PLGA) and poly(ethylene glycol) (PEG) were prepared with and without the anti-inflammatory drug diclofenac sodium. Analysis of drug release over time demonstrated a profile suitable for the treatment of acute inflammation with ?80% of drug released over the first 4 days and a subsequent release of around 0.2% per day. Effect of drug release was monitored using an in vitro osteoblast inflammation model, comprised of mouse primary calvarial osteoblasts stimulated with proinflammatory cytokines interleukin-1? (IL-1?), tumor necrosis factor-? (TNF-?), and interferon-? (IFN-?). Levels of inflammation were monitored by cell viability and cellular production of nitric oxide (NO) and prostaglandin E2 (PGE2). The osteoblast inflammation model revealed that proinflammatory cytokine addition to the medium reduced cell viability to 33%, but the release of diclofenac sodium from scaffolds inhibited this effect with a final cell viability of ?70%. However, releasing diclofenac sodium at high concentrations had a toxic effect on the cells. Proinflammatory cytokine addition led to increased NO and PGE2 production; diclofenac-sodium-releasing scaffolds inhibited NO release by ?64% and PGE2 production by ?52%, when the scaffold was loaded with the optimal concentration of drug. These observations demonstrate the potential use of PLGA/PEG scaffolds for localized delivery of anti-inflammatory drugs in bone tissue engineering applications. PMID:25104438

  12. An Autologous Bone Marrow Mesenchymal Stem Cell–Derived Extracellular Matrix Scaffold Applied with Bone Marrow Stimulation for Cartilage Repair

    PubMed Central

    Tang, Cheng; Jin, Chengzhe; Du, Xiaotao; Yan, Chao; Min, Byoung-Hyun; Xu, Yan

    2014-01-01

    Purpose: It is well known that implanting a bioactive scaffold into a cartilage defect site can enhance cartilage repair after bone marrow stimulation (BMS). However, most of the current scaffolds are derived from xenogenous tissue and/or artificial polymers. The implantation of these scaffolds adds risks of pathogen transmission, undesirable inflammation, and other immunological reactions, as well as ethical issues in clinical practice. The current study was undertaken to evaluate the effectiveness of implanting autologous bone marrow mesenchymal stem cell–derived extracellular matrix (aBMSC-dECM) scaffolds after BMS for cartilage repair. Methods: Full osteochondral defects were performed on the trochlear groove of both knees in 24 rabbits. One group underwent BMS only in the right knee (the BMS group), and the other group was treated by implantation of the aBMSC-dECM scaffold after BMS in the left knee (the aBMSC-dECM scaffold group). Results: Better repair of cartilage defects was observed in the aBMSC-dECM scaffold group than in the BMS group according to gross observation, histological assessments, immunohistochemistry, and chemical assay. The glycosaminoglycan and DNA content, the distribution of proteoglycan, and the distribution and arrangement of type II and I collagen fibers in the repaired tissue in the aBMSC-dECM scaffold group at 12 weeks after surgery were similar to that surrounding normal hyaline cartilage. Conclusions: Implanting aBMSC-dECM scaffolds can enhance the therapeutic effect of BMS on articular cartilage repair, and this combination treatment is a potential method for successful articular cartilage repair. PMID:24666429

  13. Associations between the properties of the cartilage matrix and findings from quantitative MRI in human osteoarthritic cartilage of the knee

    PubMed Central

    Wei, Bo; Du, Xiaotao; Liu, Jun; Mao, Fengyong; Zhang, Xiang; Liu, Shuai; Xu, Yan; Zang, Fengchao; Wang, Liming

    2015-01-01

    The aim of this study was to investigate the associations between the properties of the cartilage matrix and the results of T2 mapping and delayed gadolinium-enhanced magnetic resonance imaging (dGEMRIC) in human knee osteoarthritic cartilage. Osteochondral samples were harvested from the middle part of the femoral condyle and tibial plateaus of 20 patients with knee osteoarthritis (OA) during total knee arthroplasty. Sagittal T2 mapping, T1pre, and T1Gd were performed using 7.0T magnetic resonance imaging (MRI). Gycosaminoglycan (GAG) distribution was evaluated by OARSI, collagen anisotropy was assessed by polarized light microscopy (PLM), and biochemical analyses measured water, GAG, and collagen content. Associations between properties of the cartilage matrix and T2 and ?R1 (1/T1Gd-1/T1pre) values were explored using correlation analysis. T2 and ?R1 values were significantly correlated with the degree of cartilage degeneration (OARSI grade; ? = 0.53 and 0.77). T2 values were significantly correlated with water content (r = 0.69; P < 0.001), GAG content (r = -0.43; P < 0.001), and PLM grade (r = 0.47; P < 0.001), but not with collagen content (r = -0.02; P = 0.110). ?R1 values were significantly correlated with GAG content (r = -0.84; P < 0.001) and PLM grade (r = 0.41; P < 0.001). Taken together, T2 mapping and dGEMRIC results were correlated with the properties of the cartilage matrix in human knee osteoarthritic cartilage. Combination T2 mapping and dGEMRIC represents a potential non-invasive monitoring technique to detect the progress of knee OA. PMID:26097577

  14. Associations between the properties of the cartilage matrix and findings from quantitative MRI in human osteoarthritic cartilage of the knee.

    PubMed

    Wei, Bo; Du, Xiaotao; Liu, Jun; Mao, Fengyong; Zhang, Xiang; Liu, Shuai; Xu, Yan; Zang, Fengchao; Wang, Liming

    2015-01-01

    The aim of this study was to investigate the associations between the properties of the cartilage matrix and the results of T2 mapping and delayed gadolinium-enhanced magnetic resonance imaging (dGEMRIC) in human knee osteoarthritic cartilage. Osteochondral samples were harvested from the middle part of the femoral condyle and tibial plateaus of 20 patients with knee osteoarthritis (OA) during total knee arthroplasty. Sagittal T2 mapping, T1pre, and T1Gd were performed using 7.0T magnetic resonance imaging (MRI). Glycosaminoglycan (GAG) distribution was evaluated by OARSI, collagen anisotropy was assessed by polarized light microscopy (PLM), and biochemical analyses measured water, GAG, and collagen content. Associations between properties of the cartilage matrix and T2 and ?R1 (1/T1Gd-1/T1pre) values were explored using correlation analysis. T2 and ?R1 values were significantly correlated with the degree of cartilage degeneration (OARSI grade; ? = 0.53 and 0.77). T2 values were significantly correlated with water content (r = 0.69; P < 0.001), GAG content (r = -0.43; P < 0.001), and PLM grade (r = 0.47; P < 0.001), but not with collagen content (r = -0.02; P = 0.110). ?R1 values were significantly correlated with GAG content (r = -0.84; P < 0.001) and PLM grade (r = 0.41; P < 0.001). Taken together, T2 mapping and dGEMRIC results were correlated with the properties of the cartilage matrix in human knee osteoarthritic cartilage. Combination T2 mapping and dGEMRIC represents a potential non-invasive monitoring technique to detect the progress of knee OA. PMID:26097577

  15. Physico-chemical characterization of functional electrospun scaffolds for bone and cartilage tissue engineering.

    PubMed

    Mouthuy, P A; Ye, H; Triffitt, J; Oommen, G; Cui, Z

    2010-12-01

    Mimicking the zonal organization of the bone-cartilage interface will aid the production of functional osteochondral grafts for regeneration of skeletal joint defects. This study investigates the potential of the electrospinning technique to build a three-dimensional construct recapitulating the zonal matrix of this interface. Poly(lactic-co-glycolic acid) (PLGA) and PLGA-collagen solutions containing different concentrations of hydroxyapatite nanoparticles (nHAp) were electrospun on a thin layer of phosphate buffer saline solution spread on the collector in order to facilitate membrane detachment and recovery. Incorporation of increasing amounts of nHAp in PLGA solutions did not affect significantly the average diameter of the fibres, which was about 700 nm. However, in the presence of collagen, fibres with diameters below 100 nm were generally observed and the number of these fibres was inversely proportional to the ratio PLGA:collagen and proportional to the content of nHAp. PLGA membranes were rather hydrophobic, although the aqueous drop contact angles progressively fell from 125 degrees to 110 degrees when the content of nHAp was increased from 0 per cent to 50 per cent (w/v). PLGA-collagen membranes were more hydrophilic with contact angles between 60 degrees and 110 degrees; the values being proportional to the ratio PLGA:collagen and the content of nHAp. Also, the addition of nHAp from 0 per cent to 50 per cent (w/v) in the absence of collagen resulted in decreasing dramatically both the Young's modulus (Ym), from 34.3 +/- 1.8 MPa to 0.10 +/- 0.06 MPa, and the ultimate tensile strain (epsilon max), from a value higher than 40 per cent to 5 per cent. However, the presence of collagen together with nHAp allowed the creation of membranes much stiffer, although more brittle, as shown for membranes made with a ratio 8:2 and 10 per cent of nHAp, for which Ym = 70.0 +/- 6.6 MPa and epsilon max = 7 per cent. PMID:21287828

  16. Microscale Material Properties of Bone and the Mineralized Tissues of the Intervertebral Disc-Vertebral Body Interface

    NASA Astrophysics Data System (ADS)

    Paietta, Rachel C.

    The objective of this dissertation is to understand the influences of material structure on the properties, function and failure of biological connective tissues. Biological interfaces are becoming an increasingly studied system within mechanics and tissue engineering as a model for attaching dissimilar materials. The elastic modulus of bone (? 20 GPa) and cartilage (? 0.1-1 MPa) differ over orders of magnitude, which should intuitively create high stress concentrations and failure at the interface. Yet, these natural interface systems rarely fail in vivo, and the mechanism by which loads are transferred between tissues has not yet been established. Tissue quality is one major contributor to the mechanical behavior of bone and cartilage, and is defined by properties such as collagen orientation, mineral volume fraction, porosity and tissue geometry. These properties have yet to be established at the bone-cartilage interface in the spine, and the lack of quantitative data on material microstructure and behavior limits treatments and tissue engineering construct design. In this dissertation, second harmonic generation imaging, quantitative backscattered scanning electron imaging and nanoindentation are combined to characterize micrometer scale tissue quality and modulus in both bone and calcified cartilage. These techniques are utilized to: 1) determine the hierarchical micrometer to millimeter scale properties of lamellar bone, 2) quantify changes throughout development and aging at the human intervertebral disc-vertebral body junction, and 3) explore compressive fractures at this interface. This work is the first to provide quantitative data on the mineral volume fraction, collagen orientation and modulus from the same, undecalcified sections of tissue to corroborate tissue structure and mineralization and describe quantitative parameters of the interface. The principal findings from this work indicate that the underlying matrix, or collagen, organization in mineralized biological tissues and at the bone-cartilage interface plays an important mechanical role. Nanoindentation measurements in osteonal bone are affected by location within the lamellar structure, even though mineral volume fraction within a single osteon is relatively consistent compared to the differences observed between bone and calcified cartilage. While increasing mineral volume fraction contributes to increases in modulus in the calcified cartilage layer of the vertebral body-intervertebral disc interface, significant scatter remains. The collagenous matrix structure and type of collagen appear to have a significant influence on modulus as well. Collagen fibers of the disc mineralize adjacent to the bone of the vertebral body, and the persistence of this attachment zone from adolescence through senescence indicates that it likely serves a mechanical function. Fiber insertions into thick calcified cartilage regions likely create mechanically robust anchor points at the osteochondral interface.

  17. The Role of Inorganic Polyphosphates in the Formation of Bioengineered Cartilage Incorporating a Zone of Calcified Cartilage In Vitro

    NASA Astrophysics Data System (ADS)

    St-Pierre, Jean-Philippe

    The development of bioengineered cartilage for replacement of damaged articular cartilage has gained momentum in recent years. One such approach has been developed in the Kandel lab, whereby cartilage is formed by seeding primary articular chondrocytes on the top surface of a porous biodegradable calcium polyphosphate (CPP) bone substitute, permitting anchorage of the tissue within the pores of the substrate; however, the interfacial shear properties of the tissue-substrate interface of these biphasic constructs are 1 to 2 orders of magnitude lower than the native cartilage-subchondral bone interface. To overcome this limitation, a strategy was devised to generate a zone of calcified cartilage (ZCC), thereby mimicking the native architecture of the osteochondral junction; however, the ZCC was located slightly above the cartilage-CPP interface. Thus, it was hypothesized that polyphosphate released from the CPP substrate and accumulating in the tissue inhibits the formation of the ZCC at the tissue-substrate interface. Based on this information, a strategy was devised to generate biphasic constructs incorporating a properly located ZCC. This approach involved the application of a thin calcium phosphate film to the surfaces of porous CPP via a sol-gel procedure, thereby limiting the accumulation of polyphosphate in the cartilaginous tissue. This modification to the substrate surface did not negatively impact the quality of the in vitro-formed cartilage tissue or the ZCC. Interfacial shear testing of biphasic constructs demonstrated significantly improved interfacial shear properties in the presence of a properly located ZCC. These studies also led to the observation that chondrocytes produce endogenous polyphosphate and that its levels in deep zone cartilage appear inversely related to mineral deposition within the tissue. Using an in vitro model of cartilage calcification, it was demonstrated that polyphosphate levels are modulated in part by the inhibitory effects of fibroblast growth factor 18 on exopolyphosphatase activity in the tissue. Polyphosphate also appears to act in a feedback loop to control exopolyphosphatase activity. Interestingly, polyphosphate also exhibits positive effects on cartilage matrix accumulation. The potential implication of polyphosphate in the maintenance of articular cartilage homeostasis is intriguing and must be investigated further.

  18. Effects of glucosamine and risedronate alone or in combination in an experimental rabbit model of osteoarthritis

    PubMed Central

    2014-01-01

    Background The osteoarthritis (OA) treatment in humans and in animals is a major orthopaedic challenge because there is not an ideal drug for preserving the joint structure and function. The aim of this study was to assess the effects of the treatment with oral glucosamine and risedronate alone or in combination on articular cartilage, synovial membrane and subchondral bone in an experimental rabbit model of OA. Osteoarthritis was surgically induced on one knee of 32 New Zealand White rabbits using the contralateral as healthy controls. Three weeks later treatments were started and lasted 8 weeks. Animal were divided in four groups of oral treatment: the first group received only saline, the second 21.5 mg/kg/day of glucosamine sulfate, the third 0.07 mg/kg/day of risedronate; and the fourth group both drugs simultaneously at the same dosages. Following sacrifice femurs were removed and osteochondral cylinders and synovial membrane were obtained for its histological and micro-CT evaluation. Results Sample analysis revealed that the model induced osteoarthritic changes in operated knees. OA placebo group showed a significant increase in cartilage thickness respect to the control and inflammatory changes in synovial membrane; whereas subchondral bone structure and volumetric bone mineral density remained unchanged. All the treated animals showed an improvement of the cartilage swelling independent of the drug used. Treatment with glucosamine alone seemed to have no effect in the progression of cartilage pathology while risedronate treatment had better results in superficial fibrillation and in resolving the inflammatory changes of the tissues, as well as modifying the orientation of trabecular lattice. The combination of both compounds seemed to have additive effects showing better results than those treated with only one drug. Conclusions The results of this animal study suggested that glucosamine sulfate and risedronate treatment alone or in combination may be able to stop cartilage swelling. The risedronate treatment could partially stop the fibrillation and the inflammation of synovial membrane as well as modify the orientation of trabeculae in healthy and in osteoarthritic knees. PMID:24766775

  19. A history of lumbar disc herniation from Hippocrates to the 1990s.

    PubMed

    Truumees, Eeric

    2015-06-01

    In ancient times, a supernatural understanding of the syndrome of lumbar radiculopathy often involved demonic forces vexing the individual with often crippling pain. The ancient Greeks and Egyptians began to take a more naturalistic view and, critically, suspected a relationship between lumbar spinal pathology and leg symptoms. Relatively little then changed for those with sciatica until the classic works by Cotugno and Kocher arrived in the late 18th century. Early lumbar canal explorations were performed in the late 1800s and early 1900s by MacEwen, Horsley, Krause, Taylor, Dandy, and Cushing, among others. In these cases, when compressive pathologies were found and removed, the lesions typically were (mis-)identified as enchondromas or osteochondritis dissecans. To better understand the history, learn more about the first treatments of lumbar disc herniation, and evaluate the impact of the early influences on modern spine practice, searches of PubMed and Embase were performed using the search terms discectomy, medical history, lumbar spine surgery, herniated disc, herniated nucleus pulposus, sciatica, and lumbar radiculopathy. Additional sources were identified from the reference lists of the reviewed papers. Many older and ancient sources including De Ischiade Nervosa are available in English translations and were used. When full texts were not available, English abstracts were used. The first true, intentional discectomy surgery was performed by Mixter and Barr in 1932. Early on, a transdural approach was favored. In 1938, Love described the intralaminar, extradural approach. His technique, although modified with improved lighting, magnification, and retractors, remains a staple approach to disc herniations today. Other modalities such as chymopapain have been investigated. Some remain a part of the therapeutic armamentarium, whereas others have disappeared. By the 1970s, CT scanning after myelography markedly improved the clinical evaluation of patients with lumbar disc herniation. In this era, use of discectomy surgery increased rapidly. Even patients with very early symptoms were offered surgery. Later work, especially by Weber and Hakelius, showed that many patients with lumbar disc herniation would improve without surgical intervention. In the ensuing decades, the debate over operative indications and timing continued, reaching another pivotal moment with the 2006 publication of the initial results of Spine Patient Outcomes Research Trial. PMID:24752913

  20. Do Chondral Lesions of the Knee Correlate with Bone Tracer Uptake by Using SPECT/CT?

    PubMed

    Dordevic, Milos; Hirschmann, Michael T; Rechsteiner, Jan; Falkowski, Anna; Testa, Enrique; Hirschmann, Anna

    2016-01-01

    Purpose To evaluate the correlation of bone tracer uptake as determined with single photon emission computed tomography (SPECT)/computed tomography (CT) and the size and severity of chondral lesions detected with magnetic resonance (MR) imaging of the knee. Materials and Methods MR imaging and SPECT/CT images of 63 knee joints in 63 patients (mean age ± standard deviation, 49.2 years ± 12.7) with chondral or osteochondral lesions were prospectively collected and retrospectively analyzed after approval by the ethics committee. Chondral lesions were graded on MR images by using a modified Noyes grading scale (grade 0, intact; grade 1, fibrillations; grade 2, <50% defect; grade 3, >50% defect; and grade 4, grade three plus subchondral changes) and measured in two dimensions. Technetium 99m hydroxymethane diphosphonate SPECT/CT bone tracer uptake was volumetrically quantified by using validated software. Maximum values of each subchondral area (patellofemoral or medial and lateral femorotibial) were quantified, and a ratio was calculated in relation to a reference region in the femoral shaft, which represented the bone tracer uptake background activity. Grades and sizes of chondral lesions and bone tracer uptake were correlated by using an independent t test and analysis of variance (P < .05). Results Bone tracer uptake was low (mean relative uptake, 1.64 ± 0.95) in knees without any present chondral lesion. In knees with grade 3 and 4 chondral lesions, the relative ratio was significantly higher (3.62 ± 2.18, P = .002) than in knees with grade 1 and 2 lesions (2.95 ± 2.07). The larger the diameter of the chondral lesion, the higher the bone tracer uptake. Higher grades of chondral lesions (grades 3 and 4) larger than 4 cm(2) (4.96 ± 2.43) showed a significantly higher bone tracer uptake than smaller lesions (<1 cm(2), 2.72 ± 1.43 [P = .011]; and 1-4 cm(2), 3.28 ± 2.15 [P = .004]). Conclusion SPECT/CT findings significantly correlate with the degree and size of chondral lesions on MR images. Grade 3 and 4 chondral lesions of the knee, as well as larger lesions, correlate with a high bone tracer uptake. (©) RSNA, 2015. PMID:26162025