Repair and regeneration of osteochondral defects in the articular joints

People suffering from pain due to osteoarthritic or rheumatoidal changes in the joints are still waiting for a better treatment. Although some studies have achieved success in repairing small cartilage defects, there is no widely accepted method for complete repair of osteochondral defects. Also joint replacements have not yet succeeded in replacing of natural cartilage without complications. Therefore, there is room for a new medical approach, which outperforms currently used methods. The aim of this study is to show potential of using a tissue engineering approach for regeneration of osteochondral defects. The critical review of currently used methods for treatment of osteochondral defects is also provided. In this study, two kinds of hybrid scaffolds developed in Hutmacher's group have been analysed. The first biphasic scaffold consists of fibrin and PCL. The fibrin serves as a cartilage phase while the porous PCL scaffold acts as the subchondral phase. The second system comprises of PCL and PCL-TCP. The scaffolds were fabricated via fused deposition modeling which is a rapid prototyping system. Bone marrow-derived mesenchymal cells were isolated from New Zealand White rabbits, cultured in vitro and seeded into the scaffolds. Bone regenerations of the subchondral phases were quantified via micro CT analysis and the results demonstrated the potential of the porous PCL and PCL-TCP scaffolds in promoting bone healing. Fibrin was found to be lacking in this aspect as it degrades rapidly. On the other hand, the porous PCL scaffold degrades slowly hence it provides an effective mechanical support. This study shows that in the field of cartilage repair or replacement, tissue engineering may have big impact in the future. In vivo bone and cartilage engineering via combining a novel composite, biphasic scaffold technology with a MSC has been shown a high potential in the knee defect regeneration in the animal models. However, the clinical application of tissue engineering requires the future research work due to several problems, such as scaffold design, cellular delivery and implantation strategies.

In vivo evaluation of an ultra-thin polycaprolactone film as a wound dressing

The use of ultra-thin films as dressings for cutaneous wounds could prove advantageous in terms of better conformity to wound topography and improved vapour transmission. For this purpose, ultra-thin poly(epsilon-caprolactone) (PCL) films of 5-15 microm thickness were fabricated via a biaxial stretching technique. To evaluate their in vivo biocompatibility and feasibility as an external wound dressing, PCL films were applied over full and partial-thickness wounds in rat and pig models. Different groups of PCL films were used: untreated, NaOH-treated, untreated with fibrin, NaOH-treated with perforations, and NaOH-treated with fibrin and S-nitrosoglutathione. Wounds with no external dressings were used as controls. Wound contraction rate, histology and biomechanical analyses were carried out. Wounds re-epithelialized completely at a comparable rate. Formation of a neo-dermal layer and re-epithelialization were observed in all the wounds. A lower level of fibrosis was observed when PCL films were used, compared to the control wounds. Ultimate tensile strength of the regenerated tissue in rats reached 50-60% of that in native rat skin. Results indicated that biaxially-stretched PCL films did not induce inflammatory reactions when used in vivo as a wound dressing and supported the normal wound healing process in full and partial-thickness wounds.

Bone response to unloaded titanium implants in the fibula, iliac crest, and scapula: an animal study in the Yorkshire pig

The reconstruction of extended maxillary and mandibular defects with prefabricated free flaps is a two stage procedure, that allows immediate function with implant supported dentures. The appropriate delay between prefabrication and reconstruction depends on the interfacial strength of the bone–implant surface. The purpose of this animal study was to evaluate the removal torque of unloaded titanium implants in the fibula, the scapula and the iliac crest. Ninety implants with a sandblasted and acid-etched (SLA) surface were tested after healing periods of 3, 6, and 12 weeks, respectively. Removal torque values (RTV) were collected using a computerized counterclockwise torque driver. The bicortical anchored 8 mm implants in the fibula revealed values of 63.73 Ncm, 91.50 Ncm, and 101.83 Ncm at 3, 6, and 12 weeks, respectively. The monocortical anchorage in the iliac crest showed values of 71.40 Ncm, 63.14 Ncm, and 61.59 Ncm with 12 mm implants at the corresponding times. The monocortical anchorage in the scapula demonstrated mean RTV of 62.28 Ncm, 97.63 Ncm, and 99.7 Ncm with 12 mm implants at 3, 6, and 12 weeks, respectively. The study showed an increase of removal torque with increasing healing time. The interfacial strength for bicortical anchored 8 mm implants in the fibula was comparable to monocortical anchored 12 mm implants in the iliac crest and the scapula at the corresponding times. The resistance to shear seemed to be determined by the type of anchorage (monocortical vs. bicortical) and the length of the implant with greater amount of bone–implant interface.

The feasibility of vibration analysis as a technique to detect osseointegration of transfemoral implants

One of the main causes of above knee or transfemoral amputation (TFA) in the developed world is trauma to the limb. The number of people undergoing TFA due to limb trauma, particularly due to war injuries, has been increasing. Typically the trauma amputee population, including war-related amputees, are otherwise healthy, active and desire to return to employment and their usual lifestyle. Consequently there is a growing need to restore long-term mobility and limb function to this population. Traditionally transfemoral amputees are provided with an artificial or prosthetic leg that consists of a fabricated socket, knee joint mechanism and a prosthetic foot. Amputees have reported several problems related to the socket of their prosthetic limb. These include pain in the residual limb, poor socket fit, discomfort and poor mobility. Removing the socket from the prosthetic limb could eliminate or reduce these problems. A solution to this is the direct attachment of the prosthesis to the residual bone (femur) inside the residual limb. This technique has been used on a small population of transfemoral amputees since 1990. A threaded titanium implant is screwed in to the shaft of the femur and a second component connects between the implant and the prosthesis. A period of time is required to allow the implant to become fully attached to the bone, called osseointegration (OI), and be able to withstand applied load; then the prosthesis can be attached. The advantages of transfemoral osseointegration (TFOI) over conventional prosthetic sockets include better hip mobility, sitting comfort and prosthetic retention and fewer skin problems on the residual limb. However, due to the length of time required for OI to progress and to complete the rehabilitation exercises, it can take up to twelve months after implant insertion for an amputee to be able to load bear and to walk unaided. The long rehabilitation time is a significant disadvantage of TFOI and may be impeding the wider adoption of the technique. There is a need for a non-invasive method of assessing the degree of osseointegration between the bone and the implant. If such a method was capable of determining the progression of TFOI and assessing when the implant was able to withstand physiological load it could reduce the overall rehabilitation time. Vibration analysis has been suggested as a potential technique: it is a non destructive method of assessing the dynamic properties of a structure. Changes in the physical properties of a structure can be identified from changes in its dynamic properties. Consequently vibration analysis, both experimental and computational, has been used to assess bone fracture healing, prosthetic hip loosening and dental implant OI with varying degrees of success. More recently experimental vibration analysis has been used in TFOI. However further work is needed to assess the potential of the technique and fully characterise the femur-implant system. The overall aim of this study was to develop physical and computational models of the TFOI femur-implant system and use these models to investigate the feasibility of vibration analysis to detect the process of OI. Femur-implant physical models were developed and manufactured using synthetic materials to represent four key stages of OI development (identified from a physiological model), simulated using different interface conditions between the implant and femur. Experimental vibration analysis (modal analysis) was then conducted using the physical models. The femur-implant models, representing stage one to stage four of OI development, were excited and the modal parameters obtained over the range 0-5kHz. The results indicated the technique had limited capability in distinguishing between different interface conditions. The fundamental bending mode did not alter with interfacial changes. However higher modes were able to track chronological changes in interface condition by the change in natural frequency, although no one modal parameter could uniquely distinguish between each interface condition. The importance of the model boundary condition (how the model is constrained) was the key finding; variations in the boundary condition altered the modal parameters obtained. Therefore the boundary conditions need to be held constant between tests in order for the detected modal parameter changes to be attributed to interface condition changes. A three dimensional Finite Element (FE) model of the femur-implant model was then developed and used to explore the sensitivity of the modal parameters to more subtle interfacial and boundary condition changes. The FE model was created using the synthetic femur geometry and an approximation of the implant geometry. The natural frequencies of the FE model were found to match the experimental frequencies within 20% and the FE and experimental mode shapes were similar. Therefore the FE model was shown to successfully capture the dynamic response of the physical system. As was found with the experimental modal analysis, the fundamental bending mode of the FE model did not alter due to changes in interface elastic modulus. Axial and torsional modes were identified by the FE model that were not detected experimentally; the torsional mode exhibited the largest frequency change due to interfacial changes (103% between the lower and upper limits of the interface modulus range). Therefore the FE model provided additional information on the dynamic response of the system and was complementary to the experimental model. The small changes in natural frequency over a large range of interface region elastic moduli indicated the method may only be able to distinguish between early and late OI progression. The boundary conditions applied to the FE model influenced the modal parameters to a far greater extent than the interface condition variations. Therefore the FE model, as well as the experimental modal analysis, indicated that the boundary conditions need to be held constant between tests in order for the detected changes in modal parameters to be attributed to interface condition changes alone. The results of this study suggest that in a clinical setting it is unlikely that the in vivo boundary conditions of the amputated femur could be adequately controlled or replicated over time and consequently it is unlikely that any longitudinal change in frequency detected by the modal analysis technique could be attributed exclusively to changes at the femur-implant interface. Therefore further development of the modal analysis technique would require significant consideration of the clinical boundary conditions and investigation of modes other than the bending modes.

Identification of factors contributing to recurrence of venous leg ulcers

Background and Significance Venous leg ulcers are a significant cause of chronic ill-health for 1–3% of those aged over 60 years, increasing in incidence with age. The condition is difficult and costly to heal, consuming 1–2.5% of total health budgets in developed countries and up to 50% of community nursing time. Unfortunately after healing, there is a recurrence rate of 60 to 70%, frequently within the first 12 months after heaing. Although some risk factors associated with higher recurrence rates have been identified (e.g. prolonged ulcer duration, deep vein thrombosis), in general there is limited evidence on treatments to effectively prevent recurrence. Patients are generally advised to undertake activities which aim to improve the impaired venous return (e.g. compression therapy, leg elevation, exercise). However, only compression therapy has some evidence to support its effectiveness in prevention and problems with adherence to this strategy are well documented. Aim The aim of this research was to identify factors associated with recurrence by determining relationships between recurrence and demographic factors, health, physical activity, psychosocial factors and self-care activities to prevent recurrence. Methods Two studies were undertaken: a retrospective study of participants diagnosed with a venous leg ulcer which healed 12 to 36 months prior to the study (n=122); and a prospective longitudinal study of participants recruited as their ulcer healed and data collected for 12 months following healing (n=80). Data were collected from medical records on demographics, medical history and ulcer history and treatments; and from self-report questionnaires on physical activity, nutrition, psychosocial measures, ulcer history, compression and other self-care activities. Follow-up data for the prospective study were collected every three months for 12 months after healing. For the retrospective study, a logistic regression model determined the independent influences of variables on recurrence. For the prospective study, median time to recurrence was calculated using the Kaplan-Meier method and a Cox proportional-hazards regression model was used to adjust for potential confounders and determine effects of preventive strategies and psychosocial factors on recurrence. Results In total, 68% of participants in the retrospective study and 44% of participants in the prospective study suffered a recurrence. After mutual adjustment for all variables in multivariable regression models, leg elevation, compression therapy, self efficacy and physical activity were found to be consistently related to recurrence in both studies. In the retrospective study, leg elevation, wearing Class 2 or 3 compression hosiery, the level of physical activity, cardiac disease and self efficacy scores remained significantly associated (p<0.05) with recurrence. The model was significant (p <0.001); with a R2 equivalent of 0.62. Examination of relationships between psychosocial factors and adherence to wearing compression hosiery found wearing compression hosiery was significantly positively associated with participants’ knowledge of the cause of their condition (p=0.002), higher self-efficacy scores (p=0.026) and lower depression scores (p=0.009). Analysis of data from the prospective study found there were 35 recurrences (44%) in the 12 months following healing and median time to recurrence was 27 weeks. After adjustment for potential confounders, a Cox proportional hazards regression model found that at least an hour/day of leg elevation, six or more days/week in Class 2 (20–25mmHg) or 3 (30–40mmHg) compression hosiery, higher social support scale scores and higher General Self-Efficacy scores remained significantly associated (p<0.05) with a lower risk of recurrence, while male gender and a history of DVT remained significant risk factors for recurrence. Overall the model was significant (p <0.001); with an R2 equivalent 0.72. Conclusions The high rates of recurrence found in the studies highlight the urgent need for further information in this area to support development of effective strategies for prevention. Overall, results indicate leg elevation, physical activity, compression hosiery and strategies to improve self-efficacy are likely to prevent recurrence. In addition, optimal management of depression and strategies to improve patient knowledge and self-efficacy may positively influence adherence to compression therapy. This research provides important information for development of strategies to prevent recurrence of venous leg ulcers, with the potential to improve health and decrease health care costs in this population.

Psychometric validation of the growth and empowerment measure (GEM) applied with Indigenous Australians

Objective: Empowerment is a complex process of psychological, social, organizational and structural change. It allows individuals and groups to achieve positive growth and effectively address the social and psychological impacts of historical oppression, marginalization and disadvantage. The Growth and Empowerment Measure (GEM) was developed to measure change in dimensions of empowerment as defi ned and described by Aboriginal Australians who participated in the Family Well Being programme.---------- Method: The GEM has two components: a 14-item Emotional Empowerment Scale (EES14) and 12 Scenarios (12S). It is accompanied by the Kessler 6 Psychological Distress Scale (K6), supplemented by two questions assessing frequency of happy and angry feelings. For validation, the measure was applied with 184 Indigenous Australian participants involved in personal and/or organizational social health activities.---------- Results: Psychometric analyses of the new instruments support their validity and reliability and indicate two-component structures for both the EES (Self-capacity; Inner peace) and the 12S (Healing and enabling growth, Connection and purpose). Strong correlations were observed across the scales and subscales. Participants who scored higher on the newly developed scales showed lower distress on the K6, particularly when the two additional questions were included. However, exploratory factor analyses demonstrated that GEM subscales are separable from the Kessler distress measure.---------- Conclusion: The GEM shows promise in enabling measurement and enhancing understanding of both process and outcome of psychological and social empowerment within an Australian Indigenous context.

A participant’s response : recreating the circle with We Al-Li: a program for sharing and regeneration

Personal reflections on the We Al-Li Program

Leg Clubs® : a clinically and cost-effective approach to lower limb management

Leg ulcers affect 55000-90000 people, predominantly aged over 65, in the UK at any one time. Traditional care, delivered in people’s homes by district nurses or in GP clinics, is costly and often not effective, with slow healing rates and a high incidence of recurrence. A social model of leg ulcer clinics developed by the author has been shown to improve healing and reduce recurrence within a highly cost-effective framework that delivers genuine patient empowerment, public health education and social outreach. This paper outlines the rationale for the Leg Club, its clinical and social impact, and the infrastructure behind it. It also considers the challenges to establishing and running a Leg Club.

Mesenchymal stem cells

Cell based therapies as they apply to tissue engineering and regenerative medicine, require cells capable of self renewal and differentiation, and a prerequisite is to be able to prepare an effective dose of ex vivo expanded cells for autologous transplants. The in vivo identification of a source of physiologically relevant cell types suitable for cell therapies therefore figures as an integral part of tissue engineering. Stem cells serve as a reserve for biological repair, having the potential to differentiate into a number of specialised cell types within the body; they therefore represent the most useful candidates for cell based therapies. The primary goal of stem cell research is to produce cells that are both patient specific, as well as having properties suitable for the specific conditions for which they are intended to remedy. From a purely scientific perspective, stem cells allow scientists to gain a deeper understanding of developmental biology and regenerative therapies. Stem cells have acquired a number of uses for applications in regenerative medicine, immunotherapy, gene therapy, but it is in the area of tissue engineering that they generate most excitement, primarily as a result of their capacity for self-renewal and pluripotency. A unique feature of stem cells is their ability to maintain an uncommitted quiescent state in vivo and then, once triggered by conditions such as disease, injury or natural wear or tear, serve as a reservoir and natural support system to replenish lost cells. Although these cells retain the plasticity to differentiate into various tissues, being able to control this differentiation process is still one of the biggest challenges facing stem cell research. In an effort to harness the potential of these cells a number of studies have been conducted using both embryonic/foetal and adult stem cells. The use of embryonic stem cells (ESC) have been hampered by strong ethical and political concerns, this despite their perceived versatility due to their pluripotency. Ethical issues aside, other concerns raised with ESCs relates to the possibility of tumorigenesis, immune rejection and complications with immunosuppressive therapies, all of which adds layers of complications to the application ESC in research and which has led to the search for alternative sources for stem cells. The adult tissues in higher organisms harbours cells, termed adult stem cells, and these cells are reminiscent of unprogrammed stem cells. A number of sources of adult stem cells have been described. Bone marrow is by far the most accessible source of two potent populations of adult stem cells, namely haematopoietic stem cells (HSCs) and bone marrow mesenchymal stem cells (BMSCs). Autologously harvested adult stem cells can, in contrast to embryonic stem cells, readily be used in autografts, since immune rejection is not an issue; and their use in scientific research has not attracted the ethical concerns which have been the case with embryonic stem cells. The major limitation to their use, however, is the fact that adult stem cells are exceedingly rare in most tissues. This fact makes identifying and isolating these cells problematic; bone marrow being perhaps the only notable exception. Unlike the case of HSCs, there are as yet no rigorous criteria for characterizing MSCs. Changing acuity about the pluripotency of MSCs in recent studies has expanded their potential application; however, the underlying molecular pathways which impart the features distinctive to MSCs remain elusive. Furthermore, the sparse in vivo distribution of these cells imposes a clear limitation to their study in vitro. Also, when MSCs are cultured in vitro, there is a loss of the in vivo microenvironment, resulting in a progressive decline in proliferation potential and multipotentiality. This is further exacerbated with increased passage numbers in culture, characterized by the onset of senescence related changes. As a consequence, it is necessary to establish protocols for generating large numbers of MSCs but without affecting their differentiation potential. MSCs are capable of differentiating into mesenchymal tissue lineages, including bone, cartilage, fat, tendon, muscle, and marrow stroma. Recent findings indicate that adult bone marrow may also contain cells that can differentiate into the mature, nonhematopoietic cells of a number of tissues, including cells of the liver, kidney, lung, skin, gastrointestinal tract, and myocytes of heart and skeletal muscle. MSCs can readily be expanded in vitro and can be genetically modified by viral vectors and be induced to differentiate into specific cell lineages by changing the microenvironment–properties which makes these cells ideal vehicles for cellular gene therapy. MSCs can also exert profound immunosuppressive effects via modulation of both cellular and innate immune pathways, and this property allows them to overcome the issue of immune rejection. Despite the many attractive features associated with MSCs, there are still many hurdles to overcome before these cells are readily available for use in clinical applications. The main concern relates to in vivo characterization and identification of MSCs. The lack of a universal biomarker, sparse in vivo distribution, and a steady age related decline in their numbers, makes it an obvious need to decipher the reprogramming pathways and critical molecular players which govern the characteristics unique to MSCs. This book presents a comprehensive insight into the biology of adult stem cells and their utility in current regeneration therapies. The adult stem cell populations reviewed in this book include bone marrow derived MSCs, adipose derived stem cells (ASCs), umbilical cord blood stem cells, and placental stem cells. The features such as MSC circulation and trafficking, neuroprotective properties, and the nurturing roles and differentiation potential of multiple lineages have been discussed in details. In terms of therapeutic applications, the strengths of MSCs have been presented and their roles in disease treatments such as osteoarthritis, Huntington’s disease, periodontal regeneration, and pancreatic islet transplantation have been discussed. An analysis comparing osteoblast differentiation of umbilical cord blood stem cells and MSCs has been reviewed, as has a comparison of human placental stem cells and ASCs, in terms of isolation, identification and therapeutic applications of ASC in bone, cartilage regeneration, as well as myocardial regeneration. It is my sincere hope that this book will update the reader as to the research progress of MSC biology and potential use of these cells in clinical applications. It will be the best reward to all contributors of this book, if their efforts herein may in some way help the readers in any part of their study, research, and career development.

Enhancing vascularized bone formation using tissue engineered periosteum

Objectives: The periosteum plays an indispensable role in both bone formation and bone defect healing. The aim of this project is to produce tissue engineered periosteum for bone defect treatment. Methods: In this study we constructed an artificial in vitro periosteum by incorporating osteogenic differentiated bone marrow stromal cells (BMSCs) and cobalt chloride (CoCl2)-treated BMSCs. The engineered periostea were implanted both subcutaneously and into skull bone defects in SCID mice to investigate ectopic and orthotopic osteogenesis and vascularisation. After two weeks in subcutaneous and four weeks in bone defect areas, the implanted constructs were assessed for ectopic and orthotopic osteogenesis and vascularisation by micro-CT, histomorphometrical and immunohistochemical methods. Results: The results showed that CoCl2 pre-treated BMSCs induced higher degree of vascularisation and enhanced osteogenesis within the implants in both ectopic and orthotopic areas. Conclusion: This study provided a novel approach using BMSCs sourced from the same patient for both osteogenic and pro-angiogenic purposes in constructing tissue engineered periosteum to enhance vascularized osteogenesis.

Endochondral ossification in vitro is influenced by mechanical bending

Bone development is influenced by the local mechanical environment. Experimental evidence suggests that altered loading can change cell proliferation and differentiation in chondro- and osteogenesis during endochondral ossification. This study investigated the effects of three-point bending of murine fetal metatarsal bone anlagen in vitro on cartilage differentiation, matrix mineralization and bone collar formation. This is of special interest because endochondral ossification is also an important process in bone healing and regeneration. Metatarsal preparations of 15 mouse fetuses stage 17.5 dpc were dissected en bloc and cultured for 7 days. After 3 days in culture to allow adherence they were stimulated 4 days for 20 min twice daily by a controlled bending of approximately 1000-1500 microstrain at 1 Hz. The paraffin-embedded bone sections were analyzed using histological and histomorphometrical techniques. The stimulated group showed an elongated periosteal bone collar while the total bone length was not different from controls. The region of interest (ROI), comprising the two hypertrophic zones and the intermediate calcifying diaphyseal zone, was greater in the stimulated group. The mineralized fraction of the ROI was smaller in the stimulated group, while the absolute amount of mineralized area was not different. These results demonstrate that a new device developed to apply three-point bending to a mouse metatarsal bone culture model caused an elongation of the periosteal bone collar, but did not lead to a modification in cartilage differentiation and matrix mineralization. The results corroborate the influence of biophysical stimulation during endochondral bone development in vitro. Further experiments with an altered loading regime may lead to more pronounced effects on the process of endochondral ossification and may provide further insights into the underlying mechanisms of mechanoregulation which also play a role in bone regeneration.

Preclinical animal models for segmental bone defect research and tissue engineering

Currently, well-established clinical therapeutic approaches for bone reconstruction are restricted to the transplantation of autografts and allografts, and the implantation of metal devices or ceramic-based implants to assist bone regeneration. Bone grafts possess osteoconductive and osteoinductive properties, however they are limited in access and availability and associated with donor site morbidity, haemorrhage, risk of infection, insufficient transplant integration, graft devitalisation, and subsequent resorption resulting in decreased mechanical stability. As a result, recent research focuses on the development of alternative therapeutic concepts. Analysing the tissue engineering literature it can be concluded that bone regeneration has become a focus area in the field. Hence, a considerable number of research groups and commercial entities work on the development of tissue engineered constructs for bone regeneration. However, bench to bedside translations are still infrequent as the process towards approval by regulatory bodies is protracted and costly, requiring both comprehensive in vitro and in vivo studies. In translational orthopaedic research, the utilisation of large preclinical animal models is a conditio sine qua non. Consequently, to allow comparison between different studies and their outcomes, it is essential that animal models, fixation devices, surgical procedures and methods of taking measurements are well standardized to produce reliable data pools as a base for further research directions. The following chapter reviews animal models of the weight-bearing lower extremity utilized in the field which include representations of fracture-healing, segmental bone defects, and fracture non-unions.

Continuous passive motion applied to whole joints stimulates chondrocyte blosynthesis of PRG4

Continuous passive motion (CPM) is currently a part of patient rehabilitation regimens after a variety of orthopedic surgical procedures. While CPM can enhance the joint healing process, the direct effects of CPM on cartilage metabolism remain unknown. Recent in vivo and in vitro observations suggest that mechanical stimuli can regulate articular cartilage metabolism of proteoglycan 4 (PRG4), a putative lubricating and chondroprotective molecule found in synovial fluid and at the articular cartilage surface. ----- ----- Objectives: (1) Determine the topographical variation in intrinsic cartilage PRG4 secretion. (2) Apply a CPM device to whole joints in bioreactors and assess effects of CPM on PRG4 biosynthesis.----- ----- Methods: A bioreactor was developed to apply CPM to bovine stifle joints in vitro. Effects of 24 h of CPM on PRG4 biosynthesis were determined.----- ----- Results: PRG4 secretion rate varied markedly over the joint surface. Rehabilitative joint motion applied in the form of CPM regulated PRG4 biosynthesis, in a manner dependent on the duty cycle of cartilage sliding against opposing tissues. Specifically, in certain regions of the femoral condyle that were continuously or intermittently sliding against meniscus and tibial cartilage during CPM, chondrocyte PRG4 synthesis was higher with CPM than without.----- ----- Conclusions: Rehabilitative joint motion, applied in the form of CPM, stimulates chondrocyte PRG4 metabolism. The stimulation of PRG4 synthesis is one mechanism by which CPM may benefit cartilage and joint health in post-operative rehabilitation. (C) 2006 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.