Healing Of Articular Cartilage Defects Research Articles

Implication of Mesenchymal Stem Cells and Their Derivates for Osteochondral Regeneration.

Healing of articular cartilage defects presents a challenging issue, due to its regenerative shortcomings. Lacking vascularity and innervation of cartilage and low proliferative potential of chondrocytes are the main reasons for the limited healing potential of articular cartilage. Traditional reparative approaches are limited in their efficiency, hence there is a demand for novel reparative treatments. Mesenchymal stromal cells, preferred for clinical uses, can be readily derived from various sources and have been proven to have a therapeutic effect on cartilage and subchondral bone. Therefore, mesenchymal stromal cells, their derivates, and scaffolds have been utilized in research targeting osteochondral regeneration. The present review aims to comprehensively outline and discuss literature considering this topic published within last 5 years.

Mechanically stimulated osteochondral organ culture for evaluation of biomaterials in cartilage repair studies

Surgical procedures such as microfracture or autologous chondrocyte implantation have been used to treat articular cartilage lesions; however, repair often fails in terms of matrix organization and mechanical behaviour. Advanced biomaterials and tissue engineered constructs have been developed to improve cartilage repair; nevertheless, their clinical translation has been hampered by the lack of reliable in vitro models suitable for pre-clinical screening of new implants and compounds.In this study, an osteochondral defect model in a bioreactor that mimics the multi-axial motion of an articulating joint, was developed. Osteochondral explants were obtained from bovine stifle joints, and cartilage defects of 4 mm diameter were created. The explants were used as an interface against a ceramic ball applying dynamic compressive and shear loading. Osteochondral defects were filled with chondrocytes-seeded fibrin-polyurethane constructs and subjected to mechanical stimulation. Cartilage viability, proteoglycan accumulation and gene expression of seeded chondrocytes were compared to free swelling controls. Cells within both cartilage and bone remained viable throughout the 10-day culture period. Loading did not wear the cartilage, as indicated by histological evaluation and glycosaminoglycan release. The gene expression of seeded chondrocytes indicated a chondrogenic response to the mechanical stimulation. Proteoglycan 4 and cartilage oligomeric matrix protein were markedly increased, while mRNA ratios of collagen type II to type I and aggrecan to versican were also enhanced. This mechanically stimulated osteochondral defect culture model provides a viable microenvironment and will be a useful pre-clinical tool to screen new biomaterials and biological regenerative therapies under relevant complex mechanical stimuli. Statement of SignificanceArticular cartilage lesions have a poor healing capacity and reflect one of the most challenging problems in orthopedic clinical practice. The aim of current research is to develop a testing system to assess biomaterials for implants, that can permanently replace damaged cartilage with the original hyaline structure and can withstand the mechanical forces long term.Here, we present an osteochondral ex vivo culture model within a cartilage bioreactor, which mimics the complex motion of an articulating joint in vivo. The implementation of mechanical forces is essential for pre-clinical testing of novel technologies in the field of cartilage repair, biomaterial engineering and regenerative medicine. Our model provides a unique opportunity to investigate healing of articular cartilage defects in a physiological joint-like environment.

Effect of polycaprolactone-ascobic acid scaffold in repairing articular cartilage defects in rabbits

To investigate the effect of polycaprolactone-ascobic acid (PCL-AA) scaffolds in promoting repair of articular cartilage defects in a rabbit model. The cartilage defects (3.5 mm in diameter and 3.0 mm in depth) were created in the trochlear groove of the bilateral knees of eight 6-month-old male New Zealand white rabbits. The rabbit models were then randomized into 3 groups to receive implantation of PCL-AA scaffolds (group A, n=8), implantation of PCL scaffolds without AA (group B, n=5), or no treatment (group C, n=3). In groups A and B, the mixture of fibrin gel (10 µg) and thrombinogen (10 µg) was injected into the defects to fix the scaffolds during the surgery. Histological analyses and quantitative assessments of defect repair were conducted at 6 and 12 weeks after implantation of the scaffold. At 6 weeks after scaffold implantation, macroscopic observation showed better filling of the cartilage defects in group A than in group B, while no obvious defect repair was observed in group C. The rabbits in group A showed a significant improvement of the Wakitani score than those in group B (4.05∓1.11 vs 7.05∓0.98, P<0.05). HE staining revealed the presence of newly generated cells in and around the PCL-AA scaffolds without inflammatory cells. Safranin O staining showed a significantly greater ECM of the newly regenerated tissue in groups A and B than in group C (P<0.05), and the volume of the regenerated cartilage and cells was significantly greater in group A than in group B (P<0.05). Samples harvested at 12 weeks showed more hyalione-like cartilage formation than that at 6 weeks in group A. PCL-AA scaffolds have a good biocompatibility and promotes the healing of articular cartilage defects. Adding ascorbic acid into PCL scaffolds better promotes cartilage formation in terms of both quantity and quality of the regenerated tissues. PCL-AA scaffolds can serve as a promising biomaterial to promote the regeneration of articular cartilage using tissue engineering techniques.

Hyaluronan thiomer gel/matrix mediated healing of articular cartilage defects in New Zealand White rabbits\u2014a pilot study

BackgroundArticular cartilage defects are limited to their regenerative potential in human adults. Our current study evaluates tissue regeneration in a surgically induced empty defect site with hyaluronan thiomer as a provisional scaffold in a gel/matrix combination without cells on rabbit models to restore tissue formation.MethodsAn osteochondral defect of 4 mm in diameter and 5 mm in depth was induced by mechanical drilling in the femoral center of the trochlea in 18 New Zealand White rabbits. Previously evaluated from an in vitro study hyaluronan thiomer matrix, and a hyaluronan thiomer gel was used to treat the defect. As a control, the defect was left untreated. During the whole study, rabbits were clinically examined and after 4 (n = 3) or 12 (n = 3) weeks, the rabbits were sacrificed. Joints were evaluated macroscopically (Brittberg score) and by histology (O’Driscoll score). Synovial cells from the synovial fluid smear were histopathologically evaluated.ResultsThe healing of the defects varied intra-group wise at the first observation period. After 12 weeks the results concerning the cartilage repair score were inhomogeneous within each group, while the macroscopic analysis was more homogenous. In the synovial fluid smear, the mean score of infiltrated synovial and non-synovial cells was slightly increased after 4 weeks and slightly decreased after 12 weeks in both the treatment groups in comparison to the untreated control.ConclusionsTaken together with results from the in vivo study indicated that implantation of hyaluronan thiomer as a combination of gel and matrix might enhance articular cartilage regeneration in an empty defect. Despite their benefits, the intrinsic healing capacity of New Zealand rabbits is a limitation for comparative test subject in pre-clinical models of cartilage defects.

Leukocyte and Platelet Rich Plasma (L-PRP) Versus Leukocyte and Platelet Rich Fibrin (L-PRF) For Articular Cartilage Repair of the Knee: A Comparative Evaluation in an Animal Model.

Background:Articular cartilage injuries of the knee are among the most debilitating injuries leading to osteoarthritis due to limited regenerative capability of cartilaginous tissue. The use of platelet concentrates containing necessary growth factors for cartilage healing has recently emerged as a new treatment method.Objectives:The efficacy of two types of different platelet concentrates were compared in the treatment of acute articular cartilage injuries of the knee in an animal model.Materials and Methods:Eighteen adult Iranian mixed breed male dogs were used to conduct this experimental study. Full thickness articular cartilage defects (diameter 6 mm, depth 5 mm) were created in the weight bearing area of femoral condyles of both hind limbs in all dogs (n = 72). Twelve dogs were randomly selected to receive treatment and their right and left hind limb defects were treated by L-PRP and L-PRF implantation respectively, while no treatment was undertaken in six other dogs as controls. The animals were euthanized at 4, 16 and 24 weeks following surgery and the resultant repair tissue was investigated macroscopically and microscopically. At each sampling time, 4 treated dogs and 2 control dogs were euthanized, therefore 8 defects per group were evaluated.Results:Mean macroscopic scores of the treated defects were higher than the controls at all sampling times with significant differences (P < 0.05) observed between L-PRF treated and control defects (10.13 vs. 8.37) and L-PRP treated and control defects (10 vs. 8.5) at 4 and 16 weeks, respectively. A similar trend in mean total microscopic scores was observed with a significant difference (P < 0.05) between L-PRP treated and control defects at 4 (9.87 vs. 7.62) and 16 (13.38 vs. 11) weeks. No significant difference was observed between the platelet concentrate treated defects in either mean macroscopic scores or mean total microscopic scores.Conclusions:Both L-PRP and L-PRF could be used to effectively promote the healing of articular cartilage defects of the knee.

Multiphasic, Multistructured and Hierarchical Strategies for Cartilage Regeneration.

Cartilage tissue is a complex nonlinear, viscoelastic, anisotropic, and multiphasic material with a very low coefficient of friction, which allows to withstand millions of cycles of joint loading over decades of wear. Upon damage, cartilage tissue has a low self-reparative capacity due to the lack of neural connections, vascularization, and a latent pool of stem/chondro-progenitor cells. Therefore, the healing of articular cartilage defects remains a significant clinical challenge, affecting millions of people worldwide. A plethora of biomaterials have been proposed to fabricate devices for cartilage regeneration, assuming a wide range of forms and structures, such as sponges, hydrogels, capsules, fibers, and microparticles. In common, the fabricated devices were designed taking in consideration that to fully achieve the regeneration of functional cartilage it is mandatory a well-orchestrated interplay of biomechanical properties, unique hierarchical structures, extracellular matrix (ECM), and bioactive factors. In fact, the main challenge in cartilage tissue engineering is to design an engineered device able to mimic the highly organized zonal architecture of articular cartilage, specifically its spatiomechanical properties and ECM composition, while inducing chondrogenesis, either by the proliferation of chondrocytes or by stimulating the chondrogenic differentiation of stem/chondro-progenitor cells. In this chapter we present the recent advances in the development of innovative and complex biomaterials that fulfill the required structural key elements for cartilage regeneration. In particular, multiphasic, multiscale, multilayered, and hierarchical strategies composed by single or multiple biomaterials combined in a well-defined structure will be addressed. Those strategies include biomimetic scaffolds mimicking the structure of articular cartilage or engineered scaffolds as models of research to fully understand the biological mechanisms that influence the regeneration of cartilage tissue.

Influence of insulin-like growth factor I overexpression via recombinant adeno-associated vector gene transfer upon the biological activities and differentiation potential of human bone marrow-derived mesenchymal stem cells.

IntroductionThe transplantation of genetically modified progenitor cells such as bone marrow-derived mesenchymal stem cells (MSCs) is an attractive strategy to improve the natural healing of articular cartilage defects. In the present study, we examined the potential benefits of sustained overexpression of the mitogenic and pro-anabolic insulin-like growth factor I (IGF-I) via gene transfer upon the biological activities of human MSCs (hMSCs).MethodsRecombinant adeno-associated vectors (rAAV) were used to deliver a human IGF-I coding sequence in undifferentiated and chondrogenically-induced primary hMSCs in order to determine the efficacy and duration of transgene expression and the subsequent effects of the genetic modification upon the chondrogenic versus osteogenic differentiation profiles of the cells relative to control (lacZ) treatment after 21 days in vitro.ResultsSignificant and prolonged expression of IGF-I was evidenced in undifferentiated and most importantly in chondrogenically-induced hMSCs transduced with the candidate rAAV-hIGF-I vector for up to 21 days, leading to enhanced proliferative, biosynthetic, and chondrogenic activities compared with rAAV-lacZ treatment. Overexpression of IGF-I as achieved in the conditions applied here also increased the expression of hypertrophic and osteogenic markers in the treated cells.ConclusionsThese results suggest that a tight regulation of rAAV expression may be necessary for further translation of the approach in clinically relevant animal models in vivo. However, the current findings support the concept of using this type of vector as an effective tool to treat articular cartilage defects via gene- and stem cell-based procedures.

Healing of full-thickness articular cartilage defects treated with cultured autologous chondrogenic satellite cells isolated from chondral stem cell niche in rabbits

BackgroundHealing of articular cartilage has remained in question with the use of conventional treatment modalities such as subchondral drilling and microfracture. As demonstrated in the past, adult stem cells retain promising clonogenicity. Therefore, we conducted this study to elucidate the effects of cultured autologous chondrogenic satellite cells (CACSCs) compared with subchondral drilling (SCD) for the repair of full-thickness articular cartilage defects. Materials and methodsWe examined CACSCs isolated from the knee of rabbits using flow cytometry for the expression of stemness and chondrocyte-specific factors. Subsequently, we created a full-thickness cartilage defect model with a diameter of 3 mm and depth of 2 mm on the articular surface of trochlear grooves in the left knee of 24 New Zealand white rabbits. Then we drilled subchondrally through the defect in all animals and stuffed the defects with 10-μg/cm2 collagen scaffolds. In the treatment group, we instilled CACSCs at 5 × 106 cells/mL in the collagen scaffold and collected samples on days 15, 30, and 45. ResultsThe CACSCs revealed significant expression of CD106, CD44, collagen type 2, and aggrecan. In conjunction with SCD, CACSCs improved healing of the articular cartilage defect, as evidenced by the formation of hyaline-like tissue grossly and histologically. The healed tissue also revealed a significant (P < 0.05) increase in the expression of collagen type 2 and aggrecan (by real-time polymerase chain reaction) during the experiment. ConclusionsIn conjunction with SCD, CACSCs may be considered to improve articular cartilage damage.

A Spectrophotometric Analysis of Human Osteoarthritic Cartilage Explants Subjected to Specific Capacitively Coupled Electric Fields

We have previously shown that capacitively coupled electrical stimulation of either normal bovine articular chondrocytes or osteoarthritic human articular cartilage explants resulted in up-regulation of cartilage matrix gene expression and down-regulation of metalloproteinase gene expression. In addition, collagen and proteoglycan protein levels were also elevated. To determine visually the effect of specific electric fields on modifying cartilage structure, freshly harvested human full-thickness osteoarthritic cartilage explants were stimulated in the absence or presence of interleukin-1β, an inflammatory cytokine, and were examined photographically and spectrophotometrically. Hexosamine and hydroxyproline contents were also determined. Spectrophotometric analysis was used to quantify any changes in the depth of defects in the cartilage ranging from surface level (red-colored) to the deepest affected layer (blue-colored). Interleukin-1β treatment alone caused significant additional cartilage erosion. Electrical stimulation alone resulted in significant decreases in the cartilage defects. Electrical stimulation in the presence of interleukin-1β resulted in a small, but significant, surface improvement. Meta-analysis also confirmed a significant increase in the hexosamine and hydroxyproline contents (indicating matrix deposition). It was concluded that an appropriate electric field could modify osteoarthritic lesions in full-thickness cartilage plugs by increasing matrix production and/or by decreasing matrix destruction. Furthermore, it appears that spectrophotometric analysis is a relatively easy method for quantifying the “filling in” or healing of articular cartilage defects.

Hyperbaric oxygen treatment prevents nitric oxide‐induced apoptosis in articular cartilage injury via enhancement of the expression of heat shock protein 70

Heat shock proteins (HSPs), inflammatory cytokines, nitric oxide (NO), and localized hypoxia-induced apoptosis are thought to be correlated to the degree of cartilage injury. We investigated the effect of hyperbaric oxygen (HBO) on (1) interleukin-1β (IL-1β)-induced NO production and apoptosis of rabbit chondrocytes and (2) healing of articular cartilage defects. For the in vitro study, RT-PCR and Western blotting were performed to detect mRNA and protein expressions of HSP70, inducible NO synthase (iNOS), and caspase 3 in IL-1β-treated chondrocytes. To clarify that the HSP70 was necessary for anti-iNOS and anti-apoptotic activity by HBO, we treated the cells with an HSP70 inhibitor, KNK437. For the in vivo study, cartilage defects were created in rabbits. The HBO group was exposed to 100% oxygen at 2.5 ATA for 1.5 h a day for 10 weeks. The control group was exposed to normal air. After sacrifice, specimen sections were sent for examination using a scoring system. Immunohistochemical analyses were performed to detect the expressions of iNOS, HSP70, and caspase 3. Our results suggested that HBO upregulated the mRNA and protein expressions of HSP70 and suppressed those of iNOS and caspase 3 in chondrocytes. KNK437 inhibited the HBO-induced downregulation of iNOS and casapase 3 activities. The histological scores showed that HBO markedly enhanced cartilage repair. Immunohistostaining showed that HBO enhanced HSP70 expression and suppressed iNOS and caspase 3 expressions in chondrocytes. Accordingly, HBO treatment prevents NO-induced apoptosis in articular cartilage injury via enhancement of the expression of heat shock protein 70.

The Healing Effect of Bioglue in an Experimental Rabbit Model of Femoral Condyle Articular Cartilage Defect

The full-thickness articular cartilage defects of knee have a poor healing capacity that may progress to osteoarthritis and need a knee replacement. This study determines the healing effect of bioglue in fullthickness articular cartilage defect of femoral condyle in rabbit. Forty-eight male rabbits were randomly divided into four equal groups. In group A, 4 mm articular cartilage defects were created in the right and left medial femoral condyles. Then a graft from xiphoid cartilage was transferred into the defect together with a designed bioglue and the knees were closed. In group B, an articular cartilage defect was created identical to group A, but the defect size was 6 mm. In group C, 4 and 6 mm articular cartilage defects were created in the right and left medial femoral condyles respectively. The graft was transferred into the defect and the knees were stitched. In group D, articular cartilage defects were created similar to group C, just filled with bioglue and closed. The rabbits were euthanized and subgroups were defined as A1, B1, C1 and D1 after 30 days and A2, B2, C2 and D2 after 60 days. The cartilages were macroscopically and histologically investigated for any changes. Microscopic and macroscopic investigations showed that bioglue had a significant healing effect in the femoral condyle. Addition of bioglue can effectively promote the healing of articular cartilage defects.

Healing of articular cartilage defects treated with a novel drug-releasing rod-type implant after microfracture surgery

Microfracture therapy is a widely used technique for the repair of articular cartilage defects because it can be readily performed arthroscopically. However, the regenerated cartilage after microfracture surgery clearly differs from normal articular cartilage. This suggests that the clinical outcome of patients undergoing microfracture therapy could be improved. Dehydroepiandrosterone sulfate (DHEA-S) is known to protect against articular cartilage loss. Therefore, in an effort to achieve cartilage regeneration of high efficacy, we manufactured a DHEA-S-releasing rod-type implant for implantation into the holes produced by microfracture surgery. The polymeric rod-type implant was made of biodegradable poly ( d, l-lactide-co-glycolide) (PLGA) and β-tricalcium phosphate to enable controlled release of DHEA-S. The implant was dip-coated with a dilute PLGA solution to prevent the burst release of DHEA-S. The rod-type implant was sufficiently stiff to permit implantation into the holes made by microfracture. DHEA-S was released from the implant for more than four weeks. Furthermore, eight weeks after implantation into rabbit knees, the implants dramatically enhanced cartilage regeneration compared to control. Moreover, the degradation of the implant over the eight weeks from implantation into the knee did not induce any adverse effects. Therefore, this polymeric rod-type implant does not only provide an improvement in microfracture surgery, but also has great potential as a new formulation for drug delivery.

Healing of articular cartilage defects. An experimental study of vascular and minimal vascular microenvironment

The repair potential in a chondral defect with (treatment A) or without access to bone marrow elements (treatment B) at the basis of the defect sealed by a rim-sutured periosteal flap was studied using adult New Zealand rabbits (22 weeks) as an experimental model. At sacrifice, macroscopical changes, synovial fluid contents, degree of filling, thickness of the cartilage rim, and the subchondral bone were evaluated. Histomorphometric measurements of extent of filling (mainly fibrous tissue) of the defect at 36 weeks postoperatively, showed 50% filling in treatment A compared with 33% in treatment B (p = 0.011). A difference in height of the cartilage rim between the experimental groups and sham-control was measured ( p = 0.005). Cartilage degeneration was observed at the cartilage rim of the original defect, and included loss of chondrocytes and disruption of surface continuity in both experimental groups. In addition, treatment A resulted in a significantly increased thickness of the subchondral bone in the defect in comparison to treatment B at 2 weeks and at 36 weeks (p = 0.021). The increased thickness of the subchondral bone may be of concern for the bone marrow stimulation techniques regarding the long-term outcome.

Improved Tissue Repair in Articular Cartilage Defects in Vivo by rAAV-Mediated Overexpression of Human Fibroblast Growth Factor 2

Therapeutic gene transfer into articular cartilage is a potential means to stimulate reparative activities in tissue lesions. We previously demonstrated that direct application of recombinant adeno-associated virus (rAAV) vectors to articular chondrocytes in their native matrix in situ as well as sites of tissue damage allowed for efficient and sustained reporter gene expression. Here we test the hypothesis that rAAV-mediated overexpression of fibroblast growth factor 2 (FGF-2), one candidate for enhancing the repair of cartilage lesions, would lead to the production of a biologically active factor that would facilitate the healing of articular cartilage defects. In vitro, FGF-2 production from an rAAV-delivered transgene was sufficient to stimulate chondrocyte proliferation over a prolonged period of time. In vivo, application of the therapeutic vector significantly improved the overall repair, filling, architecture, and cell morphology of osteochondral defects in rabbit knee joints. Differences in matrix synthesis were also observed, although not to the point of statistical significance. This process may further benefit from cosupplementation with other factors. These results provide a basis for rAAV application to sites of articular cartilage damage to deliver agents that promote tissue repair.

The effects of cross-linking of collagen-glycosaminoglycan scaffolds on compressive stiffness, chondrocyte-mediated contraction, proliferation and biosynthesis

The healing of articular cartilage defects may be improved by the use of implantable three-dimensional matrices. The present study investigated the effects of four cross-linking methods on the compressive stiffness of collagen-glycosaminoglycan (CG) matrices and the interaction between adult canine articular chondrocytes and the matrix: dehydrothermal treatment (DHT), ultraviolet irradiation (UV), glutaraldehyde treatment (GTA), and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDAC). The degree and kinetics of chondrocyte-mediated contraction, chondrocyte proliferation, and protein and glycosaminoglycan synthesis were evaluated over a four-week period in vitro . Cell-mediated contraction of the matrices varied with cross-linking: the most compliant DHT and UV matrices contracted the most (60% reduction in matrix diameter) and stiffest EDAC matrices contracted the least (30% reduction in matrix diameter). All cross-linking protocols permitted cell proliferation and matrix synthesis as measured by DNA content and radiolabeled sulfate and proline incorporation, respectively. During the first week in culture, a lower level of proliferation was seen in the GTA matrices but over the four-week culture period, the GTA and EDAC matrices provided for the greatest cell proliferation. On day 2, there was a significantly lower rate of 3H-proline incorporation in the GTA matrices ( p<0.003) although at later time points, the EDAC and GTA matrices exhibited the highest levels of matrix synthesis. With regard to cartilage-specific matrix molecule synthesis, immunohistochemistry revealed a greater amount of type II collagen in DHT and UV matrices at the early time points. These findings serve as a foundation for future studies of tissue engineering of articular cartilage and the association of chondrocyte contraction and the processes of mitosis and biosynthesis.

BASIC SCIENCE OF ARTICULAR CARTILAGE REPAIR

As the ability to understand the peculiarities of successful healing of articular cartilage defects moves forward, it becomes clear that this complex orthopaedic problem soon will be successfully addressed. A multidisciplinary approach, combining clinical experience, cogent biomaterial designs, new cell biologic processes, biomechanical assessment, and modern molecular biology, clearly is leading toward clinically acceptable, viable, and consistent articular cartilage regeneration.

Articular cartilage chondrocytes in type I and type II collagen-GAG matrices exhibit contractile behavior in vitro.

Natural healing of articular cartilage defects generally does not occur, and untreated lesions may predispose the joint to osteoarthritis. To promote healing of cartilage defects, many researchers are turning toward a tissue engineering approach involving cultured cells and/or porous, resorbable matrices. This study investigated the contractile behavior of cultured canine chondrocytes seeded in a porous collagen-glycosaminoglycan (GAG) scaffold. Chondrocytes isolated from the knee joints of adult canines and expanded in monolayer culture were seeded into porous collagen-GAG scaffolds. Scaffolds were of two different compositions, with the predominant collagen being either type I or type II collagen, and of varying pore diameters. Over the 4-week culture period, the seeded cells contracted all of the type I and type II collagen-based matrices, despite a wide range of stiffness (145 +/- 23 Pa, for the type I scaffold, to 732 +/- 35 Pa, for the type II material). Pore diameter (25-85 microm, type I; and 53-257 microm, type II) did not affect cell-mediated contraction. Immunohistochemical staining revealed the presence of alpha-smooth muscle actin, an isoform responsible for contraction of smooth muscle cells and myofibroblasts, in the cytoplasm of the seeded cells and in chondrocytes in normal adult canine articular cartilage.

The dose effect of continuous passive motion in postoperative rehabilitation of the first metatarsophalangeal joint

Continuous passive motion (CPM) has been utilized in postoperative rehabilitation of many joints of the body. Little has been published regarding its applications in the first metatarsal phalangeal joint or other joints of the foot. A review of the basic science and clinical studies regarding the dose effects on the healing of articular cartilage defects and periarticular tissues has led to possible correlations in treating disorders of the first metatarsal phalangeal joint. Proposed protocols are being presented which may be helpful in future clinical studies to confirm the benefits of CPM in this joint of the foot.