Microfracture is frequently used as the first line of treatment for the repair of traumatic cartilage defects. We present the clinical and histological results 18 months to two-years after treatment in a 26-year-old male with a post-traumatic chondral defect of the medial femoral condyle managed by microfracture covered with chondrotissue, a cell-free cartilage implant made of a resorbable polyglycolic acid felt and hyaluronic acid

We describe the outcome at a mean follow-up of 8.75 years (7.6 to 9.8) of seven patients who had undergone osteochondral autologous transplantation for full-thickness cartilage defects of the shoulder between 1998 and 2000. These patients have been described previously at a mean of 32.6 months when eight were included. One patient has been lost to follow-up. The outcome was assessed by the Constant shoulder score and the Lysholm knee score to assess any donor-site morbidity. Standard radiographs and MR scores were obtained and compared with the pre-operative findings and the results from the previous review. No patient required any further surgery on the shoulder. The mean Constant score improved significantly until the final follow-up (p = 0.018). The Lysholm score remained excellent throughout. There was a significant progression of osteoarthritic changes from the initial surgery to the first and final follow-up but this did not appear to be related to the size of the defect, the number of cylinders required or the Constant score (p = 0.016). MRI showed that all except one patient had a congruent joint surface at the defect with full bony integration of all osteochondral cylinders. The results have remained satisfactory over a longer period with very good objective and subjective findings

In 16 mature New Zealand white rabbits mesenchymal stem cells were aspirated from the bone marrow, cultured in monolayer and implanted on to a full-thickness osteochondral defect artificially made on the patellar groove of the same rabbit. A further 13 rabbits served as a control group. The rabbits were killed after 14 weeks. Healing of the defect was investigated histologically using haematoxylin and eosin and Safranin-O staining and with immunohistochemical staining for type-II collagen. We also used a reverse transcription-polymerase chain reaction (RT-PCR) to detect mRNA of type-I and type-II collagen. The semiquantitative histological scores were significantly higher in the experimental group than in the control group (p < 0.05). In the experimental group immunohistochemical staining on newly formed cartilage was more intense for type-II collagen in the matrix and RT-PCR from regenerated cartilage detected mRNA for type-II collagen in mature chondrocytes. These findings suggest that repair of cartilage defects can be enhanced by the implantation of cultured mesenchymal stem cells

We reviewed retrospectively 11 patients who had been treated surgically by open autologous osteochondral grafting for symptomatic chondral or osteochondral defects of the dome of the talus between 1996 and 1999. The mean ages of the eight men and three women were 34.2 and 25.9 years, respectively, with a mean time to follow-up of 24 months. The results of functional outcome were prospectively obtained using the MODEMS AAOS foot and ankle follow-up questionnaire, the AOFAS ankle-hindfoot scale and the Hannover scores for the ankle.

The grafts were harvested from the ipsilateral knee. Good to excellent results were obtained for the ankle without adverse effects on the knee. We believe that autologous osteochondral grafting should be considered for the patient with a symptomatic osteochondral defect of the talus.

We investigated the clinical, arthroscopic and biomechanical outcome of transplanting autologous chondrocytes, cultured in atelocollagen gel, for the treatment of full-thickness defects of cartilage in 28 knees (26 patients) over a minimum period of 25 months. Transplantation eliminated locking of the knee and reduced pain and swelling in all patients. The mean Lysholm score improved significantly. Arthroscopic assessment indicated that 26 knees (93%) had a good or excellent outcome. There were few adverse features, except for marked hypertrophy of the graft in three knees, partial detachment of the periosteum in three and partial ossification of the graft in one. Biomechanical tests revealed that the transplants had acquired a hardness similar to that of the surrounding cartilage. We conclude that transplanting chondrocytes in a newly-formed matrix of atelocollagen gel can promote restoration of the articular cartilage of the knee

Cartilage defects of the hip cause significant pain and may lead to arthritic changes that necessitate hip replacement. We propose the use of fresh osteochondral allografts as an option for the treatment of such defects in young patients. Here we present the results of fresh osteochondral allografts for cartilage defects in 17 patients in a prospective study. The underlying diagnoses for the cartilage defects were osteochondritis dissecans in eight and avascular necrosis in six. Two had Legg-Calve-Perthes and one a femoral head fracture. Pre-operatively, an MRI was used to determine the size of the cartilage defect and the femoral head diameter. All patients underwent surgical hip dislocation with a trochanteric slide osteotomy for placement of the allograft. The mean age at surgery was 25.9 years (17 to 44) and mean follow-up was 41.6 months (3 to 74). The mean Harris hip score was significantly better after surgery (p < 0.01) and 13 patients had fair to good outcomes. One patient required a repeat allograft, one patient underwent hip replacement and two patients are awaiting hip replacement. Fresh osteochondral allograft is a reasonable treatment option for hip cartilage defects in young patients. Cite this article: Bone Joint J 2014;96-B(11 Supple A):11–16

We studied whether the presence of lateral osteophytes on plain radiographs was a predictor for the quality of cartilage in the lateral compartment of patients with varus osteoarthritic of the knee (Kellgren and Lawrence grade 2 to 3). The baseline MRIs of 344 patients from the Osteoarthritis Initiative (OAI) who had varus osteoarthritis (OA) of the knee on hip-knee-ankle radiographs were reviewed. Patients were categorised using the Osteoarthritis Research Society International (OARSI) osteophyte grading system into 174 patients with grade 0 (no osteophytes), 128 grade 1 (mild osteophytes), 28 grade 2 (moderate osteophytes) and 14 grade 3 (severe osteophytes) in the lateral compartment (tibia). All patients had Kellgren and Lawrence grade 2 or 3 arthritis of the medial compartment. The thickness and volume of the lateral cartilage and the percentage of full-thickness cartilage defects in the lateral compartment was analysed. There was no difference in the cartilage thickness or cartilage volume between knees with osteophyte grades 0 to 3. The percentage of full-thickness cartilage defects on the tibial side increased from < 2% for grade 0 and 1 to 10% for grade 3. The lateral compartment cartilage volume and thickness is not influenced by the presence of lateral compartment osteophytes in patients with varus OA of the knee. Large lateral compartment osteophytes (grade 3) increase the likelihood of full-thickness cartilage defects in the lateral compartment. Cite this article: Bone Joint J 2015;97-B:1634–9

Damage to the cartilage of the distal radioulnar joint frequently leads to pain and limitation of movement, therefore repair of this joint cartilage would be highly desirable. The purpose of this study was to investigate the fixation of scaffold in cartilage defects of this joint as part of matrix-assisted regenerative autologous cartilage techniques. Two techniques of fixation of collagen scaffolds, one involving fibrin glue alone and one with fibrin glue and sutures, were compared in artificially created cartilage defects of the distal radioulnar joint in a human cadaver. After being subjected to continuous passive rotation, the methods of fixation were evaluated for cover of the defect and pull out force. No statistically significant differences were found between the two techniques for either cover of the defect or integrity of the scaffold. However, a significantly increased mean pull out force was found for the combined procedure, 0.665 N (0.150 to 1.160) versus 0.242 N (0.060 to 0.730) for glue fixation (p = 0.001). This suggests that although successful fixation of a collagen type I/III scaffold in a distal radioulnar joint cartilage defect is feasible with both forms of fixation, fixation with glue and sutures is preferable. Cite this article: Bone Joint J 2014;96-B:508–12

Aims

Implantation of ultra-purified alginate (UPAL) gel is safe and effective in animal osteochondral defect models. This study aimed to examine the applicability of UPAL gel implantation to acellular therapy in humans with cartilage injury.

Aims

The purpose of this study was to evaluate the mid-term outcomes of autologous matrix-induced chondrogenesis (AMIC) for the treatment of larger cartilage lesions and deformity correction in hips suffering from symptomatic femoroacetabular impingement (FAI).

Composites of chondrocytes and polymerised fibrin were supplemented with insulin-like growth factor-I (IGF-I) during the arthroscopic repair of full-thickness cartilage defects in a model of extensive loss of cartilage in horses. Repairs facilitated with IGF-I and chondrocyte-fibrin composites, or control defects treated with chondrocyte-fibrin composites alone, were compared before death by the clinical appearance and repeated analysis of synovial fluid, and at termination eight months after surgery by tissue morphology, collagen typing, and biochemical assays. The structure of cartilage was evaluated histologically by Toluidine Blue reaction and collagen type-I and type-II in situ hybridisation and immunohistochemistry. Repair tissue was biochemically evaluated by DNA assay, proteoglycan quantitation and characterisation, assessment of collagen by reverse-phase high-performance liquid chromatography, and collagen typing using cyanogen bromide digestion and peptide separation by polyacrylamide gel electrophoresis. The results at eight months showed that the addition of IGF-I to chondrocyte grafts enhanced chondrogenesis in cartilage defects, including incorporation into surrounding cartilage. Gross filling of defects was improved, and the tissue contained a higher proportion of cells producing type-II collagen. Measurements of collagen type II showed improved levels in IGF-I-treated defects, supporting in situ hybridisation and immunohistochemical assessments of the defects. IGF-I improves the repair capabilities of chondrocyte-fibrin grafts in large full-thickness repair models

Gene therapy with insulin-like growth factor-1 (IGF-1) increases matrix production and enhances chondrocyte proliferation and survival in vitro. The purpose of this study was to determine whether arthroscopically-grafted chondrocytes genetically modified by an adenovirus vector encoding equine IGF-1 (AdIGF-1) would have a beneficial effect on cartilage healing in an equine femoropatellar joint model. A total of 16 horses underwent arthroscopic repair of a single 15 mm cartilage defect in each femoropatellar joint. One joint received 2 × 10. 7. AdIGF-1 modified chondrocytes and the contralateral joint received 2 × 10. 7. naive (unmodified) chondrocytes. Repairs were analysed at four weeks, nine weeks and eight months after surgery. Morphological and histological appearance, IGF-1 and collagen type II gene expression (polymerase chain reaction, in situ hybridisation and immunohistochemistry), collagen type II content (cyanogen bromide and sodium dodecyl sulphate-polyacrylamide gel electrophoresis), proteoglycan content (dimethylmethylene blue assay), and gene expression for collagen type I, matrix metalloproteinase (MMP)-1, MMP-3, MMP-13, aggrecanase-1, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and TIMP-3 were evaluated. Genetic modification of chondrocytes significantly increased IGF-1 mRNA and ligand production in repair tissue for up to nine weeks following transplantation. The gross and histological appearance of IGF-1 modified repair tissue was improved over control defects. Gross filling of defects was significantly improved at four weeks, and a more hyaline-like tissue covered the lesions at eight months. Histological outcome at four and nine weeks post-transplantation revealed greater tissue filling of defects transplanted with genetically modified chondrocytes, whereas repair tissue in control defects was thin and irregular and more fibrous. Collagen type II expression in IGF-1 gene-transduced defects was increased 100-fold at four weeks and correlated with increased collagen type II immunoreaction up to eight months. Genetic modification of chondrocytes with AdIGF-1 prior to transplantation improved early (four to nine weeks), and to a lesser degree long-term, cartilage healing in the equine model. The equine model of cartilage healing closely resembles human clinical cartilage repair. The results of this study suggest that cartilage healing can be enhanced through genetic modification of chondrocytes prior to transplantation

Autologous chondrocyte implantation (ACI) has been used most commonly as a treatment for cartilage defects in the knee and there are few studies of its use in other joints. We describe ten patients with an osteochondral lesion of the talus who underwent ACI using cartilage taken from the knee and were prospectively reviewed with a mean follow-up of 23 months. In nine patients the satisfaction score was ‘pleased’ or ‘extremely pleased’, which was sustained at four years. The mean Mazur ankle score increased by 23 points at a mean follow-up of 23 months. The Lysholm knee score returned to the pre-operative level at one year in three patients, with the remaining seven showing a reduction of 15% at 12 months, suggesting donor-site morbidity. Nine patients underwent arthroscopic examination at one year and all were shown to have filled defects and stable cartilage. Biopsies taken from graft sites showed mostly fibrocartilage with some hyaline cartilage. The short-term results of ACI for osteochondral lesions of the talus are good despite some morbidity at the donor site

Aims

This study reports mid-term outcomes after periacetabular osteotomy (PAO) exclusively in a borderline hip dysplasia (BHD) population to provide a contrast to published outcomes for arthroscopic surgery of the hip in BHD.

Aims

To identify unanswered questions about the prevention, diagnosis, treatment, and rehabilitation and delivery of care of first-time soft-tissue knee injuries (ligament injuries, patella dislocations, meniscal injuries, and articular cartilage) in children (aged 12 years and older) and adults.

Aims

Arthroscopic microfracture is a conventional form of treatment for patients with osteochondritis of the talus, involving an area of < 1.5 cm². However, some patients have persistent pain and limitation of movement in the early postoperative period. No studies have investigated the combined treatment of microfracture and shortwave treatment in these patients. The aim of this prospective single-centre, randomized, double-blind, placebo-controlled trial was to compare the outcome in patients treated with arthroscopic microfracture combined with radial extracorporeal shockwave therapy (rESWT) and arthroscopic microfracture alone, in patients with ostechondritis of the talus.

Aims

The aim of this study was to evaluate the association between chondral injury and interval from anterior cruciate ligament (ACL) tear to surgical reconstruction (ACLr).

Aims

Hip arthroscopy (HA) has become the treatment of choice for femoroacetabular impingement (FAI). However, less favourable outcomes following arthroscopic surgery are expected in patients with severe chondral lesions. The aim of this study was to assess the outcomes of HA in patients with FAI and associated chondral lesions, classified according to the Outerbridge system.

Aims

To determine the relationship between articular cartilage status and clinical outcomes after medial opening-wedge high tibial osteotomy (MOHTO) for medial compartmental knee osteoarthritis at intermediate follow-up.

Aims

Meniscal allograft transplantation (MAT) for patients with symptomatic meniscal loss has demonstrated good clinical results and survivorship. Factors that affect both functional outcome and survivorship have been reported in the literature. These are typically single-centre case series with relatively small numbers and conflicting results. Our aim was to describe an international, two-centre case series, and identify factors that affect both functional outcome and survival.

We developed a new porous scaffold made from a synthetic polymer, poly(DL-lactide-co-glycolide) (PLG), and evaluated its use in the repair of cartilage. Osteochondral defects made on the femoral trochlear of rabbits were treated by transplantation of the PLG scaffold, examined histologically and compared with an untreated control group. Fibrous tissue was initially organised in an arcade array with poor cellularity at the articular surface of the scaffold. The tissue regenerated to cartilage at the articular surface. In the subchondral area, new bone formed and the scaffold was absorbed. The histological scores were significantly higher in the defects treated by the scaffold than in the control group (p < 0.05). Our findings suggest that in an animal model the new porous PLG scaffold is effective for repairing full-thickness osteochondral defects without cultured cells and growth factors

Twenty-five patients with 30 chondral lesions of the knee were treated with an autogenous strip of costal perichondrium. The graft was fixed to the subchondral bone with Tissucol (Immuno, Vienna), a human fibrin glue. The leg was then immobilised for two weeks followed by two weeks of continuous passive motion. Weight-bearing was permitted after three months. The mean knee score (Ranawat, Insall and Shine 1976) changed from 73 before operation to 90 one year after; in 14 patients evaluated after two years there was no decrease. In 28 cases the defect was completely filled with tissue resembling articular cartilage. We conclude that in most cases perichondral arthroplasty of cartilage defects of the knee gives excellent results

We obtained intervertebral discs with cartilage endplates and underlying cancellous bone at operation from patients with degenerative disc disease and then used immunohistochemical techniques to localise the nerves and nerve endings in the specimens. We used antibodies for the ubiquitous neuronal protein gene product 9.5 (PGP 9.5). Immunoreactivity to neuropeptide Y was used to identify autonomic nerves and calcitonin gene-related peptide (CGRP) and substance P to identify sensory nerves. Blood vessels were identified by immunoreactivity with platelet-endothelial cell-adhesion molecule (CD31; PECAM). In a control group with no known history of chronic back pain, nerve fibres immunoreactive to PGP 9.5 and neuropeptide Y were most closely related to blood vessels, with occasional substance P and CGRP immunoreactivity. In patients with severe back pain and markedly reduced disc height, proliferation of blood vessels and accompanying nerve fibres was observed in the endplate region and underlying vertebral bodies. Many of these nerves were immunoreactive to substance P or CGRP, and in addition, substance P- and CGRP-immunoreactive nociceptors were seen unrelated to blood vessels. Quantification by image analysis showed a marked increase in CGRP-containing sensory nerve fibres compared with normal control subjects. We speculate that a chemotactic response to products of disc breakdown is responsible for the proliferation of vascularity and CGRP-containing sensory nerves found in the endplate region and vertebral body adjacent to degenerate discs. The neuropeptides substance P and CGRP have potent vasodilatory as well as pain-transmitting effects. The increase in sensory nerve endings suggests increase in blood flow, perhaps as an attempt to augment the nutrition of the degenerate disc. The increase in the density of sensory nerves, and the presence of endplate cartilage defects, strongly suggest that the endplates and vertebral bodies are sources of pain; this may explain the severe pain on movement experienced by some patients with degenerative disc disease

Aims

Cementless unicompartmental knee arthroplasty (UKA) has advantages over cemented UKA, including improved fixation, but has a higher risk of tibial plateau fracture, particularly in Japanese patients. The aim of this multicentre study was to determine when cementless tibial components could safely be used in Japanese patients based on the size and shape of the tibia.

Aims

The aim of this study was to evaluate cartilaginous patellotrochlear congruence and patellofemoral alignment parameters after deepening trochleoplasty in severe trochlear dysplasia.

Aims

The intra-articular administration of tranexamic acid (TXA) has been shown to be effective in reducing blood loss in unicompartmental knee arthroplasty and anterior cruciate reconstruction. The effects on human articular cartilage, however, remains unknown. Our aim, in this study, was to investigate any detrimental effect of TXA on chondrocytes, and to establish if there was a safe dose for its use in clinical practice. The hypothesis was that TXA would cause a dose-dependent damage to human articular cartilage.

Aims

Several studies have reported the safety and efficacy of subcapital re-alignment for patients with slipped capital femoral epiphysis (SCFE) using surgical dislocation of the hip and an extended retinacular flap. Instability of the hip and dislocation as a consequence of this surgery has only recently gained attention. We discuss this problem with some illustrative cases.

The aim of this study was to assess the effect of injecting genetically engineered chondrocytes expressing transforming growth factor beta 1 (TGF-β1) into the knees of patients with osteoarthritis. We assessed the resultant function, pain and quality of life.

A total of 54 patients (20 men, 34 women) who had a mean age of 58 years (50 to 66) were blinded and randomised (1:1) to receive a single injection of the active treatment or a placebo. We assessed post-treatment function, pain severity, physical function, quality of life and the incidence of treatment-associated adverse events. Patients were followed at four, 12 and 24 weeks after injection.

At final follow-up the treatment group had a significantly greater improvement in the mean International Knee Documentation Committee score than the placebo group (16 points; -18 to 49, vs 8 points; -4 to 37, respectively; p = 0.03). The treatment group also had a significantly improved mean visual analogue score at final follow-up (-25; -85 to 34, vs -11 points; -51 to 25, respectively; p = 0.032). Both cohorts showed an improvement in Western Ontario and McMaster Osteoarthritis Index and Knee Injury and Osteoarthritis Outcome Scores, but these differences were not statistically significant. One patient had an anaphylactic reaction to the preservation medium, but recovered within 24 hours. All other adverse events were localised and resolved without further action.

This technique may result in improved clinical outcomes, with the aim of slowing the degenerative process, leading to improvements in pain and function. However, imaging and direct observational studies are needed to verify cartilage regeneration. Nevertheless, this study provided a sufficient basis to proceed to further clinical testing.

Cite this article: Bone Joint J 2015;97-B:924–32.

The treatment of osteochondral lesions is of great interest to orthopaedic surgeons because most lesions do not heal spontaneously. We present the short-term clinical outcome and MRI findings of a cell-free scaffold used for the treatment of these lesions in the knee. A total of 38 patients were prospectively evaluated clinically for two years following treatment with an osteochondral nanostructured biomimetic scaffold. There were 23 men and 15 women; the mean age of the patients was 30.5 years (15 to 64). Clinical outcome was assessed using the Knee Injury and Osteoarthritis Outcome Score (KOOS), the Tegner activity scale and a Visual Analgue scale for pain. MRI data were analysed based on the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) scoring system at three, 12 and 24 months post-operatively. There was a continuous significant clinical improvement after surgery. In two patients, the scaffold treatment failed (5.3%) There was a statistically significant improvement in the MOCART precentage scores. The repair tissue filled most of the defect sufficiently. We found subchondral laminar changes in all patients. Intralesional osteophytes were found in two patients (5.3%). We conclude that this one-step scaffold-based technique can be used for osteochondral repair. The surgical technique is straightforward, and the clinical results are promising. The MRI aspects of the repair tissue continue to evolve during the first two years after surgery. However, the subchondral laminar and bone changes are a concern.

Cite this article: Bone Joint J 2015; 97-B:318–23.

We attempted to characterise the biological quality and regenerative potential of chondrocytes in osteochondritis dissecans (OCD). Dissected fragments from ten patients with OCD of the knee (mean age 27.8 years (16 to 49)) were harvested at arthroscopy. A sample of cartilage from the intercondylar notch was taken from the same joint and from the notch of ten patients with a traumatic cartilage defect (mean age 31.6 years (19 to 52)). Chondrocytes were extracted and subsequently cultured. Collagen types 1, 2, and 10 mRNA were quantified by polymerase chain reaction. Compared with the notch chondrocytes, cells from the dissecate expressed similar levels of collagen types 1 and 2 mRNA. The level of collagen type 10 message was 50 times lower after cell culture, indicating a loss of hypertrophic cells or genes. The high viability, retained capacity to differentiate and metabolic activity of the extracted cells suggests preservation of the intrinsic repair capability of these dissecates. Molecular analysis indicated a phenotypic modulation of the expanded dissecate chondrocytes towards a normal phenotype. Our findings suggest that cartilage taken from the dissecate can be reasonably used as a cell source for chondrocyte implantation procedures.

Hyaline articular cartilage has been known to be a troublesome tissue to repair once damaged. Since the introduction of autologous chondrocyte implantation (ACI) in 1994, a renewed interest in the field of cartilage repair with new repair techniques and the hope for products that are regenerative have blossomed. This article reviews the basic science structure and function of articular cartilage, and techniques that are presently available to effect repair and their expected outcomes.

The repair of chondral lesions associated with femoroacetabular impingement requires specific treatment in addition to that of the impingement. In this single-centre retrospective analysis of a consecutive series of patients we compared treatment with microfracture (MFx) with a technique of enhanced microfracture autologous matrix-induced chondrogenesis (AMIC).

Acetabular grade III and IV chondral lesions measuring between 2 cm² and 8 cm² in 147 patients were treated by MFx in 77 and AMIC in 70. The outcome was assessed using the modified Harris hip score at six months and one, two, three, four and five years post-operatively. The outcome in both groups was significantly improved at six months and one year post-operatively. During the subsequent four years the outcome in the MFx group slowly deteriorated, whereas that in the AMIC group remained stable. Six patients in the MFx group subsequently required total hip arthroplasty, compared with none in the AMIC group

We conclude that the short-term clinical outcome improves in patients with acetabular chondral damage following both MFx and AMIC. However, the AMIC group had better and more durable improvement, particularly in patients with large (≥ 4 cm²) lesions.

Cite this article: Bone Joint J 2015; 97-B:628–35.

Perilesional changes of chronic focal osteochondral defects were assessed in the knees of 23 sheep. An osteochondral defect was created in the main load-bearing region of the medial condyle of the knees in a controlled, standardised manner. The perilesional cartilage was evaluated macroscopically and biopsies were taken at the time of production of the defect (T0), during a second operation one month later (T1), and after killing animals at three (T3; n = 8), four (T4; n = 8), and seven (T7; n = 8) months. All the samples were histologically assessed by the International Cartilage Repair Society grading system and Mankin histological scores. Biopsies were taken from human patients (n = 10) with chronic articular cartilage lesions and compared with the ovine specimens. The ovine perilesional cartilage presented with macroscopic and histological signs of degeneration. At T1 the International Cartilage Repair Society ‘Subchondral Bone’ score decreased from a mean of 3.0 (sd 0) to a mean of 1.9 (sd 0.3) and the ‘Matrix’ score from a mean of 3.0 (sd 0) to a mean of 2.5 (sd 0.5). This progressed further at T3, with the International Cartilage Repair Society ‘Surface’ grading, the ‘Matrix’ grading, ‘Cell Distribution’ and ‘Cell Viability’ grading further decreasing and the Mankin score rising from a mean of 1.3 (sd 1.4) to a mean of 5.1 (sd 1.6). Human biopsies achieved Mankin grading of a mean of 4.2 (sd 1.6) and were comparable with the ovine histology at T1 and T3.

The perilesional cartilage in the animal model became chronic at one month and its histological appearance may be considered comparable with that seen in human osteochondral defects after trauma.

The aim of this study was to evaluate the cultivation potential of cartilage taken from the debrided edge of a chronic lesion of the articular surface. A total of 14 patients underwent arthroscopy of the knee for a chronic lesion on the femoral condyles or trochlea. In addition to the routine cartilage biopsy, a second biopsy of cartilage was taken from the edge of the lesion. The cells isolated from both sources underwent parallel cultivation as monolayer and three-dimensional (3D) alginate culture. The cell yield, viability, capacity for proliferation, morphology and the expressions of typical cartilage genes (collagen I, COL1; collagen II, COL2; aggrecan, AGR; and versican, VER) were assessed. The cartilage differentiation indices (COL2/COL1, AGR/VER) were calculated. The control biopsies revealed a higher mean cell yield (1346 cells/mg vs 341 cells/mg), but similar cell proliferation, viability and morphology compared with the cells from the edge of the lesion. The cartilage differentiation indices were superior in control cells: COL2/COL1 (threefold in biopsies (non-significant)); sixfold in monolayer cultures (p = 0.012), and 7.5-fold in hydrogels (non-significant), AGR/VER (sevenfold in biopsies (p = 0.04), threefold (p = 0.003) in primary cultures and 3.5-fold in hydrogels (non-significant)).

Our results suggest that the cultivation of chondrocytes solely from the edges of the lesion cannot be recommended for use in autologous chondrocyte implantation.

We reviewed 5086 patients with a mean age of 30 years (9 to 69) undergoing primary reconstruction of the anterior cruciate ligament (ACL) in order to determine the incidence of secondary pathology with respect to the time between injury and reconstruction. There was an increasing incidence of medial meniscal tears and chondral damage, but not lateral meniscal tears, with increasing intervals before surgery. The chances of requiring medial meniscal surgery was increased by a factor of two if ACL reconstruction was delayed more than five months, and increased by a factor of six if surgery was delayed by > 12 months. The effect of delaying surgery on medial meniscal injury was also pronounced in the patients aged < 17 years, where a delay of five to 12 months doubled the odds of medial meniscal surgery (odds ratio (OR) 2.0, p = 0.001) and a delay of > 12 months quadrupled the odds (OR 4.3, p = 0.001). Increasing age was associated with a greater odds of chondral damage (OR 4.6, p = 0.001) and medial meniscal injury (OR 2.9, p = 0.001), but not lateral meniscal injury. The gender split (3251 men, 1835 women) revealed that males had a greater incidence of both lateral (34% (n = 1114) vs 20% (n = 364), p = 0.001) and medial meniscal tears (28% (n = 924) vs 25% (n = 457), p = 0.006), but not chondral damage (35% (n = 1152) vs 36% (n = 665), p = 0.565). We conclude that ideally, and particularly in younger patients, ACL reconstruction should not be delayed more than five months from injury.

Cite this article: Bone Joint J 2013;95-B:59–64.

The gelatin-based haemostyptic compound Spongostan was tested as a three-dimensional (3D) chondrocyte matrix in an in vitro model for autologous chondrocyte transplantation using cells harvested from bovine knees. In a control experiment of monolayer cultures, the proliferation or de-differentiation of bovine chondrocytes was either not or only marginally influenced by the presence of Spongostan (0.3 mg/ml).

In monolayers and 3-D Minusheet culture chambers, the cartilage-specific differentiation markers aggrecan and type-II collagen were ubiquitously present in a cell-associated fashion and in the pericellular matrix. The Minusheet cultures usually showed a markedly higher mRNA expression than monolayer cultures irrespective of whether Spongostan had been present or not during culture. Although the de-differentiation marker type-I collagen was also present, the ratio of type-I to type-II collagen or aggrecan to type-I collagen remained higher in Minusheet 3-D cultures than in monolayer cultures irrespective of whether Spongostan had been included in or excluded from the monolayer cultures. The concentration of GAG in Minusheet cultures reached its maximum after 14 days with a mean of 0.83 ± 0.8 μg/10⁶ cells; mean ±, sem, but remained considerably lower than in monolayer cultures with/without Spongostan.

Our results suggest that Spongostan is in principle suitable as a 3-D chondrocyte matrix, as demonstrated in Minusheet chambers, in particular for a culture period of 14 days. Clinically, differentiating effects on chondrocytes, simple handling and optimal formability may render Spongostan an attractive 3-D scaffold for autologous chondrocyte transplantation.

Treatment strategies for osteoarthritis most commonly involve the removal or replacement of damaged joint tissue. Relatively few treatments attempt to arrest, slow down or reverse the disease process. Such options include peri-articular osteotomy around the hip or knee, and treatment of femoro-acetabular impingement, where early intervention may potentially alter the natural history of the disease. A relatively small proportion of patients with osteoarthritis have a clear predisposing factor that is both suitable for modification and who present early enough for intervention to be deemed worthwhile. This paper reviews recent advances in our understanding of the pathology, imaging and progression of early osteoarthritis.

Articular cartilage repair remains a challenge to surgeons and basic scientists. The field of tissue engineering allows the simultaneous use of material scaffolds, cells and signalling molecules to attempt to modulate the regenerative tissue. This review summarises the research that has been undertaken to date using this approach, with a particular emphasis on those techniques that have been introduced into clinical practice, via in vitro and preclinical studies.

An increasing number of patients are treated by autologous chondrocyte implantation (ACI). This study tests the hypothesis that culture within a defined chondrogenic medium containing TGF-β enhances the reexpression of a chondrocytic phenotype and the subsequent production of cartilaginous extracellular matrix by human chondrocytes used in ACI. Chondrocytes surplus to clinical requirements for ACI from 24 patients were pelleted and cultured in either DMEM (Dulbecco’s modified eagles medium)/ITS+Premix/TGF-β1 or DMEM/10%FCS (fetal calf serum) and were subsequently analysed biochemically and morphologically.

Pellets cultured in DMEM/ITS+/TGF-β1 stained positively for type-II collagen, while those maintained in DMEM/10%FCS expressed type-I collagen. The pellets cultured in DMEM/ITS+/TGF-β1 were larger and contained significantly greater amounts of DNA and glycosaminoglycans. This study suggests that the use of a defined medium containing TGF-β is necessary to induce the re-expression of a differentiated chondrocytic phenotype and the subsequent stimulation of glycosaminoglycan and type-II collagen production by human monolayer expanded chondrocytes.

When transferring tissue regenerative strategies involving skeletal stem cells to human application, consideration needs to be given to factors that may affect the function of the cells that are transferred. Local anaesthetics are frequently used during surgical procedures, either administered directly into the operative site or infiltrated subcutaneously around the wound. The aim of this study was to investigate the effects of commonly used local anaesthetics on the morphology, function and survival of human adult skeletal stem cells.

Cells from three patients who were undergoing elective hip replacement were harvested and incubated for two hours with 1% lidocaine, 0.5% levobupivacaine or 0.5% bupivacaine hydrochloride solutions. Viability was quantified using WST-1 and DNA assays. Viability and morphology were further characterised using CellTracker Green/Ethidium Homodimer-1 immunocytochemistry and function was assessed by an alkaline phosphatase assay. An additional group was cultured for a further seven days to allow potential recovery of the cells after removal of the local anaesthetic.

A statistically significant and dose dependent reduction in cell viability and number was observed in the cell cultures exposed to all three local anaesthetics at concentrations of 25% and 50%, and this was maintained even following culture for a further seven days.

This study indicates that certain local anaesthetic agents in widespread clinical use are deleterious to skeletal progenitor cells when studied in vitro; this might have relevance in clinical applications.

We retrospectively studied 14 patients with proximal and diaphyseal tumours and disappearing bone (Gorham’s) disease of the humerus treated with wide resection and reconstruction using an allograft-resurfacing composite (ARC). There were ten women and four men, with a mean age of 35 years (8 to 69). At a mean follow-up of 25 months (10 to 89), two patients had a fracture of the allograft. In one of these it was revised with a similar ARC and in the other with an intercalary prosthesis. A further patient had an infection and a fracture of the allograft that was revised with a megaprosthesis. In all patients with an ARC, healing of the ARC-host bone interface was observed. One patient had failure of the locking mechanism of the total elbow replacement. The mean post-operative Musculoskeletal Tumor Society score for the upper extremity was 77% (46.7% to 86.7%), which represents good and excellent results; one patient had a poor result (46.7%).

In the short term ARC effectively relieves pain and restores shoulder function in patients with wide resection of the proximal humerus. Fracture and infection remain significant complications.

There have been considerable recent advances in the understanding and management of femoroacetabular impingement and associated labral and chondral pathology. We have developed a classification system for acetabular chondral lesions. In our system, we use the six acetabular zones previously described by Ilizaliturri et al. The cartilage is then graded on a scale of 0 to 4 as follows: grade 0, normal articular cartilage lesions; grade 1, softening or wave sign; grade 2, cleavage lesion; grade 3, delamination; and grade 4, exposed bone. The site of the lesion is further classed as A, B or C based on whether the lesion is less than one-third of the distance from the acetabular rim to the cotyloid fossa, one-third to two-thirds of the same distance and greater than two-thirds of the distance, respectively. In order to validate the classification system, six surgeons graded ten video recordings of hip arthroscopy.

Our findings showed a high intra-observer reliability of the classification system with an intraclass correlation coefficient of 0.81 and a high interobserver reliability with an intraclass correlation coefficient of 0.88.

We have developed a simple reproducible classification system for lesions of the acetabular cartilage, which it is hoped will allow standardised documentation to be made of damage to the articular cartilage, particularly that associated with femoroacetabular impingement.

Patella subluxation assessed on dynamic MRI has previously been shown to be associated with anterior knee pain. In this MRI study of 60 patients we investigated the relationship between subluxation and multiple bony, cartilaginous and soft-tissue factors that might predispose to subluxation using discriminant function analysis.

Patella engagement (% of patella cartilage overlapping with trochlea cartilage) had the strongest relationship with subluxation. Patellae with > 30% engagement tended not to sublux; those with < 30% tended to sublux. Other factors that were associated with subluxation included the tibial tubercle-trochlea notch distance, vastus medialis obliquus distance from patella, patella alta, and the bony and cartilaginous sulcus angles in the superior part of the trochlea. No relationship was found between subluxation and sulcus angles for cartilage and bone in the middle and lower part of the trochlea, cartilage thicknesses and Wiberg classification of the patella.

This study indicates that patella engagement is a key factor associated with patellar subluxation. This suggests that in patients with anterior knee pain with subluxation, resistant to conservative management, surgery directed towards improving patella engagement should be considered. A clinical trial is necessary to test this hypothesis.

Surgical dislocation of the hip in the treatment of acetabular fractures allows the femoral head to be safely displaced from the acetabulum. This permits full intra-articular acetabular and femoral inspection for the evaluation and potential treatment of cartilage lesions of the labrum and femoral head, reduction of the fracture under direct vision and avoidance of intra-articular penetration with hardware. We report 60 patients with selected types of acetabular fracture who were treated using this approach. Six were lost to follow-up and the remaining 54 were available for clinical and radiological review at a mean follow-up of 4.4 years (2 to 9).

Substantial damage to the intra-articular cartilage was found in the anteromedial portion of the femoral head and the posterosuperior aspect of the acetabulum. Labral lesions were predominantly seen in the posterior acetabular area. Anatomical reduction was achieved in 50 hips (93%) which was considerably higher than that seen in previous reports. There were no cases of avascular necrosis. Four patients subsequently required total hip replacement. Good or excellent results were achieved in 44 hips (81.5%). The cumulative eight-year survivorship was 89.0% (95% confidence interval 84.5 to 94.1). Significant predictors of poor outcome were involvement of the acetabular dome and lesions of the femoral cartilage greater than grade 2. The functional mid-term results were better than those of previous reports.

Surgical dislocation of the hip allows accurate reduction and a predictable mid-term outcome in the management of these difficult injuries without the risk of the development of avascular necrosis.

Autologous chondrocyte implantation (ACI) is a technique used for the treatment of symptomatic osteochondral defects of the knee. A variation of the original periosteum membrane technique is the matrix-induced autologous chondrocyte implantation (MACI) technique. The MACI membrane consists of a porcine type-I/III collagen bilayer seeded with chondrocytes. Osteochondral defects deeper than 8 to 10 mm usually require bone grafting either before or at the time of transplantation of cartilage. We have used a variation of Peterson’s ACI-periosteum sandwich technique using two MACI membranes with bone graft which avoids periosteal harvesting. The procedure is suture-free and requires less operating time and surgical exposure. We performed this MACI-sandwich technique on eight patients, five of whom were assessed at six months and one year post-operatively using the modified Cincinnati knee, the Stanmore functional rating and the visual analogue pain scores.

All patients improved within six months with further improvement at one year. The clinical outcome was good or excellent in four after six months and one year. No significant graft-associated complications were observed. Our early results of the MACI-sandwich technique are encouraging although larger medium-term studies are required before there is widespread adoption of the technique.

We reviewed nine patients at a mean period of 11 years (6 to 16) after curettage and cementing of a giant-cell tumour around the knee to determine if there were any long-term adverse effects on the cartilage. Plain radiography, MRI, delayed gadolinium-enhanced MRI of the cartilage and measurement of the serum level of cartilage oligomeric matrix protein were carried out. The functional outcome was evaluated using the Lysholm knee score.

Each patient was physically active and had returned to their previous occupation. Most participated in recreational sports or exercise.

The mean Lysholm knee score was 92 (83 to 100). Only one patient was found to have cartilage damage adjacent to the cement. This patient had a history of intra-articular fracture and local recurrence, leading to degenerative changes.

Interpretation of the data obtained from delayed gadolinium-enhanced MRI of the cartilage was difficult, with variation in the T1 values which did not correlate with the clinical or radiological findings. We did not find it helpful in the early diagnosis of degeneration of cartilage. We also found no obvious correlation between the serum cartilage oligomeric matrix protein level and the radiological and MR findings, function, time after surgery and the age of the patient.

In summary, we found no evidence that the long-term presence of cement close to the knee joint was associated with the development of degenerative osteoarthritis.

We attempted to repair full-thickness defects in the articular cartilage of the trochlear groove of the femur in 30 rabbit knee joints using allogenic cultured chondrocytes embedded in a collagen gel. The repaired tissues were examined at 2, 4, 8, 12 and 24 weeks after operation using histological and histochemical methods. The articular defect filling index measurement was derived from safranin-O stained sections. Apoptotic cellular fractions were derived from analysis of apoptosis in situ using TUNEL staining, and was confirmed using caspase-3 staining along with quantification of the total cellularity. The mean articular defect filling index decreased with time. After 24 weeks it was 0.7 (sd 0.10), which was significantly lower than the measurements obtained earlier (p < 0.01). The highest mean percentage of apoptotic cells were observed at 12 weeks, although the total cellularity decreased with time. Because apoptotic cell death may play a role in delamination after chondrocyte transplantation, anti-apoptotic gene therapy may protect transplanted chondrocytes from apoptosis.

The options for treatment of the young active patient with isolated symptomatic osteoarthritis of the medial compartment and pre-existing deficiency of the anterior cruciate ligament are limited. The potential longevity of the implant and levels of activity of the patient may preclude total knee replacement, and tibial osteotomy and unicompartmental knee arthroplasty are unreliable because of the ligamentous instability. Unicompartmental knee arthroplasties tend to fail because of wear or tibial loosening resulting from eccentric loading. Therefore, we combined reconstruction of the anterior cruciate ligament with unicompartmental arthroplasty of the knee in 15 patients (ACLR group), and matched them with 15 patients who had undergone Oxford unicompartmental knee arthroplasty with an intact anterior cruciate ligament (ACLI group). The clinical and radiological data at a minimum of 2.5 years were compared for both groups.

The groups were well matched for age, gender and length of follow-up and had no significant differences in their pre-operative scores. At the last follow-up, the mean outcome scores for both the ACLR and ACLI groups were high (Oxford knee scores of 46 (37 to 48) and 43 (38 to 46), respectively, objective Knee Society scores of 99 (95 to 100) and 94 (82 to 100), and functional Knee Society scores of 96 and 96 (both 85 to 100). One patient in the ACLR group needed revision to a total knee replacement because of infection. No patient in either group had radiological evidence of component loosening. The radiological study showed no difference in the pattern of tibial loading between the groups.

The short-term clinical results of combined anterior cruciate ligament reconstruction and unicompartmental knee arthroplasty are excellent. The previous shortcomings of unicompartmental knee arthroplasty in the presence of deficiency of the anterior cruciate ligament appear to have been addressed with the combined procedure. This operation seems to be a viable treatment option for young active patients with symptomatic arthritis of the medial compartment, in whom the anterior cruciate ligament has been ruptured.

In a randomised prospective study, 20 patients with intra-articular fractures of the distal radius underwent arthroscopically- and fluoroscopically-assisted reduction and external fixation plus percutaneous pinning. Another group of 20 patients with the same fracture characteristics underwent fluoroscopically-assisted reduction alone and external fixation plus percutaneous pinning. The patients were evaluated clinically and radiologically at follow-up of 24 months. The Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire and modified Mayo wrist score were used at 3, 9, 12 and 24 months postoperatively. In the arthroscopically- and fluoroscopically-assisted group, triangular fibrocartilage complex tears were found in 12 patients (60%), complete or incomplete scapholunate ligament tears in nine (45%), and lunotriquetral ligament tears in four (20%). They were treated either arthroscopically or by open operation. Patients who underwent arthroscopically- and fluoroscopically-assisted treatment had significantly better supination, extension and flexion at all time points than those who had fluoroscopically-assisted surgery. The mean DASH scores were similar for both groups at 24 months, whereas the difference in the mean modified Mayo wrist scores remained statistically significant.

Although the groups are small, it is clear that the addition of arthroscopy to the fluoroscopically-assisted treatment of intra-articular distal radius fractures improves the outcome. Better treatment of associated intra-articular injuries might also have been a reason for the improved outcome.

Post-traumatic arthritis is a frequent consequence of articular fracture. The mechanisms leading to its development after such injuries have not been clearly delineated. A potential contributing factor is decreased viability of the articular chondrocytes. The object of this study was to characterise the regional variation in the viability of chondrocytes following joint trauma. A total of 29 osteochondral fragments from traumatic injuries to joints that could not be used in articular reconstruction were analysed for cell viability using the fluorescence live/dead assay and for apoptosis employing the TUNEL assay, and compared with cadaver control fragments.

Chondrocyte death and apoptosis were significantly greater along the edge of the fracture and in the superficial zone of the osteochondral fragments. The middle and deep zones demonstrated significantly higher viability of the chondrocytes. These findings indicate the presence of both necrotic and apoptotic chondrocytes after joint injury and may provide further insight into the role of chondrocyte death in post-traumatic arthritis.

Ovine articular chondrocytes were isolated from cartilage biopsy and culture expanded in vitro. Approximately 30 million cells per ml of cultured chondrocytes were incorporated with autologous plasma-derived fibrin to form a three-dimensional construct. Full-thickness punch hole defects were created in the lateral and medial femoral condyles. The defects were implanted with either an autologous ‘chondrocyte-fibrin’ construct (ACFC), autologous chondrocytes (ACI) or fibrin blanks (AF) as controls. Animals were killed after 12 weeks. The gross appearance of the treated defects was inspected and photographed. The repaired tissues were studied histologically and by scanning electron microscopy analysis.

All defects were assessed using the International Cartilage Repair Society (ICRS) classification. Those treated with ACFC, ACI and AF exhibited median scores which correspond to a nearly-normal appearance. On the basis of the modified O’Driscoll histological scoring scale, ACFC implantation significantly enhanced cartilage repair compared to ACI and AF. Using scanning electron microscopy, ACFC and ACI showed characteristic organisation of chondrocytes and matrices, which were relatively similar to the surrounding adjacent cartilage.

Implantation of ACFC resulted in superior hyaline-like cartilage regeneration when compared with ACI. If this result is applicable to humans, a better outcome would be obtained than by using conventional ACI.

Human bone-marrow mesenchymal stem cells have an important role in the repair of musculoskeletal tissues by migrating from the bone marrow into the injured site and undergoing differentiation. We investigated the use of autologous human serum as a substitute for fetal bovine serum in the ex vivo expansion medium to avoid the transmission of dangerous transfectants during clinical reconstruction procedures.

Autologous human serum was as effective in stimulating growth of bone-marrow stem cells as fetal bovine serum. Furthermore, medium supplemented with autologous human serum was more effective in promoting motility than medium with fetal bovine serum in all cases. Addition of B-fibroblast growth factor to medium with human serum stimulated growth, but not motility. Our results suggest that autologous human serum may provide sufficient ex vivo expansion of human bone-marrow mesenchymal stem cells possessing multidifferentiation potential and may be better than fetal bovine serum in preserving high motility.

The purpose of this study was to examine the effects of hyaluronic acid supplementation on chondrocyte metabolism in vitro. The clinical benefits of intra-articular hyaluronic acid injections are thought to occur through improved joint lubrication. Recent findings have shown that exogenous hyaluronic acid is incorporated into articular cartilage where it may have a direct biological effect on chondrocytes through CD44 receptors.

Bovine articular chondrocytes were isolated and seeded into alginate constructs. These were cultured in medium containing hyaluronic acid at varying concentrations. Samples were assayed for biochemical and histological changes.

There was a dose-dependent response to the exposure of hyaluronic acid to bovine articular chondrocytes in vitro. Low concentrations of hyaluronic acid (0.1 mg/mL and 1 mg/mL) significantly increase DNA, sulphated glycosaminoglycan and hydroxyproline synthesis. Immunohistology confirmed the maintenance of cell phenotype with increased matrix deposition of chondroitin-6-sulphate and collagen type II. These findings confirm a stimulatory effect of hyaluronic acid on chondrocyte metabolism.

In this study a combination of autologous chondrocyte implantation (ACI) and the osteochondral autograft transfer system (OATS) was used and evaluated as a treatment option for the repair of large areas of degenerative articular cartilage. We present the results at three years post-operatively. Osteochondral cores were used to restore the contour of articular cartilage in 13 patients with large lesions of the lateral femoral condyle (n = 5), medial femoral condyle (n = 7) and patella (n = 1). Autologous cultured chondrocytes were injected underneath a periosteal patch covering the cores. After one year, the patients had a significant improvement in their symptoms and after three years this level of improvement was maintained in ten of the 13 patients. Arthroscopic examination revealed that the osteochondral cores became well integrated with the surrounding cartilage. We conclude that the hybrid ACI/OATS technique provides a promising surgical approach for the treatment of patients with large degenerative osteochondral defects.

We produced large full-thickness articular cartilage defects in 33 rabbits in order to evaluate the effect of joint distraction and autologous culture-expanded bone-marrow-derived mesenchymal cell transplantation (ACBMT) at 12 weeks. After fixing the knee on a hinged external fixator, we resected the entire surface of the tibial plateau. We studied three groups: 1) with and without joint distraction; 2) with joint distraction and collagen gel, and 3) with joint distraction and ACBMT and collagen gel. The histological scores were significantly higher in the groups with ACBMT collagen gel (p < 0.05). The area of regenerated soft tissue was smaller in the group allowed to bear weight (p < 0.05). These findings suggest that the repair of large defects of cartilage can be enhanced by joint distraction, collagen gel and ACBMT

Recently, femoroacetabular impingement has been recognised as a cause of early osteoarthritis. There are two mechanisms of impingement: 1) cam impingement caused by a non-spherical head and 2) pincer impingement caused by excessive acetabular cover. We hypothesised that both mechanisms result in different patterns of articular damage. Of 302 analysed hips only 26 had an isolated cam and 16 an isolated pincer impingement. Cam impingement caused damage to the anterosuperior acetabular cartilage with separation between the labrum and cartilage. During flexion, the cartilage was sheared off the bone by the non-spherical femoral head while the labrum remained untouched. In pincer impingement, the cartilage damage was located circumferentially and included only a narrow strip. During movement the labrum is crushed between the acetabular rim and the femoral neck causing degeneration and ossification.

Both cam and pincer impingement lead to osteoarthritis of the hip. Labral damage indicates ongoing impingement and rarely occurs alone.

Critical size defects in ovine tibiae, stabilised with intramedullary interlocking nails, were used to assess whether the addition of carboxymethylcellulose to the standard osteogenic protein-1 (OP-1/BMP-7) implant would affect the implant’s efficacy for bone regeneration. The biomaterial carriers were a ‘putty’ carrier of carboxymethylcellulose and bovine-derived type-I collagen (OPP) or the standard with collagen alone (OPC). These two treatments were also compared to “ungrafted” negative controls. Efficacy of regeneration was determined using radiological, biomechanical and histological evaluations after four months of healing. The defects, filled with OPP and OPC, demonstrated radiodense material spanning the defect after one month of healing, with radiographic evidence of recorticalisation and remodelling by two months. The OPP and OPC treatment groups had equivalent structural and material properties that were significantly greater than those in the ungrafted controls. The structural properties of the OPP- and OPC-treated limbs were equivalent to those of the contralateral untreated limb (p > 0.05), yet material properties were inferior (p < 0.05). Histopathology revealed no residual inflammatory response to the biomaterial carriers or OP-1. The OPP- and OPC-treated animals had 60% to 85% lamellar bone within the defect, and less than 25% of the regenerate was composed of fibrous tissue. The defects in the untreated control animals contained less than 40% lamellar bone and more than 60% was fibrous tissue, creating full cortical thickness defects. In our studies carboxymethylcellulose did not adversely affect the capacity of the standard OP-1 implant for regenerating bone.