A Rabbit Model of Osteochondral Regeneration Using Three-Dimensional Printed Polycaprolactone-Hydroxyapatite Scaffolds Coated with Umbilical Cord Blood Mesenchymal Stem Cells and Chondrocytes.

BACKGROUND This study aimed to investigate a rabbit model of osteochondral regeneration using three-dimensional (3-D) printed polycaprolactone-hydroxyapatite (PCL-HA) scaffolds coated with umbilical cord blood mesenchymal stem cells (UCB-MSCs) and chondrocytes. MATERIAL AND METHODS Nine female New Zealand white rabbits were included in the study. The 3-D PCL-HA scaffolds were prepared using fused deposition modeling 3-D printing technology. Seeding cells were prepared by co-culture of rabbit UCB-MSCs and chondrocytes with a ratio of 3: 1. A total of 4×106 cells were seeded on 3-D PCL-HA scaffolds and implanted into rabbits with femoral trochlear defects. After 8 weeks of in vivo implantation, 12 specimens were sampled and examined using histology and scanning electron microscopy (SEM). The International Cartilage Repair Society (ICRS) macroscopic scores and histological results were recorded and compared with those of the unseeded PCL-HA scaffolds. RESULTS Mean ICRS scores for the UCB-MSCs and chondrocyte-seeded PCL-HA scaffolds (group A) were significantly higher than the normal unseeded control (NC) PCL-HA scaffold group (group B) (P<0.05). Histology with safranin-O and fast-green staining showed that the UCB chondrocyte-seeded PCL-HA scaffolds significantly promoted bone and cartilage regeneration. CONCLUSIONS In a rabbit model of osteochondral regeneration using 3-D printed PCL-HA scaffolds, the UCB chondrocyte-seeded PCL-HA scaffold promoted articular cartilage repair when compared with the control or non-seeded PCL-HA scaffolds.

Continuous low-intensity ultrasound attenuates IL-6 and TNFα-induced catabolic effects and repairs chondral fissures in bovine osteochondral explants.

BACKGROUND: Cartilage repair outcomes are compromised in a pro-inflammatory environment; therefore, the mitigation of pro-inflammatory responses is beneficial. Treatment with continuous low-intensity ultrasound (cLIUS) at the resonant frequency of 5 MHz is proposed for the repair of chondral fissures under pro-inflammatory conditions. METHODS: Bovine osteochondral explants, concentrically incised to create chondral fissures, were maintained under cLIUS (14 kPa (5 MHz, 2.5 Vpp), 20 min, 4 times/day) for a period of 28 days in the presence or absence of cytokines, interleukin-6 (IL-6) or tumor necrosis factor (TNF)α. Outcome assessments included histological and immunohistochemical staining of the explants; and the expression of catabolic and anabolic genes by qRT-PCR in bovine chondrocytes. Cell migration was assessed by scratch assays, and by visualizing migrating cells into the hydrogel core of cartilage-hydrogel constructs. RESULTS: Both in the presence and absence of cytokines, higher percent apposition along with closure of fissures were noted in cLIUS-stimulated explants as compared to non-cLIUS-stimulated explants on day 14. On day 28, the percent apposition was not significantly different between unstimulated and cLIUS-stimulated explants exposed to cytokines. As compared to non-cLIUS-stimulated controls, on day 28, cLIUS preserved the distribution of proteoglycans and collagen II in explants despite exposure to cytokines. cLIUS enhanced the cell migration irrespective of cytokine treatment. IL-6 or TNFα-induced increases in MMP13 and ADAMTS4 gene expression was rescued by cLIUS stimulation in chondrocytes. Under cLIUS, TNFα-induced increase in NF-κB expression was suppressed, and the expression of collagen II and TIMP1 genes were upregulated. CONCLUSION: cLIUS repaired chondral fissures, and elicited pro-anabolic and anti-catabolic effects, thus demonstrating the potential of cLIUS in improving cartilage repair outcomes.

Joint debridement and microfracture for treatment late-stage Freiberg-Kohler's disease: Long-term follow-up study.

BACKGROUND: Freiberg-Kohler's disease is not a common disease and although various reports have been described since 1914, treatment methods are not completely established. The purpose of the present retrospective study was to evaluate the long-term outcomes following joint debridement and microfracture procedures for the treatment of Freiberg-Kohler's disease. METHODS: Fifteen consecutive patients (16 feet) with Freiberg-Kohler's disease (Smillie's classification grade III-V) were operated between May 1996 to December 2011. All patients followed the same post-operative protocol. The objective and subjective evaluations were taken at the initial examination and at final follow-up. RESULTS: Mean follow-up was 11 years ±5.5 (range 4.2-19.7 years). The AOFAS score, VAS score and ROM of the MTP joint improved significantly after surgery (p value <0.05). The AOFAS score improved from a preoperative value of 46.7±15.5 points to 83.2±9.4 points postoperative (p<0.05). The mean preoperative joint ROM was 28°±8° and 49°±13° postoperative (p<0.05). VAS score improved from a preoperative value of 5.5±1.2 points to 1.2±1 points at last follow-up (p<0.05). At the end of follow-up 13 patients (81%) declared they were very satisfied, 3 patients (19%) satisfied and nobody unsatisfied. CONCLUSIONS: Our results suggest that joint debridement and microfracture procedure is an effective surgical treatment for late-stage Freiberg-Kohler's disease with decrease of daily pain, improved ROM, and high patient satisfaction.

Pediatric Osteochondral Lesions.

Osteochondral lesions are common in children and may arise from a variety of etiologies. Although they most frequently occur in the knee, other joints may be involved including the ankle and elbow. We describe the typical imaging appearance of osteochondral lesions with a focus on radiographs and magnetic resonance imaging. Assessment of the stability of these lesions is of paramount importance in directing management. As such, we describe staging schemes as well as imaging features differentiating stable from unstable lesions. Finally, we briefly discuss management strategies as they correlate to imaging findings.

Osteochondral lesions of the talus.

Background and purpose - The frequency of progression of osteoarthritis and persistence of symptoms in untreated osteochondral lesion of the talus (OCL) is not well known. We report the outcome of a nonoperative treatment for symptomatic OCL. Patients and methods - This study included 142 patients with OCLs from 2003 to 2013. The patients did not undergo immobilization and had no restrictions of physical activities. The mean follow-up time was 6 (3-10) years. Initial MRI and CT confirmed OCL and showed lesion size, location, and stage of the lesion. Progression of osteoarthritis was evaluated by standing radiographs. In 83 patients, CT was performed at the final follow-up for analyses of the lesion size. We surveyed patients for limitations of sports activity, and Visual Analogue Scales (VAS), AOFAS, and SF-36 were assessed. Results - No patients had progression of osteoarthritis. The lesion size as determined by CT did not change in 69/83 patients, decreased in 5, and increased in 9. The mean VAS score of the 142 patients decreased from 3.8 to 0.9 (p < 0.001), the mean AOFAS ankle-hindfoot score increased from 86 to 93 (p < 0.001), and the mean SF-36 score increased from 52 to 72 (p < 0.001). Only 9 patients reported limitations of sports activity. The size and location of the lesion did not correlate with any of the outcome scores. Interpretation - Nonoperative treatment can be considered a good option for patients with OCL.

Patient-Reported Outcomes Following Platelet-Rich Plasma Injections in Treating Osteochondral Lesions of the Talus: A Critically Appraised Topic.

Clinical Scenario: Osteochondral lesions (OCLs) of the talus can result from ankle sprains which are the most common injury in the physically active. Recently, platelet-rich plasma (PRP) has been used to develop an innovate treatment for OCLs of the talus. CLINICAL QUESTION: Do PRP injections improve self-reported pain and ankle function in patients with OCL of the talus? Summary of Key Findings: 3 randomized controlled trials were included. One of the studies compared a single dose of PRP to a single dose of hyaluronic acid (HA) or saline when added as an adjunct to microfracture surgery. Another study compared a group receiving a single dose of PRP after microfracture surgery to a group that only received microfracture surgery. The last study compared a series of 3 PRP injections to a series of 3 HA injections. In all 3 studies PRP appeared to be more effective in pain and function outcomes than comparison treatments. The superior outcomes of PRP were demonstrated at times as short as 4 weeks and as long as 25 months. Clinical Bottom Line: There is moderate to strong evidence that PRP produces favorable, short-term, pain and function results compared to HA, saline, and/or microfracture surgery alone. Strength of Recommendation: Level 2.

[Van Neck-Odelberg disease. Report of two cases]. / A van Neck-Odelberg-betegség bemutatása két eset kapcsán.

Osteochondritis ischiopubica or van Neck-Odelberg disease is characterized by atypical ossification of the ischiopubic synchondrosis. Clinical symptoms are usually pain, limping and limited range of motion of the hip joint. Radiologic images may be confused with the possibility of fracture, tumor or inflammation. In some cases it may be difficult to set up the accurate diagnosis, and during the diagnostic process it is essential that van Neck-Odelberg disease should be considered. In this paper the authors draw attention to this rare disorder and they present the history of two patients who posed diagnostic difficulties.

Effect of mesenchymal stromal cells for articular cartilage degeneration treatment: a meta-analysis.

BACKGROUND AIMS: Articular cartilage is an avascular tissue that has limited capacity for self-repair. Mesenchymal stromal cells have been considered as potential candidates for cartilage regeneration. However, clinical results of cartilage formation with the use of these cells need evaluation. We aimed to assess the effect of mesenchymal stromal cell treatment on articular cartilage defects. METHODS: We searched PubMed, Embase and the Cochrane Central Register of Controlled Trials with key words including "cartilage," "clinical trial," "mesenchymal," "stromal" and "stem cell" up to December 3, 2014. We selected the controlled trial that used treatment with mesenchymal stromal cells on cartilage injury compared with other treatment. We assessed the results of the meta-analysis by means of the error matrix approach. The outcome measures were ranked as comprehensive evaluation index, highest relevance; unilateral evaluation index, medial relevance; and single evaluation index, lowest relevance. RESULTS: Eleven trials assessing 558 patients were included in the meta-analysis. Stem cell treatment significantly improved the American Orthopedic Foot and Ankle Society Scale (Standard Mean Difference, SMD, 0.91; 95% confidence interval [CI], 0.52 to 1.29). The Osteo-Arthritis Outcome Score was also significantly improved in stem cell treatment (SMD, 2.81; 95% CI, 2.02 to 3.60). Other comprehensive evaluation indexes, such as the American Knee Society Knee Score System (SMD -0.12, 95% CI, -1.02 to 0.78), the Hospital for Special Surgery Knee Rating Scale (SMD, 0.24, 95% CI, -0.56 to 1.05) and the International Knee Documentation Committee (SMD, -0.21; 95% CI, -0.77 to 0.34), appeared to have no significant differences by use of stem cell and other treatments. Overall, there was no obvious advantage regarding the application of stem cells to treat cartilage injury, compared with other treatments. CONCLUSIONS: In conclusion, assessment of the comprehensive evaluation index indicated that there were no significant differences after stem cell treatment. However, assessment of clinical symptoms and cartilage morphology showed significant improvement after stem cell treatment.

Osteochondral lesions in pediatric and adolescent patients.

Osteochondral lesions are acquired, potentially reversible injuries of the subchondral bone with or without associated articular cartilage involvement. Injury results in delamination and potential sequestration of the affected bone. Although an association with mechanical and traumatic factors has been established, the etiology remains poorly understood. These lesions commonly occur in the knee; articular surfaces of the elbow, ankle, hip, and shoulder are also affected. Osteochondral lesions are relatively common in children and adolescents, and the incidence is increasing. Prognosis of these lesions depends on stability, location, and size of the lesion.Imaging has an essential role in the diagnosis, staging, and management of osteochondral lesions. Many of these lesions are first diagnosed by plain film. MRI adds value by identifying unstable lesions that require surgical intervention. This review focuses on the clinical and imaging features of osteochondral lesions of the knee, elbow, and ankle. Imaging criteria for staging and management are also reviewed.

Treatment of knee chondropathy with platelet rich plasma. Preliminary results at 6 months of follow-up with only one injection.

Application of new biological treatments in orthopaedics is controversial nowadays. Surgeons and practitioners know how difficult can be to choose a solution for chondral injuries. Joint damages are from little contusions, osteochondral fractures, avascular necrosis, osteochondritis and degenerative processes like osteoarthritis and rheumatisms. All mentioned have a common problem: the lack of regenerating hyaline cartilage by themselves. Recently, PRP have been used to treat early moderate chondropathies. Here we show the preliminary results of 30 patients affected by chondropathy of the knee after 6 months treated with a single intrarticular injection of PRP. Thirty patients, 18-65 years old, with a diagnosis of I to III Outerbridge chondropathy in the knee, pain for more than 3 months following conservative treatment and no bone axial defect, were treated with one intraarticular injection of PRP (GPS mini set, BIOMET), after written consent and Ethic and Legal Committee approval. VAS and KOOS scores were evaluated before PRP injection and at 1, 3 and 6 months after the treatment. ANOVA with repeated measures using the SPSS showed significantly better results in term of KOOS and VAS scores at 1, 3 and 6 months respect to the pre-injection value (p less than 0,05) We think that PRP treatment is a promising alternative for the treatment of knee chondropathy; however its efficacy has to be demonstrated with more clinical works, with longer follow up and with greater number of patients, even with controlled and randomized trials. In our study only one injection of PRP has been able to allow a clinical improvement, suggesting the possibility to avoid multiple injections protocols, and consequently reducing the health expenses. Until the efficacy of PRP will not be definitely demonstrated, surgeon should be very prudent in indications.

SPECT/CT in the management of osteochondral lesions of the talus.

BACKGROUND: The treatment of osteochondral lesion of the talus (OLT) is mainly based upon the stage of the disease so accurate imaging is crucial. SPECT/CT combines bone scan with high-resolution CT and can provide functional-anatomical images in a single stage. The purpose of this study was to assess the value of SPECT/CT in the management of OLT. MATERIALS AND METHODS: From 2004 to 2009, 22 patients with OLT were identified that had both SPECT/CT and MRI of the foot and ankle. All charts were reviewed to ascertain the reason for ordering the SPECT/CT and the additional information obtained. AOFAS outcome scores were calculated at the time of followup. RESULTS: Twelve patients underwent ankle arthroscopy for debridement or drilling of the osteochondral lesion. The mean AOFAS score in these 12 patients was 83.6. SPECT/CT helped preoperative planning by identifying the exact location of the active lesion, especially in multifocal disease or revision surgeries while showing the depth of the active lesion. Ten patients had conservative management due to minimal or no activity over the lesion on SPECT/CT images. The mean AOFAS score in these ten patients was 78.8 which was comparable to the operative group. CONCLUSION: We believe SPECT/CT was able to provide additional diagnostic value by demonstrating a co-existing pathology as a potential cause of pain and in preoperative planning by showing the depth of activity and the precise location of the active segment in multiple lesions.

Management of acute lesser toe pain.

Patients with foot pain commonly present to their primary care physicians for their initial management and treatment. These patients and their respective foot or lesser toe pain can present the physician with a complex problem with a long differential list. Depending on the timing of the pain and underlying pathology, these differentials can be divided into acute and acute exacerbation of chronic conditions. This review categorizes the history, physical exam, radiological findings, conservative treatment, and surgical management for each major cause of lesser toe pain, whether acute or chronic. The acute conditions surrounding lesser toe pain in the adult population discussed are toe fractures, toe dislocations, and metatarsal head and neck fractures. The chronic pathologies surrounding lesser toe pain in the adult population evaluated in this review include metatarsalgia, Morton's neuroma, Freiberg infraction, brachymetatarsia, bunionettes, and lesser toe disorders.

[Complex approach to the treatment of the diskal hernia of lumbosacral spine].

21 patients with lumbosacral osteochondritis and diskal hernia were treated. Diagnosis was verified with the help of radiological method. The spinal motion segment after the hernia excision was fixed with the help of fixator with the shape memory for the prevention of post-operation instability. Thioctic acid showed the high effectiveness in complex treatment of radiculopathy.

[Evaluation of the efficacy of therapeutic physical training in patients with osteochondrosis according to rheoencephalography data].

This paper reports results of clinical and rheoencephalographic examination of 40 middle-age women with cervical osteochondrosis and symptoms of insufficiency of vertebrobasiliar blood circulation. A system of methods for therapeutic physical training has beendeveloped to normalize hemodynamics in the basin of vertebral arteries. The system was tested on 20 patients during a year. It included special physical exercises, massage, and automobilization. The efficiency of therapeutic physical training was evaluated by rheoencephalography. The women involved in the testing reported a marked improvement of the health status. Their rheoencephalograms suggested diminishing of the asymmetry coefficient and beneficial effect of therapeutic physical training on the elastic properties of vertebral arteries. No such changes were documented in a control group of women with osteochondrosis.

Conservative treatment of Freiberg's infraction using foot orthoses: A tale of two prescriptions presented as a case study to open debate.

'Freiberg's infraction or disease' is an osteonecrotic process primarily affecting the 2nd & 3rd metatarsal heads. Early diagnosis is difficult, and the underlying pathogenesis remains unclear. Surgical options for late disease have been widely reported in the literature, yet details on conservative management for the early stages of Freiberg's are largely absent. Pathology should be treated where possible using an evidence-based approach, yet evidence for conservative management in acute stages of Freiberg's is lacking. A case study is presented that outlines two different prescription interventions using foot orthoses; one that attempted to 'offload' the metatarsal head by creating space beneath it; and one that attempted to 'offloaded' by increasing controlled loading of the metatarsals proximal to the head. These resulted in very different outcomes for the patient. The authors will attempt to give a 'pathomechanical rationale' for the treatment outcomes based on mechanical stress principles, and a consequential explanation as to why one type of insole prescription seemed more successful in reducing symptoms and raising activity levels, while another was not.

The Subchondral Bone Is Affected by Bone Marrow Stimulation: A Systematic Review of Preclinical Animal Studies.

OBJECTIVE: Despite the mechanical and biological roles of subchondral bone (SCB) in articular cartilage health, there remains no consensus on the postoperative morphological status of SCB following bone marrow stimulation (BMS). The purpose of this systematic review was to clarify the morphology of SCB following BMS in preclinical, translational animal models. DESIGN: The MEDLINE and EMBASE databases were systematically reviewed using specific search terms on April 19, 2016 based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The morphology of the SCB was assessed using of microcomputed tomography (bone density) and histology (microscopic architecture). RESULTS: Seventeen animal studies with 520 chondral lesions were included. The morphology of SCB did not recover following BMS. Compared with untreated chondral defects, BMS resulted in superior morphology of superficial SCB and cartilage but inferior morphology (specifically bone density, P < 0.05) of the deep SCB. Overall, the use of biological adjuvants during BMS resulted in the superior postoperative morphology of SCB. CONCLUSIONS: Alterations in the SCB following BMS were confirmed. Biologics adjuvants may improve the postoperative morphology of both SCB and articular cartilage. Refinements of BMS techniques should incorporate consideration of SCB damage and restoration. Investigations to optimize BMS techniques incorporating both minimally invasive approaches and biologically augmented platforms are further warranted.

Healing of Osteochondral Defects via Endochondral Ossification in an Ovine Model.

OBJECTIVE: The objective of this study was to describe the mechanism of healing of osteochondral defects of the distal femur in the sheep, a commonly used translational model. Information on the healing mechanism be useful to inform the design of tissue engineering devices for joint surface defect repair. DESIGN: A retrospective study was conducted examining 7-mm diameter osteochondral defects made in the distal medial femoral condyle of 40 adult female sheep, comprising control animals from 3 separate structures. The healing of the defects was studied at post mortem at up to 26 weeks. RESULTS: Osteochondral defects of the distal femur of the sheep heal through endochondral ossification as evidenced by chondrocyte hypertrophy and type X collagen expression. Neocartilage is first formed adjacent to damaged cartilage and then streams over the damaged underlying bone before filling the defect from the base upward. No intramembranous ossification or isolated mesenchymal stem cell aggregates were detected in the healing tissue. No osseous hypertrophy was detected in the defects. CONCLUSIONS: Osteochondral defects of the medial femoral condyle of the sheep heal via endochondral ossification, with neocartilage first appearing adjacent to damaged cartilage. Unlike the mechanism of healing in fracture repair, neocartilage is eventually formed directly onto damaged bone. There was most variability between animals between 8 and 12 weeks postsurgery. These results should be considered when designing devices to promote defect healing.

Freiberg Disease and Avascular Necrosis of the Metatarsal Heads.

Freiberg disease is characterized as osteochondrosis of the second metatarsal head. It is the fourth most common form of primary osteochondrosis with a significant predilection to the adolescent athletic female population, although it has been seen over a wide age range. If treated early, osteochondroses such as Freiberg disease are essentially self-limiting, often resolving with nonoperative management. When surgery is warranted, it is imperative the patient's age, activity level, and degree of articular deformity be taken into account.

Role of Mesenchymal Stem Cells Densities When Injected as Suspension in Joints with Osteochondral Defects.

OBJECTIVE: The aim of this study was to evaluate an intraarticular injection of different doses of autologous mesenchymal stem cells (MSCs) for improving repair of midterm osteochondral defect. DESIGN: At 4 weeks postoperative marrow stimulation model bilaterally (3 mm diameter; 4 mm depth) in the medial femoral condyle, autologous MSCs were injected into knee joint. Twenty-four Japanese rabbits aged 6 months were divided randomly into 4 groups ( n = 6 per group): the control group and and MSC groups including 0.125, 1.25, and 6.25 million MSCs. Repaired tissue was assessed macroscopically and histologically at 4 and 12 weeks after intraarticular injection of MSCs. RESULTS: At 12 weeks, there was no repair tissue in the control group. The gross appearance of the 1.25 and 6.25 million MSC groups revealed complete repair of the defect with white to pink tissue at 12 weeks. An osteochondral repair was histologically significantly better in the 1.25 and 6.25 million MSC groups than in the control and 0.125 million MSC groups at 4 and 12 weeks, due to presence of hyaline-like tissue in the deep layer at 4 weeks, and at 12 weeks hyaline cartilage formation at the periphery and fibrous tissue containing some chondrocytes in the deep layer of the center of the defect. Subchondral bone was restructured in the 1.25 and 6.25 million MSC groups, although it did not resemble the normal bone. CONCLUSION: An intraarticular injection of 1.25 or 6.25 million MSCs could promote the repair of subchondral bone, even in the case of midterm osteochondral defect.