Search

Objective The primary aim was to determine and compare the complication rate of different surgical treatment options for osteochondral lesions of the talus (OLTs). The secondary aim was to analyze and compare the severity and types of complications. Design A literature search was performed in MEDLINE (PubMed), EMBASE (Ovid), and the Cochrane Library. Methodological quality was assessed using the Methodological Index for Non-Randomized Studies (MINORS). Primary outcome was the complication rate per surgical treatment option. Secondary outcomes included the severity (using the Modified Clavien-Dindo-Sink Complication Classification System for Orthopedic Surgery) and types of complications. The primary outcome, the severity, and the sub-analyses were analyzed using a random effects model. A moderator test for subgroup-analysis was used to determine differences. The types of complications were presented as rates. Results In all, 178 articles from the literature search were included for analysis, comprising 6,962 OLTs with a pooled mean age of 35.5 years and follow-up of 46.3 months. Methodological quality was fair. The overall complication rate was 5% (4%-6%; treatment group effect, P = 0.0015). Analysis resulted in rates from 3% (2%-4%) for matrix-assisted bone marrow stimulation to 15% (5%-35%) for metal implants. Nerve injury was the most observed complication. Conclusions In 1 out of 20 patients treated surgically for an OLT, a complication occurs. Metal implants have a significantly higher complication rate compared with other treatment modalities. No life-threatening complications were reported.

Objective The primary aim was to determine and compare the complication rate of different surgical treatment options for osteochondral lesions of the talus (OLTs). The secondary aim was to analyze and compare the severity and types of complications. Design A literature search was performed in MEDLINE (PubMed), EMBASE (Ovid), and the Cochrane Library. Methodological quality was assessed using the Methodological Index for Non-Randomized Studies (MINORS). Primary outcome was the complication rate per surgical treatment option. Secondary outcomes included the severity (using the Modified Clavien-Dindo-Sink Complication Classification System for Orthopedic Surgery) and types of complications. The primary outcome, the severity, and the sub-analyses were analyzed using a random effects model. A moderator test for subgroup-analysis was used to determine differences. The types of complications were presented as rates. Results In all, 178 articles from the literature search were included for analysis, comprising 6,962 OLTs with a pooled mean age of 35.5 years and follow-up of 46.3 months. Methodological quality was fair. The overall complication rate was 5% (4%-6%; treatment group effect, P = 0.0015). Analysis resulted in rates from 3% (2%-4%) for matrix-assisted bone marrow stimulation to 15% (5%-35%) for metal implants. Nerve injury was the most observed complication. Conclusions In 1 out of 20 patients treated surgically for an OLT, a complication occurs. Metal implants have a significantly higher complication rate compared with other treatment modalities. No life-threatening complications were reported.

Objective The objective of this study is to establish which patient and lesion characteristics are related to the clinical outcome after microfracture of cartilage defects in the knee. Study design Systematic review. Methods After preregistration, PubMed, Embase, and Cochrane were searched for studies that analyzed prognostic factors for the outcome of microfracture treatment in the knee. The criteria for inclusion were outcome measured using Patient-Reported Outcome Measures (PROMs), a clinical study with >= 10 participants receiving microfracture, and a minimal follow-up period of 1 year. Results For none of the investigated prognostic factors, effect size reporting was sufficiently homogeneous to conduct a meta-analysis. However, a majority of the included studies identified higher age, larger lesion size, longer preoperative symptom duration, and previous surgery on the ipsilateral knee, especially meniscectomy and anterior cruciate ligament reconstruction, as factors that are reported to be correlated to a less favorable outcome. A lesion location that does not include the trochlea or the patellofemoral joint and is not weightbearing, a nondegenerative mechanism of injury, and a single lesion were reported as factors that predict a favorable outcome. As to gender, body mass index, preoperative activity level, smoking, and concomitant knee surgery, the included articles were inconclusive or no effect was reported. Conclusions Several factors correlated with the clinical result after microfracture treatment. However, the information on the effect sizes of the influence on clinical outcome is incomplete due to poor reporting. Large-scale registries or pooling of homogeneous, well-reported data is needed to work toward prognostic models. That would be an important step toward personalized treatment.

Objective The objective of this study is to establish which patient and lesion characteristics are related to the clinical outcome after microfracture of cartilage defects in the knee. Study design Systematic review. Methods After preregistration, PubMed, Embase, and Cochrane were searched for studies that analyzed prognostic factors for the outcome of microfracture treatment in the knee. The criteria for inclusion were outcome measured using Patient-Reported Outcome Measures (PROMs), a clinical study with ≥10 participants receiving microfracture, and a minimal follow-up period of 1 year. Results For none of the investigated prognostic factors, effect size reporting was sufficiently homogeneous to conduct a meta-analysis. However, a majority of the included studies identified higher age, larger lesion size, longer preoperative symptom duration, and previous surgery on the ipsilateral knee, especially meniscectomy and anterior cruciate ligament reconstruction, as factors that are reported to be correlated to a less favorable outcome. A lesion location that does not include the trochlea or the patellofemoral joint and is not weightbearing, a nondegenerative mechanism of injury, and a single lesion were reported as factors that predict a favorable outcome. As to gender, body mass index, preoperative activity level, smoking, and concomitant knee surgery, the included articles were inconclusive or no effect was reported. Conclusions Several factors correlated with the clinical result after microfracture treatment. However, the information on the effect sizes of the influence on clinical outcome is incomplete due to poor reporting. Large-scale registries or pooling of homogeneous, well-reported data is needed to work toward prognostic models. That would be an important step toward personalized treatment.

Because of limited self-healing ability, the treatment of articular cartilage defects is still an important clinical challenge. Hydrogel-based biomaterials have broad application prospects in articular cartilage repair. In this study, gelatin methacrylate (GelMA)and silk fibroin (SF) were combined to form a composite hydrogel with an interpenetrating network (IPN) structure under ultraviolet irradiation and ethanol treatment. Introducing silk fibroin into GelMA hydrogel significantly increased mechanical strength as compressive modulus reached 300 kPa in a GelMA/SF-5 (50 mg/mL silk fibroin) group. Moreover, composite IPN hydrogels demonstrated reduced swelling ratios and favorable biocompatibility and supported chondrogenesis of bone mesenchymal stem cells (BMSCs) at day 7 and day 14. Additionally, significantly higher gene expressions of Col-2, Acan, and Sox-9 (p < 0.01) were found in IPN hydrogel groups when compared with the GelMA group. An in vivo study was performed to confirm that the GelMA-SF IPN hydrogel could promote cartilage regeneration. The results showed partial regeneration of cartilage in groups treated with hydrogels only and satisfactory cartilage repair in groups of cell-seeded hydrogels, indicating the necessity of additional seeding cells in hydro-gel-based cartilage treatment. Therefore, our results suggest that the GelMA/SF IPN hydrogels may be a potential functional material in cartilage repair and regeneration.

The regeneration of cartilage and osteochondral defects remains one of the most challenging clinical problems in orthopedic surgery. Currently, tissue-engineering techniques based on the delivery of appropriate growth factors and mesenchymal stem cells (MSCs) in hydrogel scaffolds are considered as the most promising therapeutic strategy for osteochondral defects regeneration. In this study, we fabricated a heparin-conjugated fibrin (HCF) hydrogel with synovium-derived mesenchymal stem cells (SDMSCs), transforming growth factor-β1 (TGF-β1) and bone morphogenetic protein-4 (BMP-4) to repair osteochondral defects in a rabbit model. An in vitro study showed that HCF hydrogel exhibited good biocompatibility, a slow degradation rate and sustained release of TGF-β1 and BMP-4 over 4 weeks. Macroscopic and histological evaluations revealed that implantation of HCF hydrogel with SDMSCs, TGF-β1 and BMP-4 significantly enhanced the regeneration of hyaline cartilage and the subchondral bone plate in osteochondral defects within 12 weeks compared to hydrogels with SDMSCs or growth factors alone. Thus, these data suggest that combined delivery of SDMSCs with TGF-β1 and BMP-4 in HCF hydrogel may synergistically enhance the therapeutic efficacy of osteochondral defect repair of the knee joints.

Background. The relevance of the talar dome osteochondral lesions problem is assosiated with the difficulties of diagnosis, the lack of unified treatment algorythm and the great number of unsatisfactory clinical and functional results. In the last decade, there has been increasing interest in this topic in the literature, which is demonstrated by a great number of publications with series of observations or clinical cases. However, attempts to create the universal algorithm for this group of patients treatment are limited by the low level of existing studies evidence, high frequency of the new data publications, as well as the impossibility of using a number of surgical methods in different countries for legislative or other reasons. The aim is to determine the current state of the problem of the talar dome osteochondral lesions surgical treatment and to identify types of surgical interventions in patients with the studied pathology. Material and methods. 120 international articles published from 2000 to 2021, as well as 18 domestic publications for the period from 2007 to 2021 were selected for the literature analysis. The search for publications was carried out in the PubMed/MedLine and eLibrary databases. Results. The most widespread are surgical interventions aimed at stimulation of the bone marrow, and plastic surgery using osteochondral auto - and allografts. Currently, there is no consensus on the indications for different types of surgical methods, and the previously used indications are being questioned. This determines the need to improve diagnostic and treatment concepts. Conclusion. The studied literature cannot fully answer a number of questions related to the methods of surgical treatment of patients with symptomatic osteochondral lesions of the talar dome and indications for them. A more detailed assessment of the medium- and long-term clinical outcomes of various surgical methods and the development of algorithms for this group of patients treatment, specific for different countries, are needed.

Background Stress radiographs have demonstrated superior efficacy in the evaluation of ankle instability. Aim To determine if there is a degree of instability evidenced by stress radiographs that is associated with pathology concomitant with ankle ligamentous instability. Methods A retrospective review of 87 consecutive patients aged 18-74 who had stress radiographs performed at a single institution between 2014 and 2020 was performed. These manual radiographic stress views were then correlated with magnetic resonance imaging and operative findings. Results A statistically significant association was determined for the mean and median stress radiographic values and the presence of peroneal pathology (P = 0.008 for tendonitis and P = 0.020 for peroneal tendon tears). A significant inverse relationship was found between the presence of an osteochondral defect and increasing degrees of instability (P = 0.043). Conclusion Although valuable in the clinical evaluation of ankle instability, stress radiographs are not an independent predictor of conditions associated with ankle instability.

Osteochondral lesions of the talus (OLTs) are a common complication following trauma, involving both the articular cartilage and the underlying subchondral bone, with variable aetiologies and often presenting with non-specific symptoms. Diagnosis of OLTs requires a combination of clinical assessment and imaging and despite many different treatment options, there is no generalised consensus regarding which option is the most effective. Left untreated, OLTs risk progressing to osteoarthritis. Acute non-displaced OLTs can be treated non-operatively. However, OLTs refractory to non-surgical care for three to six months may be suitable for surgical care. In these cases, conservative treatments are often unsuccessful, particularly for larger and more severe defects and so the majority require surgical intervention. Although bone marrow stimulation techniques remain the “gold standard” for lesions

Background Osteochondral defects (OCD) are common in osteoarthritis (OA) and difficult to heal. Numerous tissue engineering approaches and novel biomaterials are developed to solve this challenging condition. Although most of the novel methods can successfully treat osteochondral defects in preclinical trials, their clinical application in OA patients is not satisfactory, due to a high spontaneous recovery rate of many preclinical animal models by ignoring the inflammatory environment. In this study, we developed a sustained osteochondral defect model in osteoarthritic rabbits and compared the cartilage and subchondral bone regeneration in normal and arthritic environments. Methods Rabbits were injected with papain (1.25%) in the right knee joints (OA group), and saline in the left knee joints (Non-OA group) at day 1 and day 3. One week later a cylindrical osteochondral defect of 3.2 mm in diameter and 3 mm depth was made in the femoral patellar groove. After 16 weeks, newly regenerated cartilage and bone inside the defect were evaluated by micro-CT, histomorphology and immunohistochemistry. Results One week after papain injection, extracellular matrix in the OA group demonstrated dramatically less safranin O staining intensity than in the non-OA group. Until 13 weeks of post-surgery, knee width remained significantly higher in the OA group than the non-OA control group. Sixteen weeks after surgery, the OA group had 11.3% lower International Cartilage Regeneration and Joint Preservation Society score and 32.5% lower O’Driscoll score than the non-OA group. There were less sulfated glycosaminoglycan and type II collagen but 74.1% more MMP-3 protein in the regenerated cartilage of the OA group compared with the non-OA group. As to the regenerated bone, bone volume fraction, trabecular thickness and trabecular number were all about 28% lower, while the bone mineral density was 26.7% higher in the OA group compared to the non-OA group. Dynamic histomorphometry parameters including percent labeled perimeter, mineral apposition rate and bone formation rate were lower in the OA group than in the non-OA group. Immunohistochemistry data showed that the OA group had 15.9% less type I collagen than the non-OA group. Conclusion The present study successfully established a non-self-healing osteochondral defect rabbit model in papain-induced OA, which was well simulating the clinical feature and pathology. In addition, we confirmed that both cartilage and subchondral bone regeneration were further impaired in arthritic environment. The translational potential of this article The present study provides an osteochondral defect in a small osteoarthritic model. This non-self-healing model and the evaluation protocol could be used to evaluate the efficacy and study the mechanism of newly developed biomaterials or tissue engineering methods preclinically; as methods tested in reliable preclinical models are expected to achieve improved success rate when tested clinically for treatment of OCD in OA patients.

Introduction: Fractures at the anchor site following arthroscopic rotator cuff repair are rare and only a few case reports have been described. We report two additional well-documented cases of this uncommon post-operative complication and provide a review of the current literature. Case Report: A 48-year-old male underwent arthroscopic rotator cuff repair (ARCR) due to a massive rotator cuff tear. Nine weeks postoperatively, the patient suffered a humeral head fracture at the anchor site of the ARCR after trauma. Despite subsequent surgical treatment with open reduction and internal fixation, the patient demonstrates with excellent functional outcome scores at 2-year follow-up. Conclusion: Humeral head fractures are a rare complication after ARCR. The use of intraosseous anchors requires careful consideration regarding positioning and quantity used. Keywords: Rotator cuff, arthroscopy, complication, anchor, Speed Bridge, fracture, osteochondral defect.

Objectives This study aims to investigate the effects of hyperbaric oxygen (HBO) therapy and platelet-rich plasma (PRP) on the regeneration of osteochondral defects of the rats, and the synergistic effect of this combined treatment. Materials and methods This randomized, controlled, and interventional animal study was conducted between May 2014 and August 2014 Osteochondral regeneration was evaluated in four treatment groups (control, PRP, HBO, and HBO+PRP groups) at the 30th day after iatrogenic injury. Thirty-two female Wistar albino rats (weighing 248-305 g) underwent arthrotomy and osteochondral surgery on left knees. The regenerations of defects were then examined histologically by the modified version of O'Driscoll score. Results Groups that were treated with either HBO or PRP alone regenerated significantly better than the control group (p=0.01), while no significant difference was found between the HBO- and PRP-treated groups (p>0.05). The defects in group 4 (treated with both HBO and PRP) regenerated significantly better than the control group, the HBO-treated group alone, and the PRP-treated group alone (p=0.01). Conclusion The results of this study showed a synergistic effect of HBO and PRP on knee cartilage regeneration. However, the possible underlying mechanisms should be the subject of future researches. The aggregation and activation of growth factors released from platelets whose activation is increased in the hyperbaric environment may explain this effect. This may result in a better regeneration than the effect of PRP or HBO alone.

Background: Tendon autograft has been used in Freiberg’s disease, capitellar osteochondritis dissecans, and osteochondral defect in the knee joint. The aim of this study was to evaluate the clinical and radiological results of patients treated with tendon autografts in the treatment of talus osteochondral defect (TOD), and to compare the results of this treatment with other treatment modalities in light of the literature.Methods: The study was carried out with patients who were treated for TOD with peroneus longus tendon otograft between 2009-2017. 17 ankles of 15 patients were included in the study. The patients who were operated had osteochondral lesions that were Berndt and Harty stage III-IV on radiographs, and Hepple stage III-IV-V on magnetic resonance imaging (MRI). American Orthopedic Foot and Ankle Score (AOFAS) was used for clinical evaluation. Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) classification was used for postoperative radiological evaluation.Results: The mean age of the patients was 31.9±14.1 (min 17-max 64) years. The mean follow-up period was 23.9±28.7 (min 6-max 120) months. The mean defect size was 1.7±0.7 (min 0.9-max 3.3) cm². The mean AOFAS score was 50.1±15.7 (min 24-max 77) preoperatively and 90.8±7.7 (min 70-max 100) postoperatively. The mean MOCART score was calculated as 87.1±3.1 (min 80-max 90). Postoperative osteoarthritis was not detected in any of the direct radiographs of the patients.Conclusions: Tendon autograft was considered to be a reliable, easy, cheap and one-step method that can be used in TOD treatment.

Current clinical treatments of osteochondral defects in articulating joints are frequently not successful in restoring articular surfaces. Novel scaffold-based tissue engineering strategies may help to improve current treatment options and foster a true regeneration of articulating structures. A frequently desired property of scaffolds is their ability to degrade over time and allow a full restoration of tissue and function. However, it remains largely unknown how scaffold degradation influences the mechanical stability of the tissue in a defect region and, in turn, the regenerative process. Such differing goals-supporting regeneration by degrading its own structure-can hardly be analyzed for tissue engineered constructs in clinical trials and in vivo preclinical experiments. Using an in silico analysis, we investigated the degradation-induced modifications in material and architectural properties of a scaffold with strut-like architecture over the healing course and their influence on the mechanics-dependent tissue formation in osteochondral defects. The repair outcome greatly varied depending on the degradation modality, i.e. surface erosion or bulk degradation with and without autocatalysis, and of the degradation speed, i.e. faster, equal or slower than the expected repair time. Bulk degradation with autocatalysis, independently of degradation speed, caused the mechanical failure of the scaffold prior to osteochondral defect repair and was thereby deemed inappropriate for further application. On the other hand, scaffolds with strut-like architecture degrading by both surface erosion and bulk degradation with slow degradation speed resulted in comparably good repair outcomes, thereby indicating such degradation modalities as favorable for the application in osteochondral defects.

Background: Various cell-free scaffolds are already in use for the treatment of osteochondral defects (OCDs); however, a gold standard material has not yet been defined. Purpose: This study compared the macroscopic, histological, and scanning electron microscopy (SEM) characteristics of Chondro-Gide (CG), MaioRegen (MA), and poly-d,l-lactide-co-caprolactone (PLCL) cell-free scaffolds enhanced with small-diameter microfractures (SDMs) for OCDs in a rabbit model. Study Design: Controlled laboratory study. Methods: In total, 54 knees from 27 rabbits were used in this study. Three rabbits were sacrificed at the beginning of the study to form an intact cartilage control group (group IC). An OCD model was created at the center of the trochlea, and SDMs were generated in 24 rabbits. Rabbits with OCDs were divided into 4 groups (n = 12 knees per group) according to the cell-free scaffold applied: CG (group CG), MA (group MA), PLCL (group PLCL), and a control group (group SDM). Half of the rabbits were sacrificed at 1 month after treatment, while the other half were sacrificed at 3 months after treatment. Healed cartilage was evaluated macroscopically (using International Cartilage Regeneration & Joint Preservation Society [ICRS] classification criteria) and histopathologically (using modified O’Driscoll scores and collagen staining). Additionally, cell-free scaffold morphologies were compared using SEM analysis. Results: ICRS and modified O’Driscoll classification and staining with collagen type 1 and type 2 demonstrated significant differences among groups at both 1 and 3 months after treatment ( P < .05). The histological characteristics of the group IC samples were superior to those of all other groups, except group PLCL, at 3 months after treatment ( P < .05). In addition, the histological properties of group PLCL samples were superior to those of group SDM samples at both 1 and 3 months after treatment in terms of the modified O’Driscoll scores and type 1 collagen staining ( P < .05). Concerning type 2 collagen staining intensity, the groups were ranked from highest to lowest at 3 months after treatment as follows: group PLCL (30.3 ± 2.6) > group MA (26.6 ± 1.2) > group CG (23.3 ± 2.3) > group SDM (18.9 ± 0.9). Conclusion: OCDs treated with enhanced SDM using cell-free PLCL scaffolds had superior histopathological and microenvironmental properties, more hyaline cartilage, and more type 2 collagen compared with those treated using CG or MA scaffolds. Clinical Relevance: OCDs treated with PLCL cell-free scaffolds may have superior histopathological properties and contain more type 2 collagen than do OCDs treated with CG or MA cell-free scaffolds.

Osteochondral defects of the ankle (OCD) are being increasingly identified as a clinically significant consequence of injury to the ankle, with the potential to lead to osteoarthritis if left untreated. The aim of this retrospective cohort study was to evaluate a single-stage treatment of OCD, based on bone marrow aspirate (BMA) centrifuged to produce bone marrow concentrate (BMC). In a dual syringe, the concentrate was mixed with thrombin in one syringe, whereas hyaluronan and fibrinogen were mixed in a second syringe. The two mixtures were then injected and combined into the prepared defect. Clinical outcome and quality of life scores (MOXFQ and EQ-5D) were collected at baseline and yearly thereafter. Multilevel models were used to analyse the pattern of scores over time. Ninety-four patients were treated between 2015 and 2020. The means of each of the three components of the MOXFQ significantly improved between baseline and 1 year (p < 0.001 for each component), with no further change from year 1 to year 3. The EQ-5D index also improved significantly from baseline to 1 year, with no evidence for further change. Our results strongly indicate that this BMC treatment is safe for, and well tolerated by, patients with OCD of the ankle as both primary treatment and those who have failed primary treatment. This technique provides a safe, efficacious alternative to currently employed cartilage repair techniques, with favourable outcomes and a low complication rate at 36 months.

The symptomatic full-thickness cartilage lesions or cartilage degeneration leads to the destruction of the normal chondral architecture and bone structure in affected area, causes the osteoarthritis, and general damage to the health. Knee joints are most frequently affected by this condition. The permanent damage of the articular cartilage and subchondral bone has motivated many scientists and clinicians to explore new methods of regeneration of osteochondral defects, such as novel materials. We studied the potential of the biocement based on calcium phosphate consisting of a mixture of four amino acids (glycine, proline, hydroxyproline and lysine) in the regenerating process of the artificially created osteochondral defect on the porcine medial femoral condyle in the stifle joint. The mass ratio of the amino acids in biocement CAL was 4:2:2:1. The Ca/P ratio in cement was 1.67 which correspond with ratio in hydroxyapatite. We compared the results with spontaneous healing of an artificially created cyst with that of the healthy tissue. The animal group treated with biocement paste CAL presented completely filled osteochondral defects. The results were confirmed by histological and radiological assessments, which have shown regenerated chondral and bone tissue in the examined knee joints. Macroscopic evaluation showed that neocartilage was well integrated with the adjacent native cartilage in animal group with biocement CAL, compared with healing of the artificial cyst, where treated cartilage surfaces were visibly lower than the surrounding native cartilage surface and a border between native and restored tissue was apparent. The qualitative assessment of the implant histology specimens showed full regeneration of the hyaline cartilage and subchondral bone in animals with biocement CAL. The artificial cyst group showed remarkable fibrillation. The detailed MRI analysis of cross-section of osteochondral defect confirmed the complete cartilage and subchondral bone healing where the thickness of the regenerated cartilage was 1.5 mm. The MRI imaging of defects in the artificial cyst group showed incomplete healing, neo cartilage tissue reduced up to 50%.

Background The physiologic regenerative capacity of cartilage is severely limited. Current studies on the repair of osteochondral defects (OCDs) have mainly focused on the regeneration of cartilage tissues. The antler cartilage is a unique regenerative cartilage that has the potential for cartilage repair. Methods Antler decellularized cartilage-derived matrix scaffolds (adCDMs) were prepared by combining freezing-thawing and enzymatic degradation. Their DNA, glycosaminoglycans (GAGs), and collagen content were then detected. Biosafety and biocompatibility were evaluated by pyrogen detection, hemolysis analysis, cytotoxicity evaluation, and subcutaneous implantation experiments. adCDMs were implanted into rabbit articular cartilage defects for 2 months to evaluate their therapeutic effects. Results AdCDMs were observed to be rich in collagen and GAGs and devoid of cells. AdCDMs were also determined to have good biosafety and biocompatibility. Both four- and eight-week treatments of OCDs showed a flat and smooth surface of the healing cartilage at the adCDMs filled site. The international cartilage repair society scores (ICRS) of adCDMs were significantly higher than those of controls (porcine dCDMs and normal saline) (p Conclusions We concluded that adCDMs could achieve excellent cartilage regeneration repair in a rabbit knee OCDs model. Our study stresses the importance and benefits of adCDMs in bone formation and overall anatomical reconstitution, and it provides a novel source for developing cartilage-regenerating repair materials.

Knee joint trauma can cause an osteochondral defect (OD), a risk factor for osteoarthritis and cause of debilitating pain in patients. Rodent OD models are less translatable due to their smaller joint size and open growth plate. This study proposes sheep as a translationally relevant model to understand the neuronal basis of OD pain. Unilateral 6 mm deep OD was induced in adult female sheep. 2-6 weeks post-operation, lumbar dorsal root ganglia (DRG) neurons were collected from the contralateral and OD side of operated sheep. Functional assessment of neuronal excitability and activity of the pain-related ion channels TRPV1 and P2X3 was carried out using electrophysiology and Ca2+-imaging. Immunohistochemistry was utilized to verify expression of pain-related proteins. We observed that an increased proportion of OD DRG neurons (sheep, N = 3; Ctrl neurons, n =15, OD neurons, n = 16) showed spontaneous electrical excitability (Ctrl: 20.33 ± 4.5%; OD: 50 ± 10%; p = 0.009, unpaired t-test) and an increased proportion fired a greater number of spikes above baseline in response to application of a TRPV1 agonist (capsaicin) application (Ctrl: 40%; OD: 75%; p = 0.04, chi-sq test). Capsaicin also produced Ca2+ influx in an increased proportion of OD DRG neurons isolated (Ctrl: 25%; OD: 44%; p = 0.001, chi-sq test). Neither protein expression, nor functionality of the P2X3 ion channel were altered in OD neurons. Overall, we provide evidence of increased excitability of DRG neurons (an important neural correlate of pain) and TRPV1 function in an OD sheep model. Our data show that functional assessment of sheep DRG neurons can provide important insights into the neural basis of OD pain and thus potentially prevent its progression into arthritic pain. Significance statement Pain is the primary symptom of osteoarthritis (OA) and often the main reason for patients seeking medical care. Understanding pain mechanisms in OA can boost the development of disease specific pain relief. While small animals such as mouse and rat have been widely used in OA pain studies, the genetic and anatomical differences between rodents and humans can hinder clinical translation. Here, we studied pain in an early osteochondral defect (OD) model in sheep, a commonly used large animal model in OA research. We found increased excitability and TRPV1 function in dorsal root ganglia (DRG) neurons innervating the site of OD. This study thus demonstrates the utility of using a large animal, such as sheep, for studying mechanisms of joint pain.

Background With the ageing of the population and the increase of sports injuries, the number of joint injuries has increased greatly. Tissue engineering or tissue regeneration is an important method to repair articular cartilage defects. While it has recently been paid much attention to use bilayered porous scaffolds to repair both cartilage and subchondral bone, it is interesting to examine to what extent a bilayer scaffold composed of the same kind of the biodegradable polymer poly(lactide-co-glycolide) (PLGA) can restore an osteochondral defect. Herein, we fabricated bilayered PLGA scaffolds and used a rabbit model to examine the efficacy of implanting the porous scaffolds with or without bone marrow mesenchymal stem cells (BMSCs). The present manuscript reports the regenerative potential up to 24 weeks. Methods The osteochondral defect, 4 mm in diameter and 5 mm in depth, was created in the medial condyle of each knee in 23 rabbits. The bilayered PLGA scaffolds with a pore size of 100–200 μm in the chondral layer and a pore size of 300–450 μm in the osseous layer, seeded with or without BMSCs in the chondral layer, were then transplanted into the osteochondral defect of each knee. The osteochondral defect created in the same manner was untreated to act as the control. At 12 and 24 weeks postoperatively, condyles were harvested and analyzed using histology, immunohistochemistry, real-time polymerase chain reaction, and biomechanical testing to evaluate the efficacy of osteochondral repair. Results No joint erosion, inflammation, swelling, or deformity was observed, and all animals maintained a full range of motion. Compared with the untreated blank group, the groups implanting the bilayered scaffolds with or without cells exhibited much better resurfacing, similar to the surrounding normal tissue. The histological scores of neotissues repaired by the scaffold with cells were closer to that of normal tissue. Although the biomechanical properties of neotissues were not as good as the normal tissue, no significant difference was found between the gene levels of neotissues repaired by the scaffold with or without cells and that of the normal tissue. The repair of the osteochondral defect tends to be stable 12 weeks after implantation. Conclusions Our bilayered PLGA porous scaffold supports long-term osteochondral repair via in vivo tissue engineering or regeneration, and its effect can be further facilitated under the scaffold seeded with allogenic BMSCs. The translational potential of this article The bilayered PLGA porous scaffold can facilitate the repair of osteochondral defects and has potential for application in osteochondral tissue engineering.

Background:Osteochondral lesions of the talus are frequent pathologies of the ankle joint. Especially through arthroscopy, the treatment is kept as minimally invasive as possible. However, there are some drawbacks as to the reachability because of the high congruency of the ankle joint. Here, either noninvasive distraction or maximal dorsiflexion may be an option for better access to the lesion. The purpose of this study was to evaluate maximal dorsiflexion compared to neutral position or noninvasive distraction of the ankle joint in the arthroscopic reachability of the talar dome. The hypothesis of this study was that maximal dorsiflexion would allow for greater accessibility of the talar dome compared to neutral position or noninvasive distraction of the joint.Methods:Twenty matched pairs (n=40) of anatomical ankle specimens were used. The effects of neutral position, maximal dorsiflexion, and noninvasive distraction of the ankle joint on arthroscopic accessibility of the ankle joint were tested. After disarticulation of the talus, reach was measured and compared between the 3 positions.Results:In neutral position, 13.7±1.2 mm of the talar dome was reached laterally and 14.0±1.0 mm medially. In maximal dorsiflexion, the distance was 19.0±1.1mm laterally and 19.8±1.4 mm medially, and in noninvasive distraction it was 16.1±1.5 mm laterally and 15.7±1.0 mm medially. The statistical comparison showed a significantly better reach in dorsiflexion laterally ( P = .003) and medially ( P = .026).Conclusion:Accessibility of the talar dome in maximal dorsiflexion was superior to that in neutral position or noninvasive distraction.Clinical Relevance:Results of this study may allow for better planning in arthroscopic treatment of osteochondral lesions of the talus.

The regeneration of cartilage is challenging due to its low metabolic rate and avascular nature. An effective treatment for osteochondral defects remains a clinical challenge. Glycosaminoglycans such as heparan sulfate (HS) bind and enhance the activity of prochondrogenic growth factors and thus hold potential for targeted tissue regeneration without the requirement for exogenous growth factors. In this study, we examine the use of a cell- and growth factor-free HS-based technique for osteochondral repair in a rabbit model. The binding affinity between HS and several reparative proteins (TGF-β1, BMP-2, FGF-2, PDGF-BB, and VEGF₁₆₅) was studied using surface plasmon resonance. Next, an HS-impregnated gel was implanted in a large osteochondral defect in the femoral trochlea of 19 New Zealand white rabbits to study the efficacy of the treatment. Over a 12-week period, HS showed significantly enhanced subchondral bone regeneration compared with a hydrogel control. Treatment with HS also resulted in an increased presence of hyaline cartilage in the chondral region. The use of HS in osteochondral defects appears to improve both subchondral and chondral tissue repair. Our data suggest that this effect is mediated by the ability of HS to promote endogenous growth factors. Agency for Science, Technology and Research (A*STAR) National Medical Research Council (NMRC) The authors acknowledge the funding support of Singapore's Agency for Science, Technology and Research (A*STAR) and Institute of Medical Biology (IMB). Funding was also provided by the National Medical Research Council (NMRC), Singapore (No. CIRG16may052).

The socioeconomic impact of osteochondral (OC) damage has been increasing steadily over time in the global population, and the promise of tissue engineering in generating biomimetic tissues replicating the physiological OC environment and architecture has been falling short of its projected potential. The most recent advances in OC tissue engineering are summarised in this work, with a focus on electrospun and 3D printed biomaterials combined with stem cells and biochemical stimuli, to identify what is causing this pitfall between the bench and the patients’ bedside. Even though significant progress has been achieved in electrospinning, 3D-(bio)printing, and induced pluripotent stem cell (iPSC) technologies, it is still challenging to artificially emulate the OC interface and achieve complete regeneration of bone and cartilage tissues. Their intricate architecture and the need for tight spatiotemporal control of cellular and biochemical cues hinder the attainment of long-term functional integration of tissue-engineered constructs. Moreover, this complexity and the high variability in experimental conditions used in different studies undermine the scalability and reproducibility of prospective regenerative medicine solutions. It is clear that further development of standardised, integrative, and economically viable methods regarding scaffold production, cell selection, and additional biochemical and biomechanical stimulation is likely to be the key to accelerate the clinical translation and fill the gap in OC treatment.

Osteochondral fractures of the medial femoral condyle of the knee can be diagnostically and therapeutically challenging. Various techniques of osteochondral defect treatment include fixation, abrasion chondroplasty, drilling, microfracture, autografts, allografts and chondrocyte transplantation A 37-year-old man presented with persistent left knee pain of about six months duration. Concomitant symptoms included swelling, several episodes of locking and clicking, and a sense of instability especially in walking downstairs. MRI scan revealed an unstable osteochondral lesion about 2 cm in diameter involving the medial femoral condyle. The patient underwent arthroscopic removal of the fragment and microfracturing of the defect on the medial femoral condyle. Postoperatively, he was treated with non-weight bearing for six weeks along with quadriceps strengthening and range of motion (ROM) exercises. The final outcome was good as the patient has returned to his previous activities. Microfracture technique is quite effective with regard to the improvement of daily activities with a favorable impact on pain relief and overall satisfactory functional results.

Osteochondral defects in joints require surgical intervention to relieve pain and restore function. However, no current treatment enables a complete reconstitution of the articular surface. It is known that both mechanical and biological factors play a key role on osteochondral defect healing, however the underlying principles and how they can be used in the design of treatment strategies remain largely unknown. To unravel the underlying principles of mechanobiology in osteochondral defect healing, i.e., how mechanical stimuli can guide biological tissue formation, we employed a computational approach investigating the scaffold-associated mechanical and architectural properties that would enable a guided defect healing. A previous computer model of the knee joint was further developed to simulate healing of an empty osteochondral defect. Then, scaffolds were implanted in the defect and their architectures and material properties were systematically varied to identify their relevance in osteochondral defect healing. Scaffold mechanical and architectural properties were capable of influencing osteochondral defect healing. Specifically, scaffold material elastic modulus values in the range of cancellous bone (low GPa range) and a scaffold architecture that provided stability, i.e., resistance against displacement, in both the main loading direction and perpendicular to it supported the repair process. The here presented model, despite its simplifications, is regarded as a powerful tool to screen for promising properties of novel scaffold candidates fostering osteochondral defect regeneration prior to their implementation in vivo.

Osteochondral defects in joints require surgical intervention to relieve pain and restore function. However, no current treatment enables a complete reconstitution of the articular surface. It is known that both mechanical and biological factors play a key role on osteochondral defect healing, however the underlying principles and how they can be used in the design of treatment strategies remain largely unknown. To unravel the underlying principles of mechanobiology in osteochondral defect healing, i.e., how mechanical stimuli can guide biological tissue formation, we employed a computational approach investigating the scaffold-associated mechanical and architectural properties that would enable a guided defect healing. A previous computer model of the knee joint was further developed to simulate healing of an empty osteochondral defect. Then, scaffolds were implanted in the defect and their architectures and material properties were systematically varied to identify their relevance in osteochondral defect healing. Scaffold mechanical and architectural properties were capable of influencing osteochondral defect healing. Specifically, scaffold material elastic modulus values in the range of cancellous bone (low GPa range) and a scaffold architecture that provided stability, i.e., resistance against displacement, in both the main loading direction and perpendicular to it supported the repair process. The here presented model, despite its simplifications, is regarded as a powerful tool to screen for promising properties of novel scaffold candidates fostering osteochondral defect regeneration prior to their implementation in vivo.

Novel calcium phosphate cements containing a mixture of four amino acids, glycine, proline, hydroxyproline and either lysine or arginine (CAL, CAK) were characterized and used for treatment of artificial osteochondral defects in knee. It was hypothesized that an enhanced concentration of extracellular collagen amino acids (in complex mixture), in connection with bone cement in defect sites, would support the healing of osteochondral defects with successful formation of hyaline cartilage and subchondral bone. Calcium phosphate cement mixtures were prepared by in situ reaction in a planetary ball mill at aseptic conditions and characterized. It was verified that about 30&ndash, 60% of amino acids remained adsorbed on hydroxyapatite particles in cements and the addition of amino acids caused around 60% reduction in compressive strength and refinement of hydroxyapatite particles in their microstructure. The significant over-expression of osteogenic genes after the culture of osteoblasts was demonstrated in the cement extracts containing lysine and compared with other cements. The cement pastes were inserted into artificial osteochondral defects in the medial femoral condyle of pigs and, after 3 months post-surgery, tissues were analyzed macroscopically, histologically, immunohistochemically using MRI and X-ray methods. Analysis clearly showed the excellent healing process of artificial osteochondral defects in pigs after treatment with CAL and CAK cements without any inflammation, as well as formation of subchondral bone and hyaline cartilage morphologically and structurally identical to the original tissues. Good integration of the hyaline neocartilage with the surrounding tissue, as well as perfect interconnection between the neocartilage and new subchondral bone tissue, was demonstrated. Tissues were stable after 12 months&rsquo, healing.

A stem cell-based tissue-engineering approach is a promising strategy for treatment of cartilage defects. However, there are conflicting data in the feasibility of using this approach in young recipients. A young rabbit model with an average age of 7.7 months old was used to evaluate the effect of a tissue-engineering approach on the treatment of osteochondral defects. Following in vitro evaluation of proliferation and chondrogenic capacity of infrapatellar fat pad-derived stem cells (IPFSCs) after expansion on either tissue culture plastic (TCP) or decellularized extracellular matrix (dECM), a premature tissue construct engineered from pretreated IPFSCs was used to repair osteochondral defects in young rabbits. We found that dECM expanded IPFSCs exhibited higher proliferation and chondrogenic differentiation compared to TCP expanded cells in both pellet and tissue construct culture systems. Six weeks after creation of bilateral osteochondral defects in the femoral trochlear groove of rabbits, the Empty group (left untreated) had the best cartilage resurfacing with the highest score in Modified O'Driscoll Scale (MODS) than the other groups; however, this score had no significant difference compared to that of 15-week samples, indicating that young rabbits stop growing cartilage once they reach 9 months old. Interestingly, implantation of premature tissue constructs from both dECM and TCP groups exhibited significantly improved cartilage repair at 15 weeks compared to those at six weeks (about 9 months old), indicating that a tissue-engineering approach is able to repair adult cartilage defects. We also found that implanted pre-labeled cells in premature tissue constructs were undetectable in resurfaced cartilage at both time points. This study suggests that young rabbits (less than 9 months old) might respond differently to the classical tissue-engineering approach that is considered as a potential treatment for cartilage defects in adult rabbits.

Scaffolds are thought to be a key element needed for successful cartilage repair treatments, and this prospective extension study aimed to evaluate long-term structural and clinical outcomes following osteochondral defect treatment with a cell-free biphasic scaffold. Structural outcomes were assessed using quantitative 3-D magnetic resonance imaging (MRI) and morphological segmentation to determine the percentage of defect filling and repair cartilage T2 relaxation times, and clinical outcomes were determined with the modified Cincinnati Rating System, and the Knee Injury and Osteoarthritis Outcome Score (KOOS). Seventeen subjects with osteochondral defects in the knee were treated with ChondroMimetic scaffolds, from which 15 returned for long-term evaluation at a mean follow-up of 7.9 &plusmn, 0.3 years. The defects treated were trochlear donor sites for mosaicplasty in 13 subjects, and medial femoral condyle defects in 2 subjects. MRI analysis of scaffold-treated defects found a mean total defect filling of 95.2 &plusmn, 3.6%, and a tissue mean T2 relaxation time of 52.5 &plusmn, 4.8 ms, which was identical to the T2 of ipsilateral control cartilage (52.3 &plusmn, 9.2 ms). The overall modified Cincinnati Rating System score was statistically significant from baseline (p = 0.0065), and KOOS subscales were equivalent to other cartilage repair techniques. ChondroMimetic treatment resulted in a consistently high degree of osteochondral defect filling with durable, cartilage-like repair tissue at 7.9 years, potentially associated with clinical improvement.

BackgroundArticular surface damage commonly associated with rupture of the anterior cruciate ligament (ACL). Large osteochondral defect, which consists of a severe depression fracture and a large cartilage defect, need to be treated due to deformation of the articular surface as it can impact the clinical outcome of ACL reconstruction. Although autologous chondrocyte implantation is one of the useful options in such cases, it can be questioned whether the reconstruction of the ACL and osteochondral defect should be performed in one procedure alone.Case presentationWe report a case of a 38-year-old male with a deep depression fracture extending to the edge of the lateral femoral condyle associated with ACL injury after twisting his right knee while skiing. The patient was successfully treated with tissue-engineered cartilage transplantation covered by the periosteum with an iliac bone graft combined with anatomic double-bundle ACL reconstruction. Histopathological examination of the transplanted cartilage taken at second-look arthroscopy showed a cartilage-like tissue in the middle to deep zone in which the extracellular matrix was largely stained with Safranin O. The patient was able to return to his previous level of skiing activity without any experience of knee pain. Magnetic resonance imaging at 4 years after surgery showed that the graft integrated to the border zone and subchondral bone. The operated knee showed negative Lachman test and had a full range of motion.ConclusionsTo our knowledge, this is the first report of anatomic double-bundle ACL reconstruction with tissue-engineered cartilage transplantation and an iliac bone graft to restore the lateral edge of the femoral condyle.

Background The repair of osteochondral lesions remains a challenge due to its poor vascularity and limited healing potential. Micronized cartilage matrix (MCM) is dehydrated, decellularized, micronized allogeneic cartilage matrix that contains the components of native articular tissue and is hypothesized to serve as a scaffold for the formation of hyaline-like tissue. Our objective was to demonstrate in vitro that the use of MCM combined with mesenchymal stem cells (MSCs) can lead to the formation of hyaline-like cartilage tissue in a single-stage treatment model. Design In group 1 (no wash), 250 µL MCM was reconstituted in 150 µL Dulbecco’s phosphate-buffered saline (DPBS) for 5 minutes. Group 2 (saline wash) included 250 µL MCM washed in 20 mL DPBS for 30 minutes, then aspirated to remove all DPBS and reconstituted in 150 µL DPBS. Group 3 (serum wash): 250µL MCM washed in 20 mL DPBS for 30 minutes, then aspirated and reconstituted in 150 µL fetal bovine serum. Each group was then added to 50 µL solution of MSC suspended in DPBS at a concentration of 1.2 × 106 cells/350 µL. After 3 weeks, the defects were extracted and sectioned to perform viability and histologic analyses. Results Stem cells without rehydration of the MCM showed almost no viability whereas near complete cell viability was seen after rehydration with serum or saline solution, ultimately leading to chondrogenic differentiation and adhesion to the MCM particles. Conclusion We have shown in this proof-of-concept in vitro study that MCM can serve as a scaffold for the growth of cartilage tissue for the treatment of osteochondral lesions.

International audience; The treatment of osteochondral defects remains a challenge. Four scaffolds were produced using Food and Drug Administration (FDA)-approved polymers to investigate their therapeutic potential for the regeneration of the osteochondral unit. Polycaprolactone (PCL) and poly(vinyl-pyrrolidone) (PVP) scaffolds were made by electrohydrodynamic techniques. Hydroxyapatite (HAp) and/or sodium hyaluronate (HA) can be then loaded to PCL nanofibers and/or PVP particles. The purpose of adding hydroxyapatite and sodium hyaluronate into PCL/PVP scaffolds is to increase the regenerative ability for subchondral bone and joint cartilage, respectively. Human bone marrow-derived mesenchymal stem cells (hBM-MSCs) were seeded on these biomaterials. The biocompatibility of these biomaterials in vitro and in vivo, as well as their potential to support MSC differentiation under specific chondrogenic or osteogenic conditions, were evaluated. We show here that hBM-MSCs could proliferate and differentiate both in vitro and in vivo on these biomaterials. In addition, the PCL-HAp could effectively increase the mineralization and induce the differentiation of MSCs into osteoblasts in an osteogenic condition. These results indicate that PCL-HAp biomaterials combined with MSCs could be a beneficial candidate for subchondral bone regeneration.

Background Osteochondral knee defects (OCD) are often symptomatic, causing pain and functional impairment even in young and active patients. Regenerative surgical options, aiming to stimulate natural cartilage healing, have been recently used as a first line treatment. In this study, a new hydrogel is investigated in its capacity to regenerate the ultra-structural quality of hyaline cartilage when combined with a classical microfracture technique. Material and methods Forty-six patients, affected by grade III and IV knee chondropathies, were consecutively treated between 2013 and 2015 with microfractures followed by application of a modern hydrogel in the lesion site. All patients underwent clinical evaluation (WOMAC) pre-operatively, at 6,12 and at 24 months postoperatively: the results were compared with a subsequent, consecutive, matched, control group of 23 patients treated with microfractures alone. In a parallel and separate in-vitro histological study, adipose derived mesenchymal stem cells (ADMSCs) were encapsulated in the hydrogel scaffold, induced to differentiation into chondrocytes, and observed for a 3 weeks period. Results The initial WOMAC score of 58.6 ± 11.0 in the study group was reduced by 88% at 6 months (7.1 ± 9.2) and 95% at 24 months (2.9 ± 5.9). The “in-vitro” study revealed a histological characterization typical of hyaline cartilage in study group. Separate biopsies performed at 12 months post-op in the study group also revealed type 2 collagen and hyaline-like cartilage in the regenerated tissue. Conclusion Our study demonstrated high patient satisfaction rates after microfractures combined with a modern hydrogel scaffold; histologic evaluation supported the hypothesis of creating an enhanced chondrogenic environment. Microfracture “augmentation” using modern acellular biomaterials, like hydrogels, might improve the clinical outcomes of this classical bone marrow stimulating procedure.

Background: Despite intensive research, regeneration of articular cartilage largely remains an unresolved medical concern as the clinically available modalities still suffer from long-term inconsistent data, relatively high failure rates and high prices of more promising approaches, such as cell therapy. In the present study, we aimed to evaluate the feasibility and long-term efficacy of a bilayered injectable acellular affinity-binding alginate hydrogel in a large animal model of osteochondral defects. Methods: The affinity-binding alginate hydrogel is designed for presentation and slow release of chondrogenic and osteogenic inducers (transforming growth factor-β1 and bone morphogenic protein 4, respectively) in two distinct and separate hydrogel layers. The hydrogel was injected into the osteochondral defects created in the femoral medial condyle in mini-pigs, and various outcomes were evaluated after 6 months. Results: Macroscopical and histological assessment of the defects treated with growth factor affinity-bound hydrogel showed effective reconstruction of articular cartilage layer, with major features of hyaline tissue, such as a glossy surface and cellular organisation, associated with marked deposition of proteoglycans and type II collagen. Microcomputed tomography showed incomplete bone formation in both treatment groups, which was nevertheless augmented by the presence of affinity-bound growth factors. Importantly, the physical nature of the applied hydrogel ensured its shear resistance, seamless integration and topographical matching to the surroundings and opposing articulating surface. Conclusions: The treatment with acellular injectable growth factor–loaded affinity-binding alginate hydrogel resulted in effective tissue restoration with major hallmarks of hyaline cartilage, shown in large animal model after 6-month follow-up. The translational potential of this article: This proof-of-concept study in a clinically relevant large animal model showed promising potential of an injectable acellular growth factor–loaded affinity-binding alginate hydrogel for effective repair and regeneration of articular hyaline cartilage, representing a strong candidate for future clinical development. Keywords: Affinity-binding alginate, Bone morphogenic protein 4, Hyaline cartilage, Osteochondral defect, Transforming growth factor-β1

Addressing osteochondral defects, the objective of current study was to synthesize bilayered hydrogel, where the cartilage layer was formed by alginate (Alg) polyacrylamide (PAAm) with and without the addition of TGF-beta 3 and bone layer by laponite XLS/Alg-PAAm and characterize by in vitro and in vivo experiments. Exceeding the mechanical strength of Alg-PAAm (32.95 +/- 1.23 kPa) and XLS based (317.5 +/- 21.72 kPa) hydrogels, XLS/Alg-PAAm hydrogel (469.7 +/- 6.1 kPa) activated macrophages towards M2 phenotype and stimulated the expression of anti-inflammatory factors. The addition of TGF-beta 3 accelerated transition of macrophage polarization, especially between day 4 and 7. The expression levels of MI-related genes such as CD80, iNOS and TNF-alpha decreased gradually after day 4, reaching lowest values at day 13, whereas the expression levels of M2-related genes, CD206, Argi and SFAT6 significantly increased promoting M2 macrophage polarization, which might be associated with accelerated bone repair. Moreover, bilayer structure exhibited a better cell viability as well as rcpainnent thorough the XIS contents. in vivo histological examinations verified the significant surface regularity and hyaline like tissue formation employment, along with synchronized degradation profile of the hydrogel with tissue healing at the end of 12 weeks. A mechanically durable, biocompatible and immunocompatiblc hydmgcl was formulated to be utilized in bone-cartilage engineering applications., Scientific and Technological Research Council of Turkey (TUBITAK) [117M843, 219M057]; National Research Foundation of Korea [2017K2A9A1A06037807]; Ministry of Science and ICT [NRF-2018M3A7B4089670]; TUBITAK 2211-A National Graduate Scholarship Program; TUBITAK [2211-A], This work was supported by The Scientific and Technological Research Council of Turkey (TUBITAK) under grant number 117M843 and immune response studies under grant 219M057. Y.-W.Kim and J.-Y.Sun were sup-ported under the framework of international cooperation program managed by the National Research Foundation of Korea (2017K2A9A1A06037807, FY2017) . Authors would like to acknowledge Material Technology Develop-ment Program through the National Research Foundation of Korea (NRF) funded by Ministry of Science and ICT (NRF-2018M3A7B4089670) . E.S and P.S.M gratefully acknowledge the TUBITAK 2211-A National Graduate Scholarship Program.

Background Chondrogenic mesenchymal stem cells (MSCs) have not yet been used to address the clinical demands of large osteochondral joint surface defects. In this study, self-assembling tissue intermediates (TIs) derived from human periosteum-derived stem/progenitor cells (hPDCs) were generated and validated for stable cartilage formation in vivo using two different animal models. Methods hPDCs were aggregated and cultured in the presence of a novel growth factor (GF) cocktail comprising of transforming growth factor (TGF)-β1, bone morphogenetic protein (BMP)2, growth differentiation factor (GDF)5, BMP6, and fibroblast growth factor (FGF)2. Quantitative polymerase chain reaction (PCR) and immunohistochemistry were used to study in vitro differentiation. Aggregates were then implanted ectopically in nude mice and orthotopically in critical-size osteochondral defects in nude rats and evaluated by microcomputed tomography (µCT) and immunohistochemistry. Results Gene expression analysis after 28 days of in vitro culture revealed the expression of early and late chondrogenic markers and a significant upregulation of NOGGIN as compared to human articular chondrocytes (hACs). Histological examination revealed a bilayered structure comprising of chondrocytes at different stages of maturity. Ectopically, TIs generated both bone and mineralized cartilage at 8 weeks after implantation. Osteochondral defects treated with TIs displayed glycosaminoglycan (GAG) production, type-II collagen, and lubricin expression. Immunostaining for human nuclei protein suggested that hPDCs contributed to both subchondral bone and articular cartilage repair. Conclusion Our data indicate that in vitro derived osteochondral-like tissues can be generated from hPDCs, which are capable of producing bone and cartilage ectopically and behave orthotopically as osteochondral units. Electronic supplementary material The online version of this article (10.1186/s13287-018-0787-3) contains supplementary material, which is available to authorized users.

Jyoti V Kumbhar,1 Sachin H Jadhav,2 Dhananjay S Bodas,1 Amruta Barhanpurkar-Naik,3 Mohan R Wani,3 Kishore M Paknikar,1 Jyutika M Rajwade1 1Nanobioscience, 2Animal Sciences Division, Agharkar Research Institute, 3National Centre for Cell Science, Savitribai Phule Pune University, Pune, India Abstract: Bacterial cellulose (BC) is a naturally occurring nanofibrous biomaterial which exhibits unique physical properties and is amenable to chemical modifications. To explore whether this versatile material can be used in the treatment of osteochondral defects (OCD), we developed and characterized novel BC-based nanocomposite scaffolds, for example, BC-hydroxyapatite (BC-HA) and BC-glycosaminoglycans (BC-GAG) that mimic bone and cartilage, respectively. In vitro biocompatibility of BC-HA and BC-GAG scaffolds was established using osteosarcoma cells, human articular chondrocytes, and human adipose-derived mesenchymal stem cells. On subcutaneous implantation, the scaffolds allowed tissue ingrowth and induced no adverse immunological reactions suggesting excellent in vivo biocompatibility. Implantation of acellular bilayered scaffolds in OCD created in rat knees induced progressive regeneration of cartilage tissue, deposition of extracellular matrix, and regeneration of subchondral bone by the host cells. The results of micro-CT revealed that bone mineral density and ratio of bone volume to tissue volume were significantly higher in animals receiving bilayered scaffold as compared to the control animals. To the best of our knowledge, this study proves for the first time, the functional performance of acellular BC-based bilayered scaffolds. Thus, this strategy has great potential for clinical translation and can be used in repair of OCD. Keywords: bacterial cellulose-hydroxyapatite, bacterial cellulose-glycosaminoglycan, osteochondral defect, stem cell differentiation, acellular bilayer scaffold&nbsp

Jyoti V Kumbhar,1 Sachin H Jadhav,2 Dhananjay S Bodas,1 Amruta Barhanpurkar-Naik,3 Mohan R Wani,3 Kishore M Paknikar,1 Jyutika M Rajwade1 1Nanobioscience, 2Animal Sciences Division, Agharkar Research Institute, 3National Centre for Cell Science, Savitribai Phule Pune University, Pune, India Abstract: Bacterial cellulose (BC) is a naturally occurring nanofibrous biomaterial which exhibits unique physical properties and is amenable to chemical modifications. To explore whether this versatile material can be used in the treatment of osteochondral defects (OCD), we developed and characterized novel BC-based nanocomposite scaffolds, for example, BC-hydroxyapatite (BC-HA) and BC-glycosaminoglycans (BC-GAG) that mimic bone and cartilage, respectively. In vitro biocompatibility of BC-HA and BC-GAG scaffolds was established using osteosarcoma cells, human articular chondrocytes, and human adipose-derived mesenchymal stem cells. On subcutaneous implantation, the scaffolds allowed tissue ingrowth and induced no adverse immunological reactions suggesting excellent in vivo biocompatibility. Implantation of acellular bilayered scaffolds in OCD created in rat knees induced progressive regeneration of cartilage tissue, deposition of extracellular matrix, and regeneration of subchondral bone by the host cells. The results of micro-CT revealed that bone mineral density and ratio of bone volume to tissue volume were significantly higher in animals receiving bilayered scaffold as compared to the control animals. To the best of our knowledge, this study proves for the first time, the functional performance of acellular BC-based bilayered scaffolds. Thus, this strategy has great potential for clinical translation and can be used in repair of OCD. Keywords: bacterial cellulose-hydroxyapatite, bacterial cellulose-glycosaminoglycan, osteochondral defect, stem cell differentiation, acellular bilayer scaffold&nbsp

Background A prospective analysis of the effect of autologous adipose derived mesenchymal stem cell (MSC) therapy in the treatment of an osteochondral defect of the knee with early progressive osteoarthritis following unsuccessful surgical intervention of osteochondritis dissecans (OCD). Case presentation After failed conventional management of OCD a patient undergoes intra-articular MSC therapy. Patient outcome measures included the Numeric Pain Rating Scale (NPRS), the Western Ontario and McMaster Universities Arthritis Index (WOMAC) and the Knee Injury and Osteoarthritis Outcome Score (KOOS). Structural outcome was assessed using MRI with the novel technique of T2 mapping used to indicate cartilage quality. Following MSC therapy the patient reported improvement in pain and function as measured by NPRS, WOMAC and KOOS. Repeat MRI analysis showed regeneration of cartilage. MRI T2 mapping indicated hyaline like cartilage regrowth. Conclusion In this report, the use of MSCs, after unsuccessful conventional OCD management, resulted in structural, functional and pain improvement. These results highlight the need to further study the regenerative potential of MSC therapy. Trial registration Australian and New Zealand Clinical Trial Registry Number - ACTRN12615000258550 (Date registered 19/03/2015 – retrospectively registered).

Haci Bayram Tosun,1 Murat Gürger,2 Seyit Ali Gümüştaş,1 Abuzer Uludag,1 Özlem Üçer,3 Sancar Serbest,4 Suat Çelik1 1Department of Orthopaedics and Traumatology, Faculty of Medicine, Adiyaman University, Adiyaman, 2Department of Orthopaedics and Traumatology, 3Department of Pathology, Faculty of Medicine, Firat University, Elazığ, 4Department of Orthopaedics and Traumatology, Faculty of Medicine, Kırıkkale University, Kırıkkale, Turkey Objective: In focal cartilage lesions, multipotent mesenchymal stem cells in bone marrow are aimed to be moved into the defect area using subchondral drilling or microfracture method. However, repaired tissue insufficiently fills the defect area or cannot meet natural hyaline tissue functions, due to fibrous structure. We investigated the effect of a combined solution of sodium hyaluronate + chondroitin sulfate (HA+CS) administered intra-articularly after subchondral drilling on newly formed cartilage in rabbits with focal osteochondral defects.Materials and methods: A total of 32 New Zealand White mature rabbits, whose weights ranged from 2.5 to 3 kg, were randomly divided into four groups. Full-thickness osteochondral defect was formed in the left-knee medial femur condyles of all rabbits. Subchondral drilling was then performed. The following treatment protocol was administered intra-articularly on knee joints on days 7, 14, and 21 after surgery: group 1, 0.3 mL combined solution of HA+CS (20 mg CS combined with 16 mg HA/mL); group 2, 0.3 mL HA (16 mg/mL); group 3, 0.3 mL CS (20 mg/mL); and group 4 (control group), 0.3 mL saline solution. In the sixth week, all animals were killed and then evaluated histopathologically and biochemically.Results: There was significant articular cartilage formation in the HA+CS group compared to the HA, CS, and control groups. Hyaline cartilage formation was observed only in the HA+CS group. Cartilage-surface continuity and smoothness were significantly higher in the HA+CS and HA groups compared to the other groups. Normal cartilage mineralization was found to be significantly higher in the HA+CS group compared to the other groups. Increased levels of VEGFA and IL-1β in synovial fluid were observed in the HA+CS group.Conclusion: After subchondral drilling, intra-articular HA-CS combination therapy is a good choice to promote better quality new cartilage-tissue formation in the treatment of focal osteochondral defects. Keywords: combined therapy, chondroitin sulfate, hyaluronate, osteochondral defect, subchondral drilling

Haci Bayram Tosun,1 Murat Gürger,2 Seyit Ali Gümüştaş,1 Abuzer Uludag,1 Özlem Üçer,3 Sancar Serbest,4 Suat Çelik1 1Department of Orthopaedics and Traumatology, Faculty of Medicine, Adiyaman University, Adiyaman, 2Department of Orthopaedics and Traumatology, 3Department of Pathology, Faculty of Medicine, Firat University, Elazığ, 4Department of Orthopaedics and Traumatology, Faculty of Medicine, Kırıkkale University, Kırıkkale, Turkey Objective: In focal cartilage lesions, multipotent mesenchymal stem cells in bone marrow are aimed to be moved into the defect area using subchondral drilling or microfracture method. However, repaired tissue insufficiently fills the defect area or cannot meet natural hyaline tissue functions, due to fibrous structure. We investigated the effect of a combined solution of sodium hyaluronate + chondroitin sulfate (HA+CS) administered intra-articularly after subchondral drilling on newly formed cartilage in rabbits with focal osteochondral defects.Materials and methods: A total of 32 New Zealand White mature rabbits, whose weights ranged from 2.5 to 3 kg, were randomly divided into four groups. Full-thickness osteochondral defect was formed in the left-knee medial femur condyles of all rabbits. Subchondral drilling was then performed. The following treatment protocol was administered intra-articularly on knee joints on days 7, 14, and 21 after surgery: group 1, 0.3 mL combined solution of HA+CS (20 mg CS combined with 16 mg HA/mL); group 2, 0.3 mL HA (16 mg/mL); group 3, 0.3 mL CS (20 mg/mL); and group 4 (control group), 0.3 mL saline solution. In the sixth week, all animals were killed and then evaluated histopathologically and biochemically.Results: There was significant articular cartilage formation in the HA+CS group compared to the HA, CS, and control groups. Hyaline cartilage formation was observed only in the HA+CS group. Cartilage-surface continuity and smoothness were significantly higher in the HA+CS and HA groups compared to the other groups. Normal cartilage mineralization was found to be significantly higher in the HA+CS group compared to the other groups. Increased levels of VEGFA and IL-1β in synovial fluid were observed in the HA+CS group.Conclusion: After subchondral drilling, intra-articular HA-CS combination therapy is a good choice to promote better quality new cartilage-tissue formation in the treatment of focal osteochondral defects. Keywords: combined therapy, chondroitin sulfate, hyaluronate, osteochondral defect, subchondral drilling

Category: Ankle, Trauma Introduction/Purpose: Osteochondral lesions (OCL) are described as any defect involving both the articular surface and the subchondral bone of the talus. They are commonly associated with acute ankle injuries occurring often in active population. Bone marrow stimulation with microfracture is a standard reparative treatment for OCD however decline in related functional outcome has been reported. BST-CarGel contains chitosan which binds to negatively charged cartilage surface acting as biocompatible scaffold. This allows repair tissue with significant filling volume and proper integration into the surroundings. There has been reported better quantitative and qualitative cartilage repair tissue at 12 months with BST-CarGel. We first report on clinical results of bone marrow stimulation and BST-Cargel for recalcitrant talar OCL in patients previously treated with microfracture alone in a prospective study. Methods: This prospective single surgeon series was limited to patients with symptomatic OCL who previously had arthroscopic debridement and microfracture for same lesion. The pre-operative evaluation of all patients involved clinical assessment, weight bearing plain radiographs and magnetic resonance imaging of ankle joint. Inclusion criteria were age 18-55 years, single focal OCL of talus less than 3 cm2 and previous microfracture. Exclusion criteria was evidence of ankle osteoarthritis and allergy to chitosan or known hypersensitivity to crustaceans such as shrimp, lobster, and crab. Functional outcome assessment was measured using Foot and Ankle outcome score (FAOS) and EQ5D (Health related quality of life) pre and post-operatively. We used paired Student’s t-test for statistical analysis. Values for p < 0.05 were regarded as significant. The surgical technique used have been previously described in literature for OCL of the talus treated with bone marrow stimulation and Cargel. Results: There were fourteen patients who were treated with arthroscopic BST-Cargel with BMS and followed up prospectively. There was no loss to follow-up. The mean follow-up post-operatively was 28 months. There were eight males and six females in the study group. Patient mean age at the time of operation was 42 years (21–60 years). The mean size of talar OCL treated was 2.8 cm2 . Mean FAOS score for symptoms pre-operatively was 41.7 and post-operative was 52.8 (PConclusion: We noted statistically significant improvement in each subscale of The Foot and Ankle Outcome questionnaire scores post-operatively. There was also significant improvement in generic health status instrument EQ-5D. We also noted talar OCL improvement on MRI scan taken pre and post BST-CarGel treatment. Recalcitrant OCL of talus present considerable challenge with persistent pain, functional limitations and secondary osteoarthritis. BST-Cargel treatment in our clinical study improved functional outcome scores similar to previously reported hip and knee studies. It requires standard arthroscopic technique and no complications were observed in our study.

Category: Ankle Introduction/Purpose: The purpose of this study was to present the surgical technique and to evaluate the short-term clinical and radiological outcomes of a new press-fit OATS technique for large primary and secondary talar osteochondral defects of the talus, Talar OsteoPeriostic grafting from the Iliac Crest (TOPIC). Methods: Twenty-eight underwent a press-fit TOPIC procedure. Mean age was 38 years (SD 4.6). Pre- and postoperative clinical assessment at 12 months follow-up included the American Orthopaedic Foot & Ankle Society (AOFAS) score, the Short-Form 36 (SF-36) Mental Component Scale (MCS) and Physical Component Scale (PCS), the Numeric Rating Scales (NRS) of pain at rest, during walking and stairclimbing, and the Foot and Ankle Outcome Score (FAOS) including accompanying subscales. Remodeling of the contour of the talus, bone ingrowth and consolidation of the implanted graft were assessed on computed tomography (CT) one year post-operatively. Results: 28 out of 29 patients were available for follow up. The AOFAS significantly improved from 45 to 92 (p=0.001). The NRS on pain during rest improved from 3 to 0 (p=0.001), the NRS during walking improved from 5 to 1 and the NRS during stairclimbing also improved from 5 to 1 (p=0.001). Both components of the SF-36 improved. The PCS improved from 34 to 47 (p=0.001) and the MCS improved from 37 to 66 (p=0.001). Finally all FAOS subscales significantly improved. All patients were satisfied with the procedure and indicated that the level of functioning was good or very good. On the post-operative CT scans, all patients showed remodeling of the talus and all grafts showed consolidation as well as bone ingrowth. No complications occurred. Conclusion: The TOPIC procedure appears to be a very promising surgical treatment option for large primary and secondary talar OCDs. Despite these good short-term clinical and radiological outcomes, a prospective study with longer follow-up is necessary to assess the clinical outcome and the progression of osteoarthritis at the long term.

Cartilage repair remains a major challenge and treatment of (osteo)chondral defects generally results in poor quality fibrous repair tissue. Our approach aims to address some of the major biomechanical issues encountered in scaffold-based cartilage repair, such as insufficient stiffness of the scaffolds, step formation at the interface with the native tissue and inadequate integration with the original tissue. Two osteochondral defects were created on the medial femoral trochlear ridge in each stifle of six Shetland ponies. The defects were filled with a bi-layered implant consisting of a polyetherketoneketone (PEKK) bone anchor and a polyurethane elastomer. The defects in the contralateral joint served as unfilled controls. After 12 weeks, the ponies were euthanased and tissues were evaluated macroscopically and using micro-computed tomography, histology and immunohistochemistry. Post-operative recovery was good in all ponies and minimal lameness was observed. After 12 weeks, the proximally located plug was partially covered (mean ± standard deviation [SD] percentage surface area covered 72.5 ± 19.7%) and the distal plug was nearly completely covered (mean ± SD percentage surface area covered 98.5 ± 6.1%) with stiff and smooth repair tissue. Histology and immunohistochemistry confirmed that the repair tissue was well connected to the native cartilage but contained negligible amounts of collagen type II and glycosaminoglycans (GAGs). The repair tissue was stiff and fibrous in nature and presented a nearly flush surface with the surrounding native cartilage distally. This approach therefore resolves a number of issues related to scaffold-based cartilage repair and compares favourably with results of several other studies in large animal models. However, long-term follow-up is needed to evaluate the true potential of this type of implant.

DEGIRMENCI, ERDEM/0000-0002-7988-4261 WOS: 000464895500001 PubMed: 30992060 Background: Microfracture and scaffold application in the treatment of osteochondral defects is still one of the most frequently used methods in the clinic. The most important step in this treatment method is the stabilization of fibrin clot Tranexamic acid (TA) is an antifibrinolytic agent commonly used in orthopedic surgery in recent years. This study evaluated the effect of local TA application on healing of experimentally induced osteochondral defects on rabbits. Methods: This paper contains an animal in vivo data and histological outcomes on the effect of TA. Eighteen New Zealand white rabbits were treated unilaterally and cylindrical defects having a width of 4 mm and depth of 5 mm were created in the weight-bearing surfaces of the medial and lateral condyles of the right femur. They were divided into two groups, as group 1 study and group 2 control groups, respectively. One milliliter (ml) of TA was injected into the knee joints of the subjects in group 1. All animals were sacrificed for the extraction of the femur condyles for histologic study at the fourth and eighth weeks after surgery. Histological evaluations were performed by Brittberg and O'Driscoll scores to all samples. Data were organized in a Standard Statistical Package System v.22 software package (SPSS/PC Inc., Chicago, IL) and reported as mean and median (min-max). Repeated measures ANOVA test was used to compare groups and condyle effects together for each week. p values below 0.05 were considered as statistically significant. Results: Samples were taken in the fourth and eighth weeks. The regularity of the surface in group 1 was smoother, and the tissue stability was more robust. Mean Brittberg scores in both weeks were statistically higher in group 1 when compared with group 2. In the microscopic evaluation, it was observed that the regeneration of subchondral and cartilage tissues were more rapid and organized in group 1, and the mean O' Driscoll scores in both weeks were statistically higher in group 1. Conclusions: Application of TA improves the healing time and tissue stability in osteochondral defects which are implanted a-cellular scaffold after microfracture and should be applicable to humans for the treatment of osteochondral defects. Duzce University Scientific Research Projects Support Fund Animals were obtained from the experimental animal care center of AIBU with the support of Duzce University Scientific Research Projects Support Fund.

Hongli Xiao,1,* Wenliang Huang,1,* Kun Xiong,1 Shiqiang Ruan,1 Cheng Yuan,1 Gang Mo,1 Renyuan Tian,1 Sirui Zhou,1 Rongfeng She,2 Peng Ye,3 Bin Liu,4 Jiang Deng1 1Department of Orthopedics, Third Affiliated Hospital of Zunyi Medical University, Zunyi 563000, Guizhou Province, People’s Republic of China; 2Department of Orthopedics, Guizhou Province People’s Hospital, Guiyang 550002, Guizhou Province, People’s Republic of China; 3Emergency and Trauma Ward, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, Guizhou Province, People’s Republic of China; 4Surgical Laboratory, Zunyi Medical University, Zunyi 563000, Guizhou Province, People’s Republic of China *These authors contributed equally to this work Background: One of the main problems associated with the development of osteochondral reparative materials is that the accurate imitation of the structure of the natural osteochondral tissue and fabrication of a suitable scaffold material for osteochondral repair are difficult. The long-term outcomes of single- or bilayered scaffolds are often unsatisfactory because of the absence of a progressive osteochondral structure. Therefore, only scaffolds with gradient pore sizes are suitable for osteochondral repair to achieve better proliferation and differentiation of the stem cells into osteochondral tissues to complete the repair of defects. Methods: A silk fibroin (SF) solution, chitosan (CS) solution, and nano-hydroxyapatite (nHA) suspension were mixed at the same weight fraction to obtain osteochondral scaffolds with gradient pore diameters by centrifugation, freeze-drying, and chemical cross-linking. Results: The scaffolds prepared in this study are confirmed to have a progressive structure starting from the cartilage layer to bone layer, similar to that of the normal osteochondral tissues. The prepared scaffolds are cylindrical in shape and have high internal porosity. The structure consists of regular and highly interconnected pores with a progressively increasing pore distribution as well as a progressively changing pore diameter. The scaffold strongly absorbs water, and has a suitable degradation rate, sufficient space for cell growth and proliferation, and good resistance to compression. Thus, the scaffold can provide sufficient nutrients and space for cell growth, proliferation, and migration. Further, bone marrow mesenchymal stem cells seeded onto the scaffold closely attach to the scaffold and stably grow and proliferate, indicating that the scaffold has good biocompatibility with no cytotoxicity. Conclusion: In brief, the physical properties and biocompatibility of our scaffolds fully comply with the requirements of scaffold materials required for osteochondral tissue engineering, and they are expected to become a new type of scaffolds with gradient pore sizes for osteochondral repair. Keywords: tissue engineering, bone marrow mesenchymal stem cells, bioscaffolds, osteochondral defect

Life : open access journal 11(6), 543 (2021). doi:10.3390/life11060543 special issue: "Special issue "Focal chondral defects" / special issue editors: Filippo Migliorini, guest editor; Nicola Maffulli, guest editor", Published by MDPI, Basel

A 23-year-old male sustained a gunshot to the right foot with resultant talar body fracture and a 1 cm2 osteochondral defect of the talus. The patient was treated acutely with ankle arthrodiastasis using an external circular frame allowing ankle range of motion and full weight bearing while the fracture healed and the bone and cartilage graft incorporated. The circular frame was utilized for 4 months. At follow up, the patient was able to walk pain-free, the bone graft had incorporated on radiographs, and there were no signs of joint degeneration. We were unable to find any similar reports in the English literature of a young patient with a traumatic injury treated with ankle arthrodiastasis. This technique allows more normal function during the healing period than traditional techniques to reconstruct osteochondral lesions of the talus which require prolonged nonweight bearing. While primarily used for ankle osteoarthritis to date, ankle arthrodiastasis should be investigated for other indications to determine its utility in complex injuries.

Background: Osteochondral injuries have poor endogenous healing potential, and no standard treatment has been established. The use of combined layered autologous bone and cartilage chips for treatment of osteochondral defects has shown promising short-term clinical results. Purpose/Hypothesis: This study aimed to investigate the role of cartilage chips by comparing combined layered autologous bone and cartilage chips with autologous bone implantation alone in a Göttingen minipig model. The hypothesis was that the presence of cartilage chips would improve the quality of the repair tissue. Study Design: Controlled laboratory study. Methods: Twelve Göttingen minipigs received 2 osteochondral defects in each knee. The defects were randomized to autologous bone graft (ABG) combined with autologous cartilage chips (autologous dual-tissue transplantation [ADTT]) or ABG alone. Six animals were euthanized at 6 months and 6 animals were euthanized at 12 months. Follow-up evaluation consisted of histomorphometry, immunohistochemistry, semiquantitative scoring (International Cartilage Repair Society II), and computed tomography. Results: There was significantly more hyaline cartilage in the ADTT group (25.8%) compared with the ABG group (12.8%) at 6 months after treatment. At 12 months, the fraction of hyaline cartilage in the ABG group had significantly decreased to 4.8%, whereas the fraction of hyaline cartilage in the ADTT group was unchanged (20.1%). At 6 and 12 months, there was significantly more fibrocartilage in the ADTT group (44% and 60.8%) compared with the ABG group (24.5% and 41%). The fraction of fibrous tissue was significantly lower in the ADTT group compared with the ABG group at both 6 and 12 months. The implanted cartilage chips stained >75% positive for collagen type 4 and laminin at both 6 and 12 months. Significant differences were found in a number of International Cartilage Repair Society II subcategories. The volume of the remaining bone defect significantly decreased from 6 to 12 months in both treatment groups; however, no difference in volume was found between the groups at either 6 or 12 months. Conclusion: The presence of cartilage chips in an osteochondral defect facilitated the formation of fibrocartilage as opposed to fibrous tissue at both 6 and 12 months posttreatment. The implanted chips were present in the defect and viable after 12 months. Clinical Relevance: This study substantiates the chondrogenic role of cartilage chips in osteochondral defects.