Subchondral bone fatigue injury in the parasagittal condylar grooves of the third metacarpal bone in thoroughbred racehorses elevates site-specific strain concentration.

Condylar stress fracture of the distal end of the third metacarpal/metatarsal (MC3/MT3) bones is a major cause of Thoroughbred racehorse injury and euthanasia worldwide. Functional adaptation to exercise and fatigue damage lead to structural changes in the subchondral bone that include increased modeling (resulting in sclerotic bone tissue) and targeted remodeling repair (resulting in focal resorption spaces in the parasagittal groove). Whether these focal structural changes, as detectable by standing computed tomography (sCT), lead to elevated strain at the common site of condylar stress fracture has not been demonstrated. Therefore, the goal of the present study was to compare full-field three-dimensional (3D) strain on the distopalmar aspect of MC3 bone specimens with and without focal subchondral bone injury (SBI). Thirteen forelimb specimens were collected from racing Thoroughbreds for mechanical testing ex vivo and underwent sCT. Subsequently, full-field displacement and strain at the joint surface were determined using stereo digital image correlation. Strain concentration was observed in the parasagittal groove (PSG) of the loaded condyles, and those with SBI in the PSG showed higher strain rates in this region than control bones. PSG strain rate in condyles with PSG SBI was more sensitive to CT density distribution in comparison with condyles with no sCT-detectable injury. Findings from this study help to interpret structural changes in the subchondral bone due to fatigue damage and to assess risk of incipient stress fracture in a patient-specific manner.

Magnetic resonance imaging combined with histological evaluation of repair process using the microfracture technique in an association of osteocartilaginous and meniscal surgically induced lesions of the knee. In vivo experiment on a rabbit model.

The present research study aimed to assess magnetic resonance imaging (MRI) changes and histological findings in the therapeutic effects of microfractures in the treatment of complex animal knee lesions resulting from osteochondral and meniscal defects resulting from non-total meniscectomies. The anterior cruciate ligament lesions are also proven to facilitate the development of osteoarthritis in the knee and worsen the prognosis. Surgery was performed on the right knee joint of 22 male rabbits in order to partially remove the anterior horn of the internal meniscus and to induce an osteochondral defect at the level of the internal femoral condyle. The induced lesion complex was aimed to simulate a clinical situation that occurs frequently in orthopedic practice when young adults undergo partial meniscectomy and at the time of surgery, an osteochondral defect is diagnosed. Rabbits were separated into two study groups: the control (C1) group and the microfractures (MF2) group. After the induced cartilage defect and partial meniscectomy, both groups were followed-up for six months using detailed MRI. Also, anatomical specimens were histologically analyzed to show modifications and signs of healing process, along with complications, in the study group. The results showed that the microfracture group had better results concerning articular surface defect healing in comparison to the control group. Our results suggest that microfractures do improve results concerning surface contact healing and serial MRI studies can be useful in observing the remodeling process in dynamics.

Intra-articular injection of ascorbic acid enhances microfracture-mediated cartilage repair.

Previous studies have confirmed that ascorbic acid (AA) can promote cartilage repair and improve cartilage differentiation in bone marrow mesenchymal stem cells. However, the use of microfracture (MFX) combined with AA to repair cartilage damage has not been studied. This study established a rabbit animal model and treated cartilage injury with different concentrations of AA combined with MFX. Macroscopic observations, histological analysis, immunohistochemical analysis and reverse transcription quantitative polymerase chain reaction analysis of TGF-ß, AKT/Nrf2, and VEGF mRNA expression were performed. The results showed that intra-articular injection of AA had a positive effect on cartilage repair mediated by microfractures. Moreover, 10 mg/ml AA was the most effective at promoting cartilage repair mediated by microfractures. Intra-articular injection of AA promoted the synthesis of type II collagen and the formation of glycosaminoglycans by downregulating the mRNA expression of TGF-ß and VEGF. In summary, this study confirmed that AA could promote cartilage repair after MFX surgery.

Costal Chondrocyte-Derived Pellet-Type Autologous Chondrocyte Implantation Versus Microfracture for the Treatment of Articular Cartilage Defects: A 5-Year Follow-up of a Prospective Randomized Trial.

BACKGROUND: Costal chondrocyte-derived pellet-type autologous chondrocyte implantation (CCP-ACI) has been introduced as a new therapeutic option for the treatment of articular cartilage defects. We had previously conducted a randomized controlled trial comparing CCP-ACI versus microfracture at 1 year postoperatively. PURPOSE: To compare the efficacy and safety of CCP-ACI versus microfracture for the treatment of articular cartilage defects of the knee at 5 years postoperatively. STUDY DESIGN: Randomized controlled trial; Level of evidence, 2. METHODS: This study describes the mean 5-year follow-up of a previously published prospective clinical trial. The previous prospective trial compared the results of CCP-ACI versus microfracture until 1 year of follow-up. Of the 30 patients who were included in the previous study, 25 were followed up for 5 years. Patients were evaluated based on clinical outcome scores (Lysholm score, International Knee Documentation Committee score, Knee injury and Osteoarthritis Outcome Score [KOOS], and visual analog scale for pain), magnetic resonance imaging findings, and rates of treatment failure at last follow-up. RESULTS: The MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) score in the CCP-ACI group was significantly higher than that in the microfracture group at 5 years (62.3 vs 26.7, respectively; P < .0001). The Lysholm score and KOOS score in the CCP-ACI group were significantly higher than those in the microfracture group at 5 years (84.5 vs 64.9, respectively, and 390.9 vs 303.0, respectively; P = .023 and P = .017, respectively). There was 1 case of treatment failure that occurred in the microfracture group. CONCLUSION: The present randomized controlled trial indicated that the results of both procedures clinically and statistically significantly improved at 1 and 5 years' follow-up in treating cartilage defects, but the results of CCP-ACI were superior to those of microfracture. Magnetic resonance imaging conducted at 1 year and 5 years after CCP-ACI revealed statistically significant superior structural integration with native cartilage tissue compared with microfracture. REGISTRATION: NCT03545269 (ClinicalTrials.gov).

Parathyroid hormone and trabectedin have differing effects on macrophages and stress fracture repair.

Stress fractures occur as a result of repeated mechanical stress on bone and are commonly found in the load-bearing lower extremities. Macrophages are key players in the immune system and play an important role in bone remodeling and fracture healing. However, the role of macrophages in stress fractures has not been adequately addressed. We hypothesize that macrophage infiltration into a stress fracture callus site promotes bone healing. To test this, a unilateral stress fracture induction model was employed in which the murine ulna of four-month-old, C57BL/6 J male mice was repeatedly loaded with a pre-determined force until the bone was displaced a distance below the threshold for complete fracture. Mice were treated daily with parathyroid hormone (PTH, 50 µg/kg/day) starting two days before injury and continued until 24 h before euthanasia either four or six days after injury, or treated with trabectedin (0.15 mg/kg) on the day of stress fracture and euthanized three or seven days after injury. These treatments were used due to their established effects on macrophages. While macrophages have been implicated in the anabolic effects of PTH, trabectedin, an FDA approved chemotherapeutic, compromises macrophage function and reduces bone mass. At three- and four-days post injury, callus macrophage numbers were analyzed histologically. There was a significant increase in macrophages with PTH treatment compared to vehicle in the callus site. By one week of healing, treatments differentially affected the bony callus as analyzed by microcomputed tomography. PTH enhanced callus bone volume. Conversely, callus bone volume was decreased with trabectedin treatment. Interestingly, concurrent treatment with PTH and trabectedin rescued the reduction observed in the callus with trabectedin treatment alone. This study reports on the key involvement of macrophages during stress fracture healing. Given these observed outcomes on macrophage physiology and bone healing, these findings may be important for patients actively receiving either of these FDA-approved therapeutics.

Microfracture of Acetabular Chondral Lesions Is Not Superior to Other Cartilage Repair Techniques in Patients With Femoroacetabular Impingement Syndrome: A Systematic Review.

PURPOSE: To perform a systematic review to compare clinical outcomes of hip arthroscopy patients undergoing microfracture (MFx) versus other cartilage repair procedures for chondral lesions of the acetabulum. METHODS: A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines by searching PubMed, the Cochrane Library, and Embase to identify comparative studies that directly compared outcomes between MFx and other cartilage repair procedures for full-thickness chondral lesions of the acetabulum identified during hip arthroscopy. The search phrase used was: hip AND arthroscopy AND microfracture. Patients were evaluated based on reoperation rates and patient-reported outcomes. RESULTS: Six studies (all Level III evidence) met inclusion criteria, including a total of 202 patients undergoing microfracture (group A) and 327 patients undergoing another cartilage repair procedure (group B). Mean patient age ranged from 35.0 to 45.0 years. Mean follow-up time ranged from 12.0 to 72.0 months. Significantly better patient-reported outcomes (PROs) were found in patients undergoing treatment with bone marrow aspirate concentrate, microfragmented adipose tissue concentrate, autologous matrix-induced chondrogenesis, and a combination of autologous matrix-induced chondrogenesis and bone marrow aspirate concentrate compared with MFx. No studies found significantly better postoperative PROs in group A. The reoperation rate ranged from 0% to 34.6% in group A and 0% to 15.9% in group B. Three of 5 studies reporting on reoperation rate found a significantly greater reoperation rate in group A, with no difference in the other 2 studies. CONCLUSIONS: The literature on MFx of acetabular chondral lesions is limited and heterogeneous. Based on the available data, MFx alone results in a greater or equivalent reoperation rate and inferior or equivalent PROs compared with other cartilage repair procedures for acetabular chondral lesions in patients with femoroacetabular impingement syndrome. LEVEL OF EVIDENCE: Level III, systematic review of level III studies.

Pelvic insufficiency fractures and pelvic bone metastases after neoadjuvant (chemo)radiotherapy for rectal cancer.

BACKGROUND: Pelvic insufficiency fractures (PIFs) are a late complication of radiotherapy for pelvic malignancies. We evaluated the incidence, radiologic findings, clinical course, and outcome of PIFs in patients treated with neoadjuvant (chemo)radiotherapy ((C)RT) for rectal cancer. MATERIAL AND METHODS: Data of patients diagnosed with rectal cancer from a large teaching hospital treated from 2002 to 2012 were extracted from the Dutch Cancer Registry. All hospital records were reviewed for the diagnosis of PIFs or pelvic bone metastases. An expert radiologist reassessed all imaging procedures of the lower back, abdomen, and pelvis. RESULTS: A total of 513 rectal cancer patients were identified of whom 300 patients (58.5%) were treated with neoadjuvant (C)RT (long- vs. short-course radiotherapy: 91 patients [17.7%] vs. 209 [40.7%], respectively). Twelve PIFs were diagnosed initially according to hospital records and imaging reports of all 513 patients. These 12 patients were treated with neoadjuvant (C)RT. After reassessment of all pelvic imaging procedures done in this patient group (432 patients (84.2%)), 20 additional PIFs were detected in patients treated with neoadjuvant (C)RT, resulting in a 10.7% PIF rate in irradiated patients. One PIF was detected in the group of patients not treated with neoadjuvant (C)RT for rectal cancer. This patient had palliative radiotherapy for prostate cancer and is left out of the analysis. Median follow-up time of 32 PIF patients was 49 months. Median time between start of neoadjuvant (C)RT and diagnosis of PIF was 17 months (IQR 9-28). Overall median survival for patients with PIF was 63.5 months (IQR 44-120). CONCLUSION: PIFs are a relatively common late complication of neoadjuvant (C)RT for rectal cancer but are often missed or misdiagnosed as pelvic bone metastases. The differentiation of PIFs from pelvic bone metastases is important because of a different treatment and disease outcome.

Novel Osteochondral Biotemplate Improves Long-term Cartilage Repair Compared With Microfracture in an Ovine Model.

BACKGROUND: Current cartilage repair therapies do not re-create the complex mechanical interface between cartilage and bone, which is critical for long-term repair durability. New biomaterial designs that include hard tissue-soft tissue interface structures offer promise to improve clinical outcomes. PURPOSE/HYPOTHESIS: The purpose of this study was to evaluate the efficacy and safety of a naturally derived osteochondral biotemplate with a novel contiguous hard tissue-soft tissue interface in an ovine model as a regenerative solution for articular cartilage defects. It was hypothesized that the osteochondral biotemplate would produce structurally superior repair tissue compared with microfracture over a 13-month period. STUDY DESIGN: Controlled laboratory study. METHODS: Osteochondral biotemplates were manufactured from porcine cancellous bone. Skeletally mature sheep (N = 30) were randomly allocated to 3 groups: early healing stage (euthanasia at 4 months), 6-month treatment, and 13-month treatment. In the early healing stage group, an 8 mm-diameter by 5 mm-deep osteochondral defect was created on the medial femoral condyle and treated at the time of iatrogenic injury with an osteochondral biotemplate. The contralateral limb received the same treatment 2 months later. In the 6- and 13-month treatment groups, 1 limb received the same osteochondral procedure as the early healing stage group. In the contralateral limb, an 8 mm-diameter, full-thickness cartilage defect (1-2 mm deep) was created and treated with microfracture. Cartilage repair and integration were quantitatively and qualitatively assessed with gross inspection, histological evaluation, and magnetic resonance imaging (MRI). Wilcoxon signed-rank and McNemar tests were used to compare the treatments. RESULTS: At 6 and 13 months after treatment, the biotemplate was not present histologically. At 13 months, the biotemplate treatment demonstrated statistically higher histological scores than microfracture for integration with surrounding cartilage (biotemplate: 74 ± 31; microfracture: 28 ± 39; P = .03), type 2 collagen (biotemplate: 72 ± 33; microfracture: 40 ± 38; P = .02), total cartilage (biotemplate: 71 ± 9; microfracture: 59 ± 9; P = .01), and total integration (biotemplate: 85 ± 15; microfracture: 66 ± 20; P = .04). The osteochondral biotemplate treatment produced a notable transient nonneutrophilic inflammatory response that appeared to approach resolution at 13 months. MRI results were not statistically different between the 2 treatments. CONCLUSION: Even with the inflammatory response, after 13 months, the osteochondral biotemplate outperformed microfracture in cartilage regeneration and demonstrated superiority in integration between the repair tissue and host tissue as well as integration between the newly formed cartilage and the underlying bone. CLINICAL RELEVANCE: This work has demonstrated the clinical potential of a novel biomaterial template to regenerate the complex mechanical interface between cartilage and the subchondral bone.

Outcomes of arthroscopy of the hip for femoroacetabular impingement based on intraoperative assessment using the Outerbridge classification.

Aims: Hip arthroscopy (HA) has become the treatment of choice for femoroacetabular impingement (FAI). However, less favourable outcomes following arthroscopic surgery are expected in patients with severe chondral lesions. The aim of this study was to assess the outcomes of HA in patients with FAI and associated chondral lesions, classified according to the Outerbridge system. Methods: A systematic search was performed on four databases. Studies which involved HA as the primary management of FAI and reported on chondral lesions as classified according to the Outerbridge classification were included. The study was registered on PROSPERO. Demographic data, patient-reported outcome measures (PROMs), complications, and rates of conversion to total hip arthroplasty (THA) were collected. Results: A total of 24 studies were included with a total of 3,198 patients (3,233 hips). Patients had significantly less improvement in PROMs if they had Outerbridge grade III and IV lesions (p = 0.012). Compared with microfracture, autologous matrix-induced chondrogenesis (AMIC) resulted in significantly reduced rates of conversion to THA (p = 0.042) and of revision arthroscopy (p = 0.038). Chondral repair procedures in these patients also did not significantly reduce the rates of conversion to THA (p = 0.931), or of revision arthroscopy (p = 0.218). However, compared with microfracture, AMIC significantly reduced the rates of conversion to THA (p = 0.001) and of revision arthroscopy (p = 0.011) in these patients. Those with Outerbridge grade III and IV lesions also had significantly increased rates of conversion to THA (p = 0.029) and of revision arthroscopy (p = 0.023) if they had associated lesions of the acetabulum and femoral head. Those who underwent labral debridement had a significantly increased rate of conversion to THA compared with those who underwent labral repair (p = 0.015). Conclusion: There is universal improvement in PROMs following HA in patients with FAI and associated chondral lesions. However, those with Outerbridge grade III and IV lesions had significantly less improvement in PROMs and a significantly increased rate of conversion to THA than those with Outerbridge grade I and II. This suggests that the outcome of HA in patients with FAI and severe articular cartilage damage may not be favourable.

The Subchondral Bone Condition During Microfracture Affects the Repair of the Osteochondral Unit in the Cartilage Defect in the Rat Model.

BACKGROUND: Microfracture (MF) is frequently performed as a first-line treatment for articular cartilage defects. Although good clinical outcomes are often obtained in the short term, poor clinical outcomes sometimes occur because of subchondral bone deterioration. The condition of the subchondral bone treated with MF may affect the repair of the osteochondral unit. PURPOSE: To analyze histological findings of the osteochondral unit after performing MF on subchondral bone in different states-normal, absorption, and sclerosis-in a rat model. STUDY DESIGN: Controlled laboratory study. METHODS: Full-thickness cartilage defects (5.0 × 3.0 mm) were created in the weightbearing area of the medial femoral condyle in both knees of 47 Sprague-Dawley rats. Five MF holes were created within the cartilage defect using a 0.55-mm needle to a depth of 1 mm at 0 weeks (normal group), 2 weeks (absorption group), and 4 weeks (sclerosis group) after the cartilage defect was created. In the left knee, MF holes were filled with ß-tricalcium phosphate (ß-TCP). At 2 and 4 weeks after MF, knee joints were harvested and histologically analyzed. RESULTS: MF holes were enlarged at 2 weeks and further enlarged at 4 weeks in all groups. In the absorption group, osteoclast accumulation around the MF holes and cyst formation were observed. The trabecular bone surrounding the MF holes was thickened in the sclerosis group. The diameter of the MF hole was largest in the absorption group at 2 and 4 weeks after MF compared with the other groups. No subchondral bone cysts were observed after ß-TCP implantation. Pineda scores in all groups were significantly better with ß-TCP implantation than without ß-TCP implantation at 2 and 4 weeks. CONCLUSION: MF for subchondral bone with bone absorption induced enlargement of the MF holes, cyst formation, and delay of cartilage defect coverage. Implantation of ß-TCP into the MF holes enhanced remodeling of the MF holes and improved repair of the osteochondral unit compared with MF only. Therefore, the condition of the subchondral bone treated with MF affects repair of the osteochondral unit in a cartilage defect.

Time to reconsider post arthroscopic osteonecrosis of the knee: a systematic review.

The etiology of post-arthroscopic osteonecrosis of the knee (PAONK) is still unknown. The aims of this systematic review were to analyze the main characteristics of patients who developed osteonecrosis after arthroscopy. We considered for inclusion in the review case reports, case series, retrospective and prospective clinical trial, that involved patients who developed osteonecrosis of the knee within 1 year of arthroscopy for meniscal lesion or anterior cruciate ligament rupture with or without chondropathy. In all cases, there was a pre-operative magnetic resonance imaging that excluded the presence of osteonecrosis. We used the MINORS criteria to estimate the risk of bias. A total of 13 studies that involved 125 patients were included in the review. Only 14 out of 55 patients performed the pre-operative MRI after the "window period", which we considered 6 weeks between the onset of symptoms and positive MRI findings. A diagnosis of PAONK was made for 55 patients within 1 year of surgery. Of these, 29% was treated conservatively, while 71% repeated surgery. Osteonecrosis after knee arthroscopy is a reality and surgeon shouldn't underestimate the persistence or re-emergence of symptoms after arthroscopy. It may be due to subchondral insufficiency fractures in osteopenic bone, without evidence of necrosis. However, there are not elements enough to differentiate clinical and radiological characteristics of PAONK from SPONK. Terminology should be simplified, distinguishing subchondral insufficiency fractures of the knee as a precursor of primary osteonecrosis of the knee.

Editorial Commentary: Microfracture Remains a Foundational Tool for Cartilage Restoration During Hip-Preservation Procedures: Defying the Odds.

A comprehensive approach to arthroscopic hip preservation in patients whose pathology includes cartilage defects may include microfracture; microfracture has been shown to have long-lasting positive effects in most patients treated for femoroacetabular impingement plus full-thickness chondral pathology. Although modern cartilage treatment alternatives such as autologous chondrocyte implantation, autologous matrix-induced chondrogenesis scaffolds, allograft or autograft particulate cartilage graft, and others have been described for the treatment of high-degree cartilage acetabular lesions, microfracture remains a foundational tool in cartilage restoration procedures. That said, when determining outcome, comorbidity must be considered, and, moreover, it is difficult to determine whether outcomes are only attributable to the microfracture versus concomitant procedures or changes in postoperative activity of operated patients.

Lumbar endplate microfracture injury induces Modic-like changes, intervertebral disc degeneration and spinal cord sensitization - an in vivo rat model.

BACKGROUND CONTEXT: Endplate (EP) injury plays critical roles in painful IVD degeneration since Modic changes (MCs) are highly associated with pain. Models of EP microfracture that progress to painful conditions are needed to better understand pathophysiological mechanisms and screen therapeutics. PURPOSE: Establish in vivo rat lumbar EP microfracture model and assess crosstalk between IVD, vertebra and spinal cord. STUDY DESIGN/SETTING: In vivo rat EP microfracture injury model with characterization of IVD degeneration, vertebral remodeling, spinal cord substance P (SubP), and pain-related behaviors. METHODS: EP-injury was induced in 5 month-old male Sprague-Dawley rats L4-5 and L5-6 IVDs by puncturing through the cephalad vertebral body and EP into the NP of the IVDs followed by intradiscal injections of TNFα (n=7) or PBS (n=6), compared with Sham (surgery without EP-injury, n=6). The EP-injury model was assessed for IVD height, histological degeneration, pain-like behaviors (hindpaw von Frey and forepaw grip test), lumbar spine MRI and µCT, and spinal cord SubP. RESULTS: Surgically-induced EP microfracture with PBS and TNFα injection induced IVD degeneration with decreased IVD height and MRI T2 signal, vertebral remodeling, and secondary damage to cartilage EP adjacent to the injury. Both EP injury groups showed MC-like changes around defects with hypointensity on T1-weighted and hyperintensity on T2-weighted MRI, suggestive of MC type 1. EP injuries caused significantly decreased paw withdrawal threshold, reduced axial grip, and increased spinal cord SubP, suggesting axial spinal discomfort and mechanical hypersensitivity and with spinal cord sensitization. CONCLUSIONS: Surgically-induced EP microfracture can cause crosstalk between IVD, vertebra, and spinal cord with chronic pain-like conditions. CLINICAL SIGNIFICANCE: This rat EP microfracture model was validated to induce broad spinal degenerative changes that may be useful to improve understanding of MC-like changes and for therapeutic screening.

Effect of Bone Morphogenetic Protein-2 Combined With Microfracture for Osteochondral Defect of the Talus in a Rabbit Model.

BACKGROUND: Osteochondral defects of the talus can be effectively treated using microfracture, which is technically safe, accessible, and affordable. However, fibrous tissue and fibrocartilage comprise the majority of tissue repairs resulting from these procedures. These tissue types lack the mechanical characteristics of native hyaline cartilage and might significantly contribute to the decline in long-term outcomes. Recombinant human-bone morphogenetic protein-2 (rhBMP-2) has been shown to promote matrix synthesis and increase cartilage formation, thus enhancing chondrogenesis in vitro. PURPOSE: This study aimed to evaluate the treatment ability of combining rhBMP-2 with microfracture in rabbit talus osteochondral defect. STUDY DESIGN: Controlled laboratory study. METHODS: A full-thickness chondral defect (3 × 3 × 2 mm) was constructed in the center talar dome of 24 New Zealand White male rabbits, which were then divided into 4 groups of 6. Each group received the appropriate treatment: group 1 (control; no treatment of defect), group 2 (microfracture treatment), group 3 (rhBMP-2/hydroxyapatite treatment), and group 4 (microfracture combined with rhBMP-2/hydroxyapatite treatment). Animals were sacrificed at 2, 4, and 6 weeks postoperatively. The International Cartilage Regeneration & Joint Preservation Society macroscopic score, which considers the degree of defect repair, the integration to the border zone, and the macroscopic appearance, was used to assess the repaired tissue's macroscopic appearance. Subchondral bone regeneration in defects was analyzed using micro-computed tomography, and the histological findings were graded using a modified version of the Wakitani scoring system for osteochondral repair. RESULTS: At 2, 4, and 6 weeks, micro-computed tomography analysis revealed that groups 3 and 4 exhibited subchondral bone healing that was more significantly improved compared with groups 1. No sample showed excessive bone growth from the subchondral bone area. According to macroscopic and histological results, group 4 showed higher-quality cartilage and more accelerated cartilage regeneration than the other groups over time. CONCLUSION: These findings show that osteochondral defect repair in a rabbit talus model could be effectively accelerated and improved by combining rhBMP-2 with microfracture. CLINICAL RELEVANCE: Using rhBMP-2 in combination with microfracture may enhance the repair of talar osteochondral lesions.

Tissue Regrowth and Its Vascularization Through Bone Marrow Stimulation: Microfracture at the Acetabular Rim for Irreparable Labral Tear in a Porcine Model.

BACKGROUND: The treatment of irreparable acetabular labral tear remains a great challenge. Whether fibrocartilage-like tissue can regrow with sufficient volume to fill the labral defect area through bone marrow stimulation remains unknown. PURPOSE: To characterize the healing process and vascularization course of the regrown tissue after microfracture at the acetabular rim for irreparable labral tears in a porcine model. STUDY DESIGN: Descriptive laboratory study. METHODS: Twelve pigs randomly underwent unilateral microfracture at the acetabular rim after the resection of a 10 mm-long section of labrum from 10 to 1 o'clock. Pigs were randomly sacrificed at 6 and 12 weeks postoperatively. The regrown tissues were harvested for macroscopic evaluation and histologic assessment. The regrown tissue was zoned into 2 halves to observe the vascular distribution: the capsular half (zone I) and the articular half (zone II). Each zone was divided into 2 parts: the peripheral part (IA and IIA) and the part attached to the acetabulum (IB and IIB). RESULTS: At 6 weeks, all regrown tissue was hypotrophic with <50% filling of the labral defect. Fibrochondrocytes were concentrated at the interface between the acetabulum and the regrown tissue. The vascularization was equal among each part within the regrown tissue. As compared with regrown tissue at 12 weeks, proteoglycan and collagen type 1 and 2 were more evident within the regrown tissue at 6 weeks. At 12 weeks, tissue disintegration occurred in all regrown tissue with <25% filling of the labral defect area. The vascular structure could barely be observed, with few fibrochondrocytes found at the area adjacent to the acetabulum. CONCLUSION: Fibrocartilage-like tissue did regrow with well-distributed vascular ingrowth of each part of the regrown tissue through bone marrow stimulation at the early stage. However, insufficient volume of the regrown tissue led to loss of the hip suction seal and subsequent tissue disintegration. CLINICAL RELEVANCE: Microfracture at the rim of the acetabulum alone could not restore the morphology and function of the acetabular labrum. Nonetheless, microfracture at the acetabular rim might be a viable adjunct to labral reconstruction, as the well-distributed vascularization through bone marrow stimulation might overcome the obstacle of poor vascular ingrowth of the articular half of the autograft.

Aragonite-Based Scaffold Versus Microfracture and Debridement for the Treatment of Knee Chondral and Osteochondral Lesions: Results of a Multicenter Randomized Controlled Trial.

BACKGROUND: Lesions of the articular cartilage, with or without involvement of the subchondral bone, are a common cause of pain and dysfunction in the knee. Although several treatment options have been developed, the majority of previous clinical trials examined patients with isolated or focal midsized defects, which rarely represent the condition found in the general population. Rather, cartilage lesions are often associated with the presence of mild to moderate osteoarthritic changes. PURPOSE: The present multicenter randomized controlled trial compared the clinical and radiographic outcomes of an aragonite-based osteochondral implant with a control group (arthroscopic debridement/microfractures) in patients affected by joint surface lesions of the knee, including those with concurrent mild to moderate osteoarthritis. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: A total of 251 patients were enrolled in 26 medical centers according to the following criteria: age 21 to 75 years, up to 3 cartilage defects of International Cartilage Regeneration & Joint Preservation Society grade 3a or above located on the femoral condyles and/or trochlea, total treatable area from 1 to 7 cm2, bony defect depth ≤8 mm, and knee osteoarthritis grade 0 to 3 according to Kellgren-Lawrence score. Patients were randomized to the aragonite-based implant or debridement/microfracture control arm in a 2:1 ratio. Evaluation was performed at 6, 12, 18, and 24 months based on overall Knee injury and Osteoarthritis Outcome Score (KOOS) as the primary endpoint, and the KOOS subscales (Pain, Quality of Life, Activities of Daily Living), percentage of responders, and International Knee Documentation Committee (IKDC) subjective score as the secondary endpoints. Patients also underwent magnetic resonance imaging evaluation at 12 and 24 months to assess defect fill grade. Failures (ie, need for any secondary treatment) and adverse events were also recorded. RESULTS: The implant group showed a statistically superior outcome in the primary endpoint and all secondary endpoints at each follow-up. The magnitude of improvement in the implant group was twice as large as that in the control group in terms of mean KOOS improvement at 2 years. Responder rate (defined as at least a 30-point improvement in overall KOOS) was 77.8% in the implant group as opposed to 33.6% in the control (P < .0001). Statistically superior results were seen in the IKDC score as well. At 24 months, 88.5% of the implanted group had at least 75% defect fill on magnetic resonance imaging as compared with 30.9% of controls (P < .0001). The failure rate was 7.2% for the implant group versus 21.4% for control. CONCLUSION: This aragonite-based scaffold was safe and effective in the treatment of chondral and osteochondral lesions in the knee, including patients with mild to moderate osteoarthritis, and provided superior outcomes as compared with the control group. REGISTRATION: NCT03299959 (ClinicalTrials.gov identifier).

Pathological fracture of a solitary bone cyst in the calcaneus: a case series and literature review.

INTRODUCTION: Solitary bone cysts in the calcaneus (calcaneal bone cysts) are often asymptomatic. Pathological fractures are rare, and few reports are available concerning its risk assessment. Therefore, the indication for operative interventions remains debatable, and further discussion on the treatment of symptomatic cysts and pathological fractures in calcaneal bone cysts is necessary. MATERIALS AND METHODS: Clinical data of 21 patients with calcaneal bone cysts (16 men and five women) was retrospectively reviewed. The average age was 13.3 (range, 7-23) years. Clinical data, such as concerning symptoms, radiological findings, pathological findings and outcomes, were investigated, and the pathogenesis of symptomatic cysts was studied. RESULTS: Thirteen cysts were symptomatic, and eight were incidentally discovered. Computed tomography revealed no fracture in 12 cases, microfracture in eight and complete fracture in one. The areas under the curves of the receiver operating characteristic curves calculated to establish an association between cyst size and symptoms and cyst size and pathological fractures (microfracture and complete fracture) were 0.78 and 0.71, respectively. Symptomatic cysts and pathological fractures were associated with the cyst ratio (cyst size/calcaneus ≥ 0.20). On magnetic resonance imaging (MRI), fluid levels were observed in 11 of 21 (52%) patients. At the time of surgery, blood from the haemorrhage was aspirated from 15 of 21 (71%) cysts. CONCLUSIONS: Orthopaedic surgeons should be aware that the cyst ratio is associated with clinical symptoms and pathological fractures. MRI and gross findings revealed haemorrhage in the cystic fluid. In calcaneal bone cysts, repeated microfractures and spontaneous healing might occur.

The Effect of Injection of Secretome of Umbilical Cord Mesenchymal Stem Cells in Articular Cartilage Repair in Sheep Model.

INTRODUCTION: Articular cartilage is an avascular, aneural, and lymphatic tissue with limited capacity to regenerate. Numerous techniques have been employed to repair or regenerate; however, the success rate varies. In fact, most of them result in the formation of fibrocartilage, not hyaline cartilage. The future of treating cartilage defects lies in providing biological solutions through cartilage regeneration. Mesenchymal stem cells (MSCs) represent a promising therapy for cartilage regeneration. These cells secrete factors that enhance cartilage repair. This study studied the effects of intra-articular injection of human umbilical cord MSC (hUC-MSC) secretome on cartilage damage in a sheep model. METHODS: Standardized rectangular (5x5 mm) full-thickness chondral defects were created in the lateral femoral condyle of 15 adult sheep and debrided down to the subchondral bone plate. Three treatment groups were tested: 4 microfracture perforations using 1.0mm diameter awls (group 1), intra-articular injection of hUC-MSC secretome (group 2), and a combination of microfracture and intra-articular injection of hUC-MSC secretome (group 3). The osteochondral repair was assessed at 6 months using an established macroscopic and histological analyses. RESULTS: Macroscopically, combined therapy application shows significant cartilage repair improvement compared to microfracture alone (p=0.004). Microscopically, the application of combined therapy shows significant improvement of cartilage repair compared to secretome injection alone (p=0.031). CONCLUSION: Microfracture combined with injection of hUCB-MSCs secretome could be an effective alternative for repairing articular cartilage defects in vivo.

Sustained superiority in KOOS subscores after matrix-associated chondrocyte implantation using spheroids compared to microfracture.

PURPOSE: To evaluate the safety and efficacy of matrix-associated autologous chondrocyte implantation (ACI) using spheroids in comparison to arthroscopic microfracture for the treatment of symptomatic cartilage defects of the knee. METHODS: In a prospective multicenter-controlled trial, patients aged between 18 and 50 years, with single symptomatic focal cartilage defects between 1 and 4 cm2 (mean 2.6 ± 0.8, median 2.75, range 1.44-5.00) in the knee were randomized to treatment with ACI with spheroids (n = 52) or microfracture (n = 50). Primary clinical outcome was assessed by the Knee Injury and Osteoarthritis Outcome Score (KOOS). Analyses were performed in a defined hierarchical manner where outcomes of ACI were first compared to baseline values followed by a comparison to the microfracture group with repeated-measures ANCOVA with a non-inferiority approach. Subgroup analyses were performed to investigate the influence of age and defect size on the overall KOOS. Secondary clinical outcomes were the magnetic resonance observation of cartilage repair tissue (MOCART), modified Lysholm score and International Knee Documentation Committee (IKDC) examination form. Safety data focused on adverse events. Here the 5 years results are presented at which there were 33 observed cases in the ACI group and 30 in the microfracture group. RESULTS: The overall KOOS and its five subscores were significantly improved compared to baseline for both the ACI and microfracture group. Non-inferiority of ACI to microfracture was confirmed for the overall KOOS and the subscores, while for the subscores activities of daily living, quality of life and sports and recreation of the threshold for superiority was passed. In the ACI group, a notably more rapid initial improvement of the KOOS was found at three months for the older age group compared to the younger age group and the microfracture group. No other differences were found based on age or defect size. In addition, clinical improvement was found for the MOCART, modified Lysholm and IKDC examination form both the ACI and microfracture group. No safety concern related to either treatment was observed. CONCLUSION: This study confirms the safety and efficacy of matrix-associated ACI with spheroids at a mid to long-term follow-up. Non-inferiority of ACI to microfracture was confirmed for the overall KOOS and all subscores, while superiority was reached for the subscores activities of daily living, quality of life and sports and recreation in the ACI group. This underlines the importance of ACI for the young and active patients. LEVEL OF EVIDENCE: I.

Editorial Commentary: Hip Chondral Defect Treatment Requires Cells, Signal, and Scaffold: The Chef Is In the Kitchen.

Hip cartilage defects are most common in the anterosuperior acetabulum and central femoral head, and, while chondrolabral delamination can be treated satisfactorily with repair, articular defects are variably treated, with overall heterogenous outcomes. Hip chondral lesions have consistently predicted arthroplasty following arthroscopy. Microfracture in isolation has waned in attractiveness and use in both the hip and knee, given similar results to debridement alone and the addition of intraoperative time and potential postoperative complications such as subchondral fracture and intralesional osteophyte formation. We recommend debridement for small-to-moderate (<6 cm2) full-thickness chondral defects. However, the poor prognosis for grade III to IV defects highlights the need for novel treatment options. One such approach is "biologically enhanced" microfracture in conjunction with (autologous) platelet-rich plasma, micronized allograft extracellular cartilage matrix, and fibrin glue. This certainly satisfies our biologic mantra of "cells, signal, and scaffold," providing the influx of marrow-based stromal cells, platelet-rich plasma, and matrix-associated growth factors, and fibrin-sealed defect fill.