Cartilage regeneration and long term survival in medial OA knee patients treated with HTO and OATS.

Background: Osteoarthritis (OA) of the knee, in most instances primarily, affects medial compartment of knee. Combining Osteochondral Autologous Transfer System (OATS) with Medial Open-Wedge High Tibial Osteotomy (MOWHTO) may represent an integrated approach to sustaining long-term knee functionality in OA patients. Materials and methods: From 2009 to 2016, combined OATS and MOWHTO was performed in 66 knees of 63 patients with medial compartment knee OA. Cartilage regeneration was assessed by 2nd look arthroscopy and Knee function was assessed by knee society scoring (KSS) pre-operatively and post-operatively. The survival rate of MOWHTO plus OATS was assessed. Failure is characterized by the need to convert into total knee replacement. Results: The KSS knee score (from 48.3 to 90.4) and function score (from 42.6 to 88.7) showed a statistically significant improvement (p-value of <0.0001) at a mean follow-up period of 9.49 years. Second look arthroscopy done at the time of implant removal showed 100 % cartilage regeneration with even hyaline cartilage regeneration in 49 out of 57 knees assessed and partial regeneration in 8 knees. The Kaplan Meier survivorship analysis was 96.7 % at the mean 9.49 years after surgery. Only 2 patients needed TKA conversion in follow-up. Conclusion: Combining OATs and valgus MOWHTO provides good option to successfully manage patients of OA and varus malalignment. This resulted in significant improvement in knee function, lowering pain intensity, good cartilage regeneration, and a high survivorship rate for 10 years postoperatively.

An Acellular, Self-Healed Trilayer Cryogel for Osteochondral Regeneration in Rabbits.

Osteochondral regeneration remains formidable challenges despite significant advances in microsurgery. Herein, an acellular trilayer cryogel (TC) with injectability, tunable pore sizes (80-200 µm), and appropriate compressive modulus (10.8 kPa) is manufactured from self-healable hydrogel under different gelling times through Schiff reaction between chitosan and difunctionalized polyurethane (DFPU). Bioactive molecules (Y27632 and dexamethasone) are respectively loaded in the top and bottom layers to form the Y27632/dexamethasone-loaded trilayer cryogel (Y/DEX-TC). Mesenchymal stem cells (MSCs) seeded in Y/DEX-TC proliferated ≈350% in vitro and underwent chondrogenesis or osteogenesis in response to the respective release of Y or DEX in 14 days. Acupuncture is administered to animals in an attempt to modulate the innate regulatory system and mobilize endogenous MSCs for osteochondral defect regeneration. In vivo rabbit experiments using Y/DEX-TC combined with acupuncture successfully regulate SDF-1 and TGF-ß1 levels, which possibly cause MSC migration toward Y/DEX-TC. The synergistic effect of cryogel and acupuncture on immunomodulation is verified with a ≈7.3-fold enhancement of the M2-/M1-macrophage population ratio by treatment of Y/DEX-TC combining acupuncture, significantly greater than ≈1.5-fold increase by acupuncture or ≈2.2-fold increase by Y/DEX-TC alone. This novel strategy using acellular drug-loaded cryogel and accessible acupuncture shows promise in treating osteochondral defects of joint damage.

The severity of preoperative bone marrow oedema negatively influences short-term clinical outcomes following arthroscopic bone marrow stimulation for osteochondral lesions of the talus.

PURPOSE: The purpose of this study was to study the effects of the severity of preoperative bone marrow oedema (BME) on the postoperative short-term outcomes following bone marrow stimulation (BMS) for osteochondral lesions of the talus (OLTs) and to propose a new metric that combines volume and signal density to evaluate BME. METHODS: Sixty-five patients with symptomatic OLTs (<100 mm2) and preoperative BME, who received BMS in our institution from April 2017 to July 2021 with follow-ups of 3, 6 and 12 months, were analysed retrospectively. The area, volume and signal value of the BME were collected on preoperative magnetic resonance imaging. The enroled patients were divided into two groups according to the BME index (BMEI), which was defined as the product of oedema relative signal intensity and the relation of oedema volume to total talar volume. Visual analogue scale, American Orthopedic Foot and Ankle Society (AOFAS), Tegner, Foot and Ankle Ability Measure (FAAM)-activities of daily living (ADL) and Sports scores were assessed before surgery and at each follow-up. The relationship between the scores and the volume, relative signal intensity and BMEI was explored. RESULTS: Sixty-five patients with preoperative BME were divided into the mild (n = 33) and severe (n = 32) groups based on the BMEI. A significant difference was found for each score with the general linear model for repeated measures through all follow-up time points (p < 0.001). For the preoperative and 12-month postoperative changes of the enroled patients, 53 patients (81.5%) exceeded the minimal clinically important difference of AOFAS and 26 (40.0%) exceeded that of FAAM-sports in this study. The mild group showed significantly more improvement in AOFAS scores at 12 months (89.6 ± 7.0 vs. 86.2 ± 6.2) and FAAM-ADL scores at 6 months (83.6 ± 7.6 vs. 79.7 ± 7.7) and 12 months (88.5 ± 8.5 vs. 84.4 ± 7.7) than the severe group (p < 0.05). No significant difference of all the scores between the groups was found at 3 months. No significant correlation was found in each group between BMEI and clinical outcomes. CONCLUSION: The severity of the preoperative BME negatively affected short-term clinical outcomes following arthroscopic BMS for OLTs. Worse clinical outcomes were shown at postoperative 6 and 12 months in patients with a high preoperative BMEI, which could be a favourable parameter for assessing the severity of BME and assist in developing personalised rehabilitation plans and determining the approach and timing of surgery. LEVEL OF EVIDENCE: Level III.

A hypertrophic distal fascicle of the anterior tibiofibular ligament is associated with a high rate of osteochondral lesions of the talus.

PURPOSE: The purpose of this retrospective review was to determine the prevalence of osteochondral lesions (OCLs) of the lateral talar dome in patients with anterior ankle impingement with an associated hypertrophic distal fascicle of the anterior tibio-fibular ligament. METHODS: Retrospective chart review identified 40 patients who underwent anterior ankle arthroscopy for the management of anterior ankle impingement. Clinical outcomes assessed included pre- and postoperative foot and ankle outcome score (FAOS), visual analogue scale (VAS), complications, failures, secondary surgical procedures, return-to-work data and return-to-sport data. RESULTS: Thirty-two patients with a mean follow-up time of 29.3 ± 10.4 months were included. The hypertrophic distal fascicle of the anterior tibio-fibular ligament was hypertrophic in 29 patients (90.6%), with a mean thickness of 2.5 ± 0.4 mm on MRI. There were 22 OCLs of the lateral talar dome (75.9%) with an associated hypertrophic distal fascicle of the anterior tibio-fibular ligament visualized during arthroscopy. The international cartilage repair society gradings of the lesions included 3 (13.6%) grade I lesions, 15 (68.1%) grade II lesions, 3 (13.6%) grade III lesions, and 1 (4.6%) grade IV lesion. There was a statistically significant improvement in mean FAOS and VAS scores from preoperative to postoperative (p < 0.001). No cases of syndesmotic instability were observed following resection of hypertrophic distal fascicle of the anterior tibio-fibular ligament. CONCLUSION: This retrospective case series demonstrated that a hypertrophic distal fascicle of the anterior tibio-fibular ligament was associated with an OCL of the lateral talar dome identified during arthroscopic evaluation. In addition, preoperative MRI demonstrated poor sensitivity for the detection of these OCLs. Heightened awareness is warranted for potential lateral talar dome OCLs in patients presenting with anterolateral ankle impingement with a hypertrophic ATiFLdf identified on preoperative MRI in the absence of an associated OCLs. LEVEL OF EVIDENCE: Level IV, Retrospective case series.

A Comparison of Rib Osteochondral Graft to Medial Femoral Trochlear Osteocartilaginous Graft for the Salvage of the Fragmented Scaphoid Proximal Pole: A Single-Center Experience with Minimum 2-Year Follow-Up.

Purpose Fragmented fractures of the proximal pole of the scaphoid that cannot be internally fixed may be salvaged by four-corner arthrodesis or proximal row carpectomy. Replacement of the proximal scaphoid with costal-osteochondral graft (COG) or the medial femoral trochlea (MFT) graft are two alternative solutions for this clinical presentation. The purpose of this study was to compare the clinical and radiographic results of the COG and the MFT graft with a minimum 2-year follow-up from a single centre. Methods A retrospective study was performed to investigate the outcome of COG and MFT with a minimum 2 year follow up. Demographic data and clinical assessment including wrist range of motion and grip strength measurements and Oxford Knee score were collected. Patients completed the outcome measures of Disabilities of Arm, Shoulder, and Hand (DASH), the Patient-Rated Wrist Evaluation (PRWE), and a ten-point visual analogue score for pain (VAS). Radiological examination was performed on all wrists at follow-up. Results The visual analogue score, DASH and PRWE were similar between the two groups. There was radiographic evidence of arthritis between the radial styloid and distal scaphoid in all patients that underwent COG but no evidence in those that underwent MFT graft reconstruction. There were different complications in each group. Thirty percent of patients that underwent MFT reconstruction had persistent knee pain at follow up. Conclusion Though there are notable differences in the follow-up period, patients undergoing MFT risk developing knee pain, while those undergoing COG risk radiographic progression of wrist arthritis. Level of Evidence III - Comparative study.

Age influences the efficacy of osteochondral autograft transfer: Promising results for patients under 40.

BACKGROUND: Previous research using osteochondral autograft transfer (OAT) has shown poorer outcomes with increasing patient age. The aim of this article is to evaluate a cohort of patients that received an OAT and to correlate their clinical results with their age at procedure. METHODS: Patients that underwent an OAT to treat an osteochondral (OC) lesion with a minimum 24-month follow-up were included. Patients were categorized into two groups based on their age at procedure (<40 years and ≥40 years). Postoperatively, each patient completed the Knee injury and Osteoarthritis Outcome Score (KOOS), International Knee Documentation Committee (IKDC), and Lysholm scales. RESULTS: 51 patients were included (35 < 40 years, 16 ≥ 40 years). Mean follow-up was 4.2 years (2-7). For patients < 40 years, IKDC averaged 80.8 (SD 15.9) versus 71.2 (SD 19.4) in ≥40 years (p = 0.03). For patients <40 years, Lysholm averaged 85.9 (SD 10.8) versus 77.0 (SD 21.6) in ≥40 years (p = 0.02). For patients < 40 years, KOOS averaged 78.3 (SD 11.8) versus 68.9 (SD 18.5) in ≥40 years (p = 0.01). There was a 100% sensibility in identifying all the patients with a poor IKDC and Lysholm from 34 years old (AUC 0.76 and 0.8). CONCLUSIONS: OAT has better outcomes in patients younger than 40 years compared to patients older than 40 years. Based on the prognostic capacity of age, the ideal candidate for an OAT is a patient younger than 34 years old.

Nanoclay Reinforced Integrated Scaffold for Dual-Lineage Regeneration of Cartilage and Subchondral Bone.

Tissue engineering is theoretically considered a promising approach for repairing osteochondral defects. Nevertheless, the insufficient osseous support and integration of the cartilage layer and the subchondral bone frequently lead to the failure of osteochondral repair. Drawing from this, it was proposed that incorporating glycine-modified attapulgite (GATP) into poly(1,8-octanediol-co-citrate) (POC) scaffolds via the one-step chemical cross-linking is proposed to enhance cartilage and subchondral bone defect repair simultaneously. The effects of the GATP incorporation ratio on the physicochemical properties, chondrocyte and MC3T3-E1 behavior, and osteochondral defect repair of the POC scaffold were also evaluated. In vitro studies indicated that the POC/10% GATP scaffold improved cell proliferation and adhesion, maintained cell phenotype, and upregulated chondrogenesis and osteogenesis gene expression. Animal studies suggested that the POC/10% GATP scaffold has significant repair effects on both cartilage and subchondral bone defects. Therefore, the GATP-incorporated scaffold system with dual-lineage bioactivity showed potential application in osteochondral regeneration.

Treatment of osteochondral injuries of the humeral head using fresh osteochondral allograft transplantation.

Background: Large osteochondral lesions of the humeral head can result from locked posterior dislocations, avascular necrosis, and osteochondritis dissecans. Fresh osteochondral allograft (OCA) transplantation is a treatment option for young patients with focal osteochondral defects of the humeral head. The purpose of this case series was to assess graft survivorship, subjective patient-reported outcomes, and satisfaction among 7 patients who underwent OCA transplantation of the humeral head. Methods: We identified 7 patients who underwent humeral head OCA transplantation between 2008 and 2017. A custom questionnaire including the American Shoulder and Elbow Surgeons score, Quick Disabilities of the Arm, Shoulder, and Hand score (QuickDash), Likert satisfaction, and reoperations was mailed to each patient. Clinical failure was defined as further surgery that involved removal of the allograft. Results: Median follow-up duration was 10 years (range, 4.6 to 13.5 years) with a median age of 21.6 years (range, 18.5 to 43.5 years). Most patients (86%) reported improved function and reduced pain. At the final follow-up, 71% of patients reported ongoing problems with their shoulder including pain, stiffness, clicking/grinding, limited range of motion, and instability. Return to recreational activities was high at 86% but 43% expressed limitations with activity due to their shoulder. Overall satisfaction was high at 71% with mean American Shoulder and Elbow Surgeons and QuickDASH scores at 62.4 and 29.2, respectively. Reoperation after OCA occurred in 1 patient (14%). Conclusion: Among this case series of 7 patients who underwent OCA transplantation of the humeral head, patient satisfaction was high at 10-year follow-up and most returned to recreational activity although most also had persistent shoulder symptoms.

Outcomes Following the Use of Extracellular Matrix Cartilage Allograft for the Management of Osteochondral Lesions of the Talus: A Systematic Review.

Extracellular matrix cartilage allograft (EMCA) is a novel biological strategy utilized to augment the repair of osteochondral lesions of the talus (OLTs). However, there is no consensus on the precise role and outcomes following its use in the treatment of OLTs. The purpose of this systematic review was to evaluate the clinical and radiological outcomes following the use of EMCA for the treatment of OLT. During July 2023, the PubMed, Embase, and Cochrane Library databases were systematically reviewed to identify clinical studies examining outcomes following EMCA for the management of OLTs. In total, 162 patients (162 ankles) across five studies received EMCA as part of their surgical procedure at a weighted mean follow-up time of 23.8±4.2 months. Across all five studies, there were improvements in subjective clinical outcomes following the use of EMCA, regardless of the clinical scoring tool utilized. Two studies demonstrated superior postoperative magnetic resonance observation of cartilage repair tissue (MOCART) scores in the EMCA cohort compared to the bone marrow stimulation (BMS) cohort alone. In the EMCA-BMS cohort, there were seven complications (9%) and three failures (4.1%). In the autologous osteochondral transplantation (AOT) cohort, there were 10 complications (38.5%), zero failures, and six secondary surgical procedures (23.1%). In the EMCA alone cohort, there were zero complications and three failures (4.3%), all of which underwent an unspecified revision procedure. This current systematic review demonstrated improvements in both clinical and radiological outcomes following the use of EMCA for the treatment of OLTs. Further prospective comparative studies with longer follow-up times are warranted to determine the precise role of EMCA in the management of OLT.

Effects of Preoperative Abnormality of Posterior Tibial Tendon on the Surgical Outcomes of Medial Osteochondral Lesion of the Talus.

BACKGROUND: Although surgical treatment for osteochondral lesion of the talus (OLT) can obtain good clinical outcomes, the rate of return to sports is variable. It is reported that medial OLT unrelated to trauma has abnormal structures in the medial aspect, which may induce the medial OLT due to the medial instability. The posterior tibial tendon (PTT) plays an important role in the stabilization of the foot, and high mechanical stress may be added to the PTT to compensate for medial instability in medial OLT. We investigated whether abnormal PTT findings on preoperative magnetic resonance imaging (MRI) in patients with OLT affect clinical outcomes after surgery.  Methods: Eighty-one ankles in 74 patients who were treated surgically for OLT were included in this study (41 men and 33 women; mean age, 26.0 years). Abnormalities of the PTT were evaluated using preoperative MRI. The Japanese Society for Surgery of the Foot (JSSF) scale, arch height, and ankle activity score (AAS) on standing plain radiogram were compared between patients with and those without preoperative PTT abnormalities. RESULTS: Twenty-five ankles (30.9%) had PTT abnormalities on preoperative MRI. All patients with preoperative PTT abnormalities were medial OLT. There were no significant differences in the preoperative JSSF scale in the procedures for OLT. The postoperative JSSF scale and arch height were significantly lower in patients with preoperative PTT abnormalities than those without them. AAS in patients with preoperative abnormalities significantly decreased at the final follow-up.  Conclusion: PTT abnormalities on preoperative MRI may affect clinical outcomes even in preoperative asymptomatic patients in the medial OLT unrelated to trauma.

Chondroitin Sulfate and Hyaluronic Acid-Based PolyHIPE Scaffolds for Improved Osteogenesis and Chondrogenesis In Vitro.

Osteochondral damage, affecting the articular cartilage and the underlying subchondral bone, presents significant challenges in clinical treatment. Such defects, commonly seen in knee and ankle joints, vary from small localized lesions to larger defects. Current medical therapies encounter several challenges, such as donor shortages, drug side effects, high costs, and rejection problems, often resulting in only temporary relief. Highly porous emulsion-templated polymers (polyHIPEs) offer numerous potential benefits in the fabrication of scaffolds for tissue engineering and regenerative medicine. Polymeric scaffolds synthesized using a high internal phase emulsion (HIPE) technique, called PolyHIPEs, involve polymerizing a continuous phase surrounding a dispersed internal phase to form a solid, foam-like structure. A dense, porous design encourages cell ingrowth, nutrient delivery, and waste disposal from the scaffold, mimicking the cells' natural microenvironment. This study used hydroxyethyl methacrylate (HEMA) and acrylamide (AAM) polyHIPE scaffolds combined with extracellular matrix (ECM) components of the tissue, such as methacrylated hyaluronic acid (MHA) and methacrylated chondroitin sulfate (MCS), to prepare polyHIPE scaffolds. The mouse preosteoblast MC3T3-E1 cells and primary rat chondrocytes (harvested from male Wistar rats) were seeded on the scaffolds and cultured for 21 days to assess the osteogenesis and chondrogenesis in vitro. When compared to the AAM-MHA and AAM-MCS groups at day 21, scaffold groups HEMA-MHA and HEMA-MCS showed a significant rise in alkaline phosphatase (ALP) and calcium content. Chondrogenic markers such as glycosaminoglycan (GAG) and hydroxyproline were also assessed over a 21-day time point. On day 21, it was found that GAG and hydroxyproline production were considerably higher in the HEMA-MHA and HEMA-MCS scaffolds than in the AAM-MHA and AAM-MCS scaffolds. The overall studies showed that polyHIPE monolith scaffolds could favor cell adherence, survival ability, proliferation, differentiation, and ECM formation over 21 days. Thus, incorporating ECM components enhanced osteogenesis and chondrogenesis in vitro and can be further used as tissue repair models.

Fresh osteochondral allograft transplantation for knee full-thickness articular cartilage lesions using femoral head of living donors: short-term results.

BACKGROUND: Fresh osteochondral allograft transplantation is a good treatment option of cartilage defects. However, this treatment option is not available in all countries due to limited graft availability and tissue banks limitations. The purpose of this study is to assess the short term functional and imaging outcomes of fresh osteochondral allograft transplantation in the knee using the femoral head of living donors. HYPOTHESIS: Fresh osteochondral allografts from the femoral heads of living donors is a valid graft source for management of distal Femur cartilage defects. This technique can improve functional knee scores with good radiological outcomes. STUDY DESIGN: Prospective case series. METHODS: Fifteen patients with full thickness cartilage defects of the distal femur underwent osteochondral allograft transplantation from the femoral heads of living donors. Grafts were transplanted by both shell and multiple dowels techniques. The average follow up duration was 18.3 months (range, 12-25 months). Patients were evaluated by Lysholm and International Knee Documentation Committee (IKDC) scores, radiography and MR imaging using Osteochondral Allograft MRI Scoring System (OCAMRISS). RESULTS: There was a statistically significant improvement (P < 0.001) in both Lysholm and IKDC average scores at 6 months and 12 months postoperative. Postoperative MRI was done at an average 6.8 months (range, 5-11 months) postoperative. The mean total OCAMRISS score was 3.4 (range, 1-7). A second look arthroscopy was done in four patients and showed intact articular cartilage in all three patients. CONCLUSION: Femoral head of living donors is a valid new source for fresh osteochondral allograft transplantation of knee osteochondral lesions. Short term results showed improvement in clinical assessment scores. Follow up imaging showed graft incorporation and good MRI scores.

Bioceramic-mediated chondrocyte hypertrophy promotes calcified cartilage formation for rabbit osteochondral defect repair.

Osteochondral tissue is a highly specialized and complex tissue composed of articular cartilage and subchondral bone that are separated by a calcified cartilage interface. Multilayered or gradient scaffolds, often in conjunction with stem cells and growth factors, have been developed to mimic the respective layers for osteochondral defect repair. In this study, we designed a hyaline cartilage-hypertrophic cartilage bilayer graft (RGD/RGDW) with chondrocytes. Previously, we demonstrated that RGD peptide-modified chondroitin sulfate cryogel (RGD group) is chondro-conductive and capable of hyaline cartilage formation. Here, we incorporated whitlockite (WH), a Mg2+-containing calcium phosphate, into RGD cryogel (RGDW group) to induce chondrocyte hypertrophy and form collagen X-rich hypertrophic cartilage. This is the first study to use WH to produce hypertrophic cartilage. Chondrocytes-laden RGDW cryogel exhibited significantly upregulated expression of hypertrophy markers in vitro and formed ectopic hypertrophic cartilage in vivo, which mineralized into calcified cartilage in bone microenvironment. Subsequently, RGD cryogel and RGDW cryogel were combined into bilayer (RGD/RGDW group) and implanted into rabbit osteochondral defect, where RGD layer supports hyaline cartilage regeneration and bioceramic-containing RGDW layer promotes calcified cartilage formation. While the RGD group (monolayer) formed hyaline-like neotissue that extends into the subchondral bone, the RGD/RGDW group (bilayer) regenerated hyaline cartilage tissue confined to its respective layer and promoted osseointegration for integrative defect repair.

Early signs of osteoarthritis in differing rat osteochondral defects.

Preclinical models of osteochondral defects (OCDs) are fundamental test beds to evaluate treatment modalities before clinical translation. To increase the rigor and reproducibility of translational science for a robust "go or no-go," we evaluated disease progression and pain phenotypes within the whole joint for two OCD rat models with same defect size (1.5 x 0.8 mm) placed either in the trochlea or medial condyle of femur. Remarkably, we only found subtle transitory changes to gaits of rats with trochlear defect without any discernible effect to allodynia. At 8-weeks post-surgery, anatomical evaluations of joint showed early signs of osteoarthritis with EPIC-microCT. For the trochlear defect, cartilage attenuation was increased in trochlear, medial, and lateral compartments of the femur. For condylar defect, increased cartilage attenuation was isolated to the medial condyle of the femur. Further, the medial ossicle showed signs of deterioration as indicated with decreased bone mineral density and increased bone surface area to volume ratio. Thus, OCD in a weight-bearing region of the femur gave rise to more advanced osteoarthritis phenotype within a unilateral joint compartment. Subchondral bone remodeling was evident in both models without any indication of closure of the articular cartilage surface. We conclude that rat OCD, placed in the trochlear or condylar region of the femur, leads to differing severity of osteoarthritis progression. As found herein, repair of the defect with fibrous tissue and subchondral bone is insufficient to alleviate onset of osteoarthritis. Future therapies using rat OCD model should address joint osteoarthritis in addition to repair itself.

Outcomes of Osteochondral Allograft Transplantation for Femoral Head Cartilage Lesions: Minimum 2-Year Follow-Up.

BACKGROUND: The surgical management of large osteochondral lesions of the femoral head in young, active patients remains controversial. Fresh osteochondral allograft (OCA) transplantation can be a highly effective treatment for these lesions in some patients. This study investigated survivorship as well as clinical and radiographic outcomes after fresh OCA transplantation at a minimum 2-year follow-up (mean, 6.6 years; range, 0.6 to 13.7 years). METHODS: A retrospective review of 29 patients who underwent plug OCA transplantation for focal femoral head osteochondral lesions between 2008 and 2021 was performed. Patients were assessed clinically using the modified Harris Hip score (mHHS) preoperatively and at each follow-up visit. Postoperative radiographs were evaluated for graft integrity and osteoarthritis severity. Kaplan-Meier survivorship analyses with 95% confidence intervals (CIs) were performed for the endpoint of conversion to total hip arthroplasty (THA). RESULTS: Overall graft survivorship for included patients was 78.4% (95% CI: 62.9 to 93.9) and 62.7% (95% CI: 39.6 to 85.8) at 5 and 10 years, respectively. There were ten patients (34.5%) who underwent conversion to THA. There was a significant difference using the log-rank test between survival for patients who had a preoperative diagnosis of osteonecrosis (ON) versus those who had other diagnoses (P = .002). The ten-year survival for those who had ON was 41.8% (95% CI: 4.8 to 78.8), and the ten-year survival for diagnoses other than ON was 85.7% (95% CI: 59.8 to 100). The mean mHHS score improved significantly (P < .001) from 48.9 (19 to 84) preoperatively to 77.4 (35 to 100) at the final follow-up. There were twenty patients (69.0%) who had mHHS ≥ 70 at the latest follow-up. Arthritic progression, indicated by an increase in the Kellgren and Lawrence grade, occurred in 7 hips (26.9%). CONCLUSIONS: An OCA transplantation is a viable treatment option for osteochondral defects of the femoral head in young, active patients who have minimal preexisting joint deformity. It may delay the progression of arthritis and the need for THA. Patients who had a preoperative diagnosis of ON had worse clinical outcomes than those who had other diagnoses.

A mathematical model of signalling molecule-mediated processes during regeneration of osteochondral defects after chondrocyte implantation.

Treating bone-cartilage defects is a fundamental clinical problem. The ability of damaged cartilage to self-repair is limited due to its avascularity. Left untreated, these defects can lead to osteoarthritis. Details of osteochondral defect repair are elusive, but animal models indicate healing occurs via an endochondral ossification-like process, similar to that in the growth plate. In the growth plate, the signalling molecules parathyroid hormone-related protein (PTHrP) and Indian Hedgehog (Ihh) form a feedback loop regulating chondrocyte hypertrophy, with Ihh inducing and PTHrP suppressing hypertrophy. To better understand this repair process and to explore the regulatory role of signalling molecules on the regeneration process, we formulate a reaction-diffusion mathematical model of osteochondral defect regeneration after chondrocyte implantation. The drivers of healing are assumed to be chondrocytes and osteoblasts, and their interaction via signalling molecules. We model cell proliferation, migration and chondrocyte hypertrophy, and matrix production and conversion, spatially and temporally. We further model nutrient and signalling molecule diffusion and their interaction with the cells. We consider the PTHrP-Ihh feedback loop as the backbone mechanisms but the model is flexible to incorporate extra signalling mechanisms if needed. Our mathematical model is able to represent repair of osteochondral defects, starting with cartilage formation throughout the defect. This is followed by chondrocyte hypertrophy, matrix calcification and bone formation deep inside the defect, while cartilage at the surface is maintained and eventually separated from the deeper bone by a thin layer of calcified cartilage. The complete process requires around 48 months. A key highlight of the model demonstrates that the PTHrP-Ihh loop alone is insufficient and an extra mechanism is required to initiate chondrocyte hypertrophy, represented by a critical cartilage density. A parameter sensitivity study reveals that the timing of the repair process crucially depends on parameters, such as the critical cartilage density, and those describing the actions of PTHrP to suppress hypertrophy, such as its diffusion coefficient, threshold concentration and degradation rate.

Medial malleolar osteotomy in the treatment of osteochondral lesions of the Talus - incidence and impact on functional outcome: a retrospective analysis based on data from the German Cartilage Register (KnorpelRegister DGOU).

BACKGROUND: There has long been discussion regarding the impact of medial malleolar osteotomies (MMO) as an adjunctive treatment for osteochondral lesions of the talus (OCLT). MMO may improve the visibility and accessibility of the talus, but they also pose a risk of periprocedural morbidity. There is a lack of research about the prevalence and consequences of MMO in the surgical treatment of OCLT. METHODS: This study retrospectively evaluated data from the German Cartilage Register (KnorpelRegister DGOU) from its implementation in 2015 to December 2020. The impact of MMO on patient-reported outcome measures (PROMs) was investigated. Wherever possible, subgroups were built and matched using a propensity score which matched a group undergoing OCLT without MMO. Matching included age, sex, weight, localization of the OCLT, the international cartilage repair society (ICRS) grading, surgical procedure and preoperative symptoms using the Foot and Ankle Ability Measure (FAAM) and the Activities of Daily Living Subscale (ADL). RESULTS: The prevalence of MMO in the operative treatment of OCLT was 15.9%. Most of the osteotomies were performed in OCL of the medial talar dome (76.8%) and in more serious lesions with an ICRS grade of III (29.1%) and IV (61.4%). More than half of the osteotomies (55.6%) were performed during revision surgery. A matched pair analysis of n = 44 patients who underwent AMIC® via arthrotomy and MMO vs. arthrotomy alone showed no significant differences in patient-reported outcome measures (PROMs, i.e. FAAM-ADL, and FAOS) at 6,12 and 24 months. CONCLUSIONS: MMO are mostly used in the treatment of severe (≥ ICRS grade 3) OCL of the medial talar dome and in revision surgery. Functional and patient-reported outcome measures are not significantly affected by MMO compared to arthrotomy alone. TRIAL REGISTRATION: The German Cartilage Register (KnorpelRegister DGOU) was initially registered at the German Clinical Trials Register ( https://www.drks.de , register number DRKS00005617, Date of registration 03.01.2014) and was later expanded by the ankle module.

Surface Crystal and Degradability of Shape Memory Scaffold Essentialize Osteochondral Regeneration.

The minimally invasive deployment of scaffolds is a key safety factor for the regeneration of cartilage and bone defects. Osteogenesis relies primarily on cell-matrix interactions, whereas chondrogenesis relies on cell-cell aggregation. Bone matrix expansion requires osteoconductive scaffold degradation. However, chondrogenic cell aggregation is promoted on the repellent scaffold surface, and minimal scaffold degradation supports the avascular nature of cartilage regeneration. Here, a material satisfying these requirements for osteochondral regeneration is developed by integrating osteoconductive hydroxyapatite (HAp) with a chondroconductive shape memory polymer (SMP). The shape memory function-derived fixity and recovery of the scaffold enabled minimally invasive deployment and expansion to fill irregular defects. The crystalline phases on the SMP surface inhibited cell aggregation by suppressing water penetration and subsequent protein adsorption. However, HAp conjugation SMP (H-SMP) enhanced surface roughness and consequent cell-matrix interactions by limiting cell aggregation using crystal peaks. After mouse subcutaneous implantation, hydrolytic H-SMP accelerated scaffold degradation compared to that by the minimal degradation observed for SMP alone for two months. H-SMP and SMP are found to promote osteogenesis and chondrogenesis, respectively, in vitro and in vivo, including the regeneration of rat osteochondral defects using the binary scaffold form, suggesting that this material is promising for osteochondral regeneration.

Twelve-Year Progression of Osteochondral Lesions of the Talus Observed Using Magnetic Resonance Imaging.

Osteochondral lesions of the talus are common injuries that are most often the result of trauma. The natural progression of osteochondral lesions is not well understood. It is still unclear which lesions eventually lead to joint degeneration and osteoarthritic changes and if the treatment method affects the progression. The existing literature surrounding this topic is sparse, with inconsistent findings. The presented images are taken from a 72-year-old man with bilateral osteochondral lesions of the talus. To our knowledge, this is the first published series of images illustrating the natural progression of a patient with bilateral osteochondral lesions of the talus over a 12-year time period.

Elevated Lipid Metabolites in Stored Clinical OCA Media Correlate With Chondrocyte Death.

BACKGROUND: A major limitation of osteochondral allografts (OCA) is the deterioration of cartilage health associated with cell death during prolonged storage. However, little is known about the mechanisms that contribute to chondrocyte death during storage. PURPOSE/HYPOTHESIS: This study aimed to determine whether bioactive lipid metabolites accumulate in the storage media of OCA and whether they are associated with a loss of chondrocyte viability during prolonged storage. It was hypothesized that free fatty acids (FFAs) would accumulate over time in the storage media of OCA and adversely affect cartilage health during storage. STUDY DESIGN: Controlled laboratory study. METHODS: A group of 21 (n = 6-8 OCA/treatment group) fresh human hemicondylar OCA tissues and media were analyzed after 7, 28, and 68 days of prolonged cold (4°C) storage. Targeted mass spectrometry analysis was used to quantify bioactive FFAs, as well as primary (lipid hydroperoxide [ROOH]) and secondary (malondialdehyde) lipid oxidation products. Chondrocyte viability was measured using a fluorescence-based live/dead assay and confocal microscopy. RESULTS: The concentration of all targeted fatty acid metabolites in storage media was significantly increased with increased cold storage time (P < .05). ROOH was significantly higher on day 28 of cold storage. No difference in secondary ROOH products in storage media was observed. Chondrocyte viability significantly declined in both the en face and the vertical cross-sectional analysis with increased cold storage time and inversely correlated with fatty acid metabolites (P < .05). CONCLUSION: It is well established that elevated levels of certain FFAs and lipid oxidation products can alter cell function and cause cell death via lipotoxicity and other mechanisms. This work is the first to identify elevated levels of FFA metabolites and primary oxidation lipid products in the storage media from clinical OCA. The concentrations of FFA metabolites were measured at levels (>100 µM) known to induce cell death and were directly correlated with chondrocyte viability. CLINICAL RELEVANCE: These findings provide important targets for understanding why cartilage health declines during cold storage, which can be used to optimize media formulations and improve graft health.