Chondral Defects Research Articles

Foot Strike Run Retraining forPatients With Patellofemoral Chondral Defects: A Case Series.

Military service members (SMs) demonstrate high rates of patellofemoral chondral defects (PFCDs) that are difficult to diagnosis and, if untreated, result in a cascade of events eventually leading to osteoarthritis. Running is an essential occupational task for SMs; however, there is little evidence regarding techniques to maintain running ability in individuals with cartilage defects. The purpose of this case series was to assess the clinical application of foot strike run retraining in patients with PFCDs. This case series included two active duty U.S. Marine Corps SMs who presented to outpatient physical therapy with PFCD, diagnosed via MRI. Both patients attended eight foot strike run retraining sessions. Running mechanics and patient-reported outcomes were recorded pre-training, post-training, and at a 1-month follow-up visit. Both patients successfully converted their strike pattern from a rearfoot to a non-rearfoot strike pattern with training and retained this strategy at 1-month follow-up. Post-intervention, both patients demonstrated increased running tolerance, and improvements in Numeric Pain Rating Scale and Lower Extremity Functional Scale scores. Biomechanical analysis showed that both patients demonstrated a 63% to 70% reduction in average and peak vertical ground reaction force loading rates post-treatment. Modification of foot strike pattern from rear to non-rearfoot strike during running for individuals with PFCD can reduce the magnitude of impact loading, which potentially limits disease progression. These findings suggest that foot strike run retraining may be a feasible strategy to reduce pain and improve function in SMs with PFCD who are required to run for occupational responsibilities.

Multi-Surface Cartilage Defects about the Knee Treated with Cartilage Restoration Procedures Show Good Outcomes and Survivorship at Minimum 2-Year Follow-Up.

We aimed to evaluate the outcomes, survivorship, and complications following multi-surface cartilage procedures at minimum 2-year follow-up. Patients with either (1) single-surface osteochondral allograft transplantation (OCAT) with third-generation matrix-induced autologous cultured chondrocyte implantation (MACI) or particulated juvenile cartilage implantation (DeNovo), or (2) multiple-surface OCAT ± associated MACI/DeNovo procedures for grade IV chondral or osteochondral defects about the knee with minimum 2-year follow-up were analyzed. Patient-reported outcome measures (PROMs), including International Knee Documentation Committee (IKDC) and Knee Injury and Osteoarthritis Outcome Score (KOOS) subscales, were obtained preoperatively and at minimum 2 years postoperatively. The percentage of patients who met the minimal clinically important difference (MCID) for each PROM was reported. Failure was defined as revision OCAT, conversion to patellofemoral/total/unicompartmental joint arthroplasty, or Arthrosurface HemiCAP placement. Of 257 patients identified, 35 were included. There was a significant increase in IKDC, KOOS-pain, KOOS-symptom, KOOS-sport, and KOOS-quality of life scores from preoperative to postoperative evaluation (P < 0.03 for all). More than 50% of patients met the MCID for each PROM. There were 2 failures, 1 of the patella and 1 of the medial femoral condyle, at 39.7 and 38.6 months postoperatively, respectively. Multi-surface cartilage procedures are a safe, efficacious treatment option for multifocal cartilage defects about the knee at short-term follow-up.

Immunohistochemical Analysis of Knee Chondral Defect Repair after Autologous Particulated Cartilage and Platelet-Rich Plasma Treatment in Sheep.

This study performs an analysis that will enable the evaluation of the quality, durability, and structure of repaired cartilaginous extracellular matrix tissue using an autologous-based particulated autograft cartilage and platelet-rich plasma treatment (PACI + PRP). A single-blind controlled experiment was conducted on 28 sheep to evaluate the efficacy of the PACI + PRP treatment for cartilage defects. Full-thickness 8 mm diameter defects were created in the weight-bearing area of both knees. The right knees received PACI + PRP. The left knees were treated with Ringer's lactate solution (RLS) or hyaluronic acid (HA) injections. Sheep were euthanized at 9- or 18-months post-surgery. An extensive immunohistochemical analysis was performed to assess collagen types (I, II, III, V, VI, IX, X, XI) and aggrecan positivity. A semiquantitative scoring system provided a detailed evaluation of immunostaining. Collagens and aggrecan scores in the PACI + PRP groups were similar to healthy cartilage. Significant differences were found in collagens associated with matrix maturity (II and V), degradation (IX), structure and mechanics (VI), and hypertrophy (X) between healthy cartilage and RLS- or HA-repaired cartilage. The PACI + PRP treatment advanced the repair cartilage process in chondral defects with mature hyaline cartilage and enhanced the structural and mechanical qualities with better consistent cartilage, less susceptible to degradation and without hypertrophic formation over time.

Knee Cartilage Lesion Management-Current Trends in Clinical Practice.

Many patients, particularly those aged above 40, experience knee joint pain, which hampers both sports activities and daily living. Treating isolated chondral and osteochondral defects in the knee poses a significant clinical challenge, particularly in younger patients who are not typically recommended partial or total knee arthroplasty as alternatives. Several surgical approaches have been developed to address focal cartilage defects. The treatment strategies are characterized as palliation (e.g., chondroplasty and debridement), repair (e.g., drilling and microfracture), or restoration (e.g., autologous chondrocyte implantation, osteochondral autograft, and osteochondral allograft). This review offers an overview of the commonly employed clinical methods for treating articular cartilage defects, with a specific focus on the clinical trials conducted in the last decade. Our study reveals that, currently, no single technology fully meets the essential requirements for effective cartilage healing while remaining easily applicable during surgical procedures. Nevertheless, numerous methods are available, and the choice of treatment should consider factors such as the location and size of the cartilage lesion, patient preferences, and whether it is chondral or osteochondral in nature. Promising directions for the future include tissue engineering, stem cell therapies, and the development of pre-formed scaffolds from hyaline cartilage, offering hope for improved outcomes.

Autologous Matrix Induced Chondrogenesis plus Peripheral Blood Concentrate (AMIC+PBC) in Chondral Defects of the First Metatarsophalangeal Joint: 5-Year Follow-up

Category: Other Introduction/Purpose: The aim of the study was to assess the 5-year-follow-up (5FU) after Autologous Matrix Induced Chondrogenesis plus Peripheral Blood Concentrate (AMIC+PBC) in chondral defects at the first metatarsophalangeal joint (MTP1). Methods: In a prospective consecutive non-controlled clinical follow-up study, all patients with chondral lesion at MTP1 that were treated with AMIC+PBC from July 17, 2016 to May 31, 2017 were included. Size and location of the chondral lesions, the Visual- Analogue-Scale Foot and Ankle (VAS FA) and the EFAS Score before treatment and at 5FU were analysed and compared with previous 2-year-follow-up (2FU). Peripheral Blood Concentrate (PBC) was used to impregnate a collagen I/III matrix (Chondro- Gide, Wolhusen, Switzerland) that was fixed into the chondral lesion with fibrin glue. Results: One hundred and ninety-eight patients with 238 chondral defects were included. In 21% of patients no deformities in the forefoot were registered. The average degree of osteoarthritis was 2.2. The chondral defect size was 1.0 cm2 on average. The most common location was metatarsal dorsal (33%), and in most patients one defect was registered (74%). Corrective osteotomy of the first metatarsal was performed in 79%. 176 (89%)/164 (83%) patients completed 2FU/5FU. VAS FA/EFAS Score were preoperatively 46.8/11.9 and improved to 74.1/17.1 at 2FU and 75.0/17.3 at 5FU on average. No parameter significantly differed between 2FU and 5FU. Conclusion: AMIC+PBC as treatment for chondral defects at MTP1 as part of joint preserving surgery led to improved and high validated outcome scores at 2FU and 5FU. The results between 2FU and 5FU did not differ.

ANALYSIS OF MEDIUM-TERM RESULTS ACHIEVED AFTER MICROFRACTURES AND PERFORATIONS (DRILLING) IN LOCALIZED CHONDRAL LESIONS IN THE KNEE JOINT

Introduction: The main advantage of perforative techniques is their atraumatic, non-invasiveness and possibly being done under arthroscopic control. Purpose: This study aims to compare two methods of operative techniques in the treatment of chondral lesions of the knee. Materials and methods: The clinical study included 237 symptomatic patients with chondral defects from the period of 2010 – 2018. Patients were divided into 2 groups. The first group included 49 (32.11%) patients with arthroscopic micro-fractures. The second group included 54 (35.49%) patients with arthroscopic subchondral perforation (drilling). The term of follow-up was 36 months. Each patient had at least 4 documented follow-up visits. Results: Results from grading scales – Lysholm, KOS, MRI – scales, as well as our own scale for evaluating knee function (PS) scale, were documented in each patient's separate file. The average pre-operative Lysholm score was 41.5 ± 6.6 in the microfracture group and 43.0 ± 5.6 in the perforation group. At the 36th-month average, Lysholm's score increased to 86.9 ± 7.3 in the microfracture group and to 86.1 ± 6.6 in the perforation group. During the study, it was also found that a correlation exists between the received results and the age of the patient, the size of the chondral defect, and the tracking period. Conclusion: The effectiveness of osteoperforative techniques relies on many factors: the age of the patient, the size of the defect, and the tracking period. In the end, mesenchymal stimulation of chondrogenesis results in positive mid-term results in patients with small-sized chondral lesion.

Rapid Recovery after Reparation of Full-Thickness Chondral Defects of the Knee with the Use of Hyaluronan (HA)-Based 3-D Scaffold.

Articular cartilage injuries are found in up to 60% of patients who undergo an arthroscopic knee procedure, and those that totally affect articular cartilage (grade IV) have limited regenerative capacity and extended time for recovery. 3-D scaffolds represent a novel solution to address this type of injury. Our purpose was to analyze the MRI findings and functional status of patients that underwent repair of chondral defects either by microfractures or Hyaluronan (HA) 3-D scaffolding. We conducted a retrospective study of patients with chondral defects. The outcomes analyzed in this study included anatomical changes evaluated by the Henderson score (based on MRI findings) at baseline, 6, and 12 months after surgery, and improvement in functionality evaluated by the Modified Cincinnati Knee Rating System (MCKRS) at baseline and 6 months after surgery. Clinical and demographic characteristics were similar for both groups. There was a statistically significant improvement in Henderson score for the 3-D scaffold-treated group at 6 months versus the microfracture group (p < 0.0001). Improvement in functionality, measured by the MCKRS, was more frequently found in the 3-D scaffold-treated group. In conclusion, the use of HA 3-D scaffolding was superior, with faster recovery evident 6 months after the surgery that progressed to full recovery in all patients a year after surgery. Future studies with a randomized design might help to support our findings. This study provides level III evidence.

Autologous and Allogeneic Cytotherapies for Large Knee (Osteo)Chondral Defects: Manufacturing Process Benchmarking and Parallel Functional Qualification.

Cytotherapies are often necessary for the management of symptomatic large knee (osteo)-chondral defects. While autologous chondrocyte implantation (ACI) has been clinically used for 30 years, allogeneic cells (clinical-grade FE002 primary chondroprogenitors) have been investigated in translational settings (Swiss progenitor cell transplantation program). The aim of this study was to comparatively assess autologous and allogeneic approaches (quality, safety, functional attributes) to cell-based knee chondrotherapies developed for clinical use. Protocol benchmarking from a manufacturing process and control viewpoint enabled us to highlight the respective advantages and risks. Safety data (telomerase and soft agarose colony formation assays, high passage cell senescence) and risk analyses were reported for the allogeneic FE002 cellular active substance in preparation for an autologous to allogeneic clinical protocol transposition. Validation results on autologous bioengineered grafts (autologous chondrocyte-bearing Chondro-Gide scaffolds) confirmed significant chondrogenic induction (COL2 and ACAN upregulation, extracellular matrix synthesis) after 2 weeks of co-culture. Allogeneic grafts (bearing FE002 primary chondroprogenitors) displayed comparable endpoint quality and functionality attributes. Parameters of translational relevance (transport medium, finished product suturability) were validated for the allogeneic protocol. Notably, the process-based benchmarking of both approaches highlighted the key advantages of allogeneic FE002 cell-bearing grafts (reduced cellular variability, enhanced process standardization, rationalized logistical and clinical pathways). Overall, this study built on our robust knowledge and local experience with ACI (long-term safety and efficacy), setting an appropriate standard for further clinical investigations into allogeneic progenitor cell-based orthopedic protocols.

Cartilage Defect Treatment Using High-Density Autologous Chondrocyte Implantation (HD-ACI).

Hyaline cartilage's inability to self-repair can lead to osteoarthritis and joint replacement. Various treatments, including cell therapy, have been developed for cartilage damage. Autologous chondrocyte implantation (ACI) is considered the best option for focal chondral lesions. In this article, we aimed to create a narrative review that highlights the evolution and enhancement of our chondrocyte implantation technique: High-Density-ACI (HD-ACI) Membrane-assisted Autologous Chondrocyte Implantation (MACI) improved ACI using a collagen membrane as a carrier. However, low cell density in MACI resulted in softer regenerated tissue. HD-ACI was developed to improve MACI, implanting 5 million chondrocytes per cm2, providing higher cell density. In animal models, HD-ACI formed hyaline-like cartilage, while other treatments led to fibrocartilage. HD-ACI was further evaluated in patients with knee or ankle defects and expanded to treat hip lesions and bilateral defects. HD-ACI offers a potential solution for cartilage defects, improving outcomes in regenerative medicine and cell therapy. HD-ACI, with its higher cell density, shows promise for treating chondral defects and advancing cartilage repair in regenerative medicine and cell therapy.

Gene-activated hyaluronic acid-based cryogels for cartilage tissue engineering

Articular cartilage injuries are very frequent lesions that if left untreated may degenerate into osteoarthritis. Gene transfer to mesenchymal stem cells (MSCs) provides a powerful approach to treat these lesions by promoting their chondrogenic differentiation into the appropriate cartilage phenotype. Non-viral vectors constitute the safest gene transfer tools, as they avoid important concerns of viral systems including immunogenicity and insertional mutagenesis. However, non-viral gene transfer usually led to lower transfection efficiencies when compared with their viral counterparts. Biomaterial-guided gene delivery has emerged as a promising alternative to increase non-viral gene transfer efficiency by achieving sustained delivery of the candidate gene into cellular microenvironment. In the present study, we designed hyaluronic acid-based gene-activated cryogels (HACGs) encapsulating a novel formulation of non-viral vectors based on niosomes (P80PX) to promote MSCs in situ transfection. The developed HACG P80PX systems showed suitable physicochemical properties to promote MSCs in situ transfection with very low cytotoxicity. Incorporation of a plasmid encoding for the transcription factor SOX9 (psox9) into HACG P80PX systems led to an effective MSCs chondrogenic differentiation with reduced expression of fibrocartilage and hypertrophic markers. The capacity of the developed systems to restore cartilage extracellular matrix was further confirmed in an ex vivo model of chondral defect.

Gel-Based Autologous Chondrocyte Implantation (GACI) in the Chondral Defects of the Knee: An Observational Study.

Gel-based autologous chondrocyte implantation (GACI) is known to have superior results when compared to conventional autologous chondrocyte implantation (ACI) in terms of delivery of chondrocytes to the articular cartilage surface with reproducible three-dimensional structural restoration. This study aims to evaluate the short-term outcomes of gel-based autologous chondrocyte implantation (GACI) for the treatment of large focal articular cartilage defects of the knee. This was a prospective observational study among 25 patients who underwent GACI. Primary outcome measures included Lysholm Knee Scoring Scale and IKDC score and secondary outcome measures included MRI assessment of cartilage repair using MOCART. Mean age of the population was 39.8 ± 7.5years. The study found a highly significant improvement in both Lysholm knee score (pre-op: 45.1 to post-op: 72.4) and IKDC score (pre-op: 36.7 to post-op: 78.5) (p < 0.001) at the final follow-up of 24months, even with the mean defect size being 4.5 ± 5.8 cm2. Postoperative MRI showed a mean MOCART score improvement from 39.4 to 67.4 at the final follow-up. No major complications were observed. GACI is an effective and safe treatment option for large focal articular cartilage defects around the knee, with significant improvement in functional scores and low revision rates at medium-term follow-up.

The Effect of Stem Cells on Ankle Injuries

Ankle injuries lead to joint pain, limitation of movement, occasional effusion, and quality of life impairment. It is estimated that one injury occurs for every 10,000 people each day due to inversion of the ankle. 7-10% of all admissions to hospital emergency departments are a result of ankle injuries. It was found that 70% of acute ankle sprains and fractures display some osteochondral defects (OCD) of the talus. Twenty five percent of all injuries of the musculoskeletal system are related to inversion injuries. About 50% of these injuries are related to sports. Full thickness focal chondral defects in athletes have an overall prevalence of 36%. The ankle is the most injured area of the body for 24 of 70 sports that were studied. Basketball, soccer, football, volleyball, running, and dancing are the sports in which these athletic injuries are most common. Individuals under 35 years of age demonstrate majority of these ankle injuries. The most common age group is for those are between the ages of 15 and 19 years. Etiology of ankle OCDs can either be non-traumatic or traumatic. Seventy percent of acute ankle sprains and fractures occur in the OCD of talus. Potential side effects or medical complications may result from OCD surgeries. Animal and human subjects are commonly used by researchers to investigate the overall effectiveness of stem cells for OCD injuries. Mesenchymal stem cells (MSC) are often the source of preference for orthopedic procedures as they have the ability to differentiate into a variety of tissues. These tissues include bone, muscle, cartilage, and fat. Stem cell transplantation has shown improved tissue quality and rate of healing, sustained gains functionally, decreased pain, and enhanced clinical outcomes. Researchers believed the use of stem cells may offer choices for patients with orthopedic injuries including OCD to reduce recovery time and osteoarthritis as well as enhance function.

The AMADEUS score is not a sufficient predictor for functional outcome after autologous chondrocyte implantation (ACI) of the knee: data from the German Cartilage Registry (KnorpelRegister DGOU)

IntroductionThe AMADEUS (Area Measurement And DEpth and Underlying Structures) score has advanced to a commonly used tool for MRI-based chondral defect severity grading prior to cartilage knee surgery. It was the intention of this study to assess the AMADEUS for a potential correlation with clinical data by patient-reported outcome measures (PROMs).MethodsA total of 51 patients undergoing ACI (autologous chondrocyte implantation) between 2016 and 2022 were found eligible and retrospectively analyzed. All patients were registered in the German Cartilage Registry prior to surgery and follow-up data were collected using the Knee Osteoarthritis Outcome score (KOOS), the International Knee Documentation Committee (IKDC) Form and the numeric rating scale (NRS). Pre-operative MRI images were scored by three raters using the AMADEUS classification system, and an overall AMADEUS score was calculated which was subsequently correlated with pre- and post-operative PROMs.ResultsMean patient age was 32.67 ± 8.37 years and mean defect size area 343.04 mm2 ± 139.45 mm2. No correlative capacity of the pre- and postoperative IKDC, KOOS or NRS scores was found with the AMADEUS final score or any of its subscores. From the pre- to postoperative visit, a significant improvement of the PROMs (IKDC: 45.53 ± 21.00 vs. 59.83 ± 17.93, p = 0.04; KOOS Pain: 58.00 ± 16.70 vs. 76.06 ± 19.20, p = 0.03; KOOS ADL: 64.17 ± 18.76 vs. 82.11 ± 16.68, p < 0.01; KOOS Sports: 26.11 ± 18.52 vs. 50.56 ± 23.94, p = 0.01; KOOS QOL: 25.50 ± 14.26 ± 45.28 ± 19.03, p = 0.00) was found. Intraclass correlation coefficients showed an overall good interrater agreement for the AMADEUS total score (ICC = 0.75).ConclusionsStudy results suggest no correlative capacity of the AMADEUS with routinely used PROMs in patients undergoing ACI. Therefore, radiographically assessed cartilage defect characteristics poorly translate to pre- and postoperative patient-reported outcome data.

The effect of oral hydroxychloroquine on chondral defect: An experimental study.

This study aims to evaluate the time- and dose-dependent effects of oral hydroxychloroquine (HCQ) on focal full-thickness knee chondral defect healing in a rabbit model. Cartilage defects of 4x4 mm2 were created on both medial femoral condyles of 24 New Zealand rabbits. The rabbits were divided into six groups (A-F) according to HCQ administration and sacrifice time: A (three-week control) and B (six-week control) received no additional interventions; C (20 mg/kg HCQ, three weeks); D (20 mg/kg HCQ, six weeks); E (40 mg/kg HCQ, three weeks); and F (40 mg/kg HCQ, six weeks). Osteochondral specimens were evaluated macroscopically, histologically, and immunohistochemically. The terminal deoxynucleotidyl-transferase (TdT)-mediated dUTP nick end labeling (TUNEL) method was used to detect apoptotic cells. The International Cartilage Repair Society (ICRS) scores were significantly higher in the experimental groups than in the controls (p<0.001). The Wakitani scores in Group D showed a significant improvement compared to those in Group B (p<0.01). The 20 mg/kg HCQ treatment groups showed better recovery than the controls (p<0.01). High-dose HCQ (40 mg/kg) treatment significantly reduced the intensity of collagen type 2 immunoreactivity compared to that in the groups receiving 20 mg/kg of HCQ (p<0.01). Collagen type 2 expression in Group F was significantly lower than that in Group D (p<0.01). There were more TUNEL-positive cells in the repair sites of Groups E and F than in the lower-dose experimental groups and untreated experimental groups (p<0.001). A low dose of HCQ improved cartilage repair, while higher doses of HCQ exerted a negative effect on cartilage regeneration in rabbits. In the presence of defective cartilage, the use of HCQ at an appropriate dose and time is important for cartilage health.

A Photopolymerizable Biocompatible Hyaluronic Acid Hydrogel Promotes Early Articular Cartilage Repair in a Minipig Model In Vivo.

Articular cartilage defects represent an unsolved clinical challenge. Photopolymerizable hydrogels are attractive candidates supporting repair. This study investigates the short-term safety and efficacy of two novel hyaluronic acid (HA)-triethylene glycol (TEG)-coumarin hydrogels photocrosslinked in situ in a clinically relevant large animal model. It is hypothesized that HA-hydrogel-augmented microfracture (MFX) is superior to MFX in enhancing early cartilage repair, and that the molar degree of substitution and concentration of HA affects repair. Chondral full-thickness defects in the knees of adult minipigs are treated with either 1) debridement (No MFX), 2) debridement and MFX, 3) debridement, MFX, and HA hydrogel (30% molar derivatization, 30mg mL-1 HA; F3) (MFX+F3), and 4) debridement, MFX, and HA hydrogel (40% molar derivatization, 20mg mL-1 HA; F4) (MFX+F4). After 8 weeks postoperatively, MFX+F3 significantly improves total macroscopic and histological scores compared with all other groups without negative effects, besides significantly enhancing the individual repair parameters "defect architecture," "repair tissue surface" (compared with No MFX, MFX), and "subchondral bone" (compared with MFX). These data indicate that photopolymerizable HA hydrogels enable a favorable metastable microenvironment promoting early chondrogenesis in vivo. This work also uncovers a mechanism for effective HA-augmented cartilage repair by combining lower molar derivatization with higher concentrations.

OSTEOCHONDRAL ALLOGRAFT TRANSPLANTATION IN THE KNEE: EARLY EXPERIENCE IN THE UNITED KINGDOM

AbstractBackgroundOsteochondral allograft (OCA) transplantation is a clinically and cost-effective option for symptomatic cartilage defects. In 2017 we initiated a program for OCA transplantation for complex chondral and osteochondral defects as a UK tertiary referral centre.AimTo characterise the complications, re-operation rate, graft survivorship and clinical outcomes of knee OCA transplantation.MethodologyAnalysis of a prospectively maintained database of patients treated with primary OCA transplantation from 2017 to 2021 with a minimum of one-year follow-up. Patient reported outcome measures (PROMs), complications, re-operations and failures were evaluated.Results37 patients with 37 knee OCA procedures were included (mean age 31.6 years [16–49 years]). Mean BMI 26.6 kg/m2 (19.1–35.9 kg/m2). The mean chondral defect size was 3cm2 (1.2–7.3 cm2). Mean duration of follow-up was 3.1 years (1–5.3 years). 16 patients underwent meniscal allograft transplantation (MAT), 6 underwent osteotomy and 4 underwent ligament reconstruction as concurrent procedures. Significant improvements in mean PROMs were noted at 12 months. 16 patients had reoperations of which 5 had more than one surgery. Of these patients 6 were related to OCA (mainly debridement and revision OCA in one patient), and the remainder were related to additional procedures including removal of plate in 2 patients. The overall failure rate was 1 in 37 patients (3%).ConclusionsEarly experience of OCA as a treatment option for complex chondral and osteochondral lesions in the knee shows satisfactory results. The reoperation rate is high but at mean follow-up of 3.1 years the survival rate was 97%.

Single-step ultra-purified alginate gel implantation in patients with knee chondral defects.

Implantation of ultra-purified alginate (UPAL) gel is safe and effective in animal osteochondral defect models. This study aimed to examine the applicability of UPAL gel implantation to acellular therapy in humans with cartilage injury. A total of 12 patients (12 knees) with symptomatic, post-traumatic, full-thickness cartilage lesions (1.0 to 4.0 cm2) were included in this study. UPAL gel was implanted into chondral defects after performing bone marrow stimulation technique, and assessed for up to three years postoperatively. The primary outcomes were the feasibility and safety of the procedure. The secondary outcomes were self-assessed clinical scores, arthroscopic scores, tissue biopsies, and MRI-based estimations. No obvious adverse events related to UPAL gel implantation were observed. Self-assessed clinical scores, including pain, symptoms, activities of daily living, sports activity, and quality of life, were improved significantly at three years after surgery. Defect filling was confirmed using second-look arthroscopy at 72 weeks. Significantly improved MRI scores were observed from 12 to 144 weeks postoperatively. Histological examination of biopsy specimens obtained at 72 weeks after implantation revealed an extracellular matrix rich in glycosaminoglycan and type II collagen in the reparative tissue. Histological assessment yielded a mean overall International Cartilage Regeneration & Joint Preservation Society II score of 69.1 points (SD 10.4; 50 to 80). This study provides evidence supporting the safety of acellular UPAL gel implantation in facilitating cartilage repair. Despite being a single-arm study, it demonstrated the efficacy of UPAL gel implantation, suggesting it is an easy-to-use, one-step method of cartilage tissue repair circumventing the need to harvest donor cells.

Five-Year Outcomes After Implantation of a Scaffold-Free Tissue-Engineered Construct Generated From Autologous Synovial Mesenchymal Stromal Cells for Repair of Knee Chondral Lesions.

In an earlier study, a scaffold-free tissue-engineered construct (TEC) derived from autologous synovial membrane mesenchymal stromal cells (MSCs) was developed and demonstrated to be safe and effective for cartilage repair at 2 years postoperatively. To investigate clinical outcomes and magnetic resonance imaging (MRI) findings at 5 years after implantation. Case series; Level of evidence, 4. This was an observational first-in-human study limited to 5 patients (age, 28-46 years) with symptomatic knee chondral lesions (size, 1.5-3.0 cm2) on the medial femoral condyle, lateral femoral condyle, or femoral groove. Synovial MSCs were isolated from arthroscopic biopsy specimens and cultured to develop a TEC that matched the lesion size. The TECs were then implanted into chondral defects without fixation and assessed at up to 5 years postoperatively. The patients were clinically evaluated using the visual analog scale for pain, Lysholm score, Tegner score, and Knee injury and Osteoarthritis Outcome Score. An MRI scan evaluation was also performed for morphologic and compositional quality of the repair tissue at both 2 and 5 years of follow-up. All clinical scores were significantly improved from the preoperative evaluation to the 2- and 5-year follow-ups and the results were stable over time. The MRI scan evaluation showed cartilage defects filled with newly generated tissues with good tissue integration to adjacent host cartilage over time. The cartilage thickness and surface smoothness of the repair cartilage were maintained up to 5 years postoperatively. The MOCART (magnetic resonance observation of cartilage repair tissue) 2.0 Knee Scores remained high at 5 years, although the total points decreased slightly. The results highlight the efficacy and feasibility of autologous scaffold-free TEC derived from synovial MSCs for regenerative cartilage repair via a sutureless and simple implantation procedure, showing good clinical outcomes and MRI findings with stable results at midterm follow-up. Further follow-up will be needed to assess the long-term quality of the repair tissue.

Long-term clinical and radiological outcomes following arthroscopic microfracture of the glenohumeral joint for chondral defects

The primary aim of this study was to evaluate mid- and long-term outcomes following microfracture in patients with glenohumeral chondral lesions. This prospective cohort study assessed patients with shoulder pain who were treated with arthroscopic microfracture for full-thickness chondral lesions of the glenohumeral joint. Outcomes included the Simple Shoulder Test at baseline, mid-term (approximately 1 year) and long-term (approximately 10 years), and the Oxford Shoulder Score, shoulder pain (0-10 numerical scale) and radiological assessment using a modified Samilson & Prieto score at long-term follow-up. Data were analyzed with paired t-tests and Wilcoxon's signed rank tests, which were considered significant if P<.05. Twenty-five patients with a mean age of 52.7±12.1 were enrolled. The mean Simple Shoulder Test score improved from baseline to 1 year (6.7±2.5 to 11.0±1.4, P<.001), which was maintained at long-term follow-up (10.3±2.1, P<.001). Additionally, at long-term follow-up, Oxford Shoulder Score and Verbal Pain Score scores were 43±4.8 and 1.1±1.5, respectively while median modified Samilson & Prieto scores increased from 1 preoperatively to 2 at 10 years (P<.001). Patients undergoing microfracture for full-thickness chondral lesions of the glenohumeral joint reported substantial improvements in shoulder pain and function at 1 and 10 years, despite progressive radiological degeneration.

The Dual-Responsive Interaction of Particulated Hyaline Cartilage and Plasma Rich in Growth Factors (PRGF) in the Repair of Cartilage Defects: An In Vitro Study.

The treatment of chondral and osteochondral defects is challenging. These types of lesions are painful and progress to osteoarthritis over time. Tissue engineering offers tools to address this unmet medical need. The use of an autologous cartilage construct consisting of hyaline cartilage chips embedded in plasma rich in growth factors (PRGF) has been proposed as a therapeutic alternative. The purpose of this study was to dig into the potential mechanisms behind the in vitro remodelling process that might explain the clinical success of this technique and facilitate its optimisation. Chondrocyte viability and cellular behaviour over eight weeks of in vitro culture, type II collagen synthesis, the dual delivery of growth factors by hyaline cartilage and PRGF matrix, and the ultrastructure of the construct and its remodelling were characterised. The main finding of this research is that the cartilage fragments embedded in the three-dimensional PRGF scaffold contain viable chondrocytes that are able to migrate into the fibrin network, proliferate and synthesise extracellular matrix after the second week of in vitro culture. The characterization of this three-dimensional matrix is key to unravelling the molecular kinetics responsible for its efficacy.