Large Cartilage Defects Research Articles

Lateral Meniscus Allograft Transplant With Capsulodesis and an Osteochondral Allograft to the Lateral Femoral Condyle

Background: Anterior cruciate ligament (ACL) injuries frequently present with lateral meniscal injuries, and when irreparable, this may lead to meniscectomy, increasing the risk for osteoarthritis. Lateral meniscal allograft transplant (LMAT) can restore knee function and proper contact pressures. When combined with osteochondral allograft (OCA) for chondral defects, results are highly positive. Indications: LMAT is indicated in relatively young patients (<50 years of age) with a symptomatic, meniscus-deficient knee that has failed conservative treatment. The knee must be stable, without articular cartilage damage that cannot be repaired, and patients should be able to adhere to postoperative rehabilitation and future care. Indications for OCA include young, active patients with posttraumatic osteochondral defects, osteonecrosis, osteochondritis dissecans, large focal defects, previous cartilage repair failure, or patellofemoral joint cartilage lesions. Technique Description: After a diagnostic arthroscopy is performed and concomitant injuries are ruled out, the lateral meniscal tissue is debrided to a 1- to 2-mm rim for the recipient site preparation. Tibial sockets for root fixation are created using tibial guides and passing sutures are placed. A capsulodesis is performed to reduce meniscal extrusion by securing the lateral capsule through a transtibial tunnel to the anteromedial tibial cortex with high-strength sutures. A meniscal allograft, prepared with bone plugs, is introduced through an enlarged anterolateral portal. After it is accurately positioned, it is stabilized using Fast-Fix Flex devices and circumferential sutures. The bone plug sutures are then fixed through the tibial tunnels to the anteromedial tibial cortex with a button. The large cartilage defect is addressed with an OCA transplant, involving defect measurement, careful reaming, and press-fit insertion of a donor plug, ensuring congruent articulation. Results: Patients can expect improved clinical outcomes and high patient satisfaction with LMAT and concomitant OCA. The use of bone plugs minimizes soft tissue dissection while achieving solid osseous fixation. Discussion/Conclusions: LMAT with OCA leads to restored contact pressures to near-physiological levels, a high patient satisfaction of over 85%, and mean allograft survival of 16 years. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.

Effectiveness and Safety of Matrix-Associated Autologous Chondrocyte Implantation for the Treatment of Articular Cartilage Defects: A Real-World Data Analysis in Japan

Background: The effectiveness and safety of matrix-associated autologous chondrocyte implantation with an autologous periosteal flap (pMACI) remain unclear. The Japanese Ministry of Health, Labor, and Welfare requires postmarketing surveillance of all patients undergoing pMACI using the tissue-engineered product JACC. Purpose: To evaluate the effectiveness and safety of pMACI for large articular cartilage defects (≥4 cm2) in the knee joint using real-world data analysis. Study Design: Case series; Level of evidence, 4. Methods: Data were collected from patients who underwent pMACI between 2012 and 2019, with 2 years of follow-up. The primary outcomes were the Lysholm knee score and Knee injury and Osteoarthritis Outcome Score (KOOS) at 6, 12, and 24 months. Adverse events were assessed by physical examination, magnetic resonance imaging, and/or arthroscopy. Results: Overall, 232 knees in 225 patients who presented with trauma (198 knees) or osteochondritis dissecans (34 knees) in the medial (132 knees) and lateral (44 knees) femoral condyle, patella (25 knees), trochlea (86 knees), and tibial plateau (4 knees) were included. The mean age of the patients was 40.9 ± 15.0 years, with mean cartilage defects of 5.6 ± 2.4 cm2 in size. Concomitant surgeries, such as osteotomy (50 knees), ligament reconstruction (27 knees), meniscal procedures (28 knees), osteochondral autograft transplantation (24 knees), and microfracture (14 knees), were performed in 113 (48.7%) knees. The minimal clinically important difference in the Lysholm knee score and KOOS Symptoms subscale was achieved in 79.7% and 63.5% of patients, respectively, and the Patient Acceptable Symptom State was achieved in 90.1% and 73.7%, respectively. Substantial clinical benefit was achieved in the KOOS Sports/Recreation and Quality of Life subscales at 39.6% and 37.8%, respectively. Knees that underwent concomitant microfracture had significantly worse KOOS values than the remainder of the cohort. Complications, including effusion (16.8%), graft delamination (14.7%), knee contracture (9.1%), graft hypertrophy (8.2%), and ossification (3.4%), were observed in 86 (37.1%) knees. Osteochondritis dissecans was significantly associated with graft hypertrophy and ossification, whereas concomitant surgery was significantly associated with delamination and contracture. Treatment failure required additional cartilage procedures in 11 (4.7%) knees. Conclusion: Treatment of large cartilage defects (≥4 cm2) with pMACI resulted in improved outcome scores in approximately 75% of patients. However, complications occurred in one-third of patients, and 4.7% required reoperation.

A human organoid drug screen identifies α2-adrenergic receptor signaling as a therapeutic target for cartilage regeneration.

Directed differentiation of stem cells toward chondrogenesis invitro and in situ to regenerate cartilage suffers from off-target differentiation and hypertrophic tendency. Here, we generated a cartilaginous organoid system from human expanded pluripotent stem cells (hEPSCs) carrying a COL2A1mCherry and COL10A1eGFP double reporter, enabling real-time monitoring of chondrogenesis and hypertrophy. After screening 2,040 FDA-approved drugs, we found that α-adrenergic receptor (α-AR) antagonists, especially phentolamine, stimulated chondrogenesis but repressed hypertrophy, while α2-AR agonists reduced chondrogenesis and induced hypertrophy. Phentolamine prevented cartilage degeneration in hEPSC cartilaginous organoid and human cartilage explant models and stimulated microfracture-activated endogenous skeletal stem cells toward hyaline-like cartilage regeneration without fibrotic degeneration in situ. Mechanistically, α2-AR signaling induced hypertrophic degeneration via cyclic guanosine monophosphate (cGMP)-dependent secretory leukocyte protease inhibitor (SLPI) production. SLPI-deleted cartilaginous organoid was degeneration resistant, facilitating large cartilage defect healing. Ultimately, targeting α2-AR/SLPI was a promising and clinically feasible strategy to regenerate cartilage via promoting chondrogenesis and repressing hypertrophy.

Articular Cartilage Injury; Current Status and Future Direction.

Today, treatments of cartilage and osteochondral lesions are routine clinical procedures. The avascular and hard-to-self-repair nature of cartilage tissue has posed a clinical challenge for the replacement and reconstruction of damaged cartilage. Treatment of large articular cartilage defects is technically difficult and complex, often accompanied by failure. Articular cartilage cannot repair itself after injury due to a lack of blood vessels, lymph, and nerves. Various treatments for cartilage regeneration have shown encouraging results, but unfortunately, none have been the perfect solution. New minimally invasive and effective techniques are being developed. The development of tissue engineering technology has created hope for articular cartilage reconstruction. This technology mainly supplies stem cells with various sources of pluripotent and mesenchymal stem cells. This article describes the treatments in detail, including types, grades of cartilage lesions, and immune mechanisms in cartilage injuries.

Osteophyte Cartilage as a Potential Source for Minced Cartilage Implantation: A Novel Approach for Articular Cartilage Repair in Osteoarthritis.

Osteoarthritis (OA) is a common joint disorder characterized by cartilage degeneration, often leading to pain and functional impairment. Minced cartilage implantation (MCI) has emerged as a promising one-step alternative for large cartilage defects. However, the source of chondrocytes for MCI remains a challenge, particularly in advanced OA, as normal cartilage is scarce. We performed in vitro studies to evaluate the feasibility of MCI using osteophyte cartilage, which is present in patients with advanced OA. Osteophyte and articular cartilage samples were obtained from 22 patients who underwent total knee arthroplasty. Chondrocyte migration and proliferation were assessed using cartilage fragment/atelocollagen composites to compare the characteristics and regenerative potential of osteophytes and articular cartilage. Histological analysis revealed differences in cartilage composition between osteophytes and articular cartilage, with higher expression of type X collagen and increased chondrocyte proliferation in the osteophyte cartilage. Gene expression analysis identified distinct gene expression profiles between osteophytes and articular cartilage; the expression levels of COL2A1, ACAN, and SOX9 were not significantly different. Chondrocytes derived from osteophyte cartilage exhibit enhanced proliferation, and glycosaminoglycan production is increased in both osteophytes and articular cartilage. Osteophyte cartilage may serve as a viable alternative source of MCI for treating large cartilage defects in OA.

Hydrogel-based and spheroid-based autologous chondrocyte implantation of the knee show similar 2-year functional outcomes: An analysis based on the German Cartilage Registry (KnorpelRegister DGOU).

To compare short-term patient-reported outcomes (PRO) of two contemporary matrix-associated autologous chondrocyte implantation (M-ACI) products for the treatment of large articular cartilage defects of the knee. A retrospective, registry-based, matched-pair analysis was performed, comparing PRO ofpatients undergoing isolated M-ACI with either Spherox™, a spheroid-based ACI (Sb-ACI), or NOVOCART™Inject, a hydrogel-based ACI product (Hb-ACI), for a focal full-thickness cartilage defect of the knee ≥4 cm2. Matching parameters included age, sex, body mass index, defect size, defect localization, symptom duration and previous surgeries. The Knee Injury and Osteoarthritis Outcome Score (KOOS) and the International Knee Documentation Committee (IKDC) score were obtained up to the 24-month follow-up. The total KOOS response rate and percentage of patients attaining a substantial clinical benefit (SCB) in KOOS subscores were calculated. A total of 45 patients per group were matched. The response rate after 24 months was not significantly different between the groups (Sb-ACI 64.4% vs. Hb-ACI 82.2%, p = 0.057). The number of patients with a SCB at 24 months was not significantly different in any KOOS subscore, despite significantly higher improvement of the total KOOS (14.8 ± 16.2 vs. 21.5 ± 15.4, p = 0.047) and KOOS pain in the Hb-ACI group (12.2 ± 18.6 vs. 20.6 ± 19.1, p = 0.037). The IKDC score in the Hb-ACI group was significantly higher at the 12-and 24-month follow-up (60.7 ± 20.2 vs. 70.9 ± 18.0, p = 0.013). The response rate and number of patients achieving an SCB were not significantly different between patients treated with Sb-ACI or Hb-ACI. Both procedures can achieve favourable 2-year PRO. Hb-ACI was associated with better PRO between 1 and 2 years postoperatively;however, the clinical relevance of this benefit is yet to be proven. III, Retrospective comparative study.

Development of a patient specific cartilage graft using magnetic resonance imaging and 3D printing

ObjectivesThe goal of this project was to develop and validate a patient-specific, anatomically correct graft for cartilage restoration using magnetic resonance imaging (MRI) data and 3-dimensional (3D) printing technology. The specific aim was to test the accuracy of a novel method for 3D printing and implanting individualized, anatomically shaped bio-scaffolds to treat cartilage defects in a human cadaveric model. We hypothesized that an individualized, anatomic 3D-printed scaffold designed from MRI data would provide a more optimal fill for a large cartilage defect compared to a generic flat scaffold. MethodsFour focal cartilage defects (FCDs) were created in paired human cadaver knees, age <40 years, in the weight-bearing surfaces of the medial femoral condyle (MFC), lateral femoral condyle (LFC), patella, and trochlea of each knee. MRIs were obtained, anatomic grafts were designed and 3D printed for the left knee as an experimental group, and generic flat grafts for the right knee as a control group. Grafts were implanted into corresponding defects and fixed using tissue adhesive. Repeat post-implant MRIs were obtained. Graft step-off was measured as the distance in mm between the surface of the graft and the native cartilage surface in a direction perpendicular to the subchondral bone. Graft contour was measured as the gap between the undersurface of the graft and the subchondral bone in a direction perpendicular to the joint surface. ResultsGraft step-off was statistically significantly better for the anatomic grafts compared to the generic grafts in the MFC (0.0 ​± ​0.2 ​mm vs. 0.7 ​± ​0.5 ​mm, p ​< ​0.001), LFC (0.1 ​± ​0.3 ​mm vs. 1.0 ​± ​0.2 ​mm, p ​< ​0.001), patella (−0.2 ​± ​0.3 ​mm vs. −1.2 ​± ​0.4 ​mm, p ​< ​0.001), and trochlea (−0.4 ​± ​0.3 vs. 0.4 ​± ​0.7, p ​= ​0.003). Graft contour was statistically significantly better for the anatomic grafts in the LFC (0.0 ​± ​0.0 ​mm vs. 0.2 ​± ​0.4 ​mm, p ​= ​0.022) and trochlea (0.0 ​± ​0.0 ​mm vs. 1.4 ​± ​0.7 ​mm, p ​< ​0.001). The anatomic grafts had an observed maximum step-off of −0.9 ​mm and a maximum contour mismatch of 0.8 ​mm. ConclusionThis study validates a process designed to fabricate anatomically accurate cartilage grafts using MRI and 3D printing technology. Anatomic grafts demonstrated superior fit compared to generic flat grafts. Level of evidenceLevel IV.

Comparison of Minced Cartilage Implantation with Autologous Chondrocyte Transplantation in an In Vitro Inflammation Model.

The current gold standard to treat large cartilage defects is autologous chondrocyte transplantation (ACT). As a new surgical method of cartilage regeneration, minced cartilage implantation (MCI) is increasingly coming into focus. The aim of this study is to investigate the influence of chondrogenesis between isolated and cultured chondrocytes compared to cartilage chips in a standardized inflammation model with the proinflammatory cytokine TNFα. Articular chondrocytes from bovine cartilage were cultured according to the ACT method to passage 3 and transferred to spheroid culture. At the same time, cartilage was fragmented (<1 mm3) to produce cartilage chips. TNFα (20 ng/mL) was supplemented to simulate an inflammatory process. TNFα had a stronger influence on the passaged chondrocytes compared to the non-passaged ones, affecting gene expression profiles differently between isolated chondrocytes and cartilage chips. MCI showed less susceptibility to TNFα, with reduced IL-6 release and less impact on inflammation markers. Biochemical and histological analyses supported these findings, showing a greater negative influence of TNFα on the passaged pellet cultures compared to the unpassaged cells and MCI constructs. This study demonstrated the negative influence of TNFα on chondrogenesis in a chondrocyte spheroid culture and cartilage fragment model. Passaged chondrocytes are more sensitive to cytokine influences compared to non-passaged cells and chondrons. This suggests that MCI may have superior regeneration potential in osteoarthritic conditions compared to ACT. Further investigations are necessary for the translation of these findings into clinical practice.

Implantation of hUCB-MSCs generates greater hyaline-type cartilage than microdrilling combined with high tibial osteotomy.

To compare the outcomes of treating large cartilage defects in knee osteoarthritis using human allogeneic umbilical cord blood-derived mesenchymal stem cell (hUCB-MSC) implantation or arthroscopic microdrilling as a supplementary cartilage regenerative procedure combined with high tibial osteotomy (HTO). This 1-year prospective comparative study included 25 patients with large, near full-thickness cartilage defects (International Cartilage Repair Society grade ≥ IIIB) in the medial femoral condyles and varus malalignment. Defects were treated with hUCB-MSC implantation or arthroscopic microdrilling combined with HTO. The primary outcomes were pain visual analogue scale and International Knee Documentation Committee subjective scores at 12, 24and 48 weeks. Secondary outcomes included arthroscopic, histologicaland magnetic resonance imaging assessments at 1 year. Fifteen and 10 patients were treated via hUCB-MSC implantation and microdrilling, respectively. Baseline demographics, limb alignmentand clinical outcomes did not significantly differ between the groups. Cartilage defects and total restored areas were significantly larger in the hUCB-MSC group (7.2 ± 1.9 vs. 5.2 ± 2.1 cm2, p = 0.023; 4.5 ± 1.4 vs. 3.0 ± 1.6 cm2, p = 0.035). The proportion of moderate-to-strong positive type II collagen staining was significantly higher in the hUCB-MSC group compared to that in the microdrilled group (93.3% vs. 60%, respectively). Rigidity upon probing resembled that of normal cartilage tissue more in the hUCB-MSC group (86.7% vs. 50.0%, p = 0.075). Histological findings revealed a higher proportion of hyaline cartilage in the group with implanted hUCB-MSC (p = 0.041). hUCB-MSC implantation showed comparable clinical outcomes to those of microdrilling as supplementary cartilage procedures combined with HTO in the short term, despite the significantly larger cartilage defect in the hUCB-MSC group. The repaired cartilage after hUCB-MSC implantation showed greater hyaline-type cartilage with rigidity than that after microdrilling. Level II, Prospective Comparative Cohort Study.

Responsiveness of Patient-Reported Outcome Measures After Large Knee Articular Cartilage Transplantation: A Systematic Review and Meta-analysis

Background: Cartilage transplantation is commonly used to treat large (>4 cm2) articular cartilage defects of the knee. The 2 most common transplants are osteochondral allograft transplantation and autologous chondrocyte implantation. Several patient-reported outcome measures (PROMs) have been used to determine the efficacy of treatment, but it is unknown which measures are the most effective. Purpose: To report the multiple PROMs used after large knee articular cartilage transplantation surgery and to compare the responsiveness between them. Study Design: Meta-analysis; Level of evidence, 4. Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic search of the PubMed/MEDLINE and Web of Science databases was performed. A total of 181 articles met inclusion criteria. Patient and study characteristics were extracted, including pre- and postoperative means for PROMs. From the articles that met inclusion criteria for responsiveness analysis (2+ PROMs reported, 1-year minimum follow-up, reported pre- and postoperative means and standard deviations; n = 131), the authors compared the responsiveness between PROM instruments using effect size and relative efficiency (RE) if a PROM could be compared with another in ≥10 articles. Results: A total of 10,015 patients (10,093 knees; mean age, 34.8 years; mean body mass index, 26.1) were included in this study. The mean follow-up time was 58.3 months (range, 1.5-247.2 months), imaging findings were reported in 80 articles (44.2%), patient satisfaction was reported in 39 articles (21.5%), and range of motion was reported in 10 articles (5.5%). There were 58 unique PROM instruments identified, with the most used being the International Knee Documentation Committee (IKDC) score (n = 118; 65.2%), followed by Knee injury and Osteoarthritis Outcome Score (KOOS) Pain (n = 58; 32.0%), KOOS Sport and Recreation (n = 58; 32.0%), KOOS Quality of Life (n = 57; 31.5%), KOOS Activities of Daily Living (n = 57; 31.5%), and KOOS Symptoms (n = 57; 31.5%). Overall, IKDC was found to have the greatest effect size (1.68) and the best responsiveness of the other PROMs, which include KOOS Pain (RE, 1.38), KOOS Symptoms (RE, 3.06), KOOS Activities of Daily Living (RE, 1.65), KOOS Sport and Recreation (RE, 1.44), Lysholm (RE, 1.76), and Tegner (RE, 1.56). Conclusion: The IKDC is the most responsive PROM after large knee articular cartilage transplantation surgery. The IKDC score is recommended for assessing outcomes after cartilage transplantation surgery.

Current Advances in Regenerative Medicine for Articular Cartilage Injury: Progress and Market Trends

Today, treatments of cartilage and osteochondral lesions are routine clinical procedures. Treatment of large Articular Cartilage (AC) defects is technically difficult and complex, often accompanied by failure. Articular cartilage is a highly specialized connective tissue with limited ability to repair itself after injury due to a lack of blood vessels, lymph, and nerves. Therefore, without sufficient and potent intervention, cartilage lesions can easily lead to progressive tissue degeneration, disabling joint pain, and eventually the degenerative disease, Osteoarthritis (OA). Various treatments for cartilage regeneration have shown encouraging results, but unfortunately, none of them have been the perfect solution. New minimally invasive and effective techniques are being developed. The development of tissue engineering technology has created strong promise to engineer or regenerate functional and healthy articular cartilage. In this technology, potential stem cell sources are mainly supplied with pluripotent stem cells and mesenchymal stem cells from various sources. In the meantime, some such as BioSeed®-C and NOVOCART® have been marketed. In this review, the common techniques of articular cartilage reconstruction and the clinical application of articular cartilage tissue engineering are described in detail.

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.

Hyperplastic Human Macromass Cartilage for Joint Regeneration.

Cartilage damage affects millions of people worldwide. Tissue engineering strategies hold the promise to provide off-the-shelf cartilage analogs for tissue transplantation in cartilage repair. However, current strategies hardly generate sufficient grafts, as tissues cannot maintain size growth and cartilaginous phenotypes simultaneously. Herein, a step-wise strategy is developed for fabricating expandable human macromass cartilage (macro-cartilage) in a 3D condition by employing human polydactyly chondrocytes and a screen-defined serum-free customized culture (CC). CC-induced chondrocytes demonstrate improved cell plasticity, expressing chondrogenic biomarkers after a 14.59-times expansion. Crucially, CC-chondrocytes form large-size cartilage tissues with average diameters of 3.25 ± 0.05mm, exhibiting abundant homogenous matrix and intact structure without a necrotic core. Compared with typical culture, the cell yield in CC increases 2.57 times, and the expression of cartilage marker collagen type II increases 4.70 times. Transcriptomics reveal that this step-wise culture drives a proliferation-to-differentiation process through an intermediate plastic stage, and CC-chondrocytes undergo a chondral lineage-specific differentiation with an activated metabolism. Animal studies show that CC macro-cartilage maintains a hyaline-like cartilage phenotype in vivo and significantly promotes the healing of large cartilage defects. Overall, an efficient expansion of human macro-cartilage with superior regenerative plasticity is achieved, providing a promising strategy for joint regeneration.

Poster 365: Initial outcomes after unicompartmental tibiofemoral bipolar osteochondral and meniscus allograft transplantation in the knee using high-viability tissues

Objectives: To report initial outcomes for unicompartmental tibiofemoral bipolar osteochondral allograft transplantation (OCAT) with meniscus allograft transplantation (MAT) using fresh high-cell- viability tissues for treatment of knee articular cartilage defects with meniscus deficiency. The study was designed to test the hypothesis that primary OCAT and MAT using high-viability tissues will be associated with successful short-term (2 to 6 years) outcomes based on statistically significant and clinically meaningful improvements in pain and function in the majority of patients. Methods: With IRB approval and documented informed consent, patients who underwent primary OCAT and MAT for large articular cartilage defects with meniscus deficiency involving at least one femoral condyle, tibial plateau, and meniscus, all of which were opposing (bipolar). Surgeries were defined as Uni when patients underwent OCAT and MAT involving one femoral condyle, tibial plateau, and meniscus in the same compartment or Uni-Plus when patients underwent Uni OCAT and MAT with at least one other OCA transplant to treat a large (&gt;2.5cm2) grade III or IV focal articular cartilage defect of the patella, trochlea, femoral condyle, or tibial plateau. Patients who had at least 2-year follow up data regarding complications, failures, adherence, and patient reported outcome measures (PROMs) were analyzed. Patients who required OCA and/or MAT revision or artificial arthroplasty were defined as treatment failures. Patient reported outcome measures (PROMs) including VAS pain, IKDC, SANE, PROMIS Global Health and Physical Function, were collected at 3 and 6 months and then yearly after transplantation. Outcomes were compared based on patient sex, age, and BMI, tobacco use, previous and concurrent procedures, differences in number of surfaces transplanted (Uni vs Uni-Plus), and adherence. Significance was set at P &lt; 0.05. Differences in PROMs were also assessed for minimum clinically important differences. Results: Seventy-six patients (n=52 males; 68%) met inclusion criteria (mean followup = 52 months; median = 56 months; range, 24-70 months). Mean age was 41.1 years (range, 15-69 years) and mean body mass index (BMI) was 28.9 kg/m2 (range, 17-46). Forty-eight patients underwent OCAT(s) in addition to Uni (Uni-Plus). Eight patients (10.5%) underwent concurrent ACL reconstruction, and 28 patients (36.8%) underwent ipsilateral lower extremity osteotomy in order to address co-morbidities. Twenty-three patients (30.3%) were documented to be non-adherent during the first year after transplantation. Initial (&gt;2-year) success rate was 77.6% with 8 patients (10.5%) undergoing OCA and/or MAT revision and 9 patients (11.8%) converted to arthroplasty. Variables associated with increased risk for treatment failure (revision or arthroplasty) included ipsilateral osteotomy (p = .046; OR = 3.3), ipsilateral concurrent procedure (p = .0057; OR = 5.5), and non-adherence (p = .0009; OR = 7.2). None of the patients undergoing OCA and/or MAT revision surgery in the present study required arthroplasty at the time of data analysis such that overall success rate for primary and revision unicompartmental bipolar OCA plus MAT was 88.2%. There were statistically significant (p &lt; .0001) and clinically important improvements from preoperative levels for all patient reported outcomes at each annual follow-up time point. Conclusions: Unicompartmental tibiofemoral bipolar osteochondral and meniscus allograft transplantation can result in successful short-term (2 to 6 years) outcomes and satisfaction in the majority (78%) of patients. Primary MOPS-preserved OCAT and MAT for treatment of femoral condyle and tibial plateau articular cartilage defects with concurrent meniscus deficiency was associated with statistically significant and clinically meaningful improvements in patient-reported measures of pain and function.

Development of a 3D-printed bioabsorbable composite scaffold with mechanical properties suitable for treating large, load-bearingarticular cartilage defects.

Extracellular matrix (ECM) biomaterials have shown promise for treating small artucular-joint defetcs. However, ECM-based biomaterials generally lack appropriate mechanical properties to support physiological loads and are prone to delamination in larger cartilage defects. To overcome these common mechanical limitations, a collagen hyaluronic-acid (CHyA) matrix, with proven regenerative potential, was reinforced with a bioabsorbable 3D-printed framework to support physiological loads. Polycaprolactone (PCL) was 3D-printed in two configurations, rectilinear and gyroid designs, that were extensively mechanically characterised. Both scaffold designs increased the compressive modulus of the CHyA matrices by three orders of magnitude, mimicking the physiological range (0.5-2.0 MPa) of healthy cartilage. The gyroid scaffold proved to be more flexible compared to the rectilinear scaffold, thus better contouring to the curvature of a femoral condyle. Additionally, PCL reinforcement of the CHyA matrix increased the tensile modulus and allowed for suture fixation of the scaffold to the subchondral bone, thus addressing the major challenge of biomaterial fixation to articular joint surfaces in shallow defects. In vitro evaluation confirmed successful infiltration of human mesenchymal stromal cells (MSCs) within the PCL-CHyA scaffolds, which resulted in increased production of sulphated glycosaminoglycans (sGAG/DNA; p = 0.0308) compared to non-reinforced CHyA matrices. Histological staining using alcian blue confirmed these results, while also indicating greater spatial distribution of sGAG throughout the PCL-CHyA scaffold. These findings have a great clinical importance as they provide evidence that reinforced PCL-CHyA scaffolds, with their increased chondroinductive potential and compatibility with joint fixation techniques, could be used to repair large-area chondral defects that currently lack effective treatment options.

Initial Outcomes After Unicompartmental Tibiofemoral Bipolar Osteochondral and Meniscal Allograft Transplantation in the Knee Using MOPS-Preserved Fresh (Viable) Tissues

Background: Unicompartmental tibiofemoral bipolar osteochondral allograft transplantation (OCAT) with meniscal allograft transplantation (MAT) has not historically been associated with consistently successful outcomes for treatment of knee articular cartilage defects with meniscal deficiency. Hypothesis: Primary OCAT and MAT using fresh tissues will be associated with successful short-term outcomes based on statistically significant and clinically meaningful improvements in pain and function in the majority of patients. Study Design: Case series; Level of evidence, 4. Methods: Patients were prospectively enrolled into a registry for outcomes after OCAT and MAT. Patients included those who underwent primary OCAT and MAT using Missouri Osteochondral Preservation System (MOPS)–preserved allografts for treatment of large bipolar tibiofemoral articular cartilage defects with meniscal deficiency and had a minimum of 2-year follow-up data. Results: A total of 76 patients (n = 52 male; 68%) met inclusion criteria (mean follow-up, 52 months). The mean age was 41.1 years (range, 15-69 years), and the mean body mass index was 28.9 (range, 17-46); 48 patients underwent another OCAT in addition to the unicompartmental bipolar tibiofemoral OCAT and MAT; 23 patients (30.3%) were documented to be nonadherent to the prescribed postoperative restriction and rehabilitation protocol. The initial success rate (>2 years) was 77.6%, with 8 patients (10.5%) undergoing revision and 9 (11.8%) converting to arthroplasty. Variables associated with an increased risk for treatment failure (revision or arthroplasty) included ipsilateral osteotomy (P = .046; odds ratio [OR] = 3.3), ipsilateral concurrent procedure (P = .0057; OR = 5.5), and nonadherence (P = .0009; OR = 7.2). None of the patients undergoing revision surgery required arthroplasty at the time of data analysis such that the overall success rate for primary and revision unicompartmental bipolar OCA plus MAT was 88.2%. There were statistically significant (P < .0001) and clinically important improvements for all patient-reported outcomes at each annual follow-up time point. Conclusion: Unicompartmental tibiofemoral bipolar OCAT and MAT can result in successful short-term outcomes (2-6 years) and satisfaction in the majority of patients (78%). Primary MOPS-preserved OCAT with MAT for treatment of femoral condyle and tibial plateau articular cartilage defects with concurrent meniscal deficiency was associated with statistically significant and clinically meaningful improvements in patient-reported measures of pain and function.

Atelocollagen-associated autologous chondrocyte implantation for the repair of large cartilage defects of the knee: Results at three to seven years

BackgroundRecently, various types of engineered autologous chondrocyte implantation (ACI) have been developed. Atelocollagen-associated ACI (A-ACI) is the only ACI procedure covered by Japanese Health Insurance since 2013. The indications of the A-ACI are traumatic cartilage defects and osteochondral dissecans (OCD) for knee joints. PurposeTo evaluate midterm clinical results after A-ACI for the treatment for full-thickness cartilage defects of the knee. MethodsThirteen consecutive patients who underwent A-ACI between 2014 and 2018 had been prospectively enrolled in this study. There were 11 men and 2 women with a mean age of 34 years at the time of surgery. The causes of the cartilage defect were trauma in 10 knees and OCD in 3 knees. The total number of lesions was 15, which were comprised of the medial femoral condyle in 5 knees, the lateral femoral condyle in 5 knees, and the femoral trochlea in 5 knees. The mean size of the lesion was 5.3 cm2. Each knee was clinically and radiologically evaluated preoperatively and postoperatively. ResultsThe mean Lysholm score improved significantly from 74.0 points to 94.0 points (p = 0.008) and each subscale in Knee injury and Osteoarthritis Outcome Score improved significantly (p < 0.001) at the mean final follow-up period of 51 months (range, 36–84 months). The magnetic resonance observation of cartilage repair tissue 2.0 score at the mean follow-up of 38 months was significantly higher than that at 2 months postoperatively (p = 0.014). According to the International Cartilage Repair Society (ICRS) grading scale, 3 knees were graded as normal, 3 knees as nearly normal, and 1 knee as severely abnormal in second-look arthroscopic evaluation at a mean of 22 months (range, 8–41 months) after A-ACI. ConclusionThe present study showed a significant subjective and objective clinical improvement in the A-ACI for large cartilage defects of the knee at a mean follow-up of 51 months (range, 36–84 months).

Osteochondral Allograft Transplantation

Background: Articular cartilage lesions are a significant cause of morbidity and impaired knee function, and attempts to surgically repair damaged cartilage have failed to reliably reproduce native cartilage. Thus, osteochondral allograft transplantation is an effective one-step procedure to repair large cartilage defects. Indications: Osteochondral allograft transplantation is indicated for young active patients with large focal defects, those with a history of previous cartilage repair, and those with cartilage-related degenerative disorders such as osteonecrosis, osteochondritis dissecans, and/or post-traumatic osteochondral defects. Technique Description: In short, after the focal chondral defect is identified, a socket is created with specific dimensions in depth and diameter. The donor cartilage is then secured in a graft station, and a sizing guide is placed through a bushing to confirm the allograft harvest location. Using stabilization from the graft station arm, a coring reamer is then advanced through the donor cartilage, and a saw is used to allow for easy removal of the graft from the donor condyle. The plug is then fashioned to fit the exact dimensions of the socket created earlier in the procedure. A cut on the donor plug is made to fashion the plug to the appropriate depth. A rongeur is used to make the plug more bullet shaped at the end to allow the plug to enter the socket more easily. Small holes are then drilled into the base of the socket to help promote incorporation of the plug into the socket during the healing process. After the socket is irrigated, the plug is then placed into the socket, and a tamp is used to gently tap the cartilage until it is flush with the surrounding surface. Results: After an appropriate rehabilitation protocol is followed for up to 10 months postoperatively, osteochondral allograft transplantation allows for near-to-complete restoration of patient functionality and strength, with return to full activity possible within 1 year. Conclusion: Acute repair of large focal chondral defects is effective in restoring knee strength and functionality and is associated with high patient satisfaction. The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.

Patients with Small Acetabular Cartilage Defects Caused by Femoroacetabular Impingement Do Not Benefit from Microfracture

According to current recommendations, large cartilage defects of the hip over 2 cm2 are suggested to undergo autologous chondrocyte transplantation (ACT), while small defects should be treated with microfracture. We investigated if patients with small chondral defects of the hip joint (≤100 mm2) actually benefit from microfracture. In this retrospective multicenter cohort study 40 patients with focal acetabular cartilage defects smaller than 100 mm2 and of ICRS grade ≥2 caused by femoroacetabular impingement were included. Twenty-six unrandomized patients underwent microfracture besides treatment of the underlying pathology; in 14 patients cartilage lesions were left untreated during arthroscopy. Over a mean follow-up of 28.8 months patient-reported outcome was determined using the iHOT33 (international hip outcome tool) and the VAS (visual analog scale) for pain. The untreated group showed a statistically significant improvement of the iHOT33 after 12 (p = 0.005), 24 (p = 0.019), and 36 months (p = 0.002) compared to the preoperative score, whereas iHOT33 in the microfracture group did not reveal statistically significant changes over time. There was no significant difference between both groups on any time point. Regarding pain both groups did not show a significant improvement over time in the VAS. The subjective outcome of patients with small cartilage defects of the hip (≤100 mm2) improves 12 months after arthroscopic FAIS surgery without any cartilage treatment. However, no improvement could be seen after microfracture. Therefore, a reserved surgical treatment for small cartilage defects of the hip under preservation of the subchondral bone is recommended especially if a simultaneous impingement correction is performed.

Results of ultra-fresh osteochondral allograft transplantation for large cartilage defects in the knee joint.

This study aims to investigate whether ultra-fresh osteochondral allograft (OCA) transplantation was a good therapeutic alternative for the treatment of otherwise challenging, massive osteochondral defects in the knee joint. Between April 2011 and July 2022, a total of 16 ultra-fresh knee transplantations (9 males, 7 females; median age: 30.2 years; range, 14 to 62 years) having large osteochondral defects on femoral condyles were included. The operations were performed by two surgeons. The condition of the patients were evaluated based on regular follow-up physical examinations, imaging studies and by recording and evaluating clinical scores (modified Cincinnati scores, and 2000 International Knee Documentation Committee [IKDC] scores). The median follow-up was 65±48 (range, 6 months to 12 years). At two years after transplantation, there was a significant improvement in the modified Cincinnati scores (preoperative score of 35.75 increased to 83.75; p<0.001) and also to the IKDC scores (preoperative score of 28.7 increased to 76.3; p<0.001). One patient developed an early septic complication, and another three patients underwent reoperation after the OCA transplantations for non-septic reasons. Ultra-fresh OCA transplantation is a good therapeutic alternative for the treatment of otherwise challenging, massive osteochondral defects in the knee joint. Such a shortening of the transplantation time and its positive effect on the better long-term survival of transplanted chondrocytes has not yet been proven; however, the minimizing of transplantation time may create the conditions necessary for successful OCA transplantations many years after the implantation.