Matrix-Induced Autologous Chondrocyte Implantation Versus Autologous Chondrocyte Implantation of the Knee A Retrospective Comparison.

OBJECTIVE: The purpose of this study was to compare the short-term clinical outcomes of matrix-induced autologous chondrocyte implantation (MACI) to those seen following traditional autologous chondrocyte implantation (ACI) in the management of symptomatic cartilage lesions of the knee. METHODS: This was a retrospective cohort study of patients who underwent either ACI or MACI from January 2011 to March 2018. Patients with a minimum postoperative follow-up of 18 months were contacted. Demographic information, intraoperative findings, and patient-reported functional outcomes scores were collected. Comparisons were made between the two cell-based cartilage repair techniques. RESULTS: Fifty-six patients were included in the study (39 ACI, 17 MACI). Visual analog scale (VAS) for pain scores improved significantly in both groups, with MACI patients demonstrating significantly lower postoperative pain scores compared to those treated with ACI. In the ACI group, there was a decrease in the Tegner Activity score compared to the preoperative baseline, while no significant difference was seen between pre- and postoperative activity levels in the MACI group. Patients were generally satisfied with the outcome of their procedures, and there was no significant difference in satisfaction between groups. No patients re-quired additional surgery during the follow-up period. CONCLUSION: Both ACI and MACI demonstrated good short-term postoperative clinical results with improved pain and activity levels compared to the preoperative baseline. Patients treated with the MACI technique demonstrated greater reductions in pain scores compared to ACI, and while ACI resulted in a decrease in levels of postoperative activity, activity levels for MACI remained stable.

An injectable active hydrogel based on BMSC-derived extracellular matrix for cartilage regeneration enhancement.

Articular cartilage injury impairs joint function and necessitates orthopedic intervention to restore the structure and function of the cartilage. Extracellular matrix (ECM) scaffolds derived from bone marrow mesenchymal stem cells (BMSCs) can effectively promote cell adhesion, proliferation, and chondrogenesis. However, pre-shaped ECM scaffolds have limited applicability due to their poor fit with the irregular surface of most articular cartilage defects. In this study, we fabricated an injectable active ECM hydrogel from autologous BMSCs-derived ECM by freeze-drying, liquid nitrogen milling, and enzymatic digestion. Moreover, our in vitro and in vivo results demonstrated that the prepared hydrogel enhanced chondrocyte adhesion and proliferation, chondrogenesis, cartilage regeneration, and integration with host tissue, respectively. These findings indicate that active ECM components can provide trophic support for cell proliferation and differentiation, restoring the structure and function of damaged cartilage.

Fresh Osteochondral Allograft for Large Talar Osteochondral Lesions.

Osteochondral lesions of the talus are being recognized as an increasingly common injury. Large osteochondral lesions have significant biomechanical consequences and often require resurfacing with both boney and cartilaginous graft. The current treatment options include osteochondral autograft transfer, mosaicplasty, autologous chondrocyte implantation, or osteochondral allograft transplantation. Allograft procedures have the advantage of no donor site morbidity and ability to match the defect line to line. Careful transportation, storage, and handling of the allograft are critical to success. The failure of nonoperative management, failure of arthroscopic treatment, or large defects are an indication for resurfacing.

Comparative study on clinical outcomes in autologous chondrocyte implantation using three-dimensional cultured JACC® with collagen versus periosteum coverings.

This study investigates the efficacy of a collagen membrane as a substitute for autologous periosteum in atelocollagen-assisted autologous chondrocyte implantation (ACI) using J-TEC autologous cultured cartilage (JACC®). Sixty-nine patients with knee joint chondral defects underwent ACI using JACC®-34 with periosteum-covered ACI (P-ACIs) and 35 with collagen-covered ACI (C-ACIs). Clinical outcomes were compared through patient-reported measures, International Cartilage Repair Society (ICRS) Cartilage Repair Assessment (CRA) scores at second-look arthroscopy one year postoperatively, and adverse event incidence. Postoperative subjective scores significantly improved up to two years, with no significant differences between P-ACI and C-ACI groups. However, C-ACI exhibited a lower adverse event rate (p = 0.034) and significantly higher ICRS CRA scores (p = 0.0001). Notably, C-ACI outperformed P-ACI in both femoral condyle and trochlea assessments (p = 0.0157 and 0.0005, respectively). While clinical outcomes were comparable, the use of a collagen membrane demonstrated superiority in ICRS CRA during second-look arthroscopy and adverse event occurrence.

Bioengineering autologous cartilage grafts for functional posterior lamellar eyelid reconstruction: A preliminary study in rabbits.

The reconstruction of posterior lamellar eyelid defects remains a significant challenge in clinical practice due to anatomical complexity, specialized function, and aesthetic concerns. The ideal substitute for the posterior lamellar should replicate the native tarsoconjunctival tissue, providing both mechanical support for the eyelids and a smooth surface for the globe after implantation. In this study, we present an innovative approach utilizing tissue-engineered cartilage (TEC) grafts generated from rabbit auricular chondrocytes and a commercialized type I collagen sponge to reconstruct critical-sized posterior lamellar defects in rabbits. The TEC grafts demonstrated remarkable mechanical strength and maintained a stable cartilaginous phenotype both in vitro and at 6 months post-implantation in immunodeficient mice. When employed as autografts to reconstruct tarsal plate defects in rabbits' upper eyelids, these TEC grafts successfully restored normal eyelid morphology, facilitated smooth eyelid movement, and preserved the histological structure of the conjunctival epithelium. When applied in bilayered tarsoconjunctival defect reconstruction, these TEC grafts not only maintained the normal contour of the upper eyelid but also supported conjunctival epithelial cell migration and growth from the defect margin towards the centre. These findings highlight that auricular chondrocyte-based TEC grafts hold great promise as potential candidates for clinical posterior lamellar reconstruction. STATEMENT OF SIGNIFICANCE: The complex structure and function of the posterior lamellar eyelid continue to be significant challenges for clinical reconstructive surgeries. In this study, we utilized autologous auricular chondrocyte-based TEC grafts for posterior lamellar eyelid reconstruction in a preclinical rabbit model. The TEC grafts exhibited native cartilaginous histomorphology and comparable mechanical strength to those of the native human tarsal plate. In rabbit models with either tarsal plate defects alone or bilayered tarsoconjunctival defects, TEC grafts successfully restored the normal eyelid contour and movement, as well as supported preservation and growth of conjunctival epithelium. This is the first study to demonstrate autologous TEC grafts can be employed for repairing tarsal plate defects, thereby offering an alternative therapeutic approach for treating posterior lamellar defects in clinic settings.

Total meniscus replacement with a 3D printing of network hydrogel composite scaffold in a rabbit model.

PURPOSE: The aim of this study was to evaluate the role of a novel total meniscal implant in promoting meniscal regeneration and protecting articular cartilage in a rabbit model for 3 and 6 months. METHODS: Thirty-six New Zealand rabbits were selected and divided into poly(ɛ-caprolactone) (PG-Pg) scaffold group, meniscectomy group and sham group. In this study, it was investigated whether PG-Pg scaffold can prevent articular cartilage degeneration and promote tissue degeneration, and its mechanical properties at 3 and 6 months after surgery were also explored. RESULT: The degree of articular cartilage degeneration was significantly lower in the PG-Pg scaffold group than in the meniscectomy group. The number of chondrocytes increased in the PG-Pg scaffold at 3 and 6 months, while a gradual increase in the mechanical properties of the PG-Pg stent was observed from 6 months. CONCLUSION: The PG-Pg scaffold slows down the degeneration of articular cartilage, promotes tissue regeneration and improves biomechanical properties after meniscectomy. This novel meniscus scaffold holds promise for enhancing surgical strategies and delivering superior long-term results for individuals with severe meniscus tears. LEVEL OF EVIDENCE: NA.

The role of autologous bone grafting in matrix-associated autologous chondrocyte implantation at the knee: Results from the German Cartilage Registry (KnorpelRegister DGOU).

PURPOSE: To investigate whether concomitant autologous bone grafting adversely affects clinical outcome and graft survival after matrix-associated autologous chondrocyte implantation (M-ACI). METHODS: The present study examines registry data of patients who underwent M-ACI with or without autologous bone grafting for large-sized chondral or osteochondral defects. Propensity score matching was performed to exclude potential confounders. A total of 215 patients with similar baseline characteristics were identified. Clinical outcome was assessed at the time of surgery and at 6, 12, 24, 36 and 60 months using the Knee Injury and Osteoarthritis Outcome Score (KOOS). KOOS change, clinical response rate, KOOS subcomponents and failure rate were determined. RESULTS: Patients treated with M-ACI and autologous bone grafting achieved comparable clinical outcomes compared with M-ACI alone. At 24 months postoperatively, the patient-reported outcome (PRO) of patients treated with M-ACI and autologous bone grafting was even significantly better as measured by KOOS (74.9 ± 18.8 vs. 79.2 ± 15.4; p = 0.043). However, the difference did not exceed the minimal clinically important difference (MCID). In patients with M-ACI and autologous bone grafting, a greater change in KOOS relative to baseline was observed at 6 (9.3 ± 14.7 vs. 15.0 ± 14.7; p = 0.004) and 12 months (12.6 ± 17.2 vs. 17.7 ± 14.6; p = 0.035). Overall, a high clinical response rate was observed in both groups at 24 months (75.8% vs. 82.0%; p = n.s.). The estimated survival at the endpoint of reoperation for any reason was 82.1% (SD 2.8) at 8.4 years for isolated M-ACI and 88.7% (SD 2.4) at 8.2 years for M-ACI with autologous bone grafting (p = 0.039). CONCLUSIONS: Even in the challenging cohort of large osteochondral defects, the additional treatment with autologous bone grafting leads to remarkably good clinical outcomes in patients treated with M-ACI. In fact, they tend to benefit more from surgery, have lower revision rates and achieve clinical response rates earlier. Subchondral bone management is critical to the success of M-ACI and should be addressed in the treatment of borderline defects. LEVEL OF EVIDENCE: Level III.

10-Year Prospective Clinical and Radiological Evaluation After Matrix-Induced Autologous Chondrocyte Implantation and Comparison of Tibiofemoral and Patellofemoral Graft Outcomes.

BACKGROUND: Long-term outcomes in larger cohorts after matrix-induced autologous chondrocyte implantation (MACI) are required. Furthermore, little is known about the longer-term clinical and radiological outcomes of MACI performed in the tibiofemoral versus patellofemoral knee joint. PURPOSE: To present the 10-year clinical and radiological outcomes in patients after MACI and compare outcomes in patients undergoing tibiofemoral versus patellofemoral MACI. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Between September 2002 and December 2012, 204 patients who underwent MACI were prospectively registered into a research program and assessed preoperatively and at 2, 5, and 10 years postoperatively. Of these patients, 168 were available for clinical review at 10 years, with 151 (of a total of 182) grafts also assessed via magnetic resonance imaging (MRI). Patients were evaluated using the Knee injury and Osteoarthritis Outcome Score, a visual analog scale for pain frequency and severity, satisfaction, and peak isokinetic knee extensor and flexor strength. Limb symmetry indices (LSIs) were calculated for strength measures. Grafts were scored on MRI scans via the MOCART (magnetic resonance observation of cartilage repair tissue) system, with a focus on tissue infill and an overall MRI graft composite score. RESULTS: All patient-reported outcome measures improved (P < .0001) up to 2 years after surgery. Apart from the significant increase (P = .004) in the peak isokinetic knee extensor LSI, no other patient-reported outcome measure or clinical score had changed significantly from 2 to 10 years. At the final follow-up, 92% of patients were satisfied with MACI to provide knee pain relief, with 76% satisfied with their ability to participate in sports. From 2 to 10 years, no significant change was seen for any MRI-based MOCART variable nor the overall MRI composite score. Of the 151 grafts reviewed via MRI at 10 years, 14 (9.3%) had failed, defined by graft delamination or no graft tissue on MRI scan. Furthermore, of the 36 patients (of the prospectively recruited 204) who were not available for longer-term review, 7 had already proceeded to total knee arthroplasty, and 1 patient had undergone secondary MACI at the same medial femoral condylar site because of an earlier graft failure. Therefore, 22 patients (10.8%) essentially had graft failure over the period. At the final follow-up, patients who underwent MACI in the tibiofemoral (vs patellofemoral) joint reported significantly better Knee injury and Osteoarthritis Outcome Score subscale scores for Quality of Life (P = .010) and Sport and Recreation (P < .001), as well as a greater knee extensor strength LSI (P = .002). Even though the tibiofemoral group demonstrated better 10-year MOCART scores for tissue infill (P = .027), there were no other MRI-based differences (P > .05). CONCLUSION: This study reports the long-term review of a prospective series of patients undergoing MACI, demonstrating good clinical scores, high levels of patient satisfaction, and acceptable graft survivorship at 10 years. Patients undergoing tibiofemoral (vs patellofemoral) MACI reported better long-term clinical outcomes, despite largely similar MRI-based outcomes.

Impact of Wiberg Patellar Type on Outcomes and Survival Following Cell-Based Cartilage Repair for Patellar Chondral Lesions at Midterm Follow-up.

BACKGROUND: Cell-based cartilage repair procedures of the patellofemoral joint have less reliable outcomes than those of the tibiofemoral joint. No previous studies have evaluated the influence of patellar shape on cell-based cartilage repair outcomes. Patellar dysplasia may predispose patients to worse outcomes after cell-based cartilage repair. PURPOSE/HYPOTHESIS: The purpose of this study was to evaluate the relationship between Wiberg patellar type and outcomes after cell-based cartilage repair (autologous chondrocyte implantation or particulated juvenile allograft cartilage transplantation) for the treatment of patellar chondral lesions at a minimum 2-year follow-up. It was hypothesized that Wiberg classification of patellar shape would have no effect on patient-reported outcome measures (PROMs) or graft survival. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Patients undergoing autologous chondrocyte implantation or particulated juvenile allograft cartilage transplantation for full-thickness patellar chondral defects between 2016 and 2020 were retrospectively reviewed after institutional review board approval. The change in PROMs, including International Knee Documentation Committee (IKDC), Kujala, and Veterans RAND 12-item Health Survey Mental and Physical scores, from pre- to postoperatively and the percentage of patients who achieved the minimal clinically important difference (MCID) for IKDC and Kujala scores were compared for the Wiberg type A versus Wiberg type B versus Wiberg type C groups. The log-rank test was used to evaluate for differences in survival between subgroups. RESULTS: A total of 59 patients (63 knees) were included, with a mean age of 33.3 ± 8.6 years, median body mass index of 26.0 (IQR, 21.8-30.2), and median follow-up time of 3.5 years (IQR, 2.6-4.2 years). In total, 26 (41%) patellae were Wiberg type A, 29 (46%) were Wiberg type B, and 8 (13%) were Wiberg type C. There were no differences between Wiberg type A versus Wiberg type B versus Wiberg type C groups with respect to change in PROMs from pre- to postoperatively or the percentage of patients who achieved the MCID for IKDC or Kujala scores (P > .05 for all). There were no differences in survival between groups (P = .45). CONCLUSION: Wiberg patellar type has no effect on patient-reported outcomes or graft survival at midterm follow-up. Patellar dysplasia should not be seen as a contraindication for cell-based cartilage repair procedures.

Significant improvements in clinical outcome measures and patient satisfaction after combined all-arthroscopic meniscal allograft transplantation and autologous chondrocyte implantation: A single-centre longitudinal study.

PURPOSE: The optimal treatment approach for the complex pathology of meniscal insufficiency and coexisting full-thickness cartilage defects remains unclear. The purpose of this study was to evaluate the viability, safety, and efficacy of this combined surgical approach at medium-term follow-up. METHODS: This is a single-centre longitudinal study with blinded outcome assessment. All consecutive patients treated with combined all-arthroscopic meniscal allograft transplantation (MAT) with bone bridge fixation and ACI using chondrospheres at our institution between 2001 and 2021 were eligible for inclusion. Twenty patients with an average follow-up of 72.6 ± 34.4 months were included in the statistical analysis. Clinical outcomes were assessed pre- and postoperatively using the IKDC Subjective Knee Form, Lysholm Score, Tegner Activity Scale, KOOS, and Visual Analog Scale (VAS) for patient satisfaction. Failure and reoperation rates were assessed, and cartilage regeneration tissue was evaluated on postoperative MRI. RESULTS: IKDC scores significantly improved from 52.1 ± 16.9 to 68.5 ± 16.3 (p = 0.003). Lysholm scores improved from 61.5 ± 21.7 to 78.5 ± 12.9 (p = 0.004). Tegner scores improved from 3.5 (1-4) to 4.0 (2-6) (p = 0.014). KOOS scores improved significantly across all subcategories, except 'symptoms', where improvements did not reach statistical significance. VAS for overall patient satisfaction showed improvements but did not reach statistical significance. The combined procedure was successful in 17 patients (85%). Eight patients had to undergo reoperation (40%), comprising mostly small, arthroscopic procedures. Seven reoperations were directly attributable to meniscal allograft transplantation (46.7%). Postoperative Magnetic Resonance Observation of Cartilage Repair Tissue scores were 68.9 ± 16.8 (n = 14). CONCLUSION: Combined arthroscopic MAT and autologous chondrocyte implantation (ACI) is a viable, safe, and effective treatment approach for younger patients with meniscal insufficiency and coexisting full-thickness cartilage damage, where alternative treatment options are limited. The combined surgical procedure achieved significant improvements in clinical outcome measures and patient satisfaction with acceptable failure and high arthroscopic reoperation rates. MAT is the limiting part of this combined procedure, with most failures and reoperations being attributable to MAT, as opposed to ACI. LEVEL OF EVIDENCE: Level III.

Autologous Costal Chondral/Osteochondral Transplantation and Costa-Derived Chondrocyte Implantation for Articular Cartilage Repair: Basic Science and Clinical Applications.

There has been increasing application of autologous costal chondral/osteochondral transplantation (ACCT/ACOT) and costa-derived chondrocyte implantation (ACCI) for articular cartilage repair over the past three decades. This review presents the major evidence on the properties of costal cartilage and bone and their qualifications as grafts for articular cartilage repair, the major clinical applications, and the risks and strategies for costal chondral/osteochondral graft(s) harvest. First, costal cartilage has many specific properties that help restore the articular surface. Costa, which can provide abundant cartilage and cylindrical corticocancellous bone, preserves permanent chondrocyte and is the largest source of hyaline cartilage. Second, in the past three decades, autologous costal cartilage-derived grafts, including cartilage, osteochondral graft(s), and chondrocyte, have expanded their indications in trauma and orthopaedic therapy from small to large joints, from the upper to lower limbs, and from non-weight-bearing to weight-bearing joints. Third, the rate of donor-site complications of ACCT or ACOT is low, acceptable, and controllable, and some skills and accumulated experience can help reduce the risks of ACCT and ACOT. Costal cartilage-derived autografting is a promising technique and could be an ideal option for articular chondral lesions with or without subchondral cysts. More high-quality clinical studies are urgently needed to help us further understand the clinical value of such technologies.

MR imaging after patellar MACI and MPFL reconstruction: a comparison of isolated versus combined procedures.

OBJECTIVE: To qualitatively and quantitatively evaluate the 2.5-year MRI outcome after Matrix-associated autologous chondrocyte implantation (MACI) at the patella, reconstruction of the medial patellofemoral ligament (MPFL), and combined procedures. METHODS: In 66 consecutive patients (age 22.8 ± 6.4years) with MACI at the patella (n = 16), MPFL reconstruction (MPFL; n = 31), or combined procedures (n = 19) 3T MRI was performed 2.5 years after surgery. For morphological MRI evaluation WORMS and MOCART scores were obtained. In addition quantitative cartilage T2 and T1rho relaxation times were acquired. Several clinical scores were obtained. Statistical analyses included descriptive statistics, Mann-Whitney-U-tests and Pearson correlations. RESULTS: WORMS scores at follow-up (FU) were significantly worse after combined procedures (8.7 ± 4.9) than after isolated MACI (4.3 ± 3.6, P = 0.005) and after isolated MPFL reconstruction (5.3 ± 5.7, P = 0.004). Bone marrow edema at the patella in the combined group was the only (non-significantly) worsening WORMS parameter from pre- to postoperatively. MOCART scores were significantly worse in the combined group than in the isolated MACI group (57 ± 3 vs 88 ± 9, P < 0.001). Perfect defect filling was achieved in 26% and 69% of cases in the combined and MACI group, respectively (P = 0.031). Global and patellar T2 values were higher in the combined group (Global T2: 34.0 ± 2.8ms) and MACI group (35.5 ± 3.1ms) as compared to the MPFL group (31.1 ± 3.2ms, P < 0.05). T2 values correlated significantly with clinical scores (P < 0.005). Clinical Cincinnati scores were significantly worse in the combined group (P < 0.05). CONCLUSION: After combined surgery with patellar MACI and MPFL reconstruction inferior MRI outcomes were observed than after isolated procedures. Therefore, patients with need for combined surgery may be at particular risk for osteoarthritis.

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

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

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

BACKGROUND: Recently, 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. PURPOSE: To evaluate midterm clinical results after A-ACI for the treatment for full-thickness cartilage defects of the knee. METHODS: Thirteen 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. RESULTS: The 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. CONCLUSION: The 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).

The regenerative treatment of costal osteochondral graft implantation for partial growth arrest using a rabbit model.

PURPOSE: To investigate the feasibility of cylindrical costal osteochondral graft transplantation as a novel regenerative treatment in growth arrest. METHODS: The medial portion of the proximal tibial growth plate of 6-week-old male New Zealand White rabbits was resected to establish an experimental model of partial growth plate injury. The rabbits were divided into four groups: no-treatment, bone wax transplantation, costal chondral graft, and costal osteochondral graft groups. Radiographic and micro-computed tomography scan results were analyzed to evaluate angular deformity of the tibia and bony bridge formation at the injury site. In addition, repair of the injured growth plate cartilage was assessed histologically at 4, 8, and 12 weeks postoperatively. RESULTS: Radiographic examination revealed that bone wax transplantation continuously decreased the medial proximal tibial angle (MPTA) while the costal chondral graft implantation reduced the decrease of MPTA at 12 weeks postoperatively. The costal osteochondral graft implantation recovered the MPTA, close to the normal. Histologically, the costal osteochondral grafts retained the MPTA in the injured site compared to costal chondral grafts. Additionally, hypertrophic chondrocytes were observed at the graft site in the costal osteochondral graft group at 12 weeks, suggesting that endochondral ossification may occur at the graft site similar to normal ossification. The fluorescence in situ hybridization analysis of osteochondral grafts transplanted from male to female rabbits indicated that they were replaced by cells of host origin. CONCLUSION: The costal osteochondral graft can achieve regeneration without bony bridge formation in partial growth plate injury.

Long-Term Chondrocyte Retention in Partially Decellularized Tracheal Grafts.

OBJECTIVE: Decellularized tracheal grafts possess the biological cues necessary for tissue regeneration. However, conventional decellularization approaches to target the removal of all cell populations including chondrocytes lead to a loss of mechanical support. We have created a partially decellularized tracheal graft (PDTG) that preserves donor chondrocytes and the mechanical properties of the trachea. In this study, we measured PDTG chondrocyte retention with a murine microsurgical model. STUDY DESIGN: Murine in vivo time-point study. SETTING: Research Institute affiliated with Tertiary Pediatric Hospital. METHODS: PDTG was created using a sodium dodecyl sulfate protocol. Partially decellularized and syngeneic grafts were orthotopically implanted into female C57BL/6J mice. Grafts were recovered at 1, 3, and 6 months postimplant. Pre- and postimplant grafts were processed and analyzed via quantitative immunofluorescence. Chondrocytes (SOX9+, DAPI+) present in the host and graft cartilage was evaluated using ImageJ. RESULTS: Partial decellularization resulted in the maintenance of gross tracheal architecture with the removal of epithelial and submucosal structures on histology. All grafts demonstrated SOX9+ chondrocytes throughout the study time points. Chondrocytes in PDTG were lower at 6 months compared to preimplant and syngeneic controls. CONCLUSION: PDTG retained donor graft chondrocytes at all time points. However, PDTG exhibits a reduction in chondrocytes at 6 months. The impact of these histologic changes on cartilage extracellular matrix regeneration and repair remains unclear.

Post-Implantation Inflammatory Responses to Xenogeneic Tissue-Engineered Cartilage Implanted in Rabbit Trachea: The Role of Cultured Chondrocytes in the Modification of Inflammation.

Immune responses to tissue-engineered grafts made of xenogeneic materials remain poorly studied. The scope of current investigations is limited by the lack of information on orthotopically implanted grafts. A deeper understanding of these processes is of great importance since innovative surgical approaches include the implantation of xenogeneic decellularized scaffolds seeded by cells. The purpose of our work is to study the immunological features of tracheal repair during the implantation of tissue-engineered constructs based on human xenogeneic scaffolds modified via laser radiation in rabbits. The samples were stained with hematoxylin and Safranin O, and they were immunostained with antibodies against tryptase, collagen II, vimentin, and CD34. Immunological and inflammatory responses were studied by counting immune cells and evaluating blood vessels and collagen. Leukocyte-based inflammation prevailed during the implantation of decellularized unseeded scaffolds; meanwhile, plasma cells were significantly more abundant in tissue-engineered constructs. Mast cells were insignificantly more abundant in tissue-engineered construct samples. Conclusions: The seeding of decellularized xenogeneic cartilage with chondrocytes resulted in a change in immunological reactions upon implantation, and it was associated with plasma cell infiltration. Tissue-engineered grafts widely differed in design, including the type of used cells. The question of immunological response depending on the tissue-engineered graft composition requires further investigation.

An advanced biphasic porous and injectable scaffold displays a fine balance between mechanical strength and remodeling capabilities essential for cartilage regeneration.

An important challenge in tissue engineering is the regeneration of functional articular cartilage (AC). In the field, biomimetic hydrogels are being extensively studied as scaffolds that recapitulate microenvironmental features or as mechanical supports for transplanted cells. New advanced hydrogel formulations based on salmon methacrylate gelatin (sGelMA), a cold-adapted biomaterial, are presented in this work. The psychrophilic nature of this biomaterial provides rheological advantages allowing the fabrication of scaffolds with high concentrations of the biopolymer and high mechanical strength, suitable for formulating injectable hydrogels with high mechanical strength for cartilage regeneration. However, highly intricate cell-laden scaffolds derived from highly concentrated sGelMA solutions could be deleterious for cells and scaffold remodeling. On this account, the current study proposes the use of sGelMA supplemented with a mesophilic sacrificial porogenic component. The cytocompatibility of different sGelMA-based formulations is tested through the encapsulation of osteoarthritic chondrocytes (OACs) and stimulated to synthesize extracellular matrix (ECM) components in vitro and in vivo. The sGelMA-derived scaffolds reach high levels of stiffness, and the inclusion of porogens impacts positively the scaffold degradability and molecular diffusion, improved fitness of OACs, increased the expression of cartilage-related genes, increased glycosaminoglycan (GAG) synthesis, and improved remodeling toward cartilage-like tissues. Altogether, these data support the use of sGelMA solutions in combination with mammalian solid gelatin beads for highly injectable formulations for cartilage regeneration, strengthening the importance of the balance between mechanical properties and remodeling capabilities.

Chondrocyte-laden gelatin/sodium alginate hydrogel integrating 3D printed PU scaffold for auricular cartilage reconstruction.

Clinically, modified autologous rib cartilage grafts and commercial implants are commonly used for intraoperative repair of auricular cartilage defects caused by injuries. However, scaffold implantation is often accompanied by various complications including absorption and collapse, resulting in undesirable clinical outcomes. Three-dimensional printed auricular cartilage scaffolds have the advantage of individual design and biofunctionality, which attracted tremendous attention in this field. In this study, to better simulate the mechanical properties of auricular cartilage, we tested PU treated by ultrasonication and high temperature for 30 min (PU-30) or 60 min (PU-60). The results indicated that the compression modulus of PU-30 was 2.21-2.48 MPa, which similar to that of natural auricular cartilage (2.22-7.23 MPa) and was chosen for subsequent experiments. And the pores of treated PU were filled with a gelatin/sodium alginate hydrogel loaded with chondrocytes. In vivo analysis using a rabbit model confirmed that implanted PU-30 scaffold filled with chondrocytes contained hydrogel successfully integrated with normal auricular cartilage, and that new cartilage was generated at the scaffold-tissue interface by histological examination. These findings illustrate that this engineered scaffold represents a potential strategy for repair of ear cartilage damage in clinical.

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 ± 0.05 mm, 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.