Freeze-Dried Curdlan/Whey Protein Isolate-Based Biomaterial as Promising Scaffold for Matrix-Associated Autologous Chondrocyte Transplantation—A Pilot In-Vitro Study

The purpose of this pilot study was to establish whether a novel freeze-dried curdlan/whey protein isolate-based biomaterial may be taken into consideration as a potential scaffold for matrix-associated autologous chondrocyte transplantation. For this reason, this biomaterial was initially characterized by the visualization of its micro- and macrostructures as well as evaluation of its mechanical stability, and its ability to undergo enzymatic degradation in vitro. Subsequently, the cytocompatibility of the biomaterial towards human chondrocytes (isolated from an orthopaedic patient) was assessed. It was demonstrated that the novel freeze-dried curdlan/whey protein isolate-based biomaterial possessed a porous structure and a Young’s modulus close to those of the superficial and middle zones of cartilage. It also exhibited controllable degradability in collagenase II solution over nine weeks. Most importantly, this biomaterial supported the viability and proliferation of human chondrocytes, which maintained their characteristic phenotype. Moreover, quantitative reverse transcription PCR analysis and confocal microscope observations revealed that the biomaterial may protect chondrocytes from dedifferentiation towards fibroblast-like cells during 12-day culture. Thus, in conclusion, this pilot study demonstrated that novel freeze-dried curdlan/whey protein isolate-based biomaterial may be considered as a potential scaffold for matrix-associated autologous chondrocyte transplantation.

Patellar MACI With Tibial Tubercle Osteotomy

Background: Chondral pathology is frequently encountered during knee arthroscopies with a prevalence rate of 63% to 66%. Prior studies have demonstrated that unaddressed or excised fragments result in poor knee function and arthritis. As a result, chondral-related procedures have increased in popularity, and now more than 200,000 procedures are performed annually. Indications: We present a case of an active 32-year-old woman, prior collegiate basketball player, with persistent left knee pain noted to have a full-thickness patellar articular cartilage defect and maltracking. Technique: A patellar autologous matrix-induced chondrocyte is implanted with a concomitant tibial tubercle osteotomy (TTO) and lateral retinacular lengthening. Results: At 9 weeks, the patient had no knee pain with full range of motion symmetric to the contralateral side while slowly progressing with quadriceps strengthening. Discussion/Conclusion: Successful outcomes addressing large patellar chondral defects and maltracking can be achieved with matrix autologous chondrocyte implantation and concomitant TTO with lateral retinacular lengthening.

Time Matters: Knee Cartilage Defect Expansion and High-Grade Lesion Formation while Awaiting Autologous Chondrocyte Implantation

Objective The objective of this study was to assess potential risk factors, including time delay until implantation, for knee cartilage defect expansion or new high-grade defect formation between biopsy and Autologous Chondrocyte Implantation (ACI) or Matrix Autologous Chondrocyte Implantation (MACI). Study design Consecutive knee ACI and MACI cases by a single surgeon ( n = 111) were reviewed. The relationship between time between biopsy and staged implantation and (1) progression in primary cartilage defect size and (2) development of a new high-grade (Outerbridge grade ≥3) cartilage defect were determined with adjustment for demographics, body mass index, smoking status, coronal alignment, initial cartilage status, and prior surgery. Results Average size of the primary defect at time of biopsy was 4.50 cm2. Mean time to chondrocyte implantation was 155 days. Defect expansion increased 0.11 cm2 (standard error = 0.03) per month delay to implantation ( P = 0.001). Independent predictors of defect expansion were male sex, smaller initial defect size, and delay to implantation (adjusted mean = 0.15 cm2 expansion per month). A total of 16.2% of patients ( n = 18/111) developed a new high-grade defect. Independent predictors of a new secondary defect were Outerbridge grade 2 changes (vs. 0-1) on the surface opposing the index defect and delayed implantation (per month increase, adjusted odds ratio = 1.21, 95% confidence interval: 1.01-1.44; P = 0.036). Conclusions Patients undergoing 2-stage cell-based cartilage restoration with either ACI or MACI demonstrated long delays between stages of surgery, placing them at risk for expanding defects and development of new high-grade cartilage defects. Patients who were male, had smaller initial defect size, and longer time between surgeries were at greater risk for defect expansion. Level of Evidence III, retrospective comparative study.

Repairing Cartilage with Processed Chondrocyte Constructs: A 6-Month Study Using a Porcine Model

Objective Autologous chondrocyte implantation was the first cell-based therapy that used a tissue engineering process to repair cartilage defects. Recently improved approaches and tissue-engineered cell constructs have been developed for growing patient populations. We developed a chondrocyte construct using a collagen gel and sponge scaffold and physicochemical stimuli, implanted with a surgical adhesive. We conducted a proof-of-concept study of these improvements using a cartilage defect model in miniature swine. Design We implanted the autologous chondrocyte constructs into full-thickness chondral defects in the femoral condyle, compared those results with empty and acellular scaffold controls, and compared implantation techniques with adhesive alone and with partial adhesive with suture. Two weeks after the creation of the defects and implantation of the cellular or acellular constructs, we arthroscopically confirmed that the implanted constructs remained at the chondral defects. We evaluated the regenerated tissue macro- and microscopically 6 months after the cell constructs were implanted. The tissues were stained with Safranin-O and evaluated using Sellers’ histology grading system. Results The defects implanted with processed cell constructs and acellular scaffolds were filled with chondrocyte-like round cells and with nearly normal tissue architecture that were significantly greater degree compared to empty defect control. Even with the adhesive alone and with suture alone, the cell construct was composed of the dense cartilaginous matrix that was found in the implantation using both the sutures and the adhesive. Conclusion Implantation of cell constructs promoted regeneration and integration of articular cartilage at chondral defects in swine by 6 months.

Early Efficacy of Type I Collagen-Based Matrix-Assisted Autologous Chondrocyte Transplantation for the Treatment of Articular Cartilage Lesions

Background: Articular cartilage is a complex structure that allows for low frictional gliding and effective shock absorption. Various sports injuries and inflammatory conditions can lead to lesions in the articular cartilage, which has limited regenerative potential. Type I collagen combined with autologous chondrocytes in a three-dimensional culture were used to induce the regeneration of single-layer autologous expanded chondrocytes without chondrogenic differentiation.Purpose: To assess the clinical, radiological, and histological changes following collagen-based autologous chondrocyte transplantation (MACT) for chondral knee lesions.Methods: The study prospectively enrolled 20 patients with symptomatic knee chondral lesions (mean size lesion was 2.41 ± 0.43 cm2, range: 2.0–3.4 cm2) in the lateral femoral condyle and femoral groove who underwent type I collagen-based MACT between July 2017 and July 2019. knee injury and osteoarthritis outcome score (KOOS) was assessed before the procedure, and periodic clinical follow-up was conducted every 3 months for a maximum of 12 months following the procedure and at 1-year intervals thereafter. Magnetic resonance imaging (MRI) T2 mapping of repaired cartilage was also used for the quantitative analysis of regeneration. In one patient, second-look arthroscopy was performed to assess cartilage regeneration characteristics, and a portion of regenerated cartilage was harvested for histological evaluation 12 months after implantation.Results: At pre-operation and at three, six, 12, and 24 months after the operation, KOOS pain, symptoms, daily life activities, sports and recreation, as well as the quality of life were significantly improved between every two time points. Hematoxylin and eosin (HE) staining indicated that the newly formed cartilage was comprised of naive chondrocytes. Safranin O-fast (S-O) green staining of the regenerated tissue revealed fibroblast-like cells surrounded by glycosaminoglycans. Immunohistochemistry (IHC) analysis indicated that collagen type II was uniformly distributed at the deep zone of articular cartilage and type I collagen mainly depositing in the superficial cartilage layer. The T2 values for repaired tissue gradually decreased, eventually approaching near-average values.Conclusion: The present study demonstrated that type I collagen-based MACT is a clinically effective treatment for improving functionality and pain levels. Histological evidence confirmed hyaline cartilage induction and showed that repaired cartilage tended to emerge from the deep to the superficial layer. The quantitative MRI T2 mapping test indicated that there still was a difference between the transplanted cartilage and the surrounding hyaline cartilage. Taken together, the current method represents an efficient approach for the restoration of knee cartilage lesions.

Autologous chondrocyte implantation combined with anterior cruciate ligament reconstruction: similar short-term results in comparison with isolated cartilage repair in ligament intact joints

Purpose Both acute ruptures of the anterior cruciate ligament (ACL) as well as chronic ACL insufficiency show a high association with focal cartilage defects of the knee. However, the results after combined ACL reconstruction and cartilage repair are not well investigated. The aim of the present study was to investigate the short-term outcomes after autologous chondrocyte implantation (ACI) in combination with ACL reconstruction and to compare the results with patients who underwent isolated ACI in ligament intact knees. Methods All patients who were registered in the German Cartilage Registry with ACI for focal cartilage defects in the knee joint in combination with ACL reconstruction and who completed the 24 month follow-up were included in the study group. A matched-pair procedure according to gender, defect location, defect size, and age was used to create a control group of patients with isolated ACI in ACL intact joints. The Knee Injury and Osteoarthritis Outcome Score (KOOS) and the numeric analog scale for pain (NAS) were used to assess the preoperative state as well as the clinical outcomes 12 and 24 months after surgery. Results A total of 34 patients were included in both the study group (age mean 33.3 ± SD 8.8 years) and the control group (33.6 ± 8.4 years) with a median defect size of 466 (25%-75% IQR 375–600) mm2 and 425 (IQR 375–600) mm2, respectively. In comparison with the preoperative state (median 67, IQR 52–75), the study group showed a significant increase of the total KOOS after 12 months (78, IQR 70–86; p = 0.014) and after 24 months (81, IQR 70–84; p = 0.001). The NAS for pain did not change significantly in the postoperative course. In comparison with the control group there was no significant difference for the total KOOS neither preoperative (control group median 67, IQR 52–73) nor at any postoperative time point (12 months: 82, IQR 67–93; 24 months: 81, IQR 71–91). Conclusion The clinical short-term outcomes after ACI at the knee joint in combination with ACL reconstruction are good and similar to the results after isolated ACI in ligament intact knees. Level of evidence III.

Cost-Effectiveness of Particulated Juvenile Articular Cartilage Versus Matrix-Induced Autologous Chondrocyte Implantation for Patellar Chondral Lesions (176)

Objectives: Treatment options for articular cartilage lesions of the patella have evolved over the past several years due to the development of novel cell-based cartilage restoration techniques, including particulated juvenile allograft cartilage (PJAC) and matrix-induced autologous chondrocyte implantation (MACI). The objective of this study was to evaluate the cost -effectiveness of these modalities in the management of patellar cartilage defects. Methods: A Markov state-transition model was utilized to evaluate the cost-effectiveness of three strategies for patients with patellar chondral lesions: (1) nonoperative management, (2) PJAC, and (3) MACI. Probabilities, health utilities, and costs of surgical procedures and rehabilitation protocols were derived from institutional data and literature review. Effectiveness was assessed using quality-adjusted life-year (QALY). Cost-effectiveness was evaluated from societal and payer perspectives over a 15-year time horizon. The principal outcome measure was the incremental cost-effectiveness ratio (ICER). Sensitivity analyses were performed on pertinent model parameters to assess their effect on base case conclusions. Results: From a societal perspective, nonoperative management, PJAC, and MACI cost $4,140, $52,683, and $83,073 respectively. Nonoperative management, PJAC, and MACI were associated with 4.91, 7.07, and 7.79 QALYs gained, respectively. Therefore, PJAC and MACI were cost-effective relative to nonoperative management (ICERs $22,527/QALY and $27,456/QALY, respectively; Figure 1). Although MACI was more cost-effective than PJAC in the base case, this was strongly sensitive to the estimated probabilities of full versus intermediate benefit following PJAC and MACI (Table 1). If the probabilities of full and intermediate benefit following PJAC were assumed to be the same as those following MACI (i.e., PJAC and MACI were equally effective), then PJAC dominated MACI by being cheaper and more effective. At a $100,000/QALY willingness-to-pay threshold, MACI, PJAC, and nonoperative management were the preferred strategies in 63%, 33%, and 4% of the Monte Carlo probabilistic sensitivity analyses, respectively (Figures 2 and 3). Similar results were seen from a payer perspective. Conclusions: In the management of symptomatic patellar cartilage defects, PJAC and MACI were both cost-effective compared to nonoperative treatment in the management of symptomatic patellar cartilage defects; however, MACI was the preferred strategy in our base-case analysis. The cost-effectiveness of PJAC compared to MACI depended heavily on the probability of achieving full versus intermediate benefit after PJAC and MACI.

Scaffolds for knee chondral lesions – indications and technical tips

Chondral lesions following an injury to the knee joint have poor healing potential and may lead to osteoarthritis. Nowadays, more and more research is focused on tissue regeneration and the prevention of osteoarthritis development. Efforts to restore the articular cartilage using advanced procedures like autologous chondrocyte implantation led to the development of scaffolds. Although the use of a scaffold-based technique is a reliable and effective method of cartilage repair, only the appropriate qualification can lead to good clinical outcomes.