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.

Regenerative Potential of Platelet Concentrate Lysate in Mechanically Injured Cartilage and Matrix-Associated Chondrocyte Implantation In Vitro

Adjuvant therapy in autologous chondrocyte implantation (ACI) can control the post-traumatic environment and guide graft maturation to support cartilage repair. To investigate both aspects, we examined potential chondro-regenerative effects of lysed platelet concentrate (PC) and supplementary interleukin 10 (IL-10) on mechanically injured cartilage and on clinically used ACI scaffolds. ACI remnants and human cartilage explants, which were applied to an uniaxial unconfined compression as injury model, were treated with human IL-10 and/or PC from thrombocyte concentrates. We analyzed nuclear blebbing/TUNEL, sGAG content, immunohistochemistry, and the expression of COL1A1, COL2A1, COL10A1, SOX9, and ACAN. Post-injuriously, PC was associated with less cell death, increased COL2A1 expression, and decreased COL10A1 expression and, interestingly, the combination with Il-10 or Il-10 alone had no additional effects, except on COL10A1, which was most effectively decreased by the combination of PC and Il-10. The expression of COL2A1 or SOX9 was statistically not modulated by these substances. In contrast, in chondrocytes in ACI grafts the combination of PC and IL-10 had the most pronounced effects on all parameters except ACAN. Thus, using adjuvants such as PC and IL-10, preferably in combination, is a promising strategy for enhancing repair and graft maturation of autologous transplanted chondrocytes after cartilage injury.

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.

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.

Microvalve bioprinting of MSC-Chondrocyte Co-Cultures

Recent improvements within the fields of high-throughput screening and 3D tissue culture have provided the possibility of developing in vitro micro-tissue models that can be used to study diseases and screen potential new therapies. This paper reports a proof of concept study on the use of microvalve-based bioprinting to create laminar MSC-chondrocyte co-cultures as an in vitro model of autologous chondrocyte implantation (ACI), an established cellular therapy for osteoarthritis. Microvalve-based bioprinting uses microvalves to deposit cells suspended in a liquid in a consistent and repeatable manner. In this case MSCs and chondrocytes have been sequentially deposited into an insert based transwell system in order to create a laminar co-culture, with variations in the ratios of the cell types used to investigate the potential for MSCs to stimulate improved repair. Histological and indirect immunofluorescence staining revealed the formation of dense tissue structures within the chondrocyte and MSC-chondrocyte cell co-cultures, alongside the establishment of a proliferative region at the base of the tissue. No stimulatory or inhibitory effect in terms of ECM production was observed through the introduction of MSCs, although the potential for an immunomodulatory benefit remains. This proof-of-concept study therefore provides a novel method to enable the scalable production of therapeutically relevant micro-tissue models that can be used for in vitro research to optimise ACI procedures.

Surgical management of focal chondral defects of the knee: a Bayesian network meta-analysis

Background Focal chondral defects of the knee are common. Several surgical techniques have been proposed for the management of chondral defects: microfractures (MFX), osteochondral autograft transplantation (OAT), autologous matrix-induced chondrogenesis (AMIC) and autologous chondrocyte implantation (ACI)—first generation (pACI), second generation (cACI) and third generation (mACI). A Bayesian network meta-analysis was conducted to compare these surgical strategies for chondral defects in knee at midterm follow-up. Methods This Bayesian network meta-analysis was conducted according to the PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions. PubMed, Google Scholar, Embase and Scopus databases were accessed in July 2021. All the prospective comparative clinical trials investigating two or more surgical interventions for chondral defects of the knee were accessed. The network meta-analyses were performed through a Bayesian hierarchical random-effects model analysis. The log odds ratio (LOR) effect measures were used for dichotomic variables, while the standardized mean difference (SMD) for the continuous variables. Results Data from 2220 procedures (36 articles) were retrieved. The median follow-up was 36 (24 to 60) months. The ANOVA test found good baseline comparability between symptoms duration, age, sex and body mass index. AMIC resulted in higher Lysholm score (SMD 3.97) and Tegner score (SMD 2.10). AMIC demonstrated the lowest rate of failures (LOR −0.22) and the lowest rate of revisions (LOR 0.89). As expected, MFX reported the lower rate of hypertrophy (LOR −0.17) followed by AMIC (LOR 0.21). No statistically significant inconsistency was found in the comparisons. Conclusion AMIC procedure for focal chondral defects of the knee performed better overall at approximately 3 years’ follow-up.