Three-dimensional gas-foamed scaffolds decorated with metal phenolic networks for cartilage regeneration.

Inflammation is a major impediment to the healing of cartilage injuries, yet bioactive scaffolds suitable for cartilage repair in inflammatory environments are extremely rare. Herein, we utilized electrospinning to fabricate a two-dimensional nanofiber scaffold (2DS), which was then subjected to gas foaming to obtain a three-dimensional scaffold (3DS). 3DS was modified with metal phenolic networks (MPNs) composed of epigallocatechin gallate (EGCG) and strontium ions (Sr2+) to afford a MPNs-modified 3D scaffold (3DS-E). Gas-foamed scaffold exhibited multilayered structure conducive to cellular infiltration and proliferation. Compared to other groups, 3DS-E better preserved chondrocytes under interleukin (IL)-1ß induced inflammatory environment, showing less apoptosis of chondrocytes and higher expression of cartilage matrix. Additionally, 3DS-E facilitated the regeneration of more mature cartilage in vivo, reduced cell apoptosis, and decreased the expression of pro-inflammatory cytokines. Taken together, 3DS-E may offer an ideal candidate for cartilage regeneration.

Does scaffold enhancement show significant superiority over microfracture alone for treating knee chondral defects? A systematic review and meta-analysis of randomised clinical trials.

PURPOSE: Chondral and osteochondral lesions in the knee are common conditions that significantly impair individuals' well-being and can lead to osteoarthritis, imposing substantial burdens on healthcare systems. The limited natural healing capacity of articular cartilage necessitates innovative treatment strategies. Microfracture (MF) is a widely used technique for knee chondral defects, but its long-term efficacy is often inadequate. Although recent randomised controlled trials have compared microfractures with scaffold-enhanced therapies, a comprehensive systematic review and meta-analysis are lacking. METHODS: An extensive literature search was conducted in PubMed and EMBASE databases following PRISMA guidelines. Inclusion criteria focused on randomised controlled trials (RCTs) comparing microfractures alone to matrix-induced chondrogenesis for knee chondral defects with at least a 12-month follow-up. Ten randomised controlled trials conducted between 2013 and 2024, enroling 378 patients, were included. RESULTS: The meta-analysis showed no significant superiority of scaffolds over MF (p > 0.05) in International Knee Documentation Committee, Knee Injury and Osteoarthritis Outcome, Visual Analog Scale, and Magnetic Resonance Observation of Cartilage Repair Tissue scores at 12 and 24 months. However, individual studies suggested the potential benefits of scaffolds, especially in long-term outcomes. Clinical improvements from MF typically decline after 2-3 years, underscoring the need for long-term follow-up in future research. CONCLUSION: Our meta-analysis shows no significant difference between MF and MF with scaffold in treating knee cartilage defects, though some long-term RCTs demonstrate statistically significant differences. The absence of a universally accepted algorithm for analysing knee chondral defects limits this study. Establishing reliable guidelines and standardised study protocols is essential to improve long-term patient outcomes and the quality of future papers. LEVEL OF EVIDENCE: Level I.

Mesenchymal Stem Cells and Secretome as a New Possible Approach to Treat Cartilage Damage: An In Vitro Study.

Introduction: Osteoarthritis is a degenerative condition of the cartilage, often common among the population and occurs frequently with aging. Many factors are decisive for the development of its pathogenesis such as age, obesity, trauma, mechanical load, and modification of synovial biology. The main features of osteoarthritis are chondrocytes and cartilage matrix loss, which lead to pain, loss of function of the whole joint, and disability, representing a relevant health problem. Recently, a new therapeutic approach based on cell therapy has been studying the regenerative ability of mesenchymal stem cells for osteoarthritic chondrocytes. Aim: This in vitro study clarifies the regenerative effects of multipotent adipose-derived stem cells and the pluripotent amniotic epithelial stem cells on arthrosis chondrocytes by performing co-culture experiments. Methods: We studied the regenerative potential of secretome (soluble factors and extracellular vesicles), mesenchymal stem cells, and the adipose stromal vascular fraction. The regenerative effects were evaluated by gene and protein expression analysis of articular cartilage-specific genes and proteins like col2a1, acan, and sox9. Results: Mesenchymal stem cells, secretome, and adipose stromal vascular fractions influenced the cartilage genes and protein expression. Conclusions: The results indicate that the treatment with mesenchymal stem cells could be the best biological approach for cartilage regenerative medicine.

Outcomes After Osteochondral Allograft Transplantation of the Medial Femoral Condyle in Patients With Varus and Nonvarus Alignment.

BACKGROUND: Fresh osteochondral allograft (OCA) transplantation is an effective technique for the treatment of focal chondral and osteochondral defects in the knee. Coronal-plane malalignment leads to increased contact forces within a compartment and subsequently the cartilage repair site and may lead to higher failure rates. However, the magnitude of the effect of coronal-plane malalignment on graft survivorship and clinical outcomes has not been well characterized. PURPOSE: To evaluate how varus malalignment affects graft survival and patient-reported outcomes after isolated OCA transplantation of the medial femoral condyle (MFC). STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A total of 70 patients (74 knees) who underwent primary OCA transplantation of the MFC between 2005 and 2019 were identified from a prospectively collected single-surgeon cartilage registry with a minimum 2-year follow-up. Coronal-plane alignment was evaluated utilizing standing hip-to-ankle radiographs. OCA failure, defined as removal of the graft or conversion to arthroplasty, and reoperations were recorded. Patient-reported outcomes were obtained preoperatively and postoperatively using the International Knee Documentation Committee score, Knee injury and Osteoarthritis Outcome Score, modified Merle d'Aubigné-Postel score, and overall patient satisfaction score. RESULTS: The mean mechanical tibiofemoral angle for patients with varus alignment was 3.9° of varus (range, 1.1° to 8.9°) and for patients with nonvarus alignment it was 0.02° of valgus (range, 3.6° varus to 4.6° valgus). Graft survivorship was 95.3% in the varus group and 95.8% in the nonvarus group (P = .918) at 5 years postoperatively. Reoperations after OCA transplantation occurred in 14.0% of the varus group and 22.6% of the nonvarus group (P = .336). The mean International Knee Documentation Committee total score improved from 45.2 preoperatively to 74.8 at latest follow-up in the varus group and from 40.5 preoperatively to 72.3 at latest follow-up in the nonvarus group. Patient satisfaction was >85%. CONCLUSION: Patients undergoing isolated OCA transplantation of the MFC had high rates (>90%) of graft survivorship and significant improvements in pain and function. Patients with mild preexisting varus malalignment were found to have no difference in the failure rate or clinical outcomes compared with patients with nonvarus alignment.

Development of scaffold-free tissue-engineered constructs derived from mesenchymal stem cells with serum-free media for cartilage repair and long-term preservation.

Synovial mesenchymal stem cells (sMSCs) have great potential for cartilage repair, but their therapeutic design to avoid adverse effects associated with unknown factors remains a challenge. In addition, because long-term preservation is indispensable to maintain high quality levels until implantation, it is necessary to reduce their fluctuations. This study aimed to investigate the properties and feasibility of novel scaffold-free tissue-engineered constructs using serum-free media and to develop long-term preservation methods. sMSCs were cultured in serum-free media, seeded at high density in a monolayer, and finally developed as a sheet-like construct called "gMSC1". The properties of frozen gMSC1 (Fro-gMSC1) were compared with those of refrigerated gMSC1 (Ref-gMSC1) and then examined by their profile. Chondrogenic differentiation potential was analyzed by quantitative real-time polymerase chain reaction and quantification of glycosaminoglycan content. Xenografts into the cartilage defect model in rats were evaluated by histological staining. gMSC1 showed nearly similar properties independent of the preservation conditions. The animal experiment demonstrated that the defect could be filled with cartilage-like tissue with good integration to the adjacent tissue, suggesting that gMSC1 was formed and replaced the cartilage. Furthermore, several chondrogenesis-related factors were significantly secreted inside and outside gMSC1. Morphological analysis of Fro-gMSC1 revealed comparable quality levels to those of fresh gMSC1. Thus, if cryopreserved, gMSC1, with no complicated materials or processes, could have sustained cartilage repair capacity. gMSC1 is a prominent candidate in novel clinical practice for cartilage repair, allowing for large quantities to be manufactured at one time and preserved for a long term by freezing. Supplementary Information: The online version contains supplementary material available at 10.1007/s10616-024-00637-y.

Drug-Loaded Bioscaffolds for Osteochondral Regeneration.

Osteochondral defect is a complex tissue loss disease caused by arthritis, high-energy trauma, and many other reasons. Due to the unique structural characteristics of osteochondral tissue, the repair process is sophisticated and involves the regeneration of both hyaline cartilage and subchondral bone. However, the current clinical treatments often fall short of achieving the desired outcomes. Tissue engineering bioscaffolds, especially those created via three-dimensional (3D) printing, offer promising solutions for osteochondral defects due to their precisely controllable 3D structures. The microstructure of 3D-printed bioscaffolds provides an excellent physical environment for cell adhesion and proliferation, as well as nutrient transport. Traditional 3D-printed bioscaffolds offer mere physical stimulation, while drug-loaded 3D bioscaffolds accelerate the tissue repair process by synergistically combining drug therapy with physical stimulation. In this review, the physiological characteristics of osteochondral tissue and current treatments of osteochondral defect were reviewed. Subsequently, the latest progress in drug-loaded bioscaffolds was discussed and highlighted in terms of classification, characteristics, and applications. The perspectives of scaffold design, drug control release, and biosafety were also discussed. We hope this article will serve as a valuable reference for the design and development of osteochondral regenerative bioscaffolds and pave the way for the use of drug-loaded bioscaffolds in clinical therapy.

Angiogenesis unveiled: Insights into its role and mechanisms in cartilage injury.

Osteoarthritis (OA) commonly results in compromised mobility and disability, thereby imposing a significant burden on healthcare systems. Cartilage injury is a prevalent pathological manifestation in OA and constitutes a central focus for the development of treatment strategies. Despite the considerable number of studies aimed at delaying this degenerative process, their outcomes remain unvalidated in preclinical settings. Recently, therapeutic strategies focused on angiogenesis have attracted the growing interest from researchers. Thus, we conducted a comprehensive literature review to elucidate the current progress in research and pinpoint research gaps in this domain. Additionally, it provides theoretical guidance for future research endeavors and the development of treatment strategies.

Harnessing Peptide-Based Hydrogels for Enhanced Cartilage Tissue Engineering.

Cartilage tissue engineering remains a formidable challenge due to its complex, avascular structure and limited regenerative capacity. Traditional approaches, such as microfracture, autografts, and stem cell delivery, often fail to restore functional tissue adequately. Recently, there has been a surge in the exploration of new materials that mimic the extracellular microenvironment necessary to guide tissue regeneration. This review investigates the potential of peptide-based hydrogels as an innovative solution for cartilage regeneration. These hydrogels, formed via supramolecular self-assembly, exhibit excellent properties, including biocompatibility, ECM mimicry, and controlled biodegradation, making them highly suitable for cartilage tissue engineering. This review explains the structure of cartilage and the principles of supramolecular and peptide hydrogels. It also delves into their specific properties relevant to cartilage regeneration. Additionally, this review presents recent examples and a comparative analysis of various peptide-based hydrogels used for cartilage regeneration. The review also addresses the translational challenges of these materials, highlighting regulatory hurdles and the complexities of clinical application. This comprehensive investigation provides valuable insights for biomedical researchers, tissue engineers, and clinical professionals aiming to enhance cartilage repair methodologies.

Culturing Osteochondral Explants Under Rotary Shaking or After Removing Bone Marrow Elements Increases Explant Cellular Viability.

BACKGROUND: Reduced viability in the deepest zones of osteochondral allografts (OCAs) can weaken the subchondral interface, potentially increasing the risk of failure. This reduction may result from nutritional imbalances due to uneven media distribution or interference from bone marrow elements. PURPOSE: To investigate whether culturing OCAs using a rotary shaker or removing the bone marrow elements would increase graft cellular viability. STUDY DESIGN: Controlled laboratory study. METHODS: Bovine osteochondral explants were stored for 28 days at 4°C under 3 different conditions (n = 6 explants per group): static (control group), rotary shaker at 150 rpm (shaker group), and static after removal of bone marrow elements using a Waterpik device (Waterpik group). Chondrocyte viability was assessed using live/dead staining across the entire tissue and in each zone (superficial, middle, deep). Subchondral bone viability was assessed using TUNEL (terminal deoxynucleotidal transferase-mediated biotin-deoxyuridine triphosphate nick-end labeling) staining to detect apoptotic cells. RESULTS: Both shaker (64.2%; P = .010) and Waterpik (65.6%; P = .005) conditions showed significantly higher chondrocyte viability compared with control (49.8%). When samples were analyzed by zone, the shaker and Waterpik groups displayed higher cellular viability at the middle zone (shaker = 60.6%, P < .001; Waterpik = 56.1%, P < .001) and deep zone (shaker = 63.1%, P = .018; Waterpik = 61.5%, P = .025) than the control group (25.6% at middle zone; 32.8% at deep zone). Additionally, shaker (56.7%; P = .018) and Waterpik (51.4%; P = .007) groups demonstrated a lower percentage of apoptotic cells in subchondral bone compared with control (88.0%). No significant differences were observed between the shaker and Waterpik groups in any of the analyses. CONCLUSION: Both rotary shaking and removal of bone marrow elements during storage of osteochondral explants led to higher chondrocyte viability at the middle and deep zones of the graft compared with the static storage condition. Enhancing nutrition delivery to the graft could improve its quality, potentially improving outcomes of OCA transplantation. CLINICAL RELEVANCE: The use of a rotary shaker or the removal of bone marrow elements may significantly improve the culture conditions, increasing graft viability and integrity after OCA storage.

High-precision bioactive scaffold with dECM and extracellular vesicles targeting 4E-BP inhibition for cartilage injury repair.

The restoration of cartilage injuries remains a formidable challenge in orthopedics, chiefly attributed to the absence of vascularization and innervation in cartilage. Decellularized extracellular matrix (dECM) derived from cartilage, following antigenic removal through decellularization processes, has exhibited remarkable biocompatibility and bioactivity, rendering it a viable candidate for cartilage repair. Additionally, extracellular vesicles (EVs) generated from cartilage have demonstrated a synergistic effect when combined with dECM, potentially mitigating the inhibitory impact on protein synthesis by phosphorylating 4ebp, thereby promoting the synthesis of cartilage-related proteins such as collagen. In pursuit of this objective, we have innovated a novel bioink and repair scaffold characterized by exceptional biocompatibility, bioactivity, and biodegradability, establishing a tissue-specific microenvironment conducive to chondrogenesis. Within rat osteochondral defects, the biologically active scaffold successfully prompted the formation of transparent cartilage, featuring adequate mechanical strength, favorable elasticity, and dECM deposition indicative of cartilage. In summary, this study has effectively engineered a hydrogel bioink tailored for cartilage repair and devised a bioactive cartilage repair scaffold proficient in instigating cell differentiation and fostering cartilage repair.

[Advances in clinical repair techniques for localized knee cartilage lesions].

Objective: To summarize the classic and latest treatment techniques for localized knee cartilage lesions in clinical practice and create a new comprehensive clinical decision-making process. Methods: The advantages and limitations of various treatment methods for localized knee cartilage lesions were summarized by extensive review of relevant literature at home and abroad in recent years. Results: Currently, there are various surgical methods for treating localized knee cartilage injuries in clinical practice, each with its own pros and cons. For patients with cartilage injuries less than 2 cm 2 and 2-4 cm 2 with bone loss are recommended to undergo osteochondral autograft (OAT) and osteochondral allograft (OCA) surgeries. For patients with cartilage injuries less than 2 cm 2 and 2-4 cm 2 without bone loss had treatment options including bone marrow-based techniques (micro-fracture and ogous matrix induced chondrogenesis), autologous chondrocyte implantation (ACI)/matrix-induced ACI, particulated juvenile allograft cartilage (PJAC), OAT, and OCA. For patients with cartilage injuries larger than 4 cm 2 with bone loss were recommended to undergo OCA. For patients with cartilage injuries larger than 4 cm 2 without bone loss, treatment options included ACI/matrix-induced ACI, OAT, and PJAC. Conclusion: There are many treatment techniques available for localized knee cartilage lesions. Treatment strategy selection should be based on the size and location of the lesion, the extent of involvement of the subchondral bone, and the level of evidence supporting each technique in the literature.

Treatment of osteochondral injuries of the humeral head using fresh osteochondral allograft transplantation.

Background: Large osteochondral lesions of the humeral head can result from locked posterior dislocations, avascular necrosis, and osteochondritis dissecans. Fresh osteochondral allograft (OCA) transplantation is a treatment option for young patients with focal osteochondral defects of the humeral head. The purpose of this case series was to assess graft survivorship, subjective patient-reported outcomes, and satisfaction among 7 patients who underwent OCA transplantation of the humeral head. Methods: We identified 7 patients who underwent humeral head OCA transplantation between 2008 and 2017. A custom questionnaire including the American Shoulder and Elbow Surgeons score, Quick Disabilities of the Arm, Shoulder, and Hand score (QuickDash), Likert satisfaction, and reoperations was mailed to each patient. Clinical failure was defined as further surgery that involved removal of the allograft. Results: Median follow-up duration was 10 years (range, 4.6 to 13.5 years) with a median age of 21.6 years (range, 18.5 to 43.5 years). Most patients (86%) reported improved function and reduced pain. At the final follow-up, 71% of patients reported ongoing problems with their shoulder including pain, stiffness, clicking/grinding, limited range of motion, and instability. Return to recreational activities was high at 86% but 43% expressed limitations with activity due to their shoulder. Overall satisfaction was high at 71% with mean American Shoulder and Elbow Surgeons and QuickDASH scores at 62.4 and 29.2, respectively. Reoperation after OCA occurred in 1 patient (14%). Conclusion: Among this case series of 7 patients who underwent OCA transplantation of the humeral head, patient satisfaction was high at 10-year follow-up and most returned to recreational activity although most also had persistent shoulder symptoms.

Osteocyte-derived exosomes regulate the DLX2/wnt pathway to alleviate osteoarthritis by mediating cartilage repair.

BACKGROUND: Chondrocyte viability, apoptosis, and migration are closely related to cartilage injury in osteoarthritis (OA) joints. Exosomes are identified as potential therapeutic agents for OA. OBJECTIVE: This study aimed to investigate the role of exosomes derived from osteocytes in OA, particularly focusing on their effects on cartilage repair and molecular mechanisms. METHODS: An injury cell model was established by treating chondrocytes with IL-1ß. Cartilage repair was evaluated using cell counting kit-8, flow cytometry, scratch test, and Western Blot. Molecular mechanisms were analyzed using quantitative real-time PCR, bioinformatic analysis, and Western Blot. An OA mouse model was established to explore the role of exosomal DLX2 in vivo. RESULTS: Osteocyte-released exosomes promoted cell viability and migration, and inhibited apoptosis and extracellular matrix (ECM) deposition. Moreover, exosomes upregulated DLX2 expression, and knockdown of DLX2 activated the Wnt pathway. Additionally, exosomes attenuated OA in mice by transmitting DLX2. CONCLUSION: Osteocyte-derived exosomal DLX2 alleviated IL-1ß-induced cartilage repair and inactivated the Wnt pathway, thereby alleviating OA progression. The findings suggested that osteocyte-derived exosomes may hold promise as a treatment for OA.

Dextran-tryamine hydrogel maintains position and integrity under simulated loading in a human cadaver knee model.

Objective: This dextran-tyramine hydrogel is a novel cartilage repair technique, filling focal cartilage defects to provide a cell-free scaffold for subsequent cartilage repair. We aim to asses this techniques' operative feasibility in the knee joint and its ability to maintain position and integrity under expected loading conditions. Method: Seven fresh-frozen human cadaver legs (age range 55-88) were used to create 30 cartilage defects on the medial and lateral femoral condyles dependent of cartilage quality, starting with 1.0 â€‹cm2; augmenting to 1.5 â€‹cm2 and eventually 2.0 â€‹cm2. The defects were operatively filled with the injectable hydrogel scaffold. The knees were subsequently placed on a continues passive motion machine for 30 â€‹min of non-load bearing movement, mimicking post-operative rehabilitation. High resolution digital photographs documented the hydrogel scaffold after placement and directly after movement. Three independent observers blinded for the moment compared the photographs on outline attachment, area coverage and hydrogel integrity. Results: The operative procedure was uncomplicated in all defects, application of the hydrogel was straightforward and comparable to common cartilage repair techniques. No macroscopic iatrogenic damage was observed. The hydrogel scaffold remained predominately unchanged after non-load bearing movement. Outline attachment, area coverage and hydrogel integrity were unaffected in 87%, 93% and 83% of defects respectively. Larger defects appear to be more affected than smaller defects, although not statistically significant (p â€‹> â€‹0.05). Conclusion: The results of this study show operative feasibility of this cell-free hydrogel scaffold for chondral defects of the knee joint. Sustained outline attachment, area coverage and hydrogel integrity were observed after non-load bearing knee movement.

A multicrosslinked network composite hydrogel scaffold based on DLP photocuring printing for nasal cartilage repair.

Natural hydrogels are widely employed in tissue engineering and have excellent biodegradability and biocompatibility. Unfortunately, the utilization of such hydrogels in the field of three-dimensional (3D) printing nasal cartilage is constrained by their subpar mechanical characteristics. In this study, we provide a multicrosslinked network hybrid ink made of photocurable gelatin, hyaluronic acid, and acrylamide (AM). The ink may be processed into intricate 3D hydrogel structures with good biocompatibility and high stiffness properties using 3D printing technology based on digital light processing (DLP), including intricate shapes resembling noses. By varying the AM content, the mechanical behavior and biocompatibility of the hydrogels can be adjusted. In comparison to the gelatin methacryloyl (GelMA)/hyaluronic acid methacryloyl (HAMA) hydrogel, adding AM considerably enhances the hydrogel's mechanical properties while also enhancing printing quality. Meanwhile, the biocompatibility of the multicrosslinked network hydrogels and the development of cartilage were assessed using neonatal Sprague-Dawley (SD) rat chondrocytes (CChons). Cells sown on the hydrogels considerably multiplied after 7 days of culture and kept up the expression of particular proteins. Together, our findings point to GelMA/HAMA/polyacrylamide (PAM) hydrogel as a potential material for nasal cartilage restoration. The photocuring multicrosslinked network ink composed of appropriate proportions of GelMA/HAMA/PAM is very suitable for DLP 3D printing and will play an important role in the construction of nasal cartilage, ear cartilage, articular cartilage, and other tissues and organs in the future. Notably, previous studies have not explored the application of 3D-printed GelMA/HAMA/PAM hydrogels for nasal cartilage regeneration.

Polysaccharide-protein based scaffolds for cartilage repair and regeneration.

Cartilage repair and regeneration have become a global issue that millions of patients from all over the world need surgical intervention to repair the articular cartilage annually due to the limited self-healing capability of the cartilage tissues. Cartilage tissue engineering has gained significant attention in cartilage repair and regeneration by integration of the chondrocytes (or stem cells) and the artificial scaffolds. Recently, polysaccharide-protein based scaffolds have demonstrated unique and promising mechanical and biological properties as the artificial extracellular matrix of natural cartilage. In this review, we summarize the modification methods for polysaccharides and proteins. The preparation strategies for the polysaccharide-protein based hydrogel scaffolds are presented. We discuss the mechanical, physical and biological properties of the polysaccharide-protein based scaffolds. Potential clinical translation and challenges on the artificial scaffolds are also discussed.

Acellular Aragonite-Based Scaffold for the Treatment of Joint Surface Lesions of the Knee: A Minimum 5-Year Follow-Up Study.

OBJECTIVE: A novel aragonite-based scaffold has been developed. In this study, mid-term clinical and magnetic resonance imaging (MRI) results on 12 patients affected by isolated chondral or osteochondral lesions of the knee treated by the scaffold implantation have been evaluated at a mean follow-up of 6.5 (range: 5-8) years. DESIGN: The study population consisted of 3 females and 9 males, mean age 34.4 (20-51) years. The lesion was located on the medial femoral condyle, the trochlea, and the lateral femoral condyle in 5, 5, and 2 patients, respectively. In all cases, a single lesion over grade 3 of the International Cartilage Restoration and Joint Preservation Society (ICRS) classification was treated: in 9 cases by implantation of one plug, and in 2 cases with 2 plugs; the mean size of the lesion was 2.5 cm2 (1-7). RESULTS: One patient failed and was revised with a custom-made metal implant (Episealer). Overall, Knee Injury and Osteoarthritis Outcome Score (KOOS) significantly improved from 45 ± 13 preoperatively to 86 ± 13 at final follow-up. All KOOS subscales improved significantly: pain subscale increased from 48 ± 12 to 92 ± 11; symptoms from 66 ± 13 to 91 ± 13; activity of daily living (ADL) from 60 ± 19 to 90 ± 21; sport from 23 ± 20 to 75 ± 20; finally, quality of life (QoL) increased from 27 ± 14 to 77 ± 19. Long-term MRI MOCART score was 64. CONCLUSIONS: This study shows continued significant clinical improvement and good magnetic resonance imaging (MRI) findings with a minimum 5 years follow-up after implantation of a novel aragonite derived scaffold for the treatment of cartilage lesions of the knee. One patient failed and was revised with a custom-made metal implant (Episealer).

A New Approach to Postoperative Rehabilitation following Mosaicplasty and Bone Marrow Aspiration Concentrate (BMAC) Augmentation.

BACKGROUND: Chondral defects in the knee present a significant challenge due to their limited self-healing capacity, often leading to joint degeneration and functional disability. Current treatments, including surgical approaches like mosaicplasty and regenerative therapies such as bone marrow aspirate concentrate (BMAC) augmentation, aim to address these defects and improve patient outcomes. MATERIALS AND METHODS: This study conducted a single-center, randomized controlled trial to evaluate the efficacy of different treatment approaches and rehabilitation protocols for chondral defects. Thirty-seven subjects presenting with symptomatic chondral or osteochondral defects (>3 cm2) in the weight-bearing region of the femoral condyle were partitioned into three groups, and underwent mosaicplasty with or without BMAC augmentation, followed by either a 6-week or 12-week rehabilitation program. Group 1 (n = 10) received mosaicplasty combined with BMAC augmentation and engaged in a twelve-week two-phase rehabilitation protocol. Group 2 (n = 15) underwent mosaicplasty alone and participated in the same twelve-week two-phase rehabilitation regimen. Meanwhile, Group 3 (n = 12) underwent mosaicplasty and underwent a shorter six-week one-phase rehabilitation program. Clinical assessments were performed using the visual analog scale (VAS) for pain, goniometry for the knee's range of motion (ROM), manual muscle testing (MMT) for quadricep strength, and the Western Ontario and McMaster University Arthritis Index (WOMAC) for functional evaluation in three test phases. RESULTS: Significant differences in WOMAC scale scores were observed between the three groups at the intermediate (F(2, 34) = 5.24, p < 0.010) and final (F(2, 34) = 111, p < 0.000) stages, with post hoc Tukey tests revealing variations shared among all three groups. The between-group analysis of the VAS scale demonstrated no statistically significant difference initially (F(2, 34) = 0.18, p < 0.982), but significant differences emerged following the intermediate (F(2, 34) = 11.40, p < 0.000) and final assessments (F(2, 34) = 59.87, p < 0.000), with post hoc Tukey tests revealing specific group variations, notably between Group 1 and both Group 2 and Group 3, and also between Group 3 and Group 2. The between-group analysis of quadricep muscle strength using MMT scores revealed no statistically significant differences initially (F(2, 34) = 0.376, p < 0.689) or following the intermediate assessment (F(2, 34) = 2.090, p < 0.139). The one-way ANOVA analysis showed no significant difference in the knee ROM initially (F(2, 34) = 1.037, p < 0.366), but significant differences emerged following intermediate (F(2, 34) = 9.38, p < 0.001) and final assessments (F(2, 34) = 11.60, p < 0.000). Post hoc Tukey tests revealed significant differences between Groups 1 and 2, Groups 1 and 3, and Groups 2 and 3 at intermediate and final assessments. CONCLUSIONS: The patients who received BMAC augmentation and completed a 12-week rehabilitation protocol had significantly better outcomes in pain relief, knee function, and ROM when compared to those who did not receive BMAC augmentation or those who completed a shorter rehabilitation period. Our findings suggest that combining mosaicplasty with BMAC augmentation and a comprehensive rehabilitation program can lead to superior clinical outcomes for patients with chondral defects in the knee.

Latest Advances in Chondrocyte-Based Cartilage Repair.

Chondrocyte-based cell therapy has been used for more than 30 years and is still considered to be a promising method of cartilage repair despite some limitations. This review introduces the latest developments of four generations of autologous chondrocyte implantation and current autologous chondrocyte products. The regeneration of cartilage from adult chondrocytes is limited by culture-induced dedifferentiation and patient age. Cartibeads is an innovative three-step method to produce high-quality hyaline cartilage microtissues, and it is developed from adult dedifferentiated chondrocytes with a high number of cell passages. In addition, allogeneic chondrocyte therapies using the Quantum hollow-fiber bioreactor and several signaling pathways involved in chondrocyte-based cartilage repair are mentioned, such as WNT signaling, the BMP-2/WISP1 pathway, and the FGF19 pathway.

Injectable cartilage microtissues based on 3D culture using porous gelatin microcarriers for cartilage defect treatment.

Cartilage tissues possess an extremely limited capacity for self-repair, and current clinical surgical approaches for treating articular cartilage defects can only provide short-term relief. Despite significant advances in the field of cartilage tissue engineering, avoiding secondary damage caused by invasive surgical procedures remains a challenge. In this study, injectable cartilage microtissues were developed through 3D culture of rat bone marrow mesenchymal stem cells (BMSCs) within porous gelatin microcarriers (GMs) and induced differentiation. These microtissues were then injected for the purpose of treating cartilage defects in vivo, via a minimally invasive approach. GMs were found to be noncytotoxic and favorable for cell attachment, proliferation and migration evaluated with BMSCs. Moreover, cartilage microtissues with a considerable number of cells and abundant extracellular matrix components were obtained from BMSC-laden GMs after induction differentiation culture for 28 days. Notably, ATDC5 cells were complementally tested to verify that the GMs were conducive to cell attachment, proliferation, migration and chondrogenic differentiation. The microtissues obtained from BMSC-laden GMs were then injected into articular cartilage defect areas in rats and achieved superior performance in alleviating inflammation and repairing cartilage. These findings suggest that the use of injectable cartilage microtissues in this study may hold promise for enhancing the long-term outcomes of cartilage defect treatments while minimizing the risk of secondary damage associated with traditional surgical techniques.