Cartilage Defects Research Articles

Locking plate fixation in comminuted coronoid fractures with partial loss of the articular cartilage – Of basal-1 type according to the O'Driscoll classification –

BackgroundWe have attempted to restore the arc of motion by considering trochlear-coronoid articulation as a complete circle during fixation of the coronoid, even for comminuted coronoid fractures with partial loss of articular cartilage (CCFPLAC), using various kinds of locking plates. Herein, we report the radiological and clinical outcomes after fixation of the basal-1 type of CCFPLAC (O'Driscoll classification) using our method. MethodsThirty-one patients diagnosed with CCFPLAC were admitted between January 2012 and December 2020. Sixteen of these patients met the inclusion/exclusion criteria and were enrolled in this study. Surgically, the lost area (defect of articular cartilage) was never compressed or minimized, but the original height and shape of the coronoid were preserved as is. Provisionally, a few K-wires were used to maintain the original shape and position of the CCFPLAC, and various kinds of locking plates/screws were used to fix the fragment anatomically and firmly. If needed, the plate was bent to ensure stable compression of the coronoid according to its size. In a few cases, locking plates were adjusted by cutting extra screw holes. ResultsAmong the 16 patients, the mean age was 46.2 years, and the male:female ratio was 10:6. The mean follow-up period was 3.63 years. 8, 6, and 2 patients were designated as group 1 (isolated CCFPLAC), 2 [CCFPLAC in type 4 (terrible triad) injury), and 3 (CCFPLAC in type 5 posterior olecranon fracture-dislocations), respectively. Complete union was achieved after a mean of 8.94 weeks. The mean flexion-extension and pronation-supination arcs were 127.19 ± 4.46° and 135.31.59 ± 8.06°, respectively, which were significantly different from those on the contralateral (normal) side (p < 0.001); however, the arcs were within the functional ranges for ordinary daily living. Additionally, the functional status was satisfactory in all patients. However, Mayo Elbow Performance Score and the degree of arthritis were statistically poor in group 2. ConclusionsCCFPLAC of the basal-1 type (O'Driscoll classification) can be treated satisfactorily if already designed and widely distributed locking plates are properly manipulated to maintain the original geometry of the coronoid according to the individual joint characteristics. Level of evidenceLevel IV, Retrospective case series

Interferon-gamma signaling promotes cartilage regeneration after injury

Osteoarthritis is a common chronic disease and major cause of disability and chronic pain in ageing populations. In this pathology, the entire joint is involved, and the regeneration of articular cartilage still remains one of the main challenges. Here, we investigated the molecular mechanisms underlying cartilage regeneration in young mice using a full-thickness cartilage injury (FTCI) model. FTCI-induced cartilage defects were created in the femoral trochlea of young and adult C57BL/6 mice. To identify key molecules and pathways involved in the early response to cartilage injury, we performed RNA sequencing (RNA-seq) analysis of cartilage RNA at 3 days after injury. Young mice showed superior cartilage regeneration compared to adult mice after cartilage injury. RNA-seq analysis revealed significant upregulation of genes associated with the immune response, particularly in the IFN-γ signaling pathway and qRT-PCR analysis showed macrophage polarization in the early phase of cartilage regeneration (3 days) in young mice after injury, which might promote the removal of damaged or necrotic cells and initiate cartilage regeneration in response to injury. IFN-γR1- and IFN-γ-deficient mice exhibited impaired cartilage regeneration following cartilage injury. DMM-induced and spontaneous OA phenotypes were exacerbated in IFN-γR1−/− mice than in wild-type mice. Our data support the hypothesis that IFN-γ signaling is necessary for cartilage regeneration, as well as for the amelioration of post-traumatic and age-induced OA.

Association between hip muscle strength/function and hip cartilage defects in sub-elite football players with hip/groin pain

ObjectiveTo explore associations between hip muscle strength and cartilage defects (presence and severity) on magnetic resonance imaging (MRI) in young adults with hip/groin pain participating in sub-elite football. DesignSub-elite football players with hip/groin pain (>6 months) completed assessments of isometric hip strength and functional task performance. Hip cartilage defects were assessed using the Scoring Hip Osteoarthritis with MRI tool. This exploratory, cross-sectional study used logistic and negative binomial models to assess the relationships between hip muscle strength or functional task performance and hip cartilage defects, controlling for body mass index, age, testing site and cam morphology, incorporating sex-specific interaction terms. ResultsOne hundred and eighty-two (37 women) sub-elite (soccer or Australian football) players with hip/groin pain (age 26 ± 7 years) were included. Greater hip extension strength was associated with higher cartilage total score (adjusted incidence rate ratio [aIRR] 1.01, 95%CI: 1.0 to 1.02, p = 0.013) and superolateral cartilage score (adjusted odds ratio (aOR) 1.03, 95% confidence interval (CI): 1.01 to 1.06, p < 0.01). In female sub-elite football players, greater hip external rotation strength was associated with lateral cartilage defects (aOR 1.61, 95%CI: 1.05 to 2.48, p = 0.03) and higher cartilage total score (aIRR 1.25, 95%CI: 1.01 to 1.66, p = 0.042). A one-repetition increase in one-leg rise performance was related to lower odds of superomedial cartilage defects (aOR 0.96, 95%CI: 0.94 to 0.99, p < 0.01). ConclusionsOverall, there were few associations between peak isometric hip muscle strength and overall hip cartilage defects. It is possible that other factors may have relevance in sub-elite football players. Additional studies are needed to support or refute our findings that higher one leg rise performance was associated with reduced superomedial cartilage defect severity and greater hip extension strength was related to higher cartilage defect severity scores.

Post-traumatic and OA-related lesions in the knee at baseline and 2 years after traumatic meniscal injury: Secondary analysis of a randomized controlled trial

ObjectiveTo assess the presence of early degenerative changes on Magnetic Resonance Imaging (MRI) 24 months after a traumatic meniscal tear and to compare these changes in patients treated with arthroscopic partial meniscectomy or physical therapy plus optional delayed arthroscopic partial meniscectomy. DesignWe included patients aged 18-45 years with a recent onset, traumatic, MRI verified, isolated meniscal tear without radiographic osteoarthritis. Patients were randomized to arthroscopic partial meniscectomy or standardized physical therapy with optional delayed arthroscopic partial meniscectomy. MRIs at baseline and 24 months were scored using the MRI Osteoarthritis Knee Score (MOAKS). We compared baseline MRIs to healthy controls aged 18-40 years. The outcome was the progression of bone marrow lesions (BMLs), cartilage defects and osteophytes after 24 months in patients. ResultsWe included 99 patients and 50 controls. At baseline, grade 2 and 3 BMLs were present in 26% of the patients (n=26), compared to 2% of the controls (n=1) (between group difference 24% (95% CI 15% to 34%)). In patients, 35% (n=35) had one or more cartilage defects grade 1 or higher, compared to 2% of controls (n=1) (between group difference 33% (95% CI 23% to 44%)). At 24 months MRI was available for 40 patients randomized to arthroscopic partial meniscectomy and 41 patients randomized to physical therapy. At 24 months 30% (n=12) of the patients randomized to arthroscopic partial meniscectomy showed BML worsening, compared to 22% (n=9) of the patients randomized to physical therapy (between group difference 8% (95% CI -11% to 27%)). Worsening of cartilage defects was present in 40% (n=16) of the arthroscopic partial meniscectomy group, compared to 22% (n=9) of the physical therapy group (between group difference 18% (95% CI -2% to 38%)). Of the patients who had no cartilage defect at baseline, 33% of the arthroscopic partial meniscectomy group had a new cartilage defect at follow-up compared to 14% of the physical therapy group. Osteophyte worsening was present in 18% (n=7) of the arthroscopic partial meniscectomy group and 15% (n=6) of the physical therapy group (between group difference 3% (95% CI -13% to 19%)). ConclusionsOur results might suggest more worsening of BMLs and cartilage defects with arthroscopic partial meniscectomy compared to physical therapy with optional delayed arthroscopic partial meniscectomy at 24-month follow-up in young patients with isolated traumatic meniscal tears without radiographic OA.

Cartilage stem/progenitor cells-derived exosomes facilitate knee cartilage repair in a subacute osteoarthritis rat model.

Cartilage defects in the knee are often associated with the progression of degenerative osteoarthritis (OA), and cartilage repair is a useful strategy for managing this disease. However, cartilage repair is challenging because of the unique environment within the tissue. Recently, stem cell-based therapies have shed new light on this issue. In this study, we prepared exosomes (EXOs) from cartilage stem/progenitor cells (CSPCs) and found that treatment with EXOs increased the viability, migration, and proliferation of cultured primary chondrocytes. In a subacute OA rat model, the application of EXOs facilitated cartilage regeneration as evidenced by histological staining. Exosomal protein analysis together with bioinformatics suggested that cyclin-dependent kinase 9 (CDK9) is a key factor for chondrocyte growth and migration. Functional studies confirmed this prediction, that is, inhibiting CDK9 reduced the beneficial effects induced by EXOs in primary chondrocytes; while overexpression of CDK9 recapitulated the EXOs-induced phenotypes. RNA-Seq data showed that a set of genes involved in cell growth and migration were up-regulated by EXOs in chondrocytes. These changes could be partially reproduced by CDK9 overexpression. Overall, our data suggest that EXOs derived from primary CSPCs hold great therapeutic potential for treating cartilage defect-associated disorders such as degenerative OA, and that CDK9 is a key factor in this process.

Osteochondral Allograft Transplantation for the Treatment of an Acetabular Defect: A Case Report.

A 20-year-old woman presented with a unipolar, 1.8 × 1.8-cm osteochondral defect of the left acetabulum. Osteochondral allograft transplantation was performed using a medial tibial plateau allograft resulting in excellent clinical outcomes across 4 different outcome scores and maintenance of the joint space at 4.3 years postoperatively. Although previous literature has demonstrated long-term clinical success of osteochondral allograft transplantation in knee, excellent clinical outcomes can also be obtained in the hip. Thus, osteochondral allograft transplantation may be a viable treatment option for adolescents and young adults with concomitant cartilage and subchondral bone hip defects.

Facile synthesis of mechanically robust and injectable tetra-polyethylene glycol/methacrylate chitosan double-network hydrogel cartilage repair

The development of advanced hydrogel scaffolds with good biocompatibility, mechanical strength and bioactive property is highly desirable in cell growth, proliferation, and differentiation for the cartilage tissue regeneration. Herein, we reported a simple, inexpensive, feasible, and environmentally benign strategy to synthesize a biocompatible polyethylene glycol-based methacrylate-modified chitosan (PCSMA) double network (DN) hydrogel via the reversible Schiff base reaction and successive photopolymerization between the tetra-poly (ethylene glycol) aldehyde (Tetra-PEG-CHO) and methacrylate-modified chitosan (CSMA) in mild conditions. The four-terminated CHO groups were hypothesized to not only construct the whole architectural network through the dynamic pH-responsive Schiff base but also contribute to the injectable behavior and good tissue adhesion, which may furnish the surgeon with the availability of injectable and shapeless ability to fill in the gaps. Compared to the single PCS hydrogel with the main similar components of the tetra-PEG-CHO and pure CS moieties, the post-fabrication of PCSMA DN hydrogel possessed slower degradation time, denser network, and stronger mechanical stability, which could facilitate the bone marrow mesenchymal stem cell (BMSCs) activity and promote the chondrogenic differentiation for facilitating cartilage regeneration. Our study highlights the positive effects on chondrogenic performance and supports the PCSMA hydrogel as a promising tissue-engineered scaffold for the cartilage defect repair.

Management of Articular Cartilage Defects in the Knee: An Evidence-Based Algorithm

Focal articular cartilage lesions of the knee are a challenging disease entity due to the poor regenerative properties of hyaline cartilage that often lead to degenerative joint disease. Surgery is indicated to alleviate symptoms, restore function, and return to desired activities when conservative treatment fails. Providers must consider defect size and severity, compliance with the postoperative rehabilitation protocol including weight-bearing restrictions, and patient expectations in their clinical decision-making. Smaller defects may be treated with arthroscopic chondroplasty, bone marrow stimulation, and osteochondral autologous transfer. Alternative surgical options for larger defects include osteochondral restoration using fresh vs. cryopreserved allografts, autologous chondrocyte implantation, and particulated juvenile allograft cartilage. This article will review available treatment options and provide an evidence-based treatment algorithm to guide the orthopaedic clinician's clinical decision-making.

An injectable CS-hydrogel incorporating TPGS for cartilage repair

Osteoarthritis (OA) is a progressive and degenerative disease associated with articular cartilage injury. Current conservative or surgical treatments cannot effectively terminate the progress of OA, usually leading to total joint replacement at the end stage. Also, it is still challenging to treat cartilage defect for it demands a dual-pronged approach which simultaneously addresses both cartilage repair and the relief of osteochondral inflammation. In this study, we embarked on a pioneering exploration of D-α-Tocopherol polyethylene glycol 1000 succinate (TPGS), an FDA-approved, water-soluble derivative of natural vitamin E. TPGS was found to effectively relieve inflammation both in vitro and in vivo. We further extended the application of TPGS by establishing an injectable collagen-chondroitin sulfate (CS) hydrogel incorporated with TPGS (TPGS@CS-hydrogel), and achieved excellent cartilage repair. RNA-seq showed that the anti-inflammatory effect of TPGS@CS-hydrogel were related to the interruption of interplay of oxidative stress and inflammation, thus promoting cartilage regeneration. In conclusion, both TPGS and TPGS@CS-hydrogel provided new insights for the prevention and treatment of articular inflammation and cartilage lesion.

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

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

Injectable microspheres adhering to the cartilage matrix promote rapid reconstruction of partial-thickness cartilage defects

An effective treatment for the irregular partial-thickness cartilage defect in the early stages of osteoarthritis (OA) is lacking. Cartilage tissue engineering is effective for treating full-thickness cartilage defects with limited area. In this study, we designed an injectable multifunctional poly(lactic-co-glycolic acid) (PLGA) microsphere to repair partial-thickness cartilage defects. The microsphere was grafted with an E7 peptide after loading the microsphere with kartogenin (KGN) and modifying the outer layer through dopamine self-polymerization. The microsphere could adhere to the cartilage defect, recruit synovial mesenchymal stem cells (SMSCs) in situ, and stimulate their differentiation into chondrocytes after injection into the articular cavity. Through in vivo and in vitro experiments, we demonstrated the ability of multifunctional microspheres to adhere to cartilage matrix, recruit SMSCs, and promote their differentiation into cartilage. Following treatment, the cartilage surface of the model group with partial-thickness cartilage defect showed smooth recovery, and the glycosaminoglycan content remained normal; the untreated control group showed significant progression of OA. The microsphere, a framework for cartilage tissue engineering, promoted the expression of SMSCs involved in cartilage repair while adapting to cell migration and growth. Thus, for treating partial-thickness cartilage defects in OA, this innovative carrier system based on stem cell therapy can potentially improve therapeutic outcomes. Statement of significanceMesenchymal stem cells (MSCs) therapy is effective in the repair of cartilage injury. However, because of the particularity of partial-thickness cartilage injury, it is difficult to recruit enough seed cells in situ, and there is a lack of suitable scaffolds for cell migration and growth. Here, we developed polydopamine surface-modified PLGA microspheres (PMS) containing KGN and E7 peptides. The adhesion ability of the microspheres is facilitated by the polydopamine layer wrapped in them; thus, the microspheres can adhere to the injured cartilage and recruit MSCs, thereby promoting their differentiation into chondrocytes and accomplishing cartilage repair. The multifunctional microspheres can be used as a safe and potential method to treat partial-thickness cartilage defects in OA.

Regenerative capacity of morselized cartilage in vitro and in an osteochondral defect model

IntroductionNumerous treatment modalities for focal articular cartilage defects exist, including the use of chondrons from minced cartilage morsels. However, the use of consistent and reproducible morsel sizes to heal these lesions, especially with a recently characterized alginate-Nanocellulose (NC) hydrogel scaffold, has not been investigated. MethodsCartilage was harvested and morselized into 0.5mm, 1.0mm, and 5.0mm diameters, and cultured. Cell viability and chondrogenic gene expression was analyzed. 0.5mm diameter minced cartilage morsels were harvested and used to produce the implant paste. The NC paste was filled into a rabbit articular cartilage defect, and histology was used to assess cartilage repair. ResultsChondrocyte viability of the morsels was highly maintained. Chondrogenic and proliferative genes like ACAN, COL2, COMP, PCNA, SOX9, and PRG4 all increased expression to a varying degree as morsel size decreased. 0.5mm morsels exhibited the highest chondrogenic potential. Also, NC paste containing 0.5mm morsels resulted in complete defect closure unlike marrow stimulation alone. Safranin-O staining demonstrated superior cartilage formation in the defect area. DiscussionSmaller consistent morsel size was found to be linked to increased chondrogenic potential, as hypothesized. However, since PRG4 expression was highest in 1mm morsels and MMP-13 gene expression was significantly decreased in only 0.5mm morsels, this demonstrates the need to adjust morsel size to optimize gene expression of interest. NC paste mixed with 0.5mm morsels produced the greatest regenerative capacity. Exploring the regenerative potential of unique hydrogels and chondron morsel sizes is warranted to provide insight on optimizing clinical implants to improve patient recovery.

Application of hydrogel scaffolds as a cell substrate for cartilage tissue regeneration

Cell therapy or tissue engineering is currently one of the potentially effective strategies for repairing cartilage defects. Mesenchymal stromal cells and autologous and allogeneic chondrocytes obtained from cartilage biopsies from patients undergoing arthroscopic surgery are the most commonly used cells for tissue engineering. Matrices (scaffolds) often used during cell implantation can facilitate successful cell implantation. These can be static supporting or plastic hydrogel substances obtained by various methods from natural or synthetic materials, allowing cells to be delivered to the site damaged by injection. Significant advantages of biocompatible hydrogels in cartilage injury therapy are determined based on the properties of the natural extracellular matrix and the high plasticity required for adapting to irregular surfaces of the tissue defect and allowing injectable cell delivery. These characteristics make injectable hydrogels a promising tool for cartilage bioengineering.&#x0D; This study highlights the progress in injectable hydrogels as carriers of different cells in the repair of cartilage tissue defects, as well as the current requirements and unresolved issues related to the use of such therapeutic approaches.

Gene activated reinforced scaffolds for SOX9 delivery to enhance repair of large load bearing articular cartilage defects

Gene activated reinforced scaffolds for SOX9 delivery to enhance repair of large load bearing articular cartilage defects

Multipatterned Chondrocytes' Scaffolds by FL-MOPL with a BSA-GMA Hydrogel to Regulate Chondrocytes' Morphology.

Repairing articular cartilage damage is challenging due to its low regenerative capacity. In vitro, cartilage regeneration is a potential strategy for the functional reconstruction of cartilage defects. A hydrogel is an advanced material for mimicking the extracellular matrix (ECM) due to its hydrophilicity and biocompatibility, which is known as an ideal scaffold for cartilage regeneration. However, chondrocyte culture in vitro tends to dedifferentiate, leading to fibrosis and reduced mechanical properties of the newly formed cartilage tissue. Therefore, it is necessary to understand the mechanism of modulating the chondrocytes' morphology. In this study, we synthesize photo-cross-linkable bovine serum albumin-glycidyl methacrylate (BSA-GMA) with 65% methacrylation. The scaffolds are found to be suitable for chondrocyte growth, which are fabricated by homemade femtosecond laser maskless optical projection lithography (FL-MOPL). The large-area chondrocyte scaffolds have holes with interior angles of triangle (T), quadrilateral (Q), pentagon (P), hexagonal (H), and round (R). The FL-MOPL polymerization mechanism, swelling, degradation, and biocompatibility of the BSA-GMA hydrogel have been investigated. Furthermore, cytoskeleton and nucleus staining reveals that the R-scaffold with larger interior angle is more effective in maintaining chondrocyte morphology and preventing dedifferentiation. The scaffold's ability to maintain the chondrocytes' morphology improves as its shape matches that of the chondrocytes. These results suggest that the BSA-GMA scaffold is a suitable candidate for preventing chondrocyte differentiation and supporting cartilage tissue repair and regeneration. The proposed method for chondrocyte in vitro culture by developing biocompatible materials and flexible fabrication techniques would broaden the potential application of chondrocyte transplants as a viable treatment for cartilage-related diseases.

Magnetic resonance imaging combined with histological evaluation of repair process using the microfracture technique in an association of osteocartilaginous and meniscal surgically induced lesions of the knee. In vivo experiment on a rabbit model.

The present research study aimed to assess magnetic resonance imaging (MRI) changes and histological findings in the therapeutic effects of microfractures in the treatment of complex animal knee lesions resulting from osteochondral and meniscal defects resulting from non-total meniscectomies. The anterior cruciate ligament lesions are also proven to facilitate the development of osteoarthritis in the knee and worsen the prognosis. Surgery was performed on the right knee joint of 22 male rabbits in order to partially remove the anterior horn of the internal meniscus and to induce an osteochondral defect at the level of the internal femoral condyle. The induced lesion complex was aimed to simulate a clinical situation that occurs frequently in orthopedic practice when young adults undergo partial meniscectomy and at the time of surgery, an osteochondral defect is diagnosed. Rabbits were separated into two study groups: the control (C1) group and the microfractures (MF2) group. After the induced cartilage defect and partial meniscectomy, both groups were followed-up for six months using detailed MRI. Also, anatomical specimens were histologically analyzed to show modifications and signs of healing process, along with complications, in the study group. The results showed that the microfracture group had better results concerning articular surface defect healing in comparison to the control group. Our results suggest that microfractures do improve results concerning surface contact healing and serial MRI studies can be useful in observing the remodeling process in dynamics.

Catalpol promotes articular cartilage repair by enhancing the recruitment of endogenous mesenchymal stem cells.

Articular cartilage defect is challenged by insufficient regenerative ability of cartilage. Catalpol (CA), the primary active component of Rehmanniae Radix, could exert protective effects against various diseases. However, the impact of CA on the treatment of articular cartilage injuries is still unclear. In this study, full-thickness articular cartilage defect was induced in a mouse model via surgery. The animals were intraperitoneally injected with CA for 4 or 8 weeks. According to the results of macroscopic observation, micro-computed tomography CT (μCT), histological and immunohistochemistry staining, CA treatment could promote mouse cartilage repair, resulting in cartilage regeneration, bone structure improvement and matrix anabolism. Specifically, an increase in the expression of CD90, the marker of mesenchymal stem cells (MSCs), in the cartilage was observed. In addition, we evaluated the migratory and chondrogenic effects of CA on MSCs. Different concentration of CA was added to C3H10 T1/2 cells. The results showed that CA enhanced cell migration and chondrogenesis without affecting proliferation. Collectively, our findings indicate that CA may be effective for the treatment of cartilage defects via stimulation of endogenous MSCs.

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

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

Dynamic Proteinaceous Hydrogel Enables In‐Situ Recruitment of Endogenous TGF‐β1 and Stem Cells for Cartilage Regeneration

AbstractArticular cartilage is a tissue with relatively poor self‐regeneration capacity due to insufficient blood vessels and chondrocytes in the region. Biomaterial‐assisted tissue engineering has shown great potential in cartilage regeneration. However, there are still many worries over the uses of exogenous growth factors, stem cells and scaffolds. To address these concerns, here a dynamic proteinaceous hydrogel with a self‐recruiting ability of cartilage‐inducing factor for in situ cartilage regeneration is reported. The dynamic hydrogel (Pep‐GelSH) is prepared by using thiol‐modified gelatin and thiol‐capped TGF‐β1‐affinity peptide through the Au‐S coordination. The injectability and self‐recovery of Pep‐GelSH hydrogel enabled not only minimally invasive implantation but also the adaptability of the scaffold to irregular defect shapes. Meanwhile, the dynamic hydrogel showed improved adherence to the host tissue and allowed quick infiltration of host cells. More importantly, the hydrogel significantly enhanced local enrichment of endogenous TGF‐β1 and led to the recruitment of stem cells in vivo. After implantation, the hydrogel scaffold triggered the innate repair capacity of cartilage defects by successively promoting stem cells recruitment, infiltration and differentiation, resulting in significantly enhanced chondrogenesis and improved cartilage repair. Therefore, the study in this work may provide a feasible and promising approach for in situ cartilage regeneration.

Hydrogel-Based Matrix-Associated Autologous Chondrocyte Implantation Shows Greater Substantial Clinical Benefit at 24 Months Follow-Up than Microfracture: A Propensity Score Matched-Pair Analysis.

To compare substantial clinical benefit (SCB) of a hydrogel-based, matrix-associated autologous chondrocyte implantation (M-ACI) method versus microfracture (MFx) in the treatment of knee cartilage defects. Propensity score matched-pair analysis, using the MFx control group of a phase III study as comparator for M-ACI treatment in a single-arm phase III study, resulting in 144 patients in the matched-pair set. Groups were comparable regarding baseline Knee Injury and Osteoarthritis Outcome Score (KOOS), sex, age, body mass index, symptom duration, smoking status, and previous knee surgeries. Defect sizes in the M-ACI group were significantly larger than in the MFx group (6.4 cm2 vs. 3.7 cm2). Other differences concerned location, number, and etiology of defects that were not considered to influence the interpretation of results. At 24 months, significantly more patients in the M-ACI group achieved SCB in KOOS pain (72.2% vs. 48.6%; P = 0.0108), symptoms (84.7% vs. 61.1%, P = 0.0039), sports/recreation (84.7% vs. 56.9%, P = 0.0008), and quality of life (QoL; 72.2% vs. 44.4%, P = 0.0014). The SCBs for KOOS activities in daily living and International Knee Documentation Committee score were higher for M-ACI but not significantly different from MFx. The SCB rates consistently favored M-ACI from 3 months onward. The highest improvements from baseline at 24 months in patients with SCB were observed for KOOS sports/rec. (M-ACI: 60.8 points, MFx: 55.9 points) and QoL (M-ACI: 58.1, MFx: 57.4). Hydrogel-based M-ACI demonstrated superior SCB in KOOS pain, symptoms, sports/rec., and QoL compared with MFx in patients with knee cartilage defects through 2 years follow-up.