Treatment Of Cartilage Lesions Research Articles

Factors Affecting Choice of Surgical Treatment of Cartilage Lesions of the Knee: An Analysis of Data From 5143 Patients From the German Cartilage Registry (KnorpelRegister DGOU).

Symptomatic full-thickness cartilage lesions of the knee joint are considered an indication for cartilage repair surgery. Patient- and lesion-specific factors like age, nutritional status, etiology of defect, or integrity of corresponding joint surface remain controversial in indicating cartilage repair surgery. Furthermore, the selection of the most suitable cartilage repair technique for a specific cartilage lesion remains debatable. To evaluate indications and choice of treatment method for cartilage repair surgery, depending on patient- and lesion-specific data from the German Cartilage Registry. Cross-sectional study; Level of evidence, 3. A total of 6305 consecutive patients who underwent cartilage repair surgery of the knee evaluated and 5143 complete datasets were included in the analysis (follow-up rate, 81.5%). Patient-specific (age, body mass index, smoking status, previous operations, clinical leg axis) and lesion-specific (size, grading, location, etiology) data were provided by the attending surgeon at the time of surgery. Appropriate statistical tests were used to compare data depending on type and normality of data. Multivariable logistic regressions were calculated to investigate independent factors for the choice of specific cartilage repair techniques. The median size of treated cartilage lesions was 3.6 cm2, and most defects were of degenerative origin (54.8%). Of the registered patients, 39.2% were categorized as overweight and 19.6% as obese, while 23.3% were smokers. The most prevalently documented operative techniques were the autologous chondrocyte implantation (ACI) (52.4%), bone marrow stimulation (BMS) (17.3%), and BMS augmented with collagen scaffolds (9.3%). Independent factors that made the use of ACI more likely were bigger lesion size, previous surgery at the joint, and lesions located at the trochlea or the patella. On the contrary, BMS or augmented BMS were preferred in older patients, with damaged corresponding joint surface, and with more concomitant surgeries. Cartilage repair surgery was indicated irrespective of nutritional status, smoking status, or etiology of the treated lesion. ACI was the most prevalent technique and was preferred for younger patients and patellar lesions. While older patients with degenerative changes to the joint were not excluded from cartilage repair surgery, the use of ACI was restricted.

Non-surgical pain management for hip joint disease in veterinary medicine.

The most common orthopaedic developmental disease in dogs is hip dysplasia. This condition results in coxofemoral laxity due to incongruity and lack of stabilisation of the joint by the soft tissues. Currently, there is no therapeutic plan to correct hip dysplasia without surgical intervention at a very early age. The goal of the non-surgical treatment is to relieve pain and stiffness and to increase the muscle strength, usually through hydrotherapy and the beneficial physical properties of water. Recently, there has been growing interest in regenerative medicine, which involves the use of mesenchymal stem cells (MSCs) and their products to alleviate the characteristic clinical symptoms of osteoarthritis (OA). In vivo studies with canine MSCs have shown that an intra-articular injection of MSCs into cartilage lesions leads to the excellent regeneration of the hyaline cartilage. Regenerative medicine has undergone rapid development in recent years thanks to new therapies based on the application and combination of innovative biomaterials. One of the first known regenerative methods to be used in clinical practice was platelet-rich plasma (PRP). This review summarises the use and potential of MSCs and PRP, including their in vitro properties, their therapeutic effects in the treatment of cartilage lesions in preclinical in vivo studies, their clinical efficacy in the treatment of naturally occurring OA in dogs, and the current limitations of the studies.

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

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. 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). 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. 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).

Effects of Intra-Articular Platelet Rich Plasma on Clinical Outcomes in Knee Osteoarthritis

Background and Aim: With increasing frequency, platelet-rich plasma (PRP) preparations have been used to treatcartilage lesions to regenerate tissue homeostasis and retard the progression of knee osteoarthritis (OA). The aimof our research was to study the effectiveness of intra-articular PRP injections in early-stage OA patients and toevaluate the clinical outcome and QOL at 6 months.Material and Methods: Present study was conducted on 80 patients at tertiary care institute of Gujarat for thePeriod of 1 year. Intraarticular administration of PRP was done by injecting 5 mL of platelet concentrate in thesupra-patellar pouch through supero-lateral approach with a 22-gauge needle. The patients were followed upfor reduction in pain, reduction in stiffness and improvement in physical function in accordance with WOMACscoring system on day 0 and at the end of 6th week, 3rd and 6th months and QOL in accordance with WHOQOLquestionnaire before PRP therapy and at the end of 6th month.Results: In our study of 80 patients 26 had very poor, 23 had poor and 1 had neither poor nor good QOL beforePRP injection evaluated by WHOQOL. At 6 months post PRP therapy 5 had very good, 59 had good, 15 hadneither good nor poor and 1 had poor QOL which showed highly significant improvement in QOL.Conclusion: Intra-articular injection of autologous PRP is a safe, cheap, easy to prepare and use, and has atherapeutic role in early knee OA. Hence, PRP therapy can be used in management of early stage knee OA toprovide relief from symptoms and to improve QOL with negligible complication, low cost and ultimately withgood results.

INFLUENCE OF MG-CYLINDERS ON BONE AND CARTILAGE IN OSTEOARTHRITIS

There are no efficient treatment options for osteoarthritis (OA) that delay further progression. Besides osteoinduction, there is growing evidence of also anti-inflammatory, angiogenetic and neuroprotective effects of biodegradable magnesium-based biomaterials. Their use for the treatment of cartilage lesions in contrast is not well-evaluated yet.Mg-cylinders were analysed in an in vitro and in vivo OA model. In vitro, SCP-1 stem cell line was analysed under inflammatory conditions and Mg-impact. In vivo, small Mg- and WE43 alloy-cylinders (1mm × 0,5mm) were implanted into the subchondral bone of the knee joint of 24 NZW rabbits after establishment of OA. As control, another 12 rabbits received only drill-holes. µCT-scan were performed and assessed for changes in bone volume and density. After euthanasia, cartilage was evaluated macroscopically and histologically after Safranin-O-staining. Furthermore, staining with CD271 directed antibody was performed to assess neuro-reactivity.In vitro, an increased gene expression of extracellular matrix proteins as collagen II or aggrecan even under inflammatory conditions was observed under Mg-impact. In vivo, µCT evaluation revealed twice-elevated values for bone volume in femoral condyles with Mg-cylinders compared to controls while density remained unchanged. Cartilage showed no significant differences between the groups. Mg- and WE-samples showed significantly lower levels of CD271+ cells in the cartilage and bone of the operated joints than in non-operated joints, which was not the case in the Drilling-group. Furthermore, bone in operated knees of Drilling-group showed a strong trend to an increase in CD271+ cells compared to both Cylinder-groups. Counting of CD271+ vessels revealed that this difference was attributable to a higher amount of these vessels.The in vitro results indicate a potential cartilage regenerative activity of the degradable Mg-based material. While so far there was no positive effect on the cartilage itself in vivo, implantation of Mg-cylinders seemed to reduce pain-mediating vessels.Acknowledgements: This work is funded by the German Research Foundation (DFG, project number 404534760). We thank Björn Wiese for production of the cylinders.

POST-PRINTING CHONDROGENIC DIFFERENTIATION OF STEM CELL SPHEROID CONSTRUCTS FOR CARTILAGE TISSUE ENGINEERING

Cartilage lesions often undergo irreversible progression due to low self-repair capability of this tissue. Tissue engineered approaches based in extrusion bioprinting of constructs loaded with stem cell spheroids may offer valuable alternatives for the treatment of cartilage lesions. Human mesenchymal stromal cell (hMSC) spheroids can be chondrogenically differentiated faster and more efficiently than single cells. This approach allows obtaining larger tissues in a rapid, controlled and reproducible way. However, it is challenging to control tissue architecture, construct stability, and cell viability during maturation. In this study we aimed at the development of a reproducible bioprinting process followed by post-bioprinting chondrogenic differentiation procedure using large quantities of hMSC spheroids encapsulated in a xanthan gum-alginate hydrogel. Multi-layered constructs were bioprinted, ionically crosslinked, and chondrogenically differentiated for 28 days. The expression of glycosaminoglycan, collagen II and IV were observed. After 56 days in culture, the bioprinted constructs were still stable and show satisfactory cell metabolic activity with profuse extracellular matrix production. These results showed a promising procedure to obtain 3D cartilage-like constructs that could be potential use as stable chondral tissue implants for future therapies.Acknowledgments: The National Council for Scientific and Technological Development (CNPq, Brazil – Grants # 314 724/2021-4, 307 829/2018-9, 430 860/2018-8, 142 050/2018-0 and 465 656/2014-5), the Coordination for the Improvement of Higher Educational Personnel (CAPES, Brazil – PrInt 88 887.364849/2019-00 and PrInt 88 887.310405/2018-00), the Fund for Support to Teaching, Research and Extension from the University of Campinas (FAEPEX/UNICAMP, Brazil – Grants # 2921/18, 2324/21), and the European Union's Horizon 2020 JointPromise project – Precision manufacturing of microengineered complex joint implants, under grant agreement 874 837 are acknowledged for the financial support of this study.

Differences in pretreatment symptoms of patients receiving injections or surgery to treat cartilage lesions of the knee: an International Cartilage Regeneration and Joint Preservation Society Patient Registry Study

IntroductionSome patients with cartilage defects of the knee are known to report similar quality of life (QoL) scores to patients listed for total knee arthroplasty. However, it is unknown whether patients waiting to undergo injections for a cartilage injury perceive their symptoms and QoL to be equivalent to those awaiting surgery. ObjectivesCompare the pretreatment status of patients undergoing a knee injection or surgical intervention for cartilage lesions. The hypothesis was that there would be no clinical difference in scores between the 2 cohorts. MethodsAnonymous data from the International Cartilage Regeneration and Joint Preservation Society Registry were exported: demographics, type of intervention, pretreatment Knee Osteoarthritis Outcome Scores (KOOS) and Visual Analog Scores (VAS). The required sample size was 273 per cohort. Statistical analyses were used to compare the scores of each cohort (α = 0.05). ResultsOne thousand five hundred seventy-eight patients were included (993 surgeries vs 585 injections). The surgical cohort was 30 years younger than the injection cohort (P < .0001). There were no clinically significant differences in KOOS or VAS. However, KOOS aggregate scores, KOOS pain, and VAS were statistically poorer in the injection cohort (P < .0001; P = .04; P = .001). KOOS QoL was poorer in the surgical cohort (P < .0001). ConclusionsOur null hypothesis was accepted, as there were no clinically significant differences in the scores. Thus, both cohorts perceived their level of disability and severity of symptoms to be equivalent. Nevertheless, statistical analyses suggested that the younger surgical cohort perceived their QoL to be poorer, while pain levels were worse in the older injection cohort.

Suitable characteristics in the selection of human allogeneic chondrocytes donors to increase the number of viable cells for cartilage repair.

Autologous chondrocyte implantation has shown optimal long-term outcomes in the treatment of cartilage lesions. The challenge for a single-stage approach lies in obtaining sufficient number of cells with high viability. The answer could lie in supplementing or replacing them with allogenic chondrocytes coming from cadaveric donors. In the present work, we aimed to compare the number of viable cells isolated from cartilage of live and cadaveric donors and to determine the suitable characteristics of the best donors. A total of 65 samples from donors aged from 17 to 55years, either women or men, were enrolled in this study (33 living vs. 32 cadaveric). The mean time of hours from death to processing samples in cadaveric donors was higher compared to live donors (64.3 ± 17.7 vs. 4.6±6.4). The number of isolated chondrocytes per gram of cartilage was higher in cadaveric donors (5.389 × 106 compared to 3.067 × 106 in living donors), whereas the average of cell viability was comparable in both groups (84.16% cadaveric, 87.8% alive). It is possible to obtain viable chondrocytes from cartilage harvested from cadaveric donors, reaching a similar cell number and viability to that obtained from the cartilage of living donors.

Managing the Heterogeneity of Mesenchymal Stem Cells for Cartilage Regenerative Therapy: A Review.

Articular cartilage defects commonly result from trauma and are associated with significant morbidity. Since cartilage is an avascular, aneural, and alymphatic tissue with a poor intrinsic healing ability, the regeneration of functional hyaline cartilage remains a difficult clinical problem. Mesenchymal stem cells (MSCs) are multipotent cells with multilineage differentiation potential, including the ability to differentiate into chondrocytes. Due to their availability and ease of ex vivo expansion, clinicians are increasingly applying MSCs in the treatment of cartilage lesions. However, despite encouraging pre-clinical and clinical data, inconsistencies in MSC proliferative and chondrogenic potential depending on donor, tissue source, cell subset, culture conditions, and handling techniques remain a key barrier to widespread clinical application of MSC therapy in cartilage regeneration. In this review, we highlight the strategies to manage the heterogeneity of MSCs ex vivo for more effective cartilage repair, including reducing the MSC culture expansion period, and selecting MSCs with higher chondrogenic potential through specific genetic markers, surface markers, and biophysical attributes. The accomplishment of a less heterogeneous population of culture-expanded MSCs may improve the scalability, reproducibility, and standardisation of MSC therapy for clinical application in cartilage regeneration.

Correction to: Challenges Facing the Translation of Embryonic Stem Cell Therapy for the Treatment of Cartilage Lesions

Correction to: Challenges Facing the Translation of Embryonic Stem Cell Therapy for the Treatment of Cartilage Lesions

In Vitro Comparison of 2 Clinically Applied Biomaterials for Autologous Chondrocyte Implantation: Injectable Hydrogel Versus Collagen Scaffold.

In autologous chondrocyte implantation (ACI), there is no consensus about used bioscaffolds. The aim of this study was to perform an in vitro comparative analysis of 2 clinically applied biomaterials for cartilage lesion treatment. Monolayer expanded human chondrocytes (n = 6) were embedded in a collagen scaffold (CS) and a hyaluronic acid-based hydrogel (HA). Cells were cultured in chondropermissive medium supplemented with and without interleukin-10 (IL-10) and bone morphogenetic protein-2 (BMP-2). Gene expression of chondrogenic markers (COL1A1, COL2A1, COL10A1, ACAN, SOX9) was detected via quantitative real-time-polymerase chain reaction (RT-qPCR). Biosynthesis of matrix compounds, cell viability, morphology as well as migration from surrounding native bovine cartilage into cell-free scaffolds were analyzed histologically. Adhesion of the material to adjacent cartilage was investigated by a custom-made push-out test. The shift of COL1/2 ratio toward COL2A1 was more pronounced in HA, and cells displayed a more spherical morphology compared with CS. BMP-2 and IL-10 significantly increased COL2A1, SOX9, and ACAN expression, which was paralleled by enhanced staining of glycosaminoglycans (GAGs) and type 2 collagen in histological sections of CS and HA. COL10A1 was not significantly expressed in HA and CS. Better interfacial integration and enhanced cell invasion was observed in CS. Push-out tests using CS showed higher bonding strength to native cartilage. HA-based hydrogel revealed a more chondrocyte-like phenotype but only allowed limited cell invasion, whereas CS were advantageous in terms of cellular invasion and interfacial adhesion. These differences may be clinically relevant when treating cartilaginous or osteochondral defects.

Management of Cartilage Lesions Based on Etiology : OCD versus Acute Traumatic Lesions

Treatment of articular cartilage lesions in the knee remains a challenge. A wide range of options is available nowadays, including conservative measures, simple arthroscopic interventions, marrow tapping techniques, osteochondral auto/allografting, cell-based techniques, growth factors and emerging gene therapy techniques. Osteochondritis dissecans (OCD) is first described by Konig in 1888. Its prevalence is estimated at 15 to 30 cases per 100.000. The lateral aspect of the medial femoral condyle is the classic site, repetitive trauma with microscopic fractures below the surface of the joint of clogging of the tiny blood vessels inside the bone associated with a number of differing medical conditions. OCD is commonly found in older children and adolescents who actively participate in sports. It is different from acute traumatic cartilage lession, as they happen due to a direct compaction injuries, such as occur in the patellofemoral joint. The more common mechanism is a rotational injury to the knee or shearing force across the articular cartilage. Patellar dislocation may lead to osteochondral fracture through this mechanism and is responsible for 40-50% of osteochondral lesions around the femoral condyles. It is most common in young active patients aged 20-40 years. Treatment options are variable and dependent on many factors, including patient age and activity level, location and size of the defect, meniscal status, limb alignment, concomitant knee pathologies, chronicity, and comorbidities. Treatment of cartilage lesions is differentiated not based on its etiology but based on the severity of the cartilage lesions such as size, depth, shape and description of the walls (contained, partially contained or opened), and the resource capabilities of each centre. What needs to be understood is that OCD lesions are disease-related, whereas acute traumatic lesions may occur in otherwise healthy cartilage due to mechanical trauma.

Articular Cartilage Repair After Implantation of Hyaline Cartilage Beads Engineered From Adult Dedifferentiated Chondrocytes: Cartibeads Preclinical Efficacy Study in a Large Animal Model

Background: Chondrocyte-based cell therapy to repair cartilage has been used for >25 years despite current limitations. This work presents a new treatment option for cartilage lesions. Hypothesis: High-quality hyaline cartilage microtissues called Cartibeads are capable of treating focal chondral lesions once implanted in the defect, by complete fusion of Cartibeads among themselves and their integration with the surrounding native cartilage and subchondral bone. Study Design: Controlled laboratory study. Methods: Cartibeads were first produced from human donors and characterized using histology (safranin O staining of glycosaminoglycan [GAG] and immunohistochemistry of collagen I and II) and GAG dosage. Cartibeads from 6 Göttingen minipigs were engineered and implanted in an autologous condition in the knee (4 or 5 lesions per knee). One group was followed up for 3 months and the other for 6 months. Feasibility and efficacy were measured using histological analysis and macroscopic and microscopic scores. Results: Cartibeads revealed hyaline features with strong staining of GAG and collagen II. High GAG content was obtained: 24.6-µg/mg tissue (wet weight), 15.52-µg/mg tissue (dry weight), and 35 ± 3-µg GAG/bead (mean ± SD). Histological analysis of Göttingen minipigs showed good integration of Cartibeads grafts at 3 and 6 months after implantation. The Bern Score of the histological assay comparing grafted versus empty lesions was significant at 3 months (grafted, n = 10; nongrafted, n = 4; score, 3.3 and 5.3, respectively) and 6 months (grafted, n = 11; nongrafted, n = 3; score, 1.6 and 5.1). Conclusion: We developed an innovative 3-step method allowing, for the first time, the use of fully dedifferentiated adult chondrocytes with a high number of cell passage (owing to the extensive amplification in culture). Cartibeads engineered from chondrocytes hold potential as an advanced therapy medicinal product for treating cartilage lesions with established efficacy. Clinical Relevance: This successful preclinical study, combined with standardized manufacturing of Cartibeads according to good manufacturing practice guidelines, led to the approval of first-in-human clinical trial by the ethics committee and local medical authority. The generated data highlighted a promising therapy to treat cartilage lesions from a small amount of starting biopsy specimen. With our innovative cell amplification technology, very large lesions can be treated, and older active patients can benefit from it.

Hyaline Cartilage Microtissues Engineered from Adult Dedifferentiated Chondrocytes: Safety and Role of WNT Signaling.

The repair of damaged articular cartilage is an unmet medical need. Chondrocyte-based cell therapy has been used to repair cartilage for over 20 years despite current limitations. Chondrocyte dedifferentiation upon expansion in monolayer is well known and is the main obstacle to their use as cell source for cartilage repair. Consequently, current approaches often lead to fibrocartilage, which is biomechanically different from hyaline cartilage and not effective as a long-lasting treatment. Here, we describe an innovative 3-step method to engineer hyaline-like cartilage microtissues, named Cartibeads, from high passage dedifferentiated chondrocytes. We show that WNT5A/5B/7B genes were highly expressed in dedifferentiated chondrocytes and that a decrease of the WNT signaling pathway was instrumental for full re-differentiation of chondrocytes, enabling production of hyaline matrix instead of fibrocartilage matrix. Cartibeads showed hyaline-like characteristics based on GAG quantity and type II collagen expression independently of donor age and cartilage quality. In vivo, Cartibeads were not tumorigenic when transplanted into SCID mice. This simple 3-step method allowed a standardized production of hyaline-like cartilage microtissues from a small cartilage sample, making Cartibeads a promising candidate for the treatment of cartilage lesions.

The role of arthroscopic debridement in the treatment of osteochondral lesions of the talus in the athlete

<h2>ABSTRACT</h2> Arthroscopic debridement (AD) is the most common procedure in treating cartilage lesions. However, despite its comprehensive implementation in the surgical treatment of osteochondral lesions of the talar dome (OLT) during the last century, its practice was abandoned, preferring newer techniques, and is currently omitted in most treatment algorithms. Up to date, no conclusive evidence exists regarding the superiority of bone marrow stimulation over AD, and evidence continues to be scarce on its implementation. AD represents an easy, inexpensive, technically low-demanding procedure, with potential benefits due to its rapid rehabilitation, the lack of donor-site morbidity, and without compromising the subchondral (SC) plate and bone. The SC plate and bone have been acknowledged as essential structures for cartilage health and quality of the surgical repair, participating in the load transmission of the ankle joint and linking biochemically through transport pathways with the overlying hyaline cartilage. AD alone is an OLT treatment option with potential benefits for the athlete, especially in partial-thickness cartilage injuries and non-cystic contained International Cartilage Repair Society grade III-IV OLT less than 10 mm² in size and 5 mm in depth. Additionally, AD alone can represent an appealing option for athletes looking for symptomatic relief and a fast return to sports during the season.

3D printed porous sulfonated polyetheretherketone scaffold for cartilage repair: Potential and limitation.

ObjectiveThe treatment of cartilage lesions has always been a difficult problem. Although cartilage tissue engineering provides alternative treatment options for cartilage lesions, biodegradable tissue engineering scaffolds have limitations.MethodsIn this study, we constructed a porous PEEK scaffold via 3D printing, surface-engineered with concentrated sulfuric acid for 15 s (SPK-15), 30 s (SPK-30), and 60 s (SPK-60). We systematically evaluated the physical and chemical characteristics and biofunctionalities of the scaffolds, and then evaluated the macrophage polarization modulating ability and anti-inflammatory effects of the sulfonated PEEK, and observed the cartilage-protective effect of SPK using a co-culture study. We further evaluated the repair effect of PEEK and SPK by implanting the prosthetic scaffold into a cartilage defect in a rabbit model.ResultsCompared to the PEEK, SPK-15 and SPK-60 scaffolds, SPK-30 has a good micro/nanostructure, appropriate biomechanical properties (compressive modulus, 43 ± 5 MPa; Shaw hardness, 20.6 ± 1.3 HD; close to native cartilage, 30 ± 8 MPa, 17.8 ± 0.8 HD), and superior biofunctionalities. Compared to PEEK, sulfonated PEEK can favor macrophage polarization to the M2 phenotype, which increases anti-inflammatory cytokine secretion. Furthermore, SPK can also prevent macrophage-induced cartilage degeneration. The in-vivo animal experiment demonstrates that SPK can favor new tissue ingrowth and integration, prevent peri-scaffold cartilage degeneration and patellar cartilage degeneration, inhibit inflammatory cytokine secretion, and promote cartilage function restoration.ConclusionThe present study confirmed that the 3D printed porous sulfonated PEEK scaffold could promote cartilage functional repair, and suggests a new promising strategy for treating cartilage defects with a functional prosthesis that spontaneously inhibits nearby cartilage degeneration.Translational potential of this articleIn the present study, we propose a new cartilage repair strategy based on a porous, non-biodegradable polyetheretherketone (PEEK) scaffold, which may bring up a new treatment route for elderly patients with cartilage lesions in the future.

Evaluation of Three-Dimensional Bioprinted Human Cartilage Powder Combined with Micronized Subcutaneous Adipose Tissues for the Repair of Osteochondral Defects in Beagle Dogs.

Cartilage lesions are difficult to repair due to low vascular distribution and may progress into osteoarthritis. Despite numerous attempts in the past, there is no proven method to regenerate hyaline cartilage. The purpose of this study was to investigate the ability to use a 3D printed biomatrix to repair a critical size femoral chondral defect using a canine weight-bearing model. The biomatrix was comprised of human costal-derived cartilage powder, micronized adipose tissue, and fibrin glue. Bilateral femoral condyle defects were treated on 12 mature beagles staged 12 weeks apart. Four groups, one control and three experimental, were used. Animals were euthanized at 32 weeks to collect samples. Significant differences between control and experimental groups were found in both regeneration pattern and tissue composition. In results, we observed that the experimental group with the treatment with cartilage powder and adipose tissue alleviated the inflammatory response. Moreover, it was found that the MOCART score was higher, and cartilage repair was more organized than in the other groups, suggesting that a combination of cartilage powder and adipose tissue has the potential to repair cartilage with a similarity to normal cartilage. Microscopically, there was a well-defined cartilage-like structure in which the mid junction below the surface layer was surrounded by a matrix composed of collagen type I, II, and proteoglycans. MRI examination revealed significant reduction of the inflammation level and progression of a cartilage-like growth in the experimental group. This canine study suggests a promising new surgical treatment for cartilage lesions.

The Effect of Neonatal, Juvenile, and Adult Donors on Rejuvenated Neocartilage Functional Properties.

Cartilage does not naturally heal, and cartilage lesions from trauma and wear-and-tear can lead to eventual osteoarthritis. To address long-term repair, tissue engineering of functional biologic implants to treat cartilage lesions is desirable, but the development of such implants is hindered by several limitations, including (1) donor tissue scarcity due to the presence of diseased tissues in joints, (2) dedifferentiation of chondrocytes during expansion, and (3) differences in functional output of cells dependent on donor age. Toward overcoming these challenges, (1) costal cartilage has been explored as a donor tissue, and (2) methods have been developed to rejuvenate the chondrogenic phenotype of passaged chondrocytes for generating self-assembled neocartilage. However, it remains unclear how the rejuvenation processes are influenced by donor age and, thus, how to develop strategies that specifically target age-related differences. Using histological, biochemical, proteomic, and mechanical assays, this study sought to determine the differences among neocartilage generated from neonatal, juvenile, and adult donors using the Yucatan minipig, a clinically relevant large animal model. Based on the literature, a relatively young adult population of animals was chosen due to a reduction in functional output of human articular chondrocytes after 40 years of age. After isolation, costal chondrocytes were expanded, rejuvenated, and self-assembled, and the neocartilages were assessed. The aggregate modulus values of neonatal constructs were at least 1.65-fold of those from the juvenile or adult constructs. Poisson's ratio also significantly differed among all groups, with neonatal constructs exhibiting values 49% higher than adult constructs. Surprisingly, other functional properties such as tensile modulus and glycosaminoglycan content did not significantly differ among groups. Total collagen content was slightly elevated in the adult constructs compared to neonatal and juvenile constructs. A more nuanced view using bottom-up mass spectrometry showed that Col2a1 protein was not significantly different among groups, but protein content of several other collagen subtypes (i.e., Col1a1, Col9a1, Col11a2, and Col12a1) was modulated by donor age. For example, Col12a1 protein content in adult constructs was found to be 102.9% higher than neonatal-derived constructs. Despite these differences, this study shows that different aged donors can be used to generate neocartilages of similar functional properties. Impact statement Tissue-engineered neocartilage can be generated with functional properties that mimic native cartilage tissue. However, cell sourcing challenges hinder clinical translation of tissue-engineered cartilage. Chondrocytes can be expanded and rejuvenated for the generation of functional self-assembled cartilage, making an allogeneic approach feasible. However, it is currently unclear if donor age impacts functional properties. In this study, using the Yucatan minipig as a clinically relevant large animal model, we demonstrate that functional properties of self-assembled neocartilage are relatively consistent regardless of donor age, suggesting that a wider range of donor ages may be used for cartilage tissue engineering than previously expected.

Hypothermically Stored Amniotic Membrane for the Treatment of Cartilage Lesions: A Single-Arm Prospective Study with 2-Year Follow-Up.

ObjectiveThe purpose of this study was to determine the safety and efficacy of hypothermically stored amniotic membrane (HSAM) for the treatment of cartilage lesions of the knee using imaging, patient-reported outcomes (PROs), second-look arthroscopy, and histology. Patients were treated with HSAM and followed for 2 years.DesignSubjects with focal chondral lesions of the femur (International Cartilage Repair Society grade 3-4) were enrolled in this single-arm prospective study. Standard of care imaging was completed. PROs, including the Knee Injury and Osteoarthritis Outcome Score (KOOS), Marx Activity Scale, and Visual Analog Scale (VAS), were collected at baseline and at 3, 6, 12, 18, and 24 months. Three subjects underwent an optional arthroscopy and biopsy of the repair at 24 months.ResultsTen subjects were enrolled and completed the study. At 24 months, KOOS Sports & Recreation improved 173.3% and Quality of Life improved 195.3% from baseline. Marx Activity Scale increased 266.8% from 12 to 24 months. VAS scores improved 84.8% and 81.0% from baseline to 24 months for average and maximum pain. Modified Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) scoring showed that 7 of 10 subjects had complete defect repair and filling by 24 months. Biopsy staining for collagen II revealed integration and remodeling of HSAM into a mix of hyaline-like cartilage and fibrocartilage matrix.ConclusionThis study provides evidence supporting the safety and efficacy of HSAM for treating symptomatic cartilage lesions. Subjects showed a high degree of defect fill and integration with the native cartilage and reported improvements in pain and function post-treatment. Results provide important original data for future clinical trials.

Volume index as a new measure of cartilage loss: a retrospective MRI-based study of chondral injury patterns in adult patients with knee pain.

Knee pain is one of the commonest symptoms in patients who attend the Orthopaedic outpatient clinics. Chondral defects result in a painful knee. Incidence of chondral defect is reported to be between 5 and 10% over the age of 40. It is well documented that chondral defects can lead to osteoarthritis. Early detection of these lesions and cartilage repair surgery can delay the onset of osteoarthritis. The purpose of this study is to highlight the incidence, associations and correlations between opposing cartilage defects in patients who present to the knee clinic with pain. A retrospective analysis was carried out on patients who had Magnetic Resonance Imaging scans for painful knees between June 2017 and May 2019. About 227 consecutive knees were studied for the incidence of chondral defects, number of lesions, grade and size of lesion, geographical location and associated pathology in the knee. All the 227 patients had chondral lesions. Most patients had 2-3 lesions (66.1%) with patellar lesions (76.6%) being the commonest followed by medial femoral condyle (59.9%). Significant correlation was found in grade and size between opposing surface lesions in patella-trochlea, Medial Femoral Condyle-Medial Tibial Plateau and Lateral Femoral Condyle-Lateral Tibial Plateau. Females were more predisposed to patella lesions. Significance between age and lesions were established. Incidence of cartilage defects in the knee is very high. Kissing lesions must be considered when treating cartilage lesions. Volume index could be a promising method to quantify lesions.