Articular Cartilage Restoration Research Articles

Glucosamine sulfate-loaded nanofiber reinforced carboxymethyl chitosan sponge for articular cartilage restoration

Cartilage is severely limited in self-repair after damage, and tissue engineering scaffold transplantation is considered the most promising strategy for cartilage regeneration. However, scaffolds without cells and growth factors, which can effectively avoid long cell culture times, high risk of infection, and susceptibility to contamination, remain scarce. Hence, we developed a cell- and growth factor-dual free hierarchically structured nanofibrous sponge to mimic the extracellular matrix, in which the encapsulated core–shell nanofibers served both as mechanical supports and as long-lasting carriers for bioactive biomass molecules (glucosamine sulfate). Under the protection of the nanofibers in this designed sponge, glucosamine sulfate could be released continuously for at least 30 days, which significantly accelerated the repair of cartilage tissue in a rat cartilage defect model. Moreover, the nanofibrous sponge based on carboxymethyl chitosan as the framework could effectively fill irregular cartilage defects, adapt to the dynamic changes during cartilage movement, and maintain almost 100 % elasticity even after multiple compression cycles. This strategy, which combines fiber freeze-shaping technology with a controlled-release method for encapsulating bioactivity, allows for the assembly of porous bionic scaffolds with hierarchical nanofiber structure, providing a novel and safe approach to tissue repair.

The Condition of the Meniscus and Cartilage of the Injured Knee on Preoperative Magnetic Resonance Imaging Is a Prognostic Factor Affecting Postoperative Outcomes Following Knee Cartilage Restoration Surgery

PurposeTo evaluate the relationship between preoperative whole-joint imaging evaluation of the knee with patient reported outcome measures after cartilage restoration surgery (mosaicplasty, osteochondral allograft transplantation (OCA), matrix autologous chondrocyte implantation (MACI)). MethodsWe retrospectively evaluated patients who underwent knee articular cartilage restoration at our institution from 2014 to 2020. The patients’ knee MRI was evaluated with the whole joint magnetic resonance imaging score (WORMS) and semi-quantitative synovial inflammation imaging biomarkers of the preoperative MRI. To assess patient-reported outcome (PRO) score, Lysholm score and Knee Osteoarthritis and Injury Outcome Score (KOOS) were completed at minimum 2 years follow-up. Statistical analysis was performed using Spearman rank test to obtain correlation values for WORMS score and PRO score for each survey. ResultsThere were 40 patients who were enrolled in this study. The average age at baseline was 34.5 years. The average BMI was 28.2 kg/m2 and 26 of 40 were men (range, 20-58 years). The maximum preoperative WORMS score was significantly correlated with the post-operative Lysholm score (r = -0.52, p=0.0013). The WORMS Meniscus and Cartilage sub-scales were significantly correlated with the Lysholm score (r = -0.36, p=0.024 and r = -0.37, p=0.021 respectively). The maximum WORMS score was significantly correlated with the KOOS Daily living and Sports/rec sub-scores (r= -0.47, p=0.0023 and r = -0.42, p=0.0077, respectively). Semi-quantitative synovial inflammation imaging biomarkers were not significantly correlated with PRO scores. ConclusionIncreasing preoperative degenerative change in the knee, as evidenced by a higher WORMS on preoperative MRI, was associated with inferior patient-reported outcomes at a minimum of 2 years after cartilage restoration surgery (mosaicplasty, OCA, MACI). Semi-quantitative scoring of the whole joint on preoperative MRI may allow for improved counseling regarding expected benefit for patients after cartilage restoration surgery.

Construction methods and biomedical applications of PVA-based hydrogels.

Polyvinyl alcohol (PVA) hydrogel is favored by researchers due to its good biocompatibility, high mechanical strength, low friction coefficient, and suitable water content. The widely distributed hydroxyl side chains on the PVA molecule allow the hydrogels to be branched with various functional groups. By improving the synthesis method and changing the hydrogel structure, PVA-based hydrogels can obtain excellent cytocompatibility, flexibility, electrical conductivity, viscoelasticity, and antimicrobial properties, representing a good candidate for articular cartilage restoration, electronic skin, wound dressing, and other fields. This review introduces various preparation methods of PVA-based hydrogels and their wide applications in the biomedical field.

Return to Play After Knee Articular Cartilage Restoration: Surgical Options, Rehabilitation Protocols, and Performance Outcomes.

Numerous cartilage restoration techniques have proven to be effective in the treatment of articular cartilage defects. The ultimate goal of these procedures is to improve pain and function, thereby increasing the likelihood of a patient's return to physical activity. Postoperative rehabilitation is a key component for a successful and expedient return to activities. The purpose of this article is to review the current literature regarding common surgical options, rehabilitation protocols, and performance outcomes after operative treatment of articular cartilage defects. Studies have demonstrated improved short- to long-term outcomes in a majority of techniques. However, the clinical benefits of microfracture are short-lived, which has led to the use of alternative procedures. Rehabilitation protocols are not standardized, but emphasis has been placed on bracing, weightbearing, early continuous passive range of motion, and strengthening to improve function. There is growing evidence to suggest that accelerated rehabilitation after matrix-induced autologous chondrocyte implantation may result in superior outcomes compared to delayed rehabilitation. Overall, most techniques result in satisfactory rates of return to play, though existing comparative studies typically include patients with heterogeneous pathology, complicating effective synthesis of outcomes data. In appropriately selected patients, cartilage restoration procedures after articular cartilage injury result in favorable patient-reported clinical outcomes and high rates of return to play. While studies emphasize the critical role that rehabilitation plays with respect to outcomes after surgery, there are substantial inconsistencies in protocols across techniques.

Surface-Modified Nano-Hydroxyapatite Uniformly Dispersed on High-Porous GelMA Scaffold Surfaces for Enhanced Osteochondral Regeneration.

This study aims to investigate the impact of enhancing subchondral bone repair on the efficacy of articular cartilage restoration, thereby achieving improved osteochondral regeneration outcomes. In this study, we modified the surface of nano-hydroxyapatite (n-HAp) through alkylation reactions to prepare n-HApMA. Characterization techniques, including X-ray diffraction, infrared spectroscopy scanning, thermogravimetric analysis, particle size analysis, and electron microscopy, were employed to analyze n-HApMA. Bioinks were prepared using n-HApMA, high porosity GelMA hydrogel, and adipose tissue derived stromal cells (ADSCs). The rheological properties of the bioinks during photocuring were investigated using a rheometer. Based on these bioinks, a biphasic scaffold was constructed. The viability of cells within the scaffold was observed using live-dead cell staining, while the internal morphology was examined using scanning electron microscopy. The stiffness of the scaffold was evaluated through compression testing. Scaffolds were implanted into the osteochondral defects of New Zealand rabbit knees, and microCT was utilized to observe the subchondral bone repair. Hematoxylin and eosin (H&E) staining, Masson's trichrome staining, and Safranin O/Fast Green staining were performed to assess the regeneration of subchondral bone and cartilage. Furthermore, immunohistochemical staining was employed to detect the expression of osteogenic and chondrogenic-related molecules. Scaffold characterization revealed that surface modification enables the uniform distribution of n-HApMA within the GelMA matrix. The incorporation of 5% n-HApMA notably enhanced the elastic modulus and stiffness of the 6% high-porosity GelMA in comparison to n-HAp. Moreover, in-vivo study showed that the homogeneous dispersion of n-HApMA on the GelMA matrix facilitated the osteogenic differentiation of adipose-derived stem cells (ADSCs) and promoted osteochondral tissue regeneration. These findings suggest potential applications of the n-HApMA/GelMA composite in the field of tissue engineering and regenerative medicine.

Choice of Protein, Not Its Amyloid-Fold, Determines the Success of Amyloid-Based Scaffolds for Cartilage Tissue Regeneration.

The formation of fibrocartilage during articular cartilage regeneration remains a clinical problem affecting adequate restoration of articular cartilage in joints. To stimulate chondrocytes to form articular cartilage, we investigated the use of amyloid fibril-based scaffolds. The proteins α-synuclein, β-lactoglobulin, and lysozyme were induced to self-assemble into amyloid fibrils and, during dialysis, formed micrometer scale amyloid networks that resemble the cartilage extracellular matrix. Our results show that lysozyme amyloid micronetworks supported chondrocyte viability and extracellular matrix deposition, while α-synuclein and β-lactoglobulin maintained cell viability. With this study, we not only confirm the possible use of amyloid materials for tissue regeneration but also demonstrate that the choice of protein, rather than its amyloid-fold per se, affects the cellular response and tissue formation.

Synergistic chondrogenesis promotion and arthroscopic articular cartilage restoration via injectable dual-drug-loaded sulfated hyaluronic acid hydrogel for stem cell therapy

Bone marrow stem cells (BMSCs)-loaded injectable hydrogels are promising vehicles for the restoration of articular cartilage defect (ACD), while was limited with insufficient chondrogenic capacity and poor maintenance of chondrogenic phenotype. Herein, we reported a dual-drug delivering sulfated hyaluronic acid (SHA) hydrogel with injectable capacity to promote ACD repairment. Two precursor solutions were initial prepared: the HA-CHO-SO3 solution loaded with Kartogenin (KGN), β-cyclodextrin-CHO (β-CD-CHO) and BMSCs, and the HA-NHNH2-SO3 loaded with transforming growth factor β1 (TGF-β1) and BMSCs. The HA-CHO-SO3 could adsorb TGF-β1 through sulfonic acid group, and β-CD-CHO could preabsorb KGN through a hydrophobic cavity on β-CD. The aldehyde group on β-CD-CHO could react directly with the acylhydrazide to load KGN onto the HA-NHNH2-SO3 network. The mixture of two solutions resulted in the formation of a SHA@KGN/TGF-β1 hydrogel through reversible dynamic Schiff-based cross-linking between hydrazide and aldehyde groups. The SHA@KGN/TGF-β1 hydrogel had the benefits of injectability, rapid gelation, self-healing, and firm adhesion to the host tissue due to the reaction between the amine group on the host tissue and the aldehyde group on the SHA. Additionally, it could simultaneously load both TGF-β1 and KGN through electrostatic reaction and host-guest reaction, respectively, providing sustained release kinetics for both drugs. The dual-loaded drugs in the SHA@KGN/TGF-β1 hydrogel could synergistically enhance chondrogenic differentiation and suppress the hypertrophy of BMSCs, effectively promoting cartilage regeneration at both in vitro and in vivo circumstance. The one-step construction of this hydrogel system via mixing injection endowed facile arthroscopic ACD restoration and may significantly promote clinical application.

Harnessing Growth Factor Interactions to Optimize Articular Cartilage Repair.

The failure of cartilage healing is a major impediment to recovery from joint disease or trauma. Growth factors play a central role in cell function and have been proposed as potential therapeutic agents to promote cartilage repair. Decades of investigation have identified many growth factors that promote the formation of cartilage in vitro and in vivo. However, very few of these have progressed to human trials. A growth factor that robustly augments articular cartilage healing remains elusive. This is not surprising. Articular cartilage repair involves multiple cellular processes and it is unlikely that any single agent will be able to optimally regulate all of them. It is more likely that multiple regulatory molecules may be required to optimize the maintenance and restoration of articular cartilage. If this is the case, then interactions among growth factors may be expected to play a key role in determining their therapeutic value. This review explores the hypothesis that growth factor interactions could help optimize articular cartilage healing.

Next Generation Cartilage Repair and the Pre-arthroplasty Patient

The NeoCart® implant (Histogenics Corporation, Waltham, MA) is a cell-based therapeutic for the restoration of articular cartilage defects. The implant is composed of a type I collagen scaffold, inoculated with expanded autologous chondrocytes, and preconditioned under hydrostatic loading and low oxygen tension. The process was designed to create an autogenous chondrogenic construct for application during a surgical biologic reconstruction procedure for patients with symptomatic cartilage disease. Favorable pre-clinical basic science and animal studies characterizing the regenerative potential of NeoCart led to application for United States Food and Drug Administration (FDA) approval as the first autologous tissue therapeutic for articular cartilage restoration, beginning with a Phase I safety trial in 2003. Deemed safe in Phase I and efficacious in Phase II relative to “standard of care” microfracture, a Phase III randomized controlled superiority trial versus microfracture was authorized by FDA in 2010. The primary outcome measure of a statistically significant difference in the number of responders to treatment versus control cohorts based on meeting a dual-criteria threshold of >20-point and >12-point improvement in International Knee Documentation Committee (IKDC) and Knee Injury and Osteoarthritis Outcome Score (KOOS) pain domain scores, respectively, was established. The 1-year protocol assessment metric for superiority was narrowly missed, which led to termination of the trial in 2019. Ultimately, the therapy was not approved for use by the FDA. The history of this case example: quelching a biologically safe and effective therapeutic, highlights hurdles in the complex process of bringing scientifically sound products to patients through regulatory processes in the United States.

Tissue Engineering and Cell Therapy for Cartilage Repair: Preclinical Evaluation Methods.

A chondral injury is a limiting disease that can affect the quality of life and be an economic burden due to the cost of immediate treatment and loss in work productivity. If left untreated, such an injury may progress to osteoarthritis, a degenerative and debilitating joint disease characterized by pain and functional impairment. Mesenchymal stromal cells (MSCs), which have immune-modulatory properties and the ability to differentiate into chondroblasts and osteoblasts, are a predictable source for the treatment of cartilage injuries. This article presents tools to evaluate cartilage restoration by tissue engineering and cell therapy treatment in a translational and preclinical large animal model. In this controlled experimental study with 14 miniature pigs, a scaffold-free tissue engineering construct (TEC) derived from dental pulp and synovial MSCs for cartilage therapy was tested. Total thickness cartilage defects were performed in both posterior knees. The defect was left empty in one of the knees, and the other received the TEC. The tissue repair was morphologically assessed by magnetic resonance imaging (MRI) using the three-dimensional double echo steady-state (3D-DESS) sequence, and compositional assessment was carried out based on the T2 mapping technique. The osteochondral specimens were fixed for histopathology, decalcified, subjected to standard histological processing, sectioned, and stained with hematoxylin and eosin. The sections stained for immunohistochemical detection of collagen types were digested with pepsin and chondroitinase and incubated with antibodies against them. The mechanical evaluation involved analysis of Young's modulus of the cartilage samples based on the indentation and maximum compression test. In addition, a finite element model was used to simulate and characterize properties of the osteochondral block. At 6 months after surgery, there were no complications with the animals and the MRI, histological, immunohistochemical, and biomechanical evaluations proved to be effective and qualified to differentiate good quality chondral repair from inadequate repair tissue. The proposed methods were feasible and capable to properly evaluate the defect filled with TEC containing stromal cells after 6 months of follow-up in a large animal model for articular cartilage restoration. Impact Statement Articular chondral injuries are prevalent and represent an economic burden due to the cost of treatment. The engineering of cartilage tissue can promote the repair of chondral injuries and is dependent on selecting appropriate cells and biocompatible frameworks. In this article, methods for evaluation of a scaffold-free cell delivery system made from mesenchymal stromal cells were present in a translational study that allows further clinical safety and efficacy trials.

The Effects of Crosslinking on the Rheology and Cellular Behavior of Polymer-Based 3D-Multilayered Scaffolds for Restoring Articular Cartilage

Polymer-based tri-layered (bone, intermediate and top layers) scaffolds used for the restoration of articular cartilage were prepared and characterized in this study to emulate the concentration gradient of cartilage. The scaffolds were physically or chemically crosslinked. In order to obtain adequate scaffolds for the intended application, the impact of the type of calcium phosphate used in the bone layer, the polymer used in the intermediate layer and the interlayer crosslinking process were analyzed. The correlation among SEM micrographs, physical-chemical characterization, swelling behavior, rheological measurements and cell studies were examined. Storage moduli at 1 Hz were 0.3–1.7 kPa for physically crosslinked scaffolds, and 4–5 kPa (EDC/NHS system) and 15–20 kPa (glutaraldehyde) for chemically crosslinked scaffolds. Intrinsic viscoelasticity and poroelasticity were considered in discussing the physical mechanism dominating in different time/frequency scales. Cell evaluation showed that all samples are available as alternatives to repair and/or substitute cartilage in articular osteoarthritis.

Determination of the Involvement of Autologous Mesenchymal Bone Marrow Stem Cells in Reparative Chondrogenesis

Summary. Articular cartilage injuries are observed in 60% of arthroscopies. Degenerative changes of the articular cartilage (osteoarthritis) is the most common disease of all the joints, which affects at least 10-13% of the population over the age of 60 years. Significant progress has been made in the treatment of pain and inflammation, but the evidence base for improving the articular cartilage repair remains weak. Despite the seemingly positive results of a number of studies on the use of mesenchymal stem cells (MSCs) for the articular cartilage restoration, the question of the nature of their participation in this process remains controversial. Objective. The objective of the study was to determine the involvement of autologous mesenchymal bone marrow stem cells in reparative chondrogenesis. Materials and Methods. Experimental and morphological determination of the participation of undifferentiated autologous bone marrow MSCs in reparative chondrogenesis was carried out on fifteen rabbits. MSCs of bone marrow marked with a red fluorescent dye PKH-26 (Sigma, USA) was injected into the cavity of the injured joint on the 3rd day after the articular cartilage defect formation. The presence of the transplanted labeled autologous MSCs was examined in these animals on cryostat sections on the seventh, fourteenth and twenty-first days after implantation with fluorescence microscopy. The characteristic red glow was observed in case of the presence of labeled cells in the regenerated cartilage tissue. Results. The presence of transplanted labeled autologous MSCs on cryostat sections was determined in all studied animals. On the 7th day, the cells were arranged diffusely, without noticeable accumulations. On the 14th day, the labeled cells fluoresced in the red zone of the spectrum and created compact conglomerates mainly at the defect zone. On the 21th day, the labeled cells were found only in the regenerate zone. The data obtained indicate the direct participation of autologous MSCs in the processes of chondroreparation after the exogenous implantation into the joint cavity. Conclusions. The method of autologous bone marrow MSCs labeling using PKH-26 fluorescent dyes has shown that autologous bone marrow MSCs are directly involved in the processes of chondroreparation when they are injected intraarticularly.

The Phenomenon of Hypercellularity in Osteoarthritis and Modification of Synovial Fluid

Articular cartilage is a thin layer of connective tissue that consists of tissue fluid and structural macromolecules, including collagens, proteoglycans, non-collagen proteins and glycoproteins without blood vessels, nerves or lymph nodes. It has a limited ability to self-healing. In addition, chondrocytes, which are surrounded by an extracellular matrix, cannot freely migrate to the site of damage from a healthy place, unlike most tissues. Because of this, even a small defect in the articular cartilage caused by mechanical damage can lead to a disease such as osteoarthritis. The task associated with the restoration of articular cartilage is complex, since conventional imaging methods can detect only progressive forms of osteoarthritis. Hypercellularity is one of the stages of the main processes occurring in osteoarthritis. At its early stages, hypercellularity has a remodeling, that is, restorative effect, but subsequently it goes into the stage of degradation, that is, a pathological process is observed. The problem of the transition of hypercellularity from a “restorative” to a “pathological” process, which is irreversible, has been poorly studied. This paperconsiders the aspects that could affect hypercellularity. The main goal of the work is to study the phenomenon of hypercellularity and proliferative activity of chondrocytes in the articular cartilage. The authors identifythe symptoms and causes of osteoarthritis, its stages and study the structural composition of the articular cartilage in order to consider the proliferative activity of chondrocytes in it. The paper investigates and analyzes thephenomenon of hypercellularity.

ARTICULAR CARTILAGE THICKNESS IN PEDIATRIC AND ADOLESCENT KNEES DECREASES WITH AGE AND SKELETAL MATURITY: IMPLICATIONS FOR OSTEOCHONDRAL GRAFTING PROCEDURES

Background:Quantifying native cartilage thickness in pediatric and adolescent knees can help match donor and recipient sites for articular cartilage restoration procedures such as osteochondral autograft transplantation (OATS) and osteochondral allograft transplantation (OCA).Hypothesis/Purpose:The purpose of the current study was to quantify articular cartilage thickness in pediatric and adolescent knees using magnetic resonance imaging (MRI). We hypothesized that cartilage thickness is inversely correlated with skeletal maturity and age.Methods:One hundred and twenty MRI scans were evaluated in a cohort of patients 9 to 18 years old without osteochondral lesions, chondral wear or pathology, intraarticular fractures, history of knee surgery, or inflammatory arthropathy. Measurements of articular cartilage thickness at the medial femoral condyle, lateral femoral condyle, lateral trochlea, and patella were made on axial, coronal, and sagittal MRI scans (Figure 1). Skeletal maturity was categorized as ‘open’, ‘closing’, or ‘closed’ based on the status of the proximal tibial and distal femoral growth plates. Descriptive statistics was used to evaluate cartilage thickness by age and sex. Independent samples t-test, analysis of variance (ANOVA), and linear regression were performed to investigate for associations with sex, skeletal maturity, and age.Results:On the femur, cartilage was thickest at the lateral trochlea with mean articular thickness of 4.2 ± 1.4 mm in males and 3.6 ± 1.3 mm in females (p=0.015) (Table 1). Skeletally immature patients with open physes had significantly thicker cartilage at the medial femoral condyle, lateral femoral condyle, and lateral trochlea compared to patients with closing and closed physes (Figure 2). Linear regression analysis also revealed a significant association between femoral cartilage thickness and age (Figure 3). Age explained 63% of the variance at the medial femoral condyle (B=6.1, p<0.001), 64% of the variance at the lateral femoral condyle (B=4.9, p<0.001), and 68% of the variance at the lateral trochlea (B=8.2, p<0.001) (Table 2). In contrast, cartilage thickness at the patella did not significantly vary by age, sex, or skeletal maturity (Figures 2 and 4).Conclusion:There is a strong inverse association between increasing age and cartilage thickness of the femoral condyles and lateral trochlea. In particular, pediatric knees demonstrate relatively thick cartilage at the lateral trochlea that decreases with age. This information will help surgeons understand recipient site anatomy and identify appropriate donor site tissue for articular cartilage restoration procedures such as OATS and OCA in children and adolescents.Tables:Table 1.Mean articular cartilage thickness of the femur and patellaCombined (n=120)Male(n=40)Female(n=60) p valueMedial femoral condyle3.2 ± 1.03.5 ± 1.02.9 ± 0.80.001Lateral femoral condyle2.8 ± 0.72.9 ± 0.72.7 ± 0.70.056Lateral trochlea3.9 ± 1.44.2 ± 1.43.6 ± 1.30.015Median ridge of patella4.2 ± 0.94.4 ± 0.94.1 ± 0.90.080Medial facet of patella4.7 ± 1.04.8 ± 1.04.6 ± 0.90.320Lateral facet of patella4.6 ± 0.84.7 ± 0.84.5 ± 0.80.185Table 2.Linear regression of articular cartilage thickness of the femur and patella by ageR2 B p valueMedial femoral condyle0.636.1<0.001Lateral femoral condyle0.644.9<0.001Lateral trochlea0.688.2<0.001Median ridge of patella0.024.80.090Medial facet of patella0.045.50.032Lateral facet of patella0.0014.50.741Figures:Figure 1.Measurements of patellofemoral articular cartilage thickness Measurements of articular cartilage thickness were made on (A) coronal, (B, C) sagittal, and (D) axial magnetic resonance imaging (MRI) of the knee. For the medial femoral condyle, cartilage thickness was measured at five regions: midpoint of the medial condyle (MFC) and midpoints of Cahill zones 1 (MID1), 2 (MID2), B (MIDB) and C (MIDC). Similarly, measurements of cartilage thickness of the lateral femoral condyle were made at the midpoint of the lateral condyle (LFC) and midpoints of Cahill zones 4 (MID4), 5 (MID5), B (MIDB), and C (MIDC). Measurement of the lateral trochlea was made at midpoint of Cahill zone A (MIDA). Measurements on the patella were made at the midpoint of the medial facet (MF), midpoint of the lateral facet (LF), and the median ridge (MR) on axial and sagittal MRI scans. Figure 2.Mean articular cartilage thickness of the femur and patella by growth plate statusFigure 3.Mean articular cartilage thickness of the femur by ageFigure 4.Mean articular cartilage thickness of the patella by age

Complications in knee surgery

This is a comprehensive review of complications that can occur with common knee surgical procedures. Procedures have been grouped into arthroscopic & soft-tissue knee surgery, articular cartilage restoration procedures, osteotomy, and arthroplasty. As newer implants and procedures are developed it is anticipated that new complications may arise. However, the overall trend will be towards a generalized reduction. At the same time, patient expectations are increasing in tandem with improvements in health and longevity. It is important to counsel patients regarding any risks of potential complications associated with any intervention as part of the informed consent process.

Targeting Polymeric Nanobiomaterials as a Platform for Cartilage Tissue Engineering.

Articular cartilage is a connective tissue structure that is found in anatomical areas that are important for the movement of the human body. Osteoarthritis is the ailment that most often affects the articular cartilage. Due to its poor intrinsic healing capacity, damage to the articular cartilage is highly detrimental and at present the reconstructive options for its repair are limited. Tissue engineering and the science of nanobiomaterials are two lines of research that together can contribute to the restoration of damaged tissue. The science of nanobiomaterials focuses on the development of different nanoscale structures that can be used as carriers of drugs / cells to treat and repair damaged tissues such as articular cartilage. This review article is an overview of the composition of articular cartilage, the causes and treatments of osteoarthritis, with a special emphasis on nanomaterials as carriers of drugs and cells, which reduce inflammation, promote the activation of biochemical factors and ultimately contribute to the total restoration of articular cartilage.

Restorative procedures for articular cartilage in the ankle: state-of-the-art review

Articular cartilage is a highly specialised connective tissue that serves to lubricate joint surfaces and distribute loads across the joint. Injury to articular cartilage is a significant cause of pain and dysfunction that may eventually lead to osteoarthritis or degenerative arthrosis. Management of these injuries is complicated by the complex architecture and poor vascularity of this tissue. The field of articular cartilage restoration has evolved rapidly over the past several decades and current techniques offer promising results. However, despite the fast pace of progress in the treatment and repair of articular cartilage injury, a clear gold standard in management has yet to emerge. Current techniques for managing cartilage injuries discussed in this review include bone marrow stimulation, osteochondral transplantation, chondrocyte implantation, cell-based transplantation, biological augmentation and scaffold-based therapies. Heterogeneity in study design, including surgical procedures, lesion and patient characteristics, cell collection, biologics preparation protocols and outcome measures limits interpretation of results presented in the literature. Therefore, standardisation across research protocols and collaboration among centres will be necessary. This ‘state-of-the-art review’ presents the indications and techniques for managing ankle articular cartilage lesions, as well as future directions and geographical differences in management.

Accurate Reporting of Concomitant Procedures Is Highly Variable in Studies Investigating Knee Cartilage Restoration.

Successful clinical outcomes following cartilage restoration procedures are highly dependent on addressing concomitant pathology. The purpose of this study was to document methods for evaluating concomitant procedures of the knee when performed with articular cartilage restoration techniques, and to review their reported findings in high-impact clinical orthopedic studies. We hypothesized that there are substantial inconsistencies in reporting clinical outcomes associated with concomitant procedures relative to outcomes related to isolated cartilage repair. A total of 133 clinical studies on articular cartilage repair of the knee were identified from 6 high-impact orthopedic journals between 2011 and 2017. Studies were included if they were primary research articles reporting clinical outcomes data following surgical treatment of articular cartilage lesions with a minimum sample size of 5 patients. Studies were excluded if they were review articles, meta-analyses, and articles reporting only nonclinical outcomes (e.g., imaging, histology). A full-text review was then used to evaluate details regarding study methodology and reporting on the following variables: primary cartilage repair procedure, and the utilization of concomitant procedures to address additional patient comorbidities, including malalignment, meniscus pathology, and ligamentous instability. Each study was additionally reviewed to document variation in clinical outcomes reporting in patients that had these comorbidities addressed at the time of surgery. All studies reported on the type of primary cartilage repair procedure, with autologous chondrocyte implantation (ACI) noted in 43% of studies, microfracture (MF) reported in 16.5%, osteochondral allograft (OCA) in 15%, and osteochondral autograft transplant (OAT) in 8.2%. Regarding concomitant pathology, anterior cruciate ligament (ACL) reconstruction (24.8%) and meniscus repair (23.3%) were the most commonly addressed patient comorbidities. A total of 56 studies (42.1%) excluded patients with malalignment, meniscus injury, and ligamentous instability. For studies that addressed concomitant pathology, 72.7% reported clinical outcomes separately from the cohort treated with only cartilage repair. A total of 16.5% of studies neither excluded nor addressed concomitant pathologies. There was a significant amount of variation in the patient reported outcome scores used among the studies, with the majority of studies reporting International Knee Documentation Committee (IKDC) and Knee Injury and Osteoarthritis Outcomes Score (KOOS) in 47.2% and 43.6% of articles, respectively. In this study on knee cartilage restoration, recognition and management of concomitant pathology is inadequately reported in approximately 28% of studies. Only 30% of articles reported adequate treatment of concomitant ailments while scoring their outcomes using one of a potential 18 different scoring systems. These findings highlight the need for more standardized methods to be applied in future research with regard to inclusion, exclusion, and scoring concomitant pathologies with regard to treatment of cartilage defects in the knee.

Enzymatically Cross-Linked Silk Fibroin-Based Hierarchical Scaffolds for Osteochondral Regeneration.

Osteochondral (OC) regeneration faces several limitations in orthopedic surgery, owing to the complexity of the OC tissue that simultaneously entails the restoration of articular cartilage and subchondral bone diseases. In this study, novel biofunctional hierarchical scaffolds composed of a horseradish peroxidase (HRP)-cross-linked silk fibroin (SF) cartilage-like layer (HRP-SF layer) fully integrated into a HRP-SF/ZnSr-doped β-tricalcium phosphate (β-TCP) subchondral bone-like layer (HRP-SF/dTCP layer) were proposed as a promising strategy for OC tissue regeneration. For comparative purposes, a similar bilayered structure produced with no ion incorporation (HRP-SF/TCP layer) was used. A homogeneous porosity distribution was achieved throughout the scaffolds, as shown by micro-computed tomography analysis. The ion-doped bilayered scaffolds presented a wet compressive modulus (226.56 ± 60.34 kPa) and dynamic mechanical properties (ranging from 403.56 ± 111.62 to 593.56 ± 206.90 kPa) superior to that of the control bilayered scaffolds (189.18 ± 90.80 kPa and ranging from 262.72 ± 59.92 to 347.68 ± 93.37 kPa, respectively). Apatite crystal formation, after immersion in simulated body fluid (SBF), was observed in the subchondral bone-like layers for the scaffolds incorporating TCP powders. Human osteoblasts (hOBs) and human articular chondrocytes (hACs) were co-cultured onto the bilayered structures and monocultured in the respective cartilage and subchondral bone half of the partitioned scaffolds. Both cell types showed good adhesion and proliferation in the scaffold compartments, as well as adequate integration of the interface regions. Osteoblasts produced a mineralized extracellular matrix (ECM) in the subchondral bone-like layers, and chondrocytes showed GAG deposition. The gene expression profile was different in the distinct zones of the bilayered constructs, and the intermediate regions showed pre-hypertrophic chondrocyte gene expression, especially on the BdTCP constructs. Immunofluorescence analysis supported these observations. This study showed that the proposed bilayered scaffolds allowed a specific stimulation of the chondrogenic and osteogenic cells in the co-culture system together with the formation of an osteochondral-like tissue interface. Hence, the structural adaptability, suitable mechanical properties, and biological performance of the hierarchical scaffolds make these constructs a desired strategy for OC defect regeneration.

Synthetic nanosrystalline materials оf thepoli-variant composition based on the system СаО–P2О5–CаF2–Н2О for correction of structural disturbances of sceleton

The prospects for the use of synthetic nanocrystalline materials of a multivariate composition based on the system СаО–P2О5–CаF2–Н2О and additives for correcting structural defects of the skeleton are considered. It is shown that for the synthesis of nanocrystalline powders and composites of biomedical use, materials whose compositions are described by the system СаО–P2О5–CаF2–Н2О are promising. The systems of CаО–P2О5–CаF2, СаО–P2О5–Н2О were studied. A study of the CaO-P2O5-CaF2 system in the Ca3 (PO4) 2 -CaF2 section was carried out: the position of the binary eutectics and the melting points in them was determined. The experimental verification of the calculated data on the preparations of the calculated compositions by the high-temperature microscopy method is performed. On the basis of the investigations carried out, the regions of primary crystallization of phases in the four-component systems Ca3 (PO4)2-CaCO3-CaF2-Ca (OH) 2 and Ca3(PO4)2-H2O-CaF2-Ca (OH) 2, promising for use as bioceramic compositions. Based on the studies carried out in the CaO-P2O5-CaF2-H2O system, areas promising for the synthesis of materials have been identified that can be used for their technical and biological properties: 1) to correct bone tissue defects; 2) as inorganic fillers of hybrid organo-inorganic composite materials intended for the restoration of articular cartilage; 3) for gluing bone fragments and filling cavities of pathological origin; 4) to replenish the mineral composition of bones and tooth enamel.