Shaped, stratified, scaffold-free grafts for articular cartilage defects.
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ABSTRACT:
SUBMITTER: Han EH
PROVIDER: S-EPMC2584257 | biostudies-other | 2008 Aug
REPOSITORIES: biostudies-other
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Project description:The full-thickness articular cartilage defect (FTAC) is an abnormally severe grade of articular cartilage (AC) injury. An osteochondral autograft transfer (OAT) is the recommended treatment, but the increasing morbidity rate from osteochondral plug harvesting is a limitation. Thus, the 3D-printed bilayer's bioactive-biomaterials scaffold is of major interest. Polylactic acid (PLA) and polycaprolactone (PCL) were blended with hydroxyapatite (HA) for the 3D-printed bone layer of the bilayer's bioactive-biomaterials scaffold (B-BBBS). Meanwhile, the blended PLA/PCL filament was 3D printed and combined with a chitosan (CS)/silk firoin (SF) using a lyophilization technique to fabricate the AC layer of the bilayer's bioactive-biomaterials scaffold (AC-BBBS). Material characterization and mechanical and biological tests were performed. The fabrication process consists of combining the 3D-printed structure (AC-BBBS and B-BBBS) and a lyophilized porous AC-BBBS. The morphology and printing abilities were investigated, and biological tests were performed. Finite element analysis (FEA) was performed to predict the maximum load that the bilayer's bioactive-biomaterials scaffold (BBBS) could carry. The presence of HA and CS/SF in the PLA/PCL structure increased cell proliferation. The FEA predicted the load carrying capacity to be up to 663.2 N. All tests indicated that it is possible for BBBS to be used in tissue engineering for AC and bone regeneration in FTAC treatment.
| S-EPMC7436011 | biostudies-literature
Project description:Functional repair of articular cartilage defects is always a great challenge in joint surgery clinically. Tissue engineering strategies that combine autologous cell implantation with three-dimensional scaffolds have proven effective for repairing articular cartilage tissue. However, it faces the problem of cell sources and scaffold materials. Autologous chondrocytes and bone marrow are difficult to popularize clinically due to limited donor sources and low mononuclear cell (MNC) concentrations, respectively. The density gradient centrifugation method can increase the concentration of MNCs in fresh bone marrow by nearly a hundredfold and achieve immediate enrichment. In addition, acellular cartilage matrix (ACM), with good biocompatibility and a cartilage-specific microenvironment, is considered to be an ideal candidate scaffold for cartilage regeneration. In this study, hybrid pigs were used to establish articular cartilage defect models of different sizes to determine the feasibility and maximum scope of application of ACM-based biomimetic scaffolds combined with MNCs for inducing articular cartilage regeneration. Importantly, ACM-based biomimetic scaffolds instantly enriched MNCs could improve the repair effect of articular cartilage defects in situ, which established a new model of articular cartilage regeneration that could be applied immediately and suited for large-scale clinical promotion. The current study significantly improves the repair effect of articular cartilage defects, which provides scientific evidence and detailed insights for future clinical applications of ACM-based biomimetic scaffolds combined with MNCs.
| S-EPMC9168693 | biostudies-literature
Project description:Hyaluronic acid (HA) is an extracellular matrix molecule with multiple physical and biological functions found in many tissues, including cartilage. HA has been incorporated in a number of biomaterial and scaffold systems. However, HA in the material may be difficult to control if it is not chemically modified and chemical modification of HA may negatively impact biological function. In this study, we developed a poly(ethylene glycol) hydrogel with noncovalent HA-binding capabilities and evaluated its ability to support cartilage formation in vitro and in an articular defect model. Chondrogenic differentiation of mesenchymal stem cells encapsulated in the HA-interactive scaffolds containing various amounts of exogenous HA was evaluated. The HA-binding hydrogel without exogenous HA produced the best cartilage as determined by biochemical content (glysocaminoglycan and collagen), histology (Safranin O and type II collagen staining), and gene expression analysis for aggrecan, type I collagen, type II collagen, and sox-9. This HA-binding formulation was then translated to an osteochondral defect model in the rat knee. After 6 weeks, histological analysis demonstrated improved cartilage tissue production in defects treated with the HA-interactive hydrogel compared to noninteractive control scaffolds and untreated defects. In addition to the tissue repair in the defect space, the Safranin O staining in cartilage tissue surrounding the defect was greater in treatment groups where the HA-binding scaffold was applied. In sum, incorporation of a noncovalent HA-binding functionality into biomaterials provides an ability to interact with local or exogenous HA, which can then impact tissue remodeling and ultimately new tissue production.
| S-EPMC3501122 | biostudies-literature
Project description:Focal damage to articular cartilage is common in arthroscopy patients, and may contribute to progressive tissue degeneration by altering the local mechanical environment. The effects of a focal defect, which may be oriented at various orientations relative to the subchondral bone, on the dynamics of cartilage contact and deformation are unclear. The objective of this study was to elucidate the effect of experimental full thickness focal defects, oriented at 80 degrees or 100 degrees relative to the subchondral bone, on intratissue strain and surface sliding of opposing cartilage surfaces during compression and stress relaxation. Pairs of intact bovine osteochondral blocks were compressed uniaxially by 20%, and allowed to stress relax. Tissue deformation was recorded by video microscopy. A full-thickness defect (with either 80 degrees or 100 degrees edges) was created in one block from each pair. Blocks were allowed to reswell and retested. Defect edges were then recut with the opposite orientation, allowed to reswell, and retested again. Stained nuclei were tracked by digital image correlation and used to quantify cartilage strains and surface sliding. The results indicated that loading of intact samples caused axial strain magnitudes that decreased with depth and relatively little sliding. With loading of samples containing defects, strain magnitudes were elevated in cartilage adjacent to, and opposing, defects. For samples with edge orientations of 100 degrees, sliding magnitudes were increased over surfaces adjacent to defects. These local mechanical changes due to full-thickness articular cartilage defects may contribute to altered chondrocyte metabolism, tissue damage, or accelerated wear.
| S-EPMC2862585 | biostudies-literature
Project description:Glenoid articular cartilage lesions are a source of shoulder pain and can occur in the setting of glenohumeral instability and degenerative shoulder disease. Glenolabral articular disruption lesions have been reported to be associated with worse outcomes after arthroscopic repair of labral tears. There are relatively few published studies evaluating outcomes after surgical treatment of glenoid articular lesions; however, it is generally accepted that management should consist of restoring the glenoid articular surface, minimizing exposed articular defect, and re-establishing capsulolabral integrity to achieve stability. We present arthroscopic strategies to manage these glenoid articular defects through debridement, abrasion, microfracture, capsulolabral advancement and labral interposition.
| S-EPMC9244852 | biostudies-literature
Project description:BackgroundScaffold-assisted autologous chondrocyte implantation is an effective clinical procedure for cartilage repair. From the regulatory point of view, the ovine model is one of the suggested large animal models for pre-clinical studies. The aim of our study was to evaluate the in vitro re-differentiation capacity of expanded ovine chondrocytes in biomechanically characterized polyglycolic acid (PGA)/fibrin biomaterials for scaffold-assisted cartilage repair.MethodsOvine chondrocytes harvested from adult articular cartilage were expanded in monolayer and re-assembled three-dimensionally in PGA-fibrin scaffolds. De- and re-differentiation of ovine chondrocytes in PGA-fibrin scaffolds was assessed by histological and immuno-histochemical staining as well as by real-time gene expression analysis of typical cartilage marker molecules and the matrix-remodelling enzymes matrix metalloproteinases (MMP) -1, -2 and -13 as well as their inhibitors. PGA scaffolds characteristics including degradation and stiffness were analysed by electron microscopy and biomechanical testing.ResultsHistological, immuno-histochemical and gene expression analysis showed that dedifferentiated chondrocytes re-differentiate in PGA-fibrin scaffolds and form a cartilaginous matrix. Re-differentiation was accompanied by the induction of type II collagen and aggrecan, while MMP expression decreased in prolonged tissue culture. Electron microscopy and biomechanical tests revealed that the non-woven PGA scaffold shows a textile structure with high tensile strength of 3.6 N/mm2 and a stiffness of up to 0.44 N/mm2, when combined with gel-like fibrin.ConclusionThese data suggest that PGA-fibrin is suited as a mechanically stable support structure for scaffold-assisted chondrocyte grafts, initiating chondrogenic re-differentiation of expanded chondrocytes.
| S-EPMC3509043 | biostudies-literature
Project description:ObjectiveDespite new strategies in tissue engineering, cartilage repair remains a major challenge. Our aim is to treat patients with focal lesions of articular cartilage with autologous hyaline cartilage implants using a scaffold-free approach. In this article, we describe experiments to optimize production of scaffold-free cartilage discs.DesignArticular chondrocytes were expanded in vitro, seeded in transwell inserts and redifferentiated using established chondrogenic components. Experimental variables included testing 2 different expansion media, adding bone morphogenetic protein 2 (BMP2), insulin-like growth factor 1 (IGF1), growth/differentiation factor 5 (GDF5), or fibroblast growth factor 18 (FGF18) to the differentiation medium and allowing the disc to float freely in large wells. Cartilage discs were analyzed by weight and thickness, real-time RT-qPCR (reverse transcriptase qualitative polymerase chain reaction), fluorescence immunostaining, transmission electron microscopy, second harmonic generation imaging, and measurement of Young's modulus.ResultsAddition of BMP2 to the chondrogenic differentiation medium (CDM) was essential for stable disc formation, while IGF1, GDF5, and FGF18 were redundant. Allowing discs to float freely in CDM on a moving platform increased disc thickness compared with discs kept continuously in transwell inserts. Discs cultured for 6 weeks reached a thickness of almost 2 mm and Young's modulus of >200 kPa. There was abundant type II collagen. Collagen fibrils were 25 nm thick, with a tendency to be organized perpendicular to the disc surface.ConclusionScaffold-free engineering using BMP2 and providing free movement in CDM produced firm, elastic cartilage discs with abundant type II collagen. This approach may potentially be used in clinical trials.
| S-EPMC8725371 | biostudies-literature
Project description:Introduction:Cutting the cost of manufacturing is important for extending the use of tissue-engineered therapeutic products. The present study aimed to develop a simple method for fabrication of cartilaginous tissues for regenerative therapy, utilizing the phenomenon where human articular chondrocytes grow thickness-wise and spontaneously form three-dimensionally thick tissues. Methods:Normal human articular chondrocytes (NHACs) were cultured with varying concentrations of transforming growth factor beta 1 (TGF-?1) and/or fibroblast growth factor-2 (FGF-2) to optimize the culture condition for thickness-wise growth of chondrocytes. Next, the tissues grown in the optimal condition were subjected to re-differentiation culture in attached and detached states to assess differentiation capacity by evaluating secreted factors, histological analysis, and a gene expression assay. Results:NHACs grew thickness-wise efficiently in the presence of 1 ng/mL TGF-?1 and 10 ng/mL FGF-2. After two weeks of culture, NHACs grew with 11-fold higher thickness and 16-fold higher cell number compared to cells which were neither treated with TGF-?1 nor with FGF-2. These thickness-wise-grown chondrocytes could be re-differentiated by a differentiation medium according to the increase in melanoma inhibitory activity (MIA) and positive safranin-O staining. Interestingly, the cartilaginous gene expression was considerably different between the attached and detached conditions even in the same culture medium, indicating the necessity of detachment and shrinkage to achieve further differentiation. Conclusions:Spontaneous thickness-wise growth might provide a simple tissue-engineering method for manufacturing cartilaginous 3D tissues.
| S-EPMC7005340 | biostudies-literature
Project description:Animal models play an important role in preclinical studies, especially in tissue engineering scaffolds for cartilage repair, which require large animal models to verify the safety and effectiveness for clinical use. The small ruminant models are most widely used in this field than other large animals because they are cost-effective, easy to raise, not to mention the fact that the aforementioned animal presents similar anatomical features to that of humans. This review discusses the experimental study of tissue engineering scaffolds for knee articular cartilage regeneration in small ruminant models. Firstly, the selection of these scaffold materials and the preparation process in vitro that have been already used in vivo are briefly reviewed. Moreover, the major factors influencing the rational design and the implementation as well as advantages and limitations of small ruminants are also demonstrated. As regards methodology, this paper applies principles and methods followed by most researchers in the process of experimental design and operation of this kind. By summarizing and comparing different therapeutic concepts, this paper offers suggestions aiming to increase the effectiveness of preclinical research using small ruminant models and improve the process of developing corresponding therapies.
| S-EPMC8668357 | biostudies-literature
Project description:Mesenchymal stem cells (MSCs) and hyaluronic acid (HA) have been found in previous studies to have great potential for medical use. This study aimed to investigate the therapeutic effects of bone marrow mesenchymal stem cells (BMSCs) combined with HA on articular cartilage repair in canines. Twenty-four healthy canines (48 knee-joints), male or female with weight ranging from 5 to 6 kg, were operated on to induce cartilage defect model and divided into 3 groups randomly which received different treatments: BMSCs plus HA (BMSCs-HA), HA alone, and saline. Twenty-eight weeks after treatment, all canines were sacrificed and analyzed by gross appearance, magnetic resonance imaging (MRI), hematoxylin-eosin (HE) staining, Masson staining, toluidine blue staining, type II collagen immunohistochemistry, gross grading scale and histological scores. MSCs plus HA regenerated more cartilage-like tissue than did HA alone or saline. According to the macroscopic evaluation and histological assessment score, treatment with MSCs plus HA also lead to significant improvement in cartilage defects compared to those in the other 2 treatment groups (P < 0.05). These findings suggested that allogeneic BMSCs plus HA rather than HA alone was effective in promoting the formation of cartilage-like tissue for repairing cartilage defect in canines.
| S-EPMC6028658 | biostudies-literature