scholarly journals Clinically Relevant Cell Sources for TMJ Disc Engineering

2008 ◽  
Vol 87 (6) ◽  
pp. 548-552 ◽  
Author(s):  
D.E. Johns ◽  
M.E. Wong ◽  
K.A. Athanasiou

Tissue-engineering of the temporomandibular joint (TMJ) disc aims to provide patients with TMJ disorders an option to replace diseased tissue with autologous, functional tissue. This study examined clinically relevant cell sources by comparing costal chondrocytes, dermal fibroblasts, a mixture of the two, and TMJ disc cells in a scaffoldless tissue-engineering approach. It was hypothesized that all constructs would produce matrix relevant to the TMJ disc, but the mixture constructs were expected to appear most like the TMJ disc constructs. Costal chondrocyte and mixture constructs were morphologically and biochemically superior to the TMJ disc and dermal fibroblast constructs, and their compressive properties were not significantly different. Costal chondrocyte constructs produced almost 40 times more collagen and 800 times more glycosaminoglycans than did TMJ constructs. This study demonstrates the ability of costal chondrocytes to produce extracellular matrix that may function in a TMJ disc replacement.

2020 ◽  
Vol 15 (2) ◽  
pp. 144-154
Author(s):  
Zohreh Bagher ◽  
Negin Asgari ◽  
Parisa Bozorgmehr ◽  
Seyed Kamran Kamrava ◽  
Rafieh Alizadeh ◽  
...  

The nasal septal cartilage plays an important role in the growth of midface and as a vertical strut preventing the collapse of the nasal bones. The repair of nasal cartilage defects remains a major challenge in reconstructive surgery. The tissue engineering strategy in the development of tissue has opened a new perspective to generate functional tissue for transplantation. Given the poor regenerative properties of cartilage and a limited amount of autologous cartilage availability, intense interest has evoked for tissue engineering approaches for cartilage development to provide better outcomes for patients who require nasal septal reconstruction. Despite numerous attempts to substitute the shapely hyaline cartilage in the nasal cartilages, many significant challenges remained unanswered. The aim of this research was to carry out a critical review of the literature on research work carried out on the development of septal cartilage using a tissue engineering approach, concerning different cell sources, scaffolds and growth factors, as well as its clinical pathway and trials have already been carried out.


2019 ◽  
Vol 141 (7) ◽  
Author(s):  
Ryan P. Donahue ◽  
Erik A. Gonzalez-Leon ◽  
Jerry C. Hu ◽  
Kyriacos A. Athanasiou

Fibrocartilage is found in the knee meniscus, the temporomandibular joint (TMJ) disc, the pubic symphysis, the annulus fibrosus of intervertebral disc, tendons, and ligaments. These tissues are notoriously difficult to repair due to their avascularity, and limited clinical repair and replacement options exist. Tissue engineering has been proposed as a route to repair and replace fibrocartilages. Using the knee meniscus and TMJ disc as examples, this review describes how fibrocartilages can be engineered toward translation to clinical use. Presented are fibrocartilage anatomy, function, epidemiology, pathology, and current clinical treatments because they inform design criteria for tissue engineered fibrocartilages. Methods for how native tissues are characterized histomorphologically, biochemically, and mechanically to set gold standards are described. Then provided is a review of fibrocartilage-specific tissue engineering strategies, including the selection of cell sources, scaffold or scaffold-free methods, and biochemical and mechanical stimuli. In closing, the Food and Drug Administration (FDA) paradigm is discussed to inform researchers of both the guidance that exists and the questions that remain to be answered with regard to bringing a tissue engineered fibrocartilage product to the clinic.


2021 ◽  
Vol 12 ◽  
Author(s):  
Fausta Natella ◽  
Barbara Guantario ◽  
Roberto Ambra ◽  
Giulia Ranaldi ◽  
Federica Intorre ◽  
...  

Hamamelis virginiana L. a rich source of both condensed and hydrolyzable tannins, utilized to treat dermatological disorders. Since no experimental and clinical data is available for its use as oral formulation in skin related disorders, the purpose of this study was to investigate the effects of Hamaforton™ (Hamamelis virginiana extract) metabolites on gene dysregulation induced by ultraviolet A radiation in cultured human dermal fibroblasts. A combination of in vivo and ex vivo experimental designs has been exploited in order to take into account the polyphenol metabolic transformation that occurs in humans. 12 healthy volunteers received either a capsule of Hamaforton™ or a placebo in a randomized, blinded crossover trial. After Hamaforton™ ingestion, the kinetic of appearance of galloyl derivatives was measured in plasma. Then, in the ex vivo experiment, the serum isolated after supplementation was used as a source of Hamaforton™ metabolites to enrich the culture medium of dermal fibroblasts exposed to ultraviolet A radiation. Three different gallic acid metabolites (4-O-methyl gallic acid, 4-O-methyl gallic acid sulphate and trimethyl gallic acid glucuronide) were identified in volunteer plasma. While, ultraviolet A irradiation of dermal fibroblasts affected the expression of extracellular matrix genes, the presence of Hamaforton™ metabolites in the culture media did not affect the expression of most of those genes. However, the activation of the expression of 10 different genes involved in repair processes for the maintenance of skin integrity, suggest that the metabolites can play a role in damage recovery. To our knowledge, this is the first study that demonstrates the bioavailability of Hamaforton™ phenolic compounds, and the effects of its metabolites on cultured dermal fibroblast response to ultraviolet A irradiation.


Gels ◽  
2021 ◽  
Vol 7 (1) ◽  
pp. 13
Author(s):  
Kyung Min Yoo ◽  
Sean V. Murphy ◽  
Aleksander Skardal

Hydrogels have played a significant role in many applications of regenerative medicine and tissue engineering due to their versatile properties in realizing design and functional requirements. However, as bioengineered solutions are translated towards clinical application, new hurdles and subsequent material requirements can arise. For example, in applications such as cell encapsulation, drug delivery, and biofabrication, in a clinical setting, hydrogels benefit from being comprised of natural extracellular matrix-based materials, but with defined, controllable, and modular properties. Advantages for these clinical applications include ultraviolet light-free and rapid polymerization crosslinking kinetics, and a cell-friendly crosslinking environment that supports cell encapsulation or in situ crosslinking in the presence of cells and tissue. Here we describe the synthesis and characterization of maleimide-modified hyaluronic acid (HA) and gelatin, which are crosslinked using a bifunctional thiolated polyethylene glycol (PEG) crosslinker. Synthesized products were evaluated by proton nuclear magnetic resonance (NMR), ultraviolet visibility spectrometry, size exclusion chromatography, and pH sensitivity, which confirmed successful HA and gelatin modification, molecular weights, and readiness for crosslinking. Gelation testing both by visual and NMR confirmed successful and rapid crosslinking, after which the hydrogels were characterized by rheology, swelling assays, protein release, and barrier function against dextran diffusion. Lastly, biocompatibility was assessed in the presence of human dermal fibroblasts and keratinocytes, showing continued proliferation with or without the hydrogel. These initial studies present a defined, and well-characterized extracellular matrix (ECM)-based hydrogel platform with versatile properties suitable for a variety of applications in regenerative medicine and tissue engineering.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Pernille Juhl ◽  
Sandie Bondesen ◽  
Clare Louise Hawkins ◽  
Morten Asser Karsdal ◽  
Anne-Christine Bay-Jensen ◽  
...  

Abstract Different stimulants might induce different extracellular matrix profiles. It is essential to gain an understanding and quantification of these changes to allow for focused anti-fibrotic drug development. This study investigated the expression of extracellular matrix by dermal fibroblast mimicking fibrotic skin diseases as SSc using clinically validated biomarkers. Primary healthy human dermal fibroblasts were grown in media containing FICOLL. The cells were stimulated with PDGF-AB, TGF-β1, or IL-6. Anti-fibrotic compounds (iALK-5, Nintedanib) were added together with growth factors. Biomarkers of collagen formation and degradation together with fibronectin were evaluated by ELISAs in the collected supernatant. Immunohistochemical staining was performed to visualize fibroblasts and proteins, while selected gene expression levels were examined through qPCR. TGF-β and PDGF, and to a lesser extent IL-6, increased the metabolic activity of the fibroblasts. TGF-β primarily increased type I collagen and fibronectin protein and gene expression together with αSMA. PDGF stimulation resulted in increased type III and VI collagen formation and gene expression. IL-6 decreased fibronectin levels. iALK5 could inhibit TGF-β induced fibrosis while nintedanib could halt fibrosis induced by TGF-β or PDGF. Tocilizumab could not inhibit fibrosis induced in this model. The extent and nature of fibrosis are dependent on the stimulant. The model has potential as a pre-clinical model as the fibroblasts fibrotic phenotype could be reversed by an ALK5 inhibitor and Nintedanib.


2012 ◽  
Vol 134 (1) ◽  
Author(s):  
Vincent P. Willard ◽  
Kerem N. Kalpakci ◽  
Andrew J. Reimer ◽  
Kyriacos A. Athanasiou

Understanding structure-function relationships in the temporomandibular joint (TMJ) disc is a critical first step toward creating functional tissue replacements for the large population of patients suffering from TMJ disc disorders. While many of these relationships have been identified for the collagenous fraction of the disc, this same understanding is lacking for the next most abundant extracellular matrix component, sulfated glycosaminoglycans (GAGs). Though GAGs are known to play a major role in maintaining compressive integrity in GAG-rich tissues such as articular cartilage, their role in fibrocartilaginous tissues in which GAGs are much less abundant is not clearly defined. Therefore, this study investigates the contribution of GAGs to the regional viscoelastic compressive properties of the temporomandibular joint (TMJ) disc. Chondroitinase ABC (C-ABC) was used to deplete GAGs in five different disc regions, and the time course for >95% GAG removal was defined. The compressive properties of GAG depleted regional specimens were then compared to non-treated controls using an unconfined compression stress-relaxation test. Additionally, treated and non-treated specimens were assayed biochemically and histologically to confirm GAG removal. Compared to untreated controls, the only regions affected by GAG removal in terms of biomechanical properties were in the intermediate zone, the most GAG-rich portion of the disc. Without GAGs, all intermediate zone regions showed decreased tissue viscosity, and the intermediate zone lateral region also showed a 12.5% decrease in modulus of relaxation. However, in the anterior and posterior band regions, no change in compressive properties was observed following GAG depletion, though these regions showed the highest compressive properties overall. Although GAGs are not the major extracellular matrix molecule of the TMJ disc, they are responsible for some of the viscoelastic compressive properties of the tissue. Furthermore, the mechanical role of sulfated GAGs in the disc varies regionally in the tissue, and GAG abundance does not always correlate with higher compressive properties. Overall, this study found that sulfated GAGs are important to TMJ disc mechanics in the intermediate zone, an important finding for establishing design characteristics for future tissue engineering efforts.


2017 ◽  
Vol 15 (4) ◽  
pp. e326-e333 ◽  
Author(s):  
Marina Figliuzzi ◽  
Barbara Bonandrini ◽  
Andrea Remuzzi

Renal transplantation is currently the most effective treatment for end-stage renal disease, which represents one of the major current public health problems. However, the number of available donor kidneys is drastically insufficient to meet the demand, causing prolonged waiting lists. For this reason, tissue engineering offers great potential to increase the pool of donated organs for kidney transplantation, by way of seeding cells on supporting scaffolding material. Biological scaffolds are prepared by removing cellular components from the donor organs using a decellularization process with detergents, enzymes or other cell lysing solutions. Extracellular matrix which makes up the scaffold is critical to directing the cell attachment and to creating a suitable environment for cell survival, proliferation and differentiation. Researchers are now studying whole intact scaffolds produced from the kidneys of animals or humans without adversely affecting extracellular matrix, biological activity and mechanical integrity. The process of recellularization includes cell seeding strategies and the choice of the cell source to repopulate the scaffold. This is the most difficult phase, due to the complexity of the kidney. Indeed, no studies have provided sufficient results of complete renal scaffold repopulation and differentiation. This review summarizes the research that has been conducted to obtain decellularized kidney scaffolds and to repopulate the scaffolds, evaluating the best cell sources, the cell seeding methods and the cell differentiation in kidney scaffolds.


2021 ◽  
Vol 25 (1(97)) ◽  
pp. 19-23
Author(s):  
A. Hapchenko

Biodegradable materials are promising for the development of tissue engineering constructions. At the same time, they must have a satisfactory weight loss profile, no toxicity and the ability to support cell proliferation. Polylactides and their derivatives are intensively used to reconstruct tissues and organs and in drug delivery systems, but the technology of manufacturing materials is not standardized. Electrospinning is an affordable technology that can be used to create three-dimensional nanofiber structures for tissue engineering and regenerative medicine, but their use is currently limited due to insufficient study. The aim. Creation of three-dimensional structures from polylactic acid, evaluation of their biodegradation profile, and cellular toxicity in the model of dermal fibroblasts. Material and methods. Nanofiber membranes were obtained by standard electrospinning and using NanoMatrix3D technology. The degradation study was performed in SBF solution in static and dynamic modes to determine the percentage of weight loss. Cytotoxicity studies were performed on primary dermal fibroblast culture with assessment of resazurin reduction and DAPI imaging. Conclusions. The use of electrospinning technology allows us to create nanofiber membranes that are capable of biodegradation and have a satisfactory toxicity profile. The dynamic system of degradation leads to an increase in a mass loss by membranes due to the removal of degradation products. The data indicate the possibility of using PLA-based materials for the development of structures for tissue engineering.


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