scholarly journals Current Advances in the Regeneration of Degenerated Articular Cartilage: A Literature Review on Tissue Engineering and Its Recent Clinical Translation

Materials ◽  
2021 ◽  
Vol 15 (1) ◽  
pp. 31
Author(s):  
Farah Daou ◽  
Andrea Cochis ◽  
Massimiliano Leigheb ◽  
Lia Rimondini
Keyword(s):  
Tissue Engineering ◽  
Articular Cartilage ◽  
Literature Review ◽  
Healthy Aging ◽  
Ex Vivo ◽  
Cartilage Degeneration ◽  
Clinical Translation ◽  
Predisposing Factor

Functional ability is the basis of healthy aging. Articular cartilage degeneration is amongst the most prevalent degenerative conditions that cause adverse impacts on the quality of life; moreover, it represents a key predisposing factor to osteoarthritis (OA). Both the poor capacity of articular cartilage for self-repair and the unsatisfactory outcomes of available clinical interventions make innovative tissue engineering a promising therapeutic strategy for articular cartilage repair. Significant progress was made in this field; however, a marked heterogeneity in the applied biomaterials, biofabrication, and assessments is nowadays evident by the huge number of research studies published to date. Accordingly, this literature review assimilates the most recent advances in cell-based and cell-free tissue engineering of articular cartilage and also focuses on the assessments performed via various in vitro studies, ex vivo models, preclinical in vivo animal models, and clinical studies in order to provide a broad overview of the latest findings and clinical translation in the context of degenerated articular cartilage and OA.

scholarly journals Non-viral Gene Delivery Methods for Bone and Joints

2020 ◽  
Vol 8 ◽  
Author(s):  
Benjamin Gantenbein ◽  
Shirley Tang ◽  
Julien Guerrero ◽  
Natalia Higuita-Castro ◽  
Ana I. Salazar-Puerta ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Gene Delivery ◽  
Targeted Delivery ◽  
Ex Vivo ◽  
Clinical Translation ◽  
Viral Gene ◽  
Delivery Methods ◽  
Viral Gene Delivery

Viral carrier transport efficiency of gene delivery is high, depending on the type of vector. However, viral delivery poses significant safety concerns such as inefficient/unpredictable reprogramming outcomes, genomic integration, as well as unwarranted immune responses and toxicity. Thus, non-viral gene delivery methods are more feasible for translation as these allow safer delivery of genes and can modulate gene expression transiently both in vivo, ex vivo, and in vitro. Based on current studies, the efficiency of these technologies appears to be more limited, but they are appealing for clinical translation. This review presents a summary of recent advancements in orthopedics, where primarily bone and joints from the musculoskeletal apparatus were targeted. In connective tissues, which are known to have a poor healing capacity, and have a relatively low cell-density, i.e., articular cartilage, bone, and the intervertebral disk (IVD) several approaches have recently been undertaken. We provide a brief overview of the existing technologies, using nano-spheres/engineered vesicles, lipofection, and in vivo electroporation. Here, delivery for microRNA (miRNA), and silencing RNA (siRNA) and DNA plasmids will be discussed. Recent studies will be summarized that aimed to improve regeneration of these tissues, involving the delivery of bone morphogenic proteins (BMPs), such as BMP2 for improvement of bone healing. For articular cartilage/osteochondral junction, non-viral methods concentrate on targeted delivery to chondrocytes or MSCs for tissue engineering-based approaches. For the IVD, growth factors such as GDF5 or GDF6 or developmental transcription factors such as Brachyury or FOXF1 seem to be of high clinical interest. However, the most efficient method of gene transfer is still elusive, as several preclinical studies have reported many different non-viral methods and clinical translation of these techniques still needs to be validated. Here we discuss the non-viral methods applied for bone and joint and propose methods that can be promising in clinical use.

Collagen fibrous scaffolds for sustained delivery of growth factors for meniscal tissue engineering

Nanomedicine ◽  
2022 ◽  
Author(s):  
Jihye Baek ◽  
Kwang Il Lee ◽  
Ho Jong Ra ◽  
Martin K Lotz ◽  
Darryl D D'Lima
Keyword(s):  
Tissue Engineering ◽  
Growth Factors ◽  
Sustained Release ◽  
Ex Vivo ◽  
Synovial Cell ◽  
Growth Factor Delivery ◽  
Meniscal Tissue ◽  
A Cell

Aim: To mimic the ultrastructural morphology of the meniscus with nanofiber scaffolds coupled with controlled growth factor delivery to modulate cellular performance for tissue engineering of menisci. Methods: The authors functionalized collagen nanofibers by conjugating heparin to the following growth factors for sustained release: PDGF-BB, TGF-β1 and CTGF. Results: Incorporating growth factors increased human meniscal and synovial cell viability, proliferation and infiltration in vitro, ex vivo and in vivo; upregulated key genes involved in meniscal extracellular matrix synthesis; and enhanced generation of meniscus-like tissue. Conclusion: The authors' results indicate that functionalizing collagen nanofibers can create a cell-favorable micro- and nanoenvironment and can serve as a system for sustained release of bioactive factors.

Optimization of Oxygen Delivery within Hydrogels

2021 ◽  
Author(s):  
Sophia M Mavris ◽  
Laura M Hansen
Keyword(s):  
Tissue Engineering ◽  
Oxygen Transport ◽  
Current Medical ◽  
The Body ◽  
Clinical Translation ◽  
Technological Innovations ◽  
Technological Advances ◽  
Cell Sources

Abstract The field of tissue engineering has been continuously evolving since its inception over three decades ago with numerous new advancements in biomaterials and cell sources and widening applications to most tissues in the body. Despite the substantial promise and great opportunities for the advancement of current medical therapies and procedures, the field has yet to capture wide clinical translation due to some remaining challenges, including oxygen availability within constructs, both in vitro and in vivo. While this insufficiency of nutrients, specifically oxygen, is a limitation within the current frameworks of this field, the literature shows promise in new technological advances to efficiently provide adequate delivery of nutrients to cells. This review attempts to capture the most recent advances in the field of oxygen transport in hydrogel-based tissue engineering, including a comparison of current research as it pertains to the modeling, sensing, and optimization of oxygen within hydrogel constructs as well as new technological innovations to overcome traditional diffusion-based limitations. The application of these findings can further the advancement and development of better hydrogel-based tissue engineered constructs for future clinical translation and adoption.

Removal of obturation material in endodontic retreatment: a literature review

RSBO ◽  
2019 ◽  
Vol 16 (2) ◽  
pp. 109
Author(s):  
Carina Do Nascimento Menezes ◽  
Verydianna Frota Carneiro ◽  
Mônica Sampaio do Vale
Keyword(s):  
Literature Review ◽  
Latin American ◽  
Root Canal ◽  
Ex Vivo ◽  
Filling Material ◽  
Advantages And Disadvantages ◽  
In Vivo Experiments ◽  
Automated Method

Introduction: Removal of filling material from the root canal system is required when a previous endodontic treatment fails, what may result in the permanence of an unfavorable periapical condition. The intent is to completely remove the filling material inside of the root canal to achieve sufficient cleaning and shaping for successful retreatment. Objective: The aims of this article were to provide asystematic review of the different techniques of endodontic filling material associated or not with organic solvents and to analyze them critically in terms of advantages and disadvantages of each technique. Literature review: The descriptors used were “guttapercha”, “obturation,” and “retreatment” in the following databases: PubMed, MEDLINE, Latin American and Caribbean Center on Health Sciences Information (Bireme), Latin-American and CaribbeanHealth Sciences (Lilacs), Brazilian Dentistry Bibliography (BBO), and Scientific Electronic Library Online (SciELO). Publications of in vitro/ ex vivo and in vivo experiments without language restriction between the years 2010 and 2018 were selected. Conclusion: None of the techniques were capable of performing complete root canal cleaning, and the manual method was so effective as the automated method, although it requires longer working time. Furthermore, although this review confirmed that the solvent action did not allow a significantimprovement in the removal of the filling material, ultrasoundactivated irrigation proved to be an efficient adjunctive device as it could significantly reduce the volume of intracanal residuals.

scholarly journals Prospects and Challenges of Translational Corneal Bioprinting

2020 ◽  
Vol 7 (3) ◽  
pp. 71 ◽  
Author(s):  
Matthias Fuest ◽  
Gary Hin-Fai Yam ◽  
Jodhbir S. Mehta ◽  
Daniela F. Duarte Campos
Keyword(s):  
Tissue Engineering ◽  
Ex Vivo ◽  
Corneal Transplantation ◽  
Human Cornea ◽  
Corneal Tissue ◽  
Full Thickness ◽  
Future Directions ◽  
Spatial Control

Corneal transplantation remains the ultimate treatment option for advanced stromal and endothelial disorders. Corneal tissue engineering has gained increasing interest in recent years, as it can bypass many complications of conventional corneal transplantation. The human cornea is an ideal organ for tissue engineering, as it is avascular and immune-privileged. Mimicking the complex mechanical properties, the surface curvature, and stromal cytoarchitecure of the in vivo corneal tissue remains a great challenge for tissue engineering approaches. For this reason, automated biofabrication strategies, such as bioprinting, may offer additional spatial control during the manufacturing process to generate full-thickness cell-laden 3D corneal constructs. In this review, we discuss recent advances in bioprinting and biomaterials used for in vitro and ex vivo corneal tissue engineering, corneal cell-biomaterial interactions after bioprinting, and future directions of corneal bioprinting aiming at engineering a full-thickness human cornea in the lab.

Biomechanical issues of tissue-engineered constructs for articular cartilage regeneration: in vitro and in vivo approaches

2019 ◽  
Vol 132 (1) ◽  
pp. 53-80 ◽  
Author(s):  
Lucio Cipollaro ◽  
Maria Camilla Ciardulli ◽  
Giovanna Della Porta ◽  
Giuseppe M Peretti ◽  
Nicola Maffulli
Keyword(s):  
Tissue Engineering ◽  
Articular Cartilage ◽  
Cartilage Regeneration ◽  
Biological Properties ◽  
Trophic Factors ◽  
Gene Therapies ◽  
Zonal Organization ◽  
Meta Analyses

Abstract Background Given the limited regenerative capacity of injured articular cartilage, the absence of suitable therapeutic options has encouraged tissue-engineering approaches for its regeneration or replacement. Sources of data Published articles in any language identified in PubMed and Scopus electronic databases up to August 2019 about the in vitro and in vivo properties of cartilage engineered constructs. A total of 64 articles were included following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Areas of agreement Regenerated cartilage lacks the biomechanical and biological properties of native articular cartilage. Areas of controversy There are many different approaches about the development of the architecture and the composition of the scaffolds. Growing points Novel tissue engineering strategies focus on the development of cartilaginous biomimetic materials able to repair cartilage lesions in association to cell, trophic factors and gene therapies. Areas timely for developing research A multi-layer design and a zonal organization of the constructs may lead to achieve cartilage regeneration.

scholarly journals Regenerative Medicine: where their origin makes species meet

2019 ◽  
Vol 37 (3) ◽  
pp. 6-7
Author(s):  
Jos Malda
Keyword(s):  
Articular Cartilage ◽  
Ex Vivo ◽  
Mammalian Species ◽  
Cartilage Tissue ◽  
In Vitro Assays ◽  
Cartilage Defects ◽  
In Vivo Models ◽  
Societal Pressure

The articular cartilage of joints serves diverse functions, including absorbing shock, transmitting force, and enabling low-friction joint motion. Regeneration of articular cartilage defects remains, however, a significant challenge in both human and veterinary orthopaedic practice. Ex vivo and in vivo models play a crucial role in translating novel potential regenerative treatments from bench to bedside. However, in view of the predictive power of these models and the One Medicine concept that proclaim that there should be no dividing lines between human and animal medicine to learn, it is important to understand the similarities as well as differences in the cartilage tissue between species. To this aim, osteochondral cores of the femoral condyles were studied in 58 different mammalian species ranging from mouse to elephant. Interestingly, while biochemical composition remained relatively constant, cartilage thickness and cellularity were similar underscoring the importance of the equine species as a model for human orthopaedic interventions. Nevertheless, political ambition and societal pressure are now asking for a drastically reduction of animal experimentation and have further spiked the development of more predictive in vitro and ex vivo models. In addition to a range of more sophisticated in vitro assays, this has now also provided an ex vivo osteochondral defect model that can be generated based on equine donor tissue. Although such models better represent the situation in the native tissue and can be used to assess (osteo)chondral repair strategies, they still lack some important aspects of the in vivo (patho)physiological (inflammatory) environment, as well as the exposure to mechanical loading. This illustrates the challenges that we still face in translating these novel approaches from bench to bedside.

scholarly journals Ex Vivo and In Vivo Properties of an Injectable Hydrogel Derived From Acellular Ear Cartilage Extracellular Matrix

2021 ◽  
Vol 9 ◽  
Author(s):  
Danni Gong ◽  
Fei Yu ◽  
Meng Zhou ◽  
Wei Dong ◽  
Dan Yan ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Extracellular Matrix ◽  
Histological Analysis ◽  
Ex Vivo ◽  
Positive Staining ◽  
Gelation Kinetics ◽  
Ear Cartilage ◽  
Kinetics Of

Extracellular matrix (ECM) hydrogels provide advantages such as injectability, the ability to fill an irregularly shaped space, and the adequate bioactivity of native matrix. In this study, we developed decellularized cartilage ECM (dcECM) hydrogels from porcine ears innovatively via the main method of enzymatic digestion and verified good biocompatible properties of dcECM hydrogels to deliver chondrocytes and form subcutaneous cartilage in vivo. The scanning electron microscopy and turbidimetric gelation kinetics were used to characterize the material properties and gelation kinetics of the dcECM hydrogels. Then we evaluated the biocompatibility of hydrogels via the culture of chondrocytes in vitro. To further explore the dcECM hydrogels in vivo, grafts made from the mixture of dcECM hydrogels and chondrocytes were injected subcutaneously in nude mice for the gross and histological analysis. The structural and gelation kinetics of the dcECM hydrogels altered according to the variation in the ECM concentrations. The 10 mg/ml dcECM hydrogels could support the adhesion and proliferation of chondrocytes in vitro. In vivo, at 4 weeks after transplantation, cartilage-like tissues were detected in all groups with positive staining of toluidine blue, Safranin O, and collagen II, indicating the good gelation of dcECM hydrogels. While with the increasing concentration, the tissue engineering cartilages formed by 10 mg/ml dcECM hydrogel grafts were superior in weights, volumes, collagen, and glycosaminoglycan (GAG) content compared to the dcECM hydrogels of 1 mg/ml and 5 mg/ml. At 8 weeks after grafting, dcECM hydrogel grafts at 10 mg/ml showed very similar qualities to the control, collagen I grafts. After 12 weeks of in vivo culture, the histological analysis indicated that 10 mg/ml dcECM hydrogel grafts were similar to the normal cartilage from pig ears, which was the source tissue. In conclusion, dcECM hydrogel showed the promising potential as a tissue engineering biomaterial to improve the regeneration and heal injuries of ear cartilage.

Growth Factors and Scaffold Composition Influence Properties of Tissue Engineered Human Septal Cartilage Implants in a Murine Model

2008 ◽  
Vol 21 (4) ◽  
pp. 807-816 ◽  
Author(s):  
D. Skodacek ◽  
S. Brandau ◽  
T. Deutschle ◽  
S. Lang ◽  
N. Rotter
Keyword(s):  
Tissue Engineering ◽  
Growth Factors ◽  
Ex Vivo ◽  
Septal Cartilage ◽  
Hydroxyproline Content ◽  
Wet Weight ◽  
Cell Carriers ◽  
Scaffold Properties

Several surgical disciplines apply cartilage grafts for reconstructive purposes and have to overcome the scarcity of donor sites for this unique tissue. Employing the techniques of tissue engineering, cartilage might be generated in reasonable amounts for clinical purposes. Application of growth factors together with biochemical and biomechanical scaffold properties influence the process of ex vivo transplant production. The aims of this study are: 1) to investigate the influence of IGF-1 and TGFβ-2 on tissue engineered human septal cartilage in vitro and in vivo after transplantation in nude mice; 2) to analyse the effect of the polydioxanone (PDS) content of the biodegradable Ethisorb E210™ scaffold on the properties of the implanted constructs. Cells were three-dimensionally cultured on biodegradable Ethisorb E210™ (PGA-PLA-copolymer fleeces with polydioxanone (PDS) adhesions), or on E210™ scaffolds with a reduced polydioxanone content. Wet weight (ww), GAG-, and hydroxyprolin-content, as well as the cellularity of the neocartilage constructs were quantitatively evaluated. Additionally, the in vivo resorption of the two types of cell carriers was monitored. Addition of growth factors clearly increased the wet weight of the in vitro cultured constructs before transplantation. After transplantation, high PDS content improved the in vivo stability and macroscopic morphometric appearance of the tissue engineered specimens and led to enhanced deposition of glycosaminoglycans in transplanted constructs. Hydroxyproline content of the implants was not affected by either growth factors or PDS content. These data suggest a role for IGF-1 and TGFß-2 in preparative in vitro culture of chondrocytes before implantation, while PDS content of the scaffold is important for in vivo properties of the implanted material.

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