In vitro platforms for tissue engineering: implications for basic research and clinical translation

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.

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Brazilian minipig as a large-animal model for basic research and stem cell-based tissue engineering. Characterization and in vitro differentiation of bone marrow-derived mesenchymal stem cells

Journal of Applied Oral Science ◽

10.1590/1678-775720130526 ◽

2014 ◽

Vol 22 (3) ◽

pp. 218-227 ◽

Cited By ~ 8

Author(s):

Roberta Targa STRAMANDINOLI-ZANICOTTI ◽

André Lopes CARVALHO ◽

Carmen Lúcia Kuniyoshi REBELATTO ◽

Laurindo Moacir SASSI ◽

Maria Fernanda TORRES ◽

...

Keyword(s):

Tissue Engineering ◽

Stem Cells ◽

Bone Marrow ◽

Animal Model ◽

Mesenchymal Stem Cells ◽

Basic Research ◽

Large Animal Model ◽

Large Animal ◽

In Vitro Differentiation

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An Innovative Laboratory Procedure to Expand Chondrocytes with Reduced Dedifferentiation

Cartilage ◽

10.1177/1947603517746724 ◽

2017 ◽

Vol 9 (2) ◽

pp. 202-211 ◽

Cited By ~ 6

Author(s):

Yong Mao ◽

Tyler Hoffman ◽

Amy Wu ◽

Joachim Kohn

Keyword(s):

Tissue Engineering ◽

Tissue Culture ◽

Nude Mice ◽

Cartilage Tissue Engineering ◽

Basic Research ◽

Cartilage Tissue ◽

Laboratory Procedure ◽

In Vitro Expansion ◽

Culture Surface

Objective In vitro expansion of chondrocytes is required for cartilage tissue engineering and clinical cell-based cartilage repair practices. However, the dedifferentiation of chondrocytes during in vitro expansion continues to be a challenge. This study focuses on identifying a cell culture surface to support chondrocyte expansion with reduced dedifferentiation. Design A less adhesive culture surface, non–tissue culture treated surface (NTC), was tested for its suitability for culturing chondrocytes. The cell expansion and the expression of chondrocyte markers were monitored for at least 2 passages on NTC in comparison with conventional tissue culture treated polystyrene surface (TCP). The ability of expanded chondrocytes to form cartilage tissues was evaluated using pellet culturing and subcutaneous implantation in nude mice. Results NTC supported bovine chondrocyte proliferation to a clinically relevant expansion requirement within 2 passages. Chondrocyte phenotypes were better maintained when cultured on NTC than on TCP. In vitro pellet culture studies showed that chondrocytes expanded on NTC expressed a higher level of chondrocyte extracellular matrix. Furthermore, the cells expanded on NTC or TCP were implanted subcutaneously as pellets in nude mice for 6 weeks. The recovered pellets showed cartilage-like tissue formation from cells expanded on NTC but not from the cells expanded on TCP. Conclusions This study presents an innovative and easy culturing procedure to expand chondrocytes with reduced dedifferentiation. This procedure has potential to be developed to expand chondrocytes in vitro for basic research, tissue engineering, and possibly for clinical applications.

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

Materials ◽

10.3390/ma15010031 ◽

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.

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Functional Dental Pulp Regeneration: Basic Research and Clinical Translation

International Journal of Molecular Sciences ◽

10.3390/ijms22168991 ◽

2021 ◽

Vol 22 (16) ◽

pp. 8991

Author(s):

Zhuo Xie ◽

Zongshan Shen ◽

Peimeng Zhan ◽

Jiayu Yang ◽

Qiting Huang ◽

...

Keyword(s):

Tissue Engineering ◽

Stem Cells ◽

Growth Factors ◽

Dental Pulp ◽

Clinical Signs ◽

Basic Research ◽

Clinical Translation ◽

Pulp Regeneration ◽

Biological Studies ◽

Periapical Diseases

Pulpal and periapical diseases account for a large proportion of dental visits, the current treatments for which are root canal therapy (RCT) and pulp revascularisation. Despite the clinical signs of full recovery and histological reconstruction, true regeneration of pulp tissues is still far from being achieved. The goal of regenerative endodontics is to promote normal pulp function recovery in inflamed or necrotic teeth that would result in true regeneration of the pulpodentinal complex. Recently, rapid progress has been made related to tissue engineering-mediated pulp regeneration, which combines stem cells, biomaterials, and growth factors. Since the successful isolation and characterisation of dental pulp stem cells (DPSCs) and other applicable dental mesenchymal stem cells, basic research and preclinical exploration of stem cell-mediated functional pulp regeneration via cell transplantation and cell homing have received considerably more attention. Some of this effort has translated into clinical therapeutic applications, bringing a ground-breaking revolution and a new perspective to the endodontic field. In this article, we retrospectively examined the current treatment status and clinical goals of pulpal and periapical diseases and scrutinized biological studies of functional pulp regeneration with a focus on DPSCs, biomaterials, and growth factors. Then, we reviewed preclinical experiments based on various animal models and research strategies. Finally, we summarised the current challenges encountered in preclinical or clinical regenerative applications and suggested promising solutions to address these challenges to guide tissue engineering-mediated clinical translation in the future.

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Controlling the in vitro differentiation of embryonic stem cells for myocardial tissue engineering applications

Cell Biology International ◽

10.1042/cbi20090021 ◽

2009 ◽

Author(s):

Dong-Bo Ou ◽

Rui Chen ◽

Xiong-Tao Liu ◽

Jing-Jing Guo ◽

Hong-Tao Wang ◽

...

Keyword(s):

Tissue Engineering ◽

Stem Cells ◽

Embryonic Stem Cells ◽

Embryonic Stem ◽

Myocardial Tissue ◽

In Vitro Differentiation ◽

Engineering Applications ◽

Myocardial Tissue Engineering

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Decellularized bone extracellular matrix in skeletal tissue engineering

Biochemical Society Transactions ◽

10.1042/bst20190079 ◽

2020 ◽

Vol 48 (3) ◽

pp. 755-764

Author(s):

Benjamin B. Rothrauff ◽

Rocky S. Tuan

Keyword(s):

Tissue Engineering ◽

Bone Regeneration ◽

Tissue Regeneration ◽

Animal Studies ◽

Tumor Resection ◽

Regenerative Capacity ◽

Skeletal Tissue ◽

Large Bone

Bone possesses an intrinsic regenerative capacity, which can be compromised by aging, disease, trauma, and iatrogenesis (e.g. tumor resection, pharmacological). At present, autografts and allografts are the principal biological treatments available to replace large bone segments, but both entail several limitations that reduce wider use and consistent success. The use of decellularized extracellular matrices (ECM), often derived from xenogeneic sources, has been shown to favorably influence the immune response to injury and promote site-appropriate tissue regeneration. Decellularized bone ECM (dbECM), utilized in several forms — whole organ, particles, hydrogels — has shown promise in both in vitro and in vivo animal studies to promote osteogenic differentiation of stem/progenitor cells and enhance bone regeneration. However, dbECM has yet to be investigated in clinical studies, which are needed to determine the relative efficacy of this emerging biomaterial as compared with established treatments. This mini-review highlights the recent exploration of dbECM as a biomaterial for skeletal tissue engineering and considers modifications on its future use to more consistently promote bone regeneration.

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Bioreaktoren für Knochen-Tissue-Engineering

Osteologie/Osteology ◽

10.1055/s-0038-1630123 ◽

2013 ◽

Vol 22 (03) ◽

pp. 188-195 ◽

Cited By ~ 1

Author(s):

H.-H. Hsu ◽

C. Goepfert ◽

R. Pörtner

Keyword(s):

Tissue Engineering

ZusammenfassungZur medizinischen Behandlung großer Knochendefekte oder Verletzungen werden als Alternative zu etablierten Behandlungs-methoden neue Konzepte des Tissue Engineering (TE) diskutiert. Beim Knochen-TE ist es das Ziel, eine mit Zellen besiedelte drei-dimensionale (3D), biologisch abbaubare Struktur am Ort der Verletzung zu implantieren. Techniken für die organotypische Kultivierung von Knochenzellen in vitro beruhen auf der Kultivierung von Gewebezellen in Bioreaktoren in einem definierten Kultur-medium auf porösen Matrizes (Scaffolds), um ein gewebeähnliches Wachstum in 3D-Strukturen zu ermöglichen. Ein wichtiger Faktor für die erfolgreiche 3D-Kultur ist die Schaffung adäquater Strömungsbedingungen, die wiederum Einfluss auf die biochemischen und biophysikalischen (z. B. mechanische) Reize haben, denen die Zellen ausgesetzt sind. Hier müssen neben Schereffekten auch Stofftransportlimitierungen berücksichtigt werden. Der Beitrag fasst den aktuellen Stand bei der Entwicklung von Bioreaktoren für die Generierung von Knochenersatzmaterialien zusammen.

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In vitro- / in vivo- Untersuchungen zur Biokompatibilität und Bioresorption amorpher Kieselgelfaser für das Tissue engineering humaner Knorpelgewebe

Laryngo-Rhino-Otologie ◽

10.1055/s-2004-823584 ◽

2004 ◽

Vol 83 (02) ◽

Author(s):

A Haisch ◽

A Evers ◽

K Jöhrens-Leder ◽

S Jovanovic ◽

B Sedlmaier ◽

...

Keyword(s):

Tissue Engineering

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Needleless electrospinning of PVP/PGS fibrous scaffolds for skin tissue engineering applications

10.31224/osf.io/xs64k ◽

2018 ◽

Cited By ~ 1

Author(s):

Antonios Keirouz ◽

Giuseppino Fortunato ◽

Anthony Callanan ◽

Norbert Radacsi

Keyword(s):

Tissue Engineering ◽

Tensile Modulus ◽

Dermal Fibroblasts ◽

Skin Tissue ◽

Skin Substitute ◽

Electrospinning Technique ◽

Skin Tissue Engineering ◽

Needleless Electrospinning ◽

High Concentrations

Scaffolds and implants used for tissue engineering need to be adapted for their mechanical properties with respect to their environment within the human body. Therefore, a novel composite for skin tissue engineering is presented by use of blends of Poly(vinylpyrrolidone) (PVP) and Poly(glycerol sebacate) (PGS) were fabricated via the needleless electrospinning technique. The formed PGS/PVP blends were morphologically, thermochemically and mechanically characterized. The morphology of the developed fibers related to the concentration of PGS, with high concentrations of PGS merging the fibers together plasticizing the scaffold. The tensile modulus appeared to be affected by the concentration of PGS within the blends, with an apparent decrease in the elastic modulus of the electrospun mats and an exponential increase of the elongation at break. Ultraviolet (UV) crosslinking of PGS/PVP significantly decreased and stabilized the wettability of the formed fiber mats, as indicated by contact angle measurements. In vitro examination showed good viability and proliferation of human dermal fibroblasts over the period of a week. The present findings provide important insights for tuning the elastic properties of electrospun material by incorporating this unique elastomer, as a promising future candidate for skin substitute constructs.

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