Cutting-edge platforms in cardiac tissue engineering.

PubMed

Fleischer, Sharon; Feiner, Ron; Dvir, Tal

2017-10-01

As cardiac disease takes a higher toll with each passing year, the need for new therapies to deal with the scarcity in heart donors becomes ever more pressing. Cardiac tissue engineering holds the promise of creating functional replacement tissues to repair heart tissue damage. In an attempt to bridge the gap between the lab and clinical realization, the field has made major strides. In this review, we will discuss state of the art technologies such as layer-by-layer assembly, bioprinting and bionic tissue engineering, all developed to overcome some of the major hurdles faced in the field. Copyright © 2017 Elsevier Ltd. All rights reserved.

Graphene and its nanostructure derivatives for use in bone tissue engineering: Recent advances.

PubMed

Shadjou, Nasrin; Hasanzadeh, Mohammad

2016-05-01

Tissue engineering and regenerative medicine represent areas of increasing interest because of the major progress in cell and organ transplantation, as well as advances in materials science and engineering. Tissue-engineered bone constructs have the potential to alleviate the demand arising from the shortage of suitable autograft and allograft materials for augmenting bone healing. Graphene and its derivatives have attracted much interest for applications in bone tissue engineering. For this purpose, this review focuses on more recent advances in tissue engineering based on graphene-biomaterials from 2013 to May 2015. The purpose of this article was to give a general description of studies of nanostructured graphene derivatives for bone tissue engineering. In this review, we highlight how graphene family nanomaterials are being exploited for bone tissue engineering. Firstly, the main requirements for bone tissue engineering were discussed. Then, the mechanism by which graphene based materials promote new bone formation was explained, following which the current research status of main types of nanostructured scaffolds for bone tissue engineering was reviewed and discussed. In addition, graphene-based bioactive glass, as a potential drug/growth factor carrier, was reviewed which includes the composition-structure-drug delivery relationship and the functional effect on the tissue-stimulation properties. Also, the effect of structural and textural properties of graphene based materials on development of new biomaterials for production of bone implants and bone cements were discussed. Finally, the present review intends to provide the reader an overview of the current state of the graphene based biomaterials in bone tissue engineering, its limitations and hopes as well as the future research trends for this exciting field of science. © 2016 Wiley Periodicals, Inc.

Myocardial Tissue Engineering for Regenerative Applications.

PubMed

Fujita, Buntaro; Zimmermann, Wolfram-Hubertus

2017-09-01

This review provides an overview of the current state of tissue-engineered heart repair with a special focus on the anticipated modes of action of tissue-engineered therapy candidates and particular implications as to transplant immunology. Myocardial tissue engineering technologies have made tremendous advances in recent years. Numerous different strategies are under investigation and have reached different stages on their way to clinical translation. Studies in animal models demonstrated that heart repair requires either remuscularization by delivery of bona fide cardiomyocytes or paracrine support for the activation of endogenous repair mechanisms. Tissue engineering approaches result in enhanced cardiomyocyte retention and sustained remuscularization, but may also be explored for targeted paracrine or mechanical support. Some of the more advanced tissue engineering approaches are already tested clinically; others are at late stages of pre-clinical development. Process optimization towards cGMP compatibility and clinical scalability of contractile engineered human myocardium is an essential step towards clinical translation. Long-term allograft retention can be achieved under immune suppression. HLA matching may be an option to enhance graft retention and reduce the need for comprehensive immune suppression. Tissue-engineered heart repair is entering the clinical stage of the translational pipeline. Like in any effective therapy, side effects must be anticipated and carefully controlled. Allograft implantation under immune suppression is the most likely clinical scenario. Strategies to overcome transplant rejection are evolving and may further boost the clinical acceptance of tissue-engineered heart repair.

The growth of tissue engineering.

PubMed

Lysaght, M J; Reyes, J

2001-10-01

This report draws upon data from a variety of sources to estimate the size, scope, and growth rate of the contemporary tissue engineering enterprise. At the beginning of 2001, tissue engineering research and development was being pursued by 3,300 scientists and support staff in more than 70 startup companies or business units with a combined annual expenditure of over $600 million. Spending by tissue engineering firms has been growing at a compound annual rate of 16%, and the aggregate investment since 1990 now exceeds $3.5 billion. At the beginning of 2001, the net capital value of the 16 publicly traded tissue engineering startups had reached $2.6 billion. Firms focusing on structural applications (skin, cartilage, bone, cardiac prosthesis, and the like) comprise the fastest growing segment. In contrast, efforts in biohybrid organs and other metabolic applications have contracted over the past few years. The number of companies involved in stem cells and regenerative medicine is rapidly increasing, and this area represents the most likely nidus of future growth for tissue engineering. A notable recent trend has been the emergence of a strong commercial activity in tissue engineering outside the United States, with at least 16 European or Australian companies (22% of total) now active.

Challenges in engineering osteochondral tissue grafts with hierarchical structures.

PubMed

Gadjanski, Ivana; Vunjak-Novakovic, Gordana

2015-01-01

A major hurdle in treating osteochondral (OC) defects is the different healing abilities of two types of tissues involved - articular cartilage and subchondral bone. Biomimetic approaches to OC-construct engineering, based on recapitulation of biological principles of tissue development and regeneration, have potential for providing new treatments and advancing fundamental studies of OC tissue repair. This review on state of the art in hierarchical OC tissue graft engineering is focused on tissue engineering approaches designed to recapitulate the native milieu of cartilage and bone development. These biomimetic systems are discussed with relevance to bioreactor cultivation of clinically sized, anatomically shaped human cartilage/bone constructs with physiologic stratification and mechanical properties. The utility of engineered OC tissue constructs is evaluated for their use as grafts in regenerative medicine, and as high-fidelity models in biological research. A major challenge in engineering OC tissues is to generate a functionally integrated stratified cartilage-bone structure starting from one single population of mesenchymal cells, while incorporating perfusable vasculature into the bone, and in bone-cartilage interface. To this end, new generations of advanced scaffolds and bioreactors, implementation of mechanical loading regimens and harnessing of inflammatory responses of the host will likely drive the further progress.

A bird's eye view on the use of electrospun nanofibrous scaffolds for bone tissue engineering: Current state-of-the-art, emerging directions and future trends.

PubMed

Rezvani, Zahra; Venugopal, Jayarama R; Urbanska, Aleksandra M; Mills, David K; Ramakrishna, Seeram; Mozafari, Masoud

2016-10-01

Tissue engineering aims to develop therapeutic products that utilize a combination of scaffolds with viable cell systems or responsive biomolecules derived from such cells, for the repair, restoration/regeneration of tissues. Here, the main goal is to enable the body to heal itself by the introduction of electrospun scaffolds, such that the body recognizes them as its own and in turn uses them to regenerate "neo-native" functional tissues. During the last decade, innovative nanofibrous scaffolds have attracted substantial interest in bone tissue engineering. The electrospinning process makes it possible to fabricate appropriate scaffolds for bone tissue engineering from different categories of nanobiomaterials having the ability of controlled delivery of drugs in the defective tissues. It is expected that with the progress in science and technology, better bone constructs will be proposed in the future. This review discusses the innovative approaches into electrospinning techniques for the fabrication of nanofibrous scaffolds for bone tissue engineering. Copyright © 2016 Elsevier Inc. All rights reserved.

Synthetic biology meets tissue engineering

PubMed Central

Davies, Jamie A.; Cachat, Elise

2016-01-01

Classical tissue engineering is aimed mainly at producing anatomically and physiologically realistic replacements for normal human tissues. It is done either by encouraging cellular colonization of manufactured matrices or cellular recolonization of decellularized natural extracellular matrices from donor organs, or by allowing cells to self-organize into organs as they do during fetal life. For repair of normal bodies, this will be adequate but there are reasons for making unusual, non-evolved tissues (repair of unusual bodies, interface to electromechanical prostheses, incorporating living cells into life-support machines). Synthetic biology is aimed mainly at engineering cells so that they can perform custom functions: applying synthetic biological approaches to tissue engineering may be one way of engineering custom structures. In this article, we outline the ‘embryological cycle’ of patterning, differentiation and morphogenesis and review progress that has been made in constructing synthetic biological systems to reproduce these processes in new ways. The state-of-the-art remains a long way from making truly synthetic tissues, but there are now at least foundations for future work. PMID:27284030

Use of bioreactors in maxillofacial tissue engineering.

PubMed

Depprich, Rita; Handschel, Jörg; Wiesmann, Hans-Peter; Jäsche-Meyer, Janine; Meyer, Ulrich

2008-07-01

Engineering of various oral tissues is a challenging issue in contemporary maxillofacial reconstructive research. In contrast to the classic biomaterial approach, tissue engineering is based on the understanding of cell driven tissue formation, and aims to generate new functional tissues, rather than just to implant non-living space holders. Researchers hope to reach this goal by combining knowledge from biology, physics, materials science, engineering, and medicine in an integrated manner. Several major technical advances have been made in this field during the last decade, and clinical application is at the stage of first clinical trials. A recent limitation of extracorporally engineered cellular substitutes is the problem of growing enlarged tissues ex vivo. One of the main research topics is therefore to scale up artificial tissue constructs for use in extended defect situations. To overcome the monolayer inherent two-dimensional cell assembly, efforts have been made to grow cells in a three-dimensional space. Bioreactors have therefore been in focus for a considerable time to build up enlarged tissues. The shift from the ex vivo approach of cell multiplication to the generation of a real tissue growth is mirrored by the development of bioreactors, enabling scientists to grow more complex tissue constructs. This present review intends to provide an overview of the current state of art in maxillofacial tissue engineering by the use of bioreactors, its limitations and hopes, as well as the future research trends.

Biophysical properties of dermal building-blocks affects extra cellular matrix assembly in 3D endogenous macrotissue.

PubMed

Urciuolo, F; Garziano, A; Imparato, G; Panzetta, V; Fusco, S; Casale, C; Netti, P A

2016-01-29

The fabrication of functional tissue units is one of the major challenges in tissue engineering due to their in vitro use in tissue-on-chip systems, as well as in modular tissue engineering for the construction of macrotissue analogs. In this work, we aim to engineer dermal tissue micromodules obtained by culturing human dermal fibroblasts into porous gelatine microscaffold. We proved that such stromal cells coupled with gelatine microscaffolds are able to synthesize and to assemble an endogenous extracellular matrix (ECM) resulting in tissue micromodules, which evolve their biophysical features over the time. In particular, we found a time-dependent variation of oxygen consumption kinetic parameters, of newly formed ECM stiffness and of micromodules self-aggregation properties. As consequence when used as building blocks to fabricate larger tissues, the initial tissue micromodules state strongly affects the ECM organization and maturation in the final macrotissue. Such results highlight the role of the micromodules properties in controlling the formation of three-dimensional macrotissue in vitro, defining an innovative design criterion for selecting tissue-building blocks for modular tissue engineering.

Engineered Heart Repair.

PubMed

Fujita, B; Zimmermann, W-H

2017-08-01

There is a pressing need for the development of advanced heart failure therapeutics. Current state-of-the-art is protection from neurohumoral overstimulation, which fails to address the underlying cause of heart failure, namely loss of cardiomyocytes. Implantation of stem cell-derived cardiomyocytes via tissue-engineered myocardium is being advanced to realize the remuscularization of the failing heart. Here, we discuss pharmacological challenges pertaining to the clinical translation of tissue-engineered heart repair with a focus on engineered heart muscle (EHM). © 2017 American Society for Clinical Pharmacology and Therapeutics.

Creating biomaterials with spatially organized functionality.

PubMed

Chow, Lesley W; Fischer, Jacob F

2016-05-01

Biomaterials for tissue engineering provide scaffolds to support cells and guide tissue regeneration. Despite significant advances in biomaterials design and fabrication techniques, engineered tissue constructs remain functionally inferior to native tissues. This is largely due to the inability to recreate the complex and dynamic hierarchical organization of the extracellular matrix components, which is intimately linked to a tissue's biological function. This review discusses current state-of-the-art strategies to control the spatial presentation of physical and biochemical cues within a biomaterial to recapitulate native tissue organization and function. © 2016 by the Society for Experimental Biology and Medicine.

Challenges in engineering osteochondral tissue grafts with hierarchical structures Ivana Gadjanski, Gordana Vunjak Novakovic

PubMed Central

Gadjanski, Ivana; Vunjak-Novakovic, Gordana

2015-01-01

Introduction A major hurdle in treating osteochondral (OC) defects are the different healing abilities of two types of tissues involved - articular cartilage and subchondral bone. Biomimetic approaches to OC-construct-engineering, based on recapitulation of biological principles of tissue development and regeneration, have potential for providing new treatments and advancing fundamental studies of OC tissue repair. Areas covered This review on state of the art in hierarchical OC tissue graft engineering is focused on tissue engineering approaches designed to recapitulate the native milieu of cartilage and bone development. These biomimetic systems are discussed with relevance to bioreactor cultivation of clinically sized, anatomically shaped human cartilage/bone constructs with physiologic stratification and mechanical properties. The utility of engineered OC tissue constructs is evaluated for their use as grafts in regenerative medicine, and as high-fidelity models in biological research. Expert opinion A major challenge in engineering OC tissues is to generate a functionally integrated stratified cartilage-bone structure starting from one single population of mesenchymal cells, while incorporating perfusable vasculature into the bone, and in bone-cartilage interface. To this end, new generations of advanced scaffolds and bioreactors, implementation of mechanical loading regimens, and harnessing of inflammatory responses of the host will likely drive the further progress. PMID:26195329

Biomaterial-mesenchymal stem cell constructs for immunomodulation in composite tissue engineering.

PubMed

Hanson, Summer; D'Souza, Rena N; Hematti, Peiman

2014-08-01

Cell-based treatments are being developed as a novel approach for the treatment of many diseases in an effort to repair injured tissues and regenerate lost tissues. Interest in the potential use of multipotent progenitor or stem cells has grown significantly in recent years, specifically the use of mesenchymal stem cells (MSCs), for tissue engineering in combination with extracellular matrix-based scaffolds. An area that warrants further attention is the local or systemic host responses toward the implanted cell-biomaterial constructs. Such immunological responses could play a major role in determining the clinical efficacy of the therapeutic device or biomaterials used. MSCs, due to their unique immunomodulatory properties, hold great promise in tissue engineering as they not only directly participate in tissue repair and regeneration but also modulate the host foreign body response toward the engineered constructs. The purpose of this review was to summarize the current state of knowledge and applications of MSC-biomaterial constructs as a potential immunoregulatory tool in tissue engineering. Better understanding of the interactions between biomaterials and cells could translate to the development of clinically relevant and novel cell-based therapeutics for tissue reconstruction and regenerative medicine.

Tissue engineering and peripheral nerve reconstruction: an overview.

PubMed

Geuna, Stefano; Gnavi, Sara; Perroteau, Isabelle; Tos, Pierluigi; Battiston, Bruno

2013-01-01

Nerve repair is no more regarded as merely a matter of microsurgical reconstruction. To define this evolving reconstructive/regenerative approach, the term tissue engineering is being increasingly used since it reflects the search for interdisciplinary and integrated treatment strategies. However, the drawback of this new approach is its intrinsic complexity, which is the result of the variety of scientific disciplines involved. This chapter presents a synthetic overview of the state of the art in peripheral nerve tissue engineering with a look forward at the most promising innovations emerging from basic science investigation. This review is intended to set the stage for the collection of papers in the thematic issue of the International Review of Neurobiology that is focused on the various interdisciplinary approaches in peripheral nerve tissue engineering. © 2013 Elsevier Inc. All rights reserved.

Therapeutic cloning applications for organ transplantation.

PubMed

Koh, Chester J; Atala, Anthony

2004-04-01

A severe shortage of donor organs available for transplantation in the United States leaves patients suffering from diseased and injured organs with few treatment options. Scientists in the field of tissue engineering apply the principles of cell transplantation, material science, and engineering to construct biological substitutes that will restore and maintain normal function in diseased and injured tissues. Therapeutic cloning, where the nucleus from a donor cell is transferred into an enucleated oocyte in order to extract pluripotent embryonic stem cells, offers a potentially limitless source of cells for tissue engineering applications. The present chapter reviews recent advances that have occurred in therapeutic cloning and tissue engineering and describes applications of these new technologies that may offer novel therapies for patients with end-stage organ failure. Copyright 2004 Elsevier B.V.

A novel injectable temperature-sensitive zinc doped chitosan/β-glycerophosphate hydrogel for bone tissue engineering.

PubMed

Niranjan, Ramesh; Koushik, Chandru; Saravanan, Sekaran; Moorthi, Ambigapathi; Vairamani, Mariappanadar; Selvamurugan, Nagarajan

2013-03-01

Hydrogels are hydrophilic polymers that have a wide range of biomedical applications including bone tissue engineering. In this study we report preparation and characterization of a thermosensitive hydrogel (Zn-CS/β-GP) containing zinc (Zn), chitosan (CS) and beta-glycerophosphate (β-GP) for bone tissue engineering. The prepared hydrogel exhibited a liquid state at room temperature and turned into a gel at body temperature. The hydrogel was characterized by SEM, EDX, XRD, FT-IR and swelling studies. The hydrogel enhanced antibacterial activity and promoted osteoblast differentiation. Thus, we suggest that the Zn-CS/β-GP hydrogel could have potential impact as an injectable in situ forming scaffold for bone tissue engineering applications. Copyright © 2012 Elsevier B.V. All rights reserved.

Bioreactors as engineering support to treat cardiac muscle and vascular disease.

PubMed

Massai, Diana; Cerino, Giulia; Gallo, Diego; Pennella, Francesco; Deriu, Marco A; Rodriguez, Andres; Montevecchi, Franco M; Bignardi, Cristina; Audenino, Alberto; Morbiducci, Umberto

2013-01-01

Cardiovascular disease is the leading cause of morbidity and mortality in the Western World. The inability of fully differentiated, load-bearing cardiovascular tissues to in vivo regenerate and the limitations of the current treatment therapies greatly motivate the efforts of cardiovascular tissue engineering to become an effective clinical strategy for injured heart and vessels. For the effective production of organized and functional cardiovascular engineered constructs in vitro, a suitable dynamic environment is essential, and can be achieved and maintained within bioreactors. Bioreactors are technological devices that, while monitoring and controlling the culture environment and stimulating the construct, attempt to mimic the physiological milieu. In this study, a review of the current state of the art of bioreactor solutions for cardiovascular tissue engineering is presented, with emphasis on bioreactors and biophysical stimuli adopted for investigating the mechanisms influencing cardiovascular tissue development, and for eventually generating suitable cardiovascular tissue replacements.

Strategies to engineer tendon/ligament-to-bone interface: Biomaterials, cells and growth factors.

PubMed

Font Tellado, Sonia; Balmayor, Elizabeth R; Van Griensven, Martijn

2015-11-01

Integration between tendon/ligament and bone occurs through a specialized tissue interface called enthesis. The complex and heterogeneous structure of the enthesis is essential to ensure smooth mechanical stress transfer between bone and soft tissues. Following injury, the interface is not regenerated, resulting in high rupture recurrence rates. Tissue engineering is a promising strategy for the regeneration of a functional enthesis. However, the complex structural and cellular composition of the native interface makes enthesis tissue engineering particularly challenging. Thus, it is likely that a combination of biomaterials and cells stimulated with appropriate biochemical and mechanical cues will be needed. The objective of this review is to describe the current state-of-the-art, challenges and future directions in the field of enthesis tissue engineering focusing on four key parameters: (1) scaffold and biomaterials, (2) cells, (3) growth factors and (4) mechanical stimuli. Copyright © 2015 Elsevier B.V. All rights reserved.

Synthetic biology meets tissue engineering.

PubMed

Davies, Jamie A; Cachat, Elise

2016-06-15

Classical tissue engineering is aimed mainly at producing anatomically and physiologically realistic replacements for normal human tissues. It is done either by encouraging cellular colonization of manufactured matrices or cellular recolonization of decellularized natural extracellular matrices from donor organs, or by allowing cells to self-organize into organs as they do during fetal life. For repair of normal bodies, this will be adequate but there are reasons for making unusual, non-evolved tissues (repair of unusual bodies, interface to electromechanical prostheses, incorporating living cells into life-support machines). Synthetic biology is aimed mainly at engineering cells so that they can perform custom functions: applying synthetic biological approaches to tissue engineering may be one way of engineering custom structures. In this article, we outline the 'embryological cycle' of patterning, differentiation and morphogenesis and review progress that has been made in constructing synthetic biological systems to reproduce these processes in new ways. The state-of-the-art remains a long way from making truly synthetic tissues, but there are now at least foundations for future work. © 2016 Authors; published by Portland Press Limited.

Mechanical Modulation of Nascent Stem Cell Lineage Commitment in Tissue Engineering Scaffolds

PubMed Central

Song, Min Jae; Dean, David; Tate, Melissa L. Knothe

2013-01-01

Taking inspiration from tissue morphogenesis in utero, this study tests the concept of using tissue engineering scaffolds as delivery devices to modulate emergent structure-function relationships at early stages of tissue genesis. We report on the use of a combined computational fluid dynamics (CFD) modeling, advanced manufacturing methods, and experimental fluid mechanics (micro-piv and strain mapping) for the prospective design of tissue engineering scaffold geometries that deliver spatially resolved mechanical cues to cells seeded within. When subjected to a constant magnitude global flow regime, the local scaffold geometry dictates the magnitudes of mechanical stresses and strains experienced by a given cell, and in a spatially resolved fashion, similar to patterning during morphogenesis. In addition, early markers of mesenchymal stem cell lineage commitment relate significantly to the local mechanical environment of the cell. Finally, by plotting the range of stress-strain states for all data corresponding to nascent cell lineage commitment (95% CI), we begin to “map the mechanome”, defining stress-strain states most conducive to targeted cell fates. In sum, we provide a library of reference mechanical cues that can be delivered to cells seeded on tissue engineering scaffolds to guide target tissue phenotypes in a temporally and spatially resolved manner. Knowledge of these effects allows for prospective scaffold design optimization using virtual models prior to prototyping and clinical implementation. Finally, this approach enables the development of next generation scaffolds cum delivery devices for genesis of complex tissues with heterogenous properties, e.g., organs, joints or interface tissues such as growth plates. PMID:23660249

Mechanical modulation of nascent stem cell lineage commitment in tissue engineering scaffolds.

PubMed

Song, Min Jae; Dean, David; Knothe Tate, Melissa L

2013-07-01

Taking inspiration from tissue morphogenesis in utero, this study tests the concept of using tissue engineering scaffolds as delivery devices to modulate emergent structure-function relationships at early stages of tissue genesis. We report on the use of a combined computational fluid dynamics (CFD) modeling, advanced manufacturing methods, and experimental fluid mechanics (micro-piv and strain mapping) for the prospective design of tissue engineering scaffold geometries that deliver spatially resolved mechanical cues to stem cells seeded within. When subjected to a constant magnitude global flow regime, the local scaffold geometry dictates the magnitudes of mechanical stresses and strains experienced by a given cell, and in a spatially resolved fashion, similar to patterning during morphogenesis. In addition, early markers of mesenchymal stem cell lineage commitment relate significantly to the local mechanical environment of the cell. Finally, by plotting the range of stress-strain states for all data corresponding to nascent cell lineage commitment (95% CI), we begin to "map the mechanome", defining stress-strain states most conducive to targeted cell fates. In sum, we provide a library of reference mechanical cues that can be delivered to cells seeded on tissue engineering scaffolds to guide target tissue phenotypes in a temporally and spatially resolved manner. Knowledge of these effects allows for prospective scaffold design optimization using virtual models prior to prototyping and clinical implementation. Finally, this approach enables the development of next generation scaffolds cum delivery devices for genesis of complex tissues with heterogenous properties, e.g., organs, joints or interface tissues such as growth plates. Copyright © 2013 Elsevier Ltd. All rights reserved.

Advanced Engineering Strategies for Periodontal Complex Regeneration.

PubMed

Park, Chan Ho; Kim, Kyoung-Hwa; Lee, Yong-Moo; Seol, Yang-Jo

2016-01-18

The regeneration and integration of multiple tissue types is critical for efforts to restore the function of musculoskeletal complex. In particular, the neogenesis of periodontal constructs for systematic tooth-supporting functions is a current challenge due to micron-scaled tissue compartmentalization, oblique/perpendicular orientations of fibrous connective tissues to the tooth root surface and the orchestration of multiple regenerated tissues. Although there have been various biological and biochemical achievements, periodontal tissue regeneration remains limited and unpredictable. The purpose of this paper is to discuss current advanced engineering approaches for periodontal complex formations; computer-designed, customized scaffolding architectures; cell sheet technology-based multi-phasic approaches; and patient-specific constructs using bioresorbable polymeric material and 3-D printing technology for clinical application. The review covers various advanced technologies for periodontal complex regeneration and state-of-the-art therapeutic avenues in periodontal tissue engineering.

Cardiovascular Bio-Engineering: Current State of the Art.

PubMed

Simon-Yarza, Teresa; Bataille, Isabelle; Letourneur, Didier

2017-04-01

Despite the introduction of new drugs and innovative devices contributing in the last years to improve patients' quality of life, morbidity and mortality from cardiovascular diseases remain high. There is an urgent need for addressing the underlying problem of the loss of cardiac or vascular tissues and therefore developing new therapies. Autologous vascular transplants are often limited by poor quality of donor sites and heart organ transplantation by donor shortage. Vascular and cardiac tissue engineering, whose aim is to repair or replace cardiovascular tissues by the use of cells, engineering and materials, as well as biochemical and physicochemical factors, appears in this scenario as a promising tool to repair the damaged hearts and vessels. We will present a general overview on the fundamentals in the area of cardiac and vascular tissue engineering as well as on the latest progresses and challenges.

Adipose tissue engineering: state of the art, recent advances and innovative approaches.

PubMed

Tanzi, Maria Cristina; Farè, Silvia

2009-09-01

Adipose tissue is a highly specialized connective tissue found either in white or brown forms, the white form being the most abundant in adult humans. Loss or damage of white adipose tissue due to aging or pathological conditions needs reconstructive approaches. To date, two main strategies are being investigated for generating functional adipose tissue: autologous tissue/cell transplantation and adipose tissue engineering. Free-fat transplantation rarely achieves sufficient tissue augmentation owing to delayed neovascularization, with subsequent cell necrosis and graft volume shrinkage. Tissue engineering approaches represent, instead, a more suitable alternative for adipose tissue regeneration; they can be performed either with in situ or de novo adipogenesis. In situ adipogenesis or transplantation of encapsulated cells can be useful in healing small-volume defects, whereas restoration of large defects, where vascularization and a rapid volumetric gain are strict requirements, needs de novo strategies with 3D scaffold/filling matrix combinations. For adipose tissue engineering, the use of adult mesenchymal stem cells (both adipose- and bone marrow-derived stem cells) or of preadipocytes is preferred to the use of mature adipocytes, which have low expandability and poor ability for volume retention. This review intends to assemble and describe recent work on this topic, critically presenting successes obtained and drawbacks faced to date.

Evaluating the Use of Monocytes with a Degradable Polyurethane for Vascular Tissue Regeneration

NASA Astrophysics Data System (ADS)

Battiston, Kyle Giovanni

Monocytes are one of the first cell types present following the implantation of a biomaterial or tissue engineered construct. Depending on the monocyte activation state supported by the biomaterial, monocytes and their derived macrophages (MDMs) can act as positive contributors to tissue regeneration and wound healing, or conversely promote a chronic inflammatory response that leads to fibrous encapsulation and implant rejection. A degradable polar hydrophobic iconic polyurethane (D-PHI) has been shown to reduce pro-inflammatory monocyte/macrophage response compared to tissue culture polystyrene (TCPS), a substrate routinely used for in vitro culture of cells, as well as poly(lactide- co-glycolide) (PLGA), a standard synthetic biodegradable biomaterial in the tissue engineering field. D-PHI has also shown properties suitable for use in a vascular tissue engineering context. In order to understand the mechanism through which D-PHI attenuates pro-inflammatory monocyte response, this thesis investigated the ability of D-PHI to modulate interactions with adsorbed serum proteins and the properties of D-PHI that were important for this activity. D-PHI was shown to regulate protein adsorption in a manner that produced divergent monocyte responses compared to TCPS and PLGA when coated with the serum proteins alpha2-macroglobulin or immunoglobulin G (IgG). In the case of IgG, D-PHI was shown to reduce pro-inflammatory binding site exposure as a function of the material's polar, hydrophobic, and ionic character. Due to the favourable monocyte activation state supported by D-PHI, and the importance of monocytes/macrophages in regulating the response of tissue-specific cell types in vivo, the ability of a D-PHI-stimulated monocyte/macrophage activation state to contribute to modulating the response of vascular smooth muscle cells (VSMCs) in a vascular tissue engineering context was investigated. D-PHI- stimulated monocytes promoted VSMC growth and migration through biomolecule release. Coupling monocyte-VSMC co-culture with biomechanical strain further enhanced these effects, while also promoting extracellular matrix deposition (collagen I, collagen III, and elastin) and enhancing the mechanical properties of VSMC-monocyte seeded tissue constructs. This thesis identifies the use of biomaterials with immunomodulatory capacity to harness the stimulatory potential of MDMs and contribute to tissue engineering strategies in vitro. This latter work in turn has contributed to identifying aspects of biomaterial design that can contribute to supporting desirable monocyte-biomaterial interactions that can facilitate this process.

Bone Tissue Engineering and Regeneration: From Discovery to the Clinic—An Overview

PubMed Central

2011-01-01

A National Institutes of Health sponsored workshop “Bone Tissue Engineering and Regeneration: From Discovery to the Clinic” gathered thought leaders from medicine, science, and industry to determine the state of art in the field and to define the barriers to translating new technologies to novel therapies to treat bone defects. Tissue engineering holds enormous promise to improve human health through prevention of disease and the restoration of healthy tissue functions. Bone tissue engineering, similar to that for other tissues and organs, requires integration of multiple disciplines such as cell biology, stem cells, developmental and molecular biology, biomechanics, biomaterials science, and immunology and transplantation science. Although each of the research areas has undergone enormous advances in last decade, the translation to clinical care and the development of tissue engineering composites to replace human tissues has been limited. Bone, similar to other tissue and organs, has complex structure and functions and requires exquisite interactions between cells, matrices, biomechanical forces, and gene and protein regulatory factors for sustained function. The process of engineering bone, thus, requires a comprehensive approach with broad expertise. Although in vitro and preclinical animal studies have been pursued with a large and diverse collection of scaffolds, cells, and biomolecules, the field of bone tissue engineering remains fragmented up to the point that a clear translational roadmap has yet to emerge. Translation is particularly important for unmet clinical needs such as large segmental defects and medically compromised conditions such as tumor removal and infection sites. Collectively, manuscripts in this volume provide luminary examples toward identification of barriers and strategies for translation of fundamental discoveries into clinical therapeutics. PMID:21902614

Bone tissue engineering and regeneration: from discovery to the clinic--an overview.

PubMed

O'Keefe, Regis J; Mao, Jeremy

2011-12-01

A National Institutes of Health sponsored workshop "Bone Tissue Engineering and Regeneration: From Discovery to the Clinic" gathered thought leaders from medicine, science, and industry to determine the state of art in the field and to define the barriers to translating new technologies to novel therapies to treat bone defects. Tissue engineering holds enormous promise to improve human health through prevention of disease and the restoration of healthy tissue functions. Bone tissue engineering, similar to that for other tissues and organs, requires integration of multiple disciplines such as cell biology, stem cells, developmental and molecular biology, biomechanics, biomaterials science, and immunology and transplantation science. Although each of the research areas has undergone enormous advances in last decade, the translation to clinical care and the development of tissue engineering composites to replace human tissues has been limited. Bone, similar to other tissue and organs, has complex structure and functions and requires exquisite interactions between cells, matrices, biomechanical forces, and gene and protein regulatory factors for sustained function. The process of engineering bone, thus, requires a comprehensive approach with broad expertise. Although in vitro and preclinical animal studies have been pursued with a large and diverse collection of scaffolds, cells, and biomolecules, the field of bone tissue engineering remains fragmented up to the point that a clear translational roadmap has yet to emerge. Translation is particularly important for unmet clinical needs such as large segmental defects and medically compromised conditions such as tumor removal and infection sites. Collectively, manuscripts in this volume provide luminary examples toward identification of barriers and strategies for translation of fundamental discoveries into clinical therapeutics. © Mary Ann Liebert, Inc.

Tissue-Engineered Solutions in Plastic and Reconstructive Surgery: Principles and Practice

PubMed Central

Al-Himdani, Sarah; Jessop, Zita M.; Al-Sabah, Ayesha; Combellack, Emman; Ibrahim, Amel; Doak, Shareen H.; Hart, Andrew M.; Archer, Charles W.; Thornton, Catherine A.; Whitaker, Iain S.

2017-01-01

Recent advances in microsurgery, imaging, and transplantation have led to significant refinements in autologous reconstructive options; however, the morbidity of donor sites remains. This would be eliminated by successful clinical translation of tissue-engineered solutions into surgical practice. Plastic surgeons are uniquely placed to be intrinsically involved in the research and development of laboratory engineered tissues and their subsequent use. In this article, we present an overview of the field of tissue engineering, with the practicing plastic surgeon in mind. The Medical Research Council states that regenerative medicine and tissue engineering “holds the promise of revolutionizing patient care in the twenty-first century.” The UK government highlighted regenerative medicine as one of the key eight great technologies in their industrial strategy worthy of significant investment. The long-term aim of successful biomanufacture to repair composite defects depends on interdisciplinary collaboration between cell biologists, material scientists, engineers, and associated medical specialties; however currently, there is a current lack of coordination in the field as a whole. Barriers to translation are deep rooted at the basic science level, manifested by a lack of consensus on the ideal cell source, scaffold, molecular cues, and environment and manufacturing strategy. There is also insufficient understanding of the long-term safety and durability of tissue-engineered constructs. This review aims to highlight that individualized approaches to the field are not adequate, and research collaboratives will be essential to bring together differing areas of expertise to expedite future clinical translation. The use of tissue engineering in reconstructive surgery would result in a paradigm shift but it is important to maintain realistic expectations. It is generally accepted that it takes 20–30 years from the start of basic science research to clinical utility, demonstrated by contemporary treatments such as bone marrow transplantation. Although great advances have been made in the tissue engineering field, we highlight the barriers that need to be overcome before we see the routine use of tissue-engineered solutions. PMID:28280722

Tissue-Engineered Solutions in Plastic and Reconstructive Surgery: Principles and Practice.

PubMed

Al-Himdani, Sarah; Jessop, Zita M; Al-Sabah, Ayesha; Combellack, Emman; Ibrahim, Amel; Doak, Shareen H; Hart, Andrew M; Archer, Charles W; Thornton, Catherine A; Whitaker, Iain S

2017-01-01

Recent advances in microsurgery, imaging, and transplantation have led to significant refinements in autologous reconstructive options; however, the morbidity of donor sites remains. This would be eliminated by successful clinical translation of tissue-engineered solutions into surgical practice. Plastic surgeons are uniquely placed to be intrinsically involved in the research and development of laboratory engineered tissues and their subsequent use. In this article, we present an overview of the field of tissue engineering, with the practicing plastic surgeon in mind. The Medical Research Council states that regenerative medicine and tissue engineering "holds the promise of revolutionizing patient care in the twenty-first century." The UK government highlighted regenerative medicine as one of the key eight great technologies in their industrial strategy worthy of significant investment. The long-term aim of successful biomanufacture to repair composite defects depends on interdisciplinary collaboration between cell biologists, material scientists, engineers, and associated medical specialties; however currently, there is a current lack of coordination in the field as a whole. Barriers to translation are deep rooted at the basic science level, manifested by a lack of consensus on the ideal cell source, scaffold, molecular cues, and environment and manufacturing strategy. There is also insufficient understanding of the long-term safety and durability of tissue-engineered constructs. This review aims to highlight that individualized approaches to the field are not adequate, and research collaboratives will be essential to bring together differing areas of expertise to expedite future clinical translation. The use of tissue engineering in reconstructive surgery would result in a paradigm shift but it is important to maintain realistic expectations. It is generally accepted that it takes 20-30 years from the start of basic science research to clinical utility, demonstrated by contemporary treatments such as bone marrow transplantation. Although great advances have been made in the tissue engineering field, we highlight the barriers that need to be overcome before we see the routine use of tissue-engineered solutions.

Proangiogenic scaffolds as functional templates for cardiac tissue engineering.

PubMed

Madden, Lauran R; Mortisen, Derek J; Sussman, Eric M; Dupras, Sarah K; Fugate, James A; Cuy, Janet L; Hauch, Kip D; Laflamme, Michael A; Murry, Charles E; Ratner, Buddy D

2010-08-24

We demonstrate here a cardiac tissue-engineering strategy addressing multicellular organization, integration into host myocardium, and directional cues to reconstruct the functional architecture of heart muscle. Microtemplating is used to shape poly(2-hydroxyethyl methacrylate-co-methacrylic acid) hydrogel into a tissue-engineering scaffold with architectures driving heart tissue integration. The construct contains parallel channels to organize cardiomyocyte bundles, supported by micrometer-sized, spherical, interconnected pores that enhance angiogenesis while reducing scarring. Surface-modified scaffolds were seeded with human ES cell-derived cardiomyocytes and cultured in vitro. Cardiomyocytes survived and proliferated for 2 wk in scaffolds, reaching adult heart densities. Cardiac implantation of acellular scaffolds with pore diameters of 30-40 microm showed angiogenesis and reduced fibrotic response, coinciding with a shift in macrophage phenotype toward the M2 state. This work establishes a foundation for spatially controlled cardiac tissue engineering by providing discrete compartments for cardiomyocytes and stroma in a scaffold that enhances vascularization and integration while controlling the inflammatory response.

Proangiogenic scaffolds as functional templates for cardiac tissue engineering

PubMed Central

Madden, Lauran R.; Mortisen, Derek J.; Sussman, Eric M.; Dupras, Sarah K.; Fugate, James A.; Cuy, Janet L.; Hauch, Kip D.; Laflamme, Michael A.; Murry, Charles E.; Ratner, Buddy D.

2010-01-01

We demonstrate here a cardiac tissue-engineering strategy addressing multicellular organization, integration into host myocardium, and directional cues to reconstruct the functional architecture of heart muscle. Microtemplating is used to shape poly(2-hydroxyethyl methacrylate-co-methacrylic acid) hydrogel into a tissue-engineering scaffold with architectures driving heart tissue integration. The construct contains parallel channels to organize cardiomyocyte bundles, supported by micrometer-sized, spherical, interconnected pores that enhance angiogenesis while reducing scarring. Surface-modified scaffolds were seeded with human ES cell-derived cardiomyocytes and cultured in vitro. Cardiomyocytes survived and proliferated for 2 wk in scaffolds, reaching adult heart densities. Cardiac implantation of acellular scaffolds with pore diameters of 30–40 μm showed angiogenesis and reduced fibrotic response, coinciding with a shift in macrophage phenotype toward the M2 state. This work establishes a foundation for spatially controlled cardiac tissue engineering by providing discrete compartments for cardiomyocytes and stroma in a scaffold that enhances vascularization and integration while controlling the inflammatory response. PMID:20696917

Bone Tissue Engineering: Recent Advances and Challenges

PubMed Central

Amini, Ami R.; Laurencin, Cato T.; Nukavarapu, Syam P.

2013-01-01

The worldwide incidence of bone disorders and conditions has trended steeply upward and is expected to double by 2020, especially in populations where aging is coupled with increased obesity and poor physical activity. Engineered bone tissue has been viewed as a potential alternative to the conventional use of bone grafts, due to their limitless supply and no disease transmission. However, bone tissue engineering practices have not proceeded to clinical practice due to several limitations or challenges. Bone tissue engineering aims to induce new functional bone regeneration via the synergistic combination of biomaterials, cells, and factor therapy. In this review, we discuss the fundamentals of bone tissue engineering, highlighting the current state of this field. Further, we review the recent advances of biomaterial and cell-based research, as well as approaches used to enhance bone regeneration. Specifically, we discuss widely investigated biomaterial scaffolds, micro- and nano-structural properties of these scaffolds, and the incorporation of biomimetic properties and/or growth factors. In addition, we examine various cellular approaches, including the use of mesenchymal stem cells (MSCs), embryonic stem cells (ESCs), adult stem cells, induced pluripotent stem cells (iPSCs), and platelet-rich plasma (PRP), and their clinical application strengths and limitations. We conclude by overviewing the challenges that face the bone tissue engineering field, such as the lack of sufficient vascularization at the defect site, and the research aimed at functional bone tissue engineering. These challenges will drive future research in the field. PMID:23339648

Ultrasound Imaging Techniques for Spatiotemporal Characterization of Composition, Microstructure, and Mechanical Properties in Tissue Engineering.

PubMed

Deng, Cheri X; Hong, Xiaowei; Stegemann, Jan P

2016-08-01

Ultrasound techniques are increasingly being used to quantitatively characterize both native and engineered tissues. This review provides an overview and selected examples of the main techniques used in these applications. Grayscale imaging has been used to characterize extracellular matrix deposition, and quantitative ultrasound imaging based on the integrated backscatter coefficient has been applied to estimating cell concentrations and matrix morphology in tissue engineering. Spectral analysis has been employed to characterize the concentration and spatial distribution of mineral particles in a construct, as well as to monitor mineral deposition by cells over time. Ultrasound techniques have also been used to measure the mechanical properties of native and engineered tissues. Conventional ultrasound elasticity imaging and acoustic radiation force imaging have been applied to detect regions of altered stiffness within tissues. Sonorheometry and monitoring of steady-state excitation and recovery have been used to characterize viscoelastic properties of tissue using a single transducer to both deform and image the sample. Dual-mode ultrasound elastography uses separate ultrasound transducers to produce a more potent deformation force to microscale characterization of viscoelasticity of hydrogel constructs. These ultrasound-based techniques have high potential to impact the field of tissue engineering as they are further developed and their range of applications expands.

Assessment of post-implantation integration of engineered tissues using fluorescence lifetime spectroscopy

NASA Astrophysics Data System (ADS)

Elahi, Sakib F.; Lee, Seung Y.; Lloyd, William R.; Chen, Leng-Chun; Kuo, Shiuhyang; Zhou, Ying; Kim, Hyungjin M.; Kennedy, Robert; Marcelo, Cynthia; Feinberg, Stephen E.; Mycek, Mary-Ann

2018-02-01

Clinical translation of engineered tissue constructs requires noninvasive methods to assess construct health and viability after implantation in patients. However, current practices to monitor post-implantation construct integration are either qualitative (visual assessment) or destructive (tissue histology). As label-free fluorescence lifetime sensing can noninvasively characterize pre-implantation construct viability, we employed a handheld fluorescence lifetime spectroscopy probe to quantitatively and noninvasively assess tissue constructs that were implanted in a murine model. We designed the system to be suitable for intravital measurements: portability, localization with precise maneuverability, and rapid data acquisition. Our model tissue constructs were manufactured from primary human cells to simulate patient variability and were stressed to create a range of health states. Secreted amounts of three cytokines that relate to cellular viability were measured in vitro to assess pre-implantation construct health. In vivo optical sensing assessed tissue integration of constructs at one-week and three-weeks post-implantation. At one-week post-implantation, optical parameters correlated with in vitro pre-implantation secretion levels of all three cytokines (p < 0.05). This relationship was no longer seen at three-weeks post-implantation, suggesting comparable tissue integration independent of preimplantation health. Histology confirmed re-epithelialization of these constructs independent of pre-implantation health state, supporting the lack of a correlation. These results suggest that clinical optical diagnostic tools based on label-free fluorescence lifetime sensing of endogenous tissue fluorophores could noninvasively monitor post-implantation integration of engineered tissues.

3D Bioprinting and In Vitro Cardiovascular Tissue Modeling.

PubMed

Jang, Jinah

2017-08-18

Numerous microfabrication approaches have been developed to recapitulate morphologically and functionally organized tissue microarchitectures in vitro; however, the technical and operational limitations remain to be overcome. 3D printing technology facilitates the building of a construct containing biomaterials and cells in desired organizations and shapes that have physiologically relevant geometry, complexity, and micro-environmental cues. The selection of biomaterials for 3D printing is considered one of the most critical factors to achieve tissue function. It has been reported that some printable biomaterials, having extracellular matrix-like intrinsic microenvironment factors, were capable of regulating stem cell fate and phenotype. In particular, this technology can control the spatial positions of cells, and provide topological, chemical, and complex cues, allowing neovascularization and maturation in the engineered cardiovascular tissues. This review will delineate the state-of-the-art 3D bioprinting techniques in the field of cardiovascular tissue engineering and their applications in translational medicine. In addition, this review will describe 3D printing-based pre-vascularization technologies correlated with implementing blood perfusion throughout the engineered tissue equivalent. The described engineering method may offer a unique approach that results in the physiological mimicry of human cardiovascular tissues to aid in drug development and therapeutic approaches.

Articular cartilage: from formation to tissue engineering.

PubMed

Camarero-Espinosa, Sandra; Rothen-Rutishauser, Barbara; Foster, E Johan; Weder, Christoph

2016-05-26

Hyaline cartilage is the nonlinear, inhomogeneous, anisotropic, poro-viscoelastic connective tissue that serves as friction-reducing and load-bearing cushion in synovial joints and is vital for mammalian skeletal movements. Due to its avascular nature, low cell density, low proliferative activity and the tendency of chondrocytes to de-differentiate, cartilage cannot regenerate after injury, wear and tear, or degeneration through common diseases such as osteoarthritis. Therefore severe damage usually requires surgical intervention. Current clinical strategies to generate new tissue include debridement, microfracture, autologous chondrocyte transplantation, and mosaicplasty. While articular cartilage was predicted to be one of the first tissues to be successfully engineered, it proved to be challenging to reproduce the complex architecture and biomechanical properties of the native tissue. Despite significant research efforts, only a limited number of studies have evolved up to the clinical trial stage. This review article summarizes the current state of cartilage tissue engineering in the context of relevant biological aspects, such as the formation and growth of hyaline cartilage, its composition, structure and biomechanical properties. Special attention is given to materials development, scaffold designs, fabrication methods, and template-cell interactions, which are of great importance to the structure and functionality of the engineered tissue.

3D Bioprinting and In Vitro Cardiovascular Tissue Modeling

PubMed Central

Jang, Jinah

2017-01-01

Numerous microfabrication approaches have been developed to recapitulate morphologically and functionally organized tissue microarchitectures in vitro; however, the technical and operational limitations remain to be overcome. 3D printing technology facilitates the building of a construct containing biomaterials and cells in desired organizations and shapes that have physiologically relevant geometry, complexity, and micro-environmental cues. The selection of biomaterials for 3D printing is considered one of the most critical factors to achieve tissue function. It has been reported that some printable biomaterials, having extracellular matrix-like intrinsic microenvironment factors, were capable of regulating stem cell fate and phenotype. In particular, this technology can control the spatial positions of cells, and provide topological, chemical, and complex cues, allowing neovascularization and maturation in the engineered cardiovascular tissues. This review will delineate the state-of-the-art 3D bioprinting techniques in the field of cardiovascular tissue engineering and their applications in translational medicine. In addition, this review will describe 3D printing-based pre-vascularization technologies correlated with implementing blood perfusion throughout the engineered tissue equivalent. The described engineering method may offer a unique approach that results in the physiological mimicry of human cardiovascular tissues to aid in drug development and therapeutic approaches. PMID:28952550

Esophageal tissue engineering: an in-depth review on scaffold design.

PubMed

Tan, J Y; Chua, C K; Leong, K F; Chian, K S; Leong, W S; Tan, L P

2012-01-01

Treatment of esophageal cancer often requires surgical procedures that involve removal. The current approaches to restore esophageal continuity however, are known to have limitations which may not result in full functional recovery. In theory, using a tissue engineered esophagus developed from the patient's own cells to replace the removed esophageal segment can be the ideal method of reconstruction. One of the key elements involved in the tissue engineering process is the scaffold which acts as a template for organization of cells and tissue development. While a number of scaffolds range from traditional non-biodegradable tubing to bioactive decellularized matrix have been proposed to engineer the esophagus in the past decade, results are still not yet favorable with many challenges relating to tissue quality need to be met improvements. The success of new esophageal tissue formation will ultimately depend on the success of the scaffold being able to meet the essential requirements specific to the esophageal tissue. Here, the design of the scaffold and its fabrication approaches are reviewed. In this paper, we review the current state of development in bioengineering the esophagus with particular emphasis on scaffold design. Copyright © 2011 Wiley Periodicals, Inc.

A review on powder-based additive manufacturing for tissue engineering: selective laser sintering and inkjet 3D printing

PubMed Central

Shirazi, Seyed Farid Seyed; Gharehkhani, Samira; Mehrali, Mehdi; Yarmand, Hooman; Metselaar, Hendrik Simon Cornelis; Adib Kadri, Nahrizul; Osman, Noor Azuan Abu

2015-01-01

Since most starting materials for tissue engineering are in powder form, using powder-based additive manufacturing methods is attractive and practical. The principal point of employing additive manufacturing (AM) systems is to fabricate parts with arbitrary geometrical complexity with relatively minimal tooling cost and time. Selective laser sintering (SLS) and inkjet 3D printing (3DP) are two powerful and versatile AM techniques which are applicable to powder-based material systems. Hence, the latest state of knowledge available on the use of AM powder-based techniques in tissue engineering and their effect on mechanical and biological properties of fabricated tissues and scaffolds must be updated. Determining the effective setup of parameters, developing improved biocompatible/bioactive materials, and improving the mechanical/biological properties of laser sintered and 3D printed tissues are the three main concerns which have been investigated in this article. PMID:27877783

Mechanostimulation protocols for cardiac tissue engineering.

PubMed

Govoni, Marco; Muscari, Claudio; Guarnieri, Carlo; Giordano, Emanuele

2013-01-01

Owing to the inability of self-replacement by a damaged myocardium, alternative strategies to heart transplantation have been explored within the last decades and cardiac tissue engineering/regenerative medicine is among the present challenges in biomedical research. Hopefully, several studies witness the constant extension of the toolbox available to engineer a fully functional, contractile, and robust cardiac tissue using different combinations of cells, template bioscaffolds, and biophysical stimuli obtained by the use of specific bioreactors. Mechanical forces influence the growth and shape of every tissue in our body generating changes in intracellular biochemistry and gene expression. That is why bioreactors play a central role in the task of regenerating a complex tissue such as the myocardium. In the last fifteen years a large number of dynamic culture devices have been developed and many results have been collected. The aim of this brief review is to resume in a single streamlined paper the state of the art in this field.

Mechanostimulation Protocols for Cardiac Tissue Engineering

PubMed Central

Govoni, Marco; Muscari, Claudio; Guarnieri, Carlo; Giordano, Emanuele

2013-01-01

Owing to the inability of self-replacement by a damaged myocardium, alternative strategies to heart transplantation have been explored within the last decades and cardiac tissue engineering/regenerative medicine is among the present challenges in biomedical research. Hopefully, several studies witness the constant extension of the toolbox available to engineer a fully functional, contractile, and robust cardiac tissue using different combinations of cells, template bioscaffolds, and biophysical stimuli obtained by the use of specific bioreactors. Mechanical forces influence the growth and shape of every tissue in our body generating changes in intracellular biochemistry and gene expression. That is why bioreactors play a central role in the task of regenerating a complex tissue such as the myocardium. In the last fifteen years a large number of dynamic culture devices have been developed and many results have been collected. The aim of this brief review is to resume in a single streamlined paper the state of the art in this field. PMID:23936858

A review on powder-based additive manufacturing for tissue engineering: selective laser sintering and inkjet 3D printing.

PubMed

Shirazi, Seyed Farid Seyed; Gharehkhani, Samira; Mehrali, Mehdi; Yarmand, Hooman; Metselaar, Hendrik Simon Cornelis; Adib Kadri, Nahrizul; Osman, Noor Azuan Abu

2015-06-01

Since most starting materials for tissue engineering are in powder form, using powder-based additive manufacturing methods is attractive and practical. The principal point of employing additive manufacturing (AM) systems is to fabricate parts with arbitrary geometrical complexity with relatively minimal tooling cost and time. Selective laser sintering (SLS) and inkjet 3D printing (3DP) are two powerful and versatile AM techniques which are applicable to powder-based material systems. Hence, the latest state of knowledge available on the use of AM powder-based techniques in tissue engineering and their effect on mechanical and biological properties of fabricated tissues and scaffolds must be updated. Determining the effective setup of parameters, developing improved biocompatible/bioactive materials, and improving the mechanical/biological properties of laser sintered and 3D printed tissues are the three main concerns which have been investigated in this article.

A special issue on reviews in biomedical applications of nanomaterials, tissue engineering, stem cells, bioimaging, and toxicity.

PubMed

Nalwa, Hari Singh

2014-10-01

This second special issue of the Journal of Biomedical Nanotechnology in a series contains another 30 state-of-the-art reviews focused on the biomedical applications of nanomaterials, biosensors, bone tissue engineering, MRI and bioimaging, single-cell detection, stem cells, endothelial progenitor cells, toxicity and biosafety of nanodrugs, nanoparticle-based new therapeutic approaches for cancer, hepatic and cardiovascular disease.

Biomimetic Layer-by-Layer Self-Assembly of Nanofilms, Nanocoatings, and 3D Scaffolds for Tissue Engineering.

PubMed

Zhang, Shichao; Xing, Malcolm; Li, Bingyun

2018-06-01

Achieving surface design and control of biomaterial scaffolds with nanometer- or micrometer-scaled functional films is critical to mimic the unique features of native extracellular matrices, which has significant technological implications for tissue engineering including cell-seeded scaffolds, microbioreactors, cell assembly, tissue regeneration, etc. Compared with other techniques available for surface design, layer-by-layer (LbL) self-assembly technology has attracted extensive attention because of its integrated features of simplicity, versatility, and nanoscale control. Here we present a brief overview of current state-of-the-art research related to the LbL self-assembly technique and its assembled biomaterials as scaffolds for tissue engineering. An overview of the LbL self-assembly technique, with a focus on issues associated with distinct routes and driving forces of self-assembly, is described briefly. Then, we highlight the controllable fabrication, properties, and applications of LbL self-assembly biomaterials in the forms of multilayer nanofilms, scaffold nanocoatings, and three-dimensional scaffolds to systematically demonstrate advances in LbL self-assembly in the field of tissue engineering. LbL self-assembly not only provides advances for molecular deposition but also opens avenues for the design and development of innovative biomaterials for tissue engineering.

Cell and Tissue Engineering for Liver Disease

PubMed Central

Bhatia, Sangeeta N.; Underhill, Gregory H.; Zaret, Kenneth S.; Fox, Ira J.

2015-01-01

Despite the tremendous hurdles presented by the complexity of the liver’s structure and function, advances in liver physiology, stem cell biology and reprogramming, and the engineering of tissues and devices are accelerating the development of cell-based therapies for treating liver disease and liver failure. This State of the Art Review discusses both the near and long-term prospects for such cell-based therapies and the unique challenges for clinical translation. PMID:25031271

Spatial regulation of controlled bioactive factor delivery for bone tissue engineering

PubMed Central

Samorezov, Julia E.; Alsberg, Eben

2015-01-01

Limitations of current treatment options for critical size bone defects create a significant clinical need for tissue engineered bone strategies. This review describes how control over the spatiotemporal delivery of growth factors, nucleic acids, and drugs and small molecules may aid in recapitulating signals present in bone development and healing, regenerating interfaces of bone with other connective tissues, and enhancing vascularization of tissue engineered bone. State-of-the-art technologies used to create spatially controlled patterns of bioactive factors on the surfaces of materials, to build up 3D materials with patterns of signal presentation within their bulk, and to pattern bioactive factor delivery after scaffold fabrication are presented, highlighting their applications in bone tissue engineering. As these techniques improve in areas such as spatial resolution and speed of patterning, they will continue to grow in value as model systems for understanding cell responses to spatially regulated bioactive factor signal presentation in vitro, and as strategies to investigate the capacity of the defined spatial arrangement of these signals to drive bone regeneration in vivo. PMID:25445719

European research and commercialisation activities in the field of tissue engineering and liver support in world wide competition.

PubMed

Marx, U; Bushnaq, H; Yalcin, E

1998-02-01

Tissue engineering is seen as an interesting field of technology which could improve medical therapy and could also be considered as a commercial opportunity for the European biotechnological industry. Research in the state of the art of science using the MedLine and the Science Citation Index databases, in the patent situation and of the industry dealing with tissue engineering was done. A special method, based on the Science Citation Index Journal Citation Report 1993, for evaluating scientific work was defined. The main countries working in the field of tissue engineering were evaluated in regard to their scientific performance and their patents. The R&D of German industry was investigated as an exemplary European country. Out of all activities, different tissues were rated with respect to the attention received from research and industry and with regard to the frequency in which patents were applied for. USA, Germany and Japan rank first in most tissues, especially liver. After comparing German patents with the German scientific and industrial work, it seems that the potential in German patents and research is underestimated by German industry and inefficiently exploited.

Engineering complex orthopaedic tissues via strategic biomimicry.

PubMed

Qu, Dovina; Mosher, Christopher Z; Boushell, Margaret K; Lu, Helen H

2015-03-01

The primary current challenge in regenerative engineering resides in the simultaneous formation of more than one type of tissue, as well as their functional assembly into complex tissues or organ systems. Tissue-tissue synchrony is especially important in the musculoskeletal system, wherein overall organ function is enabled by the seamless integration of bone with soft tissues such as ligament, tendon, or cartilage, as well as the integration of muscle with tendon. Therefore, in lieu of a traditional single-tissue system (e.g., bone, ligament), composite tissue scaffold designs for the regeneration of functional connective tissue units (e.g., bone-ligament-bone) are being actively investigated. Closely related is the effort to re-establish tissue-tissue interfaces, which is essential for joining these tissue building blocks and facilitating host integration. Much of the research at the forefront of the field has centered on bioinspired stratified or gradient scaffold designs which aim to recapitulate the structural and compositional inhomogeneity inherent across distinct tissue regions. As such, given the complexity of these musculoskeletal tissue units, the key question is how to identify the most relevant parameters for recapitulating the native structure-function relationships in the scaffold design. Therefore, the focus of this review, in addition to presenting the state-of-the-art in complex scaffold design, is to explore how strategic biomimicry can be applied in engineering tissue connectivity. The objective of strategic biomimicry is to avoid over-engineering by establishing what needs to be learned from nature and defining the essential matrix characteristics that must be reproduced in scaffold design. Application of this engineering strategy for the regeneration of the most common musculoskeletal tissue units (e.g., bone-ligament-bone, muscle-tendon-bone, cartilage-bone) will be discussed in this review. It is anticipated that these exciting efforts will enable integrative and functional repair of soft tissue injuries, and moreover, lay the foundation for the development of composite tissue systems and ultimately, total limb or joint regeneration.

Engineering Complex Orthopaedic Tissues via Strategic Biomimicry

PubMed Central

Qu, Dovina; Mosher, Christopher Z.; Boushell, Margaret K.; Lu, Helen H.

2014-01-01

The primary current challenge in regenerative engineering resides in the simultaneous formation of more than one type of tissue, as well as their functional assembly into complex tissues or organ systems. Tissue-tissue synchrony is especially important in the musculoskeletal system, whereby overall organ function is enabled by the seamless integration of bone with soft tissues such as ligament, tendon, or cartilage, as well as the integration of muscle with tendon. Therefore, in lieu of a traditional single-tissue system (e.g. bone, ligament), composite tissue scaffold designs for the regeneration of functional connective tissue units (e.g. bone-ligament-bone) are being actively investigated. Closely related is the effort to re-establish tissue-tissue interfaces, which is essential for joining these tissue building blocks and facilitating host integration. Much of the research at the forefront of the field has centered on bioinspired stratified or gradient scaffold designs which aim to recapitulate the structural and compositional inhomogeneity inherent across distinct tissue regions. As such, given the complexity of these musculoskeletal tissue units, the key question is how to identify the most relevant parameters for recapitulating the native structure-function relationships in the scaffold design. Therefore, the focus of this review, in addition to presenting the state-of-the-art in complex scaffold design, is to explore how strategic biomimicry can be applied in engineering tissue connectivity. The objective of strategic biomimicry is to avoid over-engineering by establishing what needs to be learned from nature and defining the essential matrix characteristics that must be reproduced in scaffold design. Application of this engineering strategy for the regeneration of the most common musculoskeletal tissue units (e.g. bone-ligament-bone, muscle-tendon-bone, cartilage-bone) will be discussed in this review. It is anticipated that these exciting efforts will enable integrative and functional repair of soft tissue injuries, and moreover, lay the foundation for the development of composite tissue systems and ultimately, total limb or joint regeneration. PMID:25465616

Nanofiber Scaffold-Based Tissue-Engineered Retinal Pigment Epithelium to Treat Degenerative Eye Diseases

PubMed Central

Khristov, Vladimir; Wan, Qin; Sharma, Ruchi; Jha, Balendu Shekhar; Lotfi, Mostafa; Maminishkis, Arvydas; Simon, Carl G.

2016-01-01

Abstract Clinical-grade manufacturing of a functional retinal pigment epithelium (RPE) monolayer requires reproducing, as closely as possible, the natural environment in which RPE grows. In vitro, this can be achieved by a tissue engineering approach, in which the RPE is grown on a nanofibrous biological or synthetic scaffold. Recent research has shown that nanofiber scaffolds perform better for cell growth and transplantability compared with their membrane counterparts and that the success of the scaffold in promoting cell growth/function is not heavily material dependent. With these strides, the field has advanced enough to begin to consider implementation of one, or a combination, of the tissue engineering strategies discussed herein. In this study, we review the current state of tissue engineering research for in vitro culture of RPE/scaffolds and the parameters for optimal scaffold design that have been uncovered during this research. Next, we discuss production methods and manufacturers that are capable of producing the nanofiber scaffolds in such a way that would be biologically, regulatory, clinically, and commercially viable. Then, a discussion of how the scaffolds could be characterized, both morphologically and mechanically, to develop a testing process that is viable for regulatory screening is performed. Finally, an example of a tissue-engineered RPE/scaffold construct is given to provide the reader a framework for understanding how these pieces could fit together to develop a tissue-engineered RPE/scaffold construct that could pass regulatory scrutiny and can be commercially successful. PMID:27110730

An improved method of renal tissue engineering, by combining renal dissociation and reaggregation with a low-volume culture technique, results in development of engineered kidneys complete with loops of Henle.

PubMed

Chang, C-Hong; Davies, Jamie A

2012-01-01

Tissue engineering of functional kidney tissue is an important goal for clinical restoration of renal function in patients damaged by infectious, toxicological, or genetic disease. One promising approach is the use of the self-organizing abilities of embryonic kidney cells to arrange themselves, from a simply reaggregated cell suspension, into engineered organs similar to fetal kidneys. The previous state-of-the-art method for this results in the formation of a branched collecting duct tree, immature nephrons (S-shaped bodies) beside and connected to it, and supportive stroma. It does not, though, result in the significant formation of morphologically detectable loops of Henle - anatomical features of the nephron that are critical to physiological function. We have combined the best existing technique for renal tissue engineering from cell suspensions with a low-volume culture technique that allows intact kidney rudiments to make loops of Henle to test whether engineered kidneys can produce these loops. The result is the formation of loops of Henle in engineered cultured 'fetal kidneys', very similar in both morphology and in number to those formed by intact organ rudiments. This brings the engineering technique one important step closer to production of a fully realistic organ. Copyright © 2012 S. Karger AG, Basel.

Temporomandibular Joint Disorders: A Review of Etiology, Clinical Management, and Tissue Engineering Strategies

PubMed Central

Murphy, Meghan K.; MacBarb, Regina F.; Wong, Mark E.; Athanasiou, Kyriacos A.

2015-01-01

Epidemiology reports state temporomandibular joint disorders (TMD) affect up to 25% of the population, yet their etiology and progression are poorly understood. As a result, treatment options are limited and fail to meet the long-term demands of the relatively young patient population. TMD are a class of degenerative musculoskeletal conditions associated with morphological and functional deformities. In up to 70% of cases, TMD are accompanied by malpositioning of the TMJ disc, termed “internal derangement.” Though onset is not well characterized, correlations between internal derangement and osteoarthritic change have been identified. Due to the complex and unique nature of each TMD case, diagnosis requires patient-specific analysis accompanied by various diagnostic modalities. Likewise, treatment requires customized plans to address the specific characteristics of each patient’s disease. In the mechanically demanding and biochemically active environment of the TMJ, therapeutic approaches capable of restoring joint functionality while responding to changes in the joint have become a necessity. Capable of integration and adaptation in the TMJ, one such approach, tissue engineering, carries significant potential in the development of repair and replacement tissues. The following review presents a synopsis of etiology, current treatment methods, and the future of tissue engineering for repairing and/or replacing diseased joint components, specifically the mandibular condyle and TMJ disc. Preceding the current trends in tissue engineering is an analysis of native tissue characterization, toward identifying tissue engineering objectives and validation metrics for restoring healthy and functional structures of the TMJ. PMID:24278954

40 CFR 52.1870 - Identification of plan.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Chemical Corporation in Allen County, Crystal Tissue Company in Butler County, U.S. Steel Corporation.... (81) On March 3, 1986, the Ohio Environmental Protection Agency (OEPA) submitted Good Engineering... Engineering Practice Stack Height Regulations”. These rules were adopted by the State on February 12, 1986 and...

Periodontics--tissue engineering and the future.

PubMed

Douglass, Gordon L

2005-03-01

Periodontics has a long history of utilizing advances in science to expand and improve periodontal therapies. Recently the American Academy of Periodontology published the findings of the Contemporary Science Workshop, which conducted state-of-the-art evidence-based reviews of current and emerging areas in periodontics. The findings of this workshop provide the basis for an evidence-based approach to periodontal therapy. While the workshop evaluated all areas of periodontics, it is in the area of tissue engineering that the most exciting advances are becoming a reality.

[Supervision, administration and standard research related to tissue engineered medical products].

PubMed

Xi, Ting-fei; Chen, Liang; Zhao, Peng

2003-11-01

Tissue engineering advance in supplying the reparative and reconstructive medicine with promising tissue engineered medical products(TEMPs) and the new therapy alternative. The related supervision and administration of TEMPs is being developed and the standard research of TEMPs is also in progress. The Food and Drug Administration(FDA) of the United States has treated TEMPs as combined products and supervised them according to the level of risk to patients. Lately, FDA has determined that the Center for Devices and Radiological Health (CDRH) should take charge of examination and approval of TEMPs, with the cooperation of the Center for Biological Evaluations and Research(CBER). The regulatory controls have been established respectively in European Union and Japan. In China, TEMPs are identified as medical devices combined with cells. The Department of Medical Device of the State Food and Drug Administration (SFDA) is responsible for the examination and approval of TEMPs, and National Institute for the Control of Pharmaceutical & Biological Products(NICPBP) is responsible for evaluation tests. The standards of TEMPs are formulated mainly by the American Society of Testing Materials(ASTM) and International Standardization Organization(ISO).

Bone tissue engineering: state of the art and future trends.

PubMed

Salgado, António J; Coutinho, Olga P; Reis, Rui L

2004-08-09

Although several major progresses have been introduced in the field of bone regenerative medicine during the years, current therapies, such as bone grafts, still have many limitations. Moreover, and in spite of the fact that material science technology has resulted in clear improvements in the field of bone substitution medicine, no adequate bone substitute has been developed and hence large bone defects/injuries still represent a major challenge for orthopaedic and reconstructive surgeons. It is in this context that TE has been emerging as a valid approach to the current therapies for bone regeneration/substitution. In contrast to classic biomaterial approach, TE is based on the understanding of tissue formation and regeneration, and aims to induce new functional tissues, rather than just to implant new spare parts. The present review pretends to give an exhaustive overview on all components needed for making bone tissue engineering a successful therapy. It begins by giving the reader a brief background on bone biology, followed by an exhaustive description of all the relevant components on bone TE, going from materials to scaffolds and from cells to tissue engineering strategies, that will lead to "engineered" bone. Scaffolds processed by using a methodology based on extrusion with blowing agents.

Bone Regeneration Based on Tissue Engineering Conceptions — A 21st Century Perspective

PubMed Central

Henkel, Jan; Woodruff, Maria A.; Epari, Devakara R.; Steck, Roland; Glatt, Vaida; Dickinson, Ian C.; Choong, Peter F. M.; Schuetz, Michael A.; Hutmacher, Dietmar W.

2013-01-01

The role of Bone Tissue Engineering in the field of Regenerative Medicine has been the topic of substantial research over the past two decades. Technological advances have improved orthopaedic implants and surgical techniques for bone reconstruction. However, improvements in surgical techniques to reconstruct bone have been limited by the paucity of autologous materials available and donor site morbidity. Recent advances in the development of biomaterials have provided attractive alternatives to bone grafting expanding the surgical options for restoring the form and function of injured bone. Specifically, novel bioactive (second generation) biomaterials have been developed that are characterised by controlled action and reaction to the host tissue environment, whilst exhibiting controlled chemical breakdown and resorption with an ultimate replacement by regenerating tissue. Future generations of biomaterials (third generation) are designed to be not only osteoconductive but also osteoinductive, i.e. to stimulate regeneration of host tissues by combining tissue engineering and in situ tissue regeneration methods with a focus on novel applications. These techniques will lead to novel possibilities for tissue regeneration and repair. At present, tissue engineered constructs that may find future use as bone grafts for complex skeletal defects, whether from post-traumatic, degenerative, neoplastic or congenital/developmental “origin” require osseous reconstruction to ensure structural and functional integrity. Engineering functional bone using combinations of cells, scaffolds and bioactive factors is a promising strategy and a particular feature for future development in the area of hybrid materials which are able to exhibit suitable biomimetic and mechanical properties. This review will discuss the state of the art in this field and what we can expect from future generations of bone regeneration concepts. PMID:26273505

State-of-the-Art Review of 3D Bioprinting for Cardiovascular Tissue Engineering.

PubMed

Duan, Bin

2017-01-01

3D bioprinting is a group of rapidly growing techniques that allows building engineered tissue constructs with complex and hierarchical structures, mechanical and biological heterogeneity. It enables implementation of various bioinks through different printing mechanisms and precise deposition of cell and/or biomolecule laden biomaterials in predefined locations. This review briefly summarizes applicable bioink materials and various bioprinting techniques, and presents the recent advances in bioprinting of cardiovascular tissues, with focusing on vascularized constructs, myocardium and heart valve conduits. Current challenges and further perspectives are also discussed to help guide the bioink and bioprinter development, improve bioprinting strategies and direct future organ bioprinting and translational applications.

Biomimetic tissue-engineered anterior cruciate ligament replacement

PubMed Central

Cooper, James A.; Sahota, Janmeet S.; Gorum, W. Jay; Carter, Janell; Doty, Stephen B.; Laurencin, Cato T.

2007-01-01

There are >200,000 anterior cruciate ligament (ACL) ruptures each year in the United States, and, due to the poor healing properties of the ACL, surgical reconstruction with autograft or allograft tissue is the current treatment of these injuries. To regenerate the ACL, the ideal matrix should be biodegradable, porous, and exhibit sufficient mechanical strength to allow formation of neoligament tissue. Researchers have developed ACL scaffolds with collagen fibers, silk, biodegradable polymers, and composites with limited success. Our group has developed a biomimetic ligament replacement by using 3D braiding technology. In this preliminary in vivo rabbit model study for ACL reconstruction, the histological and mechanical evaluation demonstrated excellent healing and regeneration with our cell-seeded, tissue-engineered ligament replacement. PMID:17360607

Scaffolds for Bone Tissue Engineering: State of the art and new perspectives.

PubMed

Roseti, Livia; Parisi, Valentina; Petretta, Mauro; Cavallo, Carola; Desando, Giovanna; Bartolotti, Isabella; Grigolo, Brunella

2017-09-01

This review is intended to give a state of the art description of scaffold-based strategies utilized in Bone Tissue Engineering. Numerous scaffolds have been tested in the orthopedic field with the aim of improving cell viability, attachment, proliferation and homing, osteogenic differentiation, vascularization, host integration and load bearing. The main traits that characterize a scaffold suitable for bone regeneration concerning its biological requirements, structural features, composition, and types of fabrication are described in detail. Attention is then focused on conventional and Rapid Prototyping scaffold manufacturing techniques. Conventional manufacturing approaches are subtractive methods where parts of the material are removed from an initial block to achieve the desired shape. Rapid Prototyping techniques, introduced to overcome standard techniques limitations, are additive fabrication processes that manufacture the final three-dimensional object via deposition of overlying layers. An important improvement is the possibility to create custom-made products by means of computer assisted technologies, starting from patient's medical images. As a conclusion, it is highlighted that, despite its encouraging results, the clinical approach of Bone Tissue Engineering has not taken place on a large scale yet, due to the need of more in depth studies, its high manufacturing costs and the difficulty to obtain regulatory approval. PUBMED search terms utilized to write this review were: "Bone Tissue Engineering", "regenerative medicine", "bioactive scaffolds", "biomimetic scaffolds", "3D printing", "3D bioprinting", "vascularization" and "dentistry". Copyright © 2017 Elsevier B.V. All rights reserved.

[Micro/nano-engineering to control growth of neuronal cells and tissue engineering applied to the central nervous system].

PubMed

Béduer, Amélie; Vaysse, Laurence; Loubinoux, Isabelle; Vieu, Christophe

2013-01-01

Central nervous system pathologies are often characterized by the loss of cell populations. A promising therapy now being developed consists in using bioactive materials, associating grafted cells to biopolymers which provide a scaffold for the in vitro building of new tissues, to be implanted in vivo. In the present article, the state of the art of this field, at crossroads between microtechnology and neuroscience, is described in detail; thereafter our own approach and results about interactions between adult human neural stem cells and microstructured polymers are summarized and discussed. In a second part, some central nervous system repair strategies, based on cerebral tissue engineering, are presented. We will report the main results of our studies to work out and characterize in vivo a cerebral bioprosthesis. © Société de Biologie, 2014.

Analytic Models of Oxygen and Nutrient Diffusion, Metabolism Dynamics, and Architecture Optimization in Three-Dimensional Tissue Constructs with Applications and Insights in Cerebral Organoids

PubMed Central

2016-01-01

Diffusion models are important in tissue engineering as they enable an understanding of gas, nutrient, and signaling molecule delivery to cells in cell cultures and tissue constructs. As three-dimensional (3D) tissue constructs become larger, more intricate, and more clinically applicable, it will be essential to understand internal dynamics and signaling molecule concentrations throughout the tissue and whether cells are receiving appropriate nutrient delivery. Diffusion characteristics present a significant limitation in many engineered tissues, particularly for avascular tissues and for cells whose viability, differentiation, or function are affected by concentrations of oxygen and nutrients. This article seeks to provide novel analytic solutions for certain cases of steady-state and nonsteady-state diffusion and metabolism in basic 3D construct designs (planar, cylindrical, and spherical forms), solutions that would otherwise require mathematical approximations achieved through numerical methods. This model is applied to cerebral organoids, where it is shown that limitations in diffusion and organoid size can be partially overcome by localizing metabolically active cells to an outer layer in a sphere, a regionalization process that is known to occur through neuroglial precursor migration both in organoids and in early brain development. The given prototypical solutions include a review of metabolic information for many cell types and can be broadly applied to many forms of tissue constructs. This work enables researchers to model oxygen and nutrient delivery to cells, predict cell viability, study dynamics of mass transport in 3D tissue constructs, design constructs with improved diffusion capabilities, and accurately control molecular concentrations in tissue constructs that may be used in studying models of development and disease or for conditioning cells to enhance survival after insults like ischemia or implantation into the body, thereby providing a framework for better understanding and exploring the characteristics and behaviors of engineered tissue constructs. PMID:26650970

Engineering hydrogels as extracellular matrix mimics

PubMed Central

Geckil, Hikmet; Xu, Feng; Zhang, Xiaohui; Moon, SangJun

2010-01-01

Extracellular matrix (ECM) is a complex cellular environment consisting of proteins, proteoglycans, and other soluble molecules. ECM provides structural support to mammalian cells and a regulatory milieu with a variety of important cell functions, including assembling cells into various tissues and organs, regulating growth and cell–cell communication. Developing a tailored in vitro cell culture environment that mimics the intricate and organized nanoscale meshwork of native ECM is desirable. Recent studies have shown the potential of hydrogels to mimic native ECM. Such an engineered native-like ECM is more likely to provide cells with rational cues for diagnostic and therapeutic studies. The research for novel biomaterials has led to an extension of the scope and techniques used to fabricate biomimetic hydrogel scaffolds for tissue engineering and regenerative medicine applications. In this article, we detail the progress of the current state-of-the-art engineering methods to create cell-encapsulating hydrogel tissue constructs as well as their applications in in vitro models in biomedicine. PMID:20394538

3D Printing of Personalized Organs and Tissues

NASA Astrophysics Data System (ADS)

Ye, Kaiming

2015-03-01

Authors: Kaiming Ye and Sha Jin, Department of Biomedical Engineering, Watson School of Engineering and Applied Science, Binghamton University, State University of New York, Binghamton, NY 13902-6000 Abstract: Creation of highly organized multicellular constructs, including tissues and organs or organoids, will revolutionize tissue engineering and regenerative medicine. The development of these technologies will enable the production of individualized organs or tissues for patient-tailored organ transplantation or cell-based therapy. For instance, a patient with damaged myocardial tissues due to an ischemic event can receive a myocardial transplant generated using the patient's own induced pluripotent stem cells (iPSCs). Likewise, a type-1 diabetic patient can be treated with lab-generated islets to restore his or her physiological insulin secretion capability. These lab-produced, high order tissues or organs can also serve as disease models for pathophysiological study and drug screening. The remarkable advances in stem cell biology, tissue engineering, microfabrication, and materials science in the last decade suggest the feasibility of generating these tissues and organoids in the laboratory. Nevertheless, major challenges still exist. One of the critical challenges that we still face today is the difficulty in constructing or fabricating multicellular assemblies that recapitulate in vivo microenvironments essential for controlling cell proliferation, migration, differentiation, maturation and assembly into a biologically functional tissue or organoid structure. These challenges can be addressed through developing 3D organ and tissue printing which enables organizing and assembling cells into desired tissue and organ structures. We have shown that human pluripotent stem cells differentiated in 3D environments are mature and possess high degree of biological function necessary for them to function in vivo.

Biomimetic engineered muscle with capacity for vascular integration and functional maturation in vivo

PubMed Central

Juhas, Mark; Engelmayr, George C.; Fontanella, Andrew N.; Palmer, Gregory M.; Bursac, Nenad

2014-01-01

Tissue-engineered skeletal muscle can serve as a physiological model of natural muscle and a potential therapeutic vehicle for rapid repair of severe muscle loss and injury. Here, we describe a platform for engineering and testing highly functional biomimetic muscle tissues with a resident satellite cell niche and capacity for robust myogenesis and self-regeneration in vitro. Using a mouse dorsal window implantation model and transduction with fluorescent intracellular calcium indicator, GCaMP3, we nondestructively monitored, in real time, vascular integration and the functional state of engineered muscle in vivo. During a 2-wk period, implanted engineered muscle exhibited a steady ingrowth of blood-perfused microvasculature along with an increase in amplitude of calcium transients and force of contraction. We also demonstrated superior structural organization, vascularization, and contractile function of fully differentiated vs. undifferentiated engineered muscle implants. The described in vitro and in vivo models of biomimetic engineered muscle represent enabling technology for novel studies of skeletal muscle function and regeneration. PMID:24706792

A Bioreactor to Identify the Driving Mechanical Stimuli of Tissue Growth and Remodeling.

PubMed

van Kelle, Mathieu A J; Oomen, Pim J A; Bulsink, Jurgen A; Janssen-van den Broek, Marloes W J T; Lopata, Richard G P; Rutten, Marcel C M; Loerakker, Sandra; Bouten, Carlijn V C

2017-06-01

Tissue growth and remodeling are essential processes that should ensure long-term functionality of tissue-engineered (TE) constructs. Even though it is widely recognized that these processes strongly depend on mechanical stimuli, the underlying mechanisms of mechanically induced growth and remodeling are only partially understood. It is generally accepted that cells sense mechanical changes and respond by altering their surroundings, by means of extracellular matrix growth and remodeling, in an attempt to return to a certain preferred mechanical homeostatic state. However, the exact mechanical cues that trigger cells to synthesize and remodel their environment remain unclear. To identify the driving mechanical stimuli of these processes, it is critical to be able to temporarily follow the mechanical state of developing tissues under physiological loading conditions. Therefore, a novel "versatile tissue growth and remodeling" (Vertigro) bioreactor was developed that is capable of tissue culture and mechanical stimulation for a prolonged time period, while simultaneously performing mechanical testing. The Vertigro's unique two-chamber design allows easy, sterile handling of circular 3D TE constructs in a dedicated culture chamber, while a separate pressure chamber facilitates a pressure-driven dynamic loading regime during culture. As a proof-of-concept, temporal changes in the mechanical state of cultured tissues were quantified using nondestructive mechanical testing by means of a classical bulge test, in which the tissue displacement was tracked using ultrasound imaging. To demonstrate the successful development of the bioreactor system, compositional, structural, and geometrical changes were qualitatively and quantitatively assessed using a series of standard analysis techniques. With this bioreactor and associated mechanical analysis technique, a powerful toolbox has been developed to quantitatively study and identify the driving mechanical stimuli of engineered tissue growth and remodeling.

Protein Corona Influences Cell-Biomaterial Interactions in Nanostructured Tissue Engineering Scaffolds.

PubMed

Serpooshan, Vahid; Mahmoudi, Morteza; Zhao, Mingming; Wei, Ke; Sivanesan, Senthilkumar; Motamedchaboki, Khatereh; Malkovskiy, Andrey V; Gladstone, Andrew B; Cohen, Jeffrey E; Yang, Phillip C; Rajadas, Jayakumar; Bernstein, Daniel; Woo, Y Joseph; Ruiz-Lozano, Pilar

2015-07-22

Biomaterials are extensively used to restore damaged tissues, in the forms of implants (e.g. tissue engineered scaffolds) or biomedical devices (e.g. pacemakers). Once in contact with the physiological environment, nanostructured biomaterials undergo modifications as a result of endogenous proteins binding to their surface. The formation of this macromolecular coating complex, known as 'protein corona', onto the surface of nanoparticles and its effect on cell-particle interactions are currently under intense investigation. In striking contrast, protein corona constructs within nanostructured porous tissue engineering scaffolds remain poorly characterized. As organismal systems are highly dynamic, it is conceivable that the formation of distinct protein corona on implanted scaffolds might itself modulate cell-extracellular matrix interactions. Here, we report that corona complexes formed onto the fibrils of engineered collagen scaffolds display specific, distinct, and reproducible compositions that are a signature of the tissue microenvironment as well as being indicative of the subject's health condition. Protein corona formed on collagen matrices modulated cellular secretome in a context-specific manner ex-vivo , demonstrating their role in regulating scaffold-cellular interactions. Together, these findings underscore the importance of custom-designing personalized nanostructured biomaterials, according to the biological milieu and disease state. We propose the use of protein corona as in situ biosensor of temporal and local biomarkers.

Structural and material approaches to bone tissue engineering in powder-based three-dimensional printing.

PubMed

Butscher, A; Bohner, M; Hofmann, S; Gauckler, L; Müller, R

2011-03-01

This article reviews the current state of knowledge concerning the use of powder-based three-dimensional printing (3DP) for the synthesis of bone tissue engineering scaffolds. 3DP is a solid free-form fabrication (SFF) technique building up complex open porous 3D structures layer by layer (a bottom-up approach). In contrast to traditional fabrication techniques generally subtracting material step by step (a top-down approach), SFF approaches allow nearly unlimited designs and a large variety of materials to be used for scaffold engineering. Today's state of the art materials, as well as the mechanical and structural requirements for bone scaffolds, are summarized and discussed in relation to the technical feasibility of their use in 3DP. Advances in the field of 3DP are presented and compared with other SFF methods. Existing strategies on material and design control of scaffolds are reviewed. Finally, the possibilities and limiting factors are addressed and potential strategies to improve 3DP for scaffold engineering are proposed. Copyright © 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Continuum theory of fibrous tissue damage mechanics using bond kinetics: application to cartilage tissue engineering.

PubMed

Nims, Robert J; Durney, Krista M; Cigan, Alexander D; Dusséaux, Antoine; Hung, Clark T; Ateshian, Gerard A

2016-02-06

This study presents a damage mechanics framework that employs observable state variables to describe damage in isotropic or anisotropic fibrous tissues. In this mixture theory framework, damage is tracked by the mass fraction of bonds that have broken. Anisotropic damage is subsumed in the assumption that multiple bond species may coexist in a material, each having its own damage behaviour. This approach recovers the classical damage mechanics formulation for isotropic materials, but does not appeal to a tensorial damage measure for anisotropic materials. In contrast with the classical approach, the use of observable state variables for damage allows direct comparison of model predictions to experimental damage measures, such as biochemical assays or Raman spectroscopy. Investigations of damage in discrete fibre distributions demonstrate that the resilience to damage increases with the number of fibre bundles; idealizing fibrous tissues using continuous fibre distribution models precludes the modelling of damage. This damage framework was used to test and validate the hypothesis that growth of cartilage constructs can lead to damage of the synthesized collagen matrix due to excessive swelling caused by synthesized glycosaminoglycans. Therefore, alternative strategies must be implemented in tissue engineering studies to prevent collagen damage during the growth process.

Continuum theory of fibrous tissue damage mechanics using bond kinetics: application to cartilage tissue engineering

PubMed Central

Nims, Robert J.; Durney, Krista M.; Cigan, Alexander D.; Hung, Clark T.; Ateshian, Gerard A.

2016-01-01

This study presents a damage mechanics framework that employs observable state variables to describe damage in isotropic or anisotropic fibrous tissues. In this mixture theory framework, damage is tracked by the mass fraction of bonds that have broken. Anisotropic damage is subsumed in the assumption that multiple bond species may coexist in a material, each having its own damage behaviour. This approach recovers the classical damage mechanics formulation for isotropic materials, but does not appeal to a tensorial damage measure for anisotropic materials. In contrast with the classical approach, the use of observable state variables for damage allows direct comparison of model predictions to experimental damage measures, such as biochemical assays or Raman spectroscopy. Investigations of damage in discrete fibre distributions demonstrate that the resilience to damage increases with the number of fibre bundles; idealizing fibrous tissues using continuous fibre distribution models precludes the modelling of damage. This damage framework was used to test and validate the hypothesis that growth of cartilage constructs can lead to damage of the synthesized collagen matrix due to excessive swelling caused by synthesized glycosaminoglycans. Therefore, alternative strategies must be implemented in tissue engineering studies to prevent collagen damage during the growth process. PMID:26855751

Heparin Stimulates Elastogenesis: Application to Silk-Based Vascular Grafts

PubMed Central

Baughman, Cassandra; Kaplan, David L.; Castellot, John J.

2013-01-01

With over 500,000 coronary artery bypass grafts (CABG) performed annually in the United States alone, there is a significant clinical need for a small diameter tissue engineered vascular graft. A principle goal in tissue engineering is to develop materials and growth conditions that encourage appropriate re-cellularization and extracellular matrix formation in vivo. A particular challenge in vascular tissue engineering results from the inability of adult cells to produce elastin, as its expression is developmentally limited. We investigated factors to stimulate elastogenesis in vitro, and found that heparin treatment of adult human vascular smooth muscle cells promoted the formation of elastic fibers. This effect was heparin-specific, and dependent on cell density and growth state. We then applied this information to a silk-based construct, and found that immobilized heparin showed essentially identical biological effects to that of soluble heparin. These findings indicate that heparinized vascular grafts may promote elastin formation and regulate restenosis, in addition to heparin’s well-established antithrombotic properties. Given the increase in elastin mRNA level and the increase in extracellular elastin present, our data suggests that there may be multiple levels of elastin regulation that are mediated by heparin treatment. PMID:21600981

Stem Cells for Cardiac Regeneration by Cell Therapy and Myocardial Tissue Engineering

NASA Astrophysics Data System (ADS)

Wu, Jun; Zeng, Faquan; Weisel, Richard D.; Li, Ren-Ke

Congestive heart failure, which often occurs progressively following a myocardial infarction, is characterized by impaired myocardial perfusion, ventricular dilatation, and cardiac dysfunction. Novel treatments are required to reverse these effects - especially in older patients whose endogenous regenerative responses to currently available therapies are limited by age. This review explores the current state of research for two related approaches to cardiac regeneration: cell therapy and tissue engineering. First, to evaluate cell therapy, we review the effectiveness of various cell types for their ability to limit ventricular dilatation and promote functional recovery following implantation into a damaged heart. Next, to assess tissue engineering, we discuss the characteristics of several biomaterials for their potential to physically support the infarcted myocardium and promote implanted cell survival following cardiac injury. Finally, looking ahead, we present recent findings suggesting that hybrid constructs combining a biomaterial with stem and supporting cells may be the most effective approaches to cardiac regeneration.

Superelastic, superabsorbent and 3D nanofiber-assembled scaffold for tissue engineering.

PubMed

Chen, Weiming; Ma, Jun; Zhu, Lei; Morsi, Yosry; -Ei-Hamshary, Hany; Al-Deyab, Salem S; Mo, Xiumei

2016-06-01

Fabrication of 3D scaffold to mimic the nanofibrous structure of the nature extracellular matrix (ECM) with appropriate mechanical properties and excellent biocompatibility, remain an important technical challenge in tissue engineering. The present study reports the strategy to fabricate a 3D nanofibrous scaffold with similar structure to collagen in ECM by combining electrospinning and freeze-drying technique. With the technique reported here, a nanofibrous structure scaffold with hydrophilic and superabsorbent properties can be readily prepared by Gelatin and Polylactic acid (PLA). In wet state the scaffold also shows a super-elastic property, which could bear a compressive strain as high as 80% and recovers its original shape afterwards. Moreover, after 6 days of culture, L-929 cells grow, proliferate and infiltrated into the scaffold. The results suggest that this 3D nanofibrous scaffold would be promising for varied field of tissue engineering application. Copyright © 2016 Elsevier B.V. All rights reserved.

Making microenvironments: A look into incorporating macromolecular crowding into in vitro experiments, to generate biomimetic microenvironments which are capable of directing cell function for tissue engineering applications.

PubMed

Benny, Paula; Raghunath, Michael

2017-01-01

Biomimetic microenvironments are key components to successful cell culture and tissue engineering in vitro. One of the most accurate biomimetic microenvironments is that made by the cells themselves. Cell-made microenvironments are most similar to the in vivo state as they are cell-specific and produced by the actual cells which reside in that specific microenvironment. However, cell-made microenvironments have been challenging to re-create in vitro due to the lack of extracellular matrix composition, volume and complexity which are required. By applying macromolecular crowding to current cell culture protocols, cell-made microenvironments, or cell-derived matrices, can be generated at significant rates in vitro. In this review, we will examine the causes and effects of macromolecular crowding and how it has been applied in several in vitro systems including tissue engineering.

Regenerative endodontics: a state of the art.

PubMed

Bansal, Rashmi; Bansal, Rajesh

2011-01-01

Scientific advances in the creation of restorative biomaterials, in vitro cell culture technology, tissue grafting, tissue engineering, molecular biology and the human genome project provide the basis for the introduction of new technologies into dentistry. Non-vital infected teeth have long been treated with root canal therapy (for mature root apex) and apexification (for immature root apex), or doomed to extraction. Although successful, current treatments fail to re-establish healthy pulp tissue in these teeth. But, what if the non-vital tooth could be made vital once again? That is the hope offered by regenerative endodontics, an emerging field focused on replacing traumatized and diseased pulp with functional pulp tissue. Restoration of vitality of non-vital tooth is based on tissue engineering and revascularization procedures. The purpose of this article is to review these biological procedures and the hurdles that must be overcome to develop regenerative endodontic procedures.

Review of vascularised bone tissue-engineering strategies with a focus on co-culture systems.

PubMed

Liu, Yuchun; Chan, Jerry K Y; Teoh, Swee-Hin

2015-02-01

Poor angiogenesis within tissue-engineered grafts has been identified as a main challenge limiting the clinical introduction of bone tissue-engineering (BTE) approaches for the repair of large bone defects. Thick BTE grafts often exhibit poor cellular viability particularly at the core, leading to graft failure and lack of integration with host tissues. Various BTE approaches have been explored for improving vascularisation in tissue-engineered constructs and are briefly discussed in this review. Recent investigations relating to co-culture systems of endothelial and osteoblast-like cells have shown evidence of BTE efficacy in increasing vascularization in thick constructs. This review provides an overview of key concepts related to bone formation and then focuses on the current state of engineered vascularized co-culture systems using bone repair as a model. It will also address key questions regarding the generation of clinically relevant vascularized bone constructs as well as potential directions and considerations for research with the objective of pursuing engineered co-culture systems in other disciplines of vascularized regenerative medicine. The final objective is to generate serious and functional long-lasting vessels for sustainable angiogenesis that will enable enhanced cellular survival within thick voluminous bone grafts, thereby aiding in bone formation and remodelling in the long term. However, more evidence about the quality of blood vessels formed and its associated functional improvement in bone formation as well as a mechanistic understanding of their interactions are necessary for designing better therapeutic strategies for translation to clinical settings. Copyright © 2012 John Wiley & Sons, Ltd.

Bone mechanobiology, gravity and tissue engineering: effects and insights.

PubMed

Ruggiu, Alessandra; Cancedda, Ranieri

2015-12-01

Bone homeostasis strongly depends on fine tuned mechanosensitive regulation signals from environmental forces into biochemical responses. Similar to the ageing process, during spaceflights an altered mechanotransduction occurs as a result of the effects of bone unloading, eventually leading to loss of functional tissue. Although spaceflights represent the best environment to investigate near-zero gravity effects, there are major limitations for setting up experimental analysis. A more feasible approach to analyse the effects of reduced mechanostimulation on the bone is represented by the 'simulated microgravity' experiments based on: (1) in vitro studies, involving cell cultures studies and the use of bioreactors with tissue engineering approaches; (2) in vivo studies, based on animal models; and (3) direct analysis on human beings, as in the case of the bed rest tests. At present, advanced tissue engineering methods allow investigators to recreate bone microenvironment in vitro for mechanobiology studies. This group and others have generated tissue 'organoids' to mimic in vitro the in vivo bone environment and to study the alteration cells can go through when subjected to unloading. Understanding the molecular mechanisms underlying the bone tissue response to mechanostimuli will help developing new strategies to prevent loss of tissue caused by altered mechanotransduction, as well as identifying new approaches for the treatment of diseases via drug testing. This review focuses on the effects of reduced gravity on bone mechanobiology by providing the up-to-date and state of the art on the available data by drawing a parallel with the suitable tissue engineering systems. Copyright © 2014 John Wiley & Sons, Ltd.

What is the future of 'organ transplantation' in the head and neck?

PubMed

Lott, David G

2014-10-01

To update readers on the current state and future of head and neck tissue transplantation. Many exciting advances have recently occurred in the field of head and neck transplantation and regenerative medicine. Larynx, face, and trachea transplants have all been successfully performed. Significant advancements in tissue engineering have occurred, including the ability to generate three-dimensional tissue structures. Transplantation of regenerated tissues has been successfully incorporated into airway reconstruction. These exciting advancements set the foundation to expand reconstructive options for dysfunctional tissues and to improve a patient's quality of life.

78 FR 63460 - Government Owned Invention Available for Licensing, United States Patent, No. 7,837,654, Issued...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-24

... Delivery Device for Promoting Healing in Living Tissue'' AGENCY: Department of the Army, DoD. SUMMARY: The...,837,654 for ''Precision Sensing and Treatment Delivery Device for Promoting Healing in Living Tissue... Development and Engineering Command, ATTN: RDMR-S3I-CST, Bldg 5400, Redstone Arsenal, AL 35898- 5000. FOR...

3D Printed Vascular Networks Enhance Viability in High-Volume Perfusion Bioreactor.

PubMed

Ball, Owen; Nguyen, Bao-Ngoc B; Placone, Jesse K; Fisher, John P

2016-12-01

There is a significant clinical need for engineered bone graft substitutes that can quickly, effectively, and safely repair large segmental bone defects. One emerging field of interest involves the growth of engineered bone tissue in vitro within bioreactors, the most promising of which are perfusion bioreactors. Using bioreactor systems, tissue engineered bone constructs can be fabricated in vitro. However, these engineered constructs lack inherent vasculature and once implanted, quickly develop a necrotic core, where no nutrient exchange occurs. Here, we utilized COMSOL modeling to predict oxygen diffusion gradients throughout aggregated alginate constructs, which allowed for the computer-aided design of printable vascular networks, compatible with any large tissue engineered construct cultured in a perfusion bioreactor. We investigated the effect of 3D printed macroscale vascular networks with various porosities on the viability of human mesenchymal stem cells in vitro, using both gas-permeable, and non-gas permeable bioreactor growth chamber walls. Through the use of 3D printed vascular structures in conjunction with a tubular perfusion system bioreactor, cell viability was found to increase by as much as 50% in the core of these constructs, with in silico modeling predicting construct viability at steady state.

3D Printed Vascular Networks Enhance Viability in High-Volume Perfusion Bioreactor

PubMed Central

Ball, Owen; Nguyen, Bao-Ngoc B.; Placone, Jesse K.; Fisher, John P.

2016-01-01

There is a significant clinical need for engineered bone graft substitutes that can quickly, effectively, and safely repair large segmental bone defects. One emerging field of interest involves the growth of engineered bone tissue in vitro within bioreactors, the most promising of which are perfusion bioreactors. Using bioreactor systems, tissue engineered bone constructs can be fabricated in vitro. However, these engineered constructs lack inherent vasculature and once implanted, quickly develop a necrotic core, where no nutrient exchange occurs. Here, we utilized COMSOL modeling to predict oxygen diffusion gradients throughout aggregated alginate constructs, which allowed for the computer-aided design of printable vascular networks, compatible with any large tissue engineered construct cultured in a perfusion bioreactor. We investigated the effect of 3D printed macroscale vascular networks with various porosities on the viability of human mesenchymal stem cells in vitro, using both gas-permeable, and non-gas permeable bioreactor growth chamber walls. Through the use of 3D printed vascular structures in conjunction with a tubular perfusion system bioreactor, cell viability was found to increase by as much as 50% in the core of these constructs, with in silico modeling predicting construct viability at steady state. PMID:27272210

The composition of engineered cartilage at the time of implantation determines the likelihood of regenerating tissue with a normal collagen architecture.

PubMed

Nagel, Thomas; Kelly, Daniel J

2013-04-01

The biomechanical functionality of articular cartilage is derived from both its biochemical composition and the architecture of the collagen network. Failure to replicate this normal Benninghoff architecture in regenerating articular cartilage may in turn predispose the tissue to failure. In this article, the influence of the maturity (or functionality) of a tissue-engineered construct at the time of implantation into a tibial chondral defect on the likelihood of recapitulating a normal Benninghoff architecture was investigated using a computational model featuring a collagen remodeling algorithm. Such a normal tissue architecture was predicted to form in the intact tibial plateau due to the interplay between the depth-dependent extracellular matrix properties, foremost swelling pressures, and external mechanical loading. In the presence of even small empty defects in the articular surface, the collagen architecture in the surrounding cartilage was predicted to deviate significantly from the native state, indicating a possible predisposition for osteoarthritic changes. These negative alterations were alleviated by the implantation of tissue-engineered cartilage, where a mature implant was predicted to result in the formation of a more native-like collagen architecture than immature implants. The results of this study highlight the importance of cartilage graft functionality to maintain and/or re-establish joint function and suggest that engineering a tissue with a native depth-dependent composition may facilitate the establishment of a normal Benninghoff collagen architecture after implantation into load-bearing defects.

Review of collagen I hydrogels for bioengineered tissue microenvironments: characterization of mechanics, structure, and transport.

PubMed

Antoine, Elizabeth E; Vlachos, Pavlos P; Rylander, Marissa Nichole

2014-12-01

Type I collagen hydrogels have been used successfully as three-dimensional substrates for cell culture and have shown promise as scaffolds for engineered tissues and tumors. A critical step in the development of collagen hydrogels as viable tissue mimics is quantitative characterization of hydrogel properties and their correlation with fabrication parameters, which enables hydrogels to be tuned to match specific tissues or fulfill engineering requirements. A significant body of work has been devoted to characterization of collagen I hydrogels; however, due to the breadth of materials and techniques used for characterization, published data are often disjoint and hence their utility to the community is reduced. This review aims to determine the parameter space covered by existing data and identify key gaps in the literature so that future characterization and use of collagen I hydrogels for research can be most efficiently conducted. This review is divided into three sections: (1) relevant fabrication parameters are introduced and several of the most popular methods of controlling and regulating them are described, (2) hydrogel properties most relevant for tissue engineering are presented and discussed along with their characterization techniques, (3) the state of collagen I hydrogel characterization is recapitulated and future directions are proposed. Ultimately, this review can serve as a resource for selection of fabrication parameters and material characterization methodologies in order to increase the usefulness of future collagen-hydrogel-based characterization studies and tissue engineering experiments.

Review of Collagen I Hydrogels for Bioengineered Tissue Microenvironments: Characterization of Mechanics, Structure, and Transport

PubMed Central

Vlachos, Pavlos P.; Rylander, Marissa Nichole

2014-01-01

Type I collagen hydrogels have been used successfully as three-dimensional substrates for cell culture and have shown promise as scaffolds for engineered tissues and tumors. A critical step in the development of collagen hydrogels as viable tissue mimics is quantitative characterization of hydrogel properties and their correlation with fabrication parameters, which enables hydrogels to be tuned to match specific tissues or fulfill engineering requirements. A significant body of work has been devoted to characterization of collagen I hydrogels; however, due to the breadth of materials and techniques used for characterization, published data are often disjoint and hence their utility to the community is reduced. This review aims to determine the parameter space covered by existing data and identify key gaps in the literature so that future characterization and use of collagen I hydrogels for research can be most efficiently conducted. This review is divided into three sections: (1) relevant fabrication parameters are introduced and several of the most popular methods of controlling and regulating them are described, (2) hydrogel properties most relevant for tissue engineering are presented and discussed along with their characterization techniques, (3) the state of collagen I hydrogel characterization is recapitulated and future directions are proposed. Ultimately, this review can serve as a resource for selection of fabrication parameters and material characterization methodologies in order to increase the usefulness of future collagen-hydrogel-based characterization studies and tissue engineering experiments. PMID:24923709

The use of total human bone marrow fraction in a direct three-dimensional expansion approach for bone tissue engineering applications: focus on angiogenesis and osteogenesis.

PubMed

Guerrero, Julien; Oliveira, Hugo; Catros, Sylvain; Siadous, Robin; Derkaoui, Sidi-Mohammed; Bareille, Reine; Letourneur, Didier; Amédée, Joëlle

2015-03-01

Current approaches in bone tissue engineering have shown limited success, mostly owing to insufficient vascularization of the construct. A common approach consists of co-culture of endothelial cells and osteoblastic cells. This strategy uses cells from different sources and differentiation states, thus increasing the complexity upstream of a clinical application. The source of reparative cells is paramount for the success of bone tissue engineering applications. In this context, stem cells obtained from human bone marrow hold much promise. Here, we analyzed the potential of human whole bone marrow cells directly expanded in a three-dimensional (3D) polymer matrix and focused on the further characterization of this heterogeneous population and on their ability to promote angiogenesis and osteogenesis, both in vitro and in vivo, in a subcutaneous model. Cellular aggregates were formed within 24 h and over the 12-day culture period expressed endothelial and bone-specific markers and a specific junctional protein. Ectopic implantation of the tissue-engineered constructs revealed osteoid tissue and vessel formation both at the periphery and within the implant. This work sheds light on the potential clinical use of human whole bone marrow for bone regeneration strategies, focusing on a simplified approach to develop a direct 3D culture without two-dimensional isolation or expansion.

Cell-Biomaterial Mechanical Interaction in the Framework of Tissue Engineering: Insights, Computational Modeling and Perspectives

PubMed Central

Sanz-Herrera, Jose A.; Reina-Romo, Esther

2011-01-01

Tissue engineering is an emerging field of research which combines the use of cell-seeded biomaterials both in vitro and/or in vivo with the aim of promoting new tissue formation or regeneration. In this context, how cells colonize and interact with the biomaterial is critical in order to get a functional tissue engineering product. Cell-biomaterial interaction is referred to here as the phenomenon involved in adherent cells attachment to the biomaterial surface, and their related cell functions such as growth, differentiation, migration or apoptosis. This process is inherently complex in nature involving many physico-chemical events which take place at different scales ranging from molecular to cell body (organelle) levels. Moreover, it has been demonstrated that the mechanical environment at the cell-biomaterial location may play an important role in the subsequent cell function, which remains to be elucidated. In this paper, the state-of-the-art research in the physics and mechanics of cell-biomaterial interaction is reviewed with an emphasis on focal adhesions. The paper is focused on the different models developed at different scales available to simulate certain features of cell-biomaterial interaction. A proper understanding of cell-biomaterial interaction, as well as the development of predictive models in this sense, may add some light in tissue engineering and regenerative medicine fields. PMID:22174660

3D printing for clinical application in otorhinolaryngology.

PubMed

Zhong, Nongping; Zhao, Xia

2017-12-01

Three-dimensional (3D) printing is a promising technology that can use a patient's image data to create complex and personalized constructs precisely. It has made great progress over the past few decades and has been widely used in medicine including medical modeling, surgical planning, medical education and training, prosthesis and implants. Three-dimensional (3D) bioprinting is a powerful tool that has the potential to fabricate bioengineered constructs of the desired shape layer-by-layer using computer-aided deposition of living cells and biomaterials. Advances in 3D printed implants and future tissue-engineered constructs will bring great progress to the field of otolaryngology. By integrating 3D printing into tissue engineering and materials, it may be possible for otolaryngologists to implant 3D printed functional grafts into patients for reconstruction of a variety of tissue defects in the foreseeable future. In this review, we will introduce the current state of 3D printing technology and highlight the applications of 3D printed prosthesis and implants, 3D printing technology combined with tissue engineering and future directions of bioprinting in the field of otolaryngology.

Tissue engineering and regenerative medicine approaches to enhance the functional response to skeletal muscle injury.

PubMed

Sicari, Brian M; Dearth, Christopher L; Badylak, Stephen F

2014-01-01

The well-recognized ability of skeletal muscle for functional and structural regeneration following injury is severely compromised in degenerative diseases and in volumetric muscle loss. Tissue engineering and regenerative medicine strategies to support muscle reconstruction have typically been cell-centric with approaches that involve the exogenous delivery of cells with myogenic potential. These strategies have been limited by poor cell viability and engraftment into host tissue. Alternative approaches have involved the use of biomaterial scaffolds as substrates or delivery vehicles for exogenous myogenic progenitor cells. Acellular biomaterial scaffolds composed of mammalian extracellular matrix (ECM) have also been used as an inductive niche to promote the recruitment and differentiation of endogenous myogenic progenitor cells. An acellular approach, which activates or utilizes endogenous cell sources, obviates the need for exogenous cell administration and provides an advantage for clinical translation. The present review examines the state of tissue engineering and regenerative medicine therapies directed at augmenting the skeletal muscle response to injury and presents the pros and cons of each with respect to clinical translation. Copyright © 2013 Wiley Periodicals, Inc.

The state of the art of nanobioscience in Japan.

PubMed

Ueno, Shoogo; Ando, Joji; Fujita, Hiroyuki; Sugawara, Tadashi; Jimbo, Yasuhiko; Itaka, Keiji; Kataoka, Kazunori; Ushida, Takashi

2006-03-01

This paper reviews a part of the state of the art of nanobioscience in Japan. The importance of combination and integration of interdisciplinary principles is emphasized for the development of nanobioscience. Biomagnetics, biomechanics, nanomachining, self-replicating cell model, neuronal network, drug delivery system, and tissue engineering are discussed.

Mixtures of tense and relaxed state polymerized human hemoglobin regulate oxygen affinity and tissue construct oxygenation

PubMed Central

Belcher, Donald Andrew; Banerjee, Uddyalok; Baehr, Christopher Michael; Richardson, Kristopher Emil; Cabrales, Pedro; Berthiaume, François

2017-01-01

Pure tense (T) and relaxed (R) quaternary state polymerized human hemoglobins (PolyhHbs) were synthesized and their biophysical properties characterized, along with mixtures of T- and R-state PolyhHbs. It was observed that the oxygen affinity of PolyhHb mixtures varied linearly with T-state mole fraction. Computational analysis of PolyhHb facilitated oxygenation of a single fiber in a hepatic hollow fiber (HF) bioreactor was performed to evaluate the oxygenation potential of T- and R-state PolyhHb mixtures. PolyhHb mixtures with T-state mole fractions greater than 50% resulted in hypoxic and hyperoxic zones occupying less than 5% of the total extra capillary space (ECS). Under these conditions, the ratio of the pericentral volume to the perivenous volume in the ECS doubled as the T-state mole fraction increased from 50 to 100%. These results show the effect of varying the T/R-state PolyhHb mole fraction on oxygenation of tissue-engineered constructs and their potential to oxygenate tissues. PMID:29020036

Business oriented EU human cell and tissue product legislation will adversely impact Member States' health care systems.

PubMed

Pirnay, Jean-Paul; Vanderkelen, Alain; De Vos, Daniel; Draye, Jean-Pierre; Rose, Thomas; Ceulemans, Carl; Ectors, Nadine; Huys, Isabelle; Jennes, Serge; Verbeken, Gilbert

2013-12-01

The transplantation of conventional human cell and tissue grafts, such as heart valve replacements and skin for severely burnt patients, has saved many lives over the last decades. The late eighties saw the emergence of tissue engineering with the focus on the development of biological substitutes that restore or improve tissue function. In the nineties, at the height of the tissue engineering hype, industry incited policymakers to create a European regulatory environment, which would facilitate the emergence of a strong single market for tissue engineered products and their starting materials (human cells and tissues). In this paper we analyze the elaboration process of this new European Union (EU) human cell and tissue product regulatory regime-i.e. the EU Cell and Tissue Directives (EUCTDs) and the Advanced Therapy Medicinal Product (ATMP) Regulation and evaluate its impact on Member States' health care systems. We demonstrate that the successful lobbying on key areas of regulatory and policy processes by industry, in congruence with Europe's risk aversion and urge to promote growth and jobs, led to excessively business oriented legislation. Expensive industry oriented requirements were introduced and contentious social and ethical issues were excluded. We found indications that this new EU safety and health legislation will adversely impact Member States' health care systems; since 30 December 2012 (the end of the ATMP transitional period) there is a clear threat to the sustainability of some lifesaving and established ATMPs that were provided by public health institutions and small and medium-sized enterprises under the frame of the EUCTDs. In the light of the current economic crisis it is not clear how social security systems will cope with the inflation of costs associated with this new regulatory regime and how priorities will be set with regard to reimbursement decisions. We argue that the ATMP Regulation should urgently be revised to focus on delivering affordable therapies to all who are in need of them and this without necessarily going to the market. The most rapid and elegant way to achieve this would be for the European Commission to publish an interpretative document on "placing on the market of ATMPs," which keeps tailor-made and niche ATMPs outside of the scope of the medicinal product regulation.

The role of Wnt regulation in heart development, cardiac repair and disease: A tissue engineering perspective.

PubMed

Pahnke, Aric; Conant, Genna; Huyer, Locke Davenport; Zhao, Yimu; Feric, Nicole; Radisic, Milica

2016-05-06

Wingless-related integration site (Wnt) signaling has proven to be a fundamental mechanism in cardiovascular development as well as disease. Understanding its particular role in heart formation has helped to develop pluripotent stem cell differentiation protocols that produce relatively pure cardiomyocyte populations. The resultant cardiomyocytes have been used to generate heart tissue for pharmaceutical testing, and to study physiological and disease states. Such protocols in combination with induced pluripotent stem cell technology have yielded patient-derived cardiomyocytes that exhibit some of the hallmarks of cardiovascular disease and are therefore being used to model disease states. While FDA approval of new treatments typically requires animal experiments, the burgeoning field of tissue engineering could act as a replacement. This would necessitate the generation of reproducible three-dimensional cardiac tissues in a well-controlled environment, which exhibit native heart properties, such as cellular density, composition, extracellular matrix composition, and structure-function. Such tissues could also enable the further study of Wnt signaling. Furthermore, as Wnt signaling has been found to have a mechanistic role in cardiac pathophysiology, e.g. heart attack, hypertrophy, atherosclerosis, and aortic stenosis, its strategic manipulation could provide a means of generating reproducible and specific, physiological and pathological cardiac models. Copyright © 2015 Elsevier Inc. All rights reserved.

77 FR 50089 - Notice of Intent To Grant Exclusive License of the United States Patent No. 7,837,654 B2, Issued...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-20

... Delivery Device for Promoting Healing in Living Tissue AGENCY: Department of the Army, DoD. ACTION: Notice... & Engineering Center, Attn: RDMR-CST (Dr. J.R. Alexander), 5400 Fowler Road, Redstone Arsenal, Alabama 35898... claims a microneedle insertable in a target cell tissue, including a manipulative end maintained exterior...

Collagenous Extracellular Matrix Biomaterials for Tissue Engineering: Lessons from the Common Sea Urchin Tissue.

PubMed

Goh, Kheng Lim; Holmes, David F

2017-04-25

Scaffolds for tissue engineering application may be made from a collagenous extracellular matrix (ECM) of connective tissues because the ECM can mimic the functions of the target tissue. The primary sources of collagenous ECM material are calf skin and bone. However, these sources are associated with the risk of having bovine spongiform encephalopathy or transmissible spongiform encephalopathy. Alternative sources for collagenous ECM materials may be derived from livestock, e.g., pigs, and from marine animals, e.g., sea urchins. Collagenous ECM of the sea urchin possesses structural features and mechanical properties that are similar to those of mammalian ones. However, even more intriguing is that some tissues such as the ligamentous catch apparatus can exhibit mutability, namely rapid reversible changes in the tissue mechanical properties. These tissues are known as mutable collagenous tissues (MCTs). The mutability of these tissues has been the subject of on-going investigations, covering the biochemistry, structural biology and mechanical properties of the collagenous components. Recent studies point to a nerve-control system for regulating the ECM macromolecules that are involved in the sliding action of collagen fibrils in the MCT. This review discusses the key attributes of the structure and function of the ECM of the sea urchin ligaments that are related to the fibril-fibril sliding action-the focus is on the respective components within the hierarchical architecture of the tissue. In this context, structure refers to size, shape and separation distance of the ECM components while function is associated with mechanical properties e.g., strength and stiffness. For simplicity, the components that address the different length scale from the largest to the smallest are as follows: collagen fibres, collagen fibrils, interfibrillar matrix and collagen molecules. Application of recent theories of stress transfer and fracture mechanisms in fibre reinforced composites to a wide variety of collagen reinforcing (non-mutable) connective tissue, has allowed us to draw general conclusions concerning the mechanical response of the MCT at specific mechanical states, namely the stiff and complaint states. The intent of this review is to provide the latest insights, as well as identify technical challenges and opportunities, that may be useful for developing methods for effective mechanical support when adapting decellularised connective tissues from the sea urchin for tissue engineering or for the design of a synthetic analogue.

Collagenous Extracellular Matrix Biomaterials for Tissue Engineering: Lessons from the Common Sea Urchin Tissue

PubMed Central

Goh, Kheng Lim; Holmes, David F.

2017-01-01

Scaffolds for tissue engineering application may be made from a collagenous extracellular matrix (ECM) of connective tissues because the ECM can mimic the functions of the target tissue. The primary sources of collagenous ECM material are calf skin and bone. However, these sources are associated with the risk of having bovine spongiform encephalopathy or transmissible spongiform encephalopathy. Alternative sources for collagenous ECM materials may be derived from livestock, e.g., pigs, and from marine animals, e.g., sea urchins. Collagenous ECM of the sea urchin possesses structural features and mechanical properties that are similar to those of mammalian ones. However, even more intriguing is that some tissues such as the ligamentous catch apparatus can exhibit mutability, namely rapid reversible changes in the tissue mechanical properties. These tissues are known as mutable collagenous tissues (MCTs). The mutability of these tissues has been the subject of on-going investigations, covering the biochemistry, structural biology and mechanical properties of the collagenous components. Recent studies point to a nerve-control system for regulating the ECM macromolecules that are involved in the sliding action of collagen fibrils in the MCT. This review discusses the key attributes of the structure and function of the ECM of the sea urchin ligaments that are related to the fibril-fibril sliding action—the focus is on the respective components within the hierarchical architecture of the tissue. In this context, structure refers to size, shape and separation distance of the ECM components while function is associated with mechanical properties e.g., strength and stiffness. For simplicity, the components that address the different length scale from the largest to the smallest are as follows: collagen fibres, collagen fibrils, interfibrillar matrix and collagen molecules. Application of recent theories of stress transfer and fracture mechanisms in fibre reinforced composites to a wide variety of collagen reinforcing (non-mutable) connective tissue, has allowed us to draw general conclusions concerning the mechanical response of the MCT at specific mechanical states, namely the stiff and complaint states. The intent of this review is to provide the latest insights, as well as identify technical challenges and opportunities, that may be useful for developing methods for effective mechanical support when adapting decellularised connective tissues from the sea urchin for tissue engineering or for the design of a synthetic analogue. PMID:28441344

Additive Manufacturing of Vascular Grafts and Vascularized Tissue Constructs.

PubMed

Elomaa, Laura; Yang, Yunzhi Peter

2017-10-01

There is a great need for engineered vascular grafts among patients with cardiovascular diseases who are in need of bypass therapy and lack autologous healthy blood vessels. In addition, because of the severe worldwide shortage of organ donors, there is an increasing need for engineered vascularized tissue constructs as an alternative to organ transplants. Additive manufacturing (AM) offers great advantages and flexibility of fabrication of cell-laden, multimaterial, and anatomically shaped vascular grafts and vascularized tissue constructs. Various inkjet-, extrusion-, and photocrosslinking-based AM techniques have been applied to the fabrication of both self-standing vascular grafts and porous, vascularized tissue constructs. This review discusses the state-of-the-art research on the use of AM for vascular applications and the key criteria for biomaterials in the AM of both acellular and cellular constructs. We envision that new smart printing materials that can adapt to their environment and encourage rapid endothelialization and remodeling will be the key factor in the future for the successful AM of personalized and dynamic vascular tissue applications.

Tissue engineering on the nanoscale: lessons from the heart.

PubMed

Fleischer, Sharon; Dvir, Tal

2013-08-01

Recognizing the limitations of biomaterials for engineering complex tissues and the desire for closer recapitulation of the natural matrix have led tissue engineers to seek new technologies for fabricating 3-dimensional (3D) cellular microenvironments. In this review, through examples from cardiac tissue engineering, we describe the nanoscale hallmarks of the extracellular matrix that tissue engineers strive to mimic. Furthermore, we discuss the use of inorganic nanoparticles and nanodevices for improving and monitoring the performance of engineered tissues. Finally, we offer our opinion on the main challenges and prospects of applying nanotechnology in tissue engineering. Copyright © 2012 Elsevier Ltd. All rights reserved.

Biomaterial-driven in situ cardiovascular tissue engineering-a multi-disciplinary perspective.

PubMed

Wissing, Tamar B; Bonito, Valentina; Bouten, Carlijn V C; Smits, Anthal I P M

2017-01-01

There is a persistent and growing clinical need for readily-available substitutes for heart valves and small-diameter blood vessels. In situ tissue engineering is emerging as a disruptive new technology, providing ready-to-use biodegradable, cell-free constructs which are designed to induce regeneration upon implantation, directly in the functional site. The induced regenerative process hinges around the host response to the implanted biomaterial and the interplay between immune cells, stem/progenitor cell and tissue cells in the microenvironment provided by the scaffold in the hemodynamic environment. Recapitulating the complex tissue microstructure and function of cardiovascular tissues is a highly challenging target. Therein the scaffold plays an instructive role, providing the microenvironment that attracts and harbors host cells, modulating the inflammatory response, and acting as a temporal roadmap for new tissue to be formed. Moreover, the biomechanical loads imposed by the hemodynamic environment play a pivotal role. Here, we provide a multidisciplinary view on in situ cardiovascular tissue engineering using synthetic scaffolds; starting from the state-of-the art, the principles of the biomaterial-driven host response and wound healing and the cellular players involved, toward the impact of the biomechanical, physical, and biochemical microenvironmental cues that are given by the scaffold design. To conclude, we pinpoint and further address the main current challenges for in situ cardiovascular regeneration, namely the achievement of tissue homeostasis, the development of predictive models for long-term performances of the implanted grafts, and the necessity for stratification for successful clinical translation.

Supporting Biomaterials for Articular Cartilage Repair

PubMed Central

Duarte Campos, Daniela Filipa; Drescher, Wolf; Rath, Björn; Tingart, Markus

2012-01-01

Orthopedic surgeons and researchers worldwide are continuously faced with the challenge of regenerating articular cartilage defects. However, until now, it has not been possible to completely mimic the biological and biochemical properties of articular cartilage using current research and development approaches. In this review, biomaterials previously used for articular cartilage repair research are addressed. Furthermore, a brief discussion of the state of the art of current cell printing procedures mimicking native cartilage is offered in light of their use as future alternatives for cartilage tissue engineering. Inkjet cell printing, controlled deposition cell printing tools, and laser cell printing are cutting-edge techniques in this context. The development of mimetic hydrogels with specific biological properties relevant to articular cartilage native tissue will support the development of improved, functional, and novel engineered tissue for clinical application. PMID:26069634

Mineralization Induction of Gingival Fibroblasts and Construction of a Sandwich Tissue-Engineered Complex for Repairing Periodontal Defects

PubMed Central

Wu, Mingxuan; Zhang, Yanning; Liu, Huijuan; Dong, Fusheng

2018-01-01

Background The ideal healing technique for periodontal tissue defects would involve the functional regeneration of the alveolar bone, cementum, and periodontal ligament, with new periodontal attachment formation. In this study, gingival fibroblasts were induced and a “sandwich” tissue-engineered complex (a tissue-engineered periodontal membrane between 2 tissue-engineered mineralized membranes) was constructed to repair periodontal defects. We evaluated the effects of gingival fibroblasts used as seed cells on the repair of periodontal defects and periodontal regeneration. Material/Methods Primitively cultured gingival fibroblasts were seeded bilaterally on Bio-Gide collagen membrane (a tissue-engineered periodontal membrane) or unilaterally on small intestinal submucosa segments, and their mineralization was induced. A tissue-engineered sandwich was constructed, comprising the tissue-engineered periodontal membrane flanked by 2 mineralized membranes. Periodontal defects in premolar regions of Beagles were repaired using the tissue-engineered sandwich or periodontal membranes. Periodontal reconstruction was compared to normal and trauma controls 10 or 20 days postoperatively. Results Periodontal defects were completely repaired by the sandwich tissue-engineered complex, with intact new alveolar bone and cementum, and a new periodontal ligament, 10 days postoperatively. Conclusions The sandwich tissue-engineered complex can achieve ideal periodontal reconstruction rapidly. PMID:29470454

Engineering complex tissues.

PubMed

Atala, Anthony; Kasper, F Kurtis; Mikos, Antonios G

2012-11-14

Tissue engineering has emerged at the intersection of numerous disciplines to meet a global clinical need for technologies to promote the regeneration of functional living tissues and organs. The complexity of many tissues and organs, coupled with confounding factors that may be associated with the injury or disease underlying the need for repair, is a challenge to traditional engineering approaches. Biomaterials, cells, and other factors are needed to design these constructs, but not all tissues are created equal. Flat tissues (skin); tubular structures (urethra); hollow, nontubular, viscus organs (vagina); and complex solid organs (liver) all present unique challenges in tissue engineering. This review highlights advances in tissue engineering technologies to enable regeneration of complex tissues and organs and to discuss how such innovative, engineered tissues can affect the clinic.

Design Approaches to Myocardial and Vascular Tissue Engineering.

PubMed

Akintewe, Olukemi O; Roberts, Erin G; Rim, Nae-Gyune; Ferguson, Michael A H; Wong, Joyce Y

2017-06-21

Engineered tissues represent an increasingly promising therapeutic approach for correcting structural defects and promoting tissue regeneration in cardiovascular diseases. One of the challenges associated with this approach has been the necessity for the replacement tissue to promote sufficient vascularization to maintain functionality after implantation. This review highlights a number of promising prevascularization design approaches for introducing vasculature into engineered tissues. Although we focus on encouraging blood vessel formation within myocardial implants, we also discuss techniques developed for other tissues that could eventually become relevant to engineered cardiac tissues. Because the ultimate solution to engineered tissue vascularization will require collaboration between wide-ranging disciplines such as developmental biology, tissue engineering, and computational modeling, we explore contributions from each field.

Tissue engineering for clinical applications.

PubMed

Bhatia, Sujata K

2010-12-01

Tissue engineering is increasingly being recognized as a beneficial means for lessening the global disease burden. One strategy of tissue engineering is to replace lost tissues or organs with polymeric scaffolds that contain specialized populations of living cells, with the goal of regenerating tissues to restore normal function. Typical constructs for tissue engineering employ biocompatible and degradable polymers, along with organ-specific and tissue-specific cells. Once implanted, the construct guides the growth and development of new tissues; the polymer scaffold degrades away to be replaced by healthy functioning tissue. The ideal biomaterial for tissue engineering not only defends against disease and supports weakened tissues or organs, it also provides the elements required for healing and repair, stimulates the body's intrinsic immunological and regenerative capacities, and seamlessly interacts with the living body. Tissue engineering has been investigated for virtually every organ system in the human body. This review describes the potential of tissue engineering to alleviate disease, as well as the latest advances in tissue regeneration. The discussion focuses on three specific clinical applications of tissue engineering: cardiac tissue regeneration for treatment of heart failure; nerve regeneration for treatment of stroke; and lung regeneration for treatment of chronic obstructive pulmonary disease. Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Gelatin as Biomaterial for Tissue Engineering.

PubMed

Echave, Mari C; Saenz del Burgo, Laura; Pedraz, Jose L; Orive, Gorka

2017-01-01

Tissue engineering is considered one of the most important therapeutic strategies of regenerative medicine. The main objective of these new technologies is the development of substitutes made with biomaterials that are able to heal, repair or regenerate injured or diseased tissues and organs. These constructs seek to unlock the limited ability of human tissues and organs to regenerate. In this review, we highlight the convenient intrinsic properties of gelatin for the design and development of advanced systems for tissue engineering. Gelatin is a natural origin protein derived from collagen hydrolysis. We outline herein a state of the art of gelatin-based composites in order to overcome limitations of this polymeric material and modulate the properties of the formulations. Control release of bioactive molecules, formulations with conductive properties or systems with improved mechanical properties can be obtained using gelatin composites. Many studies have found that the use of calcium phosphate ceramics and diverse synthetic polymers in combination with gelatin improve the mechanical properties of the structures. On the other hand, polyaniline and carbon-based nanosubstrates are interesting molecules to provide gelatin-based systems with conductive properties, especially for cardiac and nerve tissue engineering. Finally, this review provides an overview of the different types of gelatin-based structures including nanoparticles, microparticles, 3D scaffolds, electrospun nanofibers and in situ gelling formulations. Thanks to the significant progress that has already been made, along with others that will be achieved in a near future, the safe and effective clinical implementation of gelatin-based products is expected to accelerate and expand shortly. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Tissue-engineered vascular grafts composed of marine collagen and PLGA fibers using pulsatile perfusion bioreactors.

PubMed

Jeong, Sung In; Kim, So Yeon; Cho, Seong Kwan; Chong, Moo Sang; Kim, Kyung Soo; Kim, Hyuck; Lee, Sang Bong; Lee, Young Moo

2007-02-01

Novel tubular scaffolds of marine source collagen and PLGA fibers were fabricated by freeze drying and electrospinning processes for vascular grafts. The hybrid scaffolds, composed of a porous collagen matrix and a fibrous PLGA layer, had an average pore size of 150+/-50 microm. The electrospun fibrous PLGA layer on the surface of a porous tubular collagen scaffold improved the mechanical strength of the collagen scaffolds in both the dry and wet states. Smooth muscle cells (SMCs)- and endothelial cells (ECs)-cultured collagen/PLGA scaffolds exhibited mechanical properties similar to collagen/PLGA scaffolds unseeded with cells, even after culturing for 23 days. The effect of a mechanical stimulation on the proliferation and phenotype of SMCs and ECs, cultured on collagen/PLGA scaffolds, was evaluated. The pulsatile perfusion system enhanced the SMCs and ECs proliferation. In addition, a significant cell alignment in a direction radial to the distending direction was observed in tissues exposed to radial distention, which is similar to the phenomenon of native vessel tissues in vivo. On the other hand, cells in tissues engineered in the static condition were randomly aligned. Immunochemical analyses showed that the expressions of SM alpha-actin, SM myosin heavy chain, EC von Willebrand factor, and EC nitric oxide were upregulated in tissues engineered under a mechano-active condition, compared to vessel tissues engineered in the static condition. These results indicated that the co-culturing of SMCs and ECs, using collagen/PLGA hybrid scaffolds under a pulsatile perfusion system, leads to the enhancement of vascular EC development, as well as the retention of the differentiated cell phenotype.

Modeling of cryopreservation of engineered tissues with one-dimensional geometry.

PubMed

Cui, Z F; Dykhuizen, R C; Nerem, R M; Sembanis, A

2002-01-01

Long-term storage of engineered bio-artificial tissues is required to ensure the off-the-shelf availability to clinicians due to their long production cycle. Cryopreservation is likely the choice for long-term preservation. Although the cryopreservation of cells is well established for many cell types, cryopreservation of tissues is far more complicated. Cells at different locations in the tissue could experience very different local environmental changes, i.e., the change of concentration of cryoprotecting chemicals (CPA) and temperature, during the addition/removal of CPA and cooling/warming, which leads to nonuniformity in cell survival in the tissue. This is due to the limitation of mass and heat transfer within the tissue. A specific aim of cryopreservation of tissue is to ensure a maximum recovery of cells and their functionality throughout a tissue. Cells at all locations should be protected adequately by the CPA and frozen at rates conducive to survival. It is hence highly desirable to know the cell transient and final states during cryopreservation within the whole tissue, which can be best studied by mathematical modeling. In this work, a model framework for cryopreservation of one-dimensional artificial tissues is developed on the basis of solving the coupled equations to describe the mass and heat transfer within the tissue and osmotic transport through the cell membrane. Using an artificial pancreas as an example, we carried out a simulation to examine the temperature history, cell volume, solute redistribution, and other state parameters during the freezing of the spherical heterogeneous construct (a single bead). It is found that the parameters affecting the mass transfer of CPA in tissue and through the cell membrane and the freezing rate play dominant roles in affecting the cell volume transient and extracellular ice formation. Thermal conductivity and extracellular ice formation kinetics, on the other hand, have little effect on cell transient and final states, as the heat transfer rate is much faster than mass diffusion. The outcome of such a model study can be used to evaluate the construct design on its survivability during cryopreservation and to select a cryopreservation protocol to achieve maximum cell survival.

Concise Review: Human Dermis as an Autologous Source of Stem Cells for Tissue Engineering and Regenerative Medicine.

PubMed

Vapniarsky, Natalia; Arzi, Boaz; Hu, Jerry C; Nolta, Jan A; Athanasiou, Kyriacos A

2015-10-01

The exciting potential for regenerating organs from autologous stem cells is on the near horizon, and adult dermis stem cells (DSCs) are particularly appealing because of the ease and relative minimal invasiveness of skin collection. A substantial number of reports have described DSCs and their potential for regenerating tissues from mesenchymal, ectodermal, and endodermal lineages; however, the exact niches of these stem cells in various skin types and their antigenic surface makeup are not yet clearly defined. The multilineage potential of DSCs appears to be similar, despite great variability in isolation and in vitro propagation methods. Despite this great potential, only limited amounts of tissues and clinical applications for organ regeneration have been developed from DSCs. This review summarizes the literature on DSCs regarding their niches and the specific markers they express. The concept of the niches and the differentiation capacity of cells residing in them along particular lineages is discussed. Furthermore, the advantages and disadvantages of widely used methods to demonstrate lineage differentiation are considered. In addition, safety considerations and the most recent advancements in the field of tissue engineering and regeneration using DSCs are discussed. This review concludes with thoughts on how to prospectively approach engineering of tissues and organ regeneration using DSCs. Our expectation is that implementation of the major points highlighted in this review will lead to major advancements in the fields of regenerative medicine and tissue engineering. Autologous dermis-derived stem cells are generating great excitement and efforts in the field of regenerative medicine and tissue engineering. The substantial impact of this review lies in its critical coverage of the available literature and in providing insight regarding niches, characteristics, and isolation methods of stem cells derived from the human dermis. Furthermore, it provides analysis of the current state-of-the-art regenerative approaches using human-derived dermal stem cells, with consideration of current guidelines, to assist translation toward therapeutic use. ©AlphaMed Press.

Concise Review: Human Dermis as an Autologous Source of Stem Cells for Tissue Engineering and Regenerative Medicine

PubMed Central

Vapniarsky, Natalia; Arzi, Boaz; Hu, Jerry C.; Nolta, Jan A.

2015-01-01

The exciting potential for regenerating organs from autologous stem cells is on the near horizon, and adult dermis stem cells (DSCs) are particularly appealing because of the ease and relative minimal invasiveness of skin collection. A substantial number of reports have described DSCs and their potential for regenerating tissues from mesenchymal, ectodermal, and endodermal lineages; however, the exact niches of these stem cells in various skin types and their antigenic surface makeup are not yet clearly defined. The multilineage potential of DSCs appears to be similar, despite great variability in isolation and in vitro propagation methods. Despite this great potential, only limited amounts of tissues and clinical applications for organ regeneration have been developed from DSCs. This review summarizes the literature on DSCs regarding their niches and the specific markers they express. The concept of the niches and the differentiation capacity of cells residing in them along particular lineages is discussed. Furthermore, the advantages and disadvantages of widely used methods to demonstrate lineage differentiation are considered. In addition, safety considerations and the most recent advancements in the field of tissue engineering and regeneration using DSCs are discussed. This review concludes with thoughts on how to prospectively approach engineering of tissues and organ regeneration using DSCs. Our expectation is that implementation of the major points highlighted in this review will lead to major advancements in the fields of regenerative medicine and tissue engineering. Significance Autologous dermis-derived stem cells are generating great excitement and efforts in the field of regenerative medicine and tissue engineering. The substantial impact of this review lies in its critical coverage of the available literature and in providing insight regarding niches, characteristics, and isolation methods of stem cells derived from the human dermis. Furthermore, it provides analysis of the current state-of-the-art regenerative approaches using human-derived dermal stem cells, with consideration of current guidelines, to assist translation toward therapeutic use. PMID:26253713

An Overview of Recent Patents on Musculoskeletal Interface Tissue Engineering

PubMed Central

Rao, Rohit T.; Browe, Daniel P.; Lowe, Christopher J.; Freeman, Joseph W.

2018-01-01

Interface tissue engineering involves the development of engineered grafts that promote integration between multiple tissue types. Musculoskeletal tissue interfaces are critical to the safe and efficient transmission of mechanical forces between multiple musculoskeletal tissues e.g. between ligament and bone tissue. However, these interfaces often do not physiologically regenerate upon injury, resulting in impaired tissue function. Therefore, interface tissue engineering approaches are considered to be particularly relevant for the structural restoration of musculoskeletal tissues interfaces. In this article we provide an overview of the various strategies used for engineering musculoskeletal tissue interfaces with a specific focus on the recent important patents that have been issued for inventions that were specifically designed for engineering musculoskeletal interfaces as well as those that show promise to be adapted for this purpose. PMID:26577344

Delivery strategies to control inflammatory response: Modulating M1-M2 polarization in tissue engineering applications.

PubMed

Alvarez, Mario Moisés; Liu, Julie C; Trujillo-de Santiago, Grissel; Cha, Byung-Hyun; Vishwakarma, Ajaykumar; Ghaemmaghami, Amir M; Khademhosseini, Ali

2016-10-28

Macrophages are key players in many physiological scenarios including tissue homeostasis. In response to injury, typically the balance between macrophage sub-populations shifts from an M1 phenotype (pro-inflammatory) to an M2 phenotype (anti-inflammatory). In tissue engineering scenarios, after implantation of any device, it is desirable to exercise control on this M1-M2 progression and to ensure a timely and smooth transition from the inflammatory to the healing stage. In this review, we briefly introduce the current state of knowledge regarding macrophage function and nomenclature. Next, we discuss the use of controlled release strategies to tune the balance between the M1 and M2 phenotypes in the context of tissue engineering applications. We discuss recent literature related to the release of anti-inflammatory molecules (including nucleic acids) and the sequential release of cytokines to promote a timely M1-M2 shift. In addition, we describe the use of macrophages as controlled release agents upon stimulation by physical and/or mechanical cues provided by scaffolds. Moreover, we discuss current and future applications of "smart" implantable scaffolds capable of controlling the cascade of biochemical events related to healing and vascularization. Finally, we provide our opinion on the current challenges and the future research directions to improve our understanding of the M1-M2 macrophage balance and properly exploit it in tissue engineering and regenerative medicine applications. Copyright © 2016 Elsevier B.V. All rights reserved.

Delivery strategies to control inflammatory response: Modulating M1-M2 polarization in tissue engineering applications

PubMed Central

Alvarez, Mario Moisés; Liu, Julie C.; Santiago, Grissel Trujillo-de; Cha, Byung-Hyun; Vishwakarma, Ajaykumar; Ghaemmaghami, Amir; Khademhosseini, Ali

2016-01-01

Macrophages are key players in many physiological scenarios including tissue homeostasis. In response to injury, typically the balance between macrophage sub-populations shifts from an M1 phenotype (pro-inflammatory) to an M2 phenotype (anti-inflammatory). In tissue engineering scenarios, after implantation of any device, it is desirable to exercise control on this M1-M2 progression and to ensure a timely and smooth transition from the inflammatory to the healing stage. In this review, we briefly introduce the current state of knowledge regarding macrophage function and nomenclature. Next, we discuss the use of controlled release strategies to tune the balance between the M1 and M2 phenotypes in the context of tissue engineering applications. We discuss recent literature related to the release of anti-inflammatory molecules (including nucleic acids) and the sequential release of cytokines to promote a timely M1-M2 shift. In addition, we describe the use of macrophages as controlled release agents upon stimulation by physical and/or mechanical cues provided by scaffolds. Moreover, we discuss current and future applications of “smart” implantable scaffolds capable of controlling the cascade of biochemical events related to healing and vascularization. Finally, we provide our opinion on the current challenges and the future research directions to improve our understanding of the M1-M2 macrophage balance and properly exploit it in tissue engineering and regenerative medicine applications. PMID:26778695

Recent trends in bioinks for 3D printing.

PubMed

Gopinathan, Janarthanan; Noh, Insup

2018-01-01

The worldwide demand for the organ replacement or tissue regeneration is increasing steadily. The advancements in tissue engineering and regenerative medicine have made it possible to regenerate such damaged organs or tissues into functional organ or tissue with the help of 3D bioprinting. The main component of the 3D bioprinting is the bioink, which is crucial for the development of functional organs or tissue structures. The bioinks used in 3D printing technology require so many properties which are vital and need to be considered during the selection. Combination of different methods and enhancements in properties are required to develop more successful bioinks for the 3D printing of organs or tissue structures. This review consists of the recent state-of-art of polymer-based bioinks used in 3D printing for applications in tissue engineering and regenerative medicine. The subsection projects the basic requirements for the selection of successful bioinks for 3D printing and developing 3D tissues or organ structures using combinations of bioinks such as cells, biomedical polymers and biosignals. Different bioink materials and their properties related to the biocompatibility, printability, mechanical properties, which are recently reported for 3D printing are discussed in detail. Many bioinks formulations have been reported from cell-biomaterials based bioinks to cell-based bioinks such as cell aggregates and tissue spheroids for tissue engineering and regenerative medicine applications. Interestingly, more tunable bioinks, which are biocompatible for live cells, printable and mechanically stable after printing are emerging with the help of functional polymeric biomaterials, their modifications and blending of cells and hydrogels. These approaches show the immense potential of these bioinks to produce more complex tissue/organ structures using 3D bioprinting in the future.

Integration of technologies for hepatic tissue engineering.

PubMed

Nahmias, Yaakov; Berthiaume, Francois; Yarmush, Martin L

2007-01-01

The liver is the largest internal organ in the body, responsible for over 500 metabolic, regulatory, and immune functions. Loss of liver function leads to liver failure which causes over 25,000 deaths/year in the United States. Efforts in the field of hepatic tissue engineering include the design of bioartificial liver systems to prolong patient's lives during liver failure, for drug toxicity screening and for the study of liver regeneration, ischemia/reperfusion injury, fibrosis, viral infection, and inflammation. This chapter will overview the current state-of-the-art in hepatology including isolated perfused liver, culture of liver slices and tissue explants, hepatocyte culture on collagen "sandwich" and spheroids, coculture of hepatocytes with non-parenchymal cells, and the integration of these culture techniques with microfluidics and reactor design. This work will discuss the role of oxygen and medium composition in hepatocyte culture and present promising new technologies for hepatocyte proliferation and function. We will also discuss liver development, architecture, and function as they relate to these culture techniques. Finally, we will review current opportunities and major challenges in integrating cell culture, bioreactor design, and microtechnology to develop new systems for novel applications.

Engineered Three-Dimensional Cardiac Fibrotic Tissue to Study Fibrotic Remodeling

PubMed Central

Sadeghi, Amir Hossein; Shin, Su Ryon; Deddens, Janine C.; Fratta, Giuseppe; Mandla, Serena; Yazdi, Iman K.; Prakash, Gyan; Antona, Silvia; Demarchi, Danilo; Buijsrogge, Marc P.; Sluijter, Joost P.G.; Hjortnaes, Jesper

2017-01-01

Activation of cardiac fibroblasts (CF) into myofibroblasts is considered to play an essential role in cardiac remodeling and fibrosis. A limiting factor in studying this process is the spontaneous activation of CFs when cultured on two-dimensional (2D) culture plates. Here, a simplified 3D hydrogel platform of contractile cardiac tissue, stimulated by transforming growth factor-β1 (TGF-β1), is presented to recapitulate a fibrogenic micro-environment. It was hypothesized that the quiescent state of CFs can be maintained by mimicking the mechanical stiffness of native heart tissue. To test this hypothesis, a 3D cell culture model consisting of cardiomyocytes and CFs encapsulated within mechanically engineered gelatin methacryloyl (GelMA) hydrogel, was developed. The study shows that CFs maintain their quiescent phenotype in mechanically tuned hydrogels. Additionally, treatment with a beta-adrenergic agonist increased beating frequency, demonstrating physiologic-like behavior of the heart constructs. Subsequently, quiescent CFs within the constructs were activated by the exogenous addition of TGF-β1. The expression of fibrotic protein markers (and the functional changes in mechanical stiffness) in the fibrotic-like tissues were analyzed to validate the model. Overall, this 3D engineered culture model of contractile cardiac tissue enabled controlled activation of CFs, demonstrating the usability of this platform to study fibrotic remodeling. PMID:28498548

The Expanding World of Tissue Engineering: The Building Blocks and New Applications of Tissue Engineered Constructs

PubMed Central

Zorlutuna, Pinar; Vrana, Nihal Engin; Khademhosseini, Ali

2013-01-01

The field of tissue engineering has been growing in the recent years as more products have made it to the market and as new uses for the engineered tissues have emerged, motivating many researchers to engage in this multidisciplinary field of research. Engineered tissues are now not only considered as end products for regenerative medicine, but also have emerged as enabling technologies for other fields of research ranging from drug discovery to biorobotics. This widespread use necessitates a variety of methodologies for production of tissue engineered constructs. In this review, these methods together with their non-clinical applications will be described. First, we will focus on novel materials used in tissue engineering scaffolds; such as recombinant proteins and synthetic, self assembling polypeptides. The recent advances in the modular tissue engineering area will be discussed. Then scaffold-free production methods, based on either cell sheets or cell aggregates will be described. Cell sources used in tissue engineering and new methods that provide improved control over cell behavior such as pathway engineering and biomimetic microenvironments for directing cell differentiation will be discussed. Finally, we will summarize the emerging uses of engineered constructs such as model tissues for drug discovery, cancer research and biorobotics applications. PMID:23268388

Introduction to tissue engineering and application for cartilage engineering.

PubMed

de Isla, N; Huseltein, C; Jessel, N; Pinzano, A; Decot, V; Magdalou, J; Bensoussan, D; Stoltz, J-F

2010-01-01

Tissue engineering is a multidisciplinary field that applies the principles of engineering, life sciences, cell and molecular biology toward the development of biological substitutes that restore, maintain, and improve tissue function. In Western Countries, tissues or cells management for clinical uses is a medical activity governed by different laws. Three general components are involved in tissue engineering: (1) reparative cells that can form a functional matrix; (2) an appropriate scaffold for transplantation and support; and (3) bioreactive molecules, such as cytokines and growth factors that will support and choreograph formation of the desired tissue. These three components may be used individually or in combination to regenerate organs or tissues. Thus the growing development of tissue engineering needs to solve four main problems: cells, engineering development, grafting and safety studies.

Tissue engineering therapy for cardiovascular disease.

PubMed

Nugent, Helen M; Edelman, Elazer R

2003-05-30

The present treatments for the loss or failure of cardiovascular function include organ transplantation, surgical reconstruction, mechanical or synthetic devices, or the administration of metabolic products. Although routinely used, these treatments are not without constraints and complications. The emerging and interdisciplinary field of tissue engineering has evolved to provide solutions to tissue creation and repair. Tissue engineering applies the principles of engineering, material science, and biology toward the development of biological substitutes that restore, maintain, or improve tissue function. Progress has been made in engineering the various components of the cardiovascular system, including blood vessels, heart valves, and cardiac muscle. Many pivotal studies have been performed in recent years that may support the move toward the widespread application of tissue-engineered therapy for cardiovascular diseases. The studies discussed include endothelial cell seeding of vascular grafts, tissue-engineered vascular conduits, generation of heart valve leaflets, cardiomyoplasty, genetic manipulation, and in vitro conditions for optimizing tissue-engineered cardiovascular constructs.

Engineering Complex Tissues

PubMed Central

MIKOS, ANTONIOS G.; HERRING, SUSAN W.; OCHAREON, PANNEE; ELISSEEFF, JENNIFER; LU, HELEN H.; KANDEL, RITA; SCHOEN, FREDERICK J.; TONER, MEHMET; MOONEY, DAVID; ATALA, ANTHONY; VAN DYKE, MARK E.; KAPLAN, DAVID; VUNJAK-NOVAKOVIC, GORDANA

2010-01-01

This article summarizes the views expressed at the third session of the workshop “Tissue Engineering—The Next Generation,” which was devoted to the engineering of complex tissue structures. Antonios Mikos described the engineering of complex oral and craniofacial tissues as a “guided interplay” between biomaterial scaffolds, growth factors, and local cell populations toward the restoration of the original architecture and function of complex tissues. Susan Herring, reviewing osteogenesis and vasculogenesis, explained that the vascular arrangement precedes and dictates the architecture of the new bone, and proposed that engineering of osseous tissues might benefit from preconstruction of an appropriate vasculature. Jennifer Elisseeff explored the formation of complex tissue structures based on the example of stratified cartilage engineered using stem cells and hydrogels. Helen Lu discussed engineering of tissue interfaces, a problem critical for biological fixation of tendons and ligaments, and the development of a new generation of fixation devices. Rita Kandel discussed the challenges related to the re-creation of the cartilage-bone interface, in the context of tissue engineered joint repair. Frederick Schoen emphasized, in the context of heart valve engineering, the need for including the requirements derived from “adult biology” of tissue remodeling and establishing reliable early predictors of success or failure of tissue engineered implants. Mehmet Toner presented a review of biopreservation techniques and stressed that a new breakthrough in this field may be necessary to meet all the needs of tissue engineering. David Mooney described systems providing temporal and spatial regulation of growth factor availability, which may find utility in virtually all tissue engineering and regeneration applications, including directed in vitro and in vivo vascularization of tissues. Anthony Atala offered a clinician’s perspective for functional tissue regeneration, and discussed new biomaterials that can be used to develop new regenerative technologies. PMID:17518671

Developing High-Frequency Quantitative Ultrasound Techniques to Characterize Three-Dimensional Engineered Tissues

NASA Astrophysics Data System (ADS)

Mercado, Karla Patricia E.

Tissue engineering holds great promise for the repair or replacement of native tissues and organs. Further advancements in the fabrication of functional engineered tissues are partly dependent on developing new and improved technologies to monitor the properties of engineered tissues volumetrically, quantitatively, noninvasively, and nondestructively over time. Currently, engineered tissues are evaluated during fabrication using histology, biochemical assays, and direct mechanical tests. However, these techniques destroy tissue samples and, therefore, lack the capability for real-time, longitudinal monitoring. The research reported in this thesis developed nondestructive, noninvasive approaches to characterize the structural, biological, and mechanical properties of 3-D engineered tissues using high-frequency quantitative ultrasound and elastography technologies. A quantitative ultrasound technique, using a system-independent parameter known as the integrated backscatter coefficient (IBC), was employed to visualize and quantify structural properties of engineered tissues. Specifically, the IBC was demonstrated to estimate cell concentration and quantitatively detect differences in the microstructure of 3-D collagen hydrogels. Additionally, the feasibility of an ultrasound elastography technique called Single Tracking Location Acoustic Radiation Force Impulse (STL-ARFI) imaging was demonstrated for estimating the shear moduli of 3-D engineered tissues. High-frequency ultrasound techniques can be easily integrated into sterile environments necessary for tissue engineering. Furthermore, these high-frequency quantitative ultrasound techniques can enable noninvasive, volumetric characterization of the structural, biological, and mechanical properties of engineered tissues during fabrication and post-implantation.

Bioprinting for vascular and vascularized tissue biofabrication.

PubMed

Datta, Pallab; Ayan, Bugra; Ozbolat, Ibrahim T

2017-03-15

Bioprinting is a promising technology to fabricate design-specific tissue constructs due to its ability to create complex, heterocellular structures with anatomical precision. Bioprinting enables the deposition of various biologics including growth factors, cells, genes, neo-tissues and extra-cellular matrix-like hydrogels. Benefits of bioprinting have started to make a mark in the fields of tissue engineering, regenerative medicine and pharmaceutics. Specifically, in the field of tissue engineering, the creation of vascularized tissue constructs has remained a principal challenge till date. However, given the myriad advantages over other biofabrication methods, it becomes organic to expect that bioprinting can provide a viable solution for the vascularization problem, and facilitate the clinical translation of tissue engineered constructs. This article provides a comprehensive account of bioprinting of vascular and vascularized tissue constructs. The review is structured as introducing the scope of bioprinting in tissue engineering applications, key vascular anatomical features and then a thorough coverage of 3D bioprinting using extrusion-, droplet- and laser-based bioprinting for fabrication of vascular tissue constructs. The review then provides the reader with the use of bioprinting for obtaining thick vascularized tissues using sacrificial bioink materials. Current challenges are discussed, a comparative evaluation of different bioprinting modalities is presented and future prospects are provided to the reader. Biofabrication of living tissues and organs at the clinically-relevant volumes vitally depends on the integration of vascular network. Despite the great progress in traditional biofabrication approaches, building perfusable hierarchical vascular network is a major challenge. Bioprinting is an emerging technology to fabricate design-specific tissue constructs due to its ability to create complex, heterocellular structures with anatomical precision, which holds a great promise in fabrication of vascular or vascularized tissues for transplantation use. Although a great progress has recently been made on building perfusable tissues and branched vascular network, a comprehensive review on the state-of-the-art in vascular and vascularized tissue bioprinting has not reported so far. This contribution is thus significant because it discusses the use of three major bioprinting modalities in vascular tissue biofabrication for the first time in the literature and compares their strengths and limitations in details. Moreover, the use of scaffold-based and scaffold-free bioprinting is expounded within the domain of vascular tissue fabrication. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Quantitative Ultrasound for Nondestructive Characterization of Engineered Tissues and Biomaterials

PubMed Central

Dalecki, Diane; Mercado, Karla P.; Hocking, Denise C.

2015-01-01

Non-invasive, non-destructive technologies for imaging and quantitatively monitoring the development of artificial tissues are critical for the advancement of tissue engineering. Current standard techniques for evaluating engineered tissues, including histology, biochemical assays and mechanical testing, are destructive approaches. Ultrasound is emerging as a valuable tool for imaging and quantitatively monitoring the properties of engineered tissues and biomaterials longitudinally during fabrication and post-implantation. Ultrasound techniques are rapid, non-invasive, non-destructive and can be easily integrated into sterile environments necessary for tissue engineering. Furthermore, high-frequency quantitative ultrasound techniques can enable volumetric characterization of the structural, biological, and mechanical properties of engineered tissues during fabrication and post-implantation. This review provides an overview of ultrasound imaging, quantitative ultrasound techniques, and elastography, with representative examples of applications of these ultrasound-based techniques to the field of tissue engineering. PMID:26581347

Cardiac tissue engineering: from matrix design to the engineering of bionic hearts.

PubMed

Fleischer, Sharon; Feiner, Ron; Dvir, Tal

2017-04-01

The field of cardiac tissue engineering aims at replacing the scar tissue created after a patient has suffered from a myocardial infarction. Various technologies have been developed toward fabricating a functional engineered tissue that closely resembles that of the native heart. While the field continues to grow and techniques for better tissue fabrication continue to emerge, several hurdles still remain to be overcome. In this review we will focus on several key advances and recent technologies developed in the field, including biomimicking the natural extracellular matrix structure and enhancing the transfer of the electrical signal. We will also discuss recent developments in the engineering of bionic cardiac tissues which integrate the fields of tissue engineering and electronics to monitor and control tissue performance.

Emergence of Scaffold-free Approaches for Tissue Engineering Musculoskeletal Cartilages

PubMed Central

DuRaine, Grayson D.; Brown, Wendy E.; Hu, Jerry C.; Athanasiou, Kyriacos A.

2014-01-01

This review explores scaffold-free methods as an additional paradigm for tissue engineering. Musculoskeletal cartilages –for example articular cartilage, meniscus, temporomandibular joint disc, and intervertebral disc – are characterized by low vascularity and cellularity, and are amenable to scaffold-free tissue engineering approaches. Scaffold-free approaches, particularly the self-assembling process, mimic elements of developmental processes underlying these tissues. Discussed are various scaffold-free approaches for musculoskeletal cartilage tissue engineering, such as cell sheet engineering, aggregation, and the self-assembling process, as well as the availability and variety of cells used. Immunological considerations are of particular importance as engineered tissues are frequently of allogeneic, if not xenogeneic, origin. Factors that enhance the matrix production and mechanical properties of these engineered cartilages are also reviewed, as the fabrication of biomimetically suitable tissues is necessary to replicate function and ensure graft survival in vivo. The concept of combining scaffold-free and scaffold-based tissue engineering methods to address clinical needs is also discussed. Inasmuch as scaffold-based musculoskeletal tissue engineering approaches have been employed as a paradigm to generate engineered cartilages with appropriate functional properties, scaffold-free approaches are emerging as promising elements of a translational pathway not only for musculoskeletal cartilages but for other tissues as well. PMID:25331099

Imaging Strategies for Tissue Engineering Applications

PubMed Central

Nam, Seung Yun; Ricles, Laura M.; Suggs, Laura J.

2015-01-01

Tissue engineering has evolved with multifaceted research being conducted using advanced technologies, and it is progressing toward clinical applications. As tissue engineering technology significantly advances, it proceeds toward increasing sophistication, including nanoscale strategies for material construction and synergetic methods for combining with cells, growth factors, or other macromolecules. Therefore, to assess advanced tissue-engineered constructs, tissue engineers need versatile imaging methods capable of monitoring not only morphological but also functional and molecular information. However, there is no single imaging modality that is suitable for all tissue-engineered constructs. Each imaging method has its own range of applications and provides information based on the specific properties of the imaging technique. Therefore, according to the requirements of the tissue engineering studies, the most appropriate tool should be selected among a variety of imaging modalities. The goal of this review article is to describe available biomedical imaging methods to assess tissue engineering applications and to provide tissue engineers with criteria and insights for determining the best imaging strategies. Commonly used biomedical imaging modalities, including X-ray and computed tomography, positron emission tomography and single photon emission computed tomography, magnetic resonance imaging, ultrasound imaging, optical imaging, and emerging techniques and multimodal imaging, will be discussed, focusing on the latest trends of their applications in recent tissue engineering studies. PMID:25012069

Advances in bionanomaterials for bone tissue engineering.

PubMed

Scott, Timothy G; Blackburn, Gary; Ashley, Michael; Bayer, Ilker S; Ghosh, Anindya; Biris, Alexandru S; Biswas, Abhijit

2013-01-01

Bone is a specialized form of connective tissue that forms the skeleton of the body and is built at the nano and microscale levels as a multi-component composite material consisting of a hard inorganic phase (minerals) in an elastic, dense organic network. Mimicking bone structure and its properties present an important frontier in the fields of nanotechnology, materials science and bone tissue engineering, given the complex morphology of this tissue. There has been a growing interest in developing artificial bone-mimetic nanomaterials with controllable mineral content, nanostructure, chemistry for bone, cartilage tissue engineering and substitutes. This review describes recent advances in bionanomaterials for bone tissue engineering including developments in soft tissue engineering. The significance and basic process of bone tissue engineering along with different bionanomaterial bone scaffolds made of nanocomposites and nanostructured biopolymers/bioceramics and the prerequisite biomechanical functions are described. It also covers latest developments in soft-tissue reconstruction and replacement. Finally, perspectives on the future direction in nanotechnology-enabled bone tissue engineering are presented.

Present status and future potential of enhancing bone healing using nanotechnology.

PubMed

Stylios, George; Wan, Taoyu; Giannoudis, Peter

2007-03-01

An overview of the current state of tissue engineering material systems used in bone healing is presented. A variety of fabrication processes have been developed that have resulted in porous implant substrates that can address unresolved clinical problems. The merits of these biomaterial systems are evaluated in the context of the mechanical properties and biomedical performances most suitable for bone healing. An optimal scaffold for bone tissue engineering applications should be biocompatible and act as a 3D template for in vitro and in vivo bone growth; in addition, its degradation products should be non-toxic and easily excreted by the body. To achieve these features, scaffolds must consist of an interconnected porous network of micro- and nanoscale to allow extensive body fluid transport through the pores, which will trigger bone ingrowth, cell migration, tissue ingrowth, and eventually vascularization.

Biomechanics and mechanobiology in functional tissue engineering.

PubMed

Guilak, Farshid; Butler, David L; Goldstein, Steven A; Baaijens, Frank P T

2014-06-27

The field of tissue engineering continues to expand and mature, and several products are now in clinical use, with numerous other preclinical and clinical studies underway. However, specific challenges still remain in the repair or regeneration of tissues that serve a predominantly biomechanical function. Furthermore, it is now clear that mechanobiological interactions between cells and scaffolds can critically influence cell behavior, even in tissues and organs that do not serve an overt biomechanical role. Over the past decade, the field of "functional tissue engineering" has grown as a subfield of tissue engineering to address the challenges and questions on the role of biomechanics and mechanobiology in tissue engineering. Originally posed as a set of principles and guidelines for engineering of load-bearing tissues, functional tissue engineering has grown to encompass several related areas that have proven to have important implications for tissue repair and regeneration. These topics include measurement and modeling of the in vivo biomechanical environment; quantitative analysis of the mechanical properties of native tissues, scaffolds, and repair tissues; development of rationale criteria for the design and assessment of engineered tissues; investigation of the effects biomechanical factors on native and repair tissues, in vivo and in vitro; and development and application of computational models of tissue growth and remodeling. Here we further expand this paradigm and provide examples of the numerous advances in the field over the past decade. Consideration of these principles in the design process will hopefully improve the safety, efficacy, and overall success of engineered tissue replacements. Copyright © 2014 Elsevier Ltd. All rights reserved.

Ultrasound Technologies for the Spatial Patterning of Cells and Extracellular Matrix Proteins and the Vascularization of Engineered Tissue

NASA Astrophysics Data System (ADS)

Garvin, Kelley A.

Technological advancements in the field of tissue engineering could save the lives of thousands of organ transplant patients who die each year while waiting for donor organs. Currently, two of the primary challenges preventing tissue engineers from developing functional replacement tissues and organs are the need to recreate complex cell and extracellular microenvironments and to vascularize the tissue to maintain cell viability and function. Ultrasound is a form of mechanical energy that can noninvasively and nondestructively interact with tissues at the cell and protein level. In this thesis, novel ultrasound-based technologies were developed for the spatial patterning of cells and extracellular matrix proteins and the vascularization of three-dimensional engineered tissue constructs. Acoustic radiation forces associated with ultrasound standing wave fields were utilized to noninvasively control the spatial organization of cells and cell-bound extracellular matrix proteins within collagen-based engineered tissue. Additionally, ultrasound induced thermal mechanisms were exploited to site-specifically pattern various extracellular matrix collagen microstructures within a single engineered tissue construct. Finally, ultrasound standing wave field technology was used to promote the rapid and extensive vascularization of three-dimensional tissue constructs. As such, the ultrasound technologies developed in these studies have the potential to provide the field of tissue engineering with novel strategies to spatially pattern cells and extracellular matrix components and to vascularize engineered tissue, and thus, could advance the fabrication of functional replacement tissues and organs in the field of tissue engineering.

Micro- and nanotechnology in cardiovascular tissue engineering.

PubMed

Zhang, Boyang; Xiao, Yun; Hsieh, Anne; Thavandiran, Nimalan; Radisic, Milica

2011-12-09

While in nature the formation of complex tissues is gradually shaped by the long journey of development, in tissue engineering constructing complex tissues relies heavily on our ability to directly manipulate and control the micro-cellular environment in vitro. Not surprisingly, advancements in both microfabrication and nanofabrication have powered the field of tissue engineering in many aspects. Focusing on cardiac tissue engineering, this paper highlights the applications of fabrication techniques in various aspects of tissue engineering research: (1) cell responses to micro- and nanopatterned topographical cues, (2) cell responses to patterned biochemical cues, (3) controlled 3D scaffolds, (4) patterned tissue vascularization and (5) electromechanical regulation of tissue assembly and function.

Tissue engineering, stem cells, and cloning for the regeneration of urologic organs.

PubMed

Atala, Anthony

2003-10-01

Tissue engineering efforts are currently being undertaken for every type of tissue and organ within the urinary system. Most of the effort expended to engineer genitourinary tissues has occurred within the last decade. Tissue engineering techniques require a cell culture facility designed for human application. Personnel who have mastered the techniques of cell harvest, culture, and expansion as well as polymer design are essential for the successful application of this technology. Various engineered genitourinary tissues are at different stages of development, with some already being used clinically, a few in preclinical trials, and some in the discovery stage. Recent progress suggests that engineered urologic tissues may have an expanded clinical applicability in the future.

Scholte wave generation during single tracking location shear wave elasticity imaging of engineered tissues.

PubMed

Mercado, Karla P; Langdon, Jonathan; Helguera, María; McAleavey, Stephen A; Hocking, Denise C; Dalecki, Diane

2015-08-01

The physical environment of engineered tissues can influence cellular functions that are important for tissue regeneration. Thus, there is a critical need for noninvasive technologies capable of monitoring mechanical properties of engineered tissues during fabrication and development. This work investigates the feasibility of using single tracking location shear wave elasticity imaging (STL-SWEI) for quantifying the shear moduli of tissue-mimicking phantoms and engineered tissues in tissue engineering environments. Scholte surface waves were observed when STL-SWEI was performed through a fluid standoff, and confounded shear moduli estimates leading to an underestimation of moduli in regions near the fluid-tissue interface.

Cardiovascular tissue engineering: where we come from and where are we now?

PubMed

Smit, Francis E; Dohmen, Pascal M

2015-01-27

Abstract Tissue engineering was introduced by Vacanti and Langer in the 80's, exploring the potential of this new technology starting with the well-known "human ear on the mouse back". The goal is to create a substitute which supplies an individual therapy for patients with regeneration, remodeling and growth potential. The growth potential of these subjects is of special interest in congenital cardiac surgery, avoiding repeated interventions and surgery. Initial applications of tissue engineered created substitutes were relatively simple cardiovascular grafts seeded initially by end-differentiated autologous endothelial cells. Important data were collected from these initial clinical autologous endothelial cell seeded grafts in peripheral and coronary vessel disease. After these initial successfully implantation bone marrow cell were used to seed patches and pulmonary conduits were implanted in patients. Driven by the positive results of tissue engineered material implanted under low pressure circumstances, first tissue engineered patches were implanted in the systemic circulation followed by the implantation of tissue engineered aortic heart valves. Tissue engineering is an extreme dynamic technology with continuously modifications and improvements to optimize clinical products. New technologies are unified and so this has also be done with tissue engineering and new application features, so called transcatheter valve intervention. First studies are initiated to apply tissue engineered heart valves with this new transcatheter delivery system less invasive. Simultaneously studies have been started on tissue engineering of so-called whole organs since organ transplantation is restricted due to donor shortage and tissue engineering could overcome this problem. Initial studies of whole heart engineering in the rat model are promising and larger size models are initiated.

40 CFR 122.26 - Storm water discharges (applicable to State NPDES programs, see § 123.25).

Code of Federal Regulations, 2011 CFR

2011-07-01

... controls would be those suitable to the site conditions and consistent with generally accepted engineering... Wetlands Inventory as wetlands; and (9) Found to have pollutants in bottom sediments, fish tissue or...

78 FR 69645 - Ohio State University, et al.; Notice of Consolidated Decision on Applications for Duty-Free...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-20

... failure of orthopaedic implants, and also the evaluation of new materials and implant surfaces for tissue engineering applications. The cryo-preparation, cryo-transfer and cryo-imaging capabilities will enable...

Mechanical preconditioning enables electrophysiologic coupling of skeletal myoblast cells to myocardium

PubMed Central

Treskes, Philipp; Cowan, Douglas B.; Stamm, Christof; Rubach, Martin; Adelmann, Roland; Wittwer, Thorsten; Wahlers, Thorsten

2015-01-01

Objective The effect of mechanical preconditioning on skeletal myoblasts in engineered tissue constructs was investigated to resolve issues associated with conduction block between skeletal myoblast cells and cardiomyocytes. Methods Murine skeletal myoblasts were used to generate engineered tissue constructs with or without application of mechanical strain. After in vitro myotube formation, engineered tissue constructs were co-cultured for 6 days with viable embryonic heart slices. With the use of sharp electrodes, electrical coupling between engineered tissue constructs and embryonic heart slices was assessed in the presence or absence of pharmacologic agents. Results The isolation and expansion procedure for skeletal myoblasts resulted in high yields of homogeneously desmin-positive (97.1% ± 0.1%) cells. Mechanical strain was exerted on myotubes within engineered tissue constructs during gelation of the matrix, generating preconditioned engineered tissue constructs. Electrical coupling between preconditioned engineered tissue constructs and embryonic heart slices was observed; however, no coupling was apparent when engineered tissue constructs were not subjected to mechanical strain. Coupling of cells from engineered tissue constructs to cells in embryonic heart slices showed slower conduction velocities than myocardial cells with the embryonic heart slices (preconditioned engineered tissue constructs vs embryonic heart slices: 0.04 ± 0.02 ms vs 0.10 ± 0.05 ms, P = .011), lower stimulation frequencies (preconditioned engineered tissue constructs vs maximum embryonic heart slices: 4.82 ± 1.42 Hz vs 10.58 ± 1.56 Hz; P = .0009), and higher sensitivities to the gap junction inhibitor (preconditioned engineered tissue constructs vs embryonic heart slices: 0.22 ± 0.07 mmol/L vs 0.93 ± 0.15 mmol/L; P = .0004). Conclusions We have generated skeletal myoblast–based transplantable grafts that electrically couple to myocardium. PMID:22980065

Potential for Imaging Engineered Tissues with X-Ray Phase Contrast

PubMed Central

Appel, Alyssa; Anastasio, Mark A.

2011-01-01

As the field of tissue engineering advances, it is crucial to develop imaging methods capable of providing detailed three-dimensional information on tissue structure. X-ray imaging techniques based on phase-contrast (PC) have great potential for a number of biomedical applications due to their ability to provide information about soft tissue structure without exogenous contrast agents. X-ray PC techniques retain the excellent spatial resolution, tissue penetration, and calcified tissue contrast of conventional X-ray techniques while providing drastically improved imaging of soft tissue and biomaterials. This suggests that X-ray PC techniques are very promising for evaluation of engineered tissues. In this review, four different implementations of X-ray PC imaging are described and applications to tissues of relevance to tissue engineering reviewed. In addition, recent applications of X-ray PC to the evaluation of biomaterial scaffolds and engineered tissues are presented and areas for further development and application of these techniques are discussed. Imaging techniques based on X-ray PC have significant potential for improving our ability to image and characterize engineered tissues, and their continued development and optimization could have significant impact on the field of tissue engineering. PMID:21682604

Integrated approaches to spatiotemporally directing angiogenesis in host and engineered tissues.

PubMed

Kant, Rajeev J; Coulombe, Kareen L K

2018-03-15

The field of tissue engineering has turned towards biomimicry to solve the problem of tissue oxygenation and nutrient/waste exchange through the development of vasculature. Induction of angiogenesis and subsequent development of a vascular bed in engineered tissues is actively being pursued through combinations of physical and chemical cues, notably through the presentation of topographies and growth factors. Presenting angiogenic signals in a spatiotemporal fashion is beginning to generate improved vascular networks, which will allow for the creation of large and dense engineered tissues. This review provides a brief background on the cells, mechanisms, and molecules driving vascular development (including angiogenesis), followed by how biomaterials and growth factors can be used to direct vessel formation and maturation. Techniques to accomplish spatiotemporal control of vascularization include incorporation or encapsulation of growth factors, topographical engineering, and 3D bioprinting. The vascularization of engineered tissues and their application in angiogenic therapy in vivo is reviewed herein with an emphasis on the most densely vascularized tissue of the human body - the heart. Vascularization is vital to wound healing and tissue regeneration, and development of hierarchical networks enables efficient nutrient transfer. In tissue engineering, vascularization is necessary to support physiologically dense engineered tissues, and thus the field seeks to induce vascular formation using biomaterials and chemical signals to provide appropriate, pro-angiogenic signals for cells. This review critically examines the materials and techniques used to generate scaffolds with spatiotemporal cues to direct vascularization in engineered and host tissues in vitro and in vivo. Assessment of the field's progress is intended to inspire vascular applications across all forms of tissue engineering with a specific focus on highlighting the nuances of cardiac tissue engineering for the greater regenerative medicine community. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Biomechanics and mechanobiology in functional tissue engineering

PubMed Central

Guilak, Farshid; Butler, David L.; Goldstein, Steven A.; Baaijens, Frank P.T.

2014-01-01

The field of tissue engineering continues to expand and mature, and several products are now in clinical use, with numerous other preclinical and clinical studies underway. However, specific challenges still remain in the repair or regeneration of tissues that serve a predominantly biomechanical function. Furthermore, it is now clear that mechanobiological interactions between cells and scaffolds can critically influence cell behavior, even in tissues and organs that do not serve an overt biomechanical role. Over the past decade, the field of “functional tissue engineering” has grown as a subfield of tissue engineering to address the challenges and questions on the role of biomechanics and mechanobiology in tissue engineering. Originally posed as a set of principles and guidelines for engineering of load-bearing tissues, functional tissue engineering has grown to encompass several related areas that have proven to have important implications for tissue repair and regeneration. These topics include measurement and modeling of the in vivo biomechanical environment; quantitative analysis of the mechanical properties of native tissues, scaffolds, and repair tissues; development of rationale criteria for the design and assessment of engineered tissues; investigation of the effects biomechanical factors on native and repair tissues, in vivo and in vitro; and development and application of computational models of tissue growth and remodeling. Here we further expand this paradigm and provide examples of the numerous advances in the field over the past decade. Consideration of these principles in the design process will hopefully improve the safety, efficacy, and overall success of engineered tissue replacements. PMID:24818797

In vivo tissue engineering of musculoskeletal tissues.

PubMed

McCullen, Seth D; Chow, Andre G Y; Stevens, Molly M

2011-10-01

Tissue engineering of musculoskeletal tissues often involves the in vitro manipulation and culture of progenitor cells, growth factors and biomaterial scaffolds. Though in vitro tissue engineering has greatly increased our understanding of cellular behavior and cell-material interactions, this methodology is often unable to recreate tissue with the hierarchical organization and vascularization found within native tissues. Accordingly, investigators have focused on alternative in vivo tissue engineering strategies, whereby the traditional triad (cells, growth factors, scaffolds) or a combination thereof are directly implanted at the damaged tissue site or within ectopic sites capable of supporting neo-tissue formation. In vivo tissue engineering may offer a preferential route for regeneration of musculoskeletal and other tissues with distinct advantages over in vitro methods based on the specific location of endogenous cultivation, recruitment of autologous cells, and patient-specific regenerated tissues. Copyright © 2011 Elsevier Ltd. All rights reserved.

Chitosan-g-lactide copolymers for fabrication of 3D scaffolds for tissue engineering

NASA Astrophysics Data System (ADS)

Demina, T. S.; Zaytseva-Zotova, D. S.; Timashev, P. S.; Bagratashvili, V. N.; Bardakova, K. N.; Sevrin, Ch; Svidchenko, E. A.; Surin, N. M.; Markvicheva, E. A.; Grandfils, Ch; Akopova, T. A.

2015-07-01

Chitosan-g-oligo (L, D-lactide) copolymers were synthesized and assessed to fabricate a number of 3D scaffolds using a variety of technologies such as oil/water emulsion evaporation technique, freeze-drying and two-photon photopolymerization. Solid-state copolymerization method allowed us to graft up to 160 wt-% of oligolactide onto chitosan backbone via chitosan amino group acetylation with substitution degree reaching up to 0.41. Grafting of hydrophobic oligolactide side chains with polymerization degree up to 10 results in chitosan amphiphilic properties. The synthesized chitosan-g-lactide copolymers were used to design 3D scaffolds for tissue engineering such as spherical microparticles and macroporous hydrogels.

The necessity of a theory of biology for tissue engineering: metabolism-repair systems.

PubMed

Ganguli, Suman; Hunt, C Anthony

2004-01-01

Since there is no widely accepted global theory of biology, tissue engineering and bioengineering lack a theoretical understanding of the systems being engineered. By default, tissue engineering operates with a "reductionist" theoretical approach, inherited from traditional engineering of non-living materials. Long term, that approach is inadequate, since it ignores essential aspects of biology. Metabolism-repair systems are a theoretical framework which explicitly represents two "functional" aspects of living organisms: self-repair and self-replication. Since repair and replication are central to tissue engineering, we advance metabolism-repair systems as a potential theoretical framework for tissue engineering. We present an overview of the framework, and indicate directions to pursue for extending it to the context of tissue engineering. We focus on biological networks, both metabolic and cellular, as one such direction. The construction of these networks, in turn, depends on biological protocols. Together these concepts may help point the way to a global theory of biology appropriate for tissue engineering.

Towards organ printing: engineering an intra-organ branched vascular tree.

PubMed

Visconti, Richard P; Kasyanov, Vladimir; Gentile, Carmine; Zhang, Jing; Markwald, Roger R; Mironov, Vladimir

2010-03-01

Effective vascularization of thick three-dimensional engineered tissue constructs is a problem in tissue engineering. As in native organs, a tissue-engineered intra-organ vascular tree must be comprised of a network of hierarchically branched vascular segments. Despite this requirement, current tissue-engineering efforts are still focused predominantly on engineering either large-diameter macrovessels or microvascular networks. We present the emerging concept of organ printing or robotic additive biofabrication of an intra-organ branched vascular tree, based on the ability of vascular tissue spheroids to undergo self-assembly. The feasibility and challenges of this robotic biofabrication approach to intra-organ vascularization for tissue engineering based on organ-printing technology using self-assembling vascular tissue spheroids including clinically relevantly vascular cell sources are analyzed. It is not possible to engineer 3D thick tissue or organ constructs without effective vascularization. An effective intra-organ vascular system cannot be built by the simple connection of large-diameter vessels and microvessels. Successful engineering of functional human organs suitable for surgical implantation will require concomitant engineering of a 'built in' intra-organ branched vascular system. Organ printing enables biofabrication of human organ constructs with a 'built in' intra-organ branched vascular tree.

Human iPSC-derived cardiomyocytes and tissue engineering strategies for disease modeling and drug screening

PubMed Central

Smith, Alec S.T.; Macadangdang, Jesse; Leung, Winnie; Laflamme, Michael A.; Kim, Deok-Ho

2016-01-01

Improved methodologies for modeling cardiac disease phenotypes and accurately screening the efficacy and toxicity of potential therapeutic compounds are actively being sought to advance drug development and improve disease modeling capabilities. To that end, much recent effort has been devoted to the development of novel engineered biomimetic cardiac tissue platforms that accurately recapitulate the structure and function of the human myocardium. Within the field of cardiac engineering, induced pluripotent stem cells (iPSCs) are an exciting tool that offer the potential to advance the current state of the art, as they are derived from somatic cells, enabling the development of personalized medical strategies and patient specific disease models. Here we review different aspects of iPSC-based cardiac engineering technologies. We highlight methods for producing iPSC-derived cardiomyocytes (iPSC-CMs) and discuss their application to compound efficacy/toxicity screening and in vitro modeling of prevalent cardiac diseases. Special attention is paid to the application of micro- and nano-engineering techniques for the development of novel iPSC-CM based platforms and their potential to advance current preclinical screening modalities. PMID:28007615

Piezoelectric polymers as biomaterials for tissue engineering applications.

PubMed

Ribeiro, Clarisse; Sencadas, Vítor; Correia, Daniela M; Lanceros-Méndez, Senentxu

2015-12-01

Tissue engineering often rely on scaffolds for supporting cell differentiation and growth. Novel paradigms for tissue engineering include the need of active or smart scaffolds in order to properly regenerate specific tissues. In particular, as electrical and electromechanical clues are among the most relevant ones in determining tissue functionality in tissues such as muscle and bone, among others, electroactive materials and, in particular, piezoelectric ones, show strong potential for novel tissue engineering strategies, in particular taking also into account the existence of these phenomena within some specific tissues, indicating their requirement also during tissue regeneration. This referee reports on piezoelectric materials used for tissue engineering applications. The most used materials for tissue engineering strategies are reported together with the main achievements, challenges and future needs for research and actual therapies. This review provides thus a compilation of the most relevant results and strategies and a start point for novel research pathways in the most relevant and challenging open questions. Copyright © 2015 Elsevier B.V. All rights reserved.

The Crosstalk between Tissue Engineering and Pharmaceutical Biotechnology: Recent Advances and Future Directions.

PubMed

Pacheco, Daniela P; Reis, Rui L; Correlo, Vítor M; Marques, Alexandra P

2015-01-01

Tissue-engineered constructs made of biotechnology-derived materials have been preferred due to their chemical and physical composition, which offers both high versatility and a support to enclose/ incorporate relevant signaling molecules and/or genes known to therapeutically induce tissue repair. Herein, a critical overview of the impact of different biotechnology-derived materials, scaffolds, and recombinant signaling molecules over the behavior of cells, another element of tissue engineered constructs, as well its regulatory role in tissue regeneration and disease progression is given. Additionally, these tissue-engineered constructs evolved to three-dimensional (3D) tissue-like models that, as an advancement of two-dimensional standard culture methods, are expected to be a valuable tool in the field of drug discovery and pharmaceutical research. Despite the improved design and conception of current proposed 3D tissue-like models, advanced control systems to enable and accelerate streamlining and automation of the numerous labor-intensive steps intrinsic to the development of tissue-engineered constructs are still to be achieved. In this sense, this review intends to present the biotechnology- derived materials that are being explored in the field of tissue engineering to generate 3D tissue-analogues and briefly highlight their foremost breakthroughs in tissue regeneration and drug discovery. It also aims to reinforce that the crosstalk between tissue engineering and pharmaceutical biotechnology has been fostering the outcomes of tissue engineering approaches through the use of biotechnology-derived signaling molecules. Gene delivery/therapy is also discussed as a forefront area that represents another cross point between tissue engineering and pharmaceutical biotechnology, in which nucleic acids can be considered a "super pharmaceutical" to drive biological responses, including tissue regeneration.

Injectable hydrogels for cartilage and bone tissue engineering

PubMed Central

Liu, Mei; Zeng, Xin; Ma, Chao; Yi, Huan; Ali, Zeeshan; Mou, Xianbo; Li, Song; Deng, Yan; He, Nongyue

2017-01-01

Tissue engineering has become a promising strategy for repairing damaged cartilage and bone tissue. Among the scaffolds for tissue-engineering applications, injectable hydrogels have demonstrated great potential for use as three-dimensional cell culture scaffolds in cartilage and bone tissue engineering, owing to their high water content, similarity to the natural extracellular matrix (ECM), porous framework for cell transplantation and proliferation, minimal invasive properties, and ability to match irregular defects. In this review, we describe the selection of appropriate biomaterials and fabrication methods to prepare novel injectable hydrogels for cartilage and bone tissue engineering. In addition, the biology of cartilage and the bony ECM is also summarized. Finally, future perspectives for injectable hydrogels in cartilage and bone tissue engineering are discussed. PMID:28584674

[Strategies to choose scaffold materials for tissue engineering].

PubMed

Gao, Qingdong; Zhu, Xulong; Xiang, Junxi; Lü, Yi; Li, Jianhui

2016-02-01

Current therapies of organ failure or a wide range of tissue defect are often not ideal. Transplantation is the only effective way for long time survival. But it is hard to meet huge patients demands because of donor shortage, immune rejection and other problems. Tissue engineering could be a potential option. Choosing a suitable scaffold material is an essential part of it. According to different sources, tissue engineering scaffold materials could be divided into three types which are natural and its modified materials, artificial and composite ones. The purpose of tissue engineering scaffold is to repair the tissues or organs damage, so could reach the ideal recovery in its function and structure aspect. Therefore, tissue engineering scaffold should even be as close as much to the original tissue or organs in function and structure. We call it "organic scaffold" and this strategy might be the drastic perfect substitute for the tissues or organs in concern. Optimized organization with each kind scaffold materials could make up for biomimetic structure and function of the tissue or organs. Scaffold material surface modification, optimized preparation procedure and cytosine sustained-release microsphere addition should be considered together. This strategy is expected to open new perspectives for tissue engineering. Multidisciplinary approach including material science, molecular biology, and engineering might find the most ideal tissue engineering scaffold. Using the strategy of drawing on each other strength and optimized organization with each kind scaffold material to prepare a multifunctional biomimetic tissue engineering scaffold might be a good method for choosing tissue engineering scaffold materials. Our research group had differentiated bone marrow mesenchymal stem cells into bile canaliculi like cells. We prepared poly(L-lactic acid)/poly(ε-caprolactone) biliary stent. The scaffold's internal played a part in the long-term release of cytokines which mixed with sustained-release nano-microsphere containing growth factors. What's more, the stent internal surface coated with glue/collagen matrix mixing layer containing bFGF and EGF so could supplying the early release of the two cytokines. Finally, combining the poly(L-lactic acid)/poly(ε-caprolactone) biliary stent with the induced cells was the last step for preparing tissue-engineered bile duct. This literature reviewed a variety of the existing tissue engineering scaffold materials and briefly introduced the impact factors on the characteristics of tissue engineering scaffold materials such as preparation procedure, surface modification of scaffold, and so on. We explored the choosing strategy of desired tissue engineering scaffold materials.

The Application of Tissue Engineering Procedures to Repair the Larynx

ERIC Educational Resources Information Center

Ringel, Robert L.; Kahane, Joel C.; Hillsamer, Peter J.; Lee, Annie S.; Badylak, Stephen F.

2006-01-01

The field of tissue engineering/regenerative medicine combines the quantitative principles of engineering with the principles of the life sciences toward the goal of reconstituting structurally and functionally normal tissues and organs. There has been relatively little application of tissue engineering efforts toward the organs of speech, voice,…

Tissue Engineering and Regenerative Medicine 2015: A Year in Review.

PubMed

Wobma, Holly; Vunjak-Novakovic, Gordana

2016-04-01

This may be the most exciting time ever for the field of tissue engineering and regenerative medicine (TERM). After decades of progress, it has matured, integrated, and diversified into entirely new areas, and it is starting to make the pivotal shift toward translation. The most exciting science and applications continue to emerge at the boundaries of disciplines, through increasingly effective interactions between stem cell biologists, bioengineers, clinicians, and the commercial sector. In this "Year in Review," we highlight some of the major advances reported over the last year (Summer 2014-Fall 2015). Using a methodology similar to that established in previous years, we identified four areas that generated major progress in the field: (i) pluripotent stem cells, (ii) microtissue platforms for drug testing and disease modeling, (iii) tissue models of cancer, and (iv) whole organ engineering. For each area, we used some of the most impactful articles to illustrate the important concepts and results that advanced the state of the art of TERM. We conclude with reflections on emerging areas and perspectives for future development in the field.

Tissue Engineering and Regenerative Medicine 2015: A Year in Review

PubMed Central

Wobma, Holly

2016-01-01

This may be the most exciting time ever for the field of tissue engineering and regenerative medicine (TERM). After decades of progress, it has matured, integrated, and diversified into entirely new areas, and it is starting to make the pivotal shift toward translation. The most exciting science and applications continue to emerge at the boundaries of disciplines, through increasingly effective interactions between stem cell biologists, bioengineers, clinicians, and the commercial sector. In this “Year in Review,” we highlight some of the major advances reported over the last year (Summer 2014–Fall 2015). Using a methodology similar to that established in previous years, we identified four areas that generated major progress in the field: (i) pluripotent stem cells, (ii) microtissue platforms for drug testing and disease modeling, (iii) tissue models of cancer, and (iv) whole organ engineering. For each area, we used some of the most impactful articles to illustrate the important concepts and results that advanced the state of the art of TERM. We conclude with reflections on emerging areas and perspectives for future development in the field. PMID:26714410

Vascularisation to improve translational potential of tissue engineering systems for cardiac repair.

PubMed

Dilley, Rodney J; Morrison, Wayne A

2014-11-01

Cardiac tissue engineering is developing as an alternative approach to heart transplantation for treating heart failure. Shortage of organ donors and complications arising after orthotopic transplant remain major challenges to the modern field of heart transplantation. Engineering functional myocardium de novo requires an abundant source of cardiomyocytes, a biocompatible scaffold material and a functional vasculature to sustain the high metabolism of the construct. Progress has been made on several fronts, with cardiac cell biology, stem cells and biomaterials research particularly promising for cardiac tissue engineering, however currently employed strategies for vascularisation have lagged behind and limit the volume of tissue formed. Over ten years we have developed an in vivo tissue engineering model to construct vascularised tissue from various cell and tissue sources, including cardiac tissue. In this article we review the progress made with this approach and others, together with their potential to support a volume of engineered tissue for cardiac tissue engineering where contractile mass impacts directly on functional outcomes in translation to the clinic. It is clear that a scaled-up cardiac tissue engineering solution required for clinical treatment of heart failure will include a robust vascular supply for successful translation. This article is part of a directed issue entitled: Regenerative Medicine: the challenge of translation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Gene delivery for periodontal tissue engineering: current knowledge - future possibilities.

PubMed

Chen, Fa-Ming; Ma, Zhi-Wei; Wang, Qin-Tao; Wu, Zhi-Fen

2009-08-01

The cellular and molecular events of periodontal healing are coordinated and regulated by an elaborate system of signaling molecules, pointing to a primary strategy for functional periodontal compartment regeneration to replicate components of the natural cellular microenvironment by providing an artificial extracellular matrix (ECM) and by delivering growth factors. However, even with optimal carriers, the localized delivery of growth factors often requires a large amount of protein to stimulate significant effects in vivo, which increases the risk and unwanted side effects. A simple and relatively new approach to bypassing this dilemma involves converting cells into protein producing factories. This is done by a so-called gene delivery method, where therapeutic agents to be delivered are DNA plasmids that include the gene encoding desired growth factors instead of recombinant proteins. As localized depots of genes, novel gene delivery systems have the potential to release their cargo in a sustained and controlled manner and finally provide time- and space- dependent levels of encoded proteins during all stages of tissue regrowth, offering great versatility in their application and prompting new tissue engineering strategy in periodontal regenerative medicine. However, gene therapy in Periodontology is clearly in its infancy. Significant efforts still need to be made in developing safe and effective delivery platforms and clarifying how gene delivery, in combination with tissue engineering, may mimic the critical aspects of natural biological processes occurring in periodontal development and repair. The aim of this review is to trace an outline of the state-of-the-art in the application of gene delivery and tissue engineering strategies for periodontal healing and regeneration.

Controlling the Porosity and Microarchitecture of Hydrogels for Tissue Engineering

PubMed Central

Annabi, Nasim; Nichol, Jason W.; Zhong, Xia; Ji, Chengdong; Koshy, Sandeep; Khademhosseini, Ali

2010-01-01

Tissue engineering holds great promise for regeneration and repair of diseased tissues, making the development of tissue engineering scaffolds a topic of great interest in biomedical research. Because of their biocompatibility and similarities to native extracellular matrix, hydrogels have emerged as leading candidates for engineered tissue scaffolds. However, precise control of hydrogel properties, such as porosity, remains a challenge. Traditional techniques for creating bulk porosity in polymers have demonstrated success in hydrogels for tissue engineering; however, often the conditions are incompatible with direct cell encapsulation. Emerging technologies have demonstrated the ability to control porosity and the microarchitectural features in hydrogels, creating engineered tissues with structure and function similar to native tissues. In this review, we explore the various technologies for controlling the porosity and microarchitecture within hydrogels, and demonstrate successful applications of combining these techniques. PMID:20121414

Review paper: critical issues in tissue engineering: biomaterials, cell sources, angiogenesis, and drug delivery systems.

PubMed

Naderi, Hojjat; Matin, Maryam M; Bahrami, Ahmad Reza

2011-11-01

Tissue engineering is a newly emerging biomedical technology, which aids and increases the repair and regeneration of deficient and injured tissues. It employs the principles from the fields of materials science, cell biology, transplantation, and engineering in an effort to treat or replace damaged tissues. Tissue engineering and development of complex tissues or organs, such as heart, muscle, kidney, liver, and lung, are still a distant milestone in twenty-first century. Generally, there are four main challenges in tissue engineering which need optimization. These include biomaterials, cell sources, vascularization of engineered tissues, and design of drug delivery systems. Biomaterials and cell sources should be specific for the engineering of each tissue or organ. On the other hand, angiogenesis is required not only for the treatment of a variety of ischemic conditions, but it is also a critical component of virtually all tissue-engineering strategies. Therefore, controlling the dose, location, and duration of releasing angiogenic factors via polymeric delivery systems, in order to ultimately better mimic the stem cell niche through scaffolds, will dictate the utility of a variety of biomaterials in tissue regeneration. This review focuses on the use of polymeric vehicles that are made of synthetic and/or natural biomaterials as scaffolds for three-dimensional cell cultures and for locally delivering the inductive growth factors in various formats to provide a method of controlled, localized delivery for the desired time frame and for vascularized tissue-engineering therapies.

Strategies and applications for incorporating physical and chemical signal gradients in tissue engineering.

PubMed

Singh, Milind; Berkland, Cory; Detamore, Michael S

2008-12-01

From embryonic development to wound repair, concentration gradients of bioactive signaling molecules guide tissue formation and regeneration. Moreover, gradients in cellular and extracellular architecture as well as in mechanical properties are readily apparent in native tissues. Perhaps tissue engineers can take a cue from nature in attempting to regenerate tissues by incorporating gradients into engineering design strategies. Indeed, gradient-based approaches are an emerging trend in tissue engineering, standing in contrast to traditional approaches of homogeneous delivery of cells and/or growth factors using isotropic scaffolds. Gradients in tissue engineering lie at the intersection of three major paradigms in the field-biomimetic, interfacial, and functional tissue engineering-by combining physical (via biomaterial design) and chemical (with growth/differentiation factors and cell adhesion molecules) signal delivery to achieve a continuous transition in both structure and function. This review consolidates several key methodologies to generate gradients, some of which have never been employed in a tissue engineering application, and discusses strategies for incorporating these methods into tissue engineering and implant design. A key finding of this review was that two-dimensional physicochemical gradient substrates, which serve as excellent high-throughput screening tools for optimizing desired biomaterial properties, can be enhanced in the future by transitioning from two dimensions to three dimensions, which would enable studies of cell-protein-biomaterial interactions in a more native tissue-like environment. In addition, biomimetic tissue regeneration via combined delivery of graded physical and chemical signals appears to be a promising strategy for the regeneration of heterogeneous tissues and tissue interfaces. In the future, in vivo applications will shed more light on the performance of gradient-based mechanical integrity and signal delivery strategies compared to traditional tissue engineering approaches.

Cell interactions in bone tissue engineering.

PubMed

Pirraco, R P; Marques, A P; Reis, R L

2010-01-01

Bone fractures, where the innate regenerative bone response is compromised, represent between 4 and 8 hundred thousands of the total fracture cases, just in the United States. Bone tissue engineering (TE) brought the notion that, in cases such as those, it was preferable to boost the healing process of bone tissue instead of just adding artificial parts that could never properly replace the native tissue. However, despite the hype, bone TE so far could not live up to its promises and new bottom-up approaches are needed. The study of the cellular interactions between the cells relevant for bone biology can be of essential importance to that. In living bone, cells are in a context where communication with adjacent cells is almost permanent. Many fundamental works have been addressing these communications nonetheless, in a bone TE approach, the 3D perspective, being part of the microenvironment of a bone cell, is as crucial. Works combining the study of cell-to-cell interactions in a 3D environment are not as many as expected. Therefore, the bone TE field should not only gain knowledge from the field of fundamental Biology but also contribute for further understanding the biology of bone. In this review, a summary of the main works in the field of bone TE, aiming at studying cellular interactions in a 3D environment, and how they contributed towards the development of a functional engineered bone tissue, is presented.

Breast tissue engineering.

PubMed

Patrick, Charles W

2004-01-01

Tissue engineering has the potential to redefine rehabilitation for the breast cancer patient by providing a translatable strategy that restores the postmastectomy breast mound while concomitantly obviating limitations realized with contemporary reconstructive surgery procedures. The engineering design goal is to provide a sufficient volume of viable fat tissue based on a patient's own cells such that deficits in breast volume can be abrogated. To be sure, adipose tissue engineering is in its infancy, but tremendous strides have been made. Numerous studies attest to the feasibility of adipose tissue engineering. The field is now poised to challenge barriers to clinical translation that are germane to most tissue engineering applications, namely scale-up, large animal model development, and vascularization. The innovative and rapid progress of adipose engineering to date, as well as opportunities for its future growth, is presented.

Microstructural heterogeneity directs micromechanics and mechanobiology in native and engineered fibrocartilage

NASA Astrophysics Data System (ADS)

Han, Woojin M.; Heo, Su-Jin; Driscoll, Tristan P.; Delucca, John F.; McLeod, Claire M.; Smith, Lachlan J.; Duncan, Randall L.; Mauck, Robert L.; Elliott, Dawn M.

2016-04-01

Treatment strategies to address pathologies of fibrocartilaginous tissue are in part limited by an incomplete understanding of structure-function relationships in these load-bearing tissues. There is therefore a pressing need to develop micro-engineered tissue platforms that can recreate the highly inhomogeneous tissue microstructures that are known to influence mechanotransductive processes in normal and diseased tissue. Here, we report the quantification of proteoglycan-rich microdomains in developing, ageing and diseased fibrocartilaginous tissues, and the impact of these microdomains on endogenous cell responses to physiologic deformation within a native-tissue context. We also developed a method to generate heterogeneous tissue-engineered constructs (hetTECs) with non-fibrous proteoglycan-rich microdomains engineered into the fibrous structure, and show that these hetTECs match the microstructural, micromechanical and mechanobiological benchmarks of native tissue. Our tissue-engineered platform should facilitate the study of the mechanobiology of developing, homeostatic, degenerating and regenerating fibrous tissues.

Microstructural heterogeneity directs micromechanics and mechanobiology in native and engineered fibrocartilage.

PubMed

Han, Woojin M; Heo, Su-Jin; Driscoll, Tristan P; Delucca, John F; McLeod, Claire M; Smith, Lachlan J; Duncan, Randall L; Mauck, Robert L; Elliott, Dawn M

2016-04-01

Treatment strategies to address pathologies of fibrocartilaginous tissue are in part limited by an incomplete understanding of structure-function relationships in these load-bearing tissues. There is therefore a pressing need to develop micro-engineered tissue platforms that can recreate the highly inhomogeneous tissue microstructures that are known to influence mechanotransductive processes in normal and diseased tissue. Here, we report the quantification of proteoglycan-rich microdomains in developing, ageing and diseased fibrocartilaginous tissues, and the impact of these microdomains on endogenous cell responses to physiologic deformation within a native-tissue context. We also developed a method to generate heterogeneous tissue-engineered constructs (hetTECs) with non-fibrous proteoglycan-rich microdomains engineered into the fibrous structure, and show that these hetTECs match the microstructural, micromechanical and mechanobiological benchmarks of native tissue. Our tissue-engineered platform should facilitate the study of the mechanobiology of developing, homeostatic, degenerating and regenerating fibrous tissues.

Engineered elastomeric proteins with dual elasticity can be controlled by a molecular regulator.

PubMed

Cao, Yi; Li, Hongbin

2008-08-01

Elastomeric proteins are molecular springs that confer excellent mechanical properties to many biological tissues and biomaterials. Depending on the role performed by the tissue or biomaterial, elastomeric proteins can behave as molecular springs or shock absorbers. Here we combine single-molecule atomic force microscopy and protein engineering techniques to create elastomeric proteins that can switch between two distinct types of mechanical behaviour in response to the binding of a molecular regulator. The proteins are mechanically labile by design and behave as entropic springs with an elasticity that is governed by their configurational entropy. However, when a molecular regulator binds to the protein, it switches into a mechanically stable state and can act as a shock absorber. These engineered proteins effectively mimic and combine the two extreme forms of elastic behaviour found in natural elastomeric proteins, and thus represent a new type of smart nanomaterial that will find potential applications in nanomechanics and material sciences.

Applied Induced Pluripotent Stem Cells in Combination With Biomaterials in Bone Tissue Engineering.

PubMed

Ardeshirylajimi, Abdolreza

2017-10-01

Due to increasing of the orthopedic lesions and fractures in the world and limitation of current treatment methods, researchers, and surgeons paid attention to the new treatment ways especially to tissue engineering and regenerative medicine. Innovation in stem cells and biomaterials accelerate during the last decade as two main important parts of the tissue engineering. Recently, induced pluripotent stem cells (iPSCs) introduced as cells with highly proliferation and differentiation potentials that hold great promising features for used in tissue engineering and regenerative medicine. As another main part of tissue engineering, synthetic, and natural polymers have been shown daily grow up in number to increase and improve the grade of biopolymers that could be used as scaffold with or without stem cells for implantation. One of the developed areas of tissue engineering is bone tissue engineering; the aim of this review is present studies were done in the field of bone tissue engineering while used iPSCs in combination with natural and synthetic biomaterials. J. Cell. Biochem. 118: 3034-3042, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Cell-Based Strategies for Meniscus Tissue Engineering

PubMed Central

Niu, Wei; Guo, Weimin; Han, Shufeng; Zhu, Yun; Liu, Shuyun; Guo, Quanyi

2016-01-01

Meniscus injuries remain a significant challenge due to the poor healing potential of the inner avascular zone. Following a series of studies and clinical trials, tissue engineering is considered a promising prospect for meniscus repair and regeneration. As one of the key factors in tissue engineering, cells are believed to be highly beneficial in generating bionic meniscus structures to replace injured ones in patients. Therefore, cell-based strategies for meniscus tissue engineering play a fundamental role in meniscal regeneration. According to current studies, the main cell-based strategies for meniscus tissue engineering are single cell type strategies; cell coculture strategies also were applied to meniscus tissue engineering. Likewise, on the one side, the zonal recapitulation strategies based on mimicking meniscal differing cells and internal architectures have received wide attentions. On the other side, cell self-assembling strategies without any scaffolds may be a better way to build a bionic meniscus. In this review, we primarily discuss cell seeds for meniscus tissue engineering and their application strategies. We also discuss recent advances and achievements in meniscus repair experiments that further improve our understanding of meniscus tissue engineering. PMID:27274735

Combining platelet-rich plasma and tissue-engineered skin in the treatment of large skin wound.

PubMed

Han, Tong; Wang, Hao; Zhang, Ya Qin

2012-03-01

The objective of the study was to observe the effects of tissue-engineered skin in combination with platelet-rich plasma (PRP) and other preparations on the repair of large skin wound on nude mice.We first prepared PRP from venous blood by density-gradient centrifugation. Large skin wounds were created surgically on the dorsal part of nude mice. The wounds were then treated with either artificial skin, tissue-engineered skin, tissue-engineered skin combined with basic fibroblast growth factor, tissue-engineered skin combined with epidermal growth factor, or tissue-engineered skin combined with PRP. Tissue specimens were collected at different time intervals after surgery. Hematoxylin-eosin and periodic acid-Schiff staining and immunohistochemistry were performed to assess the rate of wound healing.Macroscopic observations, hematoxylin-eosin/periodic acid-Schiff staining, and immunohistochemistry revealed that the wounds treated with tissue-engineered skin in combination with PRP showed the most satisfactory wound recovery, among the 5 groups.

Reverse engineering development: Crosstalk opportunities between developmental biology and tissue engineering.

PubMed

Marcucio, Ralph S; Qin, Ling; Alsberg, Eben; Boerckel, Joel D

2017-11-01

The fields of developmental biology and tissue engineering have been revolutionized in recent years by technological advancements, expanded understanding, and biomaterials design, leading to the emerging paradigm of "developmental" or "biomimetic" tissue engineering. While developmental biology and tissue engineering have long overlapping histories, the fields have largely diverged in recent years at the same time that crosstalk opportunities for mutual benefit are more salient than ever. In this perspective article, we will use musculoskeletal development and tissue engineering as a platform on which to discuss these emerging crosstalk opportunities and will present our opinions on the bright future of these overlapping spheres of influence. The multicellular programs that control musculoskeletal development are rapidly becoming clarified, represented by shifting paradigms in our understanding of cellular function, identity, and lineage specification during development. Simultaneously, advancements in bioartificial matrices that replicate the biochemical, microstructural, and mechanical properties of developing tissues present new tools and approaches for recapitulating development in tissue engineering. Here, we introduce concepts and experimental approaches in musculoskeletal developmental biology and biomaterials design and discuss applications in tissue engineering as well as opportunities for tissue engineering approaches to inform our understanding of fundamental biology. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2356-2368, 2017. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Construction Strategy and Progress of Whole Intervertebral Disc Tissue Engineering.

PubMed

Yang, Qiang; Xu, Hai-wei; Hurday, Sookesh; Xu, Bao-shan

2016-02-01

Degenerative disc disease (DDD) is the major cause of low back pain, which usually leads to work absenteeism, medical visits and hospitalization. Because the current conservative procedures and surgical approaches to treatment of DDD only aim to relieve the symptoms of disease but not to regenerate the diseased disc, their long-term efficiency is limited. With the rapid developments in medical science, tissue engineering techniques have progressed markedly in recent years, providing a novel regenerative strategy for managing intervertebral disc disease. However, there are as yet no ideal methods for constructing tissue-engineered intervertebral discs. This paper reviews published reports pertaining to intervertebral disc tissue engineering and summarizes data concerning the seed cells and scaffold materials for tissue-engineered intervertebral discs, construction of tissue-engineered whole intervertebral discs, relevant animal experiments and effects of mechanics on the construction of tissue-engineered intervertebral disc and outlines the existing problems and future directions. Although the perfect regenerative strategy for treating DDD has not yet been developed, great progress has been achieved in the construction of tissue-engineered intervertebral discs. It is believed that ongoing research on intervertebral disc tissue engineering will result in revolutionary progress in the treatment of DDD. © 2016 Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.

* Animal Models for Periodontal Tissue Engineering: A Knowledge-Generating Process.

PubMed

Fawzy El-Sayed, Karim M; Dörfer, Christof E

2017-12-01

The human periodontium is a uniquely complex vital structure, supporting and anchoring the teeth in their alveolar sockets, thereby playing a decisive role in tooth homeostasis and function. Chronic periodontitis is a highly prevalent immune-inflammatory disease of the periodontium, affecting 15% of adult individuals, and is characterized by progressive destruction of the periodontal tooth-investing tissues, culminating in their irreversible damage. Current periodontal evidence-based treatment strategies achieve periodontal healing via repair processes, mostly combating the inflammatory component of the disease, to halt or reduce prospective periodontal tissue loss. However, complete periodontal tissue regeneration remains a hard fought-for goal in the field of periodontology and multiple in vitro and in vivo studies have been conducted, in the conquest to achieve a functional periodontal tissue regeneration in humans. The present review evaluates the current status of periodontal regeneration attempted through tissue-engineering concepts, ideal requirements for experimental animal models under investigation, the methods of induction and classification of the experimentally created periodontal defects, types of experimental defects employed in the diverse animal studies, as well as the current state of knowledge obtained from in vivo animal experiments, with special emphasis on large animal models.

High Definition Confocal Imaging Modalities for the Characterization of Tissue-Engineered Substitutes.

PubMed

Mayrand, Dominique; Fradette, Julie

2018-01-01

Optimal imaging methods are necessary in order to perform a detailed characterization of thick tissue samples from either native or engineered tissues. Tissue-engineered substitutes are featuring increasing complexity including multiple cell types and capillary-like networks. Therefore, technical approaches allowing the visualization of the inner structural organization and cellular composition of tissues are needed. This chapter describes an optical clearing technique which facilitates the detailed characterization of whole-mount samples from skin and adipose tissues (ex vivo tissues and in vitro tissue-engineered substitutes) when combined with spectral confocal microscopy and quantitative analysis on image renderings.

Co-culture systems-based strategies for articular cartilage tissue engineering.

PubMed

Zhang, Yu; Guo, Weimin; Wang, Mingjie; Hao, Chunxiang; Lu, Liang; Gao, Shuang; Zhang, Xueliang; Li, Xu; Chen, Mingxue; Li, Penghao; Jiang, Peng; Lu, Shibi; Liu, Shuyun; Guo, Quanyi

2018-03-01

Cartilage engineering facilitates repair and regeneration of damaged cartilage using engineered tissue that restores the functional properties of the impaired joint. The seed cells used most frequently in tissue engineering, are chondrocytes and mesenchymal stem cells. Seed cells activity plays a key role in the regeneration of functional cartilage tissue. However, seed cells undergo undesirable changes after in vitro processing procedures, such as degeneration of cartilage cells and induced hypertrophy of mesenchymal stem cells, which hinder cartilage tissue engineering. Compared to monoculture, which does not mimic the in vivo cellular environment, co-culture technology provides a more realistic microenvironment in terms of various physical, chemical, and biological factors. Co-culture technology is used in cartilage tissue engineering to overcome obstacles related to the degeneration of seed cells, and shows promise for cartilage regeneration and repair. In this review, we focus first on existing co-culture systems for cartilage tissue engineering and related fields, and discuss the conditions and mechanisms thereof. This is followed by methods for optimizing seed cell co-culture conditions to generate functional neo-cartilage tissue, which will lead to a new era in cartilage tissue engineering. © 2017 Wiley Periodicals, Inc.

Nanofibers and their applications in tissue engineering

PubMed Central

Vasita, Rajesh; Katti, Dhirendra S

2006-01-01

Developing scaffolds that mimic the architecture of tissue at the nanoscale is one of the major challenges in the field of tissue engineering. The development of nanofibers has greatly enhanced the scope for fabricating scaffolds that can potentially meet this challenge. Currently, there are three techniques available for the synthesis of nanofibers: electrospinning, self-assembly, and phase separation. Of these techniques, electrospinning is the most widely studied technique and has also demonstrated the most promising results in terms of tissue engineering applications. The availability of a wide range of natural and synthetic biomaterials has broadened the scope for development of nanofibrous scaffolds, especially using the electrospinning technique. The three dimensional synthetic biodegradable scaffolds designed using nanofibers serve as an excellent framework for cell adhesion, proliferation, and differentiation. Therefore, nanofibers, irrespective of their method of synthesis, have been used as scaffolds for musculoskeletal tissue engineering (including bone, cartilage, ligament, and skeletal muscle), skin tissue engineering, vascular tissue engineering, neural tissue engineering, and as carriers for the controlled delivery of drugs, proteins, and DNA. This review summarizes the currently available techniques for nanofiber synthesis and discusses the use of nanofibers in tissue engineering and drug delivery applications. PMID:17722259

Recent development on computer aided tissue engineering--a review.

PubMed

Sun, Wei; Lal, Pallavi

2002-02-01

The utilization of computer-aided technologies in tissue engineering has evolved in the development of a new field of computer-aided tissue engineering (CATE). This article reviews recent development and application of enabling computer technology, imaging technology, computer-aided design and computer-aided manufacturing (CAD and CAM), and rapid prototyping (RP) technology in tissue engineering, particularly, in computer-aided tissue anatomical modeling, three-dimensional (3-D) anatomy visualization and 3-D reconstruction, CAD-based anatomical modeling, computer-aided tissue classification, computer-aided tissue implantation and prototype modeling assisted surgical planning and reconstruction.

Regenerative therapy and tissue engineering for the treatment of end-stage cardiac failure

PubMed Central

Finosh, G.T.; Jayabalan, Muthu

2012-01-01

Regeneration of myocardium through regenerative therapy and tissue engineering is appearing as a prospective treatment modality for patients with end-stage heart failure. Focusing on this area, this review highlights the new developments and challenges in the regeneration of myocardial tissue. The role of various cell sources, calcium ion and cytokine on the functional performance of regenerative therapy is discussed. The evolution of tissue engineering and the role of tissue matrix/scaffold, cell adhesion and vascularisation on tissue engineering of cardiac tissue implant are also discussed. PMID:23507781

Regenerative therapy and tissue engineering for the treatment of end-stage cardiac failure: new developments and challenges.

PubMed

Finosh, G T; Jayabalan, Muthu

2012-01-01

Regeneration of myocardium through regenerative therapy and tissue engineering is appearing as a prospective treatment modality for patients with end-stage heart failure. Focusing on this area, this review highlights the new developments and challenges in the regeneration of myocardial tissue. The role of various cell sources, calcium ion and cytokine on the functional performance of regenerative therapy is discussed. The evolution of tissue engineering and the role of tissue matrix/scaffold, cell adhesion and vascularisation on tissue engineering of cardiac tissue implant are also discussed.

Stem Cell Extracellular Vesicles: Extended Messages of Regeneration

PubMed Central

Riazifar, Milad; Pone, Egest J.; Lötvall, Jan; Zhao, Weian

2017-01-01

Stem cells are critical to maintaining steady-state organ homeostasis and regenerating injured tissues. Recent intriguing reports implicate extracellular vesicles (EVs) as carriers for the distribution of morphogens and growth and differentiation factors from tissue parenchymal cells to stem cells, and conversely, stem cell–derived EVs carrying certain proteins and nucleic acids can support healing of injured tissues. We describe approaches to make use of engineered EVs as technology platforms in therapeutics and diagnostics in the context of stem cells. For some regenerative therapies, natural and engineered EVs from stem cells may be superior to single-molecule drugs, biologics, whole cells, and synthetic liposome or nanoparticle formulations because of the ease of bioengineering with multiple factors while retaining superior biocompatibility and biostability and posing fewer risks for abnormal differentiation or neoplastic transformation. Finally, we provide an overview of current challenges and future directions of EVs as potential therapeutic alternatives to cells for clinical applications. PMID:27814025

Cell Microenvironment Engineering and Monitoring for Tissue Engineering and Regenerative Medicine: The Recent Advances

PubMed Central

Barthes, Julien; Özçelik, Hayriye; Hindié, Mathilde; Ndreu-Halili, Albana; Hasan, Anwarul

2014-01-01

In tissue engineering and regenerative medicine, the conditions in the immediate vicinity of the cells have a direct effect on cells' behaviour and subsequently on clinical outcomes. Physical, chemical, and biological control of cell microenvironment are of crucial importance for the ability to direct and control cell behaviour in 3-dimensional tissue engineering scaffolds spatially and temporally. In this review, we will focus on the different aspects of cell microenvironment such as surface micro-, nanotopography, extracellular matrix composition and distribution, controlled release of soluble factors, and mechanical stress/strain conditions and how these aspects and their interactions can be used to achieve a higher degree of control over cellular activities. The effect of these parameters on the cellular behaviour within tissue engineering context is discussed and how these parameters are used to develop engineered tissues is elaborated. Also, recent techniques developed for the monitoring of the cell microenvironment in vitro and in vivo are reviewed, together with recent tissue engineering applications where the control of cell microenvironment has been exploited. Cell microenvironment engineering and monitoring are crucial parts of tissue engineering efforts and systems which utilize different components of the cell microenvironment simultaneously can provide more functional engineered tissues in the near future. PMID:25143954

Cell microenvironment engineering and monitoring for tissue engineering and regenerative medicine: the recent advances.

PubMed

Barthes, Julien; Özçelik, Hayriye; Hindié, Mathilde; Ndreu-Halili, Albana; Hasan, Anwarul; Vrana, Nihal Engin

2014-01-01

In tissue engineering and regenerative medicine, the conditions in the immediate vicinity of the cells have a direct effect on cells' behaviour and subsequently on clinical outcomes. Physical, chemical, and biological control of cell microenvironment are of crucial importance for the ability to direct and control cell behaviour in 3-dimensional tissue engineering scaffolds spatially and temporally. In this review, we will focus on the different aspects of cell microenvironment such as surface micro-, nanotopography, extracellular matrix composition and distribution, controlled release of soluble factors, and mechanical stress/strain conditions and how these aspects and their interactions can be used to achieve a higher degree of control over cellular activities. The effect of these parameters on the cellular behaviour within tissue engineering context is discussed and how these parameters are used to develop engineered tissues is elaborated. Also, recent techniques developed for the monitoring of the cell microenvironment in vitro and in vivo are reviewed, together with recent tissue engineering applications where the control of cell microenvironment has been exploited. Cell microenvironment engineering and monitoring are crucial parts of tissue engineering efforts and systems which utilize different components of the cell microenvironment simultaneously can provide more functional engineered tissues in the near future.

Towards organ printing: engineering an intra-organ branched vascular tree

PubMed Central

Visconti, Richard P; Kasyanov, Vladimir; Gentile, Carmine; Zhang, Jing; Markwald, Roger R; Mironov, Vladimir

2013-01-01

Importance of the field Effective vascularization of thick three-dimensional engineered tissue constructs is a problem in tissue engineering. As in native organs, a tissue-engineered intra-organ vascular tree must be comprised of a network of hierarchically branched vascular segments. Despite this requirement, current tissue-engineering efforts are still focused predominantly on engineering either large-diameter macrovessels or microvascular networks. Areas covered in this review We present the emerging concept of organ printing or robotic additive biofabrication of an intra-organ branched vascular tree, based on the ability of vascular tissue spheroids to undergo self-assembly. What the reader will gain The feasibility and challenges of this robotic biofabrication approach to intra-organ vascularization for tissue engineering based on organ-printing technology using self-assembling vascular tissue spheroids including clinically relevantly vascular cell sources are analyzed. Take home message It is not possible to engineer 3D thick tissue or organ constructs without effective vascularization. An effective intra-organ vascular system cannot be built by the simple connection of large-diameter vessels and microvessels. Successful engineering of functional human organs suitable for surgical implantation will require concomitant engineering of a ‘built in’ intra-organ branched vascular system. Organ printing enables biofabrication of human organ constructs with a ‘built in’ intra-organ branched vascular tree. PMID:20132061

Transplantation of Tissue-Engineered Cartilage in an Animal Model (Xenograft and Autograft): Construct Validation.

PubMed

Nemoto, Hitoshi; Watson, Deborah; Masuda, Koichi

2015-01-01

Tissue engineering holds great promise for cartilage repair with minimal donor-site morbidity. The in vivo maturation of a tissue-engineered construct can be tested in the subcutaneous tissues of the same species for autografts or of immunocompromised animals for allografts or xenografts. This section describes detailed protocols for the surgical transplantation of a tissue-engineered construct into an animal model to assess construct validity.

Bone tissue engineering scaffolding: computer-aided scaffolding techniques.

PubMed

Thavornyutikarn, Boonlom; Chantarapanich, Nattapon; Sitthiseripratip, Kriskrai; Thouas, George A; Chen, Qizhi

Tissue engineering is essentially a technique for imitating nature. Natural tissues consist of three components: cells, signalling systems (e.g. growth factors) and extracellular matrix (ECM). The ECM forms a scaffold for its cells. Hence, the engineered tissue construct is an artificial scaffold populated with living cells and signalling molecules. A huge effort has been invested in bone tissue engineering, in which a highly porous scaffold plays a critical role in guiding bone and vascular tissue growth and regeneration in three dimensions. In the last two decades, numerous scaffolding techniques have been developed to fabricate highly interconnective, porous scaffolds for bone tissue engineering applications. This review provides an update on the progress of foaming technology of biomaterials, with a special attention being focused on computer-aided manufacturing (Andrade et al. 2002) techniques. This article starts with a brief introduction of tissue engineering (Bone tissue engineering and scaffolds) and scaffolding materials (Biomaterials used in bone tissue engineering). After a brief reviews on conventional scaffolding techniques (Conventional scaffolding techniques), a number of CAM techniques are reviewed in great detail. For each technique, the structure and mechanical integrity of fabricated scaffolds are discussed in detail. Finally, the advantaged and disadvantage of these techniques are compared (Comparison of scaffolding techniques) and summarised (Summary).

Bioprinting for Neural Tissue Engineering.

PubMed

Knowlton, Stephanie; Anand, Shivesh; Shah, Twisha; Tasoglu, Savas

2018-01-01

Bioprinting is a method by which a cell-encapsulating bioink is patterned to create complex tissue architectures. Given the potential impact of this technology on neural research, we review the current state-of-the-art approaches for bioprinting neural tissues. While 2D neural cultures are ubiquitous for studying neural cells, 3D cultures can more accurately replicate the microenvironment of neural tissues. By bioprinting neuronal constructs, one can precisely control the microenvironment by specifically formulating the bioink for neural tissues, and by spatially patterning cell types and scaffold properties in three dimensions. We review a range of bioprinted neural tissue models and discuss how they can be used to observe how neurons behave, understand disease processes, develop new therapies and, ultimately, design replacement tissues. Copyright © 2017 Elsevier Ltd. All rights reserved.

Studying Kidney Disease Using Tissue and Genome Engineering in Human Pluripotent Stem Cells.

PubMed

Garreta, Elena; González, Federico; Montserrat, Núria

2018-01-01

Kidney morphogenesis and patterning have been extensively studied in animal models such as the mouse and zebrafish. These seminal studies have been key to define the molecular mechanisms underlying this complex multistep process. Based on this knowledge, the last 3 years have witnessed the development of a cohort of protocols allowing efficient differentiation of human pluripotent stem cells (hPSCs) towards defined kidney progenitor populations using two-dimensional (2D) culture systems or through generating organoids. Kidney organoids are three-dimensional (3D) kidney-like tissues, which are able to partially recapitulate kidney structure and function in vitro. The current possibility to combine state-of-the art tissue engineering with clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated systems 9 (Cas9)-mediated genome engineering provides an unprecedented opportunity for studying kidney disease with hPSCs. Recently, hPSCs with genetic mutations introduced through CRISPR/Cas9-mediated genome engineering have shown to produce kidney organoids able to recapitulate phenotypes of polycystic kidney disease and glomerulopathies. This mini review provides an overview of the most recent advances in differentiation of hPSCs into kidney lineages, and the latest implementation of the CRISPR/Cas9 technology in the organoid setting, as promising platforms to study human kidney development and disease. © 2017 S. Karger AG, Basel.

Tissue engineering in urethral reconstruction—an update

PubMed Central

Mangera, Altaf; Chapple, Christopher R

2013-01-01

The field of tissue engineering is rapidly progressing. Much work has gone into developing a tissue engineered urethral graft. Current grafts, when long, can create initial donor site morbidity. In this article, we evaluate the progress made in finding a tissue engineered substitute for the human urethra. Researchers have investigated cell-free and cell-seeded grafts. We discuss different approaches to developing these grafts and review their reported successes in human studies. With further work, tissue engineered grafts may facilitate the management of lengthy urethral strictures requiring oral mucosa substitution urethroplasty. PMID:23042444

Injectable thermosensitive chitosan/glycerophosphate-based hydrogels for tissue engineering and drug delivery applications: a review.

PubMed

Tahrir, Farzaneh G; Ganji, Fariba; Ahooyi, Taha M

2015-01-01

Recently, great attention has been paid to in situ gel-forming chitosan/glycerophosphate (CS/Gp) formulation due to its high biocompatibility with incorporated cells and medical agents, biodegradability and sharp thermosensitive gelation. CS/Gp is in liquid state at room temperature and after minimally invasive administration into the desired tissue, it forms a solid-like gel as a response to temperature increase. The overview of various recently patented strategies on injectable delivery systems indicates the significance of this formulation in biomedical applications. This thermosensitive hydrogel has a great potential as scaffold material in tissue engineering, due to its good biocompatibility, minimal immune reaction, high antibacterial nature, good adhesion to cells and the ability to be molded in various geometries. Moreover, CS/Gp hydrogel has been utilized as a smart drug delivery system to increase patient compliance by maintaining the drug level in the therapeutic window for a long time while avoiding the need for frequent injections of the therapeutic agent. This review paper highlights the recent patents and investigations on different formulations of CS/Gp hydrogels as tissue engineering scaffolds and carriers for therapeutic agents. Additionally, the dominant mechanism of sol-gel transition in those systems as well as their physicochemical properties and biocompatibility are discussed in detail.

Adipose-Derived Stem Cells for Tissue Engineering and Regenerative Medicine Applications

PubMed Central

Dai, Ru; Wang, Zongjie; Samanipour, Roya; Koo, Kyo-in; Kim, Keekyoung

2016-01-01

Adipose-derived stem cells (ASCs) are a mesenchymal stem cell source with properties of self-renewal and multipotential differentiation. Compared to bone marrow-derived stem cells (BMSCs), ASCs can be derived from more sources and are harvested more easily. Three-dimensional (3D) tissue engineering scaffolds are better able to mimic the in vivo cellular microenvironment, which benefits the localization, attachment, proliferation, and differentiation of ASCs. Therefore, tissue-engineered ASCs are recognized as an attractive substitute for tissue and organ transplantation. In this paper, we review the characteristics of ASCs, as well as the biomaterials and tissue engineering methods used to proliferate and differentiate ASCs in a 3D environment. Clinical applications of tissue-engineered ASCs are also discussed to reveal the potential and feasibility of using tissue-engineered ASCs in regenerative medicine. PMID:27057174

Nanomaterials for Cardiac Myocyte Tissue Engineering.

PubMed

Amezcua, Rodolfo; Shirolkar, Ajay; Fraze, Carolyn; Stout, David A

2016-07-19

Since their synthesizing introduction to the research community, nanomaterials have infiltrated almost every corner of science and engineering. Over the last decade, one such field has begun to look at using nanomaterials for beneficial applications in tissue engineering, specifically, cardiac tissue engineering. During a myocardial infarction, part of the cardiac muscle, or myocardium, is deprived of blood. Therefore, the lack of oxygen destroys cardiomyocytes, leaving dead tissue and possibly resulting in the development of arrhythmia, ventricular remodeling, and eventual heart failure. Scarred cardiac muscle results in heart failure for millions of heart attack survivors worldwide. Modern cardiac tissue engineering research has developed nanomaterial applications to combat heart failure, preserve normal heart tissue, and grow healthy myocardium around the infarcted area. This review will discuss the recent progress of nanomaterials for cardiovascular tissue engineering applications through three main nanomaterial approaches: scaffold designs, patches, and injectable materials.

Textile Technologies and Tissue Engineering: A Path Towards Organ Weaving

PubMed Central

Akbari, Mohsen; Tamayol, Ali; Bagherifard, Sara; Serex, Ludovic; Mostafalu, Pooria; Faramarzi, Negar; Mohammadi, Mohammad Hossein

2016-01-01

Textile technologies have recently attracted great attention as potential biofabrication tools for engineering tissue constructs. Using current textile technologies, fibrous structures can be designed and engineered to attain the required properties that are demanded by different tissue engineering applications. Several key parameters such as physiochemical characteristics of fibers, pore size and mechanical properties of the fabrics play important role in the effective use of textile technologies in tissue engineering. This review summarizes the current advances in the manufacturing of biofunctional fibers. Different textile methods such as knitting, weaving, and braiding are discussed and their current applications in tissue engineering are highlighted. PMID:26924450

Analyzing the Function of Cartilage Replacements: A Laboratory Activity to Teach High School Students Chemical and Tissue Engineering Concepts

ERIC Educational Resources Information Center

Renner, Julie N.; Emady, Heather N.; Galas, Richards J., Jr.; Zhange, Rong; Baertsch, Chelsey D.; Liu, Julie C.

2013-01-01

A cartilage tissue engineering laboratory activity was developed as part of the Exciting Discoveries for Girls in Engineering (EDGE) Summer Camp sponsored by the Women In Engineering Program (WIEP) at Purdue University. Our goal was to increase awareness of chemical engineering and tissue engineering in female high school students through a…

Nasal chondrocyte-based engineered autologous cartilage tissue for repair of articular cartilage defects: an observational first-in-human trial.

PubMed

Mumme, Marcus; Barbero, Andrea; Miot, Sylvie; Wixmerten, Anke; Feliciano, Sandra; Wolf, Francine; Asnaghi, Adelaide M; Baumhoer, Daniel; Bieri, Oliver; Kretzschmar, Martin; Pagenstert, Geert; Haug, Martin; Schaefer, Dirk J; Martin, Ivan; Jakob, Marcel

2016-10-22

Articular cartilage injuries have poor repair capacity, leading to progressive joint damage, and cannot be restored predictably by either conventional treatments or advanced therapies based on implantation of articular chondrocytes. Compared with articular chondrocytes, chondrocytes derived from the nasal septum have superior and more reproducible capacity to generate hyaline-like cartilage tissues, with the plasticity to adapt to a joint environment. We aimed to assess whether engineered autologous nasal chondrocyte-based cartilage grafts allow safe and functional restoration of knee cartilage defects. In a first-in-human trial, ten patients with symptomatic, post-traumatic, full-thickness cartilage lesions (2-6 cm 2 ) on the femoral condyle or trochlea were treated at University Hospital Basel in Switzerland. Chondrocytes isolated from a 6 mm nasal septum biopsy specimen were expanded and cultured onto collagen membranes to engineer cartilage grafts (30 × 40 × 2 mm). The engineered tissues were implanted into the femoral defects via mini-arthrotomy and assessed up to 24 months after surgery. Primary outcomes were feasibility and safety of the procedure. Secondary outcomes included self-assessed clinical scores and MRI-based estimation of morphological and compositional quality of the repair tissue. This study is registered with ClinicalTrials.gov, number NCT01605201. The study is ongoing, with an approved extension to 25 patients. For every patient, it was feasible to manufacture cartilaginous grafts with nasal chondrocytes embedded in an extracellular matrix rich in glycosaminoglycan and type II collagen. Engineered tissues were stable through handling with forceps and could be secured in the injured joints. No adverse reactions were recorded and self-assessed clinical scores for pain, knee function, and quality of life were improved significantly from before surgery to 24 months after surgery. Radiological assessments indicated variable degrees of defect filling and development of repair tissue approaching the composition of native cartilage. Hyaline-like cartilage tissues, engineered from autologous nasal chondrocytes, can be used clinically for repair of articular cartilage defects in the knee. Future studies are warranted to assess efficacy in large controlled trials and to investigate an extension of indications to early degenerative states or to other joints. Deutsche Arthrose-Hilfe. Copyright © 2016 Elsevier Ltd. All rights reserved.

A Cost-Minimization Analysis of Tissue-Engineered Constructs for Corneal Endothelial Transplantation

PubMed Central

Tan, Tien-En; Peh, Gary S. L.; George, Benjamin L.; Cajucom-Uy, Howard Y.; Dong, Di; Finkelstein, Eric A.; Mehta, Jodhbir S.

2014-01-01

Corneal endothelial transplantation or endothelial keratoplasty has become the preferred choice of transplantation for patients with corneal blindness due to endothelial dysfunction. Currently, there is a worldwide shortage of transplantable tissue, and demand is expected to increase further with aging populations. Tissue-engineered alternatives are being developed, and are likely to be available soon. However, the cost of these constructs may impair their widespread use. A cost-minimization analysis comparing tissue-engineered constructs to donor tissue procured from eye banks for endothelial keratoplasty was performed. Both initial investment costs and recurring costs were considered in the analysis to arrive at a final tissue cost per transplant. The clinical outcomes of endothelial keratoplasty with tissue-engineered constructs and with donor tissue procured from eye banks were assumed to be equivalent. One-way and probabilistic sensitivity analyses were performed to simulate various possible scenarios, and to determine the robustness of the results. A tissue engineering strategy was cheaper in both investment cost and recurring cost. Tissue-engineered constructs for endothelial keratoplasty could be produced at a cost of US$880 per transplant. In contrast, utilizing donor tissue procured from eye banks for endothelial keratoplasty required US$3,710 per transplant. Sensitivity analyses performed further support the results of this cost-minimization analysis across a wide range of possible scenarios. The use of tissue-engineered constructs for endothelial keratoplasty could potentially increase the supply of transplantable tissue and bring the costs of corneal endothelial transplantation down, making this intervention accessible to a larger group of patients. Tissue-engineering strategies for corneal epithelial constructs or other tissue types, such as pancreatic islet cells, should also be subject to similar pharmacoeconomic analyses. PMID:24949869

A cost-minimization analysis of tissue-engineered constructs for corneal endothelial transplantation.

PubMed

Tan, Tien-En; Peh, Gary S L; George, Benjamin L; Cajucom-Uy, Howard Y; Dong, Di; Finkelstein, Eric A; Mehta, Jodhbir S

2014-01-01

Corneal endothelial transplantation or endothelial keratoplasty has become the preferred choice of transplantation for patients with corneal blindness due to endothelial dysfunction. Currently, there is a worldwide shortage of transplantable tissue, and demand is expected to increase further with aging populations. Tissue-engineered alternatives are being developed, and are likely to be available soon. However, the cost of these constructs may impair their widespread use. A cost-minimization analysis comparing tissue-engineered constructs to donor tissue procured from eye banks for endothelial keratoplasty was performed. Both initial investment costs and recurring costs were considered in the analysis to arrive at a final tissue cost per transplant. The clinical outcomes of endothelial keratoplasty with tissue-engineered constructs and with donor tissue procured from eye banks were assumed to be equivalent. One-way and probabilistic sensitivity analyses were performed to simulate various possible scenarios, and to determine the robustness of the results. A tissue engineering strategy was cheaper in both investment cost and recurring cost. Tissue-engineered constructs for endothelial keratoplasty could be produced at a cost of US$880 per transplant. In contrast, utilizing donor tissue procured from eye banks for endothelial keratoplasty required US$3,710 per transplant. Sensitivity analyses performed further support the results of this cost-minimization analysis across a wide range of possible scenarios. The use of tissue-engineered constructs for endothelial keratoplasty could potentially increase the supply of transplantable tissue and bring the costs of corneal endothelial transplantation down, making this intervention accessible to a larger group of patients. Tissue-engineering strategies for corneal epithelial constructs or other tissue types, such as pancreatic islet cells, should also be subject to similar pharmacoeconomic analyses.

Recent developments in processing systems for cell and tissue cultures toward therapeutic application.

PubMed

Kino-oka, Masahiro; Taya, Masahito

2009-10-01

Innovative techniques of cell and tissue processing, based on tissue engineering, have been developed for therapeutic applications. Cell expansion and tissue reconstruction through ex vivo cultures are core processes used to produce engineered tissues with sufficient structural integrity and functionality. In manufacturing, strict management against contamination and human error is compelled due to direct use of un-sterilable products and the laboriousness of culture operations, respectively. Therefore, the development of processing systems for cell and tissue cultures is one of the critical issues for ensuring a stable process and quality of therapeutic products. However, the siting criterion of culture systems to date has not been made clear. This review article classifies some of the known processing systems into 'sealed-chamber' and 'sealed-vessel' culture systems based on the difference in their aseptic spaces, and describes the potential advantages of these systems and current states of culture systems, especially those established by Japanese companies. Moreover, on the basis of the guidelines for isolator systems used in aseptic processing for healthcare products, which are issued by the International Organization for Standardization, the siting criterion of the processing systems for cells and tissue cultures is discussed in perspective of manufacturing therapeutic products in consideration of the regulations according to the Good Manufacturing Practice.

Tissue engineering for urinary tract reconstruction and repair: Progress and prospect in China.

PubMed

Zou, Qingsong; Fu, Qiang

2018-04-01

Several urinary tract pathologic conditions, such as strictures, cancer, and obliterations, require reconstructive plastic surgery. Reconstruction of the urinary tract is an intractable task for urologists due to insufficient autologous tissue. Limitations of autologous tissue application prompted urologists to investigate ideal substitutes. Tissue engineering is a new direction in these cases. Advances in tissue engineering over the last 2 decades may offer alternative approaches for the urinary tract reconstruction. The main components of tissue engineering include biomaterials and cells. Biomaterials can be used with or without cultured cells. This paper focuses on cell sources, biomaterials, and existing methods of tissue engineering for urinary tract reconstruction in China. The paper also details challenges and perspectives involved in urinary tract reconstruction.

Bone tissue engineering using silica-based mesoporous nanobiomaterials:Recent progress.

PubMed

Shadjou, Nasrin; Hasanzadeh, Mohammad

2015-10-01

Bone disorders are of significant concern due to increase in the median age of our population. It is in this context that tissue engineering has been emerging as a valid approach to the current therapies for bone regeneration/substitution. Tissue-engineered bone constructs have the potential to alleviate the demand arising from the shortage of suitable autograft and allograft materials for augmenting bone healing. Silica based mesostructured nanomaterials possessing pore sizes in the range 2-50 nm and surface reactive functionalities have elicited immense interest due to their exciting prospects in bone tissue engineering. In this review we describe application of silica-based mesoporous nanomaterials for bone tissue engineering. We summarize the preparation methods, the effect of mesopore templates and composition on the mesopore-structure characteristics, and different forms of these materials, including particles, fibers, spheres, scaffolds and composites. Also, the effect of structural and textural properties of mesoporous materials on development of new biomaterials for production of bone implants and bone cements was discussed. Also, application of different mesoporous materials on construction of manufacture 3-dimensional scaffolds for bone tissue engineering was discussed. It begins by giving the reader a brief background on tissue engineering, followed by a comprehensive description of all the relevant components of silica-based mesoporous biomaterials on bone tissue engineering, going from materials to scaffolds and from cells to tissue engineering strategies that will lead to "engineered" bone. Copyright © 2015 Elsevier B.V. All rights reserved.

Computational model-informed design and bioprinting of cell-patterned constructs for bone tissue engineering.

PubMed

Carlier, Aurélie; Skvortsov, Gözde Akdeniz; Hafezi, Forough; Ferraris, Eleonora; Patterson, Jennifer; Koç, Bahattin; Van Oosterwyck, Hans

2016-05-17

Three-dimensional (3D) bioprinting is a rapidly advancing tissue engineering technology that holds great promise for the regeneration of several tissues, including bone. However, to generate a successful 3D bone tissue engineering construct, additional complexities should be taken into account such as nutrient and oxygen delivery, which is often insufficient after implantation in large bone defects. We propose that a well-designed tissue engineering construct, that is, an implant with a specific spatial pattern of cells in a matrix, will improve the healing outcome. By using a computational model of bone regeneration we show that particular cell patterns in tissue engineering constructs are able to enhance bone regeneration compared to uniform ones. We successfully bioprinted one of the most promising cell-gradient patterns by using cell-laden hydrogels with varying cell densities and observed a high cell viability for three days following the bioprinting process. In summary, we present a novel strategy for the biofabrication of bone tissue engineering constructs by designing cell-gradient patterns based on a computational model of bone regeneration, and successfully bioprinting the chosen design. This integrated approach may increase the success rate of implanted tissue engineering constructs for critical size bone defects and also can find a wider application in the biofabrication of other types of tissue engineering constructs.

Advancing biomaterials of human origin for tissue engineering

PubMed Central

Chen, Fa-Ming; Liu, Xiaohua

2015-01-01

Biomaterials have played an increasingly prominent role in the success of biomedical devices and in the development of tissue engineering, which seeks to unlock the regenerative potential innate to human tissues/organs in a state of deterioration and to restore or reestablish normal bodily function. Advances in our understanding of regenerative biomaterials and their roles in new tissue formation can potentially open a new frontier in the fast-growing field of regenerative medicine. Taking inspiration from the role and multi-component construction of native extracellular matrices (ECMs) for cell accommodation, the synthetic biomaterials produced today routinely incorporate biologically active components to define an artificial in vivo milieu with complex and dynamic interactions that foster and regulate stem cells, similar to the events occurring in a natural cellular microenvironment. The range and degree of biomaterial sophistication have also dramatically increased as more knowledge has accumulated through materials science, matrix biology and tissue engineering. However, achieving clinical translation and commercial success requires regenerative biomaterials to be not only efficacious and safe but also cost-effective and convenient for use and production. Utilizing biomaterials of human origin as building blocks for therapeutic purposes has provided a facilitated approach that closely mimics the critical aspects of natural tissue with regard to its physical and chemical properties for the orchestration of wound healing and tissue regeneration. In addition to directly using tissue transfers and transplants for repair, new applications of human-derived biomaterials are now focusing on the use of naturally occurring biomacromolecules, decellularized ECM scaffolds and autologous preparations rich in growth factors/non-expanded stem cells to either target acceleration/magnification of the body's own repair capacity or use nature's paradigms to create new tissues for restoration. In particular, there is increasing interest in separating ECMs into simplified functional domains and/or biopolymeric assemblies so that these components/constituents can be discretely exploited and manipulated for the production of bioscaffolds and new biomimetic biomaterials. Here, following an overview of tissue auto-/allo-transplantation, we discuss the recent trends and advances as well as the challenges and future directions in the evolution and application of human-derived biomaterials for reconstructive surgery and tissue engineering. In particular, we focus on an exploration of the structural, mechanical, biochemical and biological information present in native human tissue for bioengineering applications and to provide inspiration for the design of future biomaterials. PMID:27022202

Engineering Microvascularized 3D Tissue Using Alginate-Chitosan Microcapsules.

PubMed

Zhang, Wujie; Choi, Jung K; He, Xiaoming

2017-02-01

Construction of vascularized tissues is one of the major challenges of tissue engineering. The goal of this study was to engineer 3D microvascular tissues by incorporating the HUVEC-CS cells with a collagen/alginate-chitosan (AC) microcapsule scaffold. In the presence of AC microcapsules, a 3D vascular-like network was clearly observable. The results indicated the importance of AC microcapsules in engineering microvascular tissues -- providing support and guiding alignment of HUVEC-CS cells. This approach provides an alternative and promising method for constructing vascularized tissues.

Tissue engineering in dentistry.

PubMed

Abou Neel, Ensanya Ali; Chrzanowski, Wojciech; Salih, Vehid M; Kim, Hae-Won; Knowles, Jonathan C

2014-08-01

of this review is to inform practitioners with the most updated information on tissue engineering and its potential applications in dentistry. The authors used "PUBMED" to find relevant literature written in English and published from the beginning of tissue engineering until today. A combination of keywords was used as the search terms e.g., "tissue engineering", "approaches", "strategies" "dentistry", "dental stem cells", "dentino-pulp complex", "guided tissue regeneration", "whole tooth", "TMJ", "condyle", "salivary glands", and "oral mucosa". Abstracts and full text articles were used to identify causes of craniofacial tissue loss, different approaches for craniofacial reconstructions, how the tissue engineering emerges, different strategies of tissue engineering, biomaterials employed for this purpose, the major attempts to engineer different dental structures, finally challenges and future of tissue engineering in dentistry. Only those articles that dealt with the tissue engineering in dentistry were selected. There have been a recent surge in guided tissue engineering methods to manage periodontal diseases beyond the traditional approaches. However, the predictable reconstruction of the innate organisation and function of whole teeth as well as their periodontal structures remains challenging. Despite some limited progress and minor successes, there remain distinct and important challenges in the development of reproducible and clinically safe approaches for oral tissue repair and regeneration. Clearly, there is a convincing body of evidence which confirms the need for this type of treatment, and public health data worldwide indicates a more than adequate patient resource. The future of these therapies involving more biological approaches and the use of dental tissue stem cells is promising and advancing. Also there may be a significant interest of their application and wider potential to treat disorders beyond the craniofacial region. Considering the interests of the patients who could possibly be helped by applying stem cell-based therapies should be carefully assessed against current ethical concerns regarding the moral status of the early embryo. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

The role of mechanical loading in ligament tissue engineering.

PubMed

Benhardt, Hugh A; Cosgriff-Hernandez, Elizabeth M

2009-12-01

Tissue-engineered ligaments have received growing interest as a promising alternative for ligament reconstruction when traditional transplants are unavailable or fail. Mechanical stimulation was recently identified as a critical component in engineering load-bearing tissues. It is well established that living tissue responds to altered loads through endogenous changes in cellular behavior, tissue organization, and bulk mechanical properties. Without the appropriate biomechanical cues, new tissue formation lacks the necessary collagenous organization and alignment for sufficient load-bearing capacity. Therefore, tissue engineers utilize mechanical conditioning to guide tissue remodeling and improve the performance of ligament grafts. This review provides a comparative analysis of the response of ligament and tendon fibroblasts to mechanical loading in current bioreactor studies. The differential effect of mechanical stimulation on cellular processes such as protease production, matrix protein synthesis, and cell proliferation is examined in the context of tissue engineering design.

Cell-scaffold interactions in the bone tissue engineering triad.

PubMed

Murphy, Ciara M; O'Brien, Fergal J; Little, David G; Schindeler, Aaron

2013-09-20

Bone tissue engineering has emerged as one of the leading fields in tissue engineering and regenerative medicine. The success of bone tissue engineering relies on understanding the interplay between progenitor cells, regulatory signals, and the biomaterials/scaffolds used to deliver them--otherwise known as the tissue engineering triad. This review will discuss the roles of these fundamental components with a specific focus on the interaction between cell behaviour and scaffold structural properties. In terms of scaffold architecture, recent work has shown that pore size can affect both cell attachment and cellular invasion. Moreover, different materials can exert different biomechanical forces, which can profoundly affect cellular differentiation and migration in a cell type specific manner. Understanding these interactions will be critical for enhancing the progress of bone tissue engineering towards clinical applications.

Hydrogel scaffolds for tissue engineering: Progress and challenges

PubMed Central

El-Sherbiny, Ibrahim M.; Yacoub, Magdi H.

2013-01-01

Designing of biologically active scaffolds with optimal characteristics is one of the key factors for successful tissue engineering. Recently, hydrogels have received a considerable interest as leading candidates for engineered tissue scaffolds due to their unique compositional and structural similarities to the natural extracellular matrix, in addition to their desirable framework for cellular proliferation and survival. More recently, the ability to control the shape, porosity, surface morphology, and size of hydrogel scaffolds has created new opportunities to overcome various challenges in tissue engineering such as vascularization, tissue architecture and simultaneous seeding of multiple cells. This review provides an overview of the different types of hydrogels, the approaches that can be used to fabricate hydrogel matrices with specific features and the recent applications of hydrogels in tissue engineering. Special attention was given to the various design considerations for an efficient hydrogel scaffold in tissue engineering. Also, the challenges associated with the use of hydrogel scaffolds were described. PMID:24689032

Tissue Engineering of Blood Vessels: Functional Requirements, Progress, and Future Challenges.

PubMed

Kumar, Vivek A; Brewster, Luke P; Caves, Jeffrey M; Chaikof, Elliot L

2011-09-01

Vascular disease results in the decreased utility and decreased availability of autologus vascular tissue for small diameter (< 6 mm) vessel replacements. While synthetic polymer alternatives to date have failed to meet the performance of autogenous conduits, tissue-engineered replacement vessels represent an ideal solution to this clinical problem. Ongoing progress requires combined approaches from biomaterials science, cell biology, and translational medicine to develop feasible solutions with the requisite mechanical support, a non-fouling surface for blood flow, and tissue regeneration. Over the past two decades interest in blood vessel tissue engineering has soared on a global scale, resulting in the first clinical implants of multiple technologies, steady progress with several other systems, and critical lessons-learned. This review will highlight the current inadequacies of autologus and synthetic grafts, the engineering requirements for implantation of tissue-engineered grafts, and the current status of tissue-engineered blood vessel research.

Advanced nanobiomaterial strategies for the development of organized tissue engineering constructs.

PubMed

An, Jia; Chua, Chee Kai; Yu, Ting; Li, Huaqiong; Tan, Lay Poh

2013-04-01

Nanobiomaterials, a field at the interface of biomaterials and nanotechnologies, when applied to tissue engineering applications, are usually perceived to resemble the cell microenvironment components or as a material strategy to instruct cells and alter cell behaviors. Therefore, they provide a clear understanding of the relationship between nanotechnologies and resulting cellular responses. This review will cover recent advances in nanobiomaterial research for applications in tissue engineering. In particular, recent developments in nanofibrous scaffolds, nanobiomaterial composites, hydrogel systems, laser-fabricated nanostructures and cell-based bioprinting methods to produce scaffolds with nanofeatures for tissue engineering are discussed. As in native niches of cells, where nanofeatures are constantly interacting and influencing cellular behavior, new generations of scaffolds will need to have these features to enable more desirable engineered tissues. Moving forward, tissue engineering will also have to address the issues of complexity and organization in tissues and organs.

Functional and morphological ultrasonic biomicroscopy for tissue engineers

NASA Astrophysics Data System (ADS)

Mallidi, S.; Aglyamov, S. R.; Karpiouk, A. B.; Park, S.; Emelianov, S. Y.

2006-03-01

Tissue engineering is an interdisciplinary field that combines various aspects of engineering and life sciences and aims to develop biological substitutes to restore, repair or maintain tissue function. Currently, the ability to have quantitative functional assays of engineered tissues is limited to existing invasive methods like biopsy. Hence, an imaging tool for non-invasive and simultaneous evaluation of the anatomical and functional properties of the engineered tissue is needed. In this paper we present an advanced in-vivo imaging technology - ultrasound biomicroscopy combined with complementary photoacoustic and elasticity imaging techniques, capable of accurate visualization of both structural and functional changes in engineered tissues, sequential monitoring of tissue adaptation and/or regeneration, and possible assistance of drug delivery and treatment planning. The combined imaging at microscopic resolution was evaluated on tissue mimicking phantoms imaged with 25 MHz single element focused transducer. The results of our study demonstrate that the ultrasonic, photoacoustic and elasticity images synergistically complement each other in detecting features otherwise imperceptible using the individual techniques. Finally, we illustrate the feasibility of the combined ultrasound, photoacoustic and elasticity imaging techniques in accurately assessing the morphological and functional changes occurring in engineered tissue.

Strategies and Applications for Incorporating Physical and Chemical Signal Gradients in Tissue Engineering

PubMed Central

Singh, Milind; Berkland, Cory

2008-01-01

From embryonic development to wound repair, concentration gradients of bioactive signaling molecules guide tissue formation and regeneration. Moreover, gradients in cellular and extracellular architecture as well as in mechanical properties are readily apparent in native tissues. Perhaps tissue engineers can take a cue from nature in attempting to regenerate tissues by incorporating gradients into engineering design strategies. Indeed, gradient-based approaches are an emerging trend in tissue engineering, standing in contrast to traditional approaches of homogeneous delivery of cells and/or growth factors using isotropic scaffolds. Gradients in tissue engineering lie at the intersection of three major paradigms in the field—biomimetic, interfacial, and functional tissue engineering—by combining physical (via biomaterial design) and chemical (with growth/differentiation factors and cell adhesion molecules) signal delivery to achieve a continuous transition in both structure and function. This review consolidates several key methodologies to generate gradients, some of which have never been employed in a tissue engineering application, and discusses strategies for incorporating these methods into tissue engineering and implant design. A key finding of this review was that two-dimensional physicochemical gradient substrates, which serve as excellent high-throughput screening tools for optimizing desired biomaterial properties, can be enhanced in the future by transitioning from two dimensions to three dimensions, which would enable studies of cell–protein–biomaterial interactions in a more native tissue–like environment. In addition, biomimetic tissue regeneration via combined delivery of graded physical and chemical signals appears to be a promising strategy for the regeneration of heterogeneous tissues and tissue interfaces. In the future, in vivo applications will shed more light on the performance of gradient-based mechanical integrity and signal delivery strategies compared to traditional tissue engineering approaches. PMID:18803499

Applications of Tissue Engineering in Joint Arthroplasty: Current Concepts Update.

PubMed

Zeineddine, Hussein A; Frush, Todd J; Saleh, Zeina M; El-Othmani, Mouhanad M; Saleh, Khaled J

2017-07-01

Research in tissue engineering has undoubtedly achieved significant milestones in recent years. Although it is being applied in several disciplines, tissue engineering's application is particularly advanced in orthopedic surgery and in degenerative joint diseases. The literature is full of remarkable findings and trials using tissue engineering in articular cartilage disease. With the vast and expanding knowledge, and with the variety of techniques available at hand, the authors aimed to review the current concepts and advances in the use of cell sources in articular cartilage tissue engineering. Copyright © 2017 Elsevier Inc. All rights reserved.

Textile Technologies and Tissue Engineering: A Path Toward Organ Weaving.

PubMed

Akbari, Mohsen; Tamayol, Ali; Bagherifard, Sara; Serex, Ludovic; Mostafalu, Pooria; Faramarzi, Negar; Mohammadi, Mohammad Hossein; Khademhosseini, Ali

2016-04-06

Textile technologies have recently attracted great attention as potential biofabrication tools for engineering tissue constructs. Using current textile technologies, fibrous structures can be designed and engineered to attain the required properties that are demanded by different tissue engineering applications. Several key parameters such as physiochemical characteristics of fibers, microarchitecture, and mechanical properties of the fabrics play important roles in the effective use of textile technologies in tissue engineering. This review summarizes the current advances in the manufacturing of biofunctional fibers. Different textile methods such as knitting, weaving, and braiding are discussed and their current applications in tissue engineering are highlighted. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Solid Free-form Fabrication Technology and Its Application to Bone Tissue Engineering

PubMed Central

Lee, Jin Woo; Kim, Jong Young; Cho, Dong-Woo

2010-01-01

The development of scaffolds for use in cell-based therapies to repair damaged bone tissue has become a critical component in the field of bone tissue engineering. However, design of scaffolds using conventional fabrication techniques has limited further advancement, due to a lack of the required precision and reproducibility. To overcome these constraints, bone tissue engineers have focused on solid free-form fabrication (SFF) techniques to generate porous, fully interconnected scaffolds for bone tissue engineering applications. This paper reviews the potential application of SFF fabrication technologies for bone tissue engineering with respect to scaffold fabrication. In the near future, bone scaffolds made using SFF apparatus should become effective therapies for bone defects. PMID:24855546

MECHANICAL DESIGN CRITERIA FOR INTERVERTEBRAL DISC TISSUE ENGINEERING

PubMed Central

Nerurkar, Nandan L.; Elliott, Dawn M.; Mauck, Robert L.

2009-01-01

Due to the inability of current clinical practices to restore function to degenerated intervertebral discs, the arena of disc tissue engineering has received substantial attention in recent years. Despite tremendous growth and progress in this field, translation to clinical implementation has been hindered by a lack of well-defined functional benchmarks. Because successful replacement of the disc is contingent upon replication of some or all of its complex mechanical behaviour, it is critically important that disc mechanics be well characterized in order to establish discrete functional goals for tissue engineering. In this review, the key functional signatures of the intervertebral disc are discussed and used to propose a series of native tissue benchmarks to guide the development of engineered replacement tissues. These benchmarks include measures of mechanical function under tensile, compressive and shear deformations for the disc and its substructures. In some cases, important functional measures are identified that have yet to be measured in the native tissue. Ultimately, native tissue benchmark values are compared to measurements that have been made on engineered disc tissues, identifying measures where functional equivalence was achieved, and others where there remain opportunities for advancement. Several excellent reviews exist regarding disc composition and structure, as well as recent tissue engineering strategies; therefore this review will remain focused on the functional aspects of disc tissue engineering. PMID:20080239

Tissue and Organ 3D Bioprinting.

PubMed

Xia, Zengmin; Jin, Sha; Ye, Kaiming

2018-02-01

Three-dimensional (3D) bioprinting enables the creation of tissue constructs with heterogeneous compositions and complex architectures. It was initially used for preparing scaffolds for bone tissue engineering. It has recently been adopted to create living tissues, such as cartilage, skin, and heart valve. To facilitate vascularization, hollow channels have been created in the hydrogels by 3D bioprinting. This review discusses the state of the art of the technology, along with a broad range of biomaterials used for 3D bioprinting. It provides an update on recent developments in bioprinting and its applications. 3D bioprinting has profound impacts on biomedical research and industry. It offers a new way to industrialize tissue biofabrication. It has great potential for regenerating tissues and organs to overcome the shortage of organ transplantation.

The self-assembling process and applications in tissue engineering

PubMed Central

Lee, Jennifer K.; Link, Jarrett M.; Hu, Jerry C. Y.; Athanasiou, Kyriacos A.

2018-01-01

Tissue engineering strives to create neotissues capable of restoring function. Scaffold-free technologies have emerged that can recapitulate native tissue function without the use of an exogenous scaffold. This chapter will survey, in particular, the self-assembling and self-organization processes as scaffold-free techniques. Characteristics and benefits of each process are described, and key examples of tissues created using these scaffold-free processes are examined to provide guidance for future tissue engineering developments. This chapter aims to explore the potential of self-assembly and self-organization scaffold-free approaches, detailing the recent progress in the in vitro tissue engineering of biomimetic tissues with these methods, toward generating functional tissue replacements. PMID:28348174

Biomaterials for tissue engineering applications.

PubMed

Keane, Timothy J; Badylak, Stephen F

2014-06-01

With advancements in biological and engineering sciences, the definition of an ideal biomaterial has evolved over the past 50 years from a substance that is inert to one that has select bioinductive properties and integrates well with adjacent host tissue. Biomaterials are a fundamental component of tissue engineering, which aims to replace diseased, damaged, or missing tissue with reconstructed functional tissue. Most biomaterials are less than satisfactory for pediatric patients because the scaffold must adapt to the growth and development of the surrounding tissues and organs over time. The pediatric community, therefore, provides a distinct challenge for the tissue engineering community. Copyright © 2014. Published by Elsevier Inc.

Recent insights on applications of pullulan in tissue engineering.

PubMed

Singh, Ram Sarup; Kaur, Navpreet; Rana, Vikas; Kennedy, John F

2016-11-20

Tissue engineering is a recently emerging line of act which assists the regeneration of damaged tissues, unable to self-repair themselves and in turn, enhances the natural healing potential of patients. The repair of injured tissue can be induced with the help of some artificially created polymer scaffolds for successful tissue regeneration. The pullulan composite scaffolds can be used to enhance the proliferation and differentiation of cells for tissue regeneration. The unique pattern of pullulan with α-(1→4) and α-(1→6) linkages along with the presence of nine hydroxyl groups on its surface, endows the polymer with distinctive physical features required for tissue engineering. Pullulan can be used for vascular engineering, bone repair and skin tissue engineering. Pullulan composite scaffolds can also be used for treatment of injured femoral condyle bone, skull bone and full thickness skin wound of murine models, transversal mandibular and tibial osteotomy in goat, etc. This review article highlights the latest developments on applications of pullulan and its derivatives in tissue engineering. Copyright © 2016 Elsevier Ltd. All rights reserved.

Nanomaterials for Craniofacial and Dental Tissue Engineering.

PubMed

Li, G; Zhou, T; Lin, S; Shi, S; Lin, Y

2017-07-01

Tissue engineering shows great potential as a future treatment for the craniofacial and dental defects caused by trauma, tumor, and other diseases. Due to the biomimetic features and excellent physiochemical properties, nanomaterials are of vital importance in promoting cell growth and stimulating tissue regeneration in tissue engineering. For craniofacial and dental tissue engineering, the frequently used nanomaterials include nanoparticles, nanofibers, nanotubes, and nanosheets. Nanofibers are attractive for cell invasion and proliferation because of their resemblance to extracellular matrix and the presence of large pores, and they have been used as scaffolds in bone, cartilage, and tooth regeneration. Nanotubes and nanoparticles improve the mechanical and chemical properties of scaffold, increase cell attachment and migration, and facilitate tissue regeneration. In addition, nanofibers and nanoparticles are also used as a delivery system to carry the bioactive agent in bone and tooth regeneration, have better control of the release speed of agent upon degradation of the matrix, and promote tissue regeneration. Although applications of nanomaterials in tissue engineering remain in their infancy with numerous challenges to face, the current results indicate that nanomaterials have massive potential in craniofacial and dental tissue engineering.

Self-Organization and the Self-Assembling Process in Tissue Engineering

PubMed Central

Eswaramoorthy, Rajalakshmanan; Hadidi, Pasha; Hu, Jerry C.

2015-01-01

In recent years, the tissue engineering paradigm has shifted to include a new and growing subfield of scaffoldless techniques which generate self-organizing and self-assembling tissues. This review aims to provide a cogent description of this relatively new research area, with special emphasis on applications toward clinical use and research models. Particular emphasis is placed on providing clear definitions of self-organization and the self-assembling process, as delineated from other scaffoldless techniques in tissue engineering and regenerative medicine. Significantly, during formation, self-organizing and self-assembling tissues display biological processes similar to those that occur in vivo. These help lead to the recapitulation of native tissue morphological structure and organization. Notably, functional properties of these tissues also approach native tissue values; some of these engineered tissues are already in clinical trials. This review aims to provide a cohesive summary of work in this field, and to highlight the potential of self-organization and the self-assembling process to provide cogent solutions to current intractable problems in tissue engineering. PMID:23701238

Reconstruction of Craniomaxillofacial Bone Defects Using Tissue-Engineering Strategies with Injectable and Non-Injectable Scaffolds

PubMed Central

Gaihre, Bipin; Uswatta, Suren; Jayasuriya, Ambalangodage C.

2017-01-01

Engineering craniofacial bone tissues is challenging due to their complex structures. Current standard autografts and allografts have many drawbacks for craniofacial bone tissue reconstruction; including donor site morbidity and the ability to reinstate the aesthetic characteristics of the host tissue. To overcome these problems; tissue engineering and regenerative medicine strategies have been developed as a potential way to reconstruct damaged bone tissue. Different types of new biomaterials; including natural polymers; synthetic polymers and bioceramics; have emerged to treat these damaged craniofacial bone tissues in the form of injectable and non-injectable scaffolds; which are examined in this review. Injectable scaffolds can be considered a better approach to craniofacial tissue engineering as they can be inserted with minimally invasive surgery; thus protecting the aesthetic characteristics. In this review; we also focus on recent research innovations with different types of stem-cell sources harvested from oral tissue and growth factors used to develop craniofacial bone tissue-engineering strategies. PMID:29156629

Tissue-engineered oral mucosa grafts for intraoral lining reconstruction of the maxilla and mandible with a fibula flap.

PubMed

Sieira Gil, Ramón; Pagés, Carles Martí; Díez, Eloy García; Llames, Sara; Fuertes, Ada Ferrer; Vilagran, Jesús Lopez

2015-01-01

Many types of soft tissue grafts have been used for grafting or prelaminating bone flaps for intraoral lining reconstruction. The best results are achieved when prelaminating free flaps with mucosal grafts. We suggest a new approach to obtain keratinized mucosa over a fibula flap using full-thickness, engineered, autologous oral mucosa. We report on a pilot study for grafting fibula flaps for mandibular and maxilla reconstruction with full-thickness tissue-engineered autologous oral mucosa. We describe 2 different techniques: prelaminating the fibula flap and second-stage grafting of the fibula after mandibular reconstruction. Preparation of the full-thickness tissue-engineered oral mucosa is also described. The clinical outcome of the tissue-engineered intraoral lining reconstruction and response after implant placement are reported. A peri-implant granulation tissue response was not observed when prelaminating the fibula, and little response was observed when intraoral grafting was performed. Tissue engineering represents an alternative method by which to obtain sufficient autologous tissue for reconstructing mucosal oral defects. The full-thickness engineered autologous oral mucosa offers definite advantages in terms of reconstruction planning, donor site morbidity, and quality of the intraoral soft tissue reconstruction, thereby restoring native tissue and avoiding peri-implant tissue complications. Copyright © 2015 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Advanced Collaborative Emissions Study Auxiliary Findings on 2007-Compliant Diesel Engines: A Comparison With Diesel Exhaust Genotoxicity Effects Prior to 2007

PubMed Central

Hallberg, Lance M; Ward, Jonathan B; Wickliffe, Jeffrey K; Ameredes, Bill T

2017-01-01

Since its beginning, more than 117 years ago, the compression-ignition engine, or diesel engine, has grown to become a critically important part of industry and transportation. Public concerns over the health effects from diesel emissions have driven the growth of regulatory development, implementation, and technological advances in emission controls. In 2001, the United States Environmental Protection Agency and California Air Resources Board issued new diesel fuel and emission standards for heavy-duty engines. To meet these stringent standards, manufacturers used new emission after-treatment technology, and modified fuel formulations, to bring about reductions in particulate matter and nitrogen oxides within the exhaust. To illustrate the impact of that technological transition, a brief overview of pre-2007 diesel engine exhaust biomarkers of genotoxicity and health-related concerns is provided, to set the context for the results of our research findings, as part of the Advanced Collaborative Emissions Study (ACES), in which the effects of a 2007-compliant diesel engine were examined. In agreement with ACES findings reported in other tissues, we observed a lack of measurable 2007-compliant diesel treatment–associated DNA damage, in lung tissue (comet assay), blood serum (8-hydroxy-2′-deoxyguanosine [8-OHdG] assay), and hippocampus (lipid peroxidation assay), across diesel exhaust exposure levels. A time-dependent assessment of 8-OHdG and lipid peroxidation also suggested no differences in responses across diesel exhaust exposure levels more than 24 months of exposure. These results indicated that the 2007-compliant diesel engine reduced measurable reactive oxygen species–associated tissue derangements and suggested that the 2007 standards–based mitigation approaches were effective. PMID:28659715

Human iPSC-derived cardiomyocytes and tissue engineering strategies for disease modeling and drug screening.

PubMed

Smith, Alec S T; Macadangdang, Jesse; Leung, Winnie; Laflamme, Michael A; Kim, Deok-Ho

Improved methodologies for modeling cardiac disease phenotypes and accurately screening the efficacy and toxicity of potential therapeutic compounds are actively being sought to advance drug development and improve disease modeling capabilities. To that end, much recent effort has been devoted to the development of novel engineered biomimetic cardiac tissue platforms that accurately recapitulate the structure and function of the human myocardium. Within the field of cardiac engineering, induced pluripotent stem cells (iPSCs) are an exciting tool that offer the potential to advance the current state of the art, as they are derived from somatic cells, enabling the development of personalized medical strategies and patient specific disease models. Here we review different aspects of iPSC-based cardiac engineering technologies. We highlight methods for producing iPSC-derived cardiomyocytes (iPSC-CMs) and discuss their application to compound efficacy/toxicity screening and in vitro modeling of prevalent cardiac diseases. Special attention is paid to the application of micro- and nano-engineering techniques for the development of novel iPSC-CM based platforms and their potential to advance current preclinical screening modalities. Published by Elsevier Inc.

Development of a Tissue Engineered Scaffold for Meniscus Replacement

DTIC Science & Technology

2008-12-01

include loss of manpower, rehabilitation costs, waste of training time/ money , cost to retrain members as replacements, hospitalization costs, disability...injuries in the United States Armed Forces. Mil Med, 1999. 164(8 Suppl): p. 633 pages. Lauder , T.D., et al., Sports and physical training injury

Stem Cells for Skeletal Muscle Tissue Engineering.

PubMed

Pantelic, Molly N; Larkin, Lisa M

2018-04-19

Volumetric muscle loss (VML) is a debilitating condition wherein muscle loss overwhelms the body's normal physiological repair mechanism. VML is particularly common among military service members who have sustained war injuries. Because of the high social and medical cost associated with VML and suboptimal current surgical treatments, there is great interest in developing better VML therapies. Skeletal muscle tissue engineering (SMTE) is a promising alternative to traditional VML surgical treatments that use autogenic tissue grafts, and rather uses isolated stem cells with myogenic potential to generate de novo skeletal muscle tissues to treat VML. Satellite cells are the native precursors to skeletal muscle tissue, and are thus the most commonly studied starting source for SMTE. However, satellite cells are difficult to isolate and purify, and it is presently unknown whether they would be a practical source in clinical SMTE applications. Alternative myogenic stem cells, including adipose-derived stem cells, bone marrow-derived mesenchymal stem cells, perivascular stem cells, umbilical cord mesenchymal stem cells, induced pluripotent stem cells, and embryonic stem cells, each have myogenic potential and have been identified as possible starting sources for SMTE, although they have yet to be studied in detail for this purpose. These alternative stem cell varieties offer unique advantages and disadvantages that are worth exploring further to advance the SMTE field toward highly functional, safe, and practical VML treatments. The following review summarizes the current state of satellite cell-based SMTE, details the properties and practical advantages of alternative myogenic stem cells, and offers guidance to tissue engineers on how alternative myogenic stem cells can be incorporated into SMTE research.

Tissue-engineered bone constructed in a bioreactor for repairing critical-sized bone defects in sheep.

PubMed

Li, Deqiang; Li, Ming; Liu, Peilai; Zhang, Yuankai; Lu, Jianxi; Li, Jianmin

2014-11-01

Repair of bone defects, particularly critical-sized bone defects, is a considerable challenge in orthopaedics. Tissue-engineered bones provide an effective approach. However, previous studies mainly focused on the repair of bone defects in small animals. For better clinical application, repairing critical-sized bone defects in large animals must be studied. This study investigated the effect of a tissue-engineered bone for repairing critical-sized bone defect in sheep. A tissue-engineered bone was constructed by culturing bone marrow mesenchymal-stem-cell-derived osteoblast cells seeded in a porous β-tricalcium phosphate ceramic (β-TCP) scaffold in a perfusion bioreactor. A critical-sized bone defect in sheep was repaired with the tissue-engineered bone. At the eighth and 16th week after the implantation of the tissue-engineered bone, X-ray examination and histological analysis were performed to evaluate the defect. The bone defect with only the β-TCP scaffold served as the control. X-ray showed that the bone defect was successfully repaired 16 weeks after implantation of the tissue-engineered bone; histological sections showed that a sufficient volume of new bones formed in β-TCP 16 weeks after implantation. Eight and 16 weeks after implantation, the volume of new bones that formed in the tissue-engineered bone group was more than that in the β-TCP scaffold group (P < 0.05). Tissue-engineered bone improved osteogenesis in vivo and enhanced the ability to repair critical-sized bone defects in large animals.

Biomimetic stratified scaffold design for ligament-to-bone interface tissue engineering.

PubMed

Lu, Helen H; Spalazzi, Jeffrey P

2009-07-01

The emphasis in the field of orthopaedic tissue engineering is on imparting biomimetic functionality to tissue engineered bone or soft tissue grafts and enabling their translation to the clinic. A significant challenge in achieving extended graft functionality is engineering the biological fixation of these grafts with each other as well as with the host environment. Biological fixation will require re-establishment of the structure-function relationship inherent at the native soft tissue-to-bone interface on these tissue engineered grafts. To this end, strategic biomimicry must be incorporated into advanced scaffold design. To facilitate integration between distinct tissue types (e.g., bone with soft tissues such as cartilage, ligament, or tendon), a stratified or multi-phasic scaffold with distinct yet continuous tissue regions is required to pre-engineer the interface between bone and soft tissues. Using the ACL-to-bone interface as a model system, this review outlines the strategies for stratified scaffold design for interface tissue engineering, focusing on identifying the relevant design parameters derived from an understanding of the structure-function relationship inherent at the soft-to-hard tissue interface. The design approach centers on first addressing the challenge of soft tissue-to-bone integration ex vivo, and then subsequently focusing on the relatively less difficult task of bone-to-bone integration in vivo. In addition, we will review stratified scaffold design aimed at exercising spatial control over heterotypic cellular interactions, which are critical for facilitating the formation and maintenance of distinct yet continuous multi-tissue regions. Finally, potential challenges and future directions in this emerging area of advanced scaffold design will be discussed.

Real-time quantitation of internal metabolic activity of three-dimensional engineered tissues using an oxygen microelectrode and optical coherence tomography.

PubMed

Kagawa, Yuki; Haraguchi, Yuji; Tsuneda, Satoshi; Shimizu, Tatsuya

2017-05-01

Recent progress in tissue engineering technology has enabled us to develop thick tissue constructs that can then be transplanted in regenerative therapies. In clinical situations, it is vital that the engineered tissues to be implanted are safe and functional before use. However, there is currently a limited number of studies on real-time quality evaluation of thick living tissue constructs. Here we developed a system for quantifying the internal activities of engineered tissues, from which we can evaluate its quality in real-time. The evaluation was achieved by measuring oxygen concentration profiles made along the vertical axis and the thickness of the tissues estimated from cross-sectional images obtained noninvasively by an optical coherence tomography system. Using our novel system, we obtained (i) oxygen concentration just above the tissues, (ii) gradient of oxygen along vertical axis formed above the tissues within culture medium, and (iii) gradient of oxygen formed within the tissues in real-time. Investigating whether these three parameters could be used to evaluate engineered tissues during culturing, we found that only the third parameter was a good candidate. This implies that the activity of living engineered tissues can be monitored in real-time by measuring the oxygen gradient within the tissues. The proposed measuring strategy can be applied to developing more efficient culturing methods to support the fabrication of engineered thick tissues, as well as providing methods to confirm the quality in real-time. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 855-864, 2017. © 2015 Wiley Periodicals, Inc.

Cells for tissue engineering of cardiac valves.

PubMed

Jana, Soumen; Tranquillo, Robert T; Lerman, Amir

2016-10-01

Heart valve tissue engineering is a promising alternative to prostheses for the replacement of diseased or damaged heart valves, because tissue-engineered valves have the ability to remodel, regenerate and grow. To engineer heart valves, cells are harvested, seeded onto or into a three-dimensional (3D) matrix platform to generate a tissue-engineered construct in vitro, and then implanted into a patient's body. Successful engineering of heart valves requires a thorough understanding of the different types of cells that can be used to obtain the essential phenotypes that are expressed in native heart valves. This article reviews different cell types that have been used in heart valve engineering, cell sources for harvesting, phenotypic expression in constructs and suitability in heart valve tissue engineering. Natural and synthetic biomaterials that have been applied as scaffold systems or cell-delivery platforms are discussed with each cell type. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

"Deep-media culture condition" promoted lumen formation of endothelial cells within engineered three-dimensional tissues in vitro.

PubMed

Sekiya, Sachiko; Shimizu, Tatsuya; Yamato, Masayuki; Okano, Teruo

2011-03-01

In the field of tissue engineering, the induction of microvessels into tissues is an important task because of the need to overcome diffusion limitations of oxygen and nutrients within tissues. Powerful methods to create vessels in engineered tissues are needed for creating real living tissues. In this study, we utilized three-dimensional (3D) highly cell dense tissues fabricated by cell sheet technology. The 3D tissue constructs are close to living-cell dense tissue in vivo. Additionally, creating an endothelial cell (EC) network within tissues promoted neovascularization promptly within the tissue after transplantation in vivo. Compared to the conditions in vivo, however, common in vitro cell culture conditions provide a poor environment for creating lumens within 3D tissue constructs. Therefore, for determining adequate conditions for vascularizing engineered tissue in vitro, our 3D tissue constructs were cultured under a "deep-media culture conditions." Compared to the control conditions, the morphology of ECs showed a visibly strained cytoskeleton, and the density of lumen formation within tissues increased under hydrostatic pressure conditions. Moreover, the increasing expression of vascular endothelial cadherin in the lumens suggested that the vessels were stabilized in the stimulated tissues compared with the control. These findings suggested that deep-media culture conditions improved lumen formation in engineered tissues in vitro.

Recent Tissue Engineering Advances for the Treatment of Temporomandibular Joint Disorders.

PubMed

Aryaei, Ashkan; Vapniarsky, Natalia; Hu, Jerry C; Athanasiou, Kyriacos A

2016-12-01

Temporomandibular disorders (TMDs) are among the most common maxillofacial complaints and a major cause of orofacial pain. Although current treatments provide short- and long-term relief, alternative tissue engineering solutions are in great demand. Particularly, the development of strategies, providing long-term resolution of TMD to help patients regain normal function, is a high priority. An absolute prerequisite of tissue engineering is to understand normal structure and function. The current knowledge of anatomical, mechanical, and biochemical characteristics of the temporomandibular joint (TMJ) and associated tissues will be discussed, followed by a brief description of current TMD treatments. The main focus is on recent tissue engineering developments for regenerating TMJ tissue components, with or without a scaffold. The expectation for effectively managing TMD is that tissue engineering will produce biomimetic TMJ tissues that recapitulate the normal structure and function of the TMJ.

Recent tissue engineering advances for the treatment of temporomandibular joint disorders

PubMed Central

Aryaei, Ashkan; Vapniarsky, Natalia; Hu, Jerry C; Athanasiou, Kyriacos A

2016-01-01

Temporomandibular disorders (TMD) are among the most common maxillofacial complaints and a major cause of orofacial pain. Although, current treatments provide short- and long-term relief, alternative tissue engineering solutions are in great demand. Particularly, the development of strategies, providing long-term resolution of TMD to help patients regain normal function is a high priority. An absolute prerequisite of tissue engineering is to understand normal structure and function. The current knowledge of anatomical, mechanical, and biochemical characteristics of the temporomandibular joint (TMJ) and associated tissues will be discussed, followed by a brief description of current TMD treatments. The main focus is on recent tissue engineering developments for regenerating TMJ tissue components, with or without a scaffold. The expectation for effectively managing TMD is that tissue engineering will produce biomimetic TMJ tissues that recapitulate the normal structure and function of the TMJ. PMID:27704395

The potential of tissue engineering for developing alternatives to animal experiments: a systematic review.

PubMed

de Vries, Rob B M; Leenaars, Marlies; Tra, Joppe; Huijbregtse, Robbertjan; Bongers, Erik; Jansen, John A; Gordijn, Bert; Ritskes-Hoitinga, Merel

2015-07-01

An underexposed ethical issue raised by tissue engineering is the use of laboratory animals in tissue engineering research. Even though this research results in suffering and loss of life in animals, tissue engineering also has great potential for the development of alternatives to animal experiments. With the objective of promoting a joint effort of tissue engineers and alternative experts to fully realise this potential, this study provides the first comprehensive overview of the possibilities of using tissue-engineered constructs as a replacement of laboratory animals. Through searches in two large biomedical databases (PubMed, Embase) and several specialised 3R databases, 244 relevant primary scientific articles, published between 1991 and 2011, were identified. By far most articles reviewed related to the use of tissue-engineered skin/epidermis for toxicological applications such as testing for skin irritation. This review article demonstrates, however, that the potential for the development of alternatives also extends to other tissues such as other epithelia and the liver, as well as to other fields of application such as drug screening and basic physiology. This review discusses which impediments need to be overcome to maximise the contributions that the field of tissue engineering can make, through the development of alternative methods, to the reduction of the use and suffering of laboratory animals. Copyright © 2013 John Wiley & Sons, Ltd.

Vascularized Bone Tissue Engineering: Approaches for Potential Improvement

PubMed Central

Nguyen, Lonnissa H.; Annabi, Nasim; Nikkhah, Mehdi; Bae, Hojae; Binan, Loïc; Park, Sangwon; Kang, Yunqing

2012-01-01

Significant advances have been made in bone tissue engineering (TE) in the past decade. However, classical bone TE strategies have been hampered mainly due to the lack of vascularization within the engineered bone constructs, resulting in poor implant survival and integration. In an effort toward clinical success of engineered constructs, new TE concepts have arisen to develop bone substitutes that potentially mimic native bone tissue structure and function. Large tissue replacements have failed in the past due to the slow penetration of the host vasculature, leading to necrosis at the central region of the engineered tissues. For this reason, multiple microscale strategies have been developed to induce and incorporate vascular networks within engineered bone constructs before implantation in order to achieve successful integration with the host tissue. Previous attempts to engineer vascularized bone tissue only focused on the effect of a single component among the three main components of TE (scaffold, cells, or signaling cues) and have only achieved limited success. However, with efforts to improve the engineered bone tissue substitutes, bone TE approaches have become more complex by combining multiple strategies simultaneously. The driving force behind combining various TE strategies is to produce bone replacements that more closely recapitulate human physiology. Here, we review and discuss the limitations of current bone TE approaches and possible strategies to improve vascularization in bone tissue substitutes. PMID:22765012

Monitoring tissue metabolism via time-resolved laser fluorescence

NASA Astrophysics Data System (ADS)

Maerz, Holger K.; Buchholz, Rainer; Emmrich, Frank; Fink, Frank; Geddes, Clive L.; Pfeifer, Lutz; Raabe, Ferdinand; Marx, Uwe

1999-05-01

Most assays for drug screening are monitoring the metabolism of cells by detecting the NADH content, which symbolize its metabolic activity, indirectly. Nowadays, the performance of a LASER enables us to monitor the metabolic state of mammalian cells directly and on-line by using time-resolved autofluorescence detection. Therefore, we developed in combination with tissue engineering, an assay for monitoring minor toxic effects of volatile organic compounds (VOC), which are accused of inducing Sick Building Syndrome (SBS). Furthermore, we used the Laserfluoroscope (LF) for pharmacological studies on human bone marrow in vitro with special interest in chemotherapy simulation. In cancer research and therapy, the effect of chemostatica in vitro in the so-called oncobiogram is being tested; up to now without great success. However, it showed among other things that tissue structure plays a vital role. Consequently, we succeeded in simulating a chemotherapy in vitro on human bone marrow. Furthermore, after tumor ektomy we were able to distinguish between tumoric and its surrounding healthy tissue by using the LF. With its sensitive detection of metabolic changes in tissues the LF enables a wide range of applications in biotechnology, e.g. for quality control in artificial organ engineering or biocompatability testing.

Engineered heart tissues and induced pluripotent stem cells: Macro- and microstructures for disease modeling, drug screening, and translational studies.

PubMed

Tzatzalos, Evangeline; Abilez, Oscar J; Shukla, Praveen; Wu, Joseph C

2016-01-15

Engineered heart tissue has emerged as a personalized platform for drug screening. With the advent of induced pluripotent stem cell (iPSC) technology, patient-specific stem cells can be developed and expanded into an indefinite source of cells. Subsequent developments in cardiovascular biology have led to efficient differentiation of cardiomyocytes, the force-producing cells of the heart. iPSC-derived cardiomyocytes (iPSC-CMs) have provided potentially limitless quantities of well-characterized, healthy, and disease-specific CMs, which in turn has enabled and driven the generation and scale-up of human physiological and disease-relevant engineered heart tissues. The combined technologies of engineered heart tissue and iPSC-CMs are being used to study diseases and to test drugs, and in the process, have advanced the field of cardiovascular tissue engineering into the field of precision medicine. In this review, we will discuss current developments in engineered heart tissue, including iPSC-CMs as a novel cell source. We examine new research directions that have improved the function of engineered heart tissue by using mechanical or electrical conditioning or the incorporation of non-cardiomyocyte stromal cells. Finally, we discuss how engineered heart tissue can evolve into a powerful tool for therapeutic drug testing. Copyright © 2015 Elsevier B.V. All rights reserved.

Tissue-engineered vascularized bone grafts: basic science and clinical relevance to trauma and reconstructive microsurgery.

PubMed

Johnson, Elizabeth O; Troupis, Theodore; Soucacos, Panayotis N

2011-03-01

Bone grafts are an important part of orthopaedic surgeon's armamentarium. Despite well-established bone-grafting techniques, large bone defects still represent a challenge. Efforts have therefore been made to develop osteoconductive, osteoinductive, and osteogenic bone-replacement systems. The long-term clinical goal in bone tissue engineering is to reconstruct bony tissue in an anatomically functional three-dimensional morphology. Current bone tissue engineering strategies take into account that bone is known for its ability to regenerate following injury, and for its intrinsic capability to re-establish a complex hierarchical structure during regeneration. Although the tissue engineering of bone for the reconstruction of small to moderate sized bone defects technically feasible, the reconstruction of large defects remains a daunting challenge. The essential steps towards optimized clinical application of tissue-engineered bone are dependent upon recent advances in the area of neovascularization of the engineered construct. Despite these recent advances, however, a gap from bench to bedside remains; this may ultimately be bridged by a closer collaboration between basic scientists and reconstructive surgeons. The aim of this review is to introduce the basic principles of tissue engineering of bone, outline the relevant bone physiology, and discuss the recent concepts for the induction of vascularization in engineered bone tissue. Copyright © 2011 Wiley-Liss, Inc.

Microfluidic hydrogels for tissue engineering.

PubMed

Huang, Guo You; Zhou, Li Hong; Zhang, Qian Cheng; Chen, Yong Mei; Sun, Wei; Xu, Feng; Lu, Tian Jian

2011-03-01

With advanced properties similar to the native extracellular matrix, hydrogels have found widespread applications in tissue engineering. Hydrogel-based cellular constructs have been successfully developed to engineer different tissues such as skin, cartilage and bladder. Whilst significant advances have been made, it is still challenging to fabricate large and complex functional tissues due mainly to the limited diffusion capability of hydrogels. The integration of microfluidic networks and hydrogels can greatly enhance mass transport in hydrogels and spatiotemporally control the chemical microenvironment of cells, mimicking the function of native microvessels. In this review, we present and discuss recent advances in the fabrication of microfluidic hydrogels from the viewpoint of tissue engineering. Further development of new hydrogels and microengineering technologies will have a great impact on tissue engineering.

Tissue engineering strategies to study cartilage development, degeneration and regeneration.

PubMed

Bhattacharjee, Maumita; Coburn, Jeannine; Centola, Matteo; Murab, Sumit; Barbero, Andrea; Kaplan, David L; Martin, Ivan; Ghosh, Sourabh

2015-04-01

Cartilage tissue engineering has primarily focused on the generation of grafts to repair cartilage defects due to traumatic injury and disease. However engineered cartilage tissues have also a strong scientific value as advanced 3D culture models. Here we first describe key aspects of embryonic chondrogenesis and possible cell sources/culture systems for in vitro cartilage generation. We then review how a tissue engineering approach has been and could be further exploited to investigate different aspects of cartilage development and degeneration. The generated knowledge is expected to inform new cartilage regeneration strategies, beyond a classical tissue engineering paradigm. Copyright © 2014 Elsevier B.V. All rights reserved.

Research highlights: Microtechnologies for engineering the cellular environment.

PubMed

Tseng, Peter; Kunze, Anja; Kittur, Harsha; Di Carlo, Dino

2014-04-07

In this issue we highlight recent microtechnology-enabled approaches to control the physical and biomolecular environment around cells: (1) developing micropatterned surfaces to quantify cell affinity choices between two adhesive patterns, (2) controlling topographical cues to align cells and improve reprogramming to a pluripotent state, and (3) controlling gradients of biomolecules to maintain pluripotency in embryonic stem cells. Quantitative readouts of cell-surface affinity in environments with several cues should open up avenues in tissue engineering where self-assembly of complex multi-cellular structures is possible by precisely engineering relative adhesive cues in three dimensional constructs. Methods of simple and local epigenetic modification of chromatin structure with microtopography and biomolecular gradients should also be of use in regenerative medicine, as well as in high-throughput quantitative analysis of external signals that impact and can be used to control cells. Overall, approaches to engineer the cellular environment will continue to be an area of further growth in the microfluidic and lab on a chip community, as the scale of the technologies seamlessly matches that of biological systems. However, because of regulations and other complexities with tissue engineered therapies, these micro-engineering approaches will likely first impact organ-on-a-chip technologies that are poised to improve drug discovery pipelines.

Cost of Stem Cell-Based Tissue-Engineered Airway Transplants in the United Kingdom: Case Series

PubMed Central

Culme-Seymour, Emily J.; Mason, Katrina; Vallejo-Torres, Laura; Carvalho, Carla; Partington, Leanne; Crowley, Claire; Hamilton, Nick J.; Toll, Ed C.; Butler, Colin R.; Elliott, Martin J.; Birchall, Martin A.; Lowdell, Mark W.

2016-01-01

Stem cell-based tissue-engineered tracheas are at an early stage in their product development cycle. Tens of patients have been treated worldwide in predominantly compassionate use settings, demonstrating significant promise. This potentially life-saving treatment is complex, and the cost and its implications for such treatments are yet to be fully understood. The costs are compounded by varying strategies for graft preparation and transplant, resulting in differing clinical and laboratory costs from different research groups. In this study, we present a detailed breakdown of the clinical and manufacturing costs for three of the United Kingdom (UK) patients treated with such transplants. All three patients were treated under Compassionate Use legislation, within the UK National Health Service (NHS) hospital setting. The total costs for the three UK patients treated ranged from $174,420 to $740,500. All three patients were in a state of poor health at time of treatment and had a number of complexities in addition to the restricted airway. This is the first time a cost analysis has been made for a tissue-engineered organ and provides a benchmark for future studies, as well as comparative data for use in reimbursement considerations. PMID:26559535

Cost of Stem Cell-Based Tissue-Engineered Airway Transplants in the United Kingdom: Case Series.

PubMed

Culme-Seymour, Emily J; Mason, Katrina; Vallejo-Torres, Laura; Carvalho, Carla; Partington, Leanne; Crowley, Claire; Hamilton, Nick J; Toll, Ed C; Butler, Colin R; Elliott, Martin J; Birchall, Martin A; Lowdell, Mark W; Mason, Chris

2016-02-01

Stem cell-based tissue-engineered tracheas are at an early stage in their product development cycle. Tens of patients have been treated worldwide in predominantly compassionate use settings, demonstrating significant promise. This potentially life-saving treatment is complex, and the cost and its implications for such treatments are yet to be fully understood. The costs are compounded by varying strategies for graft preparation and transplant, resulting in differing clinical and laboratory costs from different research groups. In this study, we present a detailed breakdown of the clinical and manufacturing costs for three of the United Kingdom (UK) patients treated with such transplants. All three patients were treated under Compassionate Use legislation, within the UK National Health Service (NHS) hospital setting. The total costs for the three UK patients treated ranged from $174,420 to $740,500. All three patients were in a state of poor health at time of treatment and had a number of complexities in addition to the restricted airway. This is the first time a cost analysis has been made for a tissue-engineered organ and provides a benchmark for future studies, as well as comparative data for use in reimbursement considerations.

Tendon Tissue Engineering: Progress, Challenges, and Translation to the Clinic

PubMed Central

Shearn, Jason T.; Kinneberg, Kirsten R.C.; Dyment, Nathaniel A.; Galloway, Marc T.; Kenter, Keith; Wylie, Christopher; Butler, David L.

2013-01-01

The tissue engineering field has made great strides in understanding how different aspects of tissue engineered constructs (TECs) and the culture process affect final tendon repair. However, there remain significant challenges in developing strategies that will lead to a clinically effective and commercially successful product. In an effort to increase repair quality, a better understanding of normal development, and how it differs from adult tendon healing, may provide strategies to improve tissue engineering. As tendon tissue engineering continues to improve, the field needs to employ more clinically relevant models of tendon injury such as degenerative tendons. We need to translate successes to larger animal models to begin exploring the clinical implications of our treatments. By advancing the models used to validate our TECs, we can help convince our toughest customer, the surgeon, that our products will be clinically efficacious. As we address these challenges in musculoskeletal tissue engineering, the field still needs to address the commercialization of products developed in the laboratory. TEC commercialization faces numerous challenges because each injury and patient is unique. This review aims to provide tissue engineers with a summary of important issues related to engineering tendon repairs and potential strategies for producing clinically successful products. PMID:21625053

Design considerations and challenges for mechanical stretch bioreactors in tissue engineering.

PubMed

Lei, Ying; Ferdous, Zannatul

2016-05-01

With the increase in average life expectancy and growing aging population, lack of functional grafts for replacement surgeries has become a severe problem. Engineered tissues are a promising alternative to this problem because they can mimic the physiological function of the native tissues and be cultured on demand. Cyclic stretch is important for developing many engineered tissues such as hearts, heart valves, muscles, and bones. Thus a variety of stretch bioreactors and corresponding scaffolds have been designed and tested to study the underlying mechanism of tissue formation and to optimize the mechanical conditions applied to the engineered tissues. In this review, we look at various designs of stretch bioreactors and common scaffolds and offer insights for future improvements in tissue engineering applications. First, we summarize the requirements and common configuration of stretch bioreactors. Next, we present the features of different actuating and motion transforming systems and their applications. Since most bioreactors must measure detailed distributions of loads and deformations on engineered tissues, techniques with high accuracy, precision, and frequency have been developed. We also cover the key points in designing culture chambers, nutrition exchanging systems, and regimens used for specific tissues. Since scaffolds are essential for providing biophysical microenvironments for residing cells, we discuss materials and technologies used in fabricating scaffolds to mimic anisotropic native tissues, including decellularized tissues, hydrogels, biocompatible polymers, electrospinning, and 3D bioprinting techniques. Finally, we present the potential future directions for improving stretch bioreactors and scaffolds. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:543-553, 2016. © 2016 American Institute of Chemical Engineers.

Global tissue engineering trends. A scientometric and evolutive study.

PubMed

Santisteban-Espejo, Antonio; Campos, Fernando; Martin-Piedra, Laura; Durand-Herrera, Daniel; Moral-Munoz, Jose A; Campos, Antonio; Martin-Piedra, Miguel Angel

2018-04-24

Tissue engineering is defined as a multidisciplinary scientific discipline with the main objective to develop artificial bioengineered living tissues in order to regenerate damaged or lost tissues. Since its appearance in 1988, tissue engineering has globally spreaded in order to improve current therapeutical approaches, entailing a revolution in clinical practice. The aim of this study is to analyze global research trends on tissue engineering publications in order to realize the scenario of tissue engineering research from 1991 to 2016 by using document retrieval from Web of Science database and bibliometric analysis. Document type, language, source title, authorship, countries and filiation centers and citation count were evaluated in 31,859 documents. Obtained results suggest a great multidisciplinary role of tissue engineering due to a wide spectrum -up to 51- of scientific research areas identified in the corpus of literature, being predominant technological disciplines as Material Sciences or Engineering, followed by biological and biomedical areas, as Cell Biology, Biotechnology or Biochemistry. Distribution of authorship, journals and countries revealed a clear imbalance in which a minority is responsible of a majority of documents. Such imbalance is notorious in authorship, where a 0.3% of authors are involved in the half of the whole production.

A Perspective on the Clinical Translation of Scaffolds for Tissue Engineering

PubMed Central

Webber, Matthew J.; Khan, Omar F.; Sydlik, Stefanie A.; Tang, Benjamin C.; Langer, Robert

2016-01-01

Scaffolds have been broadly applied within tissue engineering and regenerative medicine to regenerate, replace, or augment diseased or damaged tissue. For a scaffold to perform optimally, several design considerations must be addressed, with an eye toward the eventual form, function, and tissue site. The chemical and mechanical properties of the scaffold must be tuned to optimize the interaction with cells and surrounding tissues. For complex tissue engineering, mass transport limitations, vascularization, and host tissue integration are important considerations. As the tissue architecture to be replaced becomes more complex and hierarchical, scaffold design must also match this complexity to recapitulate a functioning tissue. We outline these design constraints and highlight creative and emerging strategies to overcome limitations and modulate scaffold properties for optimal regeneration. We also highlight some of the most advanced strategies that have seen clinical application and discuss the hurdles that must be overcome for clinical use and commercialization of tissue engineering technologies. Finally, we provide a perspective on the future of scaffolds as a functional contributor to advancing tissue engineering and regenerative medicine. PMID:25201605

A perspective on the clinical translation of scaffolds for tissue engineering.

PubMed

Webber, Matthew J; Khan, Omar F; Sydlik, Stefanie A; Tang, Benjamin C; Langer, Robert

2015-03-01

Scaffolds have been broadly applied within tissue engineering and regenerative medicine to regenerate, replace, or augment diseased or damaged tissue. For a scaffold to perform optimally, several design considerations must be addressed, with an eye toward the eventual form, function, and tissue site. The chemical and mechanical properties of the scaffold must be tuned to optimize the interaction with cells and surrounding tissues. For complex tissue engineering, mass transport limitations, vascularization, and host tissue integration are important considerations. As the tissue architecture to be replaced becomes more complex and hierarchical, scaffold design must also match this complexity to recapitulate a functioning tissue. We outline these design constraints and highlight creative and emerging strategies to overcome limitations and modulate scaffold properties for optimal regeneration. We also highlight some of the most advanced strategies that have seen clinical application and discuss the hurdles that must be overcome for clinical use and commercialization of tissue engineering technologies. Finally, we provide a perspective on the future of scaffolds as a functional contributor to advancing tissue engineering and regenerative medicine.

Cartilage tissue engineering approaches applicable in orthopaedic surgery: the past, the present, and the future.

PubMed

Khan, Wasim S; Hardingham, Timothy E

2012-01-01

Tissue is frequently damaged or lost in injury and disease. There has been an increasing interest in stem cell applications and tissue engineering approaches in surgical practice to deal with damaged or lost tissue. Although there have been developments in almost all surgical disciplines, the greatest advances are being made in orthopaedics, especially in cartilage repair. This is due to many factors including the familiarity with bone marrow derived mesenchymal stem cells and cartilage being a relatively simpler tissue to engineer. Unfortunately significant hurdles remain to be overcome in many areas before tissue engineering becomes more routinely used in clinical practice. In this paper we discuss the structure, function and embryology of cartilage and osteoarthritis. This is followed by a review of current treatment strategies for the repair of cartilage and the use of tissue engineering.

Stem Cells in Skeletal Tissue Engineering: Technologies and Models

PubMed Central

Langhans, Mark T.; Yu, Shuting; Tuan, Rocky S.

2017-01-01

This review surveys the use of pluripotent and multipotent stem cells in skeletal tissue engineering. Specific emphasis is focused on evaluating the function and activities of these cells in the context of development in vivo, and how technologies and methods of stem cell-based tissue engineering for stem cells must draw inspiration from developmental biology. Information on the embryonic origin and in vivo differentiation of skeletal tissues is first reviewed, to shed light on the persistence and activities of adult stem cells that remain in skeletal tissues after embryogenesis. Next, the development and differentiation of pluripotent stem cells is discussed, and some of their advantages and disadvantages in the context of tissue engineering is presented. The final section highlights current use of multipotent adult mesenchymal stem cells, reviewing their origin, differentiation capacity, and potential applications to tissue engineering. PMID:26423296

Tissue Engineering-based Therapeutic Strategies for Vocal Fold Repair and Regeneration

PubMed Central

Li, Linqing; Stiadle, Jeanna M.; Lau, Hang K.; Zerdoum, Aidan B.; Jia, Xinqiao; L.Thibeault, Susan; Kiick, Kristi L.

2016-01-01

Vocal folds are soft laryngeal connective tissues with distinct layered structures and complex multicomponent matrix compositions that endow phonatory and respiratory functions. This delicate tissue is easily damaged by various environmental factors and pathological conditions, altering vocal biomechanics and causing debilitating vocal disorders that detrimentally affect the daily lives of suffering individuals. Modern techniques and advanced knowledge of regenerative medicine have led to a deeper understanding of the microstructure, microphysiology, and micropathophysiology of vocal fold tissues. State-of-the-art materials ranging from extracecullar-matrix (ECM)-derived biomaterials to synthetic polymer scaffolds have been proposed for the prevention and treatment of voice disorders including vocal fold scarring and fibrosis. This review intends to provide a thorough overview of current achievements in the field of vocal fold tissue engineering, including the fabrication of injectable biomaterials to mimic in vitro cell microenvironments, novel designs of bioreactors that capture in vivo tissue biomechanics, and establishment of various animal models to characterize the in vivo biocompatibility of these materials. The combination of polymeric scaffolds, cell transplantation, biomechanical stimulation, and delivery of antifibrotic growth factors will lead to successful restoration of functional vocal folds and improved vocal recovery in animal models, facilitating the application of these materials and related methodologies in clinical practice. PMID:27619243

3D bioprinting for vascularized tissue fabrication

PubMed Central

Richards, Dylan; Jia, Jia; Yost, Michael; Markwald, Roger; Mei, Ying

2016-01-01

3D bioprinting holds remarkable promise for rapid fabrication of 3D tissue engineering constructs. Given its scalability, reproducibility, and precise multi-dimensional control that traditional fabrication methods do not provide, 3D bioprinting provides a powerful means to address one of the major challenges in tissue engineering: vascularization. Moderate success of current tissue engineering strategies have been attributed to the current inability to fabricate thick tissue engineering constructs that contain endogenous, engineered vasculature or nutrient channels that can integrate with the host tissue. Successful fabrication of a vascularized tissue construct requires synergy between high throughput, high-resolution bioprinting of larger perfusable channels and instructive bioink that promotes angiogenic sprouting and neovascularization. This review aims to cover the recent progress in the field of 3D bioprinting of vascularized tissues. It will cover the methods of bioprinting vascularized constructs, bioink for vascularization, and perspectives on recent innovations in 3D printing and biomaterials for the next generation of 3D bioprinting for vascularized tissue fabrication. PMID:27230253

Microstructural Heterogeneity in Native and Engineered Fibrocartilage Directs Micromechanics and Mechanobiology

PubMed Central

Han, Woojin M; Heo, Su-Jin; Driscoll, Tristan P; Delucca, John F; McLeod, Claire M; Smith, Lachlan J; Duncan, Randall L; Mauck, Robert L; Elliott, Dawn M

2015-01-01

Treatment strategies to address pathologies of fibrocartilaginous tissue are in part limited by an incomplete understanding of structure-function relationships in these load-bearing tissues. There is therefore a pressing need to develop microengineered tissue platforms that can recreate the highly inhomogeneous tissue microstructures that are known to influence mechanotransductive processes in normal and diseased tissue. Here, we report the quantification of proteoglycan-rich microdomains in developing, aging, and diseased fibrocartilaginous tissues, and the impact of these microdomains on endogenous cell responses to physiologic deformation within a native-tissue context. We also developed a method to generate heterogeneous tissue engineered constructs (hetTECs) with microscale non-fibrous proteoglycan-rich microdomains engineered into the fibrous structure, and show that these hetTECs match the microstructural, micromechanical, and mechanobiological benchmarks of native tissue. Our tissue engineered platform should facilitate the study of the mechanobiology of developing, homeostatic, degenerating, and regenerating fibrous tissues. PMID:26726994

Mechanical design criteria for intervertebral disc tissue engineering.

PubMed

Nerurkar, Nandan L; Elliott, Dawn M; Mauck, Robert L

2010-04-19

Due to the inability of current clinical practices to restore function to degenerated intervertebral discs, the arena of disc tissue engineering has received substantial attention in recent years. Despite tremendous growth and progress in this field, translation to clinical implementation has been hindered by a lack of well-defined functional benchmarks. Because successful replacement of the disc is contingent upon replication of some or all of its complex mechanical behaviors, it is critically important that disc mechanics be well characterized in order to establish discrete functional goals for tissue engineering. In this review, the key functional signatures of the intervertebral disc are discussed and used to propose a series of native tissue benchmarks to guide the development of engineered replacement tissues. These benchmarks include measures of mechanical function under tensile, compressive, and shear deformations for the disc and its substructures. In some cases, important functional measures are identified that have yet to be measured in the native tissue. Ultimately, native tissue benchmark values are compared to measurements that have been made on engineered disc tissues, identifying where functional equivalence was achieved, and where there remain opportunities for advancement. Several excellent reviews exist regarding disc composition and structure, as well as recent tissue engineering strategies; therefore this review will remain focused on the functional aspects of disc tissue engineering. Copyright 2009 Elsevier Ltd. All rights reserved.

Expediting the transition from replacement medicine to tissue engineering.

PubMed

Coury, Arthur J

2016-06-01

In this article, an expansive interpretation of "Tissue Engineering" is proposed which is in congruence with classical and recent published definitions. I further simplify the definition of tissue engineering as: "Exerting systematic control of the body's cells, matrices and fluids." As a consequence, many medical therapies not commonly considered tissue engineering are placed in this category because of their effect on the body's responses. While the progress of tissue engineering strategies is inexorable and generally positive, it has been subject to setbacks as have many important medical therapies. Medical practice is currently undergoing a transition on several fronts (academics, start-up companies, going concerns) from the era of "replacement medicine" where body parts and functions are replaced by mechanical, electrical or chemical therapies to the era of tissue engineering where health is restored by regeneration generation or limitation of the body's tissues and functions by exploiting our expanding knowledge of the body's biological processes to produce natural, healthy outcomes.

Fixing Flawed Body Parts: Engineering New Tissues and Organs

MedlinePlus

... 2015 Print this issue Fixing Flawed Body Parts Engineering New Tissues and Organs En español Send us ... ones. This type of research is called tissue engineering. Exciting advances continue to emerge in this fast- ...

Improved repair of bone defects with prevascularized tissue-engineered bones constructed in a perfusion bioreactor.

PubMed

Li, De-Qiang; Li, Ming; Liu, Pei-Lai; Zhang, Yuan-Kai; Lu, Jian-Xi; Li, Jian-Min

2014-10-01

Vascularization of tissue-engineered bones is critical to achieving satisfactory repair of bone defects. The authors investigated the use of prevascularized tissue-engineered bone for repairing bone defects. The new bone was greater in the prevascularized group than in the non-vascularized group, indicating that prevascularized tissue-engineered bone improves the repair of bone defects. [Orthopedics. 2014; 37(10):685-690.]. Copyright 2014, SLACK Incorporated.

Challenges in translating vascular tissue engineering to the pediatric clinic.

PubMed

Duncan, Daniel R; Breuer, Christopher K

2011-10-14

The development of tissue-engineered vascular grafts for use in cardiovascular surgery holds great promise for improving outcomes in pediatric patients with complex congenital cardiac anomalies. Currently used synthetic grafts have a number of shortcomings in this setting but a tissue engineering approach has emerged in the past decade as a way to address these limitations. The first clinical trial of this technology showed that it is safe and effective but the primary mode of graft failure is stenosis. A variety of murine and large animal models have been developed to study and improve tissue engineering approaches with the hope of translating this technology into routine clinical use, but challenges remain. The purpose of this report is to address the clinical problem and review recent advances in vascular tissue engineering for pediatric applications. A deeper understanding of the mechanisms of neovessel formation and stenosis will enable rational design of improved tissue-engineered vascular grafts.

Biological aspects of tissue-engineered cartilage.

PubMed

Hoshi, Kazuto; Fujihara, Yuko; Yamawaki, Takanori; Harai, Motohiro; Asawa, Yukiyo; Hikita, Atsuhiko

2018-04-01

Cartilage regenerative medicine has been progressed well, and it reaches the stage of clinical application. Among various techniques, tissue engineering, which incorporates elements of materials science, is investigated earnestly, driven by high clinical needs. The cartilage tissue engineering using a poly lactide scaffold has been exploratorily used in the treatment of cleft lip-nose patients, disclosing good clinical results during 3-year observation. However, to increase the reliability of this treatment, not only accumulation of clinical evidence on safety and usefulness of the tissue-engineered products, but also establishment of scientific background on biological mechanisms, are regarded essential. In this paper, we reviewed recent trends of cartilage tissue engineering in clinical practice, summarized experimental findings on cellular and matrix changes during the cartilage regeneration, and discussed the importance of further studies on biological aspects of tissue-engineered cartilage, especially by the histological and the morphological methods.

Box 11: Tissue Engineering and Bioscience Methods Using Proton Beam Writing

NASA Astrophysics Data System (ADS)

van Kan, J. A.

Tissue engineering is a rapidly developing and highly interdisciplinary field that applies the principles of cell biology, engineering, and materials science to the culture of biological tissue. The artificially grown tissue then can be implanted directly into the body, or it can form part of a device that replaces organ functionality.

Instrumentation for Investigating the Regenerative Potential of Bone-Tissue-Engineered Scaffolds

DTIC Science & Technology

2015-05-12

With the continual aging of the population in the United States, bone fractures and diseases such as osteoporosis , osteomalacia and osteitis deformans...diseases such as osteoporosis , osteomalacia and osteitis deformans (Paget’s disease of bone) present a need for the development and perfection of

Natural Polymer-Cell Bioconstructs for Bone Tissue Engineering.

PubMed

Titorencu, Irina; Albu, Madalina Georgiana; Nemecz, Miruna; Jinga, Victor V

2017-01-01

The major goal of bone tissue engineering is to develop bioconstructs which substitute the functionality of damaged natural bone structures as much as possible if critical-sized defects occur. Scaffolds that mimic the structure and composition of bone tissue and cells play a pivotal role in bone tissue engineering applications. First, composition, properties and in vivo synthesis of bone tissue are presented for the understanding of bone formation. Second, potential sources of osteoprogenitor cells have been investigated for their capacity to induce bone repair and regeneration. Third, taking into account that the main property to qualify one scaffold as a future bioconstruct for bone tissue engineering is the biocompatibility, the assessments which prove it are reviewed in this paper. Forth, various types of natural polymer- based scaffolds consisting in proteins, polysaccharides, minerals, growth factors etc, are discussed, and interaction between scaffolds and cells which proved bone tissue engineering concept are highlighted. Finally, the future perspectives of natural polymer-based scaffolds for bone tissue engineering are considered. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Insoluble elastin reduces collagen scaffold stiffness, improves viscoelastic properties, and induces a contractile phenotype in smooth muscle cells.

PubMed

Ryan, Alan J; O'Brien, Fergal J

2015-12-01

Biomaterials with the capacity to innately guide cell behaviour while also displaying suitable mechanical properties remain a challenge in tissue engineering. Our approach to this has been to utilise insoluble elastin in combination with collagen as the basis of a biomimetic scaffold for cardiovascular tissue engineering. Elastin was found to markedly alter the mechanical and biological response of these collagen-based scaffolds. Specifically, during extensive mechanical assessment elastin was found to reduce the specific tensile and compressive moduli of the scaffolds in a concentration dependant manner while having minimal effect on scaffold microarchitecture with both scaffold porosity and pore size still within the ideal ranges for tissue engineering applications. However, the viscoelastic properties were significantly improved with elastin addition with a 3.5-fold decrease in induced creep strain, a 6-fold increase in cyclical strain recovery, and with a four-parameter viscoelastic model confirming the ability of elastin to confer resistance to long term deformation/creep. Furthermore, elastin was found to result in the modulation of SMC phenotype towards a contractile state which was determined via reduced proliferation and significantly enhanced expression of early (α-SMA), mid (calponin), and late stage (SM-MHC) contractile proteins. This allows the ability to utilise extracellular matrix proteins alone to modulate SMC phenotype without any exogenous factors added. Taken together, the ability of elastin to alter the mechanical and biological response of collagen scaffolds has led to the development of a biomimetic biomaterial highly suitable for cardiovascular tissue engineering. Copyright © 2015 Elsevier Ltd. All rights reserved.

Comparison of different cooling rates for fibroblast and keratinocyte cryopreservation.

PubMed

Naaldijk, Yahaira; Friedrich-Stöckigt, Annett; Sethe, Sebastian; Stolzing, Alexandra

2016-10-01

Easy, cost-effective and reliable cryopreservation protocols are crucial for the successful and effective application of tissue engineering. Several different protocols are in use, but no comprehensive comparisons across different machine-based and manual methods have been made. Here, we compare the effects of different cooling rates on the post-thaw survival and proliferative capacity of two basic cell lines for skin tissue engineering fibroblasts and keratinocytes, cultured and frozen in suspension or as a monolayer. We demonstrate that effectiveness of cryopreservation cannot be reliably determined immediately after thawing: the results at this stage were not indicative of cell growth in culture 3 days post-thaw. Cryopreservation of fibroblasts in an adherent state greatly diminishes their subsequent growth potential. This was not observed when freezing in suspension. In keratinocytes, however, adherent freezing is as effective as freezing in suspension, which could lead to significant cost and labour savings in a tissue-engineering environment. The 'optimal' cryopreservation protocol depends on cell type and intended use. Where time, ease and cost are dominant factors, the direct freezing into a nitrogen tank (straight freeze) approach remains a viable method. The most effective solution across the board, as measured by viability 3 days post-thaw, was the commonly used, freezing container method. Where machine-controlled cryopreservation is deemed important for tissue-engineering Good Manufacturing Practice, we present results using a portfolio of different cooling rates, identifying the 'optimal' protocol depending on cell type and culture method. Copyright © 2013 John Wiley & Sons, Ltd. Copyright © 2013 John Wiley & Sons, Ltd.

Commercial considerations in tissue engineering

PubMed Central

Mansbridge, Jonathan

2006-01-01

Tissue engineering is a field with immense promise. Using the example of an early tissue-engineered skin implant, Dermagraft, factors involved in the successful commercial development of devices of this type are explored. Tissue engineering has to strike a balance between tissue culture, which is a resource-intensive activity, and business considerations that are concerned with minimizing cost and maximizing customer convenience. Bioreactor design takes place in a highly regulated environment, so factors to be incorporated into the concept include not only tissue culture considerations but also matters related to asepsis, scaleup, automation and ease of use by the final customer. Dermagraft is an allogeneic tissue. Stasis preservation, in this case cryopreservation, is essential in allogeneic tissue engineering, allowing sterility testing, inventory control and, in the case of Dermagraft, a cellular stress that may be important for hormesis following implantation. Although the use of allogeneic cells provides advantages in manufacturing under suitable conditions, it raises the spectre of immunological rejection. Such rejection has not been experienced with Dermagraft. Possible reasons for this and the vision of further application of allogeneic tissues are important considerations in future tissue-engineered cellular devices. This review illustrates approaches that indicate some of the criteria that may provide a basis for further developments. Marketing is a further requirement for success, which entails understanding of the mechanism of action of the procedure, and is illustrated for Dermagraft. The success of a tissue-engineered product is dependent on many interacting operations, some discussed here, each of which must be performed simultaneously and well. PMID:17005024

Commercial considerations in tissue engineering.

PubMed

Mansbridge, Jonathan

2006-10-01

Tissue engineering is a field with immense promise. Using the example of an early tissue-engineered skin implant, Dermagraft, factors involved in the successful commercial development of devices of this type are explored. Tissue engineering has to strike a balance between tissue culture, which is a resource-intensive activity, and business considerations that are concerned with minimizing cost and maximizing customer convenience. Bioreactor design takes place in a highly regulated environment, so factors to be incorporated into the concept include not only tissue culture considerations but also matters related to asepsis, scaleup, automation and ease of use by the final customer. Dermagraft is an allogeneic tissue. Stasis preservation, in this case cryopreservation, is essential in allogeneic tissue engineering, allowing sterility testing, inventory control and, in the case of Dermagraft, a cellular stress that may be important for hormesis following implantation. Although the use of allogeneic cells provides advantages in manufacturing under suitable conditions, it raises the spectre of immunological rejection. Such rejection has not been experienced with Dermagraft. Possible reasons for this and the vision of further application of allogeneic tissues are important considerations in future tissue-engineered cellular devices. This review illustrates approaches that indicate some of the criteria that may provide a basis for further developments. Marketing is a further requirement for success, which entails understanding of the mechanism of action of the procedure, and is illustrated for Dermagraft. The success of a tissue-engineered product is dependent on many interacting operations, some discussed here, each of which must be performed simultaneously and well.

Cellular and multicellular form and function.

PubMed

Liu, Wendy F; Chen, Christopher S

2007-11-10

Engineering artificial tissue constructs requires the appropriate spatial arrangement of cells within scaffolds. The introduction of microengineering tools to the biological community has provided a valuable set of techniques to manipulate the cellular environment, and to examine how cell structure affects cellular function. Using micropatterning techniques, investigators have found that the geometric presentation of cell-matrix adhesions are important regulators of various cell behaviors including cell growth, proliferation, differentiation, polarity and migration. Furthermore, the presence of neighboring cells in multicellular aggregates has a significant impact on the proliferative and differentiated state of cells. Using microengineering tools, it will now be possible to manipulate the various environmental factors for practical applications such as engineering tissue constructs with greater control over the physical structure and spatial arrangement of cells within their surrounding microenvironment.

Non-photosynthetic plastids as hosts for metabolic engineering.

PubMed

Mellor, Silas Busck; Behrendorff, James B Y H; Nielsen, Agnieszka Zygadlo; Jensen, Poul Erik; Pribil, Mathias

2018-04-13

Using plants as hosts for production of complex, high-value compounds and therapeutic proteins has gained increasing momentum over the past decade. Recent advances in metabolic engineering techniques using synthetic biology have set the stage for production yields to become economically attractive, but more refined design strategies are required to increase product yields without compromising development and growth of the host system. The ability of plant cells to differentiate into various tissues in combination with a high level of cellular compartmentalization represents so far the most unexploited plant-specific resource. Plant cells contain organelles called plastids that retain their own genome, harbour unique biosynthetic pathways and differentiate into distinct plastid types upon environmental and developmental cues. Chloroplasts, the plastid type hosting the photosynthetic processes in green tissues, have proven to be suitable for high yield protein and bio-compound production. Unfortunately, chloroplast manipulation often affects photosynthetic efficiency and therefore plant fitness. In this respect, plastids of non-photosynthetic tissues, which have focused metabolisms for synthesis and storage of particular classes of compounds, might prove more suitable for engineering the production and storage of non-native metabolites without affecting plant fitness. This review provides the current state of knowledge on the molecular mechanisms involved in plastid differentiation and focuses on non-photosynthetic plastids as alternative biotechnological platforms for metabolic engineering. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Possible role of mechanical force in regulating regeneration of the vascularized fat flap inside a tissue engineering chamber.

PubMed

Ye, Yuan; Yuan, Yi; Lu, Feng; Gao, Jianhua

2015-12-01

In plastic and reconstructive surgery, adipose tissue is widely used as effective filler for tissue defects. Strategies for treating soft tissue deficiency, which include free adipose tissue grafts, use of hyaluronic acid, collagen injections, and implantation of synthetic materials, have several clinical limitations. With the aim of overcoming these limitations, researchers have recently utilized tissue engineering chambers to produce large volumes of engineered vascularized fat tissue. However, the process of growing fat tissue in a chamber is still relatively limited, and can result in unpredictable or dissatisfactory final tissue volumes. Therefore, detailed understanding of the process is both necessary and urgent. Many studies have shown that mechanical force can change the function of cells via mechanotransduction. Here, we hypothesized that, besides the inflammatory response, one of the key factors to control the regeneration of vascularized fat flap inside a tissue engineering chamber might be the balance of mechanical forces. To test our hypothesis, we intend to change the balance of forces by means of measures in order to make the equilibrium point in favor of the direction of regeneration. If those measures proved to be feasible, they could be applied in clinical practice to engineer vascularized adipose tissue of predictable size and shape, which would in turn help in the advancement of tissue engineering. Copyright © 2015 Elsevier Ltd. All rights reserved.

Vascularization strategies for tissue engineers.

PubMed

Dew, Lindsey; MacNeil, Sheila; Chong, Chuh Khiun

2015-01-01

All tissue-engineered substitutes (with the exception of cornea and cartilage) require a vascular network to provide the nutrient and oxygen supply needed for their survival in vivo. Unfortunately the process of vascular ingrowth into an engineered tissue can take weeks to occur naturally and during this time the tissues become starved of essential nutrients, leading to tissue death. This review initially gives a brief overview of the processes and factors involved in the formation of new vasculature. It then summarizes the different approaches that are being applied or developed to overcome the issue of slow neovascularization in a range of tissue-engineered substitutes. Some potential future strategies are then discussed.

Regenerative endodontics as a tissue engineering approach: past, current and future.

PubMed

Malhotra, Neeraj; Mala, Kundabala

2012-12-01

With the reported startling statistics of high incidence of tooth decay and tooth loss, the current interest is focused on the development of alternate dental tissue replacement therapies. This has led to the application of dental tissue engineering as a clinically relevant method for the regeneration of dental tissues and generation of bioengineered whole tooth. Although, tissue engineering approach requires the three main key elements of stem cells, scaffold and morphogens, a conductive environment (fourth element) is equally important for successful engineering of any tissue and/or organ. The applications of this science has evolved continuously in dentistry, beginning from the application of Ca(OH)(2) in vital pulp therapy to the development of a fully functional bioengineered tooth (mice). Thus, with advances in basic research, recent reports and studies have shown successful application of tissue engineering in the field of dentistry. However, certain practical obstacles are yet to be overcome before dental tissue regeneration can be applied as evidence-based approach in clinics. The article highlights on the past achievements, current developments and future prospects of tissue engineering and regenerative therapy in the field of endodontics and bioengineered teeth (bioteeth). © 2012 The Authors. Australian Endodontic Journal © 2012 Australian Society of Endodontology.

Effects of fabrication on the mechanics, microstructure and micromechanical environment of small intestinal submucosa scaffolds for vascular tissue engineering.

PubMed

Sánchez-Palencia, Diana M; D'Amore, Antonio; González-Mancera, Andrés; Wagner, William R; Briceño, Juan C

2014-08-22

In small intestinal submucosa scaffolds for functional tissue engineering, the impact of scaffold fabrication parameters on success rate may be related to the mechanotransductory properties of the final microstructural organization of collagen fibers. We hypothesized that two fabrication parameters, 1) preservation (P) or removal (R) of a dense collagen layer present in SIS and 2) SIS in a final dehydrated (D) or hydrated (H) state, have an effect on scaffold void area, microstructural anisotropy (fiber alignment) and mechanical anisotropy (global mechanical compliance). We further integrated our experimental measurements in a constitutive model to explore final effects on the micromechanical environment inside the scaffold volume. Our results indicated that PH scaffolds might exhibit recurrent and large force fluctuations between layers (up to 195 pN), while fluctuations in RH scaffolds might be larger (up to 256 pN) but not as recurrent. In contrast, both PD and RD groups were estimated to produce scarcer and smaller fluctuations (not larger than 50 pN). We concluded that the hydration parameter strongly affects the micromechanics of SIS and that an adequate choice of fabrication parameters, assisted by the herein developed method, might leverage the use of SIS for functional tissue engineering applications, where forces at the cellular level are of concern in the guidance of new tissue formation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Designing a 'neotissue' using the principles of biology, chemistry and engineering.

PubMed

Nannaparaju, Madhusudhan; Oragui, Emeka; Khan, Wasim S

2012-01-01

The traditional methods of treating musculoskeletal injuries and disorders are not completely effective and have several limitations. Tissue engineering involves using the principles of biology, chemistry and engineering to design a 'neotissue' that augments a malfunctioning in vivo tissue. The main requirements for functional engineered tissue include reparative cellular components that proliferate on a scaffold grown within a bioreactor that provides specific biochemical and physical signals to regulate cell differentiation and tissue assembly. In this review we provide an overview of the biology of common musculoskeletal tissue and discuss their common pathologies. We also describe the commonly used stem cells, scaffolds and bioreactors and evaluate their role in issue engineering.

Chitin Scaffolds in Tissue Engineering

PubMed Central

Jayakumar, Rangasamy; Chennazhi, Krishna Prasad; Srinivasan, Sowmya; Nair, Shantikumar V.; Furuike, Tetsuya; Tamura, Hiroshi

2011-01-01

Tissue engineering/regeneration is based on the hypothesis that healthy stem/progenitor cells either recruited or delivered to an injured site, can eventually regenerate lost or damaged tissue. Most of the researchers working in tissue engineering and regenerative technology attempt to create tissue replacements by culturing cells onto synthetic porous three-dimensional polymeric scaffolds, which is currently regarded as an ideal approach to enhance functional tissue regeneration by creating and maintaining channels that facilitate progenitor cell migration, proliferation and differentiation. The requirements that must be satisfied by such scaffolds include providing a space with the proper size, shape and porosity for tissue development and permitting cells from the surrounding tissue to migrate into the matrix. Recently, chitin scaffolds have been widely used in tissue engineering due to their non-toxic, biodegradable and biocompatible nature. The advantage of chitin as a tissue engineering biomaterial lies in that it can be easily processed into gel and scaffold forms for a variety of biomedical applications. Moreover, chitin has been shown to enhance some biological activities such as immunological, antibacterial, drug delivery and have been shown to promote better healing at a faster rate and exhibit greater compatibility with humans. This review provides an overview of the current status of tissue engineering/regenerative medicine research using chitin scaffolds for bone, cartilage and wound healing applications. We also outline the key challenges in this field and the most likely directions for future development and we hope that this review will be helpful to the researchers working in the field of tissue engineering and regenerative medicine. PMID:21673928

Fabrication of Novel Porous Chitosan Matrices as Scaffolds for Bone Tissue Engineering

DTIC Science & Technology

2005-01-01

Tissue Engineering Tao Jianga, Cyril M. Pilaneb, Cato T. Laurencina’b"c’ * a Department of Chemical Engineering , University of Virginia, Charlottesville...Chair of Orthopaedic Surgery Professor of Biomedical and Chemical Engineering 400 Ray C. Hunt Drive, Suite 330 University of Virginia Charlottesville...an alternative therapeutic approach for skeletal regeneration. Tissue engineering has been defined as the application of biological, chemical , and

Current progress in 3D printing for cardiovascular tissue engineering.

PubMed

Mosadegh, Bobak; Xiong, Guanglei; Dunham, Simon; Min, James K

2015-03-16

3D printing is a technology that allows the fabrication of structures with arbitrary geometries and heterogeneous material properties. The application of this technology to biological structures that match the complexity of native tissue is of great interest to researchers. This mini-review highlights the current progress of 3D printing for fabricating artificial tissues of the cardiovascular system, specifically the myocardium, heart valves, and coronary arteries. In addition, how 3D printed sensors and actuators can play a role in tissue engineering is discussed. To date, all the work with building 3D cardiac tissues have been proof-of-principle demonstrations, and in most cases, yielded products less effective than other traditional tissue engineering strategies. However, this technology is in its infancy and therefore there is much promise that through collaboration between biologists, engineers and material scientists, 3D bioprinting can make a significant impact on the field of cardiovascular tissue engineering.

Nanotechnology in the Regeneration of Complex Tissues

PubMed Central

Cassidy, John W.

2015-01-01

Modern medicine faces a growing crisis as demand for organ transplantations continues to far outstrip supply. By stimulating the body’s own repair mechanisms, regenerative medicine aims to reduce demand for organs, while the closely related field of tissue engineering promises to deliver “off-the-self” organs grown from patients’ own stem cells to improve supply. To deliver on these promises, we must have reliable means of generating complex tissues. Thus far, the majority of successful tissue engineering approaches have relied on macroporous scaffolds to provide cells with both mechanical support and differentiative cues. In order to engineer complex tissues, greater attention must be paid to nanoscale cues present in a cell’s microenvironment. As the extracellular matrix is capable of driving complexity during development, it must be understood and reproduced in order to recapitulate complexity in engineered tissues. This review will summarize current progress in engineering complex tissue through the integration of nanocomposites and biomimetic scaffolds. PMID:26097381

Engineering Lubrication in Articular Cartilage

PubMed Central

McNary, Sean M.; Athanasiou, Kyriacos A.

2012-01-01

Despite continuous progress toward tissue engineering of functional articular cartilage, significant challenges still remain. Advances in morphogens, stem cells, and scaffolds have resulted in enhancement of the bulk mechanical properties of engineered constructs, but little attention has been paid to the surface mechanical properties. In the near future, engineered tissues will be able to withstand and support the physiological compressive and tensile forces in weight-bearing synovial joints such as the knee. However, there is an increasing realization that these tissue-engineered cartilage constructs will fail without the optimal frictional and wear properties present in native articular cartilage. These characteristics are critical to smooth, pain-free joint articulation and a long-lasting, durable cartilage surface. To achieve optimal tribological properties, engineered cartilage therapies will need to incorporate approaches and methods for functional lubrication. Steady progress in cartilage lubrication in native tissues has pushed the pendulum and warranted a shift in the articular cartilage tissue-engineering paradigm. Engineered tissues should be designed and developed to possess both tribological and mechanical properties mirroring natural cartilage. In this article, an overview of the biology and engineering of articular cartilage structure and cartilage lubrication will be presented. Salient progress in lubrication treatments such as tribosupplementation, pharmacological, and cell-based therapies will be covered. Finally, frictional assays such as the pin-on-disk tribometer will be addressed. Knowledge related to the elements of cartilage lubrication has progressed and, thus, an opportune moment is provided to leverage these advances at a critical step in the development of mechanically and tribologically robust, biomimetic tissue-engineered cartilage. This article is intended to serve as the first stepping stone toward future studies in functional tissue engineering of articular cartilage that begins to explore and incorporate methods of lubrication. PMID:21955119

Modularity in developmental biology and artificial organs: a missing concept in tissue engineering.

PubMed

Lenas, Petros; Luyten, Frank P; Doblare, Manuel; Nicodemou-Lena, Eleni; Lanzara, Andreina Elena

2011-06-01

Tissue engineering is reviving itself, adopting the concept of biomimetics of in vivo tissue development. A basic concept of developmental biology is the modularity of the tissue architecture according to which intermediates in tissue development constitute semiautonomous entities. Both engineering and nature have chosen the modular architecture to optimize the product or organism development and evolution. Bioartificial tissues do not have a modular architecture. On the contrary, artificial organs of modular architecture have been already developed in the field of artificial organs. Therefore the conceptual support of tissue engineering by the field of artificial organs becomes critical in its new endeavor of recapitulating in vitro the in vivo tissue development. © 2011, Copyright the Authors. Artificial Organs © 2011, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Hyaluronan supplementation as a mechanical regulator of cartilage tissue development under joint-kinematic-mimicking loading.

PubMed

Wu, Yabin; Stoddart, Martin J; Wuertz-Kozak, Karin; Grad, Sibylle; Alini, Mauro; Ferguson, Stephen J

2017-08-01

Articular cartilage plays an essential role in joint lubrication and impact absorption. Through this, the mechanical signals are coupled to the tissue's physiological response. Healthy synovial fluid has been shown to reduce and homogenize the shear stress acting on the cartilage surfaces due to its unique shear-thinning viscosity. As cartilage tissues are sensitive to mechanical changes in articulation, it was hypothesized that replacing the traditional culture medium with a healthy non-Newtonian lubricant could enhance tissue development in a cartilage engineering model, where joint-kinematic-mimicking mechanical loading is applied. Different amounts of hyaluronic acid were added to the culture medium to replicate the viscosities of synovial fluid at different health states. Hyaluronic acid supplementation, especially at a physiologically healthy concentration (2.0 mg ml -1 ), promoted a better preservation of chondrocyte phenotype. The ratio of collagen II to collagen I mRNA was 4.5 times that of the control group, implying better tissue development (however, with no significant difference of measured collagen II content), with a good retention of collagen II and proteoglycan in the mechanically active region. Simulating synovial fluid properties by hyaluronic acid supplementation created a favourable mechanical environment for mechanically loaded constructs. These findings may help in understanding the influence of joint articulation on tissue homeostasis, and moreover, improve methods for functional cartilage tissue engineering. © 2017 The Author(s).

Microfluidic systems for stem cell-based neural tissue engineering.

PubMed

Karimi, Mahdi; Bahrami, Sajad; Mirshekari, Hamed; Basri, Seyed Masoud Moosavi; Nik, Amirala Bakhshian; Aref, Amir R; Akbari, Mohsen; Hamblin, Michael R

2016-07-05

Neural tissue engineering aims at developing novel approaches for the treatment of diseases of the nervous system, by providing a permissive environment for the growth and differentiation of neural cells. Three-dimensional (3D) cell culture systems provide a closer biomimetic environment, and promote better cell differentiation and improved cell function, than could be achieved by conventional two-dimensional (2D) culture systems. With the recent advances in the discovery and introduction of different types of stem cells for tissue engineering, microfluidic platforms have provided an improved microenvironment for the 3D-culture of stem cells. Microfluidic systems can provide more precise control over the spatiotemporal distribution of chemical and physical cues at the cellular level compared to traditional systems. Various microsystems have been designed and fabricated for the purpose of neural tissue engineering. Enhanced neural migration and differentiation, and monitoring of these processes, as well as understanding the behavior of stem cells and their microenvironment have been obtained through application of different microfluidic-based stem cell culture and tissue engineering techniques. As the technology advances it may be possible to construct a "brain-on-a-chip". In this review, we describe the basics of stem cells and tissue engineering as well as microfluidics-based tissue engineering approaches. We review recent testing of various microfluidic approaches for stem cell-based neural tissue engineering.

An injection molding process for manufacturing highly porous and interconnected biodegradable polymer matrices for use as tissue engineering scaffolds.

PubMed

Kramschuster, Adam; Turng, Lih-Sheng

2010-02-01

In this research, injection molding was combined with a novel material combination, supercritical fluid processing, and particulate leaching techniques to produce highly porous and interconnected structures that have the potential to act as scaffolds for tissue engineering applications. The foamed structures, molded with polylactide (PLA) and polyvinyl alcohol (PVOH) with salt as the particulate, were processed without the aid of organic solvents, which can be detrimental to tissue growth. The pore size in the scaffolds is controlled by salt particulates and interconnectivity is achieved by the co-continuous blending morphology of biodegradable PLA matrix with water-soluble PVOH. Carbon dioxide (CO(2)) at the supercritical state is used to serve as a plasticizer, thereby imparting moldability of blends even with an ultra high salt particulate content, and allows the use of low processing temperatures, which are desirable for temperature-sensitive biodegradable polymers. Interconnected pores of approximately 200 microm in diameter and porosities of approximately 75% are reported and discussed.

Nonintrusive 3D reconstruction of human bone models to simulate their bio-mechanical response

NASA Astrophysics Data System (ADS)

Alexander, Tsouknidas; Antonis, Lontos; Savvas, Savvakis; Nikolaos, Michailidis

2012-06-01

3D finite element models representing functional parts of the human skeletal system, have been repeatedly introduced over the last years, to simulate biomechanical response of anatomical characteristics or investigate surgical treatment. The reconstruction of geometrically accurate FEM models, poses a significant challenge for engineers and physicians, as recent advances in tissue engineering dictate highly customized implants, while facilitating the production of alloplast materials that are employed to restore, replace or supplement the function of human tissue. The premises of every accurate reconstruction method, is to encapture the precise geometrical characteristics of the examined tissue and thus the selection of a sufficient imaging technique is of the up-most importance. This paper reviews existing and potential applications related to the current state-of-the-art of medical imaging and simulation techniques. The procedures are examined by introducing their concepts; strengths and limitations, while the authors also present part of their recent activities in these areas. [Figure not available: see fulltext.

An overview of poly(lactic-co-glycolic) acid (PLGA)-based biomaterials for bone tissue engineering.

PubMed

Gentile, Piergiorgio; Chiono, Valeria; Carmagnola, Irene; Hatton, Paul V

2014-02-28

Poly(lactic-co-glycolic) acid (PLGA) has attracted considerable interest as a base material for biomedical applications due to its: (i) biocompatibility; (ii) tailored biodegradation rate (depending on the molecular weight and copolymer ratio); (iii) approval for clinical use in humans by the U.S. Food and Drug Administration (FDA); (iv) potential to modify surface properties to provide better interaction with biological materials; and (v) suitability for export to countries and cultures where implantation of animal-derived products is unpopular. This paper critically reviews the scientific challenge of manufacturing PLGA-based materials with suitable properties and shapes for specific biomedical applications, with special emphasis on bone tissue engineering. The analysis of the state of the art in the field reveals the presence of current innovative techniques for scaffolds and material manufacturing that are currently opening the way to prepare biomimetic PLGA substrates able to modulate cell interaction for improved substitution, restoration, or enhancement of bone tissue function.

Advanced Functional Nanomaterials for Biological Processes

DTIC Science & Technology

2014-01-01

of this project, we performed research in the area of tissue engineering/bone regeneration and cancer nanotechnology . The primary focus of the tissue...photoacoustic approach. 15. SUBJECT TERMS: Tissue Engineering, Cancer detection, Cancer destruction, Nanoparticles 16. SECURITY CLASSIFICATION OF: 17...Nanocomposite Materials with Drug Delivery Capabilities for Tissue Engineering and Bone Regeneration; and B. Multifunctional Nanoparticles for Cancer Early

Electrical stimulation: a novel tool for tissue engineering.

PubMed

Balint, Richard; Cassidy, Nigel J; Cartmell, Sarah H

2013-02-01

New advances in tissue engineering are being made through the application of different types of electrical stimuli to influence cell proliferation and differentiation. Developments made in the last decade have allowed us to improve the structure and functionality of tissue-engineered products through the use of growth factors, hormones, drugs, physical stimuli, bioreactor use, and two-dimensional (2-D) and three-dimensional (3-D) artificial extracellular matrices (with various material properties and topography). Another potential type of stimulus is electricity, which is important in the physiology and development of the majority of all human tissues. Despite its great potential, its role in tissue regeneration and its ability to influence cell migration, orientation, proliferation, and differentiation has rarely been considered in tissue engineering. This review highlights the importance of endogenous electrical stimulation, gathering the current knowledge on its natural occurrence and role in vivo, discussing the novel methods of delivering this stimulus and examining its cellular and tissue level effects, while evaluating how the technique could benefit the tissue engineering discipline in the future.

Crossing kingdoms: Using decellularized plants as perfusable tissue engineering scaffolds.

PubMed

Gershlak, Joshua R; Hernandez, Sarah; Fontana, Gianluca; Perreault, Luke R; Hansen, Katrina J; Larson, Sara A; Binder, Bernard Y K; Dolivo, David M; Yang, Tianhong; Dominko, Tanja; Rolle, Marsha W; Weathers, Pamela J; Medina-Bolivar, Fabricio; Cramer, Carole L; Murphy, William L; Gaudette, Glenn R

2017-05-01

Despite significant advances in the fabrication of bioengineered scaffolds for tissue engineering, delivery of nutrients in complex engineered human tissues remains a challenge. By taking advantage of the similarities in the vascular structure of plant and animal tissues, we developed decellularized plant tissue as a prevascularized scaffold for tissue engineering applications. Perfusion-based decellularization was modified for different plant species, providing different geometries of scaffolding. After decellularization, plant scaffolds remained patent and able to transport microparticles. Plant scaffolds were recellularized with human endothelial cells that colonized the inner surfaces of plant vasculature. Human mesenchymal stem cells and human pluripotent stem cell derived cardiomyocytes adhered to the outer surfaces of plant scaffolds. Cardiomyocytes demonstrated contractile function and calcium handling capabilities over the course of 21 days. These data demonstrate the potential of decellularized plants as scaffolds for tissue engineering, which could ultimately provide a cost-efficient, "green" technology for regenerating large volume vascularized tissue mass. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Adipose-Derived Stem Cell Delivery for Adipose Tissue Engineering: Current Status and Potential Applications in a Tissue Engineering Chamber Model.

PubMed

Zhan, Weiqing; Tan, Shaun S; Lu, Feng

2016-08-01

In reconstructive surgery, there is a clinical need for adequate implants to repair soft tissue defects caused by traumatic injury, tumor resection, or congenital abnormalities. Adipose tissue engineering may provide answers to this increasing demand. This study comprehensively reviews current approaches to adipose tissue engineering, detailing different cell carriers under investigation, with a special focus on the application of adipose-derived stem cells (ASCs). ASCs act as building blocks for new tissue growth and as modulators of the host response. Recent studies have also demonstrated that the implantation of a hollow protected chamber, combined with a vascular pedicle within the fat flaps provides blood supply and enables the growth of large-volume of engineered soft tissue. Conceptually, it would be of value to co-regulate this unique chamber model with adipose-derived stem cells to obtain a greater volume of soft tissue constructs for clinical use. Our review provides a cogent update on these advances and details the generation of possible fat substitutes.

Human adipose-derived stem cells: definition, isolation, tissue-engineering applications.

PubMed

Nae, S; Bordeianu, I; Stăncioiu, A T; Antohi, N

2013-01-01

Recent researches have demonstrated that the most effective repair system of the body is represented by stem cells - unspecialized cells, capable of self-renewal through successive mitoses, which have also the ability to transform into different cell types through differentiation. The discovery of adult stem cells represented an important step in regenerative medicine because they no longer raises ethical or legal issues and are more accessible. Only in 2002, stem cells isolated from adipose tissue were described as multipotent stem cells. Adipose tissue stem cells benefits in tissue engineering and regenerative medicine are numerous. Development of adipose tissue engineering techniques offers a great potential in surpassing the existing limits faced by the classical approaches used in plastic and reconstructive surgery. Adipose tissue engineering clinical applications are wide and varied, including reconstructive, corrective and cosmetic procedures. Nowadays, adipose tissue engineering is a fast developing field, both in terms of fundamental researches and medical applications, addressing issues related to current clinical pathology or trauma management of soft tissue injuries in different body locations.

Microfabrication of a platform to measure and manipulate the mechanics of engineered microtissues.

PubMed

Ramade, Alexandre; Legant, Wesley R; Picart, Catherine; Chen, Christopher S; Boudou, Thomas

2014-01-01

Engineered tissues can be used to understand fundamental features of biology, develop organotypic in vitro model systems, and as engineered tissue constructs for replacing damaged tissue in vivo. However, a key limitation is an inability to test the wide range of parameters that might impact the engineered tissue in a high-throughput manner and in an environment that mimics the three-dimensional (3D) native architecture. We developed a microfabricated platform to generate arrays of microtissues embedded within 3D micropatterned matrices. Microcantilevers simultaneously constrain microtissue formation and report forces generated by the microtissues in real time, opening the possibility to use high-throughput, low-volume screening for studies on engineered tissues. Thanks to the micrometer scale of the microtissues, this platform is also suitable for high-throughput monitoring of drug-induced effect on architecture and contractility in engineered tissues. Moreover, independent variations of the mechanical stiffness of the cantilevers and collagen matrix allow the measurement and manipulation of the mechanics of the microtissues. Thus, our approach will likely provide valuable opportunities to elucidate how biomechanical, electrical, biochemical, and genetic/epigenetic cues modulate the formation and maturation of 3D engineered tissues. In this chapter, we describe the microfabrication, preparation, and experimental use of such microfabricated tissue gauges. Copyright © 2014 Elsevier Inc. All rights reserved.

Mesoscopic Fluorescence Molecular Tomography for Evaluating Engineered Tissues.

PubMed

Ozturk, Mehmet S; Chen, Chao-Wei; Ji, Robin; Zhao, Lingling; Nguyen, Bao-Ngoc B; Fisher, John P; Chen, Yu; Intes, Xavier

2016-03-01

Optimization of regenerative medicine strategies includes the design of biomaterials, development of cell-seeding methods, and control of cell-biomaterial interactions within the engineered tissues. Among these steps, one paramount challenge is to non-destructively image the engineered tissues in their entirety to assess structure, function, and molecular expression. It is especially important to be able to enable cell phenotyping and monitor the distribution and migration of cells throughout the bulk scaffold. Advanced fluorescence microscopic techniques are commonly employed to perform such tasks; however, they are limited to superficial examination of tissue constructs. Therefore, the field of tissue engineering and regenerative medicine would greatly benefit from the development of molecular imaging techniques which are capable of non-destructive imaging of three-dimensional cellular distribution and maturation within a tissue-engineered scaffold beyond the limited depth of current microscopic techniques. In this review, we focus on an emerging depth-resolved optical mesoscopic imaging technique, termed laminar optical tomography (LOT) or mesoscopic fluorescence molecular tomography (MFMT), which enables longitudinal imaging of cellular distribution in thick tissue engineering constructs at depths of a few millimeters and with relatively high resolution. The physical principle, image formation, and instrumentation of LOT/MFMT systems are introduced. Representative applications in tissue engineering include imaging the distribution of human mesenchymal stem cells embedded in hydrogels, imaging of bio-printed tissues, and in vivo applications.

Temporal development of near-native functional properties and correlations with qMRI in self-assembling fibrocartilage treated with exogenous lysyl oxidase homolog 2.

PubMed

Hadidi, Pasha; Cissell, Derek D; Hu, Jerry C; Athanasiou, Kyriacos A

2017-12-01

Advances in cartilage tissue engineering have led to constructs with mechanical integrity and biochemical composition increasingly resembling that of native tissues. In particular, collagen cross-linking with lysyl oxidase has been used to significantly enhance the mechanical properties of engineered neotissues. In this study, development of collagen cross-links over time, and correlations with tensile properties, were examined in self-assembling neotissues. Additionally, quantitative MRI metrics were examined in relation to construct mechanical properties as well as pyridinoline cross-link content and other engineered tissue components. Scaffold-free meniscus fibrocartilage was cultured in the presence of exogenous lysyl oxidase, and assessed at multiple time points over 8weeks starting from the first week of culture. Engineered constructs demonstrated a 9.9-fold increase in pyridinoline content, reaching 77% of native tissue values, after 8weeks of culture. Additionally, engineered tissues reached 66% of the Young's modulus in the radial direction of native tissues. Further, collagen cross-links were found to correlate with tensile properties, contributing 67% of the tensile strength of engineered neocartilages. Finally, examination of quantitative MRI metrics revealed several correlations with mechanical and biochemical properties of engineered constructs. This study displays the importance of culture duration for collagen cross-link formation, and demonstrates the potential of quantitative MRI in investigating properties of engineered cartilages. This is the first study to demonstrate near-native cross-link content in an engineered tissue, and the first study to quantify pyridinoline cross-link development over time in a self-assembling tissue. Additionally, this work shows the relative contributions of collagen and pyridinoline to the tensile properties of collagenous tissue for the first time. Furthermore, this is the first investigation to identify a relationship between qMRI metrics and the pyridinoline cross-link content of an engineered collagenous tissue. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Nondestructive Techniques to Evaluate the Characteristics and Development of Engineered Cartilage

PubMed Central

Mansour, Joseph M.; Lee, Zhenghong; Welter, Jean F.

2016-01-01

In this review, methods for evaluating the properties of tissue engineered (TE) cartilage are described. Many of these have been developed for evaluating properties of native and osteoarthritic articular cartilage. However, with the increasing interest in engineering cartilage, specialized methods are needed for nondestructive evaluation of tissue while it is developing and after it is implanted. Such methods are needed, in part, due to the large inter- and intra-donor variability in the performance of the cellular component of the tissue, which remains a barrier to delivering reliable TE cartilage for implantation. Using conventional destructive tests, such variability makes it near-impossible to predict the timing and outcome of the tissue engineering process at the level of a specific piece of engineered tissue and also makes it difficult to assess the impact of changing tissue engineering regimens. While it is clear that the true test of engineered cartilage is its performance after it is implanted, correlation of pre and post implantation properties determined non-destructively in vitro and/or in vivo with performance should lead to predictive methods to improve quality-control and to minimize the chances of implanting inferior tissue. PMID:26817458

Tissue-engineered vascular grafts for use in the treatment of congenital heart disease: from the bench to the clinic and back again.

PubMed

Patterson, Joseph T; Gilliland, Thomas; Maxfield, Mark W; Church, Spencer; Naito, Yuji; Shinoka, Toshiharu; Breuer, Christopher K

2012-05-01

Since the first tissue-engineered vascular graft (TEVG) was implanted in a child over a decade ago, growth in the field of vascular tissue engineering has been driven by clinical demand for improved vascular prostheses with performance and durability similar to an autologous blood vessel. Great strides were made in pediatric congenital heart surgery using the classical tissue engineering paradigm, and cell seeding of scaffolds in vitro remained the cornerstone of neotissue formation. Our second-generation bone marrow cell-seeded TEVG diverged from tissue engineering dogma with a design that induces the recipient to regenerate vascular tissue in situ. New insights suggest that neovessel development is guided by cell signals derived from both seeded cells and host inflammatory cells that infiltrate the graft. The identification of these signals and the regulatory interactions that influence cell migration, phenotype and extracellular matrix deposition during TEVG remodeling are yielding a next-generation TEVG engineered to guide neotissue regeneration without the use of seeded cells. These developments represent steady progress towards our goal of an off-the-shelf tissue-engineered vascular conduit for pediatric congenital heart surgery.

[Tissue engineering applied to the trachea as a graft].

PubMed

Barrera-Ramírez, Elisa; Rico-Escobar, Edna; Garrido-Cardona, Rubén E

2016-01-01

Tissue engineering offers, through new technologies, an ex vivo generation of organs and functional tissues as grafts for transplants, for the improvement and substitution of biological functions, with an absence of immunological response. The treatment of extended tracheal lesions is a substitution of the affected segment; nevertheless, the allogeneic transplant has failed and the use of synthetic materials has not had good results. New tissue engineering technology is being developed to offer a tracheal graft for a posterior implantation. The purpose of this article is to review all the methods and components used by the engineering of tissue for tracheal grafts.

Trends in tissue engineering research.

PubMed

Hacker, Michael C; Mikos, Antonios G

2006-08-01

For more than a decade, Tissue Engineering has been devoted to the reporting and discussion of scientific advances in the interdisciplinary field of tissue engineering. In this study, 779 original articles published in the journal since its inception were analyzed and classified according to different attributes, such as focus of research and tissue of interest, to reveal trends in tissue engineering research. In addition, the use of different biomaterials, scaffold architectures, surface and bulk modification agents, cells, differentiation factors, gene delivery vectors, and animal models was examined. The results of this survey show interesting trends over time and by continental origin.

Tissue-engineered skin preserving the potential of epithelial cells to differentiate into hair after grafting.

PubMed

Larouche, Danielle; Cuffley, Kristine; Paquet, Claudie; Germain, Lucie

2011-03-01

The aim of this study was to evaluate whether tissue-engineered skin produced in vitro was able to sustain growth of hair follicles in vitro and after grafting. Different tissues were designed. Dissociated newborn mouse keratinocytes or newborn mouse hair buds (HBs) were added onto dermal constructs consisting of a tissue-engineered cell-derived matrix elaborated from either newborn mouse or adult human fibroblasts cultured with ascorbic acid. After 7-21 days of maturation at the air-liquid interface, no hair was noticed in vitro. Epidermal differentiation was observed in all tissue-engineered skin. However, human fibroblast-derived tissue-engineered dermis (hD) promoted a thicker epidermis than mouse fibroblast-derived tissue-engineered dermis (mD). In association with mD, HBs developed epithelial cyst-like inclusions presenting outer root sheath-like attributes. In contrast, epidermoid cyst-like inclusions lined by a stratified squamous epithelium were present in tissues composed of HBs and hD. After grafting, pilo-sebaceous units formed and hair grew in skin elaborated from HBs cultured 10-26 days submerged in culture medium in association with mD. However, the number of normal hair follicles decreased with longer culture time. This hair-forming capacity after grafting was not observed in tissues composed of hD overlaid with HBs. These results demonstrate that epithelial stem cells can be kept in vitro in a permissive tissue-engineered dermal environment without losing their potential to induce hair growth after grafting.

Laser-Etched Designs for Molding Hydrogel-Based Engineered Tissues

PubMed Central

Munarin, Fabiola; Kaiser, Nicholas J.; Kim, Tae Yun; Choi, Bum-Rak

2017-01-01

Rapid prototyping and fabrication of elastomeric molds for sterile culture of engineered tissues allow for the development of tissue geometries that can be tailored to different in vitro applications and customized as implantable scaffolds for regenerative medicine. Commercially available molds offer minimal capabilities for adaptation to unique conditions or applications versus those for which they are specifically designed. Here we describe a replica molding method for the design and fabrication of poly(dimethylsiloxane) (PDMS) molds from laser-etched acrylic negative masters with ∼0.2 mm resolution. Examples of the variety of mold shapes, sizes, and patterns obtained from laser-etched designs are provided. We use the patterned PDMS molds for producing and culturing engineered cardiac tissues with cardiomyocytes derived from human-induced pluripotent stem cells. We demonstrate that tight control over tissue morphology and anisotropy results in modulation of cell alignment and tissue-level conduction properties, including the appearance and elimination of reentrant arrhythmias, or circular electrical activation patterns. Techniques for handling engineered cardiac tissues during implantation in vivo in a rat model of myocardial infarction have been developed and are presented herein to facilitate development and adoption of surgical techniques for use with hydrogel-based engineered tissues. In summary, the method presented herein for engineered tissue mold generation is straightforward and low cost, enabling rapid design iteration and adaptation to a variety of applications in tissue engineering. Furthermore, the burden of equipment and expertise is low, allowing the technique to be accessible to all. PMID:28457187

Design and optimization of a tissue-engineered bone graft substitute

NASA Astrophysics Data System (ADS)

Shimko, Daniel Andrew

2004-12-01

In 2000, 3.1 million surgical procedures on the musculoskeletal system were reported in the United States. For many of these cases, bone grafting was essential for successful fracture stabilization. Current techniques use intact bone obtained either from the patient (autograft) or a cadaver (allograft) to repair large defects, however, neither source is optimal. Allografts suffer integration problems, and for autografts, the tissue supply is limited. Because of these shortcomings, and the high demand for graft tissues, alternatives are being explored. To successfully engineer a bone graft replacement, one must employ a three pronged research approach, addressing (1) the cells that will inhabit the new tissue, (2) the culture environment that these cells will be exposed to, and (3) the scaffold in which these cells will reside. The work herein examines each of these three aspects in great detail. Both adult and embryonic stem cells (ESCs) were considered for the tissue-engineered bone graft. Both exhibited desirable qualities, however, neither were optimal in all categories examined. In the end, the possibility of teratoma formation and ethical issues surrounding ESCs, made the use of adult marrow-derived stem cells in the remaining experiments obligatory. In subsequent experiments, the adult stem cells' ability to form bone was optimized. Basic fibroblast growth factor, fetal bovine serum, and extracellular calcium supplementation studies were all performed. Ultimately, adult stem cells cultured in alpha-MEM supplemented with 10% fetal bovine serum, 10mM beta-glycerophosphate, 10nM dexamethasone, 50mug/ml ascorbic acid, 1%(v/v) antibiotic/antimycotic, and 10.4mM CaCl2 performed the best, producing nearly four times more mineral than any other medium formulation. Several scaffolds were then investigated including those fabricated from poly(alpha-hydroxy esters), tantalum, and poly-methylmethacrylate. In the final study, the most appealing cell type, medium formulation, and scaffold material from all preceding studies were combined and a tissue-engineered bone graft was fabricated. The graft was exposed to long-term in vitro culture, and then mechanically evaluated to determine its clinical potential. The studies contained herein constitute the first steps in the conception and development of a viable tissue-engineered bone graft substitute and establish a solid scientific foundation for future in vivo experimentation utilizing this design.

Tissue-Engineering for the Study of Cardiac Biomechanics

PubMed Central

Ma, Stephen P.; Vunjak-Novakovic, Gordana

2016-01-01

The notion that both adaptive and maladaptive cardiac remodeling occurs in response to mechanical loading has informed recent progress in cardiac tissue engineering. Today, human cardiac tissues engineered in vitro offer complementary knowledge to that currently provided by animal models, with profound implications to personalized medicine. We review here recent advances in the understanding of the roles of mechanical signals in normal and pathological cardiac function, and their application in clinical translation of tissue engineering strategies to regenerative medicine and in vitro study of disease. PMID:26720588

Biomedical engineering for health research and development.

PubMed

Zhang, X-Y

2015-01-01

Biomedical engineering is a new area of research in medicine and biology, providing new concepts and designs for the diagnosis, treatment and prevention of various diseases. There are several types of biomedical engineering, such as tissue, genetic, neural and stem cells, as well as chemical and clinical engineering for health care. Many electronic and magnetic methods and equipments are used for the biomedical engineering such as Computed Tomography (CT) scans, Magnetic Resonance Imaging (MRI) scans, Electroencephalography (EEG), Ultrasound and regenerative medicine and stem cell cultures, preparations of artificial cells and organs, such as pancreas, urinary bladders, liver cells, and fibroblasts cells of foreskin and others. The principle of tissue engineering is described with various types of cells used for tissue engineering purposes. The use of several medical devices and bionics are mentioned with scaffold, cells and tissue cultures and various materials are used for biomedical engineering. The use of biomedical engineering methods is very important for the human health, and research and development of diseases. The bioreactors and preparations of artificial cells or tissues and organs are described here.

Cell Sheet-Based Tissue Engineering for Organizing Anisotropic Tissue Constructs Produced Using Microfabricated Thermoresponsive Substrates.

PubMed

Takahashi, Hironobu; Okano, Teruo

2015-11-18

In some native tissues, appropriate microstructures, including orientation of the cell/extracellular matrix, provide specific mechanical and biological functions. For example, skeletal muscle is made of oriented myofibers that is responsible for the mechanical function. Native artery and myocardial tissues are organized three-dimensionally by stacking sheet-like tissues of aligned cells. Therefore, to construct any kind of complex tissue, the microstructures of cells such as myotubes, smooth muscle cells, and cardiomyocytes also need to be organized three-dimensionally just as in the native tissues of the body. Cell sheet-based tissue engineering allows the production of scaffold-free engineered tissues through a layer-by-layer construction technique. Recently, using microfabricated thermoresponsive substrates, aligned cells are being harvested as single continuous cell sheets. The cell sheets act as anisotropic tissue units to build three-dimensional tissue constructs with the appropriate anisotropy. This cell sheet-based technology is straightforward and has the potential to engineer a wide variety of complex tissues. In addition, due to the scaffold-free cell-dense environment, the physical and biological cell-cell interactions of these cell sheet constructs exhibit unique cell behaviors. These advantages will provide important clues to enable the production of well-organized tissues that closely mimic the structure and function of native tissues, required for the future of tissue engineering. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Aloe Vera for Tissue Engineering Applications

PubMed Central

Rahman, Shekh; Carter, Princeton; Bhattarai, Narayan

2017-01-01

Aloe vera, also referred as Aloe barbadensis Miller, is a succulent plant widely used for biomedical, pharmaceutical and cosmetic applications. Aloe vera has been used for thousands of years. However, recent significant advances have been made in the development of aloe vera for tissue engineering applications. Aloe vera has received considerable attention in tissue engineering due to its biodegradability, biocompatibility, and low toxicity properties. Aloe vera has been reported to have many biologically active components. The bioactive components of aloe vera have effective antibacterial, anti-inflammatory, antioxidant, and immune-modulatory effects that promote both tissue regeneration and growth. The aloe vera plant, its bioactive components, extraction and processing, and tissue engineering prospects are reviewed in this article. The use of aloe vera as tissue engineering scaffolds, gels, and films is discussed, with a special focus on electrospun nanofibers. PMID:28216559

Aloe Vera for Tissue Engineering Applications.

PubMed

Rahman, Shekh; Carter, Princeton; Bhattarai, Narayan

2017-02-14

Aloe vera, also referred as Aloe barbadensis Miller, is a succulent plant widely used for biomedical, pharmaceutical and cosmetic applications. Aloe vera has been used for thousands of years. However, recent significant advances have been made in the development of aloe vera for tissue engineering applications. Aloe vera has received considerable attention in tissue engineering due to its biodegradability, biocompatibility, and low toxicity properties. Aloe vera has been reported to have many biologically active components. The bioactive components of aloe vera have effective antibacterial, anti-inflammatory, antioxidant, and immune-modulatory effects that promote both tissue regeneration and growth. The aloe vera plant, its bioactive components, extraction and processing, and tissue engineering prospects are reviewed in this article. The use of aloe vera as tissue engineering scaffolds, gels, and films is discussed, with a special focus on electrospun nanofibers.

The complementarity of the technical tools of tissue engineering and the concepts of artificial organs for the design of functional bioartificial tissues.

PubMed

Lenas, Petros; Moreno, Angel; Ikonomou, Laertis; Mayer, Joerg; Honda, Hiroyuki; Novellino, Antonio; Pizarro, Camilo; Nicodemou-Lena, Eleni; Rodergas, Silvia; Pintor, Jesus

2008-09-01

Although tissue engineering uses powerful biological tools, it still has a weak conceptual foundation, which is restricted at the cell level. The design criteria at the cell level are not directly related with the tissue functions, and consequently, such functions cannot be implemented in bioartificial tissues with the currently used methods. On the contrary, the field of artificial organs focuses on the function of the artificial organs that are treated in the design as integral entities, instead of the optimization of the artificial organ components. The field of artificial organs has already developed and tested methodologies that are based on system concepts and mathematical-computational methods that connect the component properties with the desired global organ function. Such methodologies are needed in tissue engineering for the design of bioartificial tissues with tissue functions. Under the framework of biomedical engineering, artificial organs and tissue engineering do not present competitive approaches, but are rather complementary and should therefore design a common future for the benefit of patients.

Challenges and opportunities for tissue-engineering polarized epithelium.

PubMed

Paz, Ana C; Soleas, John; Poon, James C H; Trieu, Dennis; Waddell, Thomas K; McGuigan, Alison P

2014-02-01

The epithelium is one of the most important tissue types in the body and the specific organization of the epithelial cells in these tissues is important for achieving appropriate function. Since many tissues contain an epithelial component, engineering functional epithelium and understanding the factors that control epithelial maturation and organization are important for generating whole artificial organ replacements. Furthermore, disruption of the cellular organization leads to tissue malfunction and disease; therefore, engineered epithelium could provide a valuable in vitro model to study disease phenotypes. Despite the importance of epithelial tissues, a surprisingly limited amount of effort has been focused on organizing epithelial cells into artificial polarized epithelium with an appropriate structure that resembles that seen in vivo. In this review, we provide an overview of epithelial tissue organization and highlight the importance of cell polarization to achieve appropriate epithelium function. We next describe the in vitro models that exist to create polarized epithelium and summarize attempts to engineer artificial epithelium for clinical use. Finally, we highlight the opportunities that exist to translate strategies from tissue engineering other tissues to generate polarized epithelium with a functional structure.

Endochondral Priming: A Developmental Engineering Strategy for Bone Tissue Regeneration.

PubMed

Freeman, Fiona E; McNamara, Laoise M

2017-04-01

Tissue engineering and regenerative medicine have significant potential to treat bone pathologies by exploiting the capacity for bone progenitors to grow and produce tissue constituents under specific biochemical and physical conditions. However, conventional tissue engineering approaches, which combine stem cells with biomaterial scaffolds, are limited as the constructs often degrade, due to a lack of vascularization, and lack the mechanical integrity to fulfill load bearing functions, and as such are not yet widely used for clinical treatment of large bone defects. Recent studies have proposed that in vitro tissue engineering approaches should strive to simulate in vivo bone developmental processes and, thereby, imitate natural factors governing cell differentiation and matrix production, following the paradigm recently defined as "developmental engineering." Although developmental engineering strategies have been recently developed that mimic specific aspects of the endochondral ossification bone formation process, these findings are not widely understood. Moreover, a critical comparison of these approaches to standard biomaterial-based bone tissue engineering has not yet been undertaken. For that reason, this article presents noteworthy experimental findings from researchers focusing on developing an endochondral-based developmental engineering strategy for bone tissue regeneration. These studies have established that in vitro approaches, which mimic certain aspects of the endochondral ossification process, namely the formation of the cartilage template and the vascularization of the cartilage template, can promote mineralization and vascularization to a certain extent both in vitro and in vivo. Finally, this article outlines specific experimental challenges that must be overcome to further exploit the biology of endochondral ossification and provide a tissue engineering construct for clinical treatment of large bone/nonunion defects and obviate the need for bone tissue graft.

In vitro fabrication of functional three-dimensional tissues with perfusable blood vessels

PubMed Central

Sekine, Hidekazu; Shimizu, Tatsuya; Sakaguchi, Katsuhisa; Dobashi, Izumi; Wada, Masanori; Yamato, Masayuki; Kobayashi, Eiji; Umezu, Mitsuo; Okano, Teruo

2013-01-01

In vitro fabrication of functional vascularized three-dimensional tissues has been a long-standing objective in the field of tissue engineering. Here we report a technique to engineer cardiac tissues with perfusable blood vessels in vitro. Using resected tissue with a connectable artery and vein as a vascular bed, we overlay triple-layer cardiac cell sheets produced from coculture with endothelial cells, and support the tissue construct with media perfused in a bioreactor. We show that endothelial cells connect to capillaries in the vascular bed and form tubular lumens, creating in vitro perfusable blood vessels in the cardiac cell sheets. Thicker engineered tissues can be produced in vitro by overlaying additional triple-layer cell sheets. The vascularized cardiac tissues beat and can be transplanted with blood vessel anastomoses. This technique may create new opportunities for in vitro tissue engineering and has potential therapeutic applications. PMID:23360990

Combined chemical and structural signals of biomaterials synergistically activate cell-cell communications for improving tissue regeneration.

PubMed

Xu, Yachen; Peng, Jinliang; Dong, Xin; Xu, Yuhong; Li, Haiyan; Chang, Jiang

2017-06-01

Biomaterials are only used as carriers of cells in the conventional tissue engineering. Considering the multi-cell environment and active cell-biomaterial interactions in tissue regeneration process, in this study, structural signals of aligned electrospun nanofibers and chemical signals of bioglass (BG) ionic products in cell culture medium are simultaneously applied to activate fibroblast-endothelial co-cultured cells in order to obtain an improved skin tissue engineering construct. Results demonstrate that the combined biomaterial signals synergistically activate fibroblast-endothelial co-culture skin tissue engineering constructs through promotion of paracrine effects and stimulation of gap junctional communication between cells, which results in enhanced vascularization and extracellular matrix protein synthesis in the constructs. Structural signals of aligned electrospun nanofibers play an important role in stimulating both of paracrine and gap junctional communication while chemical signals of BG ionic products mainly enhance paracrine effects. In vivo experiments reveal that the activated skin tissue engineering constructs significantly enhance wound healing as compared to control. This study indicates the advantages of synergistic effects between different bioactive signals of biomaterials can be taken to activate communication between different types of cells for obtaining tissue engineering constructs with improved functions. Tissue engineering can regenerate or replace tissue or organs through combining cells, biomaterials and growth factors. Normally, for repairing a specific tissue, only one type of cells, one kind of biomaterials, and specific growth factors are used to support cell growth. In this study, we proposed a novel tissue engineering approach by simply using co-cultured cells and combined biomaterial signals. Using a skin tissue engineering model, we successfully proved that the combined biomaterial signals such as surface nanostructures and bioactive ions could synergistically stimulate the cell-cell communication in co-culture system through paracrine effects and gap junction activation, and regulated expression of growth factors and extracellular matrix proteins, resulting in an activated tissue engineering constructs that significantly enhanced skin regeneration. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Cartilage tissue engineering: From biomaterials and stem cells to osteoarthritis treatments.

PubMed

Vinatier, C; Guicheux, J

2016-06-01

Articular cartilage is a non-vascularized and poorly cellularized connective tissue that is frequently damaged as a result of trauma and degenerative joint diseases such as osteoarthrtis. Because of the absence of vascularization, articular cartilage has low capacity for spontaneous repair. Today, and despite a large number of preclinical data, no therapy capable of restoring the healthy structure and function of damaged articular cartilage is clinically available. Tissue-engineering strategies involving the combination of cells, scaffolding biomaterials and bioactive agents have been of interest notably for the repair of damaged articular cartilage. During the last 30 years, cartilage tissue engineering has evolved from the treatment of focal lesions of articular cartilage to the development of strategies targeting the osteoarthritis process. In this review, we focus on the different aspects of tissue engineering applied to cartilage engineering. We first discuss cells, biomaterials and biological or environmental factors instrumental to the development of cartilage tissue engineering, then review the potential development of cartilage engineering strategies targeting new emerging pathogenic mechanisms of osteoarthritis. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Polymeric Nanofibers in Tissue Engineering

PubMed Central

Dahlin, Rebecca L.; Kasper, F. Kurtis

2011-01-01

Polymeric nanofibers can be produced using methods such as electrospinning, phase separation, and self-assembly, and the fiber composition, diameter, alignment, degradation, and mechanical properties can be tailored to the intended application. Nanofibers possess unique advantages for tissue engineering. The small diameter closely matches that of extracellular matrix fibers, and the relatively large surface area is beneficial for cell attachment and bioactive factor loading. This review will update the reader on the aspects of nanofiber fabrication and characterization important to tissue engineering, including control of porous structure, cell infiltration, and fiber degradation. Bioactive factor loading will be discussed with specific relevance to tissue engineering. Finally, applications of polymeric nanofibers in the fields of bone, cartilage, ligament and tendon, cardiovascular, and neural tissue engineering will be reviewed. PMID:21699434

DENTAL PULP TISSUE ENGINEERING

PubMed Central

Demarco, FF; Conde, MCM; Cavalcanti, B; Casagrande, L; Sakai, V; Nör, JE

2013-01-01

Dental pulp is a highly specialized mesenchymal tissue, which have a restrict regeneration capacity due to anatomical arrangement and post-mitotic nature of odontoblastic cells. Entire pulp amputation followed by pulp-space disinfection and filling with an artificial material cause loss of a significant amount of dentin leaving as life-lasting sequelae a non-vital and weakened tooth. However, regenerative endodontics is an emerging field of modern tissue engineering that demonstrated promising results using stem cells associated with scaffolds and responsive molecules. Thereby, this article will review the most recent endeavors to regenerate pulp tissue based on tissue engineering principles and providing insightful information to readers about the different aspects enrolled in tissue engineering. Here, we speculate that the search for the ideal combination of cells, scaffolds, and morphogenic factors for dental pulp tissue engineering may be extended over future years and result in significant advances in other areas of dental and craniofacial research. The finds collected in our review showed that we are now at a stage in which engineering a complex tissue, such as the dental pulp, is no longer an unachievable and the next decade will certainly be an exciting time for dental and craniofacial research. PMID:21519641

A review of rapid prototyping techniques for tissue engineering purposes.

PubMed

Peltola, Sanna M; Melchels, Ferry P W; Grijpma, Dirk W; Kellomäki, Minna

2008-01-01

Rapid prototyping (RP) is a common name for several techniques, which read in data from computer-aided design (CAD) drawings and manufacture automatically three-dimensional objects layer-by-layer according to the virtual design. The utilization of RP in tissue engineering enables the production of three-dimensional scaffolds with complex geometries and very fine structures. Adding micro- and nanometer details into the scaffolds improves the mechanical properties of the scaffold and ensures better cell adhesion to the scaffold surface. Thus, tissue engineering constructs can be customized according to the data acquired from the medical scans to match the each patient's individual needs. In addition RP enables the control of the scaffold porosity making it possible to fabricate applications with desired structural integrity. Unfortunately, every RP process has its own unique disadvantages in building tissue engineering scaffolds. Hence, the future research should be focused on the development of RP machines designed specifically for fabrication of tissue engineering scaffolds, although RP methods already can serve as a link between tissue and engineering.

Knee Ligament Injury and the Clinical Application of Tissue Engineering Techniques: A Systematic Review.

PubMed

Riley, Thomas C; Mafi, Reza; Mafi, Pouya; Khan, Wasim S

2018-02-23

The incidence of knee ligament injury is increasing and represents a significant cost to healthcare providers. Current interventions include tissue grafts, suture repair and non-surgical management. These techniques have demonstrated good patient outcomes but have been associated graft rejection, infection, long term immobilization and reduced joint function. The limitations of traditional management strategies have prompted research into tissue engineering of knee ligaments. This paper aims to evaluate whether tissue engineering of knee ligaments offers a viable alternative in the clinical management of knee ligament injuries. A search of existing literature was performed using OVID Medline, Embase, AMED, PubMed and Google Scholar, and a manual review of citations identified within these papers. Silk, polymer and extracellular matrix based scaffolds can all improve graft healing and collagen production. Fibroblasts and stem cells demonstrate compatibility with scaffolds, and have been shown to increase organized collagen production. These effects can be augmented using growth factors and extracellular matrix derivatives. Animal studies have shown tissue engineered ligaments can provide the biomechanical characteristics required for effective treatment of knee ligament injuries. There is a growing clinical demand for a tissue engineered alternative to traditional management strategies. Currently, there is limited consensus regarding material selection for use in tissue engineered ligaments. Further research is required to optimize tissue engineered ligament production before clinical application. Controlled clinical trials comparing the use of tissue engineered ligaments and traditional management in patients with knee ligament injury could determine whether they can provide a cost-effective alternative. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Tissue Engineering: Step Ahead in Maxillofacial Reconstruction.

PubMed

Rai, Raj; Raval, Rushik; Khandeparker, Rakshit Vijay Sinai; Chidrawar, Swati K; Khan, Abdul Ahad; Ganpat, Makne Sachin

2015-09-01

Within the precedent decade, a new field of "tissue engineering" or "tissue regeneration" emerge that offers an innovative and exhilarating substitute for maxillofacial reconstruction. It offers a new option to supplement existing treatment regimens for reconstruction/regeneration of the oral and craniofacial complex, which includes the teeth, periodontium, bones, soft tissues (oral mucosa, conjunctiva, skin), salivary glands, and the temporomandibular joint (bone and cartilage), as well as blood vessels, muscles, tendons, and nerves. Tissue engineering is based on harvesting the stem cells which are having potential to form an organ. Harvested cells are then transferred into scaffolds that are manufactured in a laboratory to resemble the structure of the desired tissue to be replaced. This article reviews the principles of tissue engineering and its various applications in oral and maxillofacial surgery.

[The method of accelerating osteanagenesis and revascularization of tissue engineered bone in big animal in vivo].

PubMed

Chen, Bin; Pei, Guo-xian; Wang, Ke; Jin, Dan; Wei, Kuan-hai; Ren, Gao-hong

2003-02-01

To study whether tissue engineered bone can repair the large segment bone defect of large animal or not. To observe what character the fascia flap played during the osteanagenesis and revascularization process of tissue engineered bone. 9 Chinese goats were made 2 cm left tibia diaphyseal defect. The repairing effect of the defects was evaluated by ECT, X-ray and histology. 27 goats were divided into three groups: group of CHAP, the defect was filled with coral hydroxyapatite (CHAP); group of tissue engineered bone, the defect was filled with CHAP + bone marrow stroma cells (BMSc); group of fascia flap, the defect was filled with CHAP + BMSc + fascia flap. After finished culturing and inducing the BMSc, CHAP of group of tissue engineered bone and of fascia flap was combined with it. Making fascia flap, different materials as described above were then implanted separately into the defects. Radionuclide bone imaging was used to monitor the revascularization of the implants at 2, 4, 8 weeks after operation. X-ray examination, optical density index of X-ray film, V-G staining of tissue slice of the implants were used at 4, 8, 12 weeks after operation, and the biomechanical character of the specimens were tested at 12 weeks post operation. In the first study, the defect showed no bone regeneration phenomenon. 2 cm tibia defect was an ideal animal model. In the second study, group of CHAP manifested a little trace of bone regeneration, as to group of tissue engineered bone, the defect was almost repaired totally. In group of fascia flap, with the assistance of fascia flap which gave more chance to making implants to get more nutrient, the repair was quite complete. The model of 2 cm caprine tibia diaphyseal defect cannot be repaired by goat itself and can satisfy the tissue engineering's demands. Tissue engineered bone had good ability to repair large segment tibia defect of goat. Fascia flap can accelerate the revascularization process of tissue engineered bone. And by this way, it augment the ability of tissue engineered bone to repair the large bone defect of goat.

Penile enhancement using autologous tissue engineering with biodegradable scaffold: a clinical and histomorphometric study.

PubMed

Perovic, Sava V; Sansalone, Salvatore; Djinovic, Rados; Ferlosio, Amedeo; Vespasiani, Giuseppe; Orlandi, Augusto

2010-09-01

Autologous tissue engineering with biodegradable scaffolds is a new treatment option for real penile girth enhancement. The aim of this article is to evaluate tissue remodeling after penile girth enhancement using this technique. Between June 2005 and May 2007, a group of 12 patients underwent repeated penile widening using biodegradable scaffolds enriched with expanded autologous scrotal dartos cells. Clinical monitoring was parallel to histological investigation of tissue remodeling. During second surgical procedure, biopsies were obtained 10-14 months after first surgery (mean 12 months, N=6) and compared with those obtained after 22-24 months (mean 23 months, N=6), and control biopsies from patients who underwent circumcision (N=5). Blind evaluation of histomorphometrical and immunohistochemical finding was performed in paraffin sections. Penile girth gain in a flaccid state ranged between 1.5 and 3.8 cm (mean 2.1 ± 0.28 cm) and in full erection between 1.2 and 4 cm (mean 1.9 ± 0.28 cm). Patients' satisfaction, defined by a questionnaire, was good (25%) and very good (75%). In biopsies obtained 10-14 months after first surgery, highly vascularized loose tissue with collagen deposition associated with small foci of mild chronic and granulomatous inflammation surrounding residual amorphous material was observed. Fibroblast-like hyperplasia and small vessel neoangiogenesis occurred intimately associated with the progressive growth of vascular-like structures from accumulation of CD34 and alpha-smooth muscle actin-positive cells surrounding residual scaffold-like amorphous material. Capillary neoangiogenesis occurred inside residual amorphous material. In biopsies obtained after 22-24 months, inflammation almost disappeared and tissue closely resembled that of the dartos fascia of control group. Autologous tissue engineering using expanded scrotal dartos cells with biodegradable scaffolds is a new and promising method for penile widening that generates progressive accumulation of stable collagen-rich, highly vascularized tissue matrix that closely resemble deep dartos fascia. © 2009 International Society for Sexual Medicine.

Nano scaffolds and stem cell therapy in liver tissue engineering

NASA Astrophysics Data System (ADS)

Montaser, Laila M.; Fawzy, Sherin M.

2015-08-01

Tissue engineering and regenerative medicine have been constantly developing of late due to the major progress in cell and organ transplantation, as well as advances in materials science and engineering. Although stem cells hold great potential for the treatment of many injuries and degenerative diseases, several obstacles must be overcome before their therapeutic application can be realized. These include the development of advanced techniques to understand and control functions of micro environmental signals and novel methods to track and guide transplanted stem cells. A major complication encountered with stem cell therapies has been the failure of injected cells to engraft to target tissues. The application of nanotechnology to stem cell biology would be able to address those challenges. Combinations of stem cell therapy and nanotechnology in tissue engineering and regenerative medicine have achieved significant advances. These combinations allow nanotechnology to engineer scaffolds with various features to control stem cell fate decisions. Fabrication of Nano fiber cell scaffolds onto which stem cells can adhere and spread, forming a niche-like microenvironment which can guide stem cells to proceed to heal damaged tissues. In this paper, current and emergent approach based on stem cells in the field of liver tissue engineering is presented for specific application. The combination of stem cells and tissue engineering opens new perspectives in tissue regeneration for stem cell therapy because of the potential to control stem cell behavior with the physical and chemical characteristics of the engineered scaffold environment.

Ethical Considerations in Tissue Engineering Research: Case Studies in Translation

PubMed Central

Baker, Hannah B.; McQuilling, John P.

2016-01-01

Tissue engineering research is a complex process that requires investigators to focus on the relationship between their research and anticipated gains in both knowledge and treatment improvements. The ethical considerations arising from tissue engineering research are similarly complex when addressing the translational progression from bench to bedside, and investigators in the field of tissue engineering act as moral agents at each step of their research along the translational pathway, from early benchwork and preclinical studies to clinical research. This review highlights the ethical considerations and challenges at each stage of research, by comparing issues surrounding two translational tissue engineering technologies: the bioartificial pancreas and a tissue engineered skeletal muscle construct. We present relevant ethical issues and questions to consider at each step along the translational pathway, from the basic science bench to preclinical research to first-in-human clinical trials. Topics at the bench level include maintaining data integrity, appropriate reporting and dissemination of results, and ensuring that studies are designed to yield results suitable for advancing research. Topics in preclinical research include the principle of “modest translational distance” and appropriate animal models. Topics in clinical research include key issues that arise in early-stage clinical trials, including selection of patient-subjects, disclosure of uncertainty, and defining success. The comparison of these two technologies and their ethical issues brings to light many challenges for translational tissue engineering research and provides guidance for investigators engaged in development of any tissue engineering technology. PMID:26282436

Ethical considerations in tissue engineering research: Case studies in translation.

PubMed

Baker, Hannah B; McQuilling, John P; King, Nancy M P

2016-04-15

Tissue engineering research is a complex process that requires investigators to focus on the relationship between their research and anticipated gains in both knowledge and treatment improvements. The ethical considerations arising from tissue engineering research are similarly complex when addressing the translational progression from bench to bedside, and investigators in the field of tissue engineering act as moral agents at each step of their research along the translational pathway, from early benchwork and preclinical studies to clinical research. This review highlights the ethical considerations and challenges at each stage of research, by comparing issues surrounding two translational tissue engineering technologies: the bioartificial pancreas and a tissue engineered skeletal muscle construct. We present relevant ethical issues and questions to consider at each step along the translational pathway, from the basic science bench to preclinical research to first-in-human clinical trials. Topics at the bench level include maintaining data integrity, appropriate reporting and dissemination of results, and ensuring that studies are designed to yield results suitable for advancing research. Topics in preclinical research include the principle of "modest translational distance" and appropriate animal models. Topics in clinical research include key issues that arise in early-stage clinical trials, including selection of patient-subjects, disclosure of uncertainty, and defining success. The comparison of these two technologies and their ethical issues brings to light many challenges for translational tissue engineering research and provides guidance for investigators engaged in development of any tissue engineering technology. Copyright © 2015 Elsevier Inc. All rights reserved.

Morphological changes in paraurethral area after introduction of tissue engineering construct on the basis of adipose tissue stromal cells.

PubMed

Makarov, A V; Arutyunyan, I V; Bol'shakova, G B; Volkov, A V; Gol'dshtein, D V

2009-10-01

We studied morphological changes in the paraurethral area of Wistar rats after introduction of tissue engineering constructs on the basis of multipotent mesenchymal stem cells and gelatin sponge. The tissue engineering construct containing autologous culture of the stromal fraction of the adipose tissue was most effective. After introduction of this construct we observed more rapid degradation of the construct matrix and more intensive formation of collagen fibers.

In vivo time-gated fluorescence imaging with biodegradable luminescent porous silicon nanoparticles.

PubMed

Gu, Luo; Hall, David J; Qin, Zhengtao; Anglin, Emily; Joo, Jinmyoung; Mooney, David J; Howell, Stephen B; Sailor, Michael J

2013-01-01

Fluorescence imaging is one of the most versatile and widely used visualization methods in biomedical research. However, tissue autofluorescence is a major obstacle confounding interpretation of in vivo fluorescence images. The unusually long emission lifetime (5-13 μs) of photoluminescent porous silicon nanoparticles can allow the time-gated imaging of tissues in vivo, completely eliminating shorter-lived (<10 ns) emission signals from organic chromophores or tissue autofluorescence. Here using a conventional animal imaging system not optimized for such long-lived excited states, we demonstrate improvement of signal to background contrast ratio by >50-fold in vitro and by >20-fold in vivo when imaging porous silicon nanoparticles. Time-gated imaging of porous silicon nanoparticles accumulated in a human ovarian cancer xenograft following intravenous injection is demonstrated in a live mouse. The potential for multiplexing of images in the time domain by using separate porous silicon nanoparticles engineered with different excited state lifetimes is discussed.

Cell sheet-based tissue engineering for fabricating 3-dimensional heart tissues.

PubMed

Shimizu, Tatsuya

2014-01-01

In addition to stem cell biology, tissue engineering is an essential research field for regenerative medicine. In contrast to cell injection, bioengineered tissue transplantation minimizes cell loss and has the potential to repair tissue defects. A popular approach is scaffold-based tissue engineering, which utilizes a biodegradable polymer scaffold for seeding cells; however, new techniques of cell sheet-based tissue engineering have been developed. Cell sheets are harvested from temperature-responsive culture dishes by simply lowering the temperature. Monolayer or stacked cell sheets are transplantable directly onto damaged tissues and cell sheet transplantation has already been clinically applied. Cardiac cell sheet stacking produces pulsatile heart tissue; however, lack of vasculature limits the viable tissue thickness to 3 layers. Multistep transplantation of triple-layer cardiac cell sheets cocultured with endothelial cells has been used to form thick vascularized cardiac tissue in vivo. Furthermore, in vitro functional blood vessel formation within 3-dimensional (3D) tissues has been realized by successfully imitating in vivo conditions. Triple-layer cardiac cell sheets containing endothelial cells were layered on vascular beds and the constructs were media-perfused using novel bioreactor systems. Interestingly, cocultured endothelial cells migrate into the vascular beds and form perfusable blood vessels. An in vitro multistep procedure has also enabled the fabrication of thick, vascularized heart tissues. Cell sheet-based tissue engineering has revealed great potential to fabricate 3D cardiac tissues and should contribute to future treatment of severe heart diseases and human tissue model production.

Biological augmentation and tissue engineering approaches in meniscus surgery.

PubMed

Moran, Cathal J; Busilacchi, Alberto; Lee, Cassandra A; Athanasiou, Kyriacos A; Verdonk, Peter C

2015-05-01

The purpose of this review was to evaluate the role of biological augmentation and tissue engineering strategies in meniscus surgery. Although clinical (human), preclinical (animal), and in vitro tissue engineering studies are included here, we have placed additional focus on addressing preclinical and clinical studies reported during the 5-year period used in this review in a systematic fashion while also providing a summary review of some important in vitro tissue engineering findings in the field over the past decade. A search was performed on PubMed for original works published from 2009 to March 31, 2014 using the term "meniscus" with all the following terms: "scaffolds," "constructs," "cells," "growth factors," "implant," "tissue engineering," and "regenerative medicine." Inclusion criteria were the following: English-language articles and original clinical, preclinical (in vivo), and in vitro studies of tissue engineering and regenerative medicine application in knee meniscus lesions published from 2009 to March 31, 2014. Three clinical studies and 18 preclinical studies were identified along with 68 tissue engineering in vitro studies. These reports show the increasing promise of biological augmentation and tissue engineering strategies in meniscus surgery. The role of stem cell and growth factor therapy appears to be particularly useful. A review of in vitro tissue engineering studies found a large number of scaffold types to be of promise for meniscus replacement. Limitations include a relatively low number of clinical or preclinical in vivo studies, in addition to the fact there is as yet no report in the literature of a tissue-engineered meniscus construct used clinically. Neither does the literature provide clarity on the optimal meniscus scaffold type or biological augmentation with which meniscus repair or replacement would be best addressed in the future. There is increasing focus on the role of mechanobiology and biomechanical and biochemical cues in this process, however, and it is hoped that this may lead to improvements in this strategy. There appears to be significant potential for biological augmentation and tissue engineering strategies in meniscus surgery to enhance options for repair and replacement. However, there are still relatively few clinical studies being reported in this regard. There is a strong need for improved translational activities and infrastructure to link the large amounts of in vitro and preclinical biological and tissue engineering data to clinical application. Level IV, systematic review of Level I-IV studies. Copyright © 2015 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Engineered Muscle Actuators: Cells and Tissues

DTIC Science & Technology

2007-01-10

tissue culture perfusion bioreactors The UNC group led the development of the final version of the integrated cell culture bioreactor . The system was...construct engineered in vitro from primary mammalian cells (C) The first demonstration of developmental improvements in engineered tendon constitutive...2007 Final Performance Report 1 Nov 2004 - 31 Oct 2006 4. TITLE AND SUBTITLE 5.. CONTRACT NUMBER Engineered Muscle Actuators: Cells and Tissues FA9550

A Novel Human Adipocyte-derived Basement Membrane for Tissue Engineering Applications

NASA Astrophysics Data System (ADS)

Damm, Aaron

Tissue engineering strategies have traditionally focused on the use of synthetic polymers as support scaffolds for cell growth. Recently, strategies have shifted towards a natural biologically derived scaffold, with the main focus on decellularized organs. Here, we report the development and engineering of a scaffold naturally secreted by human preadipocytes during differentiation. During this differentiation process, the preadipocytes remodel the extracellular matrix by releasing new extracellular proteins. Finally, we investigated the viability of the new basement membrane as a scaffold for tissue engineering using human pancreatic islets, and as a scaffold for soft tissue repair. After identifying the original scaffold material, we sought to improve the yield of material, treating the cell as a bioreactor, through various nutritional and cytokine stimuli. The results suggest that adipocytes can be used as bioreactors to produce a designer-specified engineered human extracellular matrix scaffold for specific tissue engineering applications.

Tissue engineering in endodontics.

PubMed

Saber, Shehab El-Din M

2009-12-01

Tissue engineering is the science of design and manufacture of new tissues to replace impaired or damaged ones. The key ingredients for tissue engineering are stem cells, the morphogens or growth factors that regulate their differentiation, and a scaffold of extracellular matrix that constitutes the microenvironment for their growth. Recently, there has been increasing interest in applying the concept of tissue engineering to endodontics. The aim of this study was to review the body of knowledge related to dental pulp stem cells, the most common growth factors, and the scaffolds used to control their differentiation, and a clinical technique for the management of immature non-vital teeth based on this novel concept.

Clinical translation of controlled protein delivery systems for tissue engineering.

PubMed

Spiller, Kara L; Vunjak-Novakovic, Gordana

2015-04-01

Strategies that utilize controlled release of drugs and proteins for tissue engineering have enormous potential to regenerate damaged organs and tissues. The multiple advantages of controlled release strategies merit overcoming the significant challenges to translation, including high costs and long, difficult regulatory pathways. This review highlights the potential of controlled release of proteins for tissue engineering and regenerative medicine. We specifically discuss treatment modalities that have reached preclinical and clinical trials, with emphasis on controlled release systems for bone tissue engineering, the most advanced application with several products already in clinic. Possible strategies to address translational and regulatory concerns are also discussed.

Clinical translation of controlled protein delivery systems for tissue engineering

PubMed Central

Spiller, Kara L.; Vunjak-Novakovic, Gordana

2013-01-01

Strategies that utilize controlled release of drugs and proteins for tissue engineering have enormous potential to regenerate damaged organs and tissues. The multiple advantages of controlled release strategies merit overcoming the significant challenges to translation, including high costs and long, difficult regulatory pathways. This review highlights the potential of controlled release of proteins for tissue engineering and regenerative medicine. We specifically discuss treatment modalities that have reached preclinical and clinical trials, with emphasis on controlled release systems for bone tissue engineering, the most advanced application with several products already in clinic. Possible strategies to address translational and regulatory concerns are also discussed. PMID:25787736

Design, Materials, and Mechanobiology of Biodegradable Scaffolds for Bone Tissue Engineering

PubMed Central

Velasco, Marco A.; Narváez-Tovar, Carlos A.; Garzón-Alvarado, Diego A.

2015-01-01

A review about design, manufacture, and mechanobiology of biodegradable scaffolds for bone tissue engineering is given. First, fundamental aspects about bone tissue engineering and considerations related to scaffold design are established. Second, issues related to scaffold biomaterials and manufacturing processes are discussed. Finally, mechanobiology of bone tissue and computational models developed for simulating how bone healing occurs inside a scaffold are described. PMID:25883972

Design Standards for Engineered Tissues

PubMed Central

Nawroth, Janna C.; Parker, Kevin Kit

2013-01-01

Traditional technologies are required to meet specific, quantitative standards of safety and performance. In tissue engineering, similar standards will have to be developed to enable routine clinical use and customized tissue fabrication. In this essay, we discuss a framework of concepts leading towards general design standards for tissue-engineering, focusing in particular on systematic design strategies, control of cell behavior, physiological scaling, fabrication modes and functional evaluation. PMID:23267860

Bioencapsulation technologies in tissue engineering

PubMed Central

Majewski, Rebecca L.; Zhang, Wujie; Ma, Xiaojun; Cui, Zhanfeng; Ren, Weiping; Markel, David C.

2017-01-01

Bioencapsulation technologies have played an important role in the developing successes of tissue engineering. Besides offering immunoisolation, they also show promise for cell/tissue banking and the directed differentiation of stem cells, by providing a unique microenvironment. This review describes bioencapsulation technologies and summarizes their recent progress in research into tissue engineering. The review concludes with a brief outlook regarding future research directions in this field. PMID:27716872

Stem cell applications and tissue engineering approaches in surgical practice.

PubMed

Khan, Wasim S; Malik, Atif A; Hardingham, Timothy E

2009-04-01

There has been an increasing interest in stem cell applications and tissue engineering approaches in surgical practice to deal with damaged or lost tissue. Although there have been developments in almost all surgical disciplines, the greatest advances are being made in orthopaedics, especially in bone repair. Significant hurdles however remain to be overcome before tissue engineering becomes more routinely used in surgical practice.

Tissue Engineering: Toward a New Era of Medicine.

PubMed

Shafiee, Ashkan; Atala, Anthony

2017-01-14

The goal of tissue engineering is to mitigate the critical shortage of donor organs via in vitro fabrication of functional biological structures. Tissue engineering is one of the most prominent examples of interdisciplinary fields, where scientists with different backgrounds work together to boost the quality of life by addressing critical health issues. Many different fields, such as developmental and molecular biology, as well as technologies, such as micro- and nanotechnologies and additive manufacturing, have been integral for advancing the field of tissue engineering. Over the past 20 years, spectacular advancements have been achieved to harness nature's ability to cure diseased tissues and organs. Patients have received laboratory-grown tissues and organs made out of their own cells, thus eliminating the risk of rejection. However, challenges remain when addressing more complex solid organs such as the heart, liver, and kidney. Herein, we review recent accomplishments as well as challenges that must be addressed in the field of tissue engineering and provide a perspective regarding strategies in further development.

Design control for clinical translation of 3D printed modular scaffolds.

PubMed

Hollister, Scott J; Flanagan, Colleen L; Zopf, David A; Morrison, Robert J; Nasser, Hassan; Patel, Janki J; Ebramzadeh, Edward; Sangiorgio, Sophia N; Wheeler, Matthew B; Green, Glenn E

2015-03-01

The primary thrust of tissue engineering is the clinical translation of scaffolds and/or biologics to reconstruct tissue defects. Despite this thrust, clinical translation of tissue engineering therapies from academic research has been minimal in the 27 year history of tissue engineering. Academic research by its nature focuses on, and rewards, initial discovery of new phenomena and technologies in the basic research model, with a view towards generality. Translation, however, by its nature must be directed at specific clinical targets, also denoted as indications, with associated regulatory requirements. These regulatory requirements, especially design control, require that the clinical indication be precisely defined a priori, unlike most academic basic tissue engineering research where the research target is typically open-ended, and furthermore requires that the tissue engineering therapy be constructed according to design inputs that ensure it treats or mitigates the clinical indication. Finally, regulatory approval dictates that the constructed system be verified, i.e., proven that it meets the design inputs, and validated, i.e., that by meeting the design inputs the therapy will address the clinical indication. Satisfying design control requires (1) a system of integrated technologies (scaffolds, materials, biologics), ideally based on a fundamental platform, as compared to focus on a single technology, (2) testing of design hypotheses to validate system performance as opposed to mechanistic hypotheses of natural phenomena, and (3) sequential testing using in vitro, in vivo, large preclinical and eventually clinical tests against competing therapies, as compared to single experiments to test new technologies or test mechanistic hypotheses. Our goal in this paper is to illustrate how design control may be implemented in academic translation of scaffold based tissue engineering therapies. Specifically, we propose to (1) demonstrate a modular platform approach founded on 3D printing for developing tissue engineering therapies and (2) illustrate the design control process for modular implementation of two scaffold based tissue engineering therapies: airway reconstruction and bone tissue engineering based spine fusion.

Design Control for Clinical Translation of 3D Printed Modular Scaffolds

PubMed Central

Hollister, Scott J.; Flanagan, Colleen L.; Zopf, David A.; Morrison, Robert J.; Nasser, Hassan; Patel, Janki J.; Ebramzadeh, Edward; Sangiorgio, Sophia N.; Wheeler, Matthew B.; Green, Glenn E.

2015-01-01

The primary thrust of tissue engineering is the clinical translation of scaffolds and/or biologics to reconstruct tissue defects. Despite this thrust, clinical translation of tissue engineering therapies from academic research has been minimal in the 27 year history of tissue engineering. Academic research by its nature focuses on, and rewards, initial discovery of new phenomena and technologies in the basic research model, with a view towards generality. Translation, however, by its nature must be directed at specific clinical targets, also denoted as indications, with associated regulatory requirements. These regulatory requirements, especially design control, require that the clinical indication be precisely defined a priori, unlike most academic basic tissue engineering research where the research target is typically open-ended, and furthermore requires that the tissue engineering therapy be constructed according to design inputs that ensure it treats or mitigates the clinical indication. Finally, regulatory approval dictates that the constructed system be verified, i.e., proven that it meets the design inputs, and validated, i.e., that by meeting the design inputs the therapy will address the clinical indication. Satisfying design control requires (1) a system of integrated technologies (scaffolds, materials, biologics), ideally based on a fundamental platform, as compared to focus on a single technology, (2) testing of design hypotheses to validate system performance as opposed to mechanistic hypotheses of natural phenomena, and (3) sequential testing using in vitro, in vivo, large preclinical and eventually clinical tests against competing therapies, as compared to single experiments to test new technologies or test mechanistic hypotheses. Our goal in this paper is to illustrate how design control may be implemented in academic translation of scaffold based tissue engineering therapies. Specifically, we propose to (1) demonstrate a modular platform approach founded on 3D printing for developing tissue engineering therapies and (2) illustrate the design control process for modular implementation of two scaffold based tissue engineering therapies: airway reconstruction and bone tissue engineering based spine fusion. PMID:25666115

Challenges in Cardiac Tissue Engineering

PubMed Central

Tandon, Nina; Godier, Amandine; Maidhof, Robert; Marsano, Anna; Martens, Timothy P.; Radisic, Milica

2010-01-01

Cardiac tissue engineering aims to create functional tissue constructs that can reestablish the structure and function of injured myocardium. Engineered constructs can also serve as high-fidelity models for studies of cardiac development and disease. In a general case, the biological potential of the cell—the actual “tissue engineer”—is mobilized by providing highly controllable three-dimensional environments that can mediate cell differentiation and functional assembly. For cardiac regeneration, some of the key requirements that need to be met are the selection of a human cell source, establishment of cardiac tissue matrix, electromechanical cell coupling, robust and stable contractile function, and functional vascularization. We review here the potential and challenges of cardiac tissue engineering for developing therapies that could prevent or reverse heart failure. PMID:19698068

Micro-/nano-engineered cellular responses for soft tissue engineering and biomedical applications.

PubMed

Tay, Chor Yong; Irvine, Scott Alexander; Boey, Freddy Y C; Tan, Lay Poh; Venkatraman, Subbu

2011-05-23

The development of biomedical devices and reconstruction of functional ex vivo tissues often requires the need to fabricate biomimetic surfaces with features of sub-micrometer precision. This can be achieved with the advancements in micro-/nano-engineering techniques, allowing researchers to manipulate a plethora of cellular behaviors at the cell-biomaterial interface. Systematic studies conducted on these 2D engineered surfaces have unraveled numerous novel findings that can potentially be integrated as part of the design consideration for future 2D and 3D biomaterials and will no doubt greatly benefit tissue engineering. In this review, recent developments detailing the use of micro-/nano-engineering techniques to direct cellular orientation and function pertinent to soft tissue engineering will be highlighted. Particularly, this article aims to provide valuable insights into distinctive cell interactions and reactions to controlled surfaces, which can be exploited to understand the mechanisms of cell growth on micro-/nano-engineered interfaces, and to harness this knowledge to optimize the performance of 3D artificial soft tissue grafts and biomedical applications. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Optimization of Electrical Stimulation Parameters for Cardiac Tissue Engineering

PubMed Central

Tandon, Nina; Marsano, Anna; Maidhof, Robert; Wan, Leo; Park, Hyoungshin; Vunjak-Novakovic, Gordana

2010-01-01

In vitro application of pulsatile electrical stimulation to neonatal rat cardiomyocytes cultured on polymer scaffolds has been shown to improve the functional assembly of cells into contractile cardiac tissue constrcuts. However, to date, the conditions of electrical stimulation have not been optimized. We have systematically varied the electrode material, amplitude and frequency of stimulation, to determine the conditions that are optimal for cardiac tissue engineering. Carbon electrodes, exhibiting the highest charge-injection capacity and producing cardiac tissues with the best structural and contractile properties, and were thus used in tissue engineering studies. Cardiac tissues stimulated at 3V/cm amplitude and 3Hz frequency had the highest tissue density, the highest concentrations of cardiac troponin-I and connexin-43, and the best developed contractile behavior. These findings contribute to defining bioreactor design specifications and electrical stimulation regime for cardiac tissue engineering. PMID:21604379

Combining regenerative medicine strategies to provide durable reconstructive options: auricular cartilage tissue engineering.

PubMed

Jessop, Zita M; Javed, Muhammad; Otto, Iris A; Combellack, Emman J; Morgan, Siân; Breugem, Corstiaan C; Archer, Charles W; Khan, Ilyas M; Lineaweaver, William C; Kon, Moshe; Malda, Jos; Whitaker, Iain S

2016-01-28

Recent advances in regenerative medicine place us in a unique position to improve the quality of engineered tissue. We use auricular cartilage as an exemplar to illustrate how the use of tissue-specific adult stem cells, assembly through additive manufacturing and improved understanding of postnatal tissue maturation will allow us to more accurately replicate native tissue anisotropy. This review highlights the limitations of autologous auricular reconstruction, including donor site morbidity, technical considerations and long-term complications. Current tissue-engineered auricular constructs implanted into immune-competent animal models have been observed to undergo inflammation, fibrosis, foreign body reaction, calcification and degradation. Combining biomimetic regenerative medicine strategies will allow us to improve tissue-engineered auricular cartilage with respect to biochemical composition and functionality, as well as microstructural organization and overall shape. Creating functional and durable tissue has the potential to shift the paradigm in reconstructive surgery by obviating the need for donor sites.

Advances in tissue engineering through stem cell-based co-culture.

PubMed

Paschos, Nikolaos K; Brown, Wendy E; Eswaramoorthy, Rajalakshmanan; Hu, Jerry C; Athanasiou, Kyriacos A

2015-05-01

Stem cells are the future in tissue engineering and regeneration. In a co-culture, stem cells not only provide a target cell source with multipotent differentiation capacity, but can also act as assisting cells that promote tissue homeostasis, metabolism, growth and repair. Their incorporation into co-culture systems seems to be important in the creation of complex tissues or organs. In this review, critical aspects of stem cell use in co-culture systems are discussed. Direct and indirect co-culture methodologies used in tissue engineering are described, along with various characteristics of cellular interactions in these systems. Direct cell-cell contact, cell-extracellular matrix interaction and signalling via soluble factors are presented. The advantages of stem cell co-culture strategies and their applications in tissue engineering and regenerative medicine are portrayed through specific examples for several tissues, including orthopaedic soft tissues, bone, heart, vasculature, lung, kidney, liver and nerve. A concise review of the progress and the lessons learned are provided, with a focus on recent developments and their implications. It is hoped that knowledge developed from one tissue can be translated to other tissues. Finally, we address challenges in tissue engineering and regenerative medicine that can potentially be overcome via employing strategies for stem cell co-culture use. Copyright © 2014 John Wiley & Sons, Ltd.

Biomaterials for tissue engineering: summary

NASA Technical Reports Server (NTRS)

Christenson, L.; Mikos, A. G.; Gibbons, D. F.; Picciolo, G. L.; McIntire, L. V. (Principal Investigator)

1997-01-01

This article summarizes presentations and discussion at the workshop "Enabling Biomaterial Technology for Tissue Engineering," which was held during the Fifth World Biomaterials Congress in May 1996. Presentations covered the areas of material substrate architecture, barrier effects, and cellular response, including analysis of biomaterials challenges involved in producing specific tissue-engineered products.

[Advances in research and application of beta-tricalcium phosphate, collagen and beta-tricalcium phosphate/collagen composite in bone tissue engineering].

PubMed

Han, Xiang-Yong; Fu, Yuan-Fei; Zhang, Fu-Qiang

2007-02-01

Bone defects in oral and maxillofacial region was a common problem. To repair the defect, bone grafts including autograft, allograft and artificial bone graft were used in clinic despite of their disadvantages. Nowadays, bone tissue engineering has become a commonly used method to repair bone defect. This paper reviewed the application of beta-TCP, collagen and beta-TCP/collagen composite in bone tissue engineering. It was concluded that beta-TCP/collagen composite was a promising materials in bone tissue engineering.

Engineering of M13 Bacteriophage for Development of Tissue Engineering Materials.

PubMed

Jin, Hyo-Eon; Lee, Seung-Wuk

2018-01-01

M13 bacteriophages have several qualities that make them attractive candidates as building blocks for tissue regenerating scaffold materials. Through genetic engineering, a high density of functional peptides and proteins can be simultaneously displayed on the M13 bacteriophage's outer coat proteins. The resulting phage can self-assemble into nanofibrous network structures and can guide the tissue morphogenesis through proliferation, differentiation and apoptosis. In this manuscript, we will describe methods to develop major coat-engineered M13 phages as a basic building block and aligned tissue-like matrices to develop regenerative nanomaterials.

Biologically active chitosan systems for tissue engineering and regenerative medicine.

PubMed

Jiang, Tao; Kumbar, Sangamesh G; Nair, Lakshmi S; Laurencin, Cato T

2008-01-01

Biodegradable polymeric scaffolds are widely used as a temporary extracellular matrix in tissue engineering and regenerative medicine. By physical adsorption of biomolecules on scaffold surface, physical entrapment of biomolecules in polymer microspheres or hydrogels, and chemical immobilization of oligopeptides or proteins on biomaterials, biologically active biomaterials and scaffolds can be derived. These bioactive systems show great potential in tissue engineering in rendering bioactivity and/or specificity to scaffolds. This review highlights some of the biologically active chitosan systems for tissue engineering application and the associated strategies to develop such bioactive chitosan systems.

Advances in polymeric systems for tissue engineering and biomedical applications.

PubMed

Ravichandran, Rajeswari; Sundarrajan, Subramanian; Venugopal, Jayarama Reddy; Mukherjee, Shayanti; Ramakrishna, Seeram

2012-03-01

The characteristics of tissue engineered scaffolds are major concerns in the quest to fabricate ideal scaffolds for tissue engineering applications. The polymer scaffolds employed for tissue engineering applications should possess multifunctional properties such as biocompatibility, biodegradability and favorable mechanical properties as it comes in direct contact with the body fluids in vivo. Additionally, the polymer system should also possess biomimetic architecture and should support stem cell adhesion, proliferation and differentiation. As the progress in polymer technology continues, polymeric biomaterials have taken characteristics more closely related to that desired for tissue engineering and clinical needs. Stimuli responsive polymers also termed as smart biomaterials respond to stimuli such as pH, temperature, enzyme, antigen, glucose and electrical stimuli that are inherently present in living systems. This review highlights the exciting advancements in these polymeric systems that relate to biological and tissue engineering applications. Additionally, several aspects of technology namely scaffold fabrication methods and surface modifications to confer biological functionality to the polymers have also been discussed. The ultimate objective is to emphasize on these underutilized adaptive behaviors of the polymers so that novel applications and new generations of smart polymeric materials can be realized for biomedical and tissue engineering applications. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Human urinary bladder regeneration through tissue engineering - an analysis of 131 clinical cases.

PubMed

Pokrywczynska, Marta; Adamowicz, Jan; Sharma, Arun K; Drewa, Tomasz

2014-03-01

Replacement of urinary bladder tissue with functional equivalents remains one of the most challenging problems of reconstructive urology over the last several decades. The gold standard treatment for urinary diversion after radical cystectomy is the ileal conduit or neobladder; however, this technique is associated with numerous complications including electrolyte imbalances, mucus production, and the potential for malignant transformation. Tissue engineering techniques provide the impetus to construct functional bladder substitutes de novo. Within this review, we have thoroughly perused the literature utilizing PubMed in order to identify clinical studies involving bladder reconstruction utilizing tissue engineering methodologies. The idea of urinary bladder regeneration through tissue engineering dates back to the 1950s. Many natural and synthetic biomaterials such as plastic mold, gelatin sponge, Japanese paper, preserved dog bladder, lyophilized human dura, bovine pericardium, small intestinal submucosa, bladder acellular matrix, or composite of collagen and polyglycolic acid were used for urinary bladder regeneration with a wide range of outcomes. Recent progress in the tissue engineering field suggest that in vitro engineered bladder wall substitutes may have expanded clinical applicability in near future but preclinical investigations on large animal models with defective bladders are necessary to optimize the methods of bladder reconstruction by tissue engineering in humans.

Development of Biodegradable Poly(citrate)-Polyhedral Oligomeric Silsesquioxanes Hybrid Elastomers with High Mechanical Properties and Osteogenic Differentiation Activity.

PubMed

Du, Yuzhang; Yu, Meng; Chen, Xiaofeng; Ma, Peter X; Lei, Bo

2016-02-10

Biodegradable elastomeric biomaterials have attracted much attention in tissue engineering due to their biomimetic viscoelastic behavior and biocompatibility. However, the low mechanical stability at hydrated state, fast biodegradation in vivo, and poor osteogenic activity greatly limited bioelastomers applications in bone tissue regeneration. Herein, we develop a series of poly(octanediol citrate)-polyhedral oligomeric silsesquioxanes (POC-POSS) hybrids with highly tunable elastomeric behavior (hydrated state) and biodegradation and osteoblasts biocompatibility through a facile one-pot thermal polymerization strategy. POC-POSS hybrids show significantly improved stiffness and ductility in either dry or hydrated conditions, as well as good antibiodegradation ability (20-50% weight loss in 3 months). POC-POSS hybrids exhibit significantly enhanced osteogenic differentiation through upregulating alkaline phosphatase (ALP) activity, calcium deposition, and expression of osteogenic markers (ALPL, BGLAP, and Runx2). The high mechanical stability at hydrated state and enhanced osteogenic activity make POC-POSS hybrid elastomers promising as scaffolds and nanoscale vehicles for bone tissue regeneration and drug delivery. This study may also provide a new strategy (controlling the stiffness under hydrated condition) to design advanced hybrid biomaterials with high mechanical properties under physiological condition for tissue regeneration applications.

Trends in Tissue Engineering for Blood Vessels

PubMed Central

Nemeno-Guanzon, Judee Grace; Lee, Soojung; Berg, Johan Robert; Jo, Yong Hwa; Yeo, Jee Eun; Nam, Bo Mi; Koh, Yong-Gon; Lee, Jeong Ik

2012-01-01

Over the years, cardiovascular diseases continue to increase and affect not only human health but also the economic stability worldwide. The advancement in tissue engineering is contributing a lot in dealing with this immediate need of alleviating human health. Blood vessel diseases are considered as major cardiovascular health problems. Although blood vessel transplantation is the most convenient treatment, it has been delimited due to scarcity of donors and the patient's conditions. However, tissue-engineered blood vessels are promising alternatives as mode of treatment for blood vessel defects. The purpose of this paper is to show the importance of the advancement on biofabrication technology for treatment of soft tissue defects particularly for vascular tissues. This will also provide an overview and update on the current status of tissue reconstruction especially from autologous stem cells, scaffolds, and scaffold-free cellular transplantable constructs. The discussion of this paper will be focused on the historical view of cardiovascular tissue engineering and stem cell biology. The representative studies featured in this paper are limited within the last decade in order to trace the trend and evolution of techniques for blood vessel tissue engineering. PMID:23251085

Tissue engineering of reproductive tissues and organs.

PubMed

Atala, Anthony

2012-07-01

Regenerative medicine and tissue engineering technology may soon offer new hope for patients with serious injuries and end-stage reproductive organ failure. Scientists are now applying the principles of cell transplantation, material science, and bioengineering to construct biological substitutes that can restore and maintain normal function in diseased and injured reproductive tissues. In addition, the stem cell field is advancing, and new discoveries in this field will lead to new therapeutic strategies. For example, newly discovered types of stem cells have been retrieved from uterine tissues such as amniotic fluid and placental stem cells. The process of therapeutic cloning and the creation of induced pluripotent cells provide still other potential sources of stem cells for cell-based tissue engineering applications. Although stem cells are still in the research phase, some therapies arising from tissue engineering endeavors that make use of autologous adult cells have already entered the clinic. This article discusses these tissue engineering strategies for various organs in the male and female reproductive tract. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Image-based metrology of porous tissue engineering scaffolds

NASA Astrophysics Data System (ADS)

Rajagopalan, Srinivasan; Robb, Richard A.

2006-03-01

Tissue engineering is an interdisciplinary effort aimed at the repair and regeneration of biological tissues through the application and control of cells, porous scaffolds and growth factors. The regeneration of specific tissues guided by tissue analogous substrates is dependent on diverse scaffold architectural indices that can be derived quantitatively from the microCT and microMR images of the scaffolds. However, the randomness of pore-solid distributions in conventional stochastic scaffolds presents unique computational challenges. As a result, image-based characterization of scaffolds has been predominantly qualitative. In this paper, we discuss quantitative image-based techniques that can be used to compute the metrological indices of porous tissue engineering scaffolds. While bulk averaged quantities such as porosity and surface are derived directly from the optimal pore-solid delineations, the spatially distributed geometric indices are derived from the medial axis representations of the pore network. The computational framework proposed (to the best of our knowledge for the first time in tissue engineering) in this paper might have profound implications towards unraveling the symbiotic structure-function relationship of porous tissue engineering scaffolds.

AAV vector encoding human VEGF165-transduced pectineus muscular flaps increase the formation of new tissue through induction of angiogenesis in an in vivo chamber for tissue engineering: A technique to enhance tissue and vessels in microsurgically engineered tissue.

PubMed

Moimas, Silvia; Manasseri, Benedetto; Cuccia, Giuseppe; Stagno d'Alcontres, Francesco; Geuna, Stefano; Pattarini, Lucia; Zentilin, Lorena; Giacca, Mauro; Colonna, Michele R

2015-01-01

In regenerative medicine, new approaches are required for the creation of tissue substitutes, and the interplay between different research areas, such as tissue engineering, microsurgery and gene therapy, is mandatory. In this article, we report a modification of a published model of tissue engineering, based on an arterio-venous loop enveloped in a cross-linked collagen-glycosaminoglycan template, which acts as an isolated chamber for angiogenesis and new tissue formation. In order to foster tissue formation within the chamber, which entails on the development of new vessels, we wondered whether we might combine tissue engineering with a gene therapy approach. Based on the well-described tropism of adeno-associated viral vectors for post-mitotic tissues, a muscular flap was harvested from the pectineus muscle, inserted into the chamber and transduced by either AAV vector encoding human VEGF165 or AAV vector expressing the reporter gene β-galactosidase, as a control. Histological analysis of the specimens showed that muscle transduction by AAV vector encoding human VEGF165 resulted in enhanced tissue formation, with a significant increase in the number of arterioles within the chamber in comparison with the previously published model. Pectineus muscular flap, transduced by adeno-associated viral vectors, acted as a source of the proangiogenic factor vascular endothelial growth factor, thus inducing a consistent enhancement of vessel growth into the newly formed tissue within the chamber. In conclusion, our present findings combine three different research fields such as microsurgery, tissue engineering and gene therapy, suggesting and showing the feasibility of a mixed approach for regenerative medicine.

Tissue engineering and regenerative medicine in applied research: a year in review of 2014.

PubMed

Lin, Xunxun; Huang, Jia; Shi, Yuan; Liu, Wei

2015-04-01

Tissue engineering and regenerative medicine (TERM) remains to be one of the fastest growing fields, which covers a wide scope of topics of both basic and applied biological researches. This overview article summarized the advancements in applied researches of TERM area, including stem cell-mediated tissue regeneration, material science, and TERM clinical trial. These achievements demonstrated the great potential of clinical regenerative therapy of tissue/organ disease or defect through stem cells and tissue engineering approaches.

Oligoaniline-based conductive biomaterials for tissue engineering.

PubMed

Zarrintaj, Payam; Bakhshandeh, Behnaz; Saeb, Mohammad Reza; Sefat, Farshid; Rezaeian, Iraj; Ganjali, Mohammad Reza; Ramakrishna, Seeram; Mozafari, Masoud

2018-05-01

The science and engineering of biomaterials have improved the human life expectancy. Tissue engineering is one of the nascent strategies with an aim to fulfill this target. Tissue engineering scaffolds are one of the most significant aspects of the recent tissue repair strategies; hence, it is imperative to design biomimetic substrates with suitable features. Conductive substrates can ameliorate the cellular activity through enhancement of cellular signaling. Biocompatible polymers with conductivity can mimic the cells' niche in an appropriate manner. Bioconductive polymers based on aniline oligomers can potentially actualize this purpose because of their unique and tailoring properties. The aniline oligomers can be positioned within the molecular structure of other polymers, thus painter acting with the side groups of the main polymer or acting as a comonomer in their backbone. The conductivity of oligoaniline-based conductive biomaterials can be tailored to mimic the electrical and mechanical properties of targeted tissues/organs. These bioconductive substrates can be designed with high mechanical strength for hard tissues such as the bone and with high elasticity to be used for the cardiac tissue or can be synthesized in the form of injectable hydrogels, particles, and nanofibers for noninvasive implantation; these structures can be used for applications such as drug/gene delivery and extracellular biomimetic structures. It is expected that with progress in the fields of biomaterials and tissue engineering, more innovative constructs will be proposed in the near future. This review discusses the recent advancements in the use of oligoaniline-based conductive biomaterials for tissue engineering and regenerative medicine applications. The tissue engineering applications of aniline oligomers and their derivatives have recently attracted an increasing interest due to their electroactive and biodegradable properties. However, no reports have systematically reviewed the critical role of oligoaniline-based conductive biomaterials in tissue engineering. Research on aniline oligomers is growing today opening new scenarios that expand the potential of these biomaterials from "traditional" treatments to a new era of tissue engineering. The conductivity of this class of biomaterials can be tailored similar to that of tissues/organs. To the best of our knowledge, this is the first review article in which such issue is systematically reviewed and critically discussed in the light of the existing literature. Undoubtedly, investigations on the use of oligoaniline-based conductive biomaterials in tissue engineering need further advancement and a lot of critical questions are yet to be answered. In this review, we introduce the salient features, the hurdles that must be overcome, the hopes, and practical constraints for further development. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Bridging the gap: from 2D cell culture to 3D microengineered extracellular matrices

PubMed Central

Li, Yanfen

2016-01-01

Historically the culture of mammalian cells in the laboratory has been performed on planar substrates with media cocktails that are optimized to maintain phenotype. However, it is becoming increasingly clear that much of biology discerned from 2D studies does not translate well to the 3D microenvironment. Over the last several decades, 2D and 3D microengineering approaches have been developed that better recapitulate the complex architecture and properties of in vivo tissue. Inspired by the infrastructure of the microelectronics industry, lithographic patterning approaches have taken center stage because of the ease in which cell-sized features can be engineered on surfaces and within a broad range of biocompatible materials. Patterning and templating techniques enable precise control over extracellular matrix properties including: composition, mechanics, geometry, cell-cell contact, and diffusion. In this review article we will explore how the field of engineered extracellular matrices has evolved with the development of new hydrogel chemistry and the maturation of micro- and nano- fabrication. Guided by the spatiotemporal regulation of cell state in developing tissues, we will review the maturation of micropatterning in 2D, pseudo-3D systems, and patterning within 3D hydrogels in the context of translating the information gained from 2D systems to synthetic engineered 3D tissues. PMID:26592366

Colloquium: Modeling the dynamics of multicellular systems: Application to tissue engineering

NASA Astrophysics Data System (ADS)

Kosztin, Ioan; Vunjak-Novakovic, Gordana; Forgacs, Gabor

2012-10-01

Tissue engineering is a rapidly evolving discipline that aims at building functional tissues to improve or replace damaged ones. To be successful in such an endeavor, ideally, the engineering of tissues should be based on the principles of developmental biology. Recent progress in developmental biology suggests that the formation of tissues from the composing cells is often guided by physical laws. Here a comprehensive computational-theoretical formalism is presented that is based on experimental input and incorporates biomechanical principles of developmental biology. The formalism is described and it is shown that it correctly reproduces and predicts the quantitative characteristics of the fundamental early developmental process of tissue fusion. Based on this finding, the formalism is then used toward the optimization of the fabrication of tubular multicellular constructs, such as a vascular graft, by bioprinting, a novel tissue engineering technology.

Application of Elastography for the Noninvasive Assessment of Biomechanics in Engineered Biomaterials and Tissues

PubMed Central

Kim, Woong; Ferguson, Virginia L.; Borden, Mark; Neu, Corey P.

2016-01-01

The elastic properties of engineered biomaterials and tissues impact their post-implantation repair potential and structural integrity, and are critical to help regulate cell fate and gene expression. The measurement of properties (e.g., stiffness or shear modulus) can be attained using elastography, which exploits noninvasive imaging modalities to provide functional information of a material indicative of the regeneration state. In this review, we outline the current leading elastography methodologies available to characterize the properties of biomaterials and tissues suitable for repair and mechanobiology research. We describe methods utilizing magnetic resonance, ultrasound, and optical coherent elastography, highlighting their potential for longitudinal monitoring of implanted materials in vivo, in addition to spatiotemporal limits of each method for probing changes in cell-laden constructs. Micro-elastography methods now allow acquisitions at length scales approaching 5–100 μm in two and three dimensions. Many of the methods introduced in this review are therefore capable of longitudinal monitoring in biomaterials and tissues approaching the cellular scale. However, critical factors such as anisotropy, heterogeneity and viscoelasity—inherent in many soft tissues—are often not fully described and therefore require further advancements and future developments. PMID:26790865

Future Prospects for Scaffolding Methods and Biomaterials in Skin Tissue Engineering: A Review

PubMed Central

Chaudhari, Atul A.; Vig, Komal; Baganizi, Dieudonné Radé; Sahu, Rajnish; Dixit, Saurabh; Dennis, Vida; Singh, Shree Ram; Pillai, Shreekumar R.

2016-01-01

Over centuries, the field of regenerative skin tissue engineering has had several advancements to facilitate faster wound healing and thereby restoration of skin. Skin tissue regeneration is mainly based on the use of suitable scaffold matrices. There are several scaffold types, such as porous, fibrous, microsphere, hydrogel, composite and acellular, etc., with discrete advantages and disadvantages. These scaffolds are either made up of highly biocompatible natural biomaterials, such as collagen, chitosan, etc., or synthetic materials, such as polycaprolactone (PCL), and poly-ethylene-glycol (PEG), etc. Composite scaffolds, which are a combination of natural or synthetic biomaterials, are highly biocompatible with improved tensile strength for effective skin tissue regeneration. Appropriate knowledge of the properties, advantages and disadvantages of various biomaterials and scaffolds will accelerate the production of suitable scaffolds for skin tissue regeneration applications. At the same time, emphasis on some of the leading challenges in the field of skin tissue engineering, such as cell interaction with scaffolds, faster cellular proliferation/differentiation, and vascularization of engineered tissues, is inevitable. In this review, we discuss various types of scaffolding approaches and biomaterials used in the field of skin tissue engineering and more importantly their future prospects in skin tissue regeneration efforts. PMID:27898014

Mechanical stretching for tissue engineering: two-dimensional and three-dimensional constructs.

PubMed

Riehl, Brandon D; Park, Jae-Hong; Kwon, Il Keun; Lim, Jung Yul

2012-08-01

Mechanical cell stretching may be an attractive strategy for the tissue engineering of mechanically functional tissues. It has been demonstrated that cell growth and differentiation can be guided by cell stretch with minimal help from soluble factors and engineered tissues that are mechanically stretched in bioreactors may have superior organization, functionality, and strength compared with unstretched counterparts. This review explores recent studies on cell stretching in both two-dimensional (2D) and three-dimensional (3D) setups focusing on the applications of stretch stimulation as a tool for controlling cell orientation, growth, gene expression, lineage commitment, and differentiation and for achieving successful tissue engineering of mechanically functional tissues, including cardiac, muscle, vasculature, ligament, tendon, bone, and so on. Custom stretching devices and lab-specific mechanical bioreactors are described with a discussion on capabilities and limitations. While stretch mechanotransduction pathways have been examined using 2D stretch, studying such pathways in physiologically relevant 3D environments may be required to understand how cells direct tissue development under stretch. Cell stretch study using 3D milieus may also help to develop tissue-specific stretch regimens optimized with biochemical feedback, which once developed will provide optimal tissue engineering protocols.

Mechanical Stretching for Tissue Engineering: Two-Dimensional and Three-Dimensional Constructs

PubMed Central

Riehl, Brandon D.; Park, Jae-Hong; Kwon, Il Keun

2012-01-01

Mechanical cell stretching may be an attractive strategy for the tissue engineering of mechanically functional tissues. It has been demonstrated that cell growth and differentiation can be guided by cell stretch with minimal help from soluble factors and engineered tissues that are mechanically stretched in bioreactors may have superior organization, functionality, and strength compared with unstretched counterparts. This review explores recent studies on cell stretching in both two-dimensional (2D) and three-dimensional (3D) setups focusing on the applications of stretch stimulation as a tool for controlling cell orientation, growth, gene expression, lineage commitment, and differentiation and for achieving successful tissue engineering of mechanically functional tissues, including cardiac, muscle, vasculature, ligament, tendon, bone, and so on. Custom stretching devices and lab-specific mechanical bioreactors are described with a discussion on capabilities and limitations. While stretch mechanotransduction pathways have been examined using 2D stretch, studying such pathways in physiologically relevant 3D environments may be required to understand how cells direct tissue development under stretch. Cell stretch study using 3D milieus may also help to develop tissue-specific stretch regimens optimized with biochemical feedback, which once developed will provide optimal tissue engineering protocols. PMID:22335794

Stem cell homing-based tissue engineering using bioactive materials

NASA Astrophysics Data System (ADS)

Yu, Yinxian; Sun, Binbin; Yi, Chengqing; Mo, Xiumei

2017-06-01

Tissue engineering focuses on repairing tissue and restoring tissue functions by employing three elements: scaffolds, cells and biochemical signals. In tissue engineering, bioactive material scaffolds have been used to cure tissue and organ defects with stem cell-based therapies being one of the best documented approaches. In the review, different biomaterials which are used in several methods to fabricate tissue engineering scaffolds were explained and show good properties (biocompatibility, biodegradability, and mechanical properties etc.) for cell migration and infiltration. Stem cell homing is a recruitment process for inducing the migration of the systemically transplanted cells, or host cells, to defect sites. The mechanisms and modes of stem cell homing-based tissue engineering can be divided into two types depending on the source of the stem cells: endogenous and exogenous. Exogenous stem cell-based bioactive scaffolds have the challenge of long-term culturing in vitro and for endogenous stem cells the biochemical signal homing recruitment mechanism is not clear yet. Although the stem cell homing-based bioactive scaffolds are attractive candidates for tissue defect therapies, based on in vitro studies and animal tests, there is still a long way before clinical application.

Future Prospects for Scaffolding Methods and Biomaterials in Skin Tissue Engineering: A Review.

PubMed

Chaudhari, Atul A; Vig, Komal; Baganizi, Dieudonné Radé; Sahu, Rajnish; Dixit, Saurabh; Dennis, Vida; Singh, Shree Ram; Pillai, Shreekumar R

2016-11-25

Over centuries, the field of regenerative skin tissue engineering has had several advancements to facilitate faster wound healing and thereby restoration of skin. Skin tissue regeneration is mainly based on the use of suitable scaffold matrices. There are several scaffold types, such as porous, fibrous, microsphere, hydrogel, composite and acellular, etc., with discrete advantages and disadvantages. These scaffolds are either made up of highly biocompatible natural biomaterials, such as collagen, chitosan, etc., or synthetic materials, such as polycaprolactone (PCL), and poly-ethylene-glycol (PEG), etc. Composite scaffolds, which are a combination of natural or synthetic biomaterials, are highly biocompatible with improved tensile strength for effective skin tissue regeneration. Appropriate knowledge of the properties, advantages and disadvantages of various biomaterials and scaffolds will accelerate the production of suitable scaffolds for skin tissue regeneration applications. At the same time, emphasis on some of the leading challenges in the field of skin tissue engineering, such as cell interaction with scaffolds, faster cellular proliferation/differentiation, and vascularization of engineered tissues, is inevitable. In this review, we discuss various types of scaffolding approaches and biomaterials used in the field of skin tissue engineering and more importantly their future prospects in skin tissue regeneration efforts.

Poly(glycerol sebacate) - A Novel Biodegradable Elastomer for Tissue Engineering

DTIC Science & Technology

2002-04-01

Langer’ ’Department of Chemical Engineering and 2Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA 02139, U.S.A...for Tissue Engineering DISTRIBUTION: Approved for public release, distribution unlimited This paper is part of the following report: TITLE: Materials...Materials Research Society NI 1.1 Poly(glycerol sebacate) - A Novel Biodegradable Elastomer for Tissue Engineering Yadong Wang,’ Barbara J. Sheppard,2 Robert

Tissue Engineering of Urinary Bladder and Urethra: Advances from Bench to Patients

PubMed Central

Bouhout, Sara; Chabaud, Stéphane; Bolduc, Stéphane

2013-01-01

Urinary tract is subjected to many varieties of pathologies since birth including congenital anomalies, trauma, inflammatory lesions, and malignancy. These diseases necessitate the replacement of involved organs and tissues. Shortage of organ donation, problems of immunosuppression, and complications associated with the use of nonnative tissues have urged clinicians and scientists to investigate new therapies, namely, tissue engineering. Tissue engineering follows principles of cell transplantation, materials science, and engineering. Epithelial and muscle cells can be harvested and used for reconstruction of the engineered grafts. These cells must be delivered in a well-organized and differentiated condition because water-seal epithelium and well-oriented muscle layer are needed for proper function of the substitute tissues. Synthetic or natural scaffolds have been used for engineering lower urinary tract. Harnessing autologous cells to produce their own matrix and form scaffolds is a new strategy for engineering bladder and urethra. This self-assembly technique avoids the biosafety and immunological reactions related to the use of biodegradable scaffolds. Autologous equivalents have already been produced for pigs (bladder) and human (urethra and bladder). The purpose of this paper is to present a review for the existing methods of engineering bladder and urethra and to point toward perspectives for their replacement. PMID:24453796

Multilayer scaffolds in orthopaedic tissue engineering.

PubMed

Atesok, Kivanc; Doral, M Nedim; Karlsson, Jon; Egol, Kenneth A; Jazrawi, Laith M; Coelho, Paulo G; Martinez, Amaury; Matsumoto, Tomoyuki; Owens, Brett D; Ochi, Mitsuo; Hurwitz, Shepard R; Atala, Anthony; Fu, Freddie H; Lu, Helen H; Rodeo, Scott A

2016-07-01

The purpose of this study was to summarize the recent developments in the field of tissue engineering as they relate to multilayer scaffold designs in musculoskeletal regeneration. Clinical and basic research studies that highlight the current knowledge and potential future applications of the multilayer scaffolds in orthopaedic tissue engineering were evaluated and the best evidence collected. Studies were divided into three main categories based on tissue types and interfaces for which multilayer scaffolds were used to regenerate: bone, osteochondral junction and tendon-to-bone interfaces. In vitro and in vivo studies indicate that the use of stratified scaffolds composed of multiple layers with distinct compositions for regeneration of distinct tissue types within the same scaffold and anatomic location is feasible. This emerging tissue engineering approach has potential applications in regeneration of bone defects, osteochondral lesions and tendon-to-bone interfaces with successful basic research findings that encourage clinical applications. Present data supporting the advantages of the use of multilayer scaffolds as an emerging strategy in musculoskeletal tissue engineering are promising, however, still limited. Positive impacts of the use of next generation scaffolds in orthopaedic tissue engineering can be expected in terms of decreasing the invasiveness of current grafting techniques used for reconstruction of bone and osteochondral defects, and tendon-to-bone interfaces in near future.

Decellularized material as scaffolds for tissue engineering studies in long gap esophageal atresia.

PubMed

Lee, Esmond; Milan, Anna; Urbani, Luca; De Coppi, Paolo; Lowdell, Mark W

2017-05-01

Esophageal atresia refers to an anomaly in foetal development in which the esophagus terminates in a blind end. Whilst surgical correction is achievable in most patients, when a long gap is present it still represents a major challenge associated with higher morbidity and mortality. In this context, tissue engineering could represent a successful alternative to restore oesophageal function and structure. Naturally derived biomaterials made of decellularized tissues retain native extracellular matrix architecture and composition, providing a suitable bed for the anchorage and growth of relevant cell types. Areas covered: This review outlines the various strategies and challenges in esophageal tissue engineering, highlighting the evolution of ideas in the development of decellularized scaffolds for clinical use. It explores the interplay between clinical needs, ethical dilemmas, and manufacturing challenges in the development of a tissue engineered decellularized scaffold for oesophageal atresia. Expert opinion: Current progress on oesophageal tissue engineering has enabled effective repair of patch defects, whilst the development of a full circumferential construct remains a challenge. Despite the different approaches available and the improvements achieved, a gold standard for fully functional tissue engineered oesophageal constructs has not been defined yet.

Creation of a Large Adipose Tissue Construct in Humans Using a Tissue-engineering Chamber: A Step Forward in the Clinical Application of Soft Tissue Engineering.

PubMed

Morrison, Wayne A; Marre, Diego; Grinsell, Damien; Batty, Andrew; Trost, Nicholas; O'Connor, Andrea J

2016-04-01

Tissue engineering is currently exploring new and exciting avenues for the repair of soft tissue and organ defects. Adipose tissue engineering using the tissue engineering chamber (TEC) model has yielded promising results in animals; however, to date, there have been no reports on the use of this device in humans. Five female post mastectomy patients ranging from 35 to 49years old were recruited and a pedicled thoracodorsal artery perforator fat flap ranging from 6 to 50ml was harvested, transposed onto the chest wall and covered by an acrylic perforated dome-shaped chamber ranging from 140 to 350cm(3). Magnetic resonance evaluation was performed at three and six months after chamber implantation. Chambers were removed at six months and samples were obtained for histological analysis. In one patient, newly formed tissue to a volume of 210ml was generated inside the chamber. One patient was unable to complete the trial and the other three failed to develop significant enlargement of the original fat flap, which, at the time of chamber explantation, was encased in a thick fibrous capsule. Our study provides evidence that generation of large well-vascularized tissue engineered constructs using the TEC is feasible in humans. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Next Generation Tissue Engineering of Orthopedic Soft Tissue-to-Bone Interfaces.

PubMed

Boys, Alexander J; McCorry, Mary Clare; Rodeo, Scott; Bonassar, Lawrence J; Estroff, Lara A

2017-09-01

Soft tissue-to-bone interfaces are complex structures that consist of gradients of extracellular matrix materials, cell phenotypes, and biochemical signals. These interfaces, called entheses for ligaments, tendons, and the meniscus, are crucial to joint function, transferring mechanical loads and stabilizing orthopedic joints. When injuries occur to connected soft tissue, the enthesis must be re-established to restore function, but due to structural complexity, repair has proven challenging. Tissue engineering offers a promising solution for regenerating these tissues. This prospective review discusses methodologies for tissue engineering the enthesis, outlined in three key design inputs: materials processing methods, cellular contributions, and biochemical factors.

Next Generation Tissue Engineering of Orthopedic Soft Tissue-to-Bone Interfaces

PubMed Central

Boys, Alexander J.; McCorry, Mary Clare; Rodeo, Scott; Bonassar, Lawrence J.; Estroff, Lara A.

2017-01-01

Soft tissue-to-bone interfaces are complex structures that consist of gradients of extracellular matrix materials, cell phenotypes, and biochemical signals. These interfaces, called entheses for ligaments, tendons, and the meniscus, are crucial to joint function, transferring mechanical loads and stabilizing orthopedic joints. When injuries occur to connected soft tissue, the enthesis must be re-established to restore function, but due to structural complexity, repair has proven challenging. Tissue engineering offers a promising solution for regenerating these tissues. This prospective review discusses methodologies for tissue engineering the enthesis, outlined in three key design inputs: materials processing methods, cellular contributions, and biochemical factors. PMID:29333332

Meniscus repair using mesenchymal stem cells - a comprehensive review.

PubMed

Yu, Hana; Adesida, Adetola B; Jomha, Nadr M

2015-04-30

The menisci are a pair of semilunar fibrocartilage structures that play an essential role in maintaining normal knee function. Injury to the menisci can disrupt joint stability and lead to debilitating results. Because natural meniscal healing is limited, an efficient method of repair is necessary. Tissue engineering (TE) combines the principles of life sciences and engineering to restore the unique architecture of the native meniscus. Mesenchymal stem cells (MSCs) have been investigated for their therapeutic potential both in vitro and in vivo. This comprehensive review examines the English literature identified through a database search using Medline, Embase, Engineering Village, and SPORTDiscus. The search results were classified based on MSC type, animal model, and method of MSC delivery/culture. A variety of MSC types, including bone marrow-derived, synovium-derived, adipose-derived, and meniscus-derived MSCs, has been examined. Research results were categorized into and discussed by the different animal models used; namely murine, leporine, porcine, caprine, bovine, ovine, canine, equine, and human models of meniscus defect/repair. Within each animal model, studies were categorized further according to MSC delivery/culture techniques. These techniques included direct application, fibrin glue/gel/clot, intra-articular injection, scaffold, tissue-engineered construct, meniscus tissue, pellets/aggregates, and hydrogel. The purpose of this review is to inform the reader about the current state and advances in meniscus TE using MSCs. Future directions of MSC-based meniscus TE are also suggested to help guide prospective research.

Murine tissue-engineered stomach demonstrates epithelial differentiation.

PubMed

Speer, Allison L; Sala, Frederic G; Matthews, Jamil A; Grikscheit, Tracy C

2011-11-01

Gastric cancer remains the second largest cause of cancer-related mortality worldwide. Postgastrectomy morbidity is considerable and quality of life is poor. Tissue-engineered stomach is a potential replacement solution to restore adequate food reservoir and gastric physiology. In this study, we performed a detailed investigation of the development of tissue-engineered stomach in a mouse model, specifically evaluating epithelial differentiation, proliferation, and the presence of putative stem cell markers. Organoid units were isolated from <3 wk-old mouse glandular stomach and seeded onto biodegradable scaffolds. The constructs were implanted into the omentum of adult mice. Implants were harvested at designated time points and analyzed with histology and immunohistochemistry. Tissue-engineered stomach grows as an expanding sphere with a simple columnar epithelium organized into gastric glands and an adjacent muscularis. The regenerated gastric epithelium demonstrates differentiation of all four cell types: mucous, enteroendocrine, chief, and parietal cells. Tissue-engineered stomach epithelium proliferates at a rate comparable to native glandular stomach and expresses two putative stem cell markers: DCAMKL-1 and Lgr5. This study demonstrates the successful generation of tissue-engineered stomach in a mouse model for the first time. Regenerated gastric epithelium is able to appropriately proliferate and differentiate. The generation of murine tissue-engineered stomach is a necessary advance as it provides the transgenic tools required to investigate the molecular and cellular mechanisms of this regenerative process. Delineating the mechanism of how tissue-engineered stomach develops in vivo is an important precursor to its use as a human stomach replacement therapy. Copyright © 2011 Elsevier Inc. All rights reserved.

Large Animal Models of an In Vivo Bioreactor for Engineering Vascularized Bone.

PubMed

Akar, Banu; Tatara, Alexander M; Sutradhar, Alok; Hsiao, Hui-Yi; Miller, Michael; Cheng, Ming-Huei; Mikos, Antonios G; Brey, Eric M

2018-04-12

Reconstruction of large skeletal defects is challenging due to the requirement for large volumes of donor tissue and the often complex surgical procedures. Tissue engineering has the potential to serve as a new source of tissue for bone reconstruction, but current techniques are often limited in regards to the size and complexity of tissue that can be formed. Building tissue using an in vivo bioreactor approach may enable the production of appropriate amounts of specialized tissue, while reducing issues of donor site morbidity and infection. Large animals are required to screen and optimize new strategies for growing clinically appropriate volumes of tissues in vivo. In this article, we review both ovine and porcine models that serve as models of the technique proposed for clinical engineering of bone tissue in vivo. Recent findings are discussed with these systems, as well as description of next steps required for using these models, to develop clinically applicable tissue engineering applications.

Integration of Stem Cell to Chondrocyte-Derived Cartilage Matrix in Healthy and Osteoarthritic States in the Presence of Hydroxyapatite Nanoparticles.

PubMed

Dua, Rupak; Comella, Kristin; Butler, Ryan; Castellanos, Glenda; Brazille, Bryn; Claude, Andrew; Agarwal, Arvind; Liao, Jun; Ramaswamy, Sharan

2016-01-01

We investigated the effectiveness of integrating tissue engineered cartilage derived from human bone marrow derived stem cells (HBMSCs) to healthy as well as osteoarthritic cartilage mimics using hydroxyapatite (HA) nanoparticles immersed within a hydrogel substrate. Healthy and diseased engineered cartilage from human chondrocytes (cultured in agar gels) were integrated with human bone marrow stem cell (HBMSC)-derived cartilaginous engineered matrix with and without HA, and evaluated after 28 days of growth. HBMSCs were seeded within photopolymerizable poly (ethylene glycol) diacrylate (PEGDA) hydrogels. In addition, we also conducted a preliminary in vivo evaluation of cartilage repair in rabbit knee chondral defects treated with subchondral bone microfracture and cell-free PEGDA with and without HA. Under in vitro conditions, the interfacial shear strength between tissue engineered cartilage derived from HBMSCs and osteoarthritic chondrocytes was significantly higher (p < 0.05) when HA nanoparticles were incorporated within the HBMSC culture system. Histological evidence confirmed a distinct spatial transition zone, rich in calcium phosphate deposits. Assessment of explanted rabbit knees by histology demonstrated that cellularity within the repair tissues that had filled the defects were of significantly higher number (p < 0.05) when HA was used. HA nanoparticles play an important role in treating chondral defects when osteoarthritis is a co-morbidity. We speculate that the calcified layer formation at the interface in the osteoarthritic environment in the presence of HA is likely to have attributed to higher interfacial strength found in vitro. From an in vivo standpoint, the presence of HA promoted cellularity in the tissues that subsequently filled the chondral defects. This higher presence of cells can be considered important in the context of accelerating long-term cartilage remodeling. We conclude that HA nanoparticles play an important role in engineered to native cartilage integration and cellular processes.

Low-intensity pulsed ultrasound in dentofacial tissue engineering.

PubMed

Tanaka, Eiji; Kuroda, Shingo; Horiuchi, Shinya; Tabata, Akira; El-Bialy, Tarek

2015-04-01

Oral and maxillofacial diseases affect millions of people worldwide and hence tissue engineering can be considered an interesting and clinically relevant approach to regenerate orofacial tissues after being affected by different diseases. Among several innovations for tissue regeneration, low-intensity pulsed ultrasound (LIPUS) has been used extensively in medicine as a therapeutic, operative, and diagnostic tool. LIPUS is accepted to promote bone fracture repair and regeneration. Furthermore, the effect of LIPUS on soft tissues regeneration has been paid much attention, and many studies have performed to evaluate the potential use of LIPUS to tissue engineering soft tissues. The present article provides an overview about the status of LIPUS stimulation as a tool to be used to enhance regeneration/tissue engineering. This review consists of five parts. Part 1 is a brief introduction of the acoustic description of LIPUS and mechanical action. In Part 2, biological problems in dentofacial tissue engineering are proposed. Part 3 explores biologic mechanisms of LIPUS to cells and tissues in living body. In Part 4, the effectiveness of LIPUS on cell metabolism and tissue regeneration in dentistry are summarized. Finally, Part 5 relates the possibility of clinical application of LIPUS in orthodontics. The present review brings out better understanding of the bioeffect of LIPUS therapy on orofacial tissues which is essential to the successful integration of management remedies for tissue regeneration/engineering. To develop an evidence-based approach to clinical management and treatment of orofacial degenerative diseases using LIPUS, we would like to be in full pursuit of LIPUS biotherapy. Still, there are many challenges for this relatively new strategy, but the up to date achievements using it promises to go far beyond the present possibilities.

Concise review: humanized models of tumor immunology in the 21st century: convergence of cancer research and tissue engineering.

PubMed

Holzapfel, Boris Michael; Wagner, Ferdinand; Thibaudeau, Laure; Levesque, Jean-Pierre; Hutmacher, Dietmar Werner

2015-06-01

Despite positive testing in animal studies, more than 80% of novel drug candidates fail to proof their efficacy when tested in humans. This is primarily due to the use of preclinical models that are not able to recapitulate the physiological or pathological processes in humans. Hence, one of the key challenges in the field of translational medicine is to "make the model organism mouse more human." To get answers to questions that would be prognostic of outcomes in human medicine, the mouse's genome can be altered in order to create a more permissive host that allows the engraftment of human cell systems. It has been shown in the past that these strategies can improve our understanding of tumor immunology. However, the translational benefits of these platforms have still to be proven. In the 21st century, several research groups and consortia around the world take up the challenge to improve our understanding of how to humanize the animal's genetic code, its cells and, based on tissue engineering principles, its extracellular microenvironment, its tissues, or entire organs with the ultimate goal to foster the translation of new therapeutic strategies from bench to bedside. This article provides an overview of the state of the art of humanized models of tumor immunology and highlights future developments in the field such as the application of tissue engineering and regenerative medicine strategies to further enhance humanized murine model systems. © 2015 AlphaMed Press.

Computational Modeling of Tissue Self-Assembly

NASA Astrophysics Data System (ADS)

Neagu, Adrian; Kosztin, Ioan; Jakab, Karoly; Barz, Bogdan; Neagu, Monica; Jamison, Richard; Forgacs, Gabor

As a theoretical framework for understanding the self-assembly of living cells into tissues, Steinberg proposed the differential adhesion hypothesis (DAH) according to which a specific cell type possesses a specific adhesion apparatus that combined with cell motility leads to cell assemblies of various cell types in the lowest adhesive energy state. Experimental and theoretical efforts of four decades turned the DAH into a fundamental principle of developmental biology that has been validated both in vitro and in vivo. Based on computational models of cell sorting, we have developed a DAH-based lattice model for tissues in interaction with their environment and simulated biological self-assembly using the Monte Carlo method. The present brief review highlights results on specific morphogenetic processes with relevance to tissue engineering applications. Our own work is presented on the background of several decades of theoretical efforts aimed to model morphogenesis in living tissues. Simulations of systems involving about 105 cells have been performed on high-end personal computers with CPU times of the order of days. Studied processes include cell sorting, cell sheet formation, and the development of endothelialized tubes from rings made of spheroids of two randomly intermixed cell types, when the medium in the interior of the tube was different from the external one. We conclude by noting that computer simulations based on mathematical models of living tissues yield useful guidelines for laboratory work and can catalyze the emergence of innovative technologies in tissue engineering.

3D Bio-Printing Review

NASA Astrophysics Data System (ADS)

Du, Xianbin

2018-01-01

Ultimate goal of tissue engineering is to replace pathological or necrotic body tissue or organ by artificial tissue or organ and tissue engineering is a very promising research field. 3D bio-printing is a kind of emerging technologies and a branch of tissue engineering. It has made significant progress in the past decade. 3D bio-printing can realize tissue and organ construction in vitro and has wide application in basic research and pharmacy. This paper is to make an analysis and review on 3D bio-printing from the perspectives of bioink, printing technology and technology application.

Mechanical Stimulation of Adipose-Derived Stem Cells for Functional Tissue Engineering of the Musculoskeletal System via Cyclic Hydrostatic Pressure, Simulated Microgravity, and Cyclic Tensile Strain.

PubMed

Nordberg, Rachel C; Bodle, Josie C; Loboa, Elizabeth G

2018-01-01

It is critical that human adipose stem cell (hASC) tissue-engineering therapies possess appropriate mechanical properties in order to restore function of the load bearing tissues of the musculoskeletal system. In an effort to elucidate the hASC response to mechanical stimulation and develop mechanically robust tissue engineered constructs, recent research has utilized a variety of mechanical loading paradigms including cyclic tensile strain, cyclic hydrostatic pressure, and mechanical unloading in simulated microgravity. This chapter describes methods for applying these mechanical stimuli to hASC to direct differentiation for functional tissue engineering of the musculoskeletal system.

Recent advances on biomedical applications of scaffolds in wound healing and dermal tissue engineering.

PubMed

Rahmani Del Bakhshayesh, Azizeh; Annabi, Nasim; Khalilov, Rovshan; Akbarzadeh, Abolfazl; Samiei, Mohammad; Alizadeh, Effat; Alizadeh-Ghodsi, Mohammadreza; Davaran, Soodabeh; Montaseri, Azadeh

2018-06-01

The tissue engineering field has developed in response to the shortcomings related to the replacement of the tissues lost to disease or trauma: donor tissue rejection, chronic inflammation and donor tissue shortages. The driving force behind the tissue engineering is to avoid the mentioned issues by creating the biological substitutes capable of replacing the damaged tissue. This is done by combining the scaffolds, cells and signals in order to create the living, physiological, three-dimensional tissues. A wide variety of skin substitutes are used in the treatment of full-thickness injuries. Substitutes made from skin can harbour the latent viruses, and artificial skin grafts can heal with the extensive scarring, failing to regenerate structures such as glands, nerves and hair follicles. New and practical skin scaffold materials remain to be developed. The current article describes the important information about wound healing scaffolds. The scaffold types which were used in these fields were classified according to the accepted guideline of the biological medicine. Moreover, the present article gave the brief overview on the fundamentals of the tissue engineering, biodegradable polymer properties and their application in skin wound healing. Also, the present review discusses the type of the tissue engineered skin substitutes and modern wound dressings which promote the wound healing.

[Tissue engineering with mesenchymal stem cells for cartilage and bone regeneration].

PubMed

Schaefer, D J; Klemt, C; Zhang, X H; Stark, G B

2000-09-01

Tissue engineering offers the possibility to fabricate living substitutes for tissues and organs by combining histogenic cells and biocompatible carrier materials. Pluripotent mesenchymal stem cells are isolated and subcultured ex vivo and then their histogenic differentiation is induced by external factors. The fabrication of bone and cartilage constructs, their combinations and gene therapeutic approaches are demonstrated. Advantages and disadvantages of these methods are described by in vitro and in vitro testing. The proof of histotypical function after implantation in vivo is essential. The use of autologous cells and tissue engineering methods offers the possibility to overcome the disadvantages of classical tissue reconstruction--donor site morbidity of autologous grafts, immunogenicity of allogenic grafts and loosening of alloplastic implants. Furthermore, tissue engineering widens the spectrum of surgical indications in bone and cartilage reconstruction.

Mechanical characterization of human brain tumors from patients and comparison to potential surgical phantoms.

PubMed

Stewart, Daniel C; Rubiano, Andrés; Dyson, Kyle; Simmons, Chelsey S

2017-01-01

While mechanical properties of the brain have been investigated thoroughly, the mechanical properties of human brain tumors rarely have been directly quantified due to the complexities of acquiring human tissue. Quantifying the mechanical properties of brain tumors is a necessary prerequisite, though, to identify appropriate materials for surgical tool testing and to define target parameters for cell biology and tissue engineering applications. Since characterization methods vary widely for soft biological and synthetic materials, here, we have developed a characterization method compatible with abnormally shaped human brain tumors, mouse tumors, animal tissue and common hydrogels, which enables direct comparison among samples. Samples were tested using a custom-built millimeter-scale indenter, and resulting force-displacement data is analyzed to quantify the steady-state modulus of each sample. We have directly quantified the quasi-static mechanical properties of human brain tumors with effective moduli ranging from 0.17-16.06 kPa for various pathologies. Of the readily available and inexpensive animal tissues tested, chicken liver (steady-state modulus 0.44 ± 0.13 kPa) has similar mechanical properties to normal human brain tissue while chicken crassus gizzard muscle (steady-state modulus 3.00 ± 0.65 kPa) has similar mechanical properties to human brain tumors. Other materials frequently used to mimic brain tissue in mechanical tests, like ballistic gel and chicken breast, were found to be significantly stiffer than both normal and diseased brain tissue. We have directly compared quasi-static properties of brain tissue, brain tumors, and common mechanical surrogates, though additional tests would be required to determine more complex constitutive models.

[Research progress of in vivo bioreactor as vascularization strategies in bone tissue engineering].

PubMed

Zhang, Haifeng; Han, Dong

2014-09-01

To review the application and research progress of in vivo bioreactor as vascularization strategies in bone tissue engineering. The original articles about in vivo bioreactor that can enhance vascularization of tissue engineered bone were extensively reviewed and analyzed. The in vivo bioreactor can be created by periosteum, muscle, muscularis membrane, and fascia flap as well as biomaterials. Using in vivo bioreactor can effectively promote the establishment of a microcirculation in the tissue engineered bones, especially for large bone defects. However, main correlative researches, currently, are focused on animal experiments, more clinical trials will be carried out in the future. With the rapid development of related technologies of bone tissue engineering, the use of in vivo bioreactor will to a large extent solve the bottleneck limitations and has the potential values for clinical application.

Graphene-based materials for tissue engineering.

PubMed

Shin, Su Ryon; Li, Yi-Chen; Jang, Hae Lin; Khoshakhlagh, Parastoo; Akbari, Mohsen; Nasajpour, Amir; Zhang, Yu Shrike; Tamayol, Ali; Khademhosseini, Ali

2016-10-01

Graphene and its chemical derivatives have been a pivotal new class of nanomaterials and a model system for quantum behavior. The material's excellent electrical conductivity, biocompatibility, surface area and thermal properties are of much interest to the scientific community. Two-dimensional graphene materials have been widely used in various biomedical research areas such as bioelectronics, imaging, drug delivery, and tissue engineering. In this review, we will highlight the recent applications of graphene-based materials in tissue engineering and regenerative medicine. In particular, we will discuss the application of graphene-based materials in cardiac, neural, bone, cartilage, skeletal muscle, and skin/adipose tissue engineering. We will also discuss the potential risk factors of graphene-based materials in tissue engineering. In conclusion, we will outline the opportunities in the usage of graphene-based materials for clinical applications. Published by Elsevier B.V.

Dynamic changes in high and low mammographic density human breast tissues maintained in murine tissue engineering chambers during various murine peripartum states and over time.

PubMed

Chew, G L; Huang, D; Huo, C W; Blick, T; Hill, P; Cawson, J; Frazer, H; Southey, M D; Hopper, J L; Henderson, M A; Haviv, I; Thompson, E W

2013-07-01

Mammographic density (MD) is a strong heritable risk factor for breast cancer, and may decrease with increasing parity. However, the biomolecular basis for MD-associated breast cancer remains unclear, and systemic hormonal effects on MD-associated risk is poorly understood. This study assessed the effect of murine peripartum states on high and low MD tissue maintained in a xenograft model of human MD. Method High and low MD human breast tissues were precisely sampled under radiographic guidance from prophylactic mastectomy specimens of women. The high and low MD tissues were maintained in separate vascularised biochambers in nulliparous or pregnant SCID mice for 4 weeks, or mice undergoing postpartum involution or lactation for three additional weeks. High and low MD biochamber material was harvested for histologic and radiographic comparisons during various murine peripartum states. High and low MD biochamber tissues in nulliparous mice were harvested at different timepoints for histologic and radiographic comparisons. Results High MD biochamber tissues had decreased stromal (p = 0.0027), increased adipose (p = 0.0003) and a trend to increased glandular tissue areas (p = 0.076) after murine postpartum involution. Stromal areas decreased (p = 0.042), while glandular (p = 0.001) and adipose areas (p = 0.009) increased in high MD biochamber tissues during lactation. A difference in radiographic density was observed in high (p = 0.0021) or low MD biochamber tissues (p = 0.004) between nulliparous, pregnant and involution groups. No differences in tissue composition were observed in high or low MD biochamber tissues maintained for different durations, although radiographic density increased over time. Conclusion High MD biochamber tissues had measurable histologic changes after postpartum involution or lactation. Alterations in radiographic density occurred in biochamber tissues between different peripartum states and over time. These findings demonstrate the dynamic nature of the human MD xenograft model, providing a platform for studying the biomolecular basis of MD-associated cancer risk.

Generating favorable growth factor and protease release profiles to enable extracellular matrix accumulation within an in vitro tissue engineering environment.

PubMed

Zhang, Xiaoqing; Battiston, Kyle G; Labow, Rosalind S; Simmons, Craig A; Santerre, J Paul

2017-05-01

Tissue engineering (particularly for the case of load-bearing cardiovascular and connective tissues) requires the ability to promote the production and accumulation of extracellular matrix (ECM) components (e.g., collagen, glycosaminoglycan and elastin). Although different approaches have been attempted in order to enhance ECM accumulation in tissue engineered constructs, studies of underlying signalling mechanisms that influence ECM deposition and degradation during tissue remodelling and regeneration in multi-cellular culture systems have been limited. The current study investigated vascular smooth muscle cell (VSMC)-monocyte co-culture systems using different VSMC:monocyte ratios, within a degradable polyurethane scaffold, to assess their influence on ECM generation and degradation processes, and to elucidate relevant signalling molecules involved in this in vitro vascular tissue engineering system. It was found that a desired release profile of growth factors (e.g. insulin growth factor-1 (IGF-1)) and hydrolytic proteases (e.g. matrix-metalloproteinases 2, 9, 13 and 14 (MMP2, MMP9, MMP13 and MMP14)), could be achieved in co-culture systems, yielding an accumulation of ECM (specifically for 2:1 and 4:1 VSMC:monocyte culture systems). This study has significant implications for the tissue engineering field (including vascular tissue engineering), not only because it identified important cytokines and proteases that control ECM accumulation/degradation within synthetic tissue engineering scaffolds, but also because the established culture systems could be applied to improve the development of different types of tissue constructs. Sufficient extracellular matrix accumulation within cardiovascular and connective tissue engineered constructs is a prerequisite for their appropriate function in vivo. This study established co-culture systems with tissue specific cells (vascular smooth muscle cells (VSMCs)) and defined ratios of immune cells (monocytes) to investigate extracellular matrix (ECM) generation and degradation processes, revealing important mechanisms underlying ECM turnover during vascular tissue regeneration/remodelling. A specific growth factor (IGF-1), as well as hydrolytic proteases (e.g. MMP2, MMP9, MMP13 and MMP14), were identified as playing important roles in these processes. ECM accumulation was found to be dependent on achieving a desired release profile of these ECM-promoting and ECM-degrading factors within the multi-cellular microenvironment. The findings enhance our understanding of ECM deposition and degradation during in vitro tissue engineering and would be applicable to the repair or regeneration of a variety of tissues. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Periosteum tissue engineering-a review.

PubMed

Li, Nanying; Song, Juqing; Zhu, Guanglin; Li, Xiaoyu; Liu, Lei; Shi, Xuetao; Wang, Yingjun

2016-10-18

As always, the clinical therapy of critical size bone defects caused by trauma, tumor removal surgery or congenital malformation is facing great challenges. Currently, various approaches including autograft, allograft and cell-biomaterial composite based tissue-engineering strategies have been implemented to reconstruct injured bone. However, due to damage during the transplantation processes or design negligence of the bionic scaffolds, these methods expose vulnerabilities without the assistance of periosteum, a bilayer membrane on the outer surface of the bone. Periosteum plays a significant role in bone formation and regeneration as a store for progenitor cells, a source of local growth factors and a scaffold to recruit cells and growth factors, and more and more researchers have recognized its great value in tissue engineering application. Besides direct transplantation, periosteum-derived cells can be cultured on various scaffolds for osteogenesis or chondrogenesis application due to their availability. Research studies also provide a biomimetic methodology to synthesize artificial periosteum which mimic native periosteum in structure or function. According to the studies, these tissue-engineered periostea did obviously enhance the therapeutic effects of bone graft and scaffold engineering while they could be directly used as substitutes of native periosteum. Periosteum tissue engineering, whose related research studies have provided new opportunities for the development of bone tissue engineering and therapy, has gradually become a hot spot and there are still lots to consummate. In this review, tissue-engineered periostea were classified into four kinds and discussed, which might help subsequent researchers get a more systematic view of pseudo-periosteum.

Growing Tissues in Real and Simulated Microgravity: New Methods for Tissue Engineering

PubMed Central

Wehland, Markus; Pietsch, Jessica; Aleshcheva, Ganna; Wise, Petra; van Loon, Jack; Ulbrich, Claudia; Magnusson, Nils E.; Infanger, Manfred; Bauer, Johann

2014-01-01

Tissue engineering in simulated (s-) and real microgravity (r-μg) is currently a topic in Space medicine contributing to biomedical sciences and their applications on Earth. The principal aim of this review is to highlight the advances and accomplishments in the field of tissue engineering that could be achieved by culturing cells in Space or by devices created to simulate microgravity on Earth. Understanding the biology of three-dimensional (3D) multicellular structures is very important for a more complete appreciation of in vivo tissue function and advancing in vitro tissue engineering efforts. Various cells exposed to r-μg in Space or to s-μg created by a random positioning machine, a 2D-clinostat, or a rotating wall vessel bioreactor grew in the form of 3D tissues. Hence, these methods represent a new strategy for tissue engineering of a variety of tissues, such as regenerated cartilage, artificial vessel constructs, and other organ tissues as well as multicellular cancer spheroids. These aggregates are used to study molecular mechanisms involved in angiogenesis, cancer development, and biology and for pharmacological testing of, for example, chemotherapeutic drugs or inhibitors of neoangiogenesis. Moreover, they are useful for studying multicellular responses in toxicology and radiation biology, or for performing coculture experiments. The future will show whether these tissue-engineered constructs can be used for medical transplantations. Unveiling the mechanisms of microgravity-dependent molecular and cellular changes is an up-to-date requirement for improving Space medicine and developing new treatment strategies that can be translated to in vivo models while reducing the use of laboratory animals. PMID:24597549

Growing tissues in real and simulated microgravity: new methods for tissue engineering.

PubMed

Grimm, Daniela; Wehland, Markus; Pietsch, Jessica; Aleshcheva, Ganna; Wise, Petra; van Loon, Jack; Ulbrich, Claudia; Magnusson, Nils E; Infanger, Manfred; Bauer, Johann

2014-12-01

Tissue engineering in simulated (s-) and real microgravity (r-μg) is currently a topic in Space medicine contributing to biomedical sciences and their applications on Earth. The principal aim of this review is to highlight the advances and accomplishments in the field of tissue engineering that could be achieved by culturing cells in Space or by devices created to simulate microgravity on Earth. Understanding the biology of three-dimensional (3D) multicellular structures is very important for a more complete appreciation of in vivo tissue function and advancing in vitro tissue engineering efforts. Various cells exposed to r-μg in Space or to s-μg created by a random positioning machine, a 2D-clinostat, or a rotating wall vessel bioreactor grew in the form of 3D tissues. Hence, these methods represent a new strategy for tissue engineering of a variety of tissues, such as regenerated cartilage, artificial vessel constructs, and other organ tissues as well as multicellular cancer spheroids. These aggregates are used to study molecular mechanisms involved in angiogenesis, cancer development, and biology and for pharmacological testing of, for example, chemotherapeutic drugs or inhibitors of neoangiogenesis. Moreover, they are useful for studying multicellular responses in toxicology and radiation biology, or for performing coculture experiments. The future will show whether these tissue-engineered constructs can be used for medical transplantations. Unveiling the mechanisms of microgravity-dependent molecular and cellular changes is an up-to-date requirement for improving Space medicine and developing new treatment strategies that can be translated to in vivo models while reducing the use of laboratory animals.

Articular cartilage tissue engineering: the role of signaling molecules

PubMed Central

Kwon, Heenam; Paschos, Nikolaos K.; Hu, Jerry C.; Athanasiou, Kyriacos

2017-01-01

Effective early disease modifying options for osteoarthritis remain lacking. Tissue engineering approach to generate cartilage in vitro has emerged as a promising option for articular cartilage repair and regeneration. Signaling molecules and matrix modifying agents, derived from knowledge of cartilage development and homeostasis, have been used as biochemical stimuli toward cartilage tissue engineering and have led to improvements in the functionality of engineered cartilage. Clinical translation of neocartilage faces challenges, such as phenotypic instability of the engineered cartilage, poor integration, inflammation, and catabolic factors in the arthritic environment; these can all contribute to failure of implanted neocartilage. A comprehensive understanding of signaling molecules involved in osteoarthritis pathogenesis and their actions on engineered cartilage will be crucial. Thus, while it is important to continue deriving inspiration from cartilage development and homeostasis, it has become increasing necessary to incorporate knowledge from osteoarthritis pathogenesis into cartilage tissue engineering. PMID:26811234

Microvascular Guidance: A Challenge to Support the Development of Vascularised Tissue Engineering Construct

PubMed Central

Sukmana, Irza

2012-01-01

The guidance of endothelial cell organization into a capillary network has been a long-standing challenge in tissue engineering. Some research efforts have been made to develop methods to promote capillary networks inside engineered tissue constructs. Capillary and vascular networks that would mimic blood microvessel function can be used to subsequently facilitate oxygen and nutrient transfer as well as waste removal. Vascularization of engineering tissue construct is one of the most favorable strategies to overpass nutrient and oxygen supply limitation, which is often the major hurdle in developing thick and complex tissue and artificial organ. This paper addresses recent advances and future challenges in developing three-dimensional culture systems to promote tissue construct vascularization allowing mimicking blood microvessel development and function encountered in vivo. Bioreactors systems that have been used to create fully vascularized functional tissue constructs will also be outlined. PMID:22623881

A Review of Three-Dimensional Printing in Tissue Engineering.

PubMed

Sears, Nick A; Seshadri, Dhruv R; Dhavalikar, Prachi S; Cosgriff-Hernandez, Elizabeth

2016-08-01

Recent advances in three-dimensional (3D) printing technologies have led to a rapid expansion of applications from the creation of anatomical training models for complex surgical procedures to the printing of tissue engineering constructs. In addition to achieving the macroscale geometry of organs and tissues, a print layer thickness as small as 20 μm allows for reproduction of the microarchitectures of bone and other tissues. Techniques with even higher precision are currently being investigated to enable reproduction of smaller tissue features such as hepatic lobules. Current research in tissue engineering focuses on the development of compatible methods (printers) and materials (bioinks) that are capable of producing biomimetic scaffolds. In this review, an overview of current 3D printing techniques used in tissue engineering is provided with an emphasis on the printing mechanism and the resultant scaffold characteristics. Current practical challenges and technical limitations are emphasized and future trends of bioprinting are discussed.

Developmental engineering: a new paradigm for the design and manufacturing of cell-based products. Part II: from genes to networks: tissue engineering from the viewpoint of systems biology and network science.

PubMed

Lenas, Petros; Moos, Malcolm; Luyten, Frank P

2009-12-01

The field of tissue engineering is moving toward a new concept of "in vitro biomimetics of in vivo tissue development." In Part I of this series, we proposed a theoretical framework integrating the concepts of developmental biology with those of process design to provide the rules for the design of biomimetic processes. We named this methodology "developmental engineering" to emphasize that it is not the tissue but the process of in vitro tissue development that has to be engineered. To formulate the process design rules in a rigorous way that will allow a computational design, we should refer to mathematical methods to model the biological process taking place in vitro. Tissue functions cannot be attributed to individual molecules but rather to complex interactions between the numerous components of a cell and interactions between cells in a tissue that form a network. For tissue engineering to advance to the level of a technologically driven discipline amenable to well-established principles of process engineering, a scientifically rigorous formulation is needed of the general design rules so that the behavior of networks of genes, proteins, or cells that govern the unfolding of developmental processes could be related to the design parameters. Now that sufficient experimental data exist to construct plausible mathematical models of many biological control circuits, explicit hypotheses can be evaluated using computational approaches to facilitate process design. Recent progress in systems biology has shown that the empirical concepts of developmental biology that we used in Part I to extract the rules of biomimetic process design can be expressed in rigorous mathematical terms. This allows the accurate characterization of manufacturing processes in tissue engineering as well as the properties of the artificial tissues themselves. In addition, network science has recently shown that the behavior of biological networks strongly depends on their topology and has developed the necessary concepts and methods to describe it, allowing therefore a deeper understanding of the behavior of networks during biomimetic processes. These advances thus open the door to a transition for tissue engineering from a substantially empirical endeavor to a technology-based discipline comparable to other branches of engineering.

Decellularized skin/adipose tissue flap matrix for engineering vascularized composite soft tissue flaps.

PubMed

Zhang, Qixu; Johnson, Joshua A; Dunne, Lina W; Chen, Youbai; Iyyanki, Tejaswi; Wu, Yewen; Chang, Edward I; Branch-Brooks, Cynthia D; Robb, Geoffrey L; Butler, Charles E

2016-04-15

Using a perfusion decellularization protocol, we developed a decellularized skin/adipose tissue flap (DSAF) comprising extracellular matrix (ECM) and intact vasculature. Our DSAF had a dominant vascular pedicle, microcirculatory vascularity, and a sensory nerve network and retained three-dimensional (3D) nanofibrous structures well. DSAF, which was composed of collagen and laminin with well-preserved growth factors (e.g., vascular endothelial growth factor, basic fibroblast growth factor), was successfully repopulated with human adipose-derived stem cells (hASCs) and human umbilical vein endothelial cells (HUVECs), which integrated with DSAF and formed 3D aggregates and vessel-like structures in vitro. We used microsurgery techniques to re-anastomose the recellularized DSAF into nude rats. In vivo, the engineered flap construct underwent neovascularization and constructive remodeling, which was characterized by the predominant infiltration of M2 macrophages and significant adipose tissue formation at 3months postoperatively. Our results indicate that DSAF co-cultured with hASCs and HUVECs is a promising platform for vascularized soft tissue flap engineering. This platform is not limited by the flap size, as the entire construct can be immediately perfused by the recellularized vascular network following simple re-integration into the host using conventional microsurgical techniques. Significant soft tissue loss resulting from traumatic injury or tumor resection often requires surgical reconstruction using autologous soft tissue flaps. However, the limited availability of qualitative autologous flaps as well as the donor site morbidity significantly limits this approach. Engineered soft tissue flap grafts may offer a clinically relevant alternative to the autologous flap tissue. In this study, we engineered vascularized soft tissue free flap by using skin/adipose flap extracellular matrix scaffold (DSAF) in combination with multiple types of human cells. Following vascular reanastomosis in the recipient site, the engineered products successful regenerated large-scale fat tissue in vivo. This approach may provide a translatable platform for composite soft tissue free flap engineering for microsurgical reconstruction. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

An adipoinductive role of inflammation in adipose tissue engineering: key factors in the early development of engineered soft tissues.

PubMed

Lilja, Heidi E; Morrison, Wayne A; Han, Xiao-Lian; Palmer, Jason; Taylor, Caroline; Tee, Richard; Möller, Andreas; Thompson, Erik W; Abberton, Keren M

2013-05-15

Tissue engineering and cell implantation therapies are gaining popularity because of their potential to repair and regenerate tissues and organs. To investigate the role of inflammatory cytokines in new tissue development in engineered tissues, we have characterized the nature and timing of cell populations forming new adipose tissue in a mouse tissue engineering chamber (TEC) and characterized the gene and protein expression of cytokines in the newly developing tissues. EGFP-labeled bone marrow transplant mice and MacGreen mice were implanted with TEC for periods ranging from 0.5 days to 6 weeks. Tissues were collected at various time points and assessed for cytokine expression through ELISA and mRNA analysis or labeled for specific cell populations in the TEC. Macrophage-derived factors, such as monocyte chemotactic protein-1 (MCP-1), appear to induce adipogenesis by recruiting macrophages and bone marrow-derived precursor cells to the TEC at early time points, with a second wave of nonbone marrow-derived progenitors. Gene expression analysis suggests that TNFα, LCN-2, and Interleukin 1β are important in early stages of neo-adipogenesis. Increasing platelet-derived growth factor and vascular endothelial cell growth factor expression at early time points correlates with preadipocyte proliferation and induction of angiogenesis. This study provides new information about key elements that are involved in early development of new adipose tissue.

Extraction and Assembly of Tissue-Derived Gels for Cell Culture and Tissue Engineering

PubMed Central

Uriel, Shiri; Labay, Edwardine; Francis-Sedlak, Megan; Moya, Monica L.; Weichselbaum, Ralph R.; Ervin, Natalia; Cankova, Zdravka

2009-01-01

Interactions with the extracellular matrix (ECM) play an important role in regulating cell function. Cells cultured in, or on, three-dimensional ECM recapitulate similar features to those found in vivo that are not present in traditional two-dimensional culture. In addition, both natural and synthetic materials containing ECM components have shown promise in a number of tissue engineering applications. Current materials available for cell culture and tissue engineering do not adequately reflect the diversity of ECM composition between tissues. In this paper, a method is presented for extracting solutions of proteins and glycoproteins from soft tissues and inducing assembly of these proteins into gels. The extracts contain ECM proteins specific to the tissue source with low levels of intracellular molecules. Gels formed from the tissue-derived extracts have nanostructure similar to ECM in vivo and can be used to culture cells as both a thin substrate coating and a thick gel. This technique could be used to assemble hydrogels with varying composition depending upon the tissue source, hydrogels for three-dimensional culture, as scaffolds for tissue engineering therapies, and to study cell–matrix interactions. PMID:19115821

Two Stage Repair of Composite Craniofacial Defects with Antibiotic Releasing Porous Poly(methyl methacrylate) Space Maintainers and Bone Regeneration

NASA Astrophysics Data System (ADS)

Spicer, Patrick

Craniofacial defects resulting from trauma and resection present many challenges to reconstruction due to the complex structure, combinations of tissues, and environment, with exposure to the oral, skin and nasal mucosal pathogens. Tissue engineering seeks to regenerate the tissues lost in these defects; however, the composite nature and proximity to colonizing bacteria remain difficult to overcome. Additionally, many tissue engineering approaches have further hurdles to overcome in the regulatory process to clinical translation. As such these studies investigated a two stage strategy employing an antibiotic-releasing porous polymethylmethacrylate space maintainer fabricated with materials currently part of products approved or cleared by the United States Food and Drug Administration, expediting the translation to the clinic. This porous space maintainer holds the bone defect open allowing soft tissue to heal around the defect. The space maintainer can then be removed and one regenerated in the defect. These studies investigated the individual components of this strategy. The porous space maintainer showed similar soft tissue healing and response to non-porous space maintainers in a rabbit composite tissue defect. The antibiotic-releasing space maintainers showed release of antibiotics from 1-5 weeks, which could be controlled by loading and fabrication parameters. In vivo, space maintainers releasing a high dose of antibiotics for an extended period of time increased soft tissue healing over burst release space maintainers in an infected composite tissue defect model in a rabbit mandible. Finally, stabilization of bone defects and regeneration could be improved through scaffold structures and delivery of a bone forming growth factor. These studies illustrate the possibility of the two stage strategy for repair of composite tissue defects of the craniofacial complex.

The construction of 3D-engineered tissues composed of cells and extracellular matrices by hydrogel template approach.

PubMed

Matsusaki, Michiya; Yoshida, Hiroaki; Akashi, Mitsuru

2007-06-01

The three-dimensional (3D)-engineered tissues composed of only cells and extracellular matrices (ECM) were constructed by the hydrogel template approach. The disulfide-crosslinked poly(gamma-glutamic acid) hydrogels were prepared as a template hydrogel. These template hydrogels were easily decomposed under physiological conditions using reductants such as cysteine, glutathione and dithiothreitol by cleavage of disulfide crosslinkage to thiol groups. The decomposed polymers are soluble in cell culture medium. The cleaving of disulfide bond was determined by UV-vis and FT-IR spectroscopies. We successfully prepared the 3D-engineered tissues (thickness/diameter, 2mm/1cm) composed of mouse L929 fibroblast cells and ECM by the decomposition of only the template hydrogel with cysteine after 10 days 3D-cell culture on/in the template hydrogel. The size and thickness of the 3D-engineered tissues was completely transferred from the template hydrogel. The cultured L929 cells viability in the obtained engineered tissues was confirmed by a culture test, WST-1 method and LIVE/DEAD staining assay. The engineered tissue was self-standing and highly dense composite of the cultured cells and collagen produced by the cells. This hydrogel template approach may be useful as a new class of soft-tissue engineering technology to substitute a synthetic polymer scaffold to the ECM scaffold produced from the cultured cells.

Chitosan and Its Potential Use as a Scaffold for Tissue Engineering in Regenerative Medicine

PubMed Central

Rodríguez-Vázquez, Martin; Vega-Ruiz, Brenda; Ramos-Zúñiga, Rodrigo; Saldaña-Koppel, Daniel Alexander; Quiñones-Olvera, Luis Fernando

2015-01-01

Tissue engineering is an important therapeutic strategy to be used in regenerative medicine in the present and in the future. Functional biomaterials research is focused on the development and improvement of scaffolding, which can be used to repair or regenerate an organ or tissue. Scaffolds are one of the crucial factors for tissue engineering. Scaffolds consisting of natural polymers have recently been developed more quickly and have gained more popularity. These include chitosan, a copolymer derived from the alkaline deacetylation of chitin. Expectations for use of these scaffolds are increasing as the knowledge regarding their chemical and biological properties expands, and new biomedical applications are investigated. Due to their different biological properties such as being biocompatible, biodegradable, and bioactive, they have given the pattern for use in tissue engineering for repair and/or regeneration of different tissues including skin, bone, cartilage, nerves, liver, and muscle. In this review, we focus on the intrinsic properties offered by chitosan and its use in tissue engineering, considering it as a promising alternative for regenerative medicine as a bioactive polymer. PMID:26504833

Portable bioreactor for perfusion and electrical stimulation of engineered cardiac tissue.

PubMed

Tandon, Nina; Taubman, Alanna; Cimetta, Elisa; Saccenti, Laetitia; Vunjak-Novakovic, Gordana

2013-01-01

Cardiac tissue engineering aims to create functional tissue constructs that can reestablish the structure and function of injured myocardium. Although bioreactors have facilitated the engineering of cardiac patches of clinically relevant size in vitro, a major drawback remains the transportation of the engineered tissues from a production facility to a medical operation facility while maintaining tissue viability and preventing contamination. Furthermore, after implantation, most of the cells are endangered by hypoxic conditions that exist before vascular flow is established. We developed a portable device that provides the perfusion and electrical stimulation necessary to engineer cardiac tissue in vitro, and to transport it to the site where it will be implantated. The micropump-powered perfusion apparatus may additionally function as an extracorporeal active pumping system providing nutrients and oxygen supply to the graft post-implantation. Such a system, through perfusion of oxygenated media and bioactive molecules (e.g. growth factors), could transiently support the tissue construct until it connects to the host vasculature and heart muscle, after which it could be taken away or let biodegrade.

Rapid prototyping technology and its application in bone tissue engineering*

PubMed Central

YUAN, Bo; ZHOU, Sheng-yuan; CHEN, Xiong-sheng

2017-01-01

Bone defects arising from a variety of reasons cannot be treated effectively without bone tissue reconstruction. Autografts and allografts have been used in clinical application for some time, but they have disadvantages. With the inherent drawback in the precision and reproducibility of conventional scaffold fabrication techniques, the results of bone surgery may not be ideal. This is despite the introduction of bone tissue engineering which provides a powerful approach for bone repair. Rapid prototyping technologies have emerged as an alternative and have been widely used in bone tissue engineering, enhancing bone tissue regeneration in terms of mechanical strength, pore geometry, and bioactive factors, and overcoming some of the disadvantages of conventional technologies. This review focuses on the basic principles and characteristics of various fabrication technologies, such as stereolithography, selective laser sintering, and fused deposition modeling, and reviews the application of rapid prototyping techniques to scaffolds for bone tissue engineering. In the near future, the use of scaffolds for bone tissue engineering prepared by rapid prototyping technology might be an effective therapeutic strategy for bone defects. PMID:28378568

Rapid prototyping technology and its application in bone tissue engineering.

PubMed

Yuan, Bo; Zhou, Sheng-Yuan; Chen, Xiong-Sheng

Bone defects arising from a variety of reasons cannot be treated effectively without bone tissue reconstruction. Autografts and allografts have been used in clinical application for some time, but they have disadvantages. With the inherent drawback in the precision and reproducibility of conventional scaffold fabrication techniques, the results of bone surgery may not be ideal. This is despite the introduction of bone tissue engineering which provides a powerful approach for bone repair. Rapid prototyping technologies have emerged as an alternative and have been widely used in bone tissue engineering, enhancing bone tissue regeneration in terms of mechanical strength, pore geometry, and bioactive factors, and overcoming some of the disadvantages of conventional technologies. This review focuses on the basic principles and characteristics of various fabrication technologies, such as stereolithography, selective laser sintering, and fused deposition modeling, and reviews the application of rapid prototyping techniques to scaffolds for bone tissue engineering. In the near future, the use of scaffolds for bone tissue engineering prepared by rapid prototyping technology might be an effective therapeutic strategy for bone defects.

[Research progress of cell-scaffold complex in tendon tissue engineering].

PubMed

Zhu, Ying; Li, Min

2013-04-01

To review the research progress of cell-scaffold complex in the tendon tissue engineering. Recent literature concerning cell-scaffold complex in the tendon tissue engineering was reviewed, the research situation of the cell-scaffold complex was elaborated in the aspects of seed cells, scaffolds, cell culture, and application. In tendon tissue engineering, a cell-scaffold complex is built by appropriate seed cells and engineered scaffolds. Experiments showed that modified seed cells had better therapeutic effects. Further, scaffold functionality could be improved through surface modification, growth factor cure, mechanical stimulation, and contact guidance. Among these methods, mechanical stimulation revealed the most significant results in promoting cell proliferation and function. Through a variety of defect models, it is demonstrated that the use of cell-scaffold complex could achieve satisfactory results for tendon regeneration. The cell-scaffold complex for tendon tissue engineering is a popular research topic. Although it has not yet met the requirement of clinical use, it has broad application prospects.

Current Approaches to Bone Tissue Engineering: The Interface between Biology and Engineering.

PubMed

Li, Jiao Jiao; Ebied, Mohamed; Xu, Jen; Zreiqat, Hala

2018-03-01

The successful regeneration of bone tissue to replace areas of bone loss in large defects or at load-bearing sites remains a significant clinical challenge. Over the past few decades, major progress is achieved in the field of bone tissue engineering to provide alternative therapies, particularly through approaches that are at the interface of biology and engineering. To satisfy the diverse regenerative requirements of bone tissue, the field moves toward highly integrated approaches incorporating the knowledge and techniques from multiple disciplines, and typically involves the use of biomaterials as an essential element for supporting or inducing bone regeneration. This review summarizes the types of approaches currently used in bone tissue engineering, beginning with those primarily based on biology or engineering, and moving into integrated approaches in the areas of biomaterial developments, biomimetic design, and scalable methods for treating large or load-bearing bone defects, while highlighting potential areas for collaboration and providing an outlook on future developments. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

[Development of computer aided forming techniques in manufacturing scaffolds for bone tissue engineering].

PubMed

Wei, Xuelei; Dong, Fuhui

2011-12-01

To review recent advance in the research and application of computer aided forming techniques for constructing bone tissue engineering scaffolds. The literature concerning computer aided forming techniques for constructing bone tissue engineering scaffolds in recent years was reviewed extensively and summarized. Several studies over last decade have focused on computer aided forming techniques for bone scaffold construction using various scaffold materials, which is based on computer aided design (CAD) and bone scaffold rapid prototyping (RP). CAD include medical CAD, STL, and reverse design. Reverse design can fully simulate normal bone tissue and could be very useful for the CAD. RP techniques include fused deposition modeling, three dimensional printing, selected laser sintering, three dimensional bioplotting, and low-temperature deposition manufacturing. These techniques provide a new way to construct bone tissue engineering scaffolds with complex internal structures. With rapid development of molding and forming techniques, computer aided forming techniques are expected to provide ideal bone tissue engineering scaffolds.

Recent Advances in Cartilage Tissue Engineering: From the Choice of Cell Sources to the Use of Bioreactors

NASA Astrophysics Data System (ADS)

Martin, Ivan; Démarteau, Olivier; Braccini, Alessandra

Grafting engineered cartilage tissues represents a promising approach for the repair of joint injuries. Recent animal experiments have demonstrated that tissues engineered by culturing chondrocytes on 3D scaffolds in bioreactors provide functional templates for orderly repair of large osteochondral lesions. To date, however, a reproducible generation of uniform cartilage tissues of predefined size starting from adult human cells has not been achieved. In this paper we review some of the recent advances and challenges ahead in the identification of appropriate (i) cell sources, (ii) bioactive factors, (iii) 3D scaffolds and (iv) bioreactors for human cartilage tissue engineering. We also present an example of how integrated efforts in these different areas can help addressing fundamental questions and advancing the field of cartilage tissue engineering towards clinical use. The presented experiment demonstrates that human nasal chondrocytes are responsive to dynamic loading and thus could be further investigated as a cell source for implantation in a joint environment.

Biomimetic and synthetic esophageal tissue engineering.

PubMed

Jensen, Todd; Blanchette, Alex; Vadasz, Stephanie; Dave, Apeksha; Canfarotta, Michael; Sayej, Wael N; Finck, Christine

2015-07-01

A tissue-engineered esophagus offers an alternative for the treatment of pediatric patients suffering from severe esophageal malformations, caustic injury, and cancer. Additionally, adult patients suffering from carcinoma or trauma would benefit. Donor rat esophageal tissue was physically and enzymatically digested to isolate epithelial and smooth muscle cells, which were cultured in epithelial cell medium or smooth muscle cell medium and characterized by immunofluorescence. Isolated cells were also seeded onto electrospun synthetic PLGA and PCL/PLGA scaffolds in a physiologic hollow organ bioreactor. After 2 weeks of in vitro culture, tissue-engineered constructs were orthotopically transplanted. Isolated cells were shown to give rise to epithelial, smooth muscle, and glial cell types. After 14 days in culture, scaffolds supported epithelial, smooth muscle and glial cell phenotypes. Transplanted constructs integrated into the host's native tissue and recipients of the engineered tissue demonstrated normal feeding habits. Characterization after 14 days of implantation revealed that all three cellular phenotypes were present in varying degrees in seeded and unseeded scaffolds. We demonstrate that isolated cells from native esophagus can be cultured and seeded onto electrospun scaffolds to create esophageal constructs. These constructs have potential translatable application for tissue engineering of human esophageal tissue. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Application of Sheet Technology in Cartilage Tissue Engineering.

PubMed

Ge, Yang; Gong, Yi Yi; Xu, Zhiwei; Lu, Yanan; Fu, Wei

2016-04-01

Cartilage tissue engineering started to act as a promising, even essential alternative method in the process of cartilage repair and regeneration, considering adult avascular structure has very limited self-renewal capacity of cartilage tissue in adults and a bottle-neck existed in conventional surgical treatment methods. Recent progressions in tissue engineering realized the development of more feasible strategies to treat cartilage disorders. Of these strategies, cell sheet technology has shown great clinical potentials in the regenerative areas such as cornea and esophagus and is increasingly considered as a potential way to reconstruct cartilage tissues for its non-use of scaffolds and no destruction of matrix secreted by cultured cells. Acellular matrix sheet technologies utilized in cartilage tissue engineering, with a sandwich model, can ingeniously overcome the drawbacks that occurred in a conventional acellular block, where cells are often blocked from migrating because of the non-nanoporous structure. Electrospun-based sheets with nanostructures that mimic the natural cartilage matrix offer a level of control as well as manipulation and make them appealing and widely used in cartilage tissue engineering. In this review, we focus on the utilization of these novel and promising sheet technologies to construct cartilage tissues with practical and beneficial functions.

Tissue engineering and microRNAs: future perspectives in regenerative medicine.

PubMed

Gori, Manuele; Trombetta, Marcella; Santini, Daniele; Rainer, Alberto

2015-01-01

Tissue engineering is a growing area of biomedical research, holding great promise for a broad range of potential applications in the field of regenerative medicine. In recent decades, multiple tissue engineering strategies have been adopted to mimic and improve specific biological functions of tissues and organs, including biomimetic materials, drug-releasing scaffolds, stem cells, and dynamic culture systems. MicroRNAs (miRNAs), noncoding small RNAs that negatively regulate the expression of downstream target mRNAs, are considered a novel class of molecular targets and therapeutics that may play an important role in tissue engineering. Herein, we highlight the latest achievements in regenerative medicine, focusing on the role of miRNAs as key modulators of gene expression, stem cell self-renewal, proliferation and differentiation, and eventually in driving cell fate decisions. Finally, we will discuss the contribution of miRNAs in regulating the rearrangement of the tissue microenvironment and angiogenesis, and the range of strategies for miRNA delivery into target cells and tissues. Manipulation of miRNAs is an alternative approach and an attractive strategy for controlling several aspects of tissue engineering, although some issues concerning their in vivo effects and optimal delivery methods still remain uncovered.

Biocompatible, biodegradable polymer-based, lighter than or light as water scaffolds for tissue engineering and methods for preparation and use thereof

NASA Technical Reports Server (NTRS)

Khan, Mohammed Yusuf (Inventor); Laurencin, Cato T. (Inventor); Lu, Helen H. (Inventor); Botchwey, Edward (Inventor); Pollack, Solomon R. (Inventor); Levine, Elliot (Inventor)

2012-01-01

Scaffolds for tissue engineering prepared from biocompatible, biodegradable polymer-based, lighter than or light as water microcarriers and designed for cell culturing in vitro in a rotating bioreactor are provided. Methods for preparation and use of these scaffolds as tissue engineering devices are also provided.

Recent progress in interfacial tissue engineering approaches for osteochondral defects.

PubMed

Castro, Nathan J; Hacking, S Adam; Zhang, Lijie Grace

2012-08-01

This review provides a brief synopsis of the anatomy and physiology of the osteochondral interface, scaffold-based and non-scaffold based approaches for engineering both tissues independently as well as recent developments in the manufacture of gradient constructs. Novel manufacturing techniques and nanotechnology will be discussed with potential application in osteochondral interfacial tissue engineering.

Induction of functional tissue-engineered skeletal muscle constructs by defined electrical stimulation.

PubMed

Ito, Akira; Yamamoto, Yasunori; Sato, Masanori; Ikeda, Kazushi; Yamamoto, Masahiro; Fujita, Hideaki; Nagamori, Eiji; Kawabe, Yoshinori; Kamihira, Masamichi

2014-04-24

Electrical impulses are necessary for proper in vivo skeletal muscle development. To fabricate functional skeletal muscle tissues in vitro, recapitulation of the in vivo niche, including physical stimuli, is crucial. Here, we report a technique to engineer skeletal muscle tissues in vitro by electrical pulse stimulation (EPS). Electrically excitable tissue-engineered skeletal muscle constructs were stimulated with continuous electrical pulses of 0.3 V/mm amplitude, 4 ms width, and 1 Hz frequency, resulting in a 4.5-fold increase in force at day 14. In myogenic differentiation culture, the percentage of peak twitch force (%Pt) was determined as the load on the tissue constructs during the artificial exercise induced by continuous EPS. We optimized the stimulation protocol, wherein the tissues were first subjected to 24.5%Pt, which was increased to 50-60%Pt as the tissues developed. This technique may be a useful approach to fabricate tissue-engineered functional skeletal muscle constructs.

Monitoring sinew contraction during formation of tissue-engineered fibrin-based ligament constructs.

PubMed

Paxton, Jennifer Z; Wudebwe, Uchena N G; Wang, Anqi; Woods, Daniel; Grover, Liam M

2012-08-01

The ability to study the gross morphological changes occurring during tissue formation is vital to producing tissue-engineered structures of clinically relevant dimensions in vitro. Here, we have used nondestructive methods of digital imaging and optical coherence tomography to monitor the early-stage formation and subsequent maturation of fibrin-based tissue-engineered ligament constructs. In addition, the effect of supplementation with essential promoters of collagen synthesis, ascorbic acid (AA) and proline (P), has been assessed. Contraction of the cell-seeded fibrin gel occurs unevenly within the first 5 days of culture around two fixed anchor points before forming a longitudinal ligament-like construct. AA+P supplementation accelerates gel contraction in the maturation phase of development, producing ligament-like constructs with a higher collagen content and distinct morphology to that of unsupplemented constructs. These studies highlight the importance of being able to control the methods of tissue formation and maturation in vitro to enable the production of tissue-engineered constructs with suitable replacement tissue characteristics for repair of clinical soft-tissue injuries.

Piezoelectric materials as stimulatory biomedical materials and scaffolds for bone repair.

PubMed

Tandon, Biranche; Blaker, Jonny J; Cartmell, Sarah H

2018-04-16

The process of bone repair and regeneration requires multiple physiological cues including biochemical, electrical and mechanical - that act together to ensure functional recovery. Myriad materials have been explored as bioactive scaffolds to deliver these cues locally to the damage site, amongst these piezoelectric materials have demonstrated significant potential for tissue engineering and regeneration, especially for bone repair. Piezoelectric materials have been widely explored for power generation and harvesting, structural health monitoring, and use in biomedical devices. They have the ability to deform with physiological movements and consequently deliver electrical stimulation to cells or damaged tissue without the need of an external power source. Bone itself is piezoelectric and the charges/potentials it generates in response to mechanical activity are capable of enhancing bone growth. Piezoelectric materials are capable of stimulating the physiological electrical microenvironment, and can play a vital role to stimulate regeneration and repair. This review gives an overview of the association of piezoelectric effect with bone repair, and focuses on state-of-the-art piezoelectric materials (polymers, ceramics and their composites), the fabrication routes to produce piezoelectric scaffolds, and their application in bone repair. Important characteristics of these materials from the perspective of bone tissue engineering are highlighted. Promising upcoming strategies and new piezoelectric materials for this application are presented. Electrical stimulation/electrical microenvironment are known effect the process of bone regeneration by altering the cellular response and are crucial in maintaining tissue functionality. Piezoelectric materials, owing to their capability of generating charges/potentials in response to mechanical deformations, have displayed great potential for fabricating smart stimulatory scaffolds for bone tissue engineering. The growing interest of the scientific community and compelling results of the published research articles has been the motivation of this review article. This article summarizes the significant progress in the field with a focus on the fabrication aspects of piezoelectric materials. The review of both material and cellular aspects on this topic ensures that this paper appeals to both material scientists and tissue engineers. Copyright © 2018. Published by Elsevier Ltd.

Engineering tissue constructs to mimic native aortic and pulmonary valve leaflets' structures and mechanics

NASA Astrophysics Data System (ADS)

Masoumi, Nafiseh

There are several disadvantages correlated with current heart valve replacement, including anticoagulation therapy for patients with mechanical valves and the low durability of bioprosthetic valves. The non-viable nature of such devices is a critical drawback especially for pediatric cases due to the inability of the graft to grow in vivo with the patients. A tissue engineered heart valve (TEHV) with remodeling and growth ability, is conceptually appealing to use in the surgical repair and could serve as a permanent replacements when operating for pediatric valvular lesions. It is critical that scaffolds for functional heart valve tissue engineering, be capable of mimicking the native leaflet's structure and mechanical properties at the time of implantation. Meanwhile, the scaffolds should be able to support cellular proliferation and native-like tissue formation as the TEHV remodels toward a scaffold-free state. Our overall hypothesis is that an "ideal" engineered construct, designed based on native leaflet's structure and mechanics, will complement a native heart valve leaflet in providing benchmarks for use in the design of clinically-applicable TEHV. This hypothesis was addressed through several experiments conducted in the present study. To establish a functional biomimetic TEHV, we developed scaffolds capable of matching the anisotropic stiffness of native leaflet while promoting native-like cell and collagen content and supporting the ECM generation. Scaffolds with various polymer contents (e.g., poly (glycerol sebacate) (PGS) and poly (epsilon-caprolactone) (PCL)) and structural designs (e.g., microfabricated and microfibrous scaffolds), were fabricated based on native leaflet's structure and mechanics. It was found that the tri-layered scaffold, designed with assembly of microfabricated PGS and microfibrous PGS/PCL was a functional leaflet capable of promoting tissue formation. Furthermore, to investigate the effect of cyclic stress and flexure individually on the TEHV development, we designed a simple and novel stretch-flexure bioreactor in which samples were subjected to well-defined stimulations with a controlled strain-rate. The stretch and flexure was found to accelerate and increase tissue formation on the microfabricated PGS scaffolds cultivated in the bioreactors.

Vascular and micro-environmental influences on MSC-coral hydroxyapatite construct-based bone tissue engineering.

PubMed

Cai, Lei; Wang, Qian; Gu, Congmin; Wu, Jingguo; Wang, Jian; Kang, Ning; Hu, Jiewei; Xie, Fang; Yan, Li; Liu, Xia; Cao, Yilin; Xiao, Ran

2011-11-01

Bone tissue engineering (BTE) has been demonstrated an effective approach to generate bone tissue and repair bone defect in ectopic and orthotopic sites. The strategy of using a prevascularized tissue-engineered bone grafts (TEBG) fabricated ectopically to repair bone defects, which is called live bone graft surgery, has not been reported. And the quantitative advantages of vascularization and osteogenic environment in promoting engineered bone formation have not been defined yet. In the current study we generated a tissue engineered bone flap with a vascular pedicle of saphenous arteriovenous in which an organized vascular network was observed after 4 weeks implantation, and followed by a successful repaire of fibular defect in beagle dogs. Besides, after a 9 months long term observation of engineered bone formation in ectopic and orthotopic sites, four CHA (coral hydroxyapatite) scaffold groups were evaluated by CT (computed tomography) analysis. By the comparison of bone formation and scaffold degradation between different groups, the influences of vascularization and micro-environment on tissue engineered bone were quantitatively analyzed. The results showed that in the first 3 months vascularization improved engineered bone formation by 2 times of non-vascular group and bone defect micro-environment improved it by 3 times of ectopic group, and the CHA-scaffold degradation was accelerated as well. Copyright © 2011 Elsevier Ltd. All rights reserved.

Bio-inspired 3D microenvironments: a new dimension in tissue engineering.

PubMed

Magin, Chelsea M; Alge, Daniel L; Anseth, Kristi S

2016-03-04

Biomaterial scaffolds have been a foundational element of the tissue engineering paradigm since the inception of the field. Over the years there has been a progressive move toward the rational design and fabrication of bio-inspired materials that mimic the composition as well as the architecture and 3D structure of tissues. In this review, we chronicle advances in the field that address key challenges in tissue engineering as well as some emerging applications. Specifically, a summary of the materials and chemistries used to engineer bio-inspired 3D matrices that mimic numerous aspects of the extracellular matrix is provided, along with an overview of bioprinting, an additive manufacturing approach, for the fabrication of engineered tissues with precisely controlled 3D structures and architectures. To emphasize the potential clinical impact of the bio-inspired paradigm in biomaterials engineering, some applications of bio-inspired matrices are discussed in the context of translational tissue engineering. However, focus is also given to recent advances in the use of engineered 3D cellular microenvironments for fundamental studies in cell biology, including photoresponsive systems that are shedding new light on how matrix properties influence cell phenotype and function. In an outlook for future work, the need for high-throughput methods both for screening and fabrication is highlighted. Finally, microscale organ-on-a-chip technologies are highlighted as a promising area for future investment in the application of bio-inspired microenvironments.

It's all in the timing: modeling isovolumic contraction through development and disease with a dynamic dual electromechanical bioreactor system.

PubMed

Morgan, Kathy Ye; Black, Lauren Deems

2014-01-01

This commentary discusses the rationale behind our recently reported work entitled "Mimicking isovolumic contraction with combined electromechanical stimulation improves the development of engineered cardiac constructs," introduces new data supporting our hypothesis, and discusses future applications of our bioreactor system. The ability to stimulate engineered cardiac tissue in a bioreactor system that combines both electrical and mechanical stimulation offers a unique opportunity to simulate the appropriate dynamics between stretch and contraction and model isovolumic contraction in vitro. Our previous study demonstrated that combined electromechanical stimulation that simulated the timing of isovolumic contraction in healthy tissue improved force generation via increased contractile and calcium handling protein expression and improved hypertrophic pathway activation. In new data presented here, we further demonstrate that modification of the timing between electrical and mechanical stimulation to mimic a non-physiological process negatively impacts the functionality of the engineered constructs. We close by exploring the various disease states that have altered timing between the electrical and mechanical stimulation signals as potential future directions for the use of this system.

Cell therapy, 3D culture systems and tissue engineering for cardiac regeneration.

PubMed

Emmert, Maximilian Y; Hitchcock, Robert W; Hoerstrup, Simon P

2014-04-01

Ischemic Heart Disease (IHD) still represents the "Number One Killer" worldwide accounting for the death of numerous patients. However the capacity for self-regeneration of the adult heart is very limited and the loss of cardiomyocytes in the infarcted heart leads to continuous adverse cardiac-remodeling which often leads to heart-failure (HF). The concept of regenerative medicine comprising cell-based therapies, bio-engineering technologies and hybrid solutions has been proposed as a promising next-generation approach to address IHD and HF. Numerous strategies are under investigation evaluating the potential of regenerative medicine on the failing myocardium including classical cell-therapy concepts, three-dimensional culture techniques and tissue-engineering approaches. While most of these regenerative strategies have shown great potential in experimental studies, the translation into a clinical setting has either been limited or too rapid leaving many key questions unanswered. This review summarizes the current state-of-the-art, important challenges and future research directions as to regenerative approaches addressing IHD and resulting HF. Copyright © 2014 Elsevier B.V. All rights reserved.

Mechanics of oriented electrospun nanofibrous scaffolds for annulus fibrosus tissue engineering.

PubMed

Nerurkar, Nandan L; Elliott, Dawn M; Mauck, Robert L

2007-08-01

Engineering a functional replacement for the annulus fibrosus (AF) of the intervertebral disc is contingent upon recapitulation of AF structure, composition, and mechanical properties. In this study, we propose a new paradigm for AF tissue engineering that focuses on the reconstitution of anatomic fiber architecture and uses constitutive modeling to evaluate construct function. A modified electrospinning technique was utilized to generate aligned nanofibrous polymer scaffolds for engineering the basic functional unit of the AF, a single lamella. Scaffolds were tested in uniaxial tension at multiple fiber orientations, demonstrating a nonlinear dependence of modulus on fiber angle that mimicked the nonlinearity and anisotropy of native AF. A homogenization model previously applied to native AF successfully described scaffold mechanical response, and parametric studies demonstrated that nonfibrillar matrix, along with fiber connectivity, are key contributors to tensile mechanics for engineered AF. We demonstrated that AF cells orient themselves along the aligned scaffolds and deposit matrix that contributes to construct mechanics under loading conditions relevant to the in vivo environment. The homogenization model was applied to cell-seeded constructs and provided quantitative measures for the evolution of matrix and interfibrillar interactions. Finally, the model demonstrated that at fiber angles of the AF (28 degrees -44 degrees ), engineered material behaved much like native tissue, suggesting that engineered constructs replicate the physiologic behavior of the single AF lamella. Constitutive modeling provides a powerful tool for analysis of engineered AF neo-tissue and native AF tissue alike, highlighting key mechanical design criteria for functional AF tissue engineering.

Silk scaffolds in bone tissue engineering: An overview.

PubMed

Bhattacharjee, Promita; Kundu, Banani; Naskar, Deboki; Kim, Hae-Won; Maiti, Tapas K; Bhattacharya, Debasis; Kundu, Subhas C

2017-11-01

Bone tissue plays multiple roles in our day-to-day functionality. The frequency of accidental bone damage and disorder is increasing worldwide. Moreover, as the world population continues to grow, the percentage of the elderly population continues to grow, which results in an increased number of bone degenerative diseases. This increased elderly population pushes the need for artificial bone implants that specifically employ biocompatible materials. A vast body of literature is available on the use of silk in bone tissue engineering. The current work presents an overview of this literature from materials and fabrication perspective. As silk is an easy-to-process biopolymer; this allows silk-based biomaterials to be molded into diverse forms and architectures, which further affects the degradability. This makes silk-based scaffolds suitable for treating a variety of bone reconstruction and regeneration objectives. Silk surfaces offer active sites that aid the mineralization and/or bonding of bioactive molecules that facilitate bone regeneration. Silk has also been blended with a variety of polymers and minerals to enhance its advantageous properties or introduce new ones. Several successful works, both in vitro and in vivo, have been reported using silk-based scaffolds to regenerate bone tissues or other parts of the skeletal system such as cartilage and ligament. A growing trend is observed toward the use of mineralized and nanofibrous scaffolds along with the development of technology that allows to control scaffold architecture, its biodegradability and the sustained releasing property of scaffolds. Further development of silk-based scaffolds for bone tissue engineering, taking them up to and beyond the stage of human trials, is hoped to be achieved in the near future through a cross-disciplinary coalition of tissue engineers, material scientists and manufacturing engineers. The state-of-art of silk biomaterials in bone tissue engineering, covering their wide applications as cell scaffolding matrices to micro-nano carriers for delivering bone growth factors and therapeutic molecules to diseased or damaged sites to facilitate bone regeneration, is emphasized here. The review rationalizes that the choice of silk protein as a biomaterial is not only because of its natural polymeric nature, mechanical robustness, flexibility and wide range of cell compatibility but also because of its ability to template the growth of hydroxyapatite, the chief inorganic component of bone mineral matrix, resulting in improved osteointegration. The discussion extends to the role of inorganic ions such as Si and Ca as matrix components in combination with silk to influence bone regrowth. The effect of ions or growth factor-loaded vehicle incorporation into regenerative matrix, nanotopography is also considered. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Designing of PLA scaffolds for bone tissue replacement fabricated by ordinary commercial 3D printer.

PubMed

Gregor, Aleš; Filová, Eva; Novák, Martin; Kronek, Jakub; Chlup, Hynek; Buzgo, Matěj; Blahnová, Veronika; Lukášová, Věra; Bartoš, Martin; Nečas, Alois; Hošek, Jan

2017-01-01

The primary objective of Tissue engineering is a regeneration or replacement of tissues or organs damaged by disease, injury, or congenital anomalies. At present, Tissue engineering repairs damaged tissues and organs with artificial supporting structures called scaffolds. These are used for attachment and subsequent growth of appropriate cells. During the cell growth gradual biodegradation of the scaffold occurs and the final product is a new tissue with the desired shape and properties. In recent years, research workplaces are focused on developing scaffold by bio-fabrication techniques to achieve fast, precise and cheap automatic manufacturing of these structures. Most promising techniques seem to be Rapid prototyping due to its high level of precision and controlling. However, this technique is still to solve various issues before it is easily used for scaffold fabrication. In this article we tested printing of clinically applicable scaffolds with use of commercially available devices and materials. Research presented in this article is in general focused on "scaffolding" on a field of bone tissue replacement. Commercially available 3D printer and Polylactic acid were used to create originally designed and possibly suitable scaffold structures for bone tissue engineering. We tested printing of scaffolds with different geometrical structures. Based on the osteosarcoma cells proliferation experiment and mechanical testing of designed scaffold samples, it will be stated that it is likely not necessary to keep the recommended porosity of the scaffold for bone tissue replacement at about 90%, and it will also be clarified why this fact eliminates mechanical properties issue. Moreover, it is demonstrated that the size of an individual pore could be double the size of the recommended range between 0.2-0.35 mm without affecting the cell proliferation. Rapid prototyping technique based on Fused deposition modelling was used for the fabrication of designed scaffold structures. All the experiments were performed in order to show how to possibly solve certain limitations and issues that are currently reported by research workplaces on the field of scaffold bio-fabrication. These results should provide new valuable knowledge for further research.

Three-dimensional bioprinting in tissue engineering and regenerative medicine.

PubMed

Gao, Guifang; Cui, Xiaofeng

2016-02-01

With the advances of stem cell research, development of intelligent biomaterials and three-dimensional biofabrication strategies, highly mimicked tissue or organs can be engineered. Among all the biofabrication approaches, bioprinting based on inkjet printing technology has the promises to deliver and create biomimicked tissue with high throughput, digital control, and the capacity of single cell manipulation. Therefore, this enabling technology has great potential in regenerative medicine and translational applications. The most current advances in organ and tissue bioprinting based on the thermal inkjet printing technology are described in this review, including vasculature, muscle, cartilage, and bone. In addition, the benign side effect of bioprinting to the printed mammalian cells can be utilized for gene or drug delivery, which can be achieved conveniently during precise cell placement for tissue construction. With layer-by-layer assembly, three-dimensional tissues with complex structures can be printed using converted medical images. Therefore, bioprinting based on thermal inkjet is so far the most optimal solution to engineer vascular system to the thick and complex tissues. Collectively, bioprinting has great potential and broad applications in tissue engineering and regenerative medicine. The future advances of bioprinting include the integration of different printing mechanisms to engineer biphasic or triphasic tissues with optimized scaffolds and further understanding of stem cell biology.

An overview on autologous fibrin glue in bone tissue engineering of maxillofacial surgery

PubMed Central

Khodakaram-Tafti, Azizollah; Mehrabani, Davood; Shaterzadeh-Yazdi, Hanieh

2017-01-01

The purpose of this review is to have an overview on the applications on the autologous fibrin glue as a bone graft substitute in maxillofacial injuries and defects. A search was conducted using the databases such as Medline or PubMed and Google Scholar for articles from 1985 to 2016. The criteria were “Autograft,” “Fibrin tissue adhesive,” “Tissue engineering,” “Maxillofacial injury,” and “Regenerative medicine.” Bone tissue engineering is a new promising approach for bone defect reconstruction. In this technique, cells are combined with three-dimensional scaffolds to provide a tissue-like structure to replace lost parts of the tissue. Fibrin as a natural scaffold, because of its biocompatibility and biodegradability, and the initial stability of the grafted stem cells is introduced as an excellent scaffold for tissue engineering. It promotes cell migration, proliferation, and matrix making through acceleration in angiogenesis. Growth factors in fibrin glue can stimulate and promote tissue repair. Autologous fibrin scaffolds are excellent candidates for tissue engineering so that they can be produced faster, cheaper, and in larger quantities. In addition, they are easy to use and the probability of viral or prion transmission may be decreased. Therefore, autologous fibrin glue appears to be promising scaffold in regenerative maxillofacial surgery. PMID:28584530

An update to space biomedical research: tissue engineering in microgravity bioreactors.

PubMed

Barzegari, Abolfazl; Saei, Amir Ata

2012-01-01

The severe need for constructing replacement tissues in organ transplanta-tion has necessitated the development of tissue engineering approaches and bioreactors that can bring these approaches to reality. The inherent limitations of conventional bioreactors in generating realistic tissue constructs led to the devise of the microgravity tissue engineering that uses Rotating Wall Vessel (RWV) bioreactors initially developed by NASA. In this review article, we intend to highlight some major advances and accomplishments in the rapidly-growing field of tissue engineering that could not be achieved without using microgravity. Research is now focused on assembly of 3 dimensional (3D) tissue fragments from various cell types in human body such as chon-drocytes, osteoblasts, embryonic and mesenchymal stem cells, hepatocytes and pancreas islet cells. Hepatocytes cultured under microgravity are now being used in extracorporeal bioartificial liver devices. Tissue constructs can be used not only in organ replacement therapy, but also in pharmaco-toxicology and food safety assessment. 3D models of vari-ous cancers may be used in studying cancer development and biology or in high-throughput screening of anticancer drug candidates. Finally, 3D heterogeneous assemblies from cancer/immune cells provide models for immunotherapy of cancer. Tissue engineering in (simulated) microgravity has been one of the stunning impacts of space research on biomedical sciences and their applications on earth.

Lineage plasticity and cell biology of fibrocartilage and hyaline cartilage: its significance in cartilage repair and replacement.

PubMed

Freemont, Anthony J; Hoyland, Judith

2006-01-01

Cartilage repair is a major goal of modern tissue engineering. To produce novel engineered implants requires a knowledge of the basic biology of the tissues that are to be replaced or reproduced. Hyaline articular cartilage and meniscal fibrocartilage are two tissues that have excited attention because of the frequency with which they are damaged. A basic strategy is to re-engineer these tissues ex vivo by stimulating stem cells to differentiate into the cells of the mature tissue capable of producing an intact functional matrix. In this brief review, the sources of cells for tissue engineering cartilage and the culture conditions that have promoted differentiation are discussed within the context of natural cartilage repair. In particular, the role of cell density, cytokines, load, matrices and oxygen tension are discussed.

Imaging stem cell distribution, growth, migration, and differentiation in 3-D scaffolds for bone tissue engineering using mesoscopic fluorescence tomography.

PubMed

Tang, Qinggong; Piard, Charlotte; Lin, Jonathan; Nan, Kai; Guo, Ting; Caccamese, John; Fisher, John; Chen, Yu

2018-01-01

Regenerative medicine has emerged as an important discipline that aims to repair injury or replace damaged tissues or organs by introducing living cells or functioning tissues. Successful regenerative medicine strategies will likely depend upon a simultaneous optimization strategy for the design of biomaterials, cell-seeding methods, cell-biomaterial interactions, and molecular signaling within the engineered tissues. It remains a challenge to image three-dimensional (3-D) structures and functions of the cell-seeded scaffold in mesoscopic scale (>2 ∼ 3 mm). In this study, we utilized angled fluorescence laminar optical tomography (aFLOT), which allows depth-resolved molecular characterization of engineered tissues in 3-D to investigate cell viability, migration, and bone mineralization within bone tissue engineering scaffolds in situ. © 2017 Wiley Periodicals, Inc.

[Current status of bone/cartilage tissue engineering towards clinical applications].

PubMed

Ohgushi, Hajime

2014-10-01

Osteo/chondrogenic differentiation capabilities are seen after in vivo implantation of mesenchymal stem cells (MSCs), which are currently used for the patients having bone/cartilage defects. Importantly, the differentiation capabilities are induced by culturing technology, resulting in in vitro bone/cartilage formation. Especially, the in vitro bone tissue is useful for bone tissue regeneration. For cartilage regeneration, culture expanded chondrocytes derived from patient's normal cartilage are also used for the patients having cartilage damages. Recently, the cultured chondrocytes embedded in atelocollagen gel are obtainable as tissue engineered products distributed by Japan Tissue Engineering Co. Ltd. The products are available in the well-regulated hospitals by qualified orthopedic surgeons. The criteria for these hospitals/surgeons have been established. This review paper focuses on current status of bone/cartilage tissue engineering towards clinical applications in Japan.

Scaffolds in Tendon Tissue Engineering

PubMed Central

Longo, Umile Giuseppe; Lamberti, Alfredo; Petrillo, Stefano; Maffulli, Nicola; Denaro, Vincenzo

2012-01-01

Tissue engineering techniques using novel scaffold materials offer potential alternatives for managing tendon disorders. Tissue engineering strategies to improve tendon repair healing include the use of scaffolds, growth factors, cell seeding, or a combination of these approaches. Scaffolds have been the most common strategy investigated to date. Available scaffolds for tendon repair include both biological scaffolds, obtained from mammalian tissues, and synthetic scaffolds, manufactured from chemical compounds. Preliminary studies support the idea that scaffolds can provide an alternative for tendon augmentation with an enormous therapeutic potential. However, available data are lacking to allow definitive conclusion on the use of scaffolds for tendon augmentation. We review the current basic science and clinical understanding in the field of scaffolds and tissue engineering for tendon repair. PMID:22190961

Evaluation of Functionalized Spider Silk Matrices: Choice of Cell Types and Controls are Important for Detecting Specific Effects

DOE Office of Scientific and Technical Information (OSTI.GOV)

Johansson, Jan, E-mail: janne.johansson@ki.se; Rising, Anna, E-mail: janne.johansson@ki.se; Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, Uppsala

2014-11-06

The ideal scaffold for engineering and regeneration of tissues would be a replica of the extracellular matrix (ECM), which is unique for each tissue type. The scaffold should mimic the mechanical properties of the targeted tissue and serve as matrix for adhesion, growth, migration, and differentiation of endogenous and/or implanted cells. Recent research has highlighted the potential of targeting also the environment of the intermediate states that are formed during tissue repair, since progenitor cells that contribute to tissue formation in a regenerative niche exist in an environment that is different from the final tissue (e.g., the fracture callus thatmore » is formed during osteogenesis is softer than mature bone tissue) (Polo-Corrales et al., 2014). In addition, the scaffold should not evoke inappropriate immune responses and should be degradable. To improve cell interactions, ECM-derived cell-binding peptide motifs have been extensively used (Sengupta and Heilshorn, 2010; Maia et al.,).« less

From natural bone grafts to tissue engineering therapeutics: Brainstorming on pharmaceutical formulative requirements and challenges.

PubMed

Baroli, Biancamaria

2009-04-01

Tissue engineering is an emerging multidisciplinary field of investigation focused on the regeneration of diseased or injured tissues through the delivery of appropriate molecular and mechanical signals. Therefore, bone tissue engineering covers all the attempts to reestablish a normal physiology or to speed up healing of bone in all musculoskeletal disorders and injuries that are lashing modern societies. This article attempts to give a pharmaceutical perspective on the production of engineered man-made bone grafts that are described as implantable tissue engineering therapeutics, and to highlight the importance of understanding bone composition and structure, as well as osteogenesis and bone healing processes, to improve the design and development of such implants. In addition, special emphasis is given to pharmaceutical aspects that are frequently minimized, but that, instead, may be useful for formulation developments and in vitro/in vivo correlations.

Genetic engineering for skeletal regenerative medicine.

PubMed

Gersbach, Charles A; Phillips, Jennifer E; García, Andrés J

2007-01-01

The clinical challenges of skeletal regenerative medicine have motivated significant advances in cellular and tissue engineering in recent years. In particular, advances in molecular biology have provided the tools necessary for the design of gene-based strategies for skeletal tissue repair. Consequently, genetic engineering has emerged as a promising method to address the need for sustained and robust cellular differentiation and extracellular matrix production. As a result, gene therapy has been established as a conventional approach to enhance cellular activities for skeletal tissue repair. Recent literature clearly demonstrates that genetic engineering is a principal factor in constructing effective methods for tissue engineering approaches to bone, cartilage, and connective tissue regeneration. This review highlights this literature, including advances in the development of efficacious gene carriers, novel cell sources, successful delivery strategies, and optimal target genes. The current status of the field and the challenges impeding the clinical realization of these approaches are also discussed.

New tools for non-invasive exploration of collagen network in cartilaginous tissue-engineered substitute.

PubMed

Henrionnet, Christel; Dumas, Dominique; Hupont, Sébastien; Stoltz, Jean François; Mainard, Didier; Gillet, Pierre; Pinzano, Astrid

2017-01-01

In tissue engineering approaches, the quality of substitutes is a key element to determine its ability to treat cartilage defects. However, in clinical practice, the evaluation of tissue-engineered cartilage substitute quality is not possible due to the invasiveness of the standard procedure, which is to date histology. The aim of this work was to validate a new innovative system performed from two-photon excitation laser adapted to an optical macroscope to evaluate at macroscopic scale the collagen network in cartilage tissue-engineered substitutes in confrontation with gold standard histologic techniques or immunohistochemistry to visualize type II collagen. This system permitted to differentiate the quality of collagen network between ITS and TGF-β1 treatments. Multiscale large field imaging combined to multimodality approaches (SHG-TCSPC) at macroscopical scale represent an innovative and non-invasive technique to monitor the quality of collagen network in cartilage tissue-engineered substitutes before in vivo implantation.

An exploratory survey on the views of European tissue engineers concerning the ethical issues of tissue engineering research.

PubMed

Trommelmans, Leen; Selling, Joseph; Dierickx, Kris

2009-09-01

We present the first exploratory survey about the views of tissue engineers on the ethical issues of tissue engineering (TE), conducted among participants of a large European TE consortium. We analyzed the topics for which ethical guidance is necessary and the preferred dissemination channels, which are relevant issues and goals of clinical trials with human tissue-engineered products, and which information is to be given to trial participants. The need for comprehensive, specific ethical guidance of TE is a first key finding of this survey. Second, it becomes clear that little clarity exists on some crucial issues in the setup and conduct of clinical trials in TE. Identifying the unique features of TE and their repercussions for the ethical conduct of TE research and therapy is necessary. Third, prospective trial participants are to be informed about a wide variety of issues before taking part in the trial.

Advances in pulmonary therapy and drug development: Lung tissue engineering to lung-on-a-chip.

PubMed

Doryab, Ali; Amoabediny, Ghassem; Salehi-Najafabadi, Amir

2016-01-01

Lung disease is one of the major causes of death, and the rate of pulmonary diseases has been increasing for decades. Although lung transplantation is the only treatment for majority of patients, this method has been limited due to lack of donors. Therefore, recently, attentions have increased to some new strategies with the aid of tissue engineering and microfluidics techniques not only for the functional analysis, but also for drug screening. In fact, in tissue engineering, the engineered tissue is able to grow by using the patient's own cells without intervention in the immune system. On the other hand, microfluidics devices are applied in order to evaluate drug screenings, function analysis and toxicity. This article reviews new advances in lung tissue engineering and lung-on-a-chip. Furthermore, future directions, difficulties and drawbacks of pulmonary therapy in these areas are discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

Metallic Scaffolds for Bone Regeneration

PubMed Central

Alvarez, Kelly; Nakajima, Hideo

2009-01-01

Bone tissue engineering is an emerging interdisciplinary field in Science, combining expertise in medicine, material science and biomechanics. Hard tissue engineering research is focused mainly in two areas, osteo and dental clinical applications. There is a lot of exciting research being performed worldwide in developing novel scaffolds for tissue engineering. Although, nowadays the majority of the research effort is in the development of scaffolds for non-load bearing applications, primarily using soft natural or synthetic polymers or natural scaffolds for soft tissue engineering; metallic scaffolds aimed for hard tissue engineering have been also the subject of in vitro and in vivo research and industrial development. In this article, descriptions of the different manufacturing technologies available to fabricate metallic scaffolds and a compilation of the reported biocompatibility of the currently developed metallic scaffolds have been performed. Finally, we highlight the positive aspects and the remaining problems that will drive future research in metallic constructs aimed for the reconstruction and repair of bone.

In vitro bone formation using muscle-derived cells: a new paradigm for bone tissue engineering using polymer-bone morphogenetic protein matrices.

PubMed

Lu, Helen H; Kofron, Michelle D; El-Amin, Saadiq F; Attawia, Mohammed A; Laurencin, Cato T

2003-06-13

Over 800,000 bone grafting procedures are performed in the United States annually, creating a demand for viable alternatives to autogenous bone, the grafting standard in osseous repair. The objective of this study was to examine the efficacy of a BMP-polymer matrix in inducing the expression of the osteoblastic phenotype and in vitro bone formation by muscle-derived cells. Specifically, we evaluated the ability of bone morphogenetic protein-7 (BMP-7), delivered from a poly(lactide-co-glycolide) (PLAGA) matrix, to induce the differentiation of cells derived from rabbit skeletal muscle into osteoblast-like cells and subsequently form mineralized tissue. Results confirmed that muscle-derived cells attached and proliferated on the PLAGA substrates. BMP-7 released from PLAGA induced the muscle-derived cells to increase bone marker expression and form mineralized cultures. These results demonstrate the efficacy of a BMP-polymer matrix in inducing the expression of the osteoblastic phenotype by muscle-derived cells and present a new paradigm for bone tissue engineering.

Multiscale Mathematical Modeling in Dental Tissue Engineering: Toward Computer-Aided Design of a Regenerative System Based on Hydroxyapatite Granules, Focussing on Early and Mid-Term Stiffness Recovery

PubMed Central

Scheiner, Stefan; Komlev, Vladimir S.; Gurin, Alexey N.; Hellmich, Christian

2016-01-01

We here explore for the very first time how an advanced multiscale mathematical modeling approach may support the design of a provenly successful tissue engineering concept for mandibular bone. The latter employs double-porous, potentially cracked, single millimeter-sized granules packed into an overall conglomerate-type scaffold material, which is then gradually penetrated and partially replaced by newly grown bone tissue. During this process, the newly developing scaffold-bone compound needs to attain the stiffness of mandibular bone under normal physiological conditions. In this context, the question arises how the compound stiffness is driven by the key design parameters of the tissue engineering system: macroporosity, crack density, as well as scaffold resorption/bone formation rates. We here tackle this question by combining the latest state-of-the-art mathematical modeling techniques in the field of multiscale micromechanics, into an unprecedented suite of highly efficient, semi-analytically defined computation steps resolving several levels of hierarchical organization, from the millimeter- down to the nanometer-scale. This includes several types of homogenization schemes, namely such for porous polycrystals with elongated solid elements, for cracked matrix-inclusion composites, as well as for assemblies of coated spherical compounds. Together with the experimentally known stiffnesses of hydroxyapatite crystals and mandibular bone tissue, the new mathematical model suggests that early stiffness recovery (i.e., within several weeks) requires total avoidance of microcracks in the hydroxyapatite scaffolds, while mid-term stiffness recovery (i.e., within several months) is additionally promoted by provision of small granule sizes, in combination with high bone formation and low scaffold resorption rates. PMID:27708584

A novel axial-stress bioreactor system combined with a substance exchanger for tissue engineering of 3D constructs.

PubMed

Li, Song-Tao; Liu, Yong; Zhou, Qiang; Lue, Ren-Fa; Song, Lei; Dong, Shi-Wu; Guo, Ping; Kopjar, Branko

2014-03-01

This study introduced a prototype of an axial-stress bioreactor system that supports long-term growth and development of engineered tissues. The main features of this bioreactor are an integrated substance exchanger and feedback control of pH and PO₂. A 21-day study was conducted to validate the system's ability to maintain a stable environment, while remaining sterile. Our results showed that the pH, PO₂, and nutrient (glucose) remained balanced at appropriate levels, while metabolic waste (lactic acid) was removed. No bacteria or fungi were detected in the system or tissue; thus, demonstrating that it was sterile. These data indicate the bioreactor's strong potential for long-term tissue culture. To explore this idea, the effect of dynamic culture, including cyclic compression and automatic substance exchange, on mouse bone-marrow mesenchymal stem cells (BMSCs) seeded in decalcified bone matrix was studied using the bioreactor prototype. Histological sections of the engineered tissues showed higher cell densities in scaffolds in dynamic culture compared to those in static culture, while cell cycle analysis showed that dynamic culture promoted BMSC proliferation (proliferation index, PI=34.02±1.77) more effectively than static culture (PI=26.66±1.81). The results from a methyl thiazolyl tetrazolium assay were consistent with the loading experimental data. Furthermore, elevated alkaline phosphatase activity and calcium content were observed in dynamic condition compared to static culture. In conclusion, this bioreactor system supplies a method of modulating the pH and PO₂ in defined ranges with only small fluctuations; it can be used as a physiological or pathological analog. Automatic control of the environment is a practical solution for long-term, steady-state culture for future commercialization.

Surface functionalization of nanobiomaterials for application in stem cell culture, tissue engineering, and regenerative medicine.

PubMed

Rana, Deepti; Ramasamy, Keerthana; Leena, Maria; Jiménez, Constanza; Campos, Javier; Ibarra, Paula; Haidar, Ziyad S; Ramalingam, Murugan

2016-05-01

Stem cell-based approaches offer great application potential in tissue engineering and regenerative medicine owing to their ability of sensing the microenvironment and respond accordingly (dynamic behavior). Recently, the combination of nanobiomaterials with stem cells has paved a great way for further exploration. Nanobiomaterials with engineered surfaces could mimic the native microenvironment to which the seeded stem cells could adhere and migrate. Surface functionalized nanobiomaterial-based scaffolds could then be used to regulate or control the cellular functions to culture stem cells and regenerate damaged tissues or organs. Therefore, controlling the interactions between nanobiomaterials and stem cells is a critical factor. However, surface functionalization or modification techniques has provided an alternative approach for tailoring the nanobiomaterials surface in accordance to the physiological surrounding of a living cells; thereby, enhancing the structural and functional properties of the engineered tissues and organs. Currently, there are a variety of methods and technologies available to modify the surface of biomaterials according to the specific cell or tissue properties to be regenerated. This review highlights the trends in surface modification techniques for nanobiomaterials and the biological relevance in stem cell-based tissue engineering and regenerative medicine. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:554-567, 2016. © 2016 American Institute of Chemical Engineers.

Development of hydrogels for regenerative engineering.

PubMed

Guan, Xiaofei; Avci-Adali, Meltem; Alarçin, Emine; Cheng, Hao; Kashaf, Sara Saheb; Li, Yuxiao; Chawla, Aditya; Jang, Hae Lin; Khademhosseini, Ali

2017-05-01

The aim of regenerative engineering is to restore complex tissues and biological systems through convergence in the fields of advanced biomaterials, stem cell science, and developmental biology. Hydrogels are one of the most attractive biomaterials for regenerative engineering, since they can be engineered into tissue mimetic 3D scaffolds to support cell growth due to their similarity to native extracellular matrix. Advanced nano- and micro-technologies have dramatically increased the ability to control properties and functionalities of hydrogel materials by facilitating biomimetic fabrication of more sophisticated compositions and architectures, thus extending our understanding of cell-matrix interactions at the nanoscale. With this perspective, this review discusses the most commonly used hydrogel materials and their fabrication strategies for regenerative engineering. We highlight the physical, chemical, and functional modulation of hydrogels to design and engineer biomimetic tissues based on recent achievements in nano- and micro-technologies. In addition, current hydrogel-based regenerative engineering strategies for treating multiple tissues, such as musculoskeletal, nervous and cardiac tissue, are also covered in this review. The interaction of multiple disciplines including materials science, cell biology, and chemistry, will further play an important role in the design of functional hydrogels for the regeneration of complex tissues. Copyright © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Adult mesenchymal stem cells and cell-based tissue engineering

PubMed Central

Tuan, Rocky S; Boland, Genevieve; Tuli, Richard

2003-01-01

The identification of multipotential mesenchymal stem cells (MSCs) derived from adult human tissues, including bone marrow stroma and a number of connective tissues, has provided exciting prospects for cell-based tissue engineering and regeneration. This review focuses on the biology of MSCs, including their differentiation potentials in vitro and in vivo, and the application of MSCs in tissue engineering. Our current understanding of MSCs lags behind that of other stem cell types, such as hematopoietic stem cells. Future research should aim to define the cellular and molecular fingerprints of MSCs and elucidate their endogenous role(s) in normal and abnormal tissue functions. PMID:12716446

Different methods of dentin processing for application in bone tissue engineering: A systematic review.

PubMed

Tabatabaei, Fahimeh Sadat; Tatari, Saeed; Samadi, Ramin; Moharamzadeh, Keyvan

2016-10-01

Dentin has become an interesting potential biomaterial for tissue engineering of oral hard tissues. It can be used as a scaffold or as a source of growth factors in bone tissue engineering. Different forms of dentin have been studied for their potential use as bone substitutes. Here, we systematically review different methods of dentin preparation and the efficacy of processed dentin in bone tissue engineering. An electronic search was carried out in PubMed and Scopus databases for articles published from 2000 to 2016. Studies on dentin preparation for application in bone tissue engineering were selected. The initial search yielded a total of 1045 articles, of which 37 were finally selected. Review of studies showed that demineralization was the most commonly used dentin preparation process for use in tissue engineering. Dentin extract, dentin particles (tooth ash), freeze-dried dentin, and denatured dentin are others method of dentin preparation. Based on our literature review, we can conclude that preparation procedure and the size and shape of dentin particles play an important role in its osteoinductive and osteoconductive properties. Standardization of these methods is important to draw a conclusion in this regard. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2616-2627, 2016. © 2016 Wiley Periodicals, Inc.

A comparative study of the chondrogenic potential between synthetic and natural scaffolds in an in vivo bioreactor

NASA Astrophysics Data System (ADS)

Huang, Jung-Ju; Yang, Shu-Rui; Chu, I.-Ming; Brey, Eric M.; Hsiao, Hui-Yi; Cheng, Ming-Huei

2013-10-01

The clinical demand for cartilage tissue engineering is potentially large for reconstruction defects resulting from congenital deformities or degenerative disease due to limited donor sites for autologous tissue and donor site morbidities. Cartilage tissue engineering has been successfully applied to the medical field: a scaffold pre-cultured with chondrocytes was used prior to implantation in an animal model. We have developed a surgical approach in which tissues are engineered by implantation with a vascular pedicle as an in vivo bioreactor in bone and adipose tissue engineering. Collagen type II, chitosan, poly(lactic-co-glycolic acid) (PLGA) and polycaprolactone (PCL) were four commonly applied scaffolds in cartilage tissue engineering. To expand the application of the same animal model in cartilage tissue engineering, these four scaffolds were selected and compared for their ability to generate cartilage with chondrocytes in the same model with an in vivo bioreactor. Gene expression and immunohistochemistry staining methods were used to evaluate the chondrogenesis and osteogenesis of specimens. The result showed that the PLGA and PCL scaffolds exhibited better chondrogenesis than chitosan and type II collagen in the in vivo bioreactor. Among these four scaffolds, the PCL scaffold presented the most significant result of chondrogenesis embedded around the vascular pedicle in the long-term culture incubation phase.

Tissue engineered constructs for peripheral nerve surgery

PubMed Central

Johnson, P. J.; Wood, M. D.; Moore, A. M.; Mackinnon, S. E.

2013-01-01

Summary Background Tissue engineering has been defined as “an interdisciplinary field that applies the principles of engineering and life sciences toward the development of biological substitutes that restore, maintain, or improve tissue function or a whole organ”. Traumatic peripheral nerve injury resulting in significant tissue loss at the zone of injury necessitates the need for a bridge or scaffold for regenerating axons from the proximal stump to reach the distal stump. Methods A review of the literature was used to provide information on the components necessary for the development of a tissue engineered peripheral nerve substitute. Then, a comprehensive review of the literature is presented composed of the studies devoted to this goal. Results Extensive research has been directed toward the development of a tissue engineered peripheral nerve substitute to act as a bridge for regenerating axons from the proximal nerve stump seeking the distal nerve. Ideally this nerve substitute would consist of a scaffold component that mimics the extracellular matrix of the peripheral nerve and a cellular component that serves to stimulate and support regenerating peripheral nerve axons. Conclusions The field of tissue engineering should consider its challenge to not only meet the autograft “gold standard” but also to understand what drives and inhibits nerve regeneration in order to surpass the results of an autograft. PMID:24385980

Interdigitated array of Pt electrodes for electrical stimulation and engineering of aligned muscle tissue.

PubMed

Ahadian, Samad; Ramón-Azcón, Javier; Ostrovidov, Serge; Camci-Unal, Gulden; Hosseini, Vahid; Kaji, Hirokazu; Ino, Kosuke; Shiku, Hitoshi; Khademhosseini, Ali; Matsue, Tomokazu

2012-09-21

Engineered skeletal muscle tissues could be useful for applications in tissue engineering, drug screening, and bio-robotics. It is well-known that skeletal muscle cells are able to differentiate under electrical stimulation (ES), with an increase in myosin production, along with the formation of myofibers and contractile proteins. In this study, we describe the use of an interdigitated array of electrodes as a novel platform to electrically stimulate engineered muscle tissues. The resulting muscle myofibers were analyzed and quantified in terms of their myotube characteristics and gene expression. The engineered muscle tissues stimulated through the interdigitated array of electrodes demonstrated superior performance and maturation compared to the corresponding tissues stimulated through a conventional setup (i.e., through Pt wires in close proximity to the muscle tissue). In particular, the ES of muscle tissue (voltage 6 V, frequency 1 Hz and duration 10 ms for 1 day) through the interdigitated array of electrodes resulted in a higher degree of C2C12 myotube alignment (∼80%) as compared to ES using Pt wires (∼65%). In addition, higher amounts of C2C12 myotube coverage area, myotube length, muscle transcription factors and protein biomarkers were found for myotubes stimulated through the interdigitated array of electrodes compared to those stimulated using the Pt wires. Due to the wide array of potential applications of ES for two- and three-dimensional (2D and 3D) engineered tissues, the suggested platform could be employed for a variety of cell and tissue structures to more efficiently investigate their response to electrical fields.

Scaffold-based Anti-infection Strategies in Bone Repair

PubMed Central

Johnson, Christopher T.; García, Andrés J.

2014-01-01

Bone fractures and non-union defects often require surgical intervention where biomaterials are used to correct the defect, and approximately 10% of these procedures are compromised by bacterial infection. Currently, treatment options are limited to sustained, high doses of antibiotics and surgical debridement of affected tissue, leaving a significant, unmet need for the development of therapies to combat device-associated biofilm and infections. Engineering implants to prevent infection is a desirable material characteristic. Tissue engineered scaffolds for bone repair provide a means to both regenerate bone and serve as a base for adding antimicrobial agents. Incorporating anti-infection properties into regenerative medicine therapies could improve clinical outcomes and reduce the morbidity and mortality associated with biomaterial implant-associated infections. This review focuses on current animal models and technologies available to assess bone repair in the context of infection, antimicrobial agents to fight infection, the current state of antimicrobial scaffolds, and future directions in the field. PMID:25476163

Ultraporous, Compressible, Wettable Polylactide/Polycaprolactone Sponges for Tissue Engineering.

PubMed

Mader, Michael; Jérôme, Valérie; Freitag, Ruth; Agarwal, Seema; Greiner, Andreas

2018-05-14

Ultraporous, degradable sponges made of either polylactide or of blends of polylactide/poly(ε-caprolactone) are prepared by freeze-drying of dispersions of short electrospun fibers and subsequent thermal annealing. The sponges feature ultrahigh porosity (99.6%), a hierarchical cellular structure, and high reversible compressibility with fast recovery from deformation in the dry as well as in the wet state. The sponge properties depend on the fiber dispersion concentration and the annealing temperature. Sponge characteristics like fiber density (2.5-20 mg/cm 3 ), size, shape, crystallinity, mechanical strength, wetability, and structural integrity are user adjustable. Cell culture experiments were successfully performed with Jurkat cells with Confocal Laser Scanning Microscopy and MTT staining showing rapid cell proliferation. Live/Dead staining demonstrated high viability of the seeded cells. The sponge characteristics and modifications investigated and presented here reveal that these sponges are highly promising for tissue engineering applications.

Application of cell and biomaterial-based tissue engineering methods in the treatment of cartilage, menisci and ligament injuries.

PubMed

Trzeciak, Tomasz; Richter, Magdalena; Suchorska, Wiktoria; Augustyniak, Ewelina; Lach, Michał; Kaczmarek, Małgorzata; Kaczmarczyk, Jacek

2016-03-01

Over 20 years ago it was realized that the traditional methods of the treatment of injuries to joint components: cartilage, menisci and ligaments, did not give satisfactory results and so there is a need of employing novel, more effective therapeutic techniques. Recent advances in molecular biology, biotechnology and polymer science have led to both the experimental and clinical application of various cell types, adapting their culture conditions in order to ensure a directed differentiation of the cells into a desired cell type, and employing non-toxic and non-immunogenic biomaterial in the treatment of knee joint injuries. In the present review the current state of knowledge regarding novel cell sources, in vitro conditions of cell culture and major important biomaterials, both natural and synthetic, used in cartilage, meniscus and ligament repair by tissue engineering techniques are described, and the assets and drawbacks of their clinical application are critically evaluated.

Harnessing cell–biomaterial interactions for osteochondral tissue regeneration.

PubMed

Kim, Kyobum; Yoon, Diana M; Mikos, Antonios; Kasper, F Kurtis

2012-01-01

Articular cartilage that is damaged or diseased often requires surgical intervention to repair the tissue; therefore, tissue engineering strategies have been developed to aid in cartilage regeneration. Tissue engineering approaches often require the integration of cells, biomaterials, and growth factors to direct and support tissue formation. A variety of cell types have been isolated from adipose, bone marrow, muscle, and skin tissue to promote cartilage regeneration. The interaction of cells with each other and with their surrounding environment has been shown to play a key role in cartilage engineering. In tissue engineering approaches, biomaterials are commonly used to provide an initial framework for cell recruitment and proliferation and tissue formation. Modifications of the properties of biomaterials, such as creating sites for cell binding, altering their physicochemical characteristics, and regulating the delivery of growth factors, can have a significant influence on chondrogenesis. Overall, the goal is to completely restore healthy cartilage within an articular cartilage defect. This chapter aims to provide information about the importance of cell–biomaterial interactions for the chondrogenic differentiation of various cell populations that can eventually produce functional cartilage matrix that is indicative of healthy cartilage tissue.

Design and fabrication of porous biodegradable scaffolds: a strategy for tissue engineering.

PubMed

Raeisdasteh Hokmabad, Vahideh; Davaran, Soodabeh; Ramazani, Ali; Salehi, Roya

2017-11-01

Current strategies of tissue engineering are focused on the reconstruction and regeneration of damaged or deformed tissues by grafting of cells with scaffolds and biomolecules. Recently, much interest is given to scaffolds which are based on mimic the extracellular matrix that have induced the formation of new tissues. To return functionality of the organ, the presence of a scaffold is essential as a matrix for cell colonization, migration, growth, differentiation and extracellular matrix deposition, until the tissues are totally restored or regenerated. A wide variety of approaches has been developed either in scaffold materials and production procedures or cell sources and cultivation techniques to regenerate the tissues/organs in tissue engineering applications. This study has been conducted to present an overview of the different scaffold fabrication techniques such as solvent casting and particulate leaching, electrospinning, emulsion freeze-drying, thermally induced phase separation, melt molding and rapid prototyping with their properties, limitations, theoretical principles and their prospective in tailoring appropriate micro-nanostructures for tissue regeneration applications. This review also includes discussion on recent works done in the field of tissue engineering.

Motivation, characterization, and strategy for tissue engineering the temporomandibular joint disc.

PubMed

Detamore, Michael S; Athanasiou, Kyriacos A

2003-12-01

The purpose of this review is to serve as the standard point of reference in guiding researchers investigating the tissue engineering of the temporomandibular joint (TMJ) disc. Tissue engineering of the TMJ disc is in its infancy, and currently there exists a gap between the tissue engineering community and the TMJ characterization community. The primary goal is to help bridge that gap by consolidating the characterization studies here as a reference to researchers attempting to tissue engineer the TMJ disc. A brief review of TMJ anatomy is provided, along with a description of relevant pathology, current treatment, and a rationale for engineering the TMJ disc. The biochemical composition and organization of the disc are reviewed, including glycosaminoglycan (GAG) and collagen content. The collagen of the disc is almost exclusively type I and primarily runs anteroposteriorly through the center and in a ringlike fashion around the periphery. The GAG content is approximately an order of magnitude less than that of hyaline cartilage, and although the distribution is not entirely clear, it seems as though chondroitin and dermatan sulfate are by far the primary GAGs. Cellular characterization and mechanical properties under compression, tension, and shear are reviewed as well. The cells of the disc are not chondrocytes, but rather resemble fibrocytes and fibrochondrocytes and may be of the same lineage. Mechanically, the disc is certainly anisotropic and nonhomogeneous. Finally, a review of efforts in tissue engineering and cell culture studies of the disc is provided and we close with a description of the direction we envision/propose for successful tissue engineering of the TMJ disc.

Microscale Technologies and Modular Approaches for Tissue Engineering: Moving toward the Fabrication of Complex Functional Structures

PubMed Central

Gauvin, Robert; Khademhosseini, Ali

2011-01-01

Micro- and nanoscale technologies have emerged as powerful tools in the fabrication of engineered tissues and organs. Here we focus on the application of these techniques to improve engineered tissue architecture and function using modular and directed self-assembly and highlight the emergence of this new class of materials for biomedical applications. PMID:21627163

Metallic ions as therapeutic agents in tissue engineering scaffolds: an overview of their biological applications and strategies for new developments

PubMed Central

Mouriño, Viviana; Cattalini, Juan Pablo; Boccaccini, Aldo R.

2012-01-01

This article provides an overview on the application of metallic ions in the fields of regenerative medicine and tissue engineering, focusing on their therapeutic applications and the need to design strategies for controlling the release of loaded ions from biomaterial scaffolds. A detailed summary of relevant metallic ions with potential use in tissue engineering approaches is presented. Remaining challenges in the field and directions for future research efforts with focus on the key variables needed to be taken into account when considering the controlled release of metallic ions in tissue engineering therapeutics are also highlighted. PMID:22158843

Review: Polymeric-Based 3D Printing for Tissue Engineering.

PubMed

Wu, Geng-Hsi; Hsu, Shan-Hui

Three-dimensional (3D) printing, also referred to as additive manufacturing, is a technology that allows for customized fabrication through computer-aided design. 3D printing has many advantages in the fabrication of tissue engineering scaffolds, including fast fabrication, high precision, and customized production. Suitable scaffolds can be designed and custom-made based on medical images such as those obtained from computed tomography. Many 3D printing methods have been employed for tissue engineering. There are advantages and limitations for each method. Future areas of interest and progress are the development of new 3D printing platforms, scaffold design software, and materials for tissue engineering applications.

Progress and opportunities for tissue-engineered skin

NASA Astrophysics Data System (ADS)

MacNeil, Sheila

2007-02-01

Tissue-engineered skin is now a reality. For patients with extensive full-thickness burns, laboratory expansion of skin cells to achieve barrier function can make the difference between life and death, and it was this acute need that drove the initiation of tissue engineering in the 1980s. A much larger group of patients have ulcers resistant to conventional healing, and treatments using cultured skin cells have been devised to restart the wound-healing process. In the laboratory, the use of tissue-engineered skin provides insight into the behaviour of skin cells in healthy skin and in diseases such as vitiligo, melanoma, psoriasis and blistering disorders.

Application of conductive polymers, scaffolds and electrical stimulation for nerve tissue engineering.

PubMed

Ghasemi-Mobarakeh, Laleh; Prabhakaran, Molamma P; Morshed, Mohammad; Nasr-Esfahani, Mohammad Hossein; Baharvand, Hossein; Kiani, Sahar; Al-Deyab, Salem S; Ramakrishna, Seeram

2011-04-01

Among the numerous attempts to integrate tissue engineering concepts into strategies to repair nearly all parts of the body, neuronal repair stands out. This is partially due to the complexity of the nervous anatomical system, its functioning and the inefficiency of conventional repair approaches, which are based on single components of either biomaterials or cells alone. Electrical stimulation has been shown to enhance the nerve regeneration process and this consequently makes the use of electrically conductive polymers very attractive for the construction of scaffolds for nerve tissue engineering. In this review, by taking into consideration the electrical properties of nerve cells and the effect of electrical stimulation on nerve cells, we discuss the most commonly utilized conductive polymers, polypyrrole (PPy) and polyaniline (PANI), along with their design and modifications, thus making them suitable scaffolds for nerve tissue engineering. Other electrospun, composite, conductive scaffolds, such as PANI/gelatin and PPy/poly(ε-caprolactone), with or without electrical stimulation, are also discussed. Different procedures of electrical stimulation which have been used in tissue engineering, with examples on their specific applications in tissue engineering, are also discussed. Copyright © 2011 John Wiley & Sons, Ltd.

Research progress on reconstruction of meniscus in tissue engineering.

PubMed

Zhang, Yu; Li, Pengsong; Wang, Hai; Wang, Yiwei; Song, Kedong; Li, Tianqing

2017-05-01

Meniscus damages are most common in sports injuries and aged knees. One third of meniscus lesions are known as white-white zone or nonvascular zones, which are composed of chondrocyte and extracellular matrix composition only. Due to low vascularization the ability of regeneration in such zones is inherently limited, leading to impossible self-regeneration post damage. Meniscus tissue engineering is known for emerging techniques for treating meniscus damage, but there are questions that need to be answered, including an optimal and suitable cell source, the usability of growth factor, the selectivity of optimal biomaterial scaffolds as well as the technology for improving partial reconstruction of meniscus tears. This review focuses on current research on the in vitro reconstruction of the meniscus using tissue engineering methods with the expectation to develop a series of tissue engineering meniscus products for the benefit of sports injuries. With rapid growth of clinical demand, the key breakthrough of meniscus tissue engineering research foundation is enlarged to a great extent. This review discusses aspects of meniscus tissue engineering, which is relative to the clinical treatment of meniscus injuries for further support and establishment of fundamental and clinical studies.

Cartilage engineering in reconstructive surgery: auricular, nasal and tracheal engineering from a surgical perspective.

PubMed

Wiggenhauser, Paul Severin; Schantz, Jan Thorsten; Rotter, Nicole

2017-04-01

This review provides an update on cartilage tissue engineering with particular focus on the head and neck. It is aimed at scientists and clinicians who are interested in tissue engineering and its clinical applicability. Principal tissue engineering strategies are summarized in the first part of this review. In the second part, current clinical approaches to auricular, nasal and tracheal reconstruction are discussed from a surgical perspective. By this approach, the requirements for clinical applicability are outlined and new insight into relevant aims of research is given to accelerate the transfer from bench to bedside.

Engineering β-sheet peptide assemblies for biomedical applications.

PubMed

Yu, Zhiqiang; Cai, Zheng; Chen, Qiling; Liu, Menghua; Ye, Ling; Ren, Jiaoyan; Liao, Wenzhen; Liu, Shuwen

2016-03-01

Hydrogels have been widely studied in various biomedical applications, such as tissue engineering, cell culture, immunotherapy and vaccines, and drug delivery. Peptide-based nanofibers represent a promising new strategy for current drug delivery approaches and cell carriers for tissue engineering. This review focuses on the recent advances in the use of self-assembling engineered β-sheet peptide assemblies for biomedical applications. The applications of peptide nanofibers in biomedical fields, such as drug delivery, tissue engineering, immunotherapy, and vaccines, are highlighted. The current challenges and future perspectives for self-assembling peptide nanofibers in biomedical applications are discussed.

[Progress in application of 3D bioprinting in cartilage regeneration and reconstruction for tissue engineering].

PubMed

Liao, Junlin; Wang, Shaohua; Chen, Jia; Xie, Hongju; Zhou, Jianda

2017-02-28

Three-dimensional (3D) bioprinting provides an advanced technology for tissue engineering and regenerative medicine because of its ability to produce the models or organs with higher precision and more suitable for human body. It has been successfully used to produce a variety of cartilage scaffold materials. In addition, 3D bioprinter can directly to print tissue and organs with live chondrocytes. In conclusion, 3D bioprinting may have broad prospect for cartilage regeneration and reconstruction in tissue engineering.

A review of fibrin and fibrin composites for bone tissue engineering

PubMed Central

Noori, Alireza; Ashrafi, Seyed Jamal; Vaez-Ghaemi, Roza; Hatamian-Zaremi, Ashraf; Webster, Thomas J

2017-01-01

Tissue engineering has emerged as a new treatment approach for bone repair and regeneration seeking to address limitations associated with current therapies, such as autologous bone grafting. While many bone tissue engineering approaches have traditionally focused on synthetic materials (such as polymers or hydrogels), there has been a lot of excitement surrounding the use of natural materials due to their biologically inspired properties. Fibrin is a natural scaffold formed following tissue injury that initiates hemostasis and provides the initial matrix useful for cell adhesion, migration, proliferation, and differentiation. Fibrin has captured the interest of bone tissue engineers due to its excellent biocompatibility, controllable biodegradability, and ability to deliver cells and biomolecules. Fibrin is particularly appealing because its precursors, fibrinogen, and thrombin, which can be derived from the patient’s own blood, enable the fabrication of completely autologous scaffolds. In this article, we highlight the unique properties of fibrin as a scaffolding material to treat bone defects. Moreover, we emphasize its role in bone tissue engineering nanocomposites where approaches further emulate the natural nanostructured features of bone when using fibrin and other nanomaterials. We also review the preparation methods of fibrin glue and then discuss a wide range of fibrin applications in bone tissue engineering. These include the delivery of cells and/or biomolecules to a defect site, distributing cells, and/or growth factors throughout other pre-formed scaffolds and enhancing the physical as well as biological properties of other biomaterials. Thoughts on the future direction of fibrin research for bone tissue engineering are also presented. In the future, the development of fibrin precursors as recombinant proteins will solve problems associated with using multiple or single-donor fibrin glue, and the combination of nanomaterials that allow for the incorporation of biomolecules with fibrin will significantly improve the efficacy of fibrin for numerous bone tissue engineering applications. PMID:28761338

A review of fibrin and fibrin composites for bone tissue engineering.

PubMed

Noori, Alireza; Ashrafi, Seyed Jamal; Vaez-Ghaemi, Roza; Hatamian-Zaremi, Ashraf; Webster, Thomas J

2017-01-01

Tissue engineering has emerged as a new treatment approach for bone repair and regeneration seeking to address limitations associated with current therapies, such as autologous bone grafting. While many bone tissue engineering approaches have traditionally focused on synthetic materials (such as polymers or hydrogels), there has been a lot of excitement surrounding the use of natural materials due to their biologically inspired properties. Fibrin is a natural scaffold formed following tissue injury that initiates hemostasis and provides the initial matrix useful for cell adhesion, migration, proliferation, and differentiation. Fibrin has captured the interest of bone tissue engineers due to its excellent biocompatibility, controllable biodegradability, and ability to deliver cells and biomolecules. Fibrin is particularly appealing because its precursors, fibrinogen, and thrombin, which can be derived from the patient's own blood, enable the fabrication of completely autologous scaffolds. In this article, we highlight the unique properties of fibrin as a scaffolding material to treat bone defects. Moreover, we emphasize its role in bone tissue engineering nanocomposites where approaches further emulate the natural nanostructured features of bone when using fibrin and other nanomaterials. We also review the preparation methods of fibrin glue and then discuss a wide range of fibrin applications in bone tissue engineering. These include the delivery of cells and/or biomolecules to a defect site, distributing cells, and/or growth factors throughout other pre-formed scaffolds and enhancing the physical as well as biological properties of other biomaterials. Thoughts on the future direction of fibrin research for bone tissue engineering are also presented. In the future, the development of fibrin precursors as recombinant proteins will solve problems associated with using multiple or single-donor fibrin glue, and the combination of nanomaterials that allow for the incorporation of biomolecules with fibrin will significantly improve the efficacy of fibrin for numerous bone tissue engineering applications.

Current Therapeutic Strategies for Adipose Tissue Defects/Repair Using Engineered Biomaterials and Biomolecule Formulations.

PubMed

Mahoney, Christopher M; Imbarlina, Cayla; Yates, Cecelia C; Marra, Kacey G

2018-01-01

Tissue engineered scaffolds for adipose restoration/repair has significantly evolved in recent years. Patients requiring soft tissue reconstruction, caused by defects or pathology, require biomaterials that will restore void volume with new functional tissue. The gold standard of autologous fat grafting (AFG) is not a reliable option. This review focuses on the latest therapeutic strategies for the treatment of adipose tissue defects using biomolecule formulations and delivery, and specifically engineered biomaterials. Additionally, the clinical need for reliable off-the-shelf therapies, animal models, and challenges facing current technologies are discussed.

Cell culture-based tissue engineering as an alternative to bone grafts in implant dentistry: a literature review.

PubMed

Boeckel, Daniel Gonçalves; Shinkai, Rosemary Sadami Arai; Grossi, Márcio Lima; Teixeira, Eduardo Rolim

2012-09-01

Several biomaterials and techniques for bone grafting have been described in the literature for atresic bone tissue replacement caused by edentulism, surgical resectioning, and traumas. A new technique involves tissue engineering, a promising option to replace bone tissue and solve problems associated with morbidity of autogenous grafting. This literature review aims to describe tissue-engineering techniques using ex vivo cell culture as an alternative to repair bone maxillary atresias and discuss the concepts and potentials of bone regeneration through cell culture techniques as an option for restorative maxillofacial surgery.

Engineering on the straight and narrow: the mechanics of nanofibrous assemblies for fiber-reinforced tissue regeneration.

PubMed

Mauck, Robert L; Baker, Brendon M; Nerurkar, Nandan L; Burdick, Jason A; Li, Wan-Ju; Tuan, Rocky S; Elliott, Dawn M

2009-06-01

Tissue engineering of fibrous tissues of the musculoskeletal system represents a considerable challenge because of the complex architecture and mechanical properties of the component structures. Natural healing processes in these dense tissues are limited as a result of the mechanically challenging environment of the damaged tissue and the hypocellularity and avascular nature of the extracellular matrix. When healing does occur, the ordered structure of the native tissue is replaced with a disorganized fibrous scar with inferior mechanical properties, engendering sites that are prone to re-injury. To address the engineering of such tissues, we and others have adopted a structurally motivated approach based on organized nanofibrous assemblies. These scaffolds are composed of ultrafine polymeric fibers that can be fabricated in such a way to recreate the structural anisotropy typical of fiber-reinforced tissues. This straight-and-narrow topography not only provides tailored mechanical properties, but also serves as a 3D biomimetic micropattern for directed tissue formation. This review describes the underlying technology of nanofiber production and focuses specifically on the mechanical evaluation and theoretical modeling of these structures as it relates to native tissue structure and function. Applying the same mechanical framework for understanding native and engineered fiber-reinforced tissues provides a functional method for evaluating the utility and maturation of these unique engineered constructs. We further describe several case examples where these principles have been put to test, and discuss the remaining challenges and opportunities in forwarding this technology toward clinical implementation.

Engineering on the Straight and Narrow: The Mechanics of Nanofibrous Assemblies for Fiber-Reinforced Tissue Regeneration

PubMed Central

Baker, Brendon M.; Nerurkar, Nandan L.; Burdick, Jason A.; Li, Wan-Ju; Tuan, Rocky S.; Elliott, Dawn M.

2009-01-01

Tissue engineering of fibrous tissues of the musculoskeletal system represents a considerable challenge because of the complex architecture and mechanical properties of the component structures. Natural healing processes in these dense tissues are limited as a result of the mechanically challenging environment of the damaged tissue and the hypocellularity and avascular nature of the extracellular matrix. When healing does occur, the ordered structure of the native tissue is replaced with a disorganized fibrous scar with inferior mechanical properties, engendering sites that are prone to re-injury. To address the engineering of such tissues, we and others have adopted a structurally motivated approach based on organized nanofibrous assemblies. These scaffolds are composed of ultrafine polymeric fibers that can be fabricated in such a way to recreate the structural anisotropy typical of fiber-reinforced tissues. This straight-and-narrow topography not only provides tailored mechanical properties, but also serves as a 3D biomimetic micropattern for directed tissue formation. This review describes the underlying technology of nanofiber production and focuses specifically on the mechanical evaluation and theoretical modeling of these structures as it relates to native tissue structure and function. Applying the same mechanical framework for understanding native and engineered fiber-reinforced tissues provides a functional method for evaluating the utility and maturation of these unique engineered constructs. We further describe several case examples where these principles have been put to test, and discuss the remaining challenges and opportunities in forwarding this technology toward clinical implementation. PMID:19207040

The Impact of Biomechanics in Tissue Engineering and Regenerative Medicine

PubMed Central

Butler, David L.; Goldstein, Steven A.; Guo, X. Edward; Kamm, Roger; Laurencin, Cato T.; McIntire, Larry V.; Mow, Van C.; Nerem, Robert M.; Sah, Robert L.; Soslowsky, Louis J.; Spilker, Robert L.; Tranquillo, Robert T.

2009-01-01

Biomechanical factors profoundly influence the processes of tissue growth, development, maintenance, degeneration, and repair. Regenerative strategies to restore damaged or diseased tissues in vivo and create living tissue replacements in vitro have recently begun to harness advances in understanding of how cells and tissues sense and adapt to their mechanical environment. It is clear that biomechanical considerations will be fundamental to the successful development of clinical therapies based on principles of tissue engineering and regenerative medicine for a broad range of musculoskeletal, cardiovascular, craniofacial, skin, urinary, and neural tissues. Biomechanical stimuli may in fact hold the key to producing regenerated tissues with high strength and endurance. However, many challenges remain, particularly for tissues that function within complex and demanding mechanical environments in vivo. This paper reviews the present role and potential impact of experimental and computational biomechanics in engineering functional tissues using several illustrative examples of past successes and future grand challenges. PMID:19583462

Two-layer tissue engineered urethra using oral epithelial and muscle derived cells.

PubMed

Mikami, Hiroshi; Kuwahara, Go; Nakamura, Nobuyuki; Yamato, Masayuki; Tanaka, Masatoshi; Kodama, Shohta

2012-05-01

We fabricated novel tissue engineered urethral grafts using autologously harvested oral cells. We report their viability in a canine model. Oral tissues were harvested by punch biopsy and divided into mucosal and muscle sections. Epithelial cells from mucosal sections were cultured as epithelial cell sheets. Simultaneously muscle derived cells were seeded on collagen mesh matrices to form muscle cell sheets. At 2 weeks the sheets were joined and tubularized to form 2-layer tissue engineered urethras, which were autologously grafted to surgically induced urethral defects in 10 dogs in the experimental group. Tissue engineered grafts were not applied to the induced urethral defect in control dogs. The dogs were followed 12 weeks postoperatively. Urethrogram and histological examination were done to evaluate the grafting outcome. We successfully fabricated 2-layer tissue engineered urethras in vitro and transplanted them in dogs in the experimental group. The 12-week complication-free rate was significantly higher in the experimental group than in controls. Urethrogram confirmed urethral patency without stricture in the complication-free group at 12 weeks. Histologically urethras in the transplant group showed a stratified epithelial layer overlying well differentiated submucosa. In contrast, urethras in controls showed severe fibrosis without epithelial layer formation. Two-layer tissue engineered urethras were engineered using cells harvested by minimally invasive oral punch biopsy. Results suggest that this technique can encourage regeneration of a functional urethra. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Bottom-Up Engineering of Well-Defined 3D Microtissues Using Microplatforms and Biomedical Applications.

PubMed

Lee, Geon Hui; Lee, Jae Seo; Wang, Xiaohong; Lee, Sang Hoon

2016-01-07

During the last decades, the engineering of well-defined 3D tissues has attracted great attention because it provides in vivo mimicking environment and can be a building block for the engineering of bioartificial organs. In this Review, diverse engineering methods of 3D tissues using microscale devices are introduced. Recent progress of microtechnologies has enabled the development of microplatforms for bottom-up assembly of diverse shaped 3D tissues consisting of various cells. Micro hanging-drop plates, microfluidic chips, and arrayed microwells are the typical examples. The encapsulation of cells in hydrogel microspheres and microfibers allows the engineering of 3D microtissues with diverse shapes. Applications of 3D microtissues in biomedical fields are described, and the future direction of microplatform-based engineering of 3D micro-tissues is discussed. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Enhanced elastin synthesis and maturation in human vascular smooth muscle tissue derived from induced-pluripotent stem cells.

PubMed

Eoh, Joon H; Shen, Nian; Burke, Jacqueline A; Hinderer, Svenja; Xia, Zhiyong; Schenke-Layland, Katja; Gerecht, Sharon

2017-04-01

Obtaining vascular smooth muscle tissue with mature, functional elastic fibers is a key obstacle in tissue-engineered blood vessels. Poor elastin secretion and organization leads to a loss of specialization in contractile smooth muscle cells, resulting in over proliferation and graft failure. In this study, human induced-pluripotent stem cells (hiPSCs) were differentiated into early smooth muscle cells, seeded onto a hybrid poly(ethylene glycol) dimethacrylate/poly (l-lactide) (PEGdma-PLA) scaffold and cultured in a bioreactor while exposed to pulsatile flow, towards maturation into contractile smooth muscle tissue. We evaluated the effects of pulsatile flow on cellular organization as well as elastin expression and assembly in the engineered tissue compared to a static control through immunohistochemistry, gene expression and functionality assays. We show that culturing under pulsatile flow resulted in organized and functional hiPSC derived smooth muscle tissue. Immunohistochemistry analysis revealed hiPSC-smooth muscle tissue with robust, well-organized cells and elastic fibers and the supporting microfibril proteins necessary for elastic fiber assembly. Through qRT-PCR analysis, we found significantly increased expression of elastin, fibronectin, and collagen I, indicating the synthesis of necessary extracellular matrix components. Functionality assays revealed that hiPSC-smooth muscle tissue cultured in the bioreactor had an increased calcium signaling and contraction in response to a cholinergic agonist, significantly higher mature elastin content and improved mechanical properties in comparison to the static control. The findings presented here detail an effective approach to engineering elastic human vascular smooth muscle tissue with the functionality necessary for tissue engineering and regenerative medicine applications. Obtaining robust, mature elastic fibers is a key obstacle in tissue-engineered blood vessels. Human induced-pluripotent stem cells have become of interest due to their ability to supplement tissue engineered scaffolds. Their ability to differentiate into cells of vascular lineages with defined phenotypes serves as a potential solution to a major cause of graft failure in which phenotypic shifts in smooth muscle cells lead to over proliferation and occlusion of the graft. Herein, we have differentiated human induced-pluripotent stem cells in a pulsatile flow bioreactor, resulting in vascular smooth muscle tissue with robust elastic fibers and enhanced functionality. This study highlights an effective approach to engineering elastic functional vascular smooth muscle tissue for tissue engineering and regenerative medicine applications. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Biocompatible magnetic core-shell nanocomposites for engineered magnetic tissues

NASA Astrophysics Data System (ADS)

Rodriguez-Arco, Laura; Rodriguez, Ismael A.; Carriel, Victor; Bonhome-Espinosa, Ana B.; Campos, Fernando; Kuzhir, Pavel; Duran, Juan D. G.; Lopez-Lopez, Modesto T.

2016-04-01

The inclusion of magnetic nanoparticles into biopolymer matrixes enables the preparation of magnetic field-responsive engineered tissues. Here we describe a synthetic route to prepare biocompatible core-shell nanostructures consisting of a polymeric core and a magnetic shell, which are used for this purpose. We show that using a core-shell architecture is doubly advantageous. First, gravitational settling for core-shell nanocomposites is slower because of the reduction of the composite average density connected to the light polymer core. Second, the magnetic response of core-shell nanocomposites can be tuned by changing the thickness of the magnetic layer. The incorporation of the composites into biopolymer hydrogels containing cells results in magnetic field-responsive engineered tissues whose mechanical properties can be controlled by external magnetic forces. Indeed, we obtain a significant increase of the viscoelastic moduli of the engineered tissues when exposed to an external magnetic field. Because the composites are functionalized with polyethylene glycol, the prepared bio-artificial tissue-like constructs also display excellent ex vivo cell viability and proliferation. When implanted in vivo, the engineered tissues show good biocompatibility and outstanding interaction with the host tissue. Actually, they only cause a localized transitory inflammatory reaction at the implantation site, without any effect on other organs. Altogether, our results suggest that the inclusion of magnetic core-shell nanocomposites into biomaterials would enable tissue engineering of artificial substitutes whose mechanical properties could be tuned to match those of the potential target tissue. In a wider perspective, the good biocompatibility and magnetic behavior of the composites could be beneficial for many other applications.The inclusion of magnetic nanoparticles into biopolymer matrixes enables the preparation of magnetic field-responsive engineered tissues. Here we describe a synthetic route to prepare biocompatible core-shell nanostructures consisting of a polymeric core and a magnetic shell, which are used for this purpose. We show that using a core-shell architecture is doubly advantageous. First, gravitational settling for core-shell nanocomposites is slower because of the reduction of the composite average density connected to the light polymer core. Second, the magnetic response of core-shell nanocomposites can be tuned by changing the thickness of the magnetic layer. The incorporation of the composites into biopolymer hydrogels containing cells results in magnetic field-responsive engineered tissues whose mechanical properties can be controlled by external magnetic forces. Indeed, we obtain a significant increase of the viscoelastic moduli of the engineered tissues when exposed to an external magnetic field. Because the composites are functionalized with polyethylene glycol, the prepared bio-artificial tissue-like constructs also display excellent ex vivo cell viability and proliferation. When implanted in vivo, the engineered tissues show good biocompatibility and outstanding interaction with the host tissue. Actually, they only cause a localized transitory inflammatory reaction at the implantation site, without any effect on other organs. Altogether, our results suggest that the inclusion of magnetic core-shell nanocomposites into biomaterials would enable tissue engineering of artificial substitutes whose mechanical properties could be tuned to match those of the potential target tissue. In a wider perspective, the good biocompatibility and magnetic behavior of the composites could be beneficial for many other applications. Electronic supplementary information (ESI) available. See DOI: 10.1039/c6nr00224b

Robot-aided electrospinning toward intelligent biomedical engineering.

PubMed

Tan, Rong; Yang, Xiong; Shen, Yajing

2017-01-01

The rapid development of robotics offers new opportunities for the traditional biofabrication in higher accuracy and controllability, which provides great potentials for the intelligent biomedical engineering. This paper reviews the state of the art of robotics in a widely used biomaterial fabrication process, i.e., electrospinning, including its working principle, main applications, challenges, and prospects. First, the principle and technique of electrospinning are introduced by categorizing it to melt electrospinning, solution electrospinning, and near-field electrospinning. Then, the applications of electrospinning in biomedical engineering are introduced briefly from the aspects of drug delivery, tissue engineering, and wound dressing. After that, we conclude the existing problems in traditional electrospinning such as low production, rough nanofibers, and uncontrolled morphology, and then discuss how those problems are addressed by robotics via four case studies. Lastly, the challenges and outlooks of robotics in electrospinning are discussed and prospected.

Fabrication of scaffolds in tissue engineering: A review

NASA Astrophysics Data System (ADS)

Zhao, Peng; Gu, Haibing; Mi, Haoyang; Rao, Chengchen; Fu, Jianzhong; Turng, Lih-sheng

2018-03-01

Tissue engineering (TE) is an integrated discipline that involves engineering and natural science in the development of biological materials to replace, repair, and improve the function of diseased or missing tissues. Traditional medical and surgical treatments have been reported to have side effects on patients caused by organ necrosis and tissue loss. However, engineered tissues and organs provide a new way to cure specific diseases. Scaffold fabrication is an important step in the TE process. This paper summarizes and reviews the widely used scaffold fabrication methods, including conventional methods, electrospinning, three-dimensional printing, and a combination of molding techniques. Furthermore, the differences among the properties of tissues, such as pore size and distribution, porosity, structure, and mechanical properties, are elucidated and critically reviewed. Some studies that combine two or more methods are also reviewed. Finally, this paper provides some guidance and suggestions for the future of scaffold fabrication.

3D Bioprinting Technologies for Hard Tissue and Organ Engineering

PubMed Central

Wang, Xiaohong; Ao, Qiang; Tian, Xiaohong; Fan, Jun; Wei, Yujun; Hou, Weijian; Tong, Hao; Bai, Shuling

2016-01-01

Hard tissues and organs, including the bones, teeth and cartilage, are the most extensively exploited and rapidly developed areas in regenerative medicine field. One prominent character of hard tissues and organs is that their extracellular matrices mineralize to withstand weight and pressure. Over the last two decades, a wide variety of 3D printing technologies have been adapted to hard tissue and organ engineering. These 3D printing technologies have been defined as 3D bioprinting. Especially for hard organ regeneration, a series of new theories, strategies and protocols have been proposed. Some of the technologies have been applied in medical therapies with some successes. Each of the technologies has pros and cons in hard tissue and organ engineering. In this review, we summarize the advantages and disadvantages of the historical available innovative 3D bioprinting technologies for used as special tools for hard tissue and organ engineering. PMID:28773924

A silk-based scaffold platform with tunable architecture for engineering critically-sized tissue constructs.

PubMed

Wray, Lindsay S; Rnjak-Kovacina, Jelena; Mandal, Biman B; Schmidt, Daniel F; Gil, Eun Seok; Kaplan, David L

2012-12-01

In the field of tissue engineering and regenerative medicine there is significant unmet need for critically-sized, fully degradable biomaterial scaffold systems with tunable properties for optimizing tissue formation in vitro and tissue regeneration in vivo. To address this need, we have developed a silk-based scaffold platform that has tunable material properties, including localized and bioactive functionalization, degradation rate, and mechanical properties and that provides arrays of linear hollow channels for delivery of oxygen and nutrients throughout the scaffold bulk. The scaffolds can be assembled with dimensions that range from millimeters to centimeters, addressing the need for a critically-sized platform for tissue formation. We demonstrate that the hollow channel arrays support localized and confluent endothelialization. This new platform offers a unique and versatile tool for engineering 'tailored' scaffolds for a range of tissue engineering and regenerative medicine needs. Copyright © 2012 Elsevier Ltd. All rights reserved.

Fiber-Based Tissue Engineering: Progress, Challenges, and Opportunities

PubMed Central

Tamayol, Ali; Akbari, Mohsen; Annabi, Nasim; Paul, Arghya; Khademhosseini, Ali; Juncker, David

2013-01-01

Tissue engineering aims to improve the function of diseased or damaged organs by creating biological substitutes. To fabricate a functional tissue, the engineered construct should mimic the physiological environment including its structural, topographical, and mechanical properties. Moreover, the construct should facilitate nutrients and oxygen diffusion as well as removal of metabolic waste during tissue regeneration. In the last decade, fiber-based techniques such as weaving, knitting, braiding, as well as electrospinning, and direct writing have emerged as promising platforms for making 3D tissue constructs that can address the above mentioned challenges. Here, we critically review the techniques used to form cell-free and cell-laden fibers and to assemble them into scaffolds. We compare their mechanical properties, morphological features and biological activity. We discuss current challenges and future opportunities of fiber-based tissue engineering (FBTE) for use in research and clinical practice. PMID:23195284

Hydrostatic Pressure in Articular Cartilage Tissue Engineering: From Chondrocytes to Tissue Regeneration

PubMed Central

Elder, Benjamin D.

2009-01-01

Cartilage has a poor intrinsic healing response, and neither the innate healing response nor current clinical treatments can restore its function. Therefore, articular cartilage tissue engineering is a promising approach for the regeneration of damaged tissue. Because cartilage is exposed to mechanical forces during joint loading, many tissue engineering strategies use exogenous stimuli to enhance the biochemical or biomechanical properties of the engineered tissue. Hydrostatic pressure (HP) is emerging as arguably one of the most important mechanical stimuli for cartilage, although no optimal treatment has been established across all culture systems. Therefore, this review evaluates prior studies on articular cartilage involving the use of HP, with a particular emphasis on the treatments that appear promising for use in future studies. Additionally, this review addresses HP bioreactor design, chondroprotective effects of HP, the use of HP for chondrogenic differentiation, the effects of high pressures, and HP mechanotransduction. PMID:19196119

Hydrostatic pressure in articular cartilage tissue engineering: from chondrocytes to tissue regeneration.

PubMed

Elder, Benjamin D; Athanasiou, Kyriacos A

2009-03-01

Cartilage has a poor intrinsic healing response, and neither the innate healing response nor current clinical treatments can restore its function. Therefore, articular cartilage tissue engineering is a promising approach for the regeneration of damaged tissue. Because cartilage is exposed to mechanical forces during joint loading, many tissue engineering strategies use exogenous stimuli to enhance the biochemical or biomechanical properties of the engineered tissue. Hydrostatic pressure (HP) is emerging as arguably one of the most important mechanical stimuli for cartilage, although no optimal treatment has been established across all culture systems. Therefore, this review evaluates prior studies on articular cartilage involving the use of HP, with a particular emphasis on the treatments that appear promising for use in future studies. Additionally, this review addresses HP bioreactor design, chondroprotective effects of HP, the use of HP for chondrogenic differentiation, the effects of high pressures, and HP mechanotransduction.

3D Bioprinting Technologies for Hard Tissue and Organ Engineering.

PubMed

Wang, Xiaohong; Ao, Qiang; Tian, Xiaohong; Fan, Jun; Wei, Yujun; Hou, Weijian; Tong, Hao; Bai, Shuling

2016-09-27

Hard tissues and organs, including the bones, teeth and cartilage, are the most extensively exploited and rapidly developed areas in regenerative medicine field. One prominent character of hard tissues and organs is that their extracellular matrices mineralize to withstand weight and pressure. Over the last two decades, a wide variety of 3D printing technologies have been adapted to hard tissue and organ engineering. These 3D printing technologies have been defined as 3D bioprinting. Especially for hard organ regeneration, a series of new theories, strategies and protocols have been proposed. Some of the technologies have been applied in medical therapies with some successes. Each of the technologies has pros and cons in hard tissue and organ engineering. In this review, we summarize the advantages and disadvantages of the historical available innovative 3D bioprinting technologies for used as special tools for hard tissue and organ engineering.

Engineering Functional Epithelium for Regenerative Medicine and In Vitro Organ Models: A Review

PubMed Central

Vrana, Nihal E.; Lavalle, Philippe; Dokmeci, Mehmet R.; Dehghani, Fariba; Ghaemmaghami, Amir M.

2013-01-01

Recent advances in the fields of microfabrication, biomaterials, and tissue engineering have provided new opportunities for developing biomimetic and functional tissues with potential applications in disease modeling, drug discovery, and replacing damaged tissues. An intact epithelium plays an indispensable role in the functionality of several organs such as the trachea, esophagus, and cornea. Furthermore, the integrity of the epithelial barrier and its degree of differentiation would define the level of success in tissue engineering of other organs such as the bladder and the skin. In this review, we focus on the challenges and requirements associated with engineering of epithelial layers in different tissues. Functional epithelial layers can be achieved by methods such as cell sheets, cell homing, and in situ epithelialization. However, for organs composed of several tissues, other important factors such as (1) in vivo epithelial cell migration, (2) multicell-type differentiation within the epithelium, and (3) epithelial cell interactions with the underlying mesenchymal cells should also be considered. Recent successful clinical trials in tissue engineering of the trachea have highlighted the importance of a functional epithelium for long-term success and survival of tissue replacements. Hence, using the trachea as a model tissue in clinical use, we describe the optimal structure of an artificial epithelium as well as challenges of obtaining a fully functional epithelium in macroscale. One of the possible remedies to address such challenges is the use of bottom-up fabrication methods to obtain a functional epithelium. Modular approaches for the generation of functional epithelial layers are reviewed and other emerging applications of microscale epithelial tissue models for studying epithelial/mesenchymal interactions in healthy and diseased (e.g., cancer) tissues are described. These models can elucidate the epithelial/mesenchymal tissue interactions at the microscale and provide the necessary tools for the next generation of multicellular engineered tissues and organ-on-a-chip systems. PMID:23705900

Engineering functional epithelium for regenerative medicine and in vitro organ models: a review.

PubMed

Vrana, Nihal E; Lavalle, Philippe; Dokmeci, Mehmet R; Dehghani, Fariba; Ghaemmaghami, Amir M; Khademhosseini, Ali

2013-12-01

Recent advances in the fields of microfabrication, biomaterials, and tissue engineering have provided new opportunities for developing biomimetic and functional tissues with potential applications in disease modeling, drug discovery, and replacing damaged tissues. An intact epithelium plays an indispensable role in the functionality of several organs such as the trachea, esophagus, and cornea. Furthermore, the integrity of the epithelial barrier and its degree of differentiation would define the level of success in tissue engineering of other organs such as the bladder and the skin. In this review, we focus on the challenges and requirements associated with engineering of epithelial layers in different tissues. Functional epithelial layers can be achieved by methods such as cell sheets, cell homing, and in situ epithelialization. However, for organs composed of several tissues, other important factors such as (1) in vivo epithelial cell migration, (2) multicell-type differentiation within the epithelium, and (3) epithelial cell interactions with the underlying mesenchymal cells should also be considered. Recent successful clinical trials in tissue engineering of the trachea have highlighted the importance of a functional epithelium for long-term success and survival of tissue replacements. Hence, using the trachea as a model tissue in clinical use, we describe the optimal structure of an artificial epithelium as well as challenges of obtaining a fully functional epithelium in macroscale. One of the possible remedies to address such challenges is the use of bottom-up fabrication methods to obtain a functional epithelium. Modular approaches for the generation of functional epithelial layers are reviewed and other emerging applications of microscale epithelial tissue models for studying epithelial/mesenchymal interactions in healthy and diseased (e.g., cancer) tissues are described. These models can elucidate the epithelial/mesenchymal tissue interactions at the microscale and provide the necessary tools for the next generation of multicellular engineered tissues and organ-on-a-chip systems.

Two-photon induced collagen cross-linking in bioartificial cardiac tissue

NASA Astrophysics Data System (ADS)

Kuetemeyer, Kai; Kensah, George; Heidrich, Marko; Meyer, Heiko; Martin, Ulrich; Gruh, Ina; Heisterkamp, Alexander

2011-08-01

Cardiac tissue engineering is a promising strategy for regenerative therapies to overcome the shortage of donor organs for transplantation. Besides contractile function, the stiffness of tissue engineered constructs is crucial to generate transplantable tissue surrogates with sufficient mechanical stability to withstand the high pressure present in the heart. Although several collagen cross-linking techniques have proven to be efficient in stabilizing biomaterials, they cannot be applied to cardiac tissue engineering, as cell death occurs in the treated area. Here, we present a novel method using femtosecond (fs) laser pulses to increase the stiffness of collagen-based tissue constructs without impairing cell viability. Raster scanning of the fs laser beam over riboflavin-treated tissue induced collagen cross-linking by two-photon photosensitized singlet oxygen production. One day post-irradiation, stress-strain measurements revealed increased tissue stiffness by around 40% being dependent on the fibroblast content in the tissue. At the same time, cells remained viable and fully functional as demonstrated by fluorescence imaging of cardiomyocyte mitochondrial activity and preservation of active contraction force. Our results indicate that two-photon induced collagen cross-linking has great potential for studying and improving artificially engineered tissue for regenerative therapies.

Comparative study of chitosan and chitosan-gelatin scaffold for tissue engineering

NASA Astrophysics Data System (ADS)

Kumar, Pawan; Dehiya, Brijnandan S.; Sindhu, Anil

2017-12-01

A number of orthopedic disorders and bone defect issues are solved by scaffold-based therapy in tissue engineering. The biocompatibility of chitosan (polysaccharide) and its similarity with glycosaminoglycan makes it a bone-grafting material. The current work focus on the synthesis of chitosan and chitosan-gelatin scaffold for hard tissue engineering. The chitosan and chitosan-gelatin scaffold have shown improved specific surface area, density, porosity, mechanical properties, biodegradability and absorption. These scaffolds can lead to the development or artificial fabrication of hard tissue alternates. The porous scaffold samples were prepared by freeze-drying method. The microstructure, mechanical and degradable properties of chitosan and chitosan-gelatin scaffolds were analyzed and results revealed that the scaffolds prepared from chitosan-gelatin can be utilized as a useful matrix for tissue engineering.

Biomaterial based cardiac tissue engineering and its applications

PubMed Central

Huyer, Locke Davenport; Montgomery, Miles; Zhao, Yimu; Xiao, Yun; Conant, Genevieve; Korolj, Anastasia; Radisic, Milica

2015-01-01

Cardiovascular disease is a leading cause of death worldwide, necessitating the development of effective treatment strategies. A myocardial infarction involves the blockage of a coronary artery leading to depletion of nutrient and oxygen supply to cardiomyocytes and massive cell death in a region of the myocardium. Cardiac tissue engineering is the growth of functional cardiac tissue in vitro on biomaterial scaffolds for regenerative medicine application. This strategy relies on the optimization of the complex relationship between cell networks and biomaterial properties. In this review, we discuss important biomaterial properties for cardiac tissue engineering applications, such as elasticity, degradation, and induced host response, and their relationship to engineered cardiac cell environments. With these properties in mind, we also emphasize in vitro use of cardiac tissues for high-throughput drug screening and disease modelling. PMID:25989939

Progress on materials and scaffold fabrications applied to esophageal tissue engineering.

PubMed

Shen, Qiuxiang; Shi, Peina; Gao, Mongna; Yu, Xuechan; Liu, Yuxin; Luo, Ling; Zhu, Yabin

2013-05-01

The mortality rate from esophageal disease like atresia, carcinoma, tracheoesophageal fistula, etc. is increasing rapidly all over the world. Traditional therapies such as surgery, radiotherapy or chemotherapy have been met with very limited success resulting in reduced survival rate and quality of patients' life. Tissue-engineered esophagus, a novel substitute possessing structure and function similar to native tissue, is believed to be an effective therapy and a promising replacement in the future. However, research on esophageal tissue engineering is still at an early stage. Considerable research has been focused on developing ideal scaffolds with optimal materials and methods of fabrication. This article gives a review of materials and scaffold fabrications currently applied in esophageal tissue engineering research. Copyright © 2013 Elsevier B.V. All rights reserved.

Bioprinting a cardiac valve.

PubMed

Jana, Soumen; Lerman, Amir

2015-12-01

Heart valve tissue engineering could be a possible solution for the limitations of mechanical and biological prostheses, which are commonly used for heart valve replacement. In tissue engineering, cells are seeded into a 3-dimensional platform, termed the scaffold, to make the engineered tissue construct. However, mimicking the mechanical and spatial heterogeneity of a heart valve structure in a fabricated scaffold with uniform cell distribution is daunting when approached conventionally. Bioprinting is an emerging technique that can produce biological products containing matrix and cells, together or separately with morphological, structural and mechanical diversity. This advance increases the possibility of fabricating the structure of a heart valve in vitro and using it as a functional tissue construct for implantation. This review describes the use of bioprinting technology in heart valve tissue engineering. Copyright © 2015 Elsevier Inc. All rights reserved.

Epithelial-Mesenchymal Interactions in Urinary Bladder and Small Intestine and How to Apply Them in Tissue Engineering.

PubMed

Jerman, Urška Dragin; Kreft, Mateja Erdani; Veranič, Peter

2015-12-01

Reciprocal interactions between the epithelium and mesenchyme are essential for the establishment of proper tissue morphology during organogenesis and tissue regeneration as well as for the maintenance of cell differentiation. With this review, we highlight the importance of epithelial-mesenchymal cross talk in healthy tissue and further discuss its significance in engineering functional tissues in vitro. We focus on the urinary bladder and small intestine, organs that are often compromised by disease and are as such in need of research that would advance effective treatment or tissue replacement. To date, the understanding of epithelial-mesenchymal reciprocal interactions has enabled the development of in vitro biomimetic tissue equivalents that have provided many possibilities in treating defective, damaged, or even cancerous tissues. Although research of the past several years has advanced the field of bladder and small intestine tissue engineering, one must be aware of its current limitations in successfully and above all safely introducing tissue-engineered constructs into clinical practice. Special attention is in particular needed when treating cancerous tissues, as initially successful tumor excision and tissue reconstruction may later on result in cancer recurrence due to oncogenic signals originating from an altered stroma. Recent rather poor outcomes in pioneering clinical trials of bladder reconstructions should serve as a reminder that recreating a functional organ to replace a dysfunctional one is an objective far more difficult to reach than initially foreseen. When considering effective tissue engineering approaches for diseased tissues in humans, it is imperative to introduce animal models with dysfunctional or, even more importantly, cancerous organs, which would greatly contribute to predicting possible complications and, hence, reducing risks when translating to the clinic.