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.

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.

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.

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.

Engineering Orthopedic Tissue Interfaces

PubMed Central

Yang, Peter J.

2009-01-01

While a wide variety of approaches to engineering orthopedic tissues have been proposed, less attention has been paid to the interfaces, the specialized areas that connect two tissues of different biochemical and mechanical properties. The interface tissue plays an important role in transitioning mechanical load between disparate tissues. Thus, the relatively new field of interfacial tissue engineering presents new challenges—to not only consider the regeneration of individual orthopedic tissues, but also to design the biochemical and cellular composition of the linking tissue. Approaches to interfacial tissue engineering may be distinguished based on if the goal is to recreate the interface itself, or generate an entire integrated tissue unit (such as an osteochondral plug). As background for future efforts in engineering orthopedic interfaces, a brief review of the biology and mechanics of each interface (cartilage–bone, ligament–bone, meniscus–bone, and muscle–tendon) is presented, followed by an overview of the state-of-the-art in engineering each tissue, including advances and challenges specific to regenerating the interfaces. PMID:19231983

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

Tissue engineering of urinary bladder - current state of art and future perspectives.

PubMed

Adamowicz, Jan; Kowalczyk, Tomasz; Drewa, Tomasz

2013-01-01

Tissue engineering and biomaterials science currently offer the technology needed to replace the urinary tract wall. This review addresses current achievements and barriers for the regeneration of the urinary blad- der based on tissue engineering methods. Medline was search for urinary bladder tissue engineering regenerative medicine and stem cells. Numerous studies to develop a substitute for the native urinary bladder wall us- ing the tissue engineering approach are ongoing. Stem cells combined with biomaterials open new treatment methods, including even de novo urinary bladder construction. However, there are still many issues before advances in tissue engineering can be introduced for clinical application. Before tissue engineering techniques could be recognize as effective and safe for patients, more research stud- ies performed on large animal models and with long follow-up are needed to carry on in the future.

[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,…

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.

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.

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.

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.

Vital roles of stem cells and biomaterials in skin tissue engineering

PubMed Central

Mohd Hilmi, Abu Bakar; Halim, Ahmad Sukari

2015-01-01

Tissue engineering essentially refers to technology for growing new human tissue and is distinct from regenerative medicine. Currently, pieces of skin are already being fabricated for clinical use and many other tissue types may be fabricated in the future. Tissue engineering was first defined in 1987 by the United States National Science Foundation which critically discussed the future targets of bioengineering research and its consequences. The principles of tissue engineering are to initiate cell cultures in vitro, grow them on scaffolds in situ and transplant the composite into a recipient in vivo. From the beginning, scaffolds have been necessary in tissue engineering applications. Regardless, the latest technology has redirected established approaches by omitting scaffolds. Currently, scientists from diverse research institutes are engineering skin without scaffolds. Due to their advantageous properties, stem cells have robustly transformed the tissue engineering field as part of an engineered bilayered skin substitute that will later be discussed in detail. Additionally, utilizing biomaterials or skin replacement products in skin tissue engineering as strategy to successfully direct cell proliferation and differentiation as well as to optimize the safety of handling during grafting is beneficial. This approach has also led to the cells’ application in developing the novel skin substitute that will be briefly explained in this review. PMID:25815126

Vital roles of stem cells and biomaterials in skin tissue engineering.

PubMed

Mohd Hilmi, Abu Bakar; Halim, Ahmad Sukari

2015-03-26

Tissue engineering essentially refers to technology for growing new human tissue and is distinct from regenerative medicine. Currently, pieces of skin are already being fabricated for clinical use and many other tissue types may be fabricated in the future. Tissue engineering was first defined in 1987 by the United States National Science Foundation which critically discussed the future targets of bioengineering research and its consequences. The principles of tissue engineering are to initiate cell cultures in vitro, grow them on scaffolds in situ and transplant the composite into a recipient in vivo. From the beginning, scaffolds have been necessary in tissue engineering applications. Regardless, the latest technology has redirected established approaches by omitting scaffolds. Currently, scientists from diverse research institutes are engineering skin without scaffolds. Due to their advantageous properties, stem cells have robustly transformed the tissue engineering field as part of an engineered bilayered skin substitute that will later be discussed in detail. Additionally, utilizing biomaterials or skin replacement products in skin tissue engineering as strategy to successfully direct cell proliferation and differentiation as well as to optimize the safety of handling during grafting is beneficial. This approach has also led to the cells' application in developing the novel skin substitute that will be briefly explained in this review.

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.

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.

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).

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

Adipose and mammary epithelial tissue engineering.

PubMed

Zhu, Wenting; Nelson, Celeste M

2013-01-01

Breast reconstruction is a type of surgery for women who have had a mastectomy, and involves using autologous tissue or prosthetic material to construct a natural-looking breast. Adipose tissue is the major contributor to the volume of the breast, whereas epithelial cells comprise the functional unit of the mammary gland. Adipose-derived stem cells (ASCs) can differentiate into both adipocytes and epithelial cells and can be acquired from autologous sources. ASCs are therefore an attractive candidate for clinical applications to repair or regenerate the breast. Here we review the current state of adipose tissue engineering methods, including the biomaterials used for adipose tissue engineering and the application of these techniques for mammary epithelial tissue engineering. Adipose tissue engineering combined with microfabrication approaches to engineer the epithelium represents a promising avenue to replicate the native structure of the breast.

Adipose and mammary epithelial tissue engineering

PubMed Central

Zhu, Wenting; Nelson, Celeste M.

2013-01-01

Breast reconstruction is a type of surgery for women who have had a mastectomy, and involves using autologous tissue or prosthetic material to construct a natural-looking breast. Adipose tissue is the major contributor to the volume of the breast, whereas epithelial cells comprise the functional unit of the mammary gland. Adipose-derived stem cells (ASCs) can differentiate into both adipocytes and epithelial cells and can be acquired from autologous sources. ASCs are therefore an attractive candidate for clinical applications to repair or regenerate the breast. Here we review the current state of adipose tissue engineering methods, including the biomaterials used for adipose tissue engineering and the application of these techniques for mammary epithelial tissue engineering. Adipose tissue engineering combined with microfabrication approaches to engineer the epithelium represents a promising avenue to replicate the native structure of the breast. PMID:23628872

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…

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.

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.

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

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.

Tissue engineering: confronting the transplantation crisis.

PubMed

Nerem, R M

2000-01-01

Tissue engineering is the development of biological substitutes and/or the fostering of tissue regeneration/remodelling. It is emerging as a technology which has the potential to confront the crisis in transplantation caused by the shortage of donor tissues and organs. With the development of this technology, ther is emerging a new industry which is at the interface of biotechnology and the traditional medical implant field. For this technology and the associated industry to realize their full potential, there are core, enabling technologies that need to be developed. This is the focus of the Georgia Tech/Emory Center for the Engineering of Living Tissues, newly established in the United States, with an Engineering Research Center Award from the National Science Foundation. With the development of these core technologies, tissue engineering will evolve from an art form to a technology based on science and engineering.

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

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 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

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.

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.

Biomimetic strategies for engineering composite tissues.

PubMed

Lee, Nancy; Robinson, Jennifer; Lu, Helen

2016-08-01

The formation of multiple tissue types and their integration into composite tissue units presents a frontier challenge in regenerative engineering. Tissue-tissue synchrony is crucial in providing structural support for internal organs and enabling daily activities. This review highlights the state-of-the-art in composite tissue scaffold design, and explores how biomimicry can be strategically applied to avoid over-engineering the scaffold. Given the complexity of biological tissues, determining the most relevant parameters for recapitulating native structure-function relationships through strategic biomimicry will reduce the burden for clinical translation. It is anticipated that these exciting efforts in composite tissue engineering will enable integrative and functional repair of common soft tissue injuries and lay the foundation for total joint or limb regeneration. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

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.

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.

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.

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.

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

New Methods in Tissue Engineering: Improved Models for Viral Infection.

PubMed

Ramanan, Vyas; Scull, Margaret A; Sheahan, Timothy P; Rice, Charles M; Bhatia, Sangeeta N

2014-11-01

New insights in the study of virus and host biology in the context of viral infection are made possible by the development of model systems that faithfully recapitulate the in vivo viral life cycle. Standard tissue culture models lack critical emergent properties driven by cellular organization and in vivo-like function, whereas animal models suffer from limited susceptibility to relevant human viruses and make it difficult to perform detailed molecular manipulation and analysis. Tissue engineering techniques may enable virologists to create infection models that combine the facile manipulation and readouts of tissue culture with the virus-relevant complexity of animal models. Here, we review the state of the art in tissue engineering and describe how tissue engineering techniques may alleviate some common shortcomings of existing models of viral infection, with a particular emphasis on hepatotropic viruses. We then discuss possible future applications of tissue engineering to virology, including current challenges and potential solutions.

New Methods in Tissue Engineering

PubMed Central

Sheahan, Timothy P.; Rice, Charles M.; Bhatia, Sangeeta N.

2015-01-01

New insights in the study of virus and host biology in the context of viral infection are made possible by the development of model systems that faithfully recapitulate the in vivo viral life cycle. Standard tissue culture models lack critical emergent properties driven by cellular organization and in vivo–like function, whereas animal models suffer from limited susceptibility to relevant human viruses and make it difficult to perform detailed molecular manipulation and analysis. Tissue engineering techniques may enable virologists to create infection models that combine the facile manipulation and readouts of tissue culture with the virus-relevant complexity of animal models. Here, we review the state of the art in tissue engineering and describe how tissue engineering techniques may alleviate some common shortcomings of existing models of viral infection, with a particular emphasis on hepatotropic viruses. We then discuss possible future applications of tissue engineering to virology, including current challenges and potential solutions. PMID:25893203

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.

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.

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.

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.

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.

[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

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

Therapeutic cloning and tissue engineering.

PubMed

Koh, Chester J; Atala, Anthony

2004-01-01

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.

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.

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.

MicroRNAs in liver tissue engineering - New promises for failing organs.

PubMed

Raschzok, Nathanael; Sallmon, Hannes; Pratschke, Johann; Sauer, Igor M

2015-07-01

miRNA-based technologies provide attractive tools for several liver tissue engineering approaches. Herein, we review the current state of miRNA applications in liver tissue engineering. Several miRNAs have been implicated in hepatic disease and proper hepatocyte function. However, the clinical translation of these findings into tissue engineering has just begun. miRNAs have been successfully used to induce proliferation of mature hepatocytes and improve the differentiation of hepatic precursor cells. Nonetheless, miRNA-based approaches beyond cell generation have not yet entered preclinical or clinical investigations. Moreover, miRNA-based concepts for the biliary tree have yet to be developed. Further research on miRNA based modifications, however, holds the promise of enabling significant improvements to liver tissue engineering approaches due to their ability to regulate and fine-tune all biological processes relevant to hepatic tissue engineering, such as proliferation, differentiation, growth, and cell function. Copyright © 2015 Elsevier B.V. All rights reserved.

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.

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.

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.

Cardiac tissue engineering: state of the art.

PubMed

Hirt, Marc N; Hansen, Arne; Eschenhagen, Thomas

2014-01-17

The engineering of 3-dimensional (3D) heart muscles has undergone exciting progress for the past decade. Profound advances in human stem cell biology and technology, tissue engineering and material sciences, as well as prevascularization and in vitro assay technologies make the first clinical application of engineered cardiac tissues a realistic option and predict that cardiac tissue engineering techniques will find widespread use in the preclinical research and drug development in the near future. Tasks that need to be solved for this purpose include standardization of human myocyte production protocols, establishment of simple methods for the in vitro vascularization of 3D constructs and better maturation of myocytes, and, finally, thorough definition of the predictive value of these methods for preclinical safety pharmacology. The present article gives an overview of the present state of the art, bottlenecks, and perspectives of cardiac tissue engineering for cardiac repair and in vitro testing.

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.

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.

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.

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.

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.

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.

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.

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

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

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

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.

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.

Stem cells for regenerative medicine: advances in the engineering of tissues and organs

NASA Astrophysics Data System (ADS)

Ringe, Jochen; Kaps, Christian; Burmester, Gerd-Rüdiger; Sittinger, Michael

2002-07-01

The adult bone marrow stroma contains a subset of nonhematopoietic cells referred to as mesenchymal stem or mesenchymal progenitor cells (MSC). These cells have the capacity to undergo extensive replication in an undifferentiated state ex vivo. In addition, MSC have the potential to develop either in vitro or in vivo into distinct mesenchymal tissues, including bone, cartilage, fat, tendon, muscle, and marrow stroma, which suggest these cells as an attractive cell source for tissue engineering approaches. The interest in modern biological technologies such as tissue engineering has dramatically increased since it is feasible to isolate living, healthy cells from the body, expand them under cell culture conditions, combine them with biocompatible carrier materials and retransplant them into patients. Therefore, tissue engineering gives the opportunity to generate living substitutes for tissues and organs, which may overcome the drawbacks of classical tissue reconstruction: lacking quality and quantity of autologous grafts, immunogenicity of allogenic grafts and loosening of alloplastic implants. Due to the prerequisite for tissue engineering to ensure a sufficient number of tissue specific cells without donor site morbidity, much attention has been drawn to multipotential progenitor cells such as embryonic stem cells, periosteal cells and mesenchymal stem cells. In this report we review the state of the art in tissue engineering with mesenchymal stem and mesenchymal progenitor cells with emphasis on bone and cartilage reconstruction. Furthermore, several issues of importance, especially with regard to the clinical application of mesenchymal stem cells, are discussed.

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.

Current state of cartilage tissue engineering

PubMed Central

Tuli, Richard; Li, Wan-Ju; Tuan, Rocky S

2003-01-01

Damage to cartilage is of great clinical consequence given the tissue's limited intrinsic potential for healing. Current treatments for cartilage repair are less than satisfactory, and rarely restore full function or return the tissue to its native normal state. The rapidly emerging field of tissue engineering holds great promise for the generation of functional cartilage tissue substitutes. The general approach involves a biocompatible, structurally and mechanically sound scaffold, with an appropriate cell source, which is loaded with bioactive molecules that promote cellular differentiation and/or maturation. This review highlights aspects of current progress in cartilage tissue engineering. PMID:12932283

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.

Powder-based 3D printing for bone tissue engineering.

PubMed

Brunello, G; Sivolella, S; Meneghello, R; Ferroni, L; Gardin, C; Piattelli, A; Zavan, B; Bressan, E

2016-01-01

Bone tissue engineered 3-D constructs customized to patient-specific needs are emerging as attractive biomimetic scaffolds to enhance bone cell and tissue growth and differentiation. The article outlines the features of the most common additive manufacturing technologies (3D printing, stereolithography, fused deposition modeling, and selective laser sintering) used to fabricate bone tissue engineering scaffolds. It concentrates, in particular, on the current state of knowledge concerning powder-based 3D printing, including a description of the properties of powders and binder solutions, the critical phases of scaffold manufacturing, and its applications in bone tissue engineering. Clinical aspects and future applications are also discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

[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.

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.

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.

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.

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.

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

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.

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

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.

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.

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.

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.

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.

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

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.

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.

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

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

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

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.

Nanostructured Biomaterials for Tissue Engineered Bone Tissue Reconstruction

PubMed Central

Chiara, Gardin; Letizia, Ferroni; Lorenzo, Favero; Edoardo, Stellini; Diego, Stomaci; Stefano, Sivolella; Eriberto, Bressan; Barbara, Zavan

2012-01-01

Bone tissue engineering strategies are emerging as attractive alternatives to autografts and allografts in bone tissue reconstruction, in particular thanks to their association with nanotechnologies. Nanostructured biomaterials, indeed, mimic the extracellular matrix (ECM) of the natural bone, creating an artificial microenvironment that promotes cell adhesion, proliferation and differentiation. At the same time, the possibility to easily isolate mesenchymal stem cells (MSCs) from different adult tissues together with their multi-lineage differentiation potential makes them an interesting tool in the field of bone tissue engineering. This review gives an overview of the most promising nanostructured biomaterials, used alone or in combination with MSCs, which could in future be employed as bone substitutes. Recent works indicate that composite scaffolds made of ceramics/metals or ceramics/polymers are undoubtedly more effective than the single counterparts in terms of osteoconductivity, osteogenicity and osteoinductivity. A better understanding of the interactions between MSCs and nanostructured biomaterials will surely contribute to the progress of bone tissue engineering. PMID:22312283

Establishing Early Functional Perfusion and Structure in Tissue Engineered Cardiac Constructs

PubMed Central

Wang, Bo; Patnaik, Sourav S.; Brazile, Bryn; Butler, J. Ryan; Claude, Andrew; Zhang, Ge; Guan, Jianjun; Hong, Yi; Liao, Jun

2016-01-01

Myocardial infarction (MI) causes massive heart muscle death and remains a leading cause of death in the world. Cardiac tissue engineering aims to replace the infarcted tissues with functional engineered heart muscles or revitalize the infarcted heart by delivering cells, bioactive factors, and/or biomaterials. One major challenge of cardiac tissue engineering and regeneration is the establishment of functional perfusion and structure to achieve timely angiogenesis and effective vascularization, which are essential to the survival of thick implants and the integration of repaired tissue with host heart. In this paper, we review four major approaches to promoting angiogenesis and vascularization in cardiac tissue engineering and regeneration: delivery of pro-angiogenic factors/molecules, direct cell implantation/cell sheet grafting, fabrication of prevascularized cardiac constructs, and the use of bioreactors to promote angiogenesis and vascularization. We further provide a detailed review and discussion on the early perfusion design in nature-derived biomaterials, synthetic biodegradable polymers, tissue-derived acellular scaffolds/whole hearts, and hydrogel derived from extracellular matrix. A better understanding of the current approaches and their advantages, limitations, and hurdles could be useful for developing better materials for future clinical applications. PMID:27480586

From stem to roots: Tissue engineering in endodontics

PubMed Central

Kala, M.; Banthia, Priyank; Banthia, Ruchi

2012-01-01

The vitality of dentin-pulp complex is fundamental to the life of tooth and is a priority for targeting clinical management strategies. Loss of the tooth, jawbone or both, due to periodontal disease, dental caries, trauma or some genetic disorders, affects not only basic mouth functions but aesthetic appearance and quality of life. One novel approach to restore tooth structure is based on biology: regenerative endodontic procedure by application of tissue engineering. Regenerative endodontics is an exciting new concept that seeks to apply the advances in tissue engineering to the regeneration of the pulp-dentin complex. The basic logic behind this approach is that patient-specific tissue-derived cell populations can be used to functionally replace integral tooth tissues. The development of such ‘test tube teeth’ requires precise regulation of the regenerative events in order to achieve proper tooth size and shape, as well as the development of new technologies to facilitate these processes. This article provides an extensive review of literature on the concept of tissue engineering and its application in endodontics, providing an insight into the new developmental approaches on the horizon. Key words:Regenerative, tissue engineering, stem cells, scaffold. PMID:24558528

A novel method for isolation of epithelial cells from ovine esophagus for tissue engineering.

PubMed

Macheiner, Tanja; Kuess, Anna; Dye, Julian; Saxena, Amulya K

2014-01-01

The yield of a critical number of basal epithelial cells with high mitotic rates from native tissue is a challenge in the field of tissue engineering. There are many protocols that use enzymatic methods for isolation of epithelial cells with unsatisfactory results for tissue engineering. This study aimed to develop a protocol for isolating a sufficient number of epithelial cells with a high Proliferating Index from ovine esophagus for tissue engineering applications. Esophageal mucosa was pretreated with dispase-collagenase solution and plated on collagen-coated culture dishes. Distinction of the various types of epithelial cells and developmental stages was done with specific primary antibodies to Cytokeratins and to Proliferating Cell Nuclear Antigen (PCNA). Up to approximately 8100 epithelial cells/mm2 of mucosa tissue were found after one week of migration. Cytokeratin 14 (CK 14) was positive identified in cells even after 83 days. At the same time the Proliferating Index was 71%. Our protocol for isolation of basal epithelial cells was successful to yield sufficient numbers of cells predominantly with proliferative character and without noteworthy negative enzymatic affection. The results at this study offer the possibility of generation critical cell numbers for tissue engineering applications.

Engineered cartilaginous tubes for tracheal tissue replacement via self-assembly and fusion of human mesenchymal stem cell constructs.

PubMed

Dikina, Anna D; Strobel, Hannah A; Lai, Bradley P; Rolle, Marsha W; Alsberg, Eben

2015-06-01

There is a critical need to engineer a neotrachea because currently there are no long-term treatments for tracheal stenoses affecting large portions of the airway. In this work, a modular tracheal tissue replacement strategy was developed. High-cell density, scaffold-free human mesenchymal stem cell-derived cartilaginous rings and tubes were successfully generated through employment of custom designed culture wells and a ring-to-tube assembly system. Furthermore, incorporation of transforming growth factor-β1-delivering gelatin microspheres into the engineered tissues enhanced chondrogenesis with regard to tissue size and matrix production and distribution in the ring- and tube-shaped constructs, as well as luminal rigidity of the tubes. Importantly, all engineered tissues had similar or improved biomechanical properties compared to rat tracheas, which suggests they could be transplanted into a small animal model for airway defects. The modular, bottom up approach used to grow stem cell-based cartilaginous tubes in this report is a promising platform to engineer complex organs (e.g., trachea), with control over tissue size and geometry, and has the potential to be used to generate autologous tissue implants for human clinical applications. Copyright © 2015 Elsevier Ltd. All rights reserved.

Establishing Early Functional Perfusion and Structure in Tissue Engineered Cardiac Constructs.

PubMed

Wang, Bo; Patnaik, Sourav S; Brazile, Bryn; Butler, J Ryan; Claude, Andrew; Zhang, Ge; Guan, Jianjun; Hong, Yi; Liao, Jun

2015-01-01

Myocardial infarction (MI) causes massive heart muscle death and remains a leading cause of death in the world. Cardiac tissue engineering aims to replace the infarcted tissues with functional engineered heart muscles or revitalize the infarcted heart by delivering cells, bioactive factors, and/or biomaterials. One major challenge of cardiac tissue engineering and regeneration is the establishment of functional perfusion and structure to achieve timely angiogenesis and effective vascularization, which are essential to the survival of thick implants and the integration of repaired tissue with host heart. In this paper, we review four major approaches to promoting angiogenesis and vascularization in cardiac tissue engineering and regeneration: delivery of pro-angiogenic factors/molecules, direct cell implantation/cell sheet grafting, fabrication of prevascularized cardiac constructs, and the use of bioreactors to promote angiogenesis and vascularization. We further provide a detailed review and discussion on the early perfusion design in nature-derived biomaterials, synthetic biodegradable polymers, tissue-derived acellular scaffolds/whole hearts, and hydrogel derived from extracellular matrix. A better understanding of the current approaches and their advantages, limitations, and hurdles could be useful for developing better materials for future clinical applications.

A modular approach to creating large engineered cartilage surfaces.

PubMed

Ford, Audrey C; Chui, Wan Fung; Zeng, Anne Y; Nandy, Aditya; Liebenberg, Ellen; Carraro, Carlo; Kazakia, Galateia; Alliston, Tamara; O'Connell, Grace D

2018-01-23

Native articular cartilage has limited capacity to repair itself from focal defects or osteoarthritis. Tissue engineering has provided a promising biological treatment strategy that is currently being evaluated in clinical trials. However, current approaches in translating these techniques to developing large engineered tissues remains a significant challenge. In this study, we present a method for developing large-scale engineered cartilage surfaces through modular fabrication. Modular Engineered Tissue Surfaces (METS) uses the well-known, but largely under-utilized self-adhesion properties of de novo tissue to create large scaffolds with nutrient channels. Compressive mechanical properties were evaluated throughout METS specimens, and the tensile mechanical strength of the bonds between attached constructs was evaluated over time. Raman spectroscopy, biochemical assays, and histology were performed to investigate matrix distribution. Results showed that by Day 14, stable connections had formed between the constructs in the METS samples. By Day 21, bonds were robust enough to form a rigid sheet and continued to increase in size and strength over time. Compressive mechanical properties and glycosaminoglycan (GAG) content of METS and individual constructs increased significantly over time. The METS technique builds on established tissue engineering accomplishments of developing constructs with GAG composition and compressive properties approaching native cartilage. This study demonstrated that modular fabrication is a viable technique for creating large-scale engineered cartilage, which can be broadly applied to many tissue engineering applications and construct geometries. Copyright © 2017 Elsevier Ltd. All rights reserved.

Guidelines for managing data and processes in bone and cartilage tissue engineering.

PubMed

Viti, Federica; Scaglione, Silvia; Orro, Alessandro; Milanesi, Luciano

2014-01-01

In the last decades, a wide number of researchers/clinicians involved in tissue engineering field published several works about the possibility to induce a tissue regeneration guided by the use of biomaterials. To this aim, different scaffolds have been proposed, and their effectiveness tested through in vitro and/or in vivo experiments. In this context, integration and meta-analysis approaches are gaining importance for analyses and reuse of data as, for example, those concerning the bone and cartilage biomarkers, the biomolecular factors intervening in cell differentiation and growth, the morphology and the biomechanical performance of a neo-formed tissue, and, in general, the scaffolds' ability to promote tissue regeneration. Therefore standards and ontologies are becoming crucial, to provide a unifying knowledge framework for annotating data and supporting the semantic integration and the unambiguous interpretation of novel experimental results. In this paper a conceptual framework has been designed for bone/cartilage tissue engineering domain, by now completely lacking standardized methods. A set of guidelines has been provided, defining the minimum information set necessary for describing an experimental study involved in bone and cartilage regenerative medicine field. In addition, a Bone/Cartilage Tissue Engineering Ontology (BCTEO) has been developed to provide a representation of the domain's concepts, specifically oriented to cells, and chemical composition, morphology, physical characterization of biomaterials involved in bone/cartilage tissue engineering research. Considering that tissue engineering is a discipline that traverses different semantic fields and employs many data types, the proposed instruments represent a first attempt to standardize the domain knowledge and can provide a suitable means to integrate data across the field.

Tissue engineering of the bladder--reality or myth? A systematic review.

PubMed

Sloff, Marije; Simaioforidis, Vasileios; de Vries, Rob; Oosterwijk, Egbert; Feitz, Wout

2014-10-01

We systematically reviewed preclinical studies in the literature to evaluate the potential of tissue engineering of the bladder. Study outcomes were compared to the available clinical evidence to assess the feasibility of tissue engineering for future clinical use. Preclinical studies of tissue engineering for bladder augmentation were identified through a systematic search of PubMed and Embase™ from January 1, 1980 to January 1, 2014. Primary studies in English were included if bladder reconstruction after partial cystectomy was performed using a tissue engineered biomaterial in any animal species, with cystometric bladder capacity as an outcome measure. Outcomes were compared to clinical studies available at http://www.clinicaltrials.gov and published clinical studies. A total of 28 preclinical studies are included, demonstrating remarkable heterogeneity in study characteristics and design. Studies in which preoperative bladder volumes were compared to postoperative volumes were considered the most clinically relevant (18 studies). Bladder augmentation through tissue engineering resulted in a normal bladder volume in healthy animals, with the influence of a cellular component being negligible. Furthermore, experiments in large animal models (pigs and dogs) approximated the desired bladder volume more accurately than in smaller species. The initial clinical experience was based on seemingly predictive healthy animal models with a promising outcome. Unfortunately these results were not substantiated in all clinical trials, revealing dissimilar outcomes in different clinical/disease backgrounds. Thus, the translational predictability of a model using healthy animals might be questioned. Through this systematic approach we present an unbiased overview of all published preclinical studies investigating the effect of bladder tissue engineering on cystometric bladder capacity. Preclinical research in healthy animals appears to show the feasibility of bladder augmentation by tissue engineering. However, in view of the disappointing clinical results based on healthy animal models new approaches should also be evaluated in preclinical models using dysfunctional/diseased bladders. This endeavor may aid in the development of clinically applicable tissue engineered bladder augmentation with satisfactory long-term outcome. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Dynamic Mechanical and Nanofibrous Topological Combinatory Cues Designed for Periodontal Ligament Engineering.

PubMed

Kim, Joong-Hyun; Kang, Min Sil; Eltohamy, Mohamed; Kim, Tae-Hyun; Kim, Hae-Won

2016-01-01

Complete reconstruction of damaged periodontal pockets, particularly regeneration of periodontal ligament (PDL) has been a significant challenge in dentistry. Tissue engineering approach utilizing PDL stem cells and scaffolding matrices offers great opportunity to this, and applying physical and mechanical cues mimicking native tissue conditions are of special importance. Here we approach to regenerate periodontal tissues by engineering PDL cells supported on a nanofibrous scaffold under a mechanical-stressed condition. PDL stem cells isolated from rats were seeded on an electrospun polycaprolactone/gelatin directionally-oriented nanofiber membrane and dynamic mechanical stress was applied to the cell/nanofiber construct, providing nanotopological and mechanical combined cues. Cells recognized the nanofiber orientation, aligning in parallel, and the mechanical stress increased the cell alignment. Importantly, the cells cultured on the oriented nanofiber combined with the mechanical stress produced significantly stimulated PDL specific markers, including periostin and tenascin with simultaneous down-regulation of osteogenesis, demonstrating the roles of topological and mechanical cues in altering phenotypic change in PDL cells. Tissue compatibility of the tissue-engineered constructs was confirmed in rat subcutaneous sites. Furthermore, in vivo regeneration of PDL and alveolar bone tissues was examined under the rat premaxillary periodontal defect models. The cell/nanofiber constructs engineered under mechanical stress showed sound integration into tissue defects and the regenerated bone volume and area were significantly improved. This study provides an effective tissue engineering approach for periodontal regeneration-culturing PDL stem cells with combinatory cues of oriented nanotopology and dynamic mechanical stretch.

Mechanical Characterization of Tissue-Engineered Cartilage Using Microscopic Magnetic Resonance Elastography

PubMed Central

Yin, Ziying; Schmid, Thomas M.; Yasar, Temel K.; Liu, Yifei; Royston, Thomas J.

2014-01-01

Knowledge of mechanical properties of tissue-engineered cartilage is essential for the optimization of cartilage tissue engineering strategies. Microscopic magnetic resonance elastography (μMRE) is a recently developed MR-based technique that can nondestructively visualize shear wave motion. From the observed wave pattern in MR phase images the tissue mechanical properties (e.g., shear modulus or stiffness) can be extracted. For quantification of the dynamic shear properties of small and stiff tissue-engineered cartilage, μMRE needs to be performed at frequencies in the kilohertz range. However, at frequencies greater than 1 kHz shear waves are rapidly attenuated in soft tissues. In this study μMRE, with geometric focusing, was used to overcome the rapid wave attenuation at high frequencies, enabling the measurement of the shear modulus of tissue-engineered cartilage. This methodology was first tested at a frequency of 5 kHz using a model system composed of alginate beads embedded in agarose, and then applied to evaluate extracellular matrix development in a chondrocyte pellet over a 3-week culture period. The shear stiffness in the pellet was found to increase over time (from 6.4 to 16.4 kPa), and the increase was correlated with both the proteoglycan content and the collagen content of the chondrocyte pellets (R2=0.776 and 0.724, respectively). Our study demonstrates that μMRE when performed with geometric focusing can be used to calculate and map the shear properties within tissue-engineered cartilage during its development. PMID:24266395

Dynamic Mechanical and Nanofibrous Topological Combinatory Cues Designed for Periodontal Ligament Engineering

PubMed Central

Kim, Joong-Hyun; Kang, Min Sil; Eltohamy, Mohamed; Kim, Tae-Hyun; Kim, Hae-Won

2016-01-01

Complete reconstruction of damaged periodontal pockets, particularly regeneration of periodontal ligament (PDL) has been a significant challenge in dentistry. Tissue engineering approach utilizing PDL stem cells and scaffolding matrices offers great opportunity to this, and applying physical and mechanical cues mimicking native tissue conditions are of special importance. Here we approach to regenerate periodontal tissues by engineering PDL cells supported on a nanofibrous scaffold under a mechanical-stressed condition. PDL stem cells isolated from rats were seeded on an electrospun polycaprolactone/gelatin directionally-oriented nanofiber membrane and dynamic mechanical stress was applied to the cell/nanofiber construct, providing nanotopological and mechanical combined cues. Cells recognized the nanofiber orientation, aligning in parallel, and the mechanical stress increased the cell alignment. Importantly, the cells cultured on the oriented nanofiber combined with the mechanical stress produced significantly stimulated PDL specific markers, including periostin and tenascin with simultaneous down-regulation of osteogenesis, demonstrating the roles of topological and mechanical cues in altering phenotypic change in PDL cells. Tissue compatibility of the tissue-engineered constructs was confirmed in rat subcutaneous sites. Furthermore, in vivo regeneration of PDL and alveolar bone tissues was examined under the rat premaxillary periodontal defect models. The cell/nanofiber constructs engineered under mechanical stress showed sound integration into tissue defects and the regenerated bone volume and area were significantly improved. This study provides an effective tissue engineering approach for periodontal regeneration—culturing PDL stem cells with combinatory cues of oriented nanotopology and dynamic mechanical stretch. PMID:26989897

Tissue Engineering Under Microgravity Conditions-Use of Stem Cells and Specialized Cells.

PubMed

Grimm, Daniela; Egli, Marcel; Krüger, Marcus; Riwaldt, Stefan; Corydon, Thomas J; Kopp, Sascha; Wehland, Markus; Wise, Petra; Infanger, Manfred; Mann, Vivek; Sundaresan, Alamelu

2018-03-29

Experimental cell research studying three-dimensional (3D) tissues in space and on Earth using new techniques to simulate microgravity is currently a hot topic in Gravitational Biology and Biomedicine. This review will focus on the current knowledge of the use of stem cells and specialized cells for tissue engineering under simulated microgravity conditions. We will report on recent advancements in the ability to construct 3D aggregates from various cell types using devices originally created to prepare for spaceflights such as the random positioning machine (RPM), the clinostat, or the NASA-developed rotating wall vessel (RWV) bioreactor, to engineer various tissues such as preliminary vessels, eye tissue, bone, cartilage, multicellular cancer spheroids, and others from different cells. In addition, stem cells had been investigated under microgravity for the purpose to engineer adipose tissue, cartilage, or bone. Recent publications have discussed different changes of stem cells when exposed to microgravity and the relevant pathways involved in these biological processes. Tissue engineering in microgravity is a new technique to produce organoids, spheroids, or tissues with and without scaffolds. These 3D aggregates can be used for drug testing studies or for coculture models. Multicellular tumor spheroids may be interesting for radiation experiments in the future and to reduce the need for in vivo experiments. Current achievements using cells from patients engineered on the RWV or on the RPM represent an important step in the advancement of techniques that may be applied in translational Regenerative Medicine.

Tissue-engineered lymphatic graft for the treatment of lymphedema

PubMed Central

Kanapathy, Muholan; Patel, Nikhil M.; Kalaskar, Deepak M.; Mosahebi, Afshin; Mehrara, Babak J.; Seifalian, Alexander M.

2015-01-01

Background Lymphedema is a chronic debilitating condition and curative treatment is yet to be found. Tissue engineering approach, which combines cellular components, scaffold, and molecular signals hold great potential in the treatment of secondary lymphedema with the advent of lymphatic graft to reconstruct damaged collecting lymphatic vessel. This review highlights the ideal characteristics of lymphatic graft, the limitation and challenges faced, and the approaches in developing tissue-engineered lymphatic graft. Methods Literature on tissue engineering of lymphatic system and lymphatic tissue biology was reviewed. Results The prime challenge in the design and manufacturing of this graft is producing endothelialized conduit with intraluminal valves. Suitable scaffold material is needed to ensure stability and functionality of the construct. Endothelialization of the construct can be enhanced via biofunctionalization and nanotopography, which mimics extracellular matrix. Nanocomposite polymers with improved performance over existing biomaterials are likely to benefit the development of lymphatic graft. Conclusions With the in-depth understanding of tissue engineering, nanotechnology, and improved knowledge on the biology of lymphatic regeneration, the aspiration to develop successful lymphatic graft is well achievable. PMID:25248852

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.

Recent Advances in Tissue Engineering Strategies for the Treatment of Joint Damage.

PubMed

Stephenson, Makeda K; Farris, Ashley L; Grayson, Warren L

2017-08-01

While the clinical potential of tissue engineering for treating joint damage has yet to be realized, research and commercialization efforts in the field are geared towards overcoming major obstacles to clinical translation, as well as towards achieving engineered grafts that recapitulate the unique structures, function, and physiology of the joint. In this review, we describe recent advances in technologies aimed at obtaining biomaterials, stem cells, and bioreactors that will enable the development of effective tissue-engineered treatments for repairing joint damage. 3D printing of scaffolds is aimed at improving the mechanical structure and microenvironment necessary for bone regeneration within a damaged joint. Advances in our understanding of stem cell biology and cell manufacturing processes are informing translational strategies for the therapeutic use of allogeneic and autologous cells. Finally, bioreactors used in combination with cells and biomaterials are promising strategies for generating large tissue grafts for repairing damaged tissues in pre-clinical models. Together, these advances along with ongoing research directions are making tissue engineering increasingly viable for the treatment of joint damage.

Tissue engineering for lateral ridge augmentation with recombinant human bone morphogenetic protein 2 combination therapy: a case report.

PubMed

Mandelaris, George A; Spagnoli, Daniel B; Rosenfeld, Alan L; McKee, James; Lu, Mei

2015-01-01

This case report describes a tissue-engineered reconstruction with recombinant human bone morphogenetic protein 2/acellular collagen sponge (rhBMP-2/ ACS) + cancellous allograft and space maintenance via Medpor Contain mesh in the treatment of a patient requiring maxillary and mandibular horizontal ridge augmentation to enable implant placement. The patient underwent a previously unsuccessful corticocancellous bone graft at these sites. Multiple and contiguous sites in the maxilla and in the mandibular anterior, demonstrating advanced lateral ridge deficiencies, were managed using a tissue engineering approach as an alternative to autogenous bone harvesting. Four maxillary and three mandibular implants were placed 9 and 10 months, respectively, after tissue engineering reconstruction, and all were functioning successfully after 24 months of follow-up. Histomorphometric analysis of a bone core obtained at the time of the maxillary implant placement demonstrated a mean of 76.1% new vital bone formation, 22.2% marrow/cells, and 1.7% residual graft tissue. Tissue engineering for lateral ridge augmentation with combination therapy requires further research to determine predictability and limitations.

Musculoskeletal tissue engineering with human umbilical cord mesenchymal stromal cells

PubMed Central

Wang, Limin; Ott, Lindsey; Seshareddy, Kiran; Weiss, Mark L; Detamore, Michael S

2011-01-01

Multipotent mesenchymal stromal cells (MSCs) hold tremendous promise for tissue engineering and regenerative medicine, yet with so many sources of MSCs, what are the primary criteria for selecting leading candidates? Ideally, the cells will be multipotent, inexpensive, lack donor site morbidity, donor materials should be readily available in large numbers, immunocompatible, politically benign and expandable in vitro for several passages. Bone marrow MSCs do not meet all of these criteria and neither do embryonic stem cells. However, a promising new cell source is emerging in tissue engineering that appears to meet these criteria: MSCs derived from Wharton’s jelly of umbilical cord MSCs. Exposed to appropriate conditions, umbilical cord MSCs can differentiate in vitro along several cell lineages such as the chondrocyte, osteoblast, adipocyte, myocyte, neuronal, pancreatic or hepatocyte lineages. In animal models, umbilical cord MSCs have demonstrated in vivo differentiation ability and promising immunocompatibility with host organs/tissues, even in xenotransplantation. In this article, we address their cellular characteristics, multipotent differentiation ability and potential for tissue engineering with an emphasis on musculoskeletal tissue engineering. PMID:21175290

Engineering Parameters in Bioreactor's Design: A Critical Aspect in Tissue Engineering

PubMed Central

Amoabediny, Ghassem; Pouran, Behdad; Tabesh, Hadi; Shokrgozar, Mohammad Ali; Haghighipour, Nooshin; Khatibi, Nahid; Mottaghy, Khosrow; Zandieh-Doulabi, Behrouz

2013-01-01

Bioreactors are important inevitable part of any tissue engineering (TE) strategy as they aid the construction of three-dimensional functional tissues. Since the ultimate aim of a bioreactor is to create a biological product, the engineering parameters, for example, internal and external mass transfer, fluid velocity, shear stress, electrical current distribution, and so forth, are worth to be thoroughly investigated. The effects of such engineering parameters on biological cultures have been addressed in only a few preceding studies. Furthermore, it would be highly inefficient to determine the optimal engineering parameters by trial and error method. A solution is provided by emerging modeling and computational tools and by analyzing oxygen, carbon dioxide, and nutrient and metabolism waste material transports, which can simulate and predict the experimental results. Discovering the optimal engineering parameters is crucial not only to reduce the cost and time of experiments, but also to enhance efficacy and functionality of the tissue construct. This review intends to provide an inclusive package of the engineering parameters together with their calculation procedure in addition to the modeling techniques in TE bioreactors. PMID:24000327

Engineering parameters in bioreactor's design: a critical aspect in tissue engineering.

PubMed

Salehi-Nik, Nasim; Amoabediny, Ghassem; Pouran, Behdad; Tabesh, Hadi; Shokrgozar, Mohammad Ali; Haghighipour, Nooshin; Khatibi, Nahid; Anisi, Fatemeh; Mottaghy, Khosrow; Zandieh-Doulabi, Behrouz

2013-01-01

Bioreactors are important inevitable part of any tissue engineering (TE) strategy as they aid the construction of three-dimensional functional tissues. Since the ultimate aim of a bioreactor is to create a biological product, the engineering parameters, for example, internal and external mass transfer, fluid velocity, shear stress, electrical current distribution, and so forth, are worth to be thoroughly investigated. The effects of such engineering parameters on biological cultures have been addressed in only a few preceding studies. Furthermore, it would be highly inefficient to determine the optimal engineering parameters by trial and error method. A solution is provided by emerging modeling and computational tools and by analyzing oxygen, carbon dioxide, and nutrient and metabolism waste material transports, which can simulate and predict the experimental results. Discovering the optimal engineering parameters is crucial not only to reduce the cost and time of experiments, but also to enhance efficacy and functionality of the tissue construct. This review intends to provide an inclusive package of the engineering parameters together with their calculation procedure in addition to the modeling techniques in TE bioreactors.

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

Tissue engineering for human urethral reconstruction: systematic review of recent literature.

PubMed

de Kemp, Vincent; de Graaf, Petra; Fledderus, Joost O; Ruud Bosch, J L H; de Kort, Laetitia M O

2015-01-01

Techniques to treat urethral stricture and hypospadias are restricted, as substitution of the unhealthy urethra with tissue from other origins (skin, bladder or buccal mucosa) has some limitations. Therefore, alternative sources of tissue for use in urethral reconstructions are considered, such as ex vivo engineered constructs. To review recent literature on tissue engineering for human urethral reconstruction. A search was made in the PubMed and Embase databases restricted to the last 25 years and the English language. A total of 45 articles were selected describing the use of tissue engineering in urethral reconstruction. The results are discussed in four groups: autologous cell cultures, matrices/scaffolds, cell-seeded scaffolds, and clinical results of urethral reconstructions using these materials. Different progenitor cells were used, isolated from either urine or adipose tissue, but slightly better results were obtained with in vitro expansion of urothelial cells from bladder washings, tissue biopsies from the bladder (urothelium) or the oral cavity (buccal mucosa). Compared with a synthetic scaffold, a biological scaffold has the advantage of bioactive extracellular matrix proteins on its surface. When applied clinically, a non-seeded matrix only seems suited for use as an onlay graft. When a tubularized substitution is the aim, a cell-seeded construct seems more beneficial. Considerable experience is available with tissue engineering of urethral tissue in vitro, produced with cells of different origin. Clinical and in vivo experiments show promising results.

Porous decellularized tissue engineered hypertrophic cartilage as a scaffold for large bone defect healing.

PubMed

Cunniffe, Gráinne M; Vinardell, Tatiana; Murphy, J Mary; Thompson, Emmet M; Matsiko, Amos; O'Brien, Fergal J; Kelly, Daniel J

2015-09-01

Clinical translation of tissue engineered therapeutics is hampered by the significant logistical and regulatory challenges associated with such products, prompting increased interest in the use of decellularized extracellular matrix (ECM) to enhance endogenous regeneration. Most bones develop and heal by endochondral ossification, the replacement of a hypertrophic cartilaginous intermediary with bone. The hypothesis of this study is that a porous scaffold derived from decellularized tissue engineered hypertrophic cartilage will retain the necessary signals to instruct host cells to accelerate endogenous bone regeneration. Cartilage tissue (CT) and hypertrophic cartilage tissue (HT) were engineered using human bone marrow derived mesenchymal stem cells, decellularized and the remaining ECM was freeze-dried to generate porous scaffolds. When implanted subcutaneously in nude mice, only the decellularized HT-derived scaffolds were found to induce vascularization and de novo mineral accumulation. Furthermore, when implanted into critically-sized femoral defects, full bridging was observed in half of the defects treated with HT scaffolds, while no evidence of such bridging was found in empty controls. Host cells which had migrated throughout the scaffold were capable of producing new bone tissue, in contrast to fibrous tissue formation within empty controls. These results demonstrate the capacity of decellularized engineered tissues as 'off-the-shelf' implants to promote tissue regeneration. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Bioactive scaffold for bone tissue engineering: An in vivo study

NASA Astrophysics Data System (ADS)

Livingston, Treena Lynne

Massive bone loss of the proximal femur is a common problem in revision cases of total hip implants. Allograft is typically used to reconstruct the site for insertion of the new prosthesis. However, for long term fixation and function, it is desirable that the allograft becomes fully replaced by bone tissue and aids in the regeneration of bone to that site. However, allograft use is typically associated with delayed incorporation and poor remodeling. Due to these profound limitations, alternative approaches are needed. Tissue engineering is an attractive approach to designing improved graft materials. By combining osteogenic activity with a resorbable scaffold, bone formation can be stimulated while providing structure and stability to the limb during incorporation and remodeling of the scaffold. Porous, surface modified bioactive ceramic scaffolds (pSMC) have been developed which stimulate the expression of the osteoblastic phenotype and production of bone-like tissue in vitro. The scaffold and two tissue-engineered constructs, osteoprogenitor cells seeded onto scaffolds or cells expanded in culture to form bone tissue on the scaffolds prior to implantation, were investigated in a long bone defect model. The rate of incorporation was assessed. Both tissue-engineered constructs stimulated bone formation and comparable repair at 2 weeks. In a rat femoral window defect model, bone formation increased over time for all groups in concert with scaffold resorption, leading to a 40% increase in bone and 40% reduction of the scaffold in the defect by 12 weeks. Both tissue-engineered constructs enhanced the rate of mechanical repair of long bones due to better bony union with the host cortex. Long bones treated with tissue engineered constructs demonstrated a return in normal torsional properties by 4 weeks as compared to 12 weeks for long bones treated with pSMC. Culture expansion of cells to produce bone tissue in vitro did not accelerate incorporation over the treatment with cells seeded at the time of surgery. Porous, surface modified bioactive ceramic is a promising scaffold material for tissue-engineered bone repair. Bone formation and scaffold resorption act in concert for maintenance and improvement of the structural properties of the long bones over time. As determined histomorphometrically and mechanically, the rate of incorporation of the scaffold was enhanced with the tissue-engineered constructs.

Finite Element Method (FEM), Mechanobiology and Biomimetic Scaffolds in Bone Tissue Engineering

PubMed Central

Boccaccio, A.; Ballini, A.; Pappalettere, C.; Tullo, D.; Cantore, S.; Desiate, A.

2011-01-01

Techniques of bone reconstructive surgery are largely based on conventional, non-cell-based therapies that rely on the use of durable materials from outside the patient's body. In contrast to conventional materials, bone tissue engineering is an interdisciplinary field that applies the principles of engineering and life sciences towards the development of biological substitutes that restore, maintain, or improve bone tissue function. Bone tissue engineering has led to great expectations for clinical surgery or various diseases that cannot be solved with traditional devices. For example, critical-sized defects in bone, whether induced by primary tumor resection, trauma, or selective surgery have in many cases presented insurmountable challenges to the current gold standard treatment for bone repair. The primary purpose of bone tissue engineering is to apply engineering principles to incite and promote the natural healing process of bone which does not occur in critical-sized defects. The total market for bone tissue regeneration and repair was valued at $1.1 billion in 2007 and is projected to increase to nearly $1.6 billion by 2014. Usually, temporary biomimetic scaffolds are utilized for accommodating cell growth and bone tissue genesis. The scaffold has to promote biological processes such as the production of extra-cellular matrix and vascularisation, furthermore the scaffold has to withstand the mechanical loads acting on it and to transfer them to the natural tissues located in the vicinity. The design of a scaffold for the guided regeneration of a bony tissue requires a multidisciplinary approach. Finite element method and mechanobiology can be used in an integrated approach to find the optimal parameters governing bone scaffold performance. In this paper, a review of the studies that through a combined use of finite element method and mechano-regulation algorithms described the possible patterns of tissue differentiation in biomimetic scaffolds for bone tissue engineering is given. Firstly, the generalities of the finite element method of structural analysis are outlined; second, the issues related to the generation of a finite element model of a given anatomical site or of a bone scaffold are discussed; thirdly, the principles on which mechanobiology is based, the principal theories as well as the main applications of mechano-regulation models in bone tissue engineering are described; finally, the limitations of the mechanobiological models and the future perspectives are indicated. PMID:21278921

Biomaterials for Bone Regenerative Engineering.

PubMed

Yu, Xiaohua; Tang, Xiaoyan; Gohil, Shalini V; Laurencin, Cato T

2015-06-24

Strategies for bone tissue regeneration have been continuously evolving for the last 25 years since the introduction of the "tissue engineering" concept. The convergence of the life, physical, and engineering sciences has brought in several advanced technologies available to tissue engineers and scientists. This resulted in the creation of a new multidisciplinary field termed as "regenerative engineering". In this article, the role of biomaterials in bone regenerative engineering is systematically reviewed to elucidate the new design criteria for the next generation of biomaterials for bone regenerative engineering. The exemplary design of biomaterials harnessing various materials characteristics towards successful bone defect repair and regeneration is highlighted. Particular attention is given to the attempts of incorporating advanced materials science, stem cell technologies, and developmental biology into biomaterials design to engineer and develop the next generation bone grafts. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Hyaluronan Benzyl Ester as a Scaffold for Tissue Engineering

PubMed Central

Vindigni, Vincenzo; Cortivo, Roberta; Iacobellis, Laura; Abatangelo, Giovanni; Zavan, Barbara

2009-01-01

Tissue engineering is a multidisciplinary field focused on in vitro reconstruction of mammalian tissues. In order to allow a similar three-dimensional organization of in vitro cultured cells, biocompatible scaffolds are needed. This need has provided immense momentum for research on “smart scaffolds” for use in cell culture. One of the most promising materials for tissue engineering and regenerative medicine is a hyaluronan derivative: a benzyl ester of hyaluronan (HYAFF®). HYAFF® can be processed to obtain several types of devices such as tubes, membranes, non-woven fabrics, gauzes, and sponges. All these scaffolds are highly biocompatible. In the human body they do not elicit any adverse reactions and are resorbed by the host tissues. Human hepatocytes, dermal fibroblasts and keratinocytes, chondrocytes, Schwann cells, bone marrow derived mesenchymal stem cells and adipose tissue derived mesenchymal stem cells have been successfully cultured in these meshes. The same scaffolds, in tube meshes, has been applied for vascular tissue engineering that has emerged as a promising technology for the design of an ideal, responsive, living conduit with properties similar to that of native tissue. PMID:19742179

Dynamic Bioreactor Culture of High Volume Engineered Bone Tissue

PubMed Central

Nguyen, Bao-Ngoc B.; Ko, Henry; Moriarty, Rebecca A.; Etheridge, Julie M.

2016-01-01

Within the field of tissue engineering and regenerative medicine, the fabrication of tissue grafts of any significant size—much less a whole organ or tissue—remains a major challenge. Currently, tissue-engineered constructs cultured in vitro have been restrained in size primarily due to the diffusion limit of oxygen and nutrients to the center of these grafts. Previously, we developed a novel tubular perfusion system (TPS) bioreactor, which allows the dynamic culture of bead-encapsulated cells and increases the supply of nutrients to the entire cell population. More interestingly, the versatility of TPS bioreactor allows a large range of engineered tissue volumes to be cultured, including large bone grafts. In this study, we utilized alginate-encapsulated human mesenchymal stem cells for the culture of a tissue-engineered bone construct in the size and shape of the superior half of an adult human femur (∼200 cm3), a 20-fold increase over previously reported volumes of in vitro engineered bone grafts. Dynamic culture in TPS bioreactor not only resulted in high cell viability throughout the femur graft, but also showed early signs of stem cell differentiation through increased expression of osteogenic genes and proteins, consistent with our previous models of smaller bone constructs. This first foray into full-scale bone engineering provides the foundation for future clinical applications of bioengineered bone grafts. PMID:26653703

Functional tissue engineering of tendon: Establishing biological success criteria for improving tendon repair.

PubMed

Breidenbach, Andrew P; Gilday, Steven D; Lalley, Andrea L; Dyment, Nathaniel A; Gooch, Cynthia; Shearn, Jason T; Butler, David L

2014-06-27

Improving tendon repair using Functional Tissue Engineering (FTE) principles has been the focus of our laboratory over the last decade. Although our primary goals were initially focused only on mechanical outcomes, we are now carefully assessing the biological properties of our tissue-engineered tendon repairs so as to link biological influences with mechanics. However, given the complexities of tendon development and healing, it remains challenging to determine which aspects of tendon biology are the most important to focus on in the context of tissue engineering. To address this problem, we have formalized a strategy to identify, prioritize, and evaluate potential biological success criteria for tendon repair. We have defined numerous biological properties of normal tendon relative to cellular phenotype, extracellular matrix and tissue ultra-structure that we would like to reproduce in our tissue-engineered repairs and prioritized these biological criteria by examining their relative importance during both normal development and natural tendon healing. Here, we propose three specific biological criteria which we believe are essential for normal tendon function: (1) scleraxis-expressing cells; (2) well-organized and axially-aligned collagen fibrils having bimodal diameter distribution; and (3) a specialized tendon-to-bone insertion site. Moving forward, these biological success criteria will be used in conjunction with our already established mechanical success criteria to evaluate the effectiveness of our tissue-engineered tendon repairs. © 2013 Published by Elsevier Ltd.

Production of three-dimensional tissue-engineered cartilage through mutual fusion of chondrocyte pellets.

PubMed

Hoshi, K; Fujihara, Y; Mori, Y; Asawa, Y; Kanazawa, S; Nishizawa, S; Misawa, M; Numano, T; Inoue, H; Sakamoto, T; Watanabe, M; Komura, M; Takato, T

2016-09-01

In this study, the mutual fusion of chondrocyte pellets was promoted in order to produce large-sized tissue-engineered cartilage with a three-dimensional (3D) shape. Five pellets of human auricular chondrocytes were first prepared, which were then incubated in an agarose mold. After 3 weeks of culture in matrix production-promoting medium under 5.78g/cm(2) compression, the tissue-engineered cartilage showed a sufficient mechanical strength. To confirm the usefulness of these methods, a transplantation experiment was performed using beagles. Tissue-engineered cartilage prepared with 50 pellets of beagle chondrocytes was transplanted subcutaneously into the cell-donor dog for 2 months. The tissue-engineered cartilage of the beagles maintained a rod-like shape, even after harvest. Histology showed fair cartilage regeneration. Furthermore, 20 pellets were made and placed on a beta-tricalcium phosphate prism, and this was then incubated within the agarose mold for 3 weeks. The construct was transplanted into a bone/cartilage defect in the cell-donor beagle. After 2 months, bone and cartilage regeneration was identified on micro-computed tomography and magnetic resonance imaging. This approach involving the fusion of small pellets into a large structure enabled the production of 3D tissue-engineered cartilage that was close to physiological cartilage tissue in property, without conventional polyper scaffolds. Copyright © 2016. Published by Elsevier Ltd.

Cell-based tissue engineering strategies used in the clinical repair of articular cartilage.

PubMed

Huang, Brian J; Hu, Jerry C; Athanasiou, Kyriacos A

2016-08-01

One of the most important issues facing cartilage tissue engineering is the inability to move technologies into the clinic. Despite the multitude of current research in the field, it is known that 90% of new drugs that advance past animal studies fail clinical trials. The objective of this review is to provide readers with an understanding of the scientific details of tissue engineered cartilage products that have demonstrated a certain level of efficacy in humans, so that newer technologies may be developed upon this foundation. Compared to existing treatments, such as microfracture or autologous chondrocyte implantation, a tissue engineered product can potentially provide more consistent clinical results in forming hyaline repair tissue and in filling the entirety of the defect. The various tissue engineering strategies (e.g., cell expansion, scaffold material, media formulations, biomimetic stimuli, etc.) used in forming these products, as collected from published literature, company websites, and relevant patents, are critically discussed. The authors note that many details about these products remain proprietary, not all information is made public, and that advancements to the products are continuously made. Nevertheless, by understanding the design and production processes of these emerging technologies, one can gain tremendous insight into how to best use them and also how to design the next generation of tissue engineered cartilage products. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cell-based tissue engineering strategies used in the clinical repair of articular cartilage

PubMed Central

Huang, Brian J.; Hu, Jerry C.; Athanasiou, Kyriacos A.

2016-01-01

One of the most important issues facing cartilage tissue engineering is the inability to move technologies into the clinic. Despite the multitude of review articles on the paradigm of biomaterials, signals, and cells, it is reported that 90% of new drugs that advance past animal studies fail clinical trials (1). The intent of this review is to provide readers with an understanding of the scientific details of tissue engineered cartilage products that have demonstrated a certain level of efficacy in humans, so that newer technologies may be developed upon this foundation. Compared to existing treatments, such as microfracture or autologous chondrocyte implantation, a tissue engineered product can potentially provide more consistent clinical results in forming hyaline repair tissue and in filling the entirety of the defect. The various tissue engineering strategies (e.g., cell expansion, scaffold material, media formulations, biomimetic stimuli, etc.) used in forming these products, as collected from published literature, company websites, and relevant patents, are critically discussed. The authors note that many details about these products remain proprietary, not all information is made public, and that advancements to the products are continuously made. Nevertheless, by fully understanding the design and production processes of these emerging technologies, one can gain tremendous insight into how to best use them and also how to design the next generation of tissue engineered cartilage products. PMID:27177218

Controlled Bioactive Molecules Delivery Strategies for Tendon and Ligament Tissue Engineering using Polymeric Nanofibers.

PubMed

Hiong Teh, Thomas Kok; Hong Goh, James Cho; Toh, Siew Lok

2015-01-01

The interest in polymeric nanofibers has escalated over the past decade given its promise as tissue engineering scaffolds that can mimic the nanoscale structure of the native extracellular matrix. With functionalization of the polymeric nanofibers using bioactive molecules, localized signaling moieties can be established for the attached cells, to stimulate desired biological effects and direct cellular or tissue response. The inherently high surface area per unit mass of polymeric nanofibers can enhance cell adhesion, bioactive molecules loading and release efficiencies, and mass transfer properties. In this review article, the application of polymeric nanofibers for controlled bioactive molecules delivery will be discussed, with a focus on tendon and ligament tissue engineering. Various polymeric materials of different mechanical and degradation properties will be presented along with the nanofiber fabrication techniques explored. The bioactive molecules of interest for tendon and ligament tissue engineering, including growth factors and small molecules, will also be reviewed and compared in terms of their nanofiber incorporation strategies and release profiles. This article will also highlight and compare various innovative strategies to control the release of bioactive molecules spatiotemporally and explore an emerging tissue engineering strategy involving controlled multiple bioactive molecules sequential release. Finally, the review article concludes with challenges and future trends in the innovation and development of bioactive molecules delivery using polymeric nanofibers for tendon and ligament tissue engineering.

A comprehensive review of cryogels and their roles in tissue engineering applications.

PubMed

Hixon, Katherine R; Lu, Tracy; Sell, Scott A

2017-10-15

The extracellular matrix is fundamental in providing an appropriate environment for cell interaction and signaling to occur. Replicating such a matrix is advantageous in the support of tissue ingrowth and regeneration through the field of tissue engineering. While scaffolds can be fabricated in many ways, cryogels have recently become a popular approach due to their macroporous structure and durability. Produced through the crosslinking of gel precursors followed by a subsequent controlled freeze/thaw cycle, the resulting cryogel provides a unique, sponge-like structure. Therefore, cryogels have proven advantageous for many tissue engineering applications including roles in bioreactor systems, cell separation, and scaffolding. Specifically, the matrix has been demonstrated to encourage the production of various molecules, such as antibodies, and has also been used for cryopreservation. Cryogels can pose as a bioreactor for the expansion of cell lines, as well as a vehicle for cell separation. Lastly, this matrix has shown excellent potential as a tissue engineered scaffold, encouraging regrowth at numerous damaged tissue sites in vivo. This review will briefly discuss the fabrication of cryogels, with an emphasis placed on their application in various facets of tissue engineering to provide an overview of this unique scaffold's past and future roles. Cryogels are unique scaffolds produced through the controlled freezing and thawing of a polymer solution. There is an ever-growing body of literature that demonstrates their applicability in the realm of tissue engineering as extracellular matrix analogue scaffolds; with extensive information having been provided regarding the fabrication, porosity, and mechanical integrity of the scaffolds. Additionally, cryogels have been reviewed with respect to their role in bioseparation and as cellular incubators. This all-inclusive view of the roles that cryogels can play is critical to advancing the technology and expanding its niche within biomaterials and tissue engineering research. To the best of the authors' knowledge, this is the first comprehensive review of cryogel applications in tissue engineering that includes specific looks at their growing roles as extracellular matrix analogues, incubators, and in bioseparation processes. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Burn Wound Healing and Tissue Engineering.

PubMed

Singer, Adam J; Boyce, Steven T

In 2016 the American Burn Association held a State of the Science conference to help identify burn research priorities for the next decade. The current paper summarizes the work of the sub-committee on Burn Wound Healing and Tissue Engineering. We first present the priorities in wound healing research over the next 10 years. We then summarize the current state of the science related to burn wound healing and tissue engineering including determination of burn depth, limiting burn injury progression, eschar removal, management of microbial contamination and wound infection, measuring wound closure, accelerating wound healing and durable wound closure, and skin substitutes and tissue engineering. Finally, a summary of the round table discussion is presented.

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.

Dynamic culture induces a cell type-dependent response impacting on the thickness of engineered connective tissues.

PubMed

Fortier, Guillaume Marceau; Gauvin, Robert; Proulx, Maryse; Vallée, Maud; Fradette, Julie

2013-04-01

Mesenchymal cells are central to connective tissue homeostasis and are widely used for tissue-engineering applications. Dermal fibroblasts and adipose-derived stromal cells (ASCs) allow successful tissue reconstruction by the self-assembly approach of tissue engineering. This method leads to the production of multilayered tissues, devoid of exogenous biomaterials, that can be used as stromal compartments for skin or vesical reconstruction. These tissues are formed by combining cell sheets, generated through cell stimulation with ascorbic acid, which favours the cell-derived production/organization of matrix components. Since media motion can impact on cell behaviour, we investigated the effect of dynamic culture on mesenchymal cells during tissue reconstruction, using the self-assembly method. Tissues produced using ASCs in the presence of a wave-like movement were nearly twice thicker than under standard conditions, while no difference was observed for tissues produced from dermal fibroblasts. The increased matrix deposition was not correlated with an increased proliferation of ASCs, or by higher transcript levels of fibronectin or collagens I and III. A 30% increase of type V collagen mRNA was observed. Interestingly, tissues engineered from dermal fibroblasts featured a four-fold higher level of MMP-1 transcripts under dynamic conditions. Mechanical properties were similar for tissues reconstructed using dynamic or static conditions. Finally, cell sheets produced using ASCs under dynamic conditions could readily be manipulated, resulting in a 2 week reduction of the production time (from 5 to 3 weeks). Our results describe a distinctive property of ASCs' response to media motion, indicating that their culture under dynamic conditions leads to optimized tissue engineering. Copyright © 2011 John Wiley & Sons, Ltd.

Dental pulp stem cells express tendon markers under mechanical loading and are a potential cell source for tissue engineering of tendon-like tissue.

PubMed

Chen, Yu-Ying; He, Sheng-Teng; Yan, Fu-Hua; Zhou, Peng-Fei; Luo, Kai; Zhang, Yan-Ding; Xiao, Yin; Lin, Min-Kui

2016-12-16

Postnatal mesenchymal stem cells have the capacity to differentiate into multiple cell lineages. This study explored the possibility of dental pulp stem cells (DPSCs) for potential application in tendon tissue engineering. The expression of tendon-related markers such as scleraxis, tenascin-C, tenomodulin, eye absent homologue 2, collagens I and VI was detected in dental pulp tissue. Interestingly, under mechanical stimulation, these tendon-related markers were significantly enhanced when DPSCs were seeded in aligned polyglycolic acid (PGA) fibre scaffolds. Furthermore, mature tendon-like tissue was formed after transplantation of DPSC-PGA constructs under mechanical loading conditions in a mouse model. This study demonstrates that DPSCs could be a potential stem cell source for tissue engineering of tendon-like tissue.

A new osteonecrosis animal model of the femoral head induced by microwave heating and repaired with tissue engineered bone

PubMed Central

Han, Rui; Geng, Chengkui; Wang, Yongnian; Wei, Lei

2008-01-01

The objective of this research was to induce a new animal model of osteonecrosis of the femoral head (ONFH) by microwave heating and then repair with tissue engineered bone. The bilateral femoral heads of 84 rabbits were heated by microwave at various temperatures. Tissue engineered bone was used to repair the osteonecrosis of femoral heads induced by microwave heating. The roentgenographic and histological examinations were used to evaluate the results. The femoral heads heated at 55°C for ten minutes showed low density and cystic changes in X-ray photographs, osteonecrosis and repair occurred simultaneously in histology at four and eight weeks, and 69% femoral heads collapsed at 12 weeks. The ability of tissue engineered bone to repair the osteonecrosis was close to that of cancellous bone autograft. The new animal model of ONFH could be induced by microwave heating, and the tissue engineering technique will provide an effective treatment. PMID:18956184

Recellularization of decellularized heart valves: Progress toward the tissue-engineered heart valve

PubMed Central

VeDepo, Mitchell C; Detamore, Michael S; Hopkins, Richard A; Converse, Gabriel L

2017-01-01

The tissue-engineered heart valve portends a new era in the field of valve replacement. Decellularized heart valves are of great interest as a scaffold for the tissue-engineered heart valve due to their naturally bioactive composition, clinical relevance as a stand-alone implant, and partial recellularization in vivo. However, a significant challenge remains in realizing the tissue-engineered heart valve: assuring consistent recellularization of the entire valve leaflets by phenotypically appropriate cells. Many creative strategies have pursued complete biological valve recellularization; however, identifying the optimal recellularization method, including in situ or in vitro recellularization and chemical and/or mechanical conditioning, has proven difficult. Furthermore, while many studies have focused on individual parameters for increasing valve interstitial recellularization, a general understanding of the interacting dynamics is likely necessary to achieve success. Therefore, the purpose of this review is to explore and compare the various processing strategies used for the decellularization and subsequent recellularization of tissue-engineered heart valves. PMID:28890780

Neoproteoglycans in tissue engineering.

PubMed

Weyers, Amanda; Linhardt, Robert J

2013-05-01

Proteoglycans, comprised of a core protein to which glycosaminoglycan chains are covalently linked, are an important structural and functional family of macromolecules found in the extracellular matrix. Advances in our understanding of biological interactions have lead to a greater appreciation for the need to design tissue engineering scaffolds that incorporate mimetics of key extracellular matrix components. A variety of synthetic and semisynthetic molecules and polymers have been examined by tissue engineers that serve as structural, chemical and biological replacements for proteoglycans. These proteoglycan mimetics have been referred to as neoproteoglycans and serve as functional and therapeutic replacements for natural proteoglycans that are often unavailable for tissue engineering studies. Although neoproteoglycans have important limitations, such as limited signaling ability and biocompatibility, they have shown promise in replacing the natural activity of proteoglycans through cell and protein binding interactions. This review focuses on the recent in vivo and in vitro tissue engineering applications of three basic types of neoproteoglycan structures, protein-glycosaminoglycan conjugates, nano-glycosaminoglycan composites and polymer-glycosaminoglycan complexes. © 2013 The Authors Journal compilation © 2013 FEBS.

Neoproteoglycans in tissue engineering

PubMed Central

Weyers, Amanda; Linhardt, Robert J.

2014-01-01

Proteoglycans, comprised of a core protein to which glycosaminoglycan chains are covalently linked, are an important structural and functional family of macromolecules found in the extracellular matrix. Advances in our understanding of biological interactions have lead to a greater appreciation for the need to design tissue engineering scaffolds that incorporate mimetics of key extracellular matrix components. A variety of synthetic and semisynthetic molecules and polymers have been examined by tissue engineers that serve as structural, chemical and biological replacements for proteoglycans. These proteoglycan mimetics have been referred to as neoproteoglycans and serve as functional and therapeutic replacements for natural proteoglycans that are often unavailable for tissue engineering studies. Although neoproteoglycans have important limitations, such as limited signaling ability and biocompatibility, they have shown promise in replacing the natural activity of proteoglycans through cell and protein binding interactions. This review focuses on the recent in vivo and in vitro tissue engineering applications of three basic types of neoproteoglycan structures, protein–glycosaminoglycan conjugates, nano-glycosaminoglycan composites and polymer–glycosaminoglycan complexes. PMID:23399318

Potential applications of three-dimensional structure of silk fibroin/poly(ester-urethane) urea nanofibrous scaffold in heart valve tissue engineering

NASA Astrophysics Data System (ADS)

Du, Juan; Zhu, Tonghe; Yu, Haiyan; Zhu, Jingjing; Sun, Changbing; Wang, Jincheng; Chen, Sihao; Wang, Jihu; Guo, Xuran

2018-07-01

Tissue engineering heart valves (TEHV) are thought to have many advantages in low immunogenicity, good histocompatibility, excellent mechanical properties. In this paper, we reported the fabrication and characterization of a novel composite nanofibrous scaffold consisting of silk fibroin (SF) and poly(ester-urethane) urea (LDI-PEUU) by using electrospinning. Chemical and physical properties of scaffolds were evaluated using scanning electron microscopy, attenuated total reflectance Fourier transform infrared, X-ray diffraction, contact angle measurement, thermogravimetric analysis, biodegradation test and tensile strength analysis. We determined that the composite scaffolds supported the growth of human umbilical vein endothelial cell (HUVEC). The results of cell proliferation and cell morphology indicate that SF/LDI-PEUU nanofibers promoted cell viability, which supporting the application in tissue engineering. All results clarified that SF/LDI-PEUU (40:60) nanofibrous scaffolds meet the required specifications for tissue engineering and could be used as a promising construct for heart valve tissue engineering.

Artificial membrane-binding proteins stimulate oxygenation of stem cells during engineering of large cartilage tissue

NASA Astrophysics Data System (ADS)

Armstrong, James P. K.; Shakur, Rameen; Horne, Joseph P.; Dickinson, Sally C.; Armstrong, Craig T.; Lau, Katherine; Kadiwala, Juned; Lowe, Robert; Seddon, Annela; Mann, Stephen; Anderson, J. L. Ross; Perriman, Adam W.; Hollander, Anthony P.

2015-06-01

Restricted oxygen diffusion can result in central cell necrosis in engineered tissue, a problem that is exacerbated when engineering large tissue constructs for clinical application. Here we show that pre-treating human mesenchymal stem cells (hMSCs) with synthetic membrane-active myoglobin-polymer-surfactant complexes can provide a reservoir of oxygen capable of alleviating necrosis at the centre of hyaline cartilage. This is achieved through the development of a new cell functionalization methodology based on polymer-surfactant conjugation, which allows the delivery of functional proteins to the hMSC membrane. This new approach circumvents the need for cell surface engineering using protein chimerization or genetic transfection, and we demonstrate that the surface-modified hMSCs retain their ability to proliferate and to undergo multilineage differentiation. The functionalization technology is facile, versatile and non-disruptive, and in addition to tissue oxygenation, it should have far-reaching application in a host of tissue engineering and cell-based therapies.

Skeletal Muscle Tissue Engineering: Methods to Form Skeletal Myotubes and Their Applications

PubMed Central

Ostrovidov, Serge; Hosseini, Vahid; Ahadian, Samad; Fujie, Toshinori; Parthiban, Selvakumar Prakash; Ramalingam, Murugan; Bae, Hojae; Kaji, Hirokazu

2014-01-01

Skeletal muscle tissue engineering (SMTE) aims to repair or regenerate defective skeletal muscle tissue lost by traumatic injury, tumor ablation, or muscular disease. However, two decades after the introduction of SMTE, the engineering of functional skeletal muscle in the laboratory still remains a great challenge, and numerous techniques for growing functional muscle tissues are constantly being developed. This article reviews the recent findings regarding the methodology and various technical aspects of SMTE, including cell alignment and differentiation. We describe the structure and organization of muscle and discuss the methods for myoblast alignment cultured in vitro. To better understand muscle formation and to enhance the engineering of skeletal muscle, we also address the molecular basics of myogenesis and discuss different methods to induce myoblast differentiation into myotubes. We then provide an overview of different coculture systems involving skeletal muscle cells, and highlight major applications of engineered skeletal muscle tissues. Finally, potential challenges and future research directions for SMTE are outlined. PMID:24320971

Fundamentals of biomechanics in tissue engineering of bone.

PubMed

Athanasiou, K A; Zhu, C; Lanctot, D R; Agrawal, C M; Wang, X

2000-08-01

The objective of this review is to provide basic information pertaining to biomechanical aspects of bone as they relate to tissue engineering. The review is written for the general tissue engineering reader, who may not have a biomechanical engineering background. To this end, biomechanical characteristics and properties of normal and repair cortical and cancellous bone are presented. Also, this chapter intends to describe basic structure-function relationships of these two types of bone. Special emphasis is placed on salient classical and modern testing methods, with both material and structural properties described.

Nanotechnology in vascular tissue engineering: from nanoscaffolding towards rapid vessel biofabrication.

PubMed

Mironov, Vladimir; Kasyanov, Vladimir; Markwald, Roger R

2008-06-01

The existing methods of biofabrication for vascular tissue engineering are still bioreactor-based, extremely expensive, laborious and time consuming and, furthermore, not automated, which would be essential for an economically successful large-scale commercialization. The advances in nanotechnology can bring additional functionality to vascular scaffolds, optimize internal vascular graft surface and even help to direct the differentiation of stem cells into the vascular cell phenotype. The development of rapid nanotechnology-based methods of vascular tissue biofabrication represents one of most important recent technological breakthroughs in vascular tissue engineering because it dramatically accelerates vascular tissue assembly and, importantly, also eliminates the need for a bioreactor-based scaffold cellularization process.

The prospective opportunities offered by magnetic scaffolds for bone tissue engineering: a review

PubMed Central

ORTOLANI, ALESSANDRO; BIANCHI, MICHELE; MOSCA, MASSIMILIANO; CARAVELLI, SILVIO; FUIANO, MARIO; MARCACCI, MAURILIO; RUSSO, ALESSANDRO

2016-01-01

Magnetic scaffolds are becoming increasingly attractive in tissue engineering, due to their ability to enhance bone tissue formation by attracting soluble factors, such as growth factors, hormones and polypeptides, directly to the implantation site, as well as their potential to improve the fixation and stability of the implant. Moreover, there is increasing evidence that the synergistic effects of magnetic scaffolds and magnetic fields can promote bone repair and regeneration. In this manuscript we review the recent innovations in bone tissue engineering that exploit magnetic biomaterials combined with static magnetic fields to enhance bone cell adhesion and proliferation, and thus bone tissue growth. PMID:28217659

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.

Multiscale assembly for tissue engineering and regenerative medicine

PubMed Central

Inci, Fatih; Tasoglu, Savas; Erkmen, Burcu; Demirci, Utkan

2015-01-01

Our understanding of cell biology and its integration with materials science has led to technological innovations in the bioengineering of tissue-mimicking grafts that can be utilized in clinical and pharmaceutical applications. Bio-engineering of native-like multiscale building blocks provides refined control over the cellular microenvironment, thus enabling functional tissues. In this review, we focus on assembling building blocks from the biomolecular level to the millimeter scale. We also provide an overview of techniques for assembling molecules, cells, spheroids, and microgels and achieving bottom-up tissue engineering. Additionally, we discuss driving mechanisms for self- and guided assembly to create micro-to-macro scale tissue structures. PMID:25796488

Synthetic Materials for Osteochondral Tissue Engineering.

PubMed

Iulian, Antoniac; Dan, Laptoiu; Camelia, Tecu; Claudia, Milea; Sebastian, Gradinaru

2018-01-01

The objective of an articular cartilage repair treatment is to repair the affected surface of an articular joint's hyaline cartilage. Currently, both biological and tissue engineering research is concerned with discovering the clues needed to stimulate cells to regenerate tissues and organs totally or partially. The latest findings on nanotechnology advances along with the processability of synthetic biomaterials have succeeded in creating a new range of materials to develop into the desired biological responses to the cellular level. 3D printing has a great ability to establish functional tissues or organs to cure or replace abnormal and necrotic tissue, providing a promising solution for serious tissue/organ failure. The 4D print process has the potential to continually revolutionize the current tissue and organ manufacturing platforms. A new active research area is the development of intelligent materials with high biocompatibility to suit 4D printing technology. As various researchers and tissue engineers have demonstrated, the role of growth factors in tissue engineering for repairing osteochondral and cartilage defects is a very important one. Following animal testing, cell-assisted and growth-factor scaffolds produced much better results, while growth-free scaffolds showed a much lower rate of healing.

Negating Tissue Contracture Improves Volume Maintenance and Longevity of In Vivo Engineered Tissues.

PubMed

Lytle, Ian F; Kozlow, Jeffrey H; Zhang, Wen X; Buffington, Deborah A; Humes, H David; Brown, David L

2015-10-01

Engineering large, complex tissues in vivo requires robust vascularization to optimize survival, growth, and function. Previously, the authors used a "chamber" model that promotes intense angiogenesis in vivo as a platform for functional three-dimensional muscle and renal engineering. A silicone membrane used to define the structure and to contain the constructs is successful in the short term. However, over time, generated tissues contract and decrease in size in a manner similar to capsular contracture seen around many commonly used surgical implants. The authors hypothesized that modification of the chamber structure or internal surface would promote tissue adherence and maintain construct volume. Three chamber configurations were tested against volume maintenance. Previously studied, smooth silicone surfaces were compared to chambers modified for improved tissue adherence, with multiple transmembrane perforations or lined with a commercially available textured surface. Tissues were allowed to mature long term in a rat model, before analysis. On explantation, average tissue masses were 49, 102, and 122 mg; average volumes were 74, 158 and 176 μl; and average cross-sectional areas were 1.6, 6.7, and 8.7 mm for the smooth, perforated, and textured groups, respectively. Both perforated and textured designs demonstrated significantly greater measures than the smooth-surfaced constructs in all respects. By modifying the design of chambers supporting vascularized, three-dimensional, in vivo tissue engineering constructs, generated tissue mass, volume, and area can be maintained over a long time course. Successful progress in the scale-up of construct size should follow, leading to improved potential for development of increasingly complex engineered tissues.

Carbon Nanostructures in Bone Tissue Engineering

PubMed Central

Perkins, Brian Lee; Naderi, Naghmeh

2016-01-01

Background: Recent advances in developing biocompatible materials for treating bone loss or defects have dramatically changed clinicians’ reconstructive armory. Current clinically available reconstructive options have certain advantages, but also several drawbacks that prevent them from gaining universal acceptance. A wide range of synthetic and natural biomaterials is being used to develop tissue-engineered bone. Many of these materials are currently in the clinical trial stage. Methods: A selective literature review was performed for carbon nanostructure composites in bone tissue engineering. Results: Incorporation of carbon nanostructures significantly improves the mechanical properties of various biomaterials to mimic that of natural bone. Recently, carbon-modified biomaterials for bone tissue engineering have been extensively investigated to potentially revolutionize biomaterials for bone regeneration. Conclusion: This review summarizes the chemical and biophysical properties of carbon nanostructures and discusses their functionality in bone tissue regeneration. PMID:28217212

Angiogenesis in tissue engineering: from concept to the vascularization of scaffold construct

NASA Astrophysics Data System (ADS)

Amirah Ishak, Siti; Pangestu Djuansjah, J. R.; Kadir, M. R. Abdul; Sukmana, Irza

2014-06-01

Angiogenesis, the formation of micro-vascular network from the preexisting vascular vessels, has been studied in the connection to the normal developmental process as well as numerous diseases. In tissue engineering research, angiogenesis is also essential to promote micro-vascular network inside engineered tissue constructs, mimicking a functional blood vessel in vivo. Micro-vascular network can be used to maintain adequate tissue oxygenation, nutrient transfer and waste removal. One of the problems faced by angiogenesis researchers is to find suitable in vitro assays and methods for assessing the effect of regulators on angiogenesis and micro-vessel formation. The assay would be reliable and repeatable with easily quantifiable with physiologically relevant. This review aims to highlights recent advanced and future challenges in developing and using an in vitro angiogenesis assay for the application on biomedical and tissue engineering research.

Optical Spectroscopy and Imaging for the Noninvasive Evaluation of Engineered Tissues

PubMed Central

Rice, William L.; Hronik-Tupaj, Marie; Kaplan, David L.

2008-01-01

Optical spectroscopy and imaging approaches offer the potential to noninvasively assess different aspects of the cellular, extracellular matrix, and scaffold components of engineered tissues. In addition, the combination of multiple imaging modalities within a single instrument is highly feasible, allowing acquisition of complementary information related to the structure, organization, biochemistry, and physiology of the sample. The ability to characterize and monitor the dynamic interactions that take place as engineered tissues develop promises to enhance our understanding of the interdependence of processes that ultimately leads to functional tissue outcomes. It is expected that this information will impact significantly upon our abilities to optimize the design of biomaterial scaffolds, bioreactors, and cell systems. Here, we review the principles and performance characteristics of the main methodologies that have been exploited thus far, and we present examples of corresponding tissue engineering studies. PMID:18844604

Human umbilical cord derived matrix: A scaffold suitable for tissue engineering application.

PubMed

Dan, Pan; Velot, Émilie; Mesure, Benjamin; Groshenry, Guillaume; Bacharouche, Jalal; Decot, Véronique; Menu, Patrick

2017-01-01

Human tissue derived natural extracellular matrix (ECM) has great potential in tissue engineering. We sought to isolate extracellular matrix derived from human umbilical cord and test its potential in tissue engineering. An enzymatic method was applied to isolate and solubilized complete human umbilical cord derived matrix (hUCM). The obtained solution was analyzed for growth factors, collagen and residual DNA contents, then used to coat 2D and 3D surfaces for cell culture application. The hUCM was successfully isolated with trypsin digestion to acquire a solution containing various growth factors and collagen but no residual DNA. This hUCM solution can form a coating on 2D and 3D substrates suitable cell culture. We developed a new matrix derived from human source that can be further used in tissue engineering.

Tissue engineering of ligaments for reconstructive surgery.

PubMed

Hogan, MaCalus V; Kawakami, Yohei; Murawski, Christopher D; Fu, Freddie H

2015-05-01

The use of musculoskeletal bioengineering and regenerative medicine applications in orthopaedic surgery has continued to evolve. The aim of this systematic review was to address tissue-engineering strategies for knee ligament reconstruction. A systematic review of PubMed/Medline using the terms "knee AND ligament" AND "tissue engineering" OR "regenerative medicine" was performed. Two authors performed the search, independently assessed the studies for inclusion, and extracted the data for inclusion in the review. Both preclinical and clinical studies were reviewed, and the articles deemed most relevant were included in this article to provide relevant basic science and recent clinical translational knowledge concerning "tissue-engineering" strategies currently used in knee ligament reconstruction. A total of 224 articles were reviewed in our initial PubMed search. Non-English-language studies were excluded. Clinical and preclinical studies were identified, and those with a focus on knee ligament tissue-engineering strategies including stem cell-based therapies, growth factor administration, hybrid biomaterial, and scaffold development, as well as mechanical stimulation modalities, were reviewed. The body of knowledge surrounding tissue-engineering strategies for ligament reconstruction continues to expand. Presently, various tissue-engineering techniques have some potential advantages, including faster recovery, better ligamentization, and possibly, a reduction of recurrence. Preclinical research of these novel therapies continues to provide promising results. There remains a need for well-designed, high-powered comparative clinical studies to serve as a foundation for successful translation into the clinical setting going forward. Level IV, systematic review of Level IV studies. Copyright © 2015 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Cell Patterning for Liver Tissue Engineering via Dielectrophoretic Mechanisms

PubMed Central

Yahya, Wan Nurlina Wan; Kadri, Nahrizul Adib; Ibrahim, Fatimah

2014-01-01

Liver transplantation is the most common treatment for patients with end-stage liver failure. However, liver transplantation is greatly limited by a shortage of donors. Liver tissue engineering may offer an alternative by providing an implantable engineered liver. Currently, diverse types of engineering approaches for in vitro liver cell culture are available, including scaffold-based methods, microfluidic platforms, and micropatterning techniques. Active cell patterning via dielectrophoretic (DEP) force showed some advantages over other methods, including high speed, ease of handling, high precision and being label-free. This article summarizes liver function and regenerative mechanisms for better understanding in developing engineered liver. We then review recent advances in liver tissue engineering techniques and focus on DEP-based cell patterning, including microelectrode design and patterning configuration. PMID:24991941

Biomechanical properties of the spinal cord: implications for tissue engineering and clinical translation.

PubMed

Bartlett, Richard D; Choi, David; Phillips, James B

2016-10-01

Spinal cord injury is a severely debilitating condition which can leave individuals paralyzed and suffering from autonomic dysfunction. Regenerative medicine may offer a promising solution to this problem. Previous research has focused primarily on exploring the cellular and biological aspects of the spinal cord, yet relatively little remains known about the biomechanical properties of spinal cord tissue. Given that a number of regenerative strategies aim to deliver cells and materials in the form of tissue-engineered therapies, understanding the biomechanical properties of host spinal cord tissue is important. We review the relevant biomechanical properties of spinal cord tissue and provide the baseline knowledge required to apply these important physical concepts to spinal cord tissue engineering.

Engineering vascularized soft tissue flaps in an animal model using human adipose–derived stem cells and VEGF+PLGA/PEG microspheres on a collagen-chitosan scaffold with a flow-through vascular pedicle

PubMed Central

Zhang, Qixu; Hubenak, Justin; Iyyanki, Tejaswi; Alred, Erik; Turza, Kristin C.; Davis, Greg; Chang, Edward I.; Branch-Brooks, Cynthia D.; Beahm, Elisabeth K.; Butler, Charles E.

2015-01-01

Insufficient neovascularization is associated with high levels of resorption and necrosis in autologous and engineered fat grafts. We tested the hypothesis that incorporating angiogenic growth factor into a scaffold–stem cell construct and implanting this construct around a vascular pedicle improves neovascularization and adipogenesis for engineering soft tissue flaps. Poly(lactic-co-glycolic-acid/polyethylene glycol (PLGA/PEG) microspheres containing vascular endothelial growth factor (VEGF) were impregnated into collagen-chitosan scaffolds seeded with human adipose-derived stem cells (hASCs). This setup was analyzed in vitro and then implanted into isolated chambers around a discrete vascular pedicle in nude rats. Engineered tissue samples within the chambers were harvested and analyzed for differences in vascularization and adipose tissue growth. In vitro testing showed that the collagen-chitosan scaffold provided a supportive environment for hASC integration and proliferation. PLGA/PEG microspheres with slow-release VEGF had no negative effect on cell survival in collagen-chitosan scaffolds. In vivo, the system resulted in a statistically significant increase in neovascularization that in turn led to a significant increase in adipose tissue persistence after 8 weeks versus control constructs. These data indicate that our model—hASCs integrated with a collagen-chitosan scaffold incorporated with VEGF-containing PLGA/PEG microspheres supported by a predominant vascular vessel inside a chamber—provides a promising, clinically translatable platform for engineering vascularized soft tissue flap. The engineered adipose tissue with a vascular pedicle could conceivably be transferred as a vascularized soft tissue pedicle flap or free flap to a recipient site for the repair of soft-tissue defects. PMID:26410787

Engineering vascularized soft tissue flaps in an animal model using human adipose-derived stem cells and VEGF+PLGA/PEG microspheres on a collagen-chitosan scaffold with a flow-through vascular pedicle.

PubMed

Zhang, Qixu; Hubenak, Justin; Iyyanki, Tejaswi; Alred, Erik; Turza, Kristin C; Davis, Greg; Chang, Edward I; Branch-Brooks, Cynthia D; Beahm, Elisabeth K; Butler, Charles E

2015-12-01

Insufficient neovascularization is associated with high levels of resorption and necrosis in autologous and engineered fat grafts. We tested the hypothesis that incorporating angiogenic growth factor into a scaffold-stem cell construct and implanting this construct around a vascular pedicle improves neovascularization and adipogenesis for engineering soft tissue flaps. Poly(lactic-co-glycolic-acid/polyethylene glycol (PLGA/PEG) microspheres containing vascular endothelial growth factor (VEGF) were impregnated into collagen-chitosan scaffolds seeded with human adipose-derived stem cells (hASCs). This setup was analyzed in vitro and then implanted into isolated chambers around a discrete vascular pedicle in nude rats. Engineered tissue samples within the chambers were harvested and analyzed for differences in vascularization and adipose tissue growth. In vitro testing showed that the collagen-chitosan scaffold provided a supportive environment for hASC integration and proliferation. PLGA/PEG microspheres with slow-release VEGF had no negative effect on cell survival in collagen-chitosan scaffolds. In vivo, the system resulted in a statistically significant increase in neovascularization that in turn led to a significant increase in adipose tissue persistence after 8 weeks versus control constructs. These data indicate that our model-hASCs integrated with a collagen-chitosan scaffold incorporated with VEGF-containing PLGA/PEG microspheres supported by a predominant vascular vessel inside a chamber-provides a promising, clinically translatable platform for engineering vascularized soft tissue flap. The engineered adipose tissue with a vascular pedicle could conceivably be transferred as a vascularized soft tissue pedicle flap or free flap to a recipient site for the repair of soft-tissue defects. Copyright © 2015 Elsevier Ltd. All rights reserved.

Repair of articular cartilage defects by tissue-engineered cartilage constructed with adipose-derived stem cells and acellular cartilaginous matrix in rabbits.

PubMed

Wang, Z J; An, R Z; Zhao, J Y; Zhang, Q; Yang, J; Wang, J B; Wen, G Y; Yuan, X H; Qi, X W; Li, S J; Ye, X C

2014-06-18

After injury, inflammation, or degeneration, articular cartilage has limited self-repair ability. We aimed to explore the feasibility of repair of articular cartilage defects with tissue-engineered cartilage constructed by acellular cartilage matrices (ACMs) seeded with adipose-derived stem cells (ADSCs). The ADSCs were isolated from 3-month-old New Zealand albino rabbit by using collagenase and cultured and amplified in vitro. Fresh cartilage isolated from adult New Zealand albino rabbit were freeze-dried for 12 h and treated with Triton X-100, DNase, and RNase to obtain ACMs. ADSCs were seeded in the acellular cartilaginous matrix at 2x10(7)/mL, and cultured in chondrogenic differentiation medium for 2 weeks to construct tissue-engineered cartilage. Twenty-four New Zealand white rabbits were randomly divided into A, B, and C groups. Engineered cartilage was transplanted into cartilage defect position of rabbits in group A, group B obtained ACMs, and group C did not receive any transplants. The rabbits were sacrificed in week 12. The restored tissue was evaluated using macroscopy, histology, immunohistochemistry, and transmission electron microscopy (TEM). In the tissue-engineered cartilage group (group A), articular cartilage defects of the rabbits were filled with chondrocyte-like tissue with smooth surface. Immunohistochemistry showed type II-collagen expression and Alcian blue staining was positive. TEM showed chondrocytes in the recesses, with plenty of secretary matrix particles. In the scaffold group (group B), the defect was filled with fibrous tissue. No repaired tissue was found in the blank group (group C). Tissue-engineered cartilage using ACM seeded with ADSCs can help repair articular cartilage defects in rabbits.

Engineered skeletal muscle tissue for soft robotics: fabrication strategies, current applications, and future challenges.

PubMed

Duffy, Rebecca M; Feinberg, Adam W

2014-01-01

Skeletal muscle is a scalable actuator system used throughout nature from the millimeter to meter length scales and over a wide range of frequencies and force regimes. This adaptability has spurred interest in using engineered skeletal muscle to power soft robotics devices and in biotechnology and medical applications. However, the challenges to doing this are similar to those facing the tissue engineering and regenerative medicine fields; specifically, how do we translate our understanding of myogenesis in vivo to the engineering of muscle constructs in vitro to achieve functional integration with devices. To do this researchers are developing a number of ways to engineer the cellular microenvironment to guide skeletal muscle tissue formation. This includes understanding the role of substrate stiffness and the mechanical environment, engineering the spatial organization of biochemical and physical cues to guide muscle alignment, and developing bioreactors for mechanical and electrical conditioning. Examples of engineered skeletal muscle that can potentially be used in soft robotics include 2D cantilever-based skeletal muscle actuators and 3D skeletal muscle tissues engineered using scaffolds or directed self-organization. Integration into devices has led to basic muscle-powered devices such as grippers and pumps as well as more sophisticated muscle-powered soft robots that walk and swim. Looking forward, current, and future challenges include identifying the best source of muscle precursor cells to expand and differentiate into myotubes, replacing cardiomyocytes with skeletal muscle tissue as the bio-actuator of choice for soft robots, and vascularization and innervation to enable control and nourishment of larger muscle tissue constructs. © 2013 Wiley Periodicals, Inc.

Physical non-viral gene delivery methods for tissue engineering.

PubMed

Mellott, Adam J; Forrest, M Laird; Detamore, Michael S

2013-03-01

The integration of gene therapy into tissue engineering to control differentiation and direct tissue formation is not a new concept; however, successful delivery of nucleic acids into primary cells, progenitor cells, and stem cells has proven exceptionally challenging. Viral vectors are generally highly effective at delivering nucleic acids to a variety of cell populations, both dividing and non-dividing, yet these viral vectors are marred by significant safety concerns. Non-viral vectors are preferred for gene therapy, despite lower transfection efficiencies, and possess many customizable attributes that are desirable for tissue engineering applications. However, there is no single non-viral gene delivery strategy that "fits-all" cell types and tissues. Thus, there is a compelling opportunity to examine different non-viral vectors, especially physical vectors, and compare their relative degrees of success. This review examines the advantages and disadvantages of physical non-viral methods (i.e., microinjection, ballistic gene delivery, electroporation, sonoporation, laser irradiation, magnetofection, and electric field-induced molecular vibration), with particular attention given to electroporation because of its versatility, with further special emphasis on Nucleofection™. In addition, attributes of cellular character that can be used to improve differentiation strategies are examined for tissue engineering applications. Ultimately, electroporation exhibits a high transfection efficiency in many cell types, which is highly desirable for tissue engineering applications, but electroporation and other physical non-viral gene delivery methods are still limited by poor cell viability. Overcoming the challenge of poor cell viability in highly efficient physical non-viral techniques is the key to using gene delivery to enhance tissue engineering applications.

Physical non-viral gene delivery methods for tissue engineering

PubMed Central

Mellott, Adam J.; Forrest, M. Laird; Detamore, Michael S.

2016-01-01

The integration of gene therapy into tissue engineering to control differentiation and direct tissue formation is not a new concept; however, successful delivery of nucleic acids into primary cells, progenitor cells, and stem cells has proven exceptionally challenging. Viral vectors are generally highly effective at delivering nucleic acids to a variety of cell populations, both dividing and non-dividing, yet these viral vectors are marred by significant safety concerns. Non-viral vectors are preferred for gene therapy, despite lower transfection efficiencies, and possess many customizable attributes that are desirable for tissue engineering applications. However, there is no single non-viral gene delivery strategy that “fits-all” cell types and tissues. Thus, there is a compelling opportunity to examine different non-viral vectors, especially physical vectors, and compare their relative degrees of success. This review examines the advantages and disadvantages of physical non-viral methods (i.e., microinjection, ballistic gene delivery, electroporation, sonoporation, laser irradiation, magnetofection, and electric field-induced molecular vibration), with particular attention given to electroporation because of its versatility, with further special emphasis on Nucleofection™. In addition, attributes of cellular character that can be used to improve differentiation strategies are examined for tissue engineering applications. Ultimately, electroporation exhibits a high transfection efficiency in many cell types, which is highly desirable for tissue engineering applications, but electroporation and other physical non-viral gene delivery methods are still limited by poor cell viability. Overcoming the challenge of poor cell viability in highly efficient physical non-viral techniques is the key to using gene delivery to enhance tissue engineering applications. PMID:23099792

Comparative analysis of poly-glycolic acid-based hybrid polymer starter matrices for in vitro tissue engineering.

PubMed

Generali, Melanie; Kehl, Debora; Capulli, Andrew K; Parker, Kevin K; Hoerstrup, Simon P; Weber, Benedikt

2017-10-01

Biodegradable scaffold matrixes form the basis of any in vitro tissue engineering approach by acting as a temporary matrix for cell proliferation and extracellular matrix deposition until the scaffold is replaced by neo-tissue. In this context several synthetic polymers have been investigated, however a concise systematic comparative analyses is missing. Therefore, the present study systematically compares three frequently used polymers for the in vitro engineering of extracellular matrix based on poly-glycolic acid (PGA) under static as well as dynamic conditions. Ultra-structural analysis was used to examine the polymers structure. For tissue engineering (TE) three human fibroblast cell lines were seeded on either PGA-poly-4-hydroxybutyrate (P4HB), PGA-poly-lactic acid (PLA) or PGA-poly-caprolactone (PCL) patches. These patches were analyzed after 21days of culture qualitative by histology and quantitative by determining the amount of DNA, glycosaminoglycan and hydroxyproline. We found that PGA-P4HB and PGA-PLA scaffolds enhance tissue formation significantly higher than PGA-PCL scaffolds (p<0.05). Polymer remnants were visualized by polarization microscopy. In addition, biomechanical properties of the tissue engineered patches were determined in comparison to native tissue. This study may allow future studies to specifically select certain polymer starter matrices aiming at specific tissue properties of the bioengineered constructs in vitro. Copyright © 2017 Elsevier B.V. All rights reserved.

The implications of recent advances in carboxymethyl chitosan based targeted drug delivery and tissue engineering applications.

PubMed

Upadhyaya, Laxmi; Singh, Jay; Agarwal, Vishnu; Tewari, Ravi Prakash

2014-07-28

Over the last decade carboxymethyl chitosan (CMCS) has emerged as a promising biopolymer for the development of new drug delivery systems and improved scaffolds along with other tissue engineering devices for regenerative medicine that is currently one of the most rapidly growing fields in the life sciences. CMCS is amphiprotic ether, derived from chitosan, exhibiting enhanced aqueous solubility, excellent biocompatibility, controllable biodegradability, osteogenesis ability and numerous other outstanding physicochemical and biological properties. More strikingly, it can load hydrophobic drugs and displays strong bioactivity which highlight its suitability and extensive usage for preparing different drug delivery and tissue engineering formulations respectively. This review provides a comprehensive introduction to various types of CMCS based formulations for delivery of therapeutic agents and tissue regeneration and further describes their preparation procedures and applications in different tissues/organs. Detailed information of CMCS based nano/micro systems for targeted delivery of drugs with emphasis on cancer specific and organ specific drug delivery have been described. Further, we have discussed various CMCS based tissue engineering biomaterials along with their preparation procedures and applications in different tissues/organs. The article then, gives a brief account of therapy combining drug delivery and tissue engineering. Finally, identification of major challenges and opportunities for current and ongoing application of CMCS based systems in the field are summarised. Copyright © 2014 Elsevier B.V. All rights reserved.

Tension stimulation drives tissue formation in scaffold-free systems

NASA Astrophysics Data System (ADS)

Lee, Jennifer K.; Huwe, Le W.; Paschos, Nikolaos; Aryaei, Ashkan; Gegg, Courtney A.; Hu, Jerry C.; Athanasiou, Kyriacos A.

2017-08-01

Scaffold-free systems have emerged as viable approaches for engineering load-bearing tissues. However, the tensile properties of engineered tissues have remained far below the values for native tissue. Here, by using self-assembled articular cartilage as a model to examine the effects of intermittent and continuous tension stimulation on tissue formation, we show that the application of tension alone, or in combination with matrix remodelling and synthesis agents, leads to neocartilage with tensile properties approaching those of native tissue. Implantation of tension-stimulated tissues results in neotissues that are morphologically reminiscent of native cartilage. We also show that tension stimulation can be translated to a human cell source to generate anisotropic human neocartilage with enhanced tensile properties. Tension stimulation, which results in nearly sixfold improvements in tensile properties over unstimulated controls, may allow the engineering of mechanically robust biological replacements of native tissue.

Bioengineered silk scaffolds in 3D tissue modeling with focus on mammary tissues.

PubMed

Maghdouri-White, Yas; Bowlin, Gary L; Lemmon, Christopher A; Dréau, Didier

2016-02-01

In vitro generation of three-dimensional (3D) biological tissues and organ-like structures is a promising strategy to study and closely model complex aspects of the molecular, cellular, and physiological interactions of tissue. In particular, in vitro 3D tissue modeling holds promises to further our understanding of breast development. Indeed, biologically relevant 3D structures that combine mammary cells and engineered matrices have improved our knowledge of mammary tissue growth, organization, and differentiation. Several polymeric biomaterials have been used as scaffolds to engineer 3D mammary tissues. Among those, silk fibroin-based biomaterials have many biologically relevant properties and have been successfully used in multiple medical applications. Here, we review the recent advances in engineered scaffolds with an emphasis on breast-like tissue generation and the benefits of modified silk-based scaffolds. Copyright © 2015 Elsevier B.V. All rights reserved.

Bioengineering a vaginal replacement using a small biopsy of autologous tissue.

PubMed

Dorin, Ryan P; Atala, Anthony; Defilippo, Roger E

2011-01-01

Many congenital and acquired diseases result in the absence of a normal vagina. Patients with these conditions often require reconstructive surgery to achieve satisfactory cosmesis and physiological function, and a variety of materials have been used as tissue sources. Currently employed graft materials such as collagen scaffolds and small intestine are not ideal in that they fail to mimic the physiology of normal vaginal tissue. Engineering of true vaginal tissue from a small biopsy of autologous vagina should produce a superior graft material for vaginal reconstruction. This review describes our current experience with the engineering of such tissue and its use for vaginal reconstruction in animal models. Our successful construction and implantation of neovaginas through tissue engineering techniques demonstrates the feasibility of similar endeavors in human patients. Additionally, the use of pluripotent stem cells instead of autologous tissue could provide an "off-the-shelf" tissue source for vaginal reconstruction.

The case for applying tissue engineering methodologies to instruct human organoid morphogenesis.

PubMed

Marti-Figueroa, Carlos R; Ashton, Randolph S

2017-05-01

Three-dimensional organoids derived from human pluripotent stem cell (hPSC) derivatives have become widely used in vitro models for studying development and disease. Their ability to recapitulate facets of normal human development during in vitro morphogenesis produces tissue structures with unprecedented biomimicry. Current organoid derivation protocols primarily rely on spontaneous morphogenesis processes to occur within 3-D spherical cell aggregates with minimal to no exogenous control. This yields organoids containing microscale regions of biomimetic tissues, but at the macroscale (i.e. 100's of microns to millimeters), the organoids' morphology, cytoarchitecture, and cellular composition are non-biomimetic and variable. The current lack of control over in vitro organoid morphogenesis at the microscale induces aberrations at the macroscale, which impedes realization of the technology's potential to reproducibly form anatomically correct human tissue units that could serve as optimal human in vitro models and even transplants. Here, we review tissue engineering methodologies that could be used to develop powerful approaches for instructing multiscale, 3-D human organoid morphogenesis. Such technological mergers are critically needed to harness organoid morphogenesis as a tool for engineering functional human tissues with biomimetic anatomy and physiology. Human PSC-derived 3-D organoids are revolutionizing the biomedical sciences. They enable the study of development and disease within patient-specific genetic backgrounds and unprecedented biomimetic tissue microenvironments. However, their uncontrolled, spontaneous morphogenesis at the microscale yields inconsistences in macroscale organoid morphology, cytoarchitecture, and cellular composition that limits their standardization and application. Integration of tissue engineering methods with organoid derivation protocols could allow us to harness their potential by instructing standardized in vitro morphogenesis to generate organoids with biomimicry at all scales. Such advancements would enable the use of organoids as a basis for 'next-generation' tissue engineering of functional, anatomically mimetic human tissues and potentially novel organ transplants. Here, we discuss critical aspects of organoid morphogenesis where application of innovative tissue engineering methodologies would yield significant advancement towards this goal. Copyright © 2017. Published by Elsevier Ltd.

Potential of 3-D tissue constructs engineered from bovine chondrocytes / silk fibroin-chitosan for in vitro cartilage tissue engineering

PubMed Central

Bhardwaj, Nandana; Nguyen, Quynhhoa T; Chen, Albert C; Kaplan, David L.; Sah, Robert L; Kundu, Subhas C

2011-01-01

The use of cell-scaffold constructs is a promising tissue engineering approach to repair cartilage defects and to study cartilaginous tissue formation. In this study, silk fibroin/chitosan blended scaffolds were fabricated and studied for cartilage tissue engineering. Silk fibroin served as a substrate for cell adhesion and proliferation while chitosan has a structure similar to that of glycosaminoglycans, and shows promise for cartilage repair. We compared the formation of cartilaginous tissue in silk fibroin/chitosan blended scaffolds seeded with bovine chondrocytes and cultured in vitro for 2 weeks. The constructs were analyzed for cell viability, histology, extracellular matrix components glycosaminoglycan and collagen types I and II, and biomechanical properties. Silk fibroin/chitosan scaffolds supported cell attachment and growth, and chondrogenic phenotype as indicated by Alcian Blue histochemistry and relative expression of type II versus type I collagen. Glycosaminoglycan and collagen accumulated in all the scaffolds and was highest in the silk fibroin/chitosan (1:1) blended scaffolds. Static and dynamic stiffness at high frequencies was higher in cell-seeded constructs than non-seeded controls. The results suggest that silk/chitosan scaffolds may be a useful alternative to synthetic cell scaffolds for cartilage tissue engineering. PMID:21601277

The materials used in bone tissue engineering

NASA Astrophysics Data System (ADS)

Tereshchenko, V. P.; Kirilova, I. A.; Sadovoy, M. A.; Larionov, P. M.

2015-11-01

Bone tissue engineering looking for an alternative solution to the problem of skeletal injuries. The method is based on the creation of tissue engineered bone tissue equivalent with stem cells, osteogenic factors, and scaffolds - the carriers of these cells. For production of tissue engineered bone equivalent is advisable to create scaffolds similar in composition to natural extracellular matrix of the bone. This will provide optimal conditions for the cells, and produce favorable physico-mechanical properties of the final construction. This review article gives an analysis of the most promising materials for the manufacture of cell scaffolds. Biodegradable synthetic polymers are the basis for the scaffold, but it alone cannot provide adequate physical and mechanical properties of the construction, and favorable conditions for the cells. Addition of natural polymers improves the strength characteristics and bioactivity of constructions. Of the inorganic compounds, to create cell scaffolds the most widely used calcium phosphates, which give the structure adequate stiffness and significantly increase its osteoinductive capacity. Signaling molecules do not affect the physico-mechanical properties of the scaffold, but beneficial effect is on the processes of adhesion, proliferation and differentiation of cells. Biodegradation of the materials will help to fulfill the main task of bone tissue engineering - the ability to replace synthetic construct by natural tissues that will restore the original anatomical integrity of the bone.

Gap Junction Intercellular Communication: A Review of a Potential Platform to Modulate Craniofacial Tissue Engineering

PubMed Central

Rossello, Ricardo A.; Kohn, David H.

2009-01-01

Defects in craniofacial tissues, resulting from trauma, congenital abnormalities, oncologic resection or progressive deforming diseases, may result in aesthetic deformity, pain and reduced function. Restoring the structure, function and aesthetics of craniofacial tissues represents a substantial clinical problem in need of new solutions. More biologically-interactive biomaterials could potentially improve the treatment of craniofacial defects, and an understanding of developmental processes may help identify strategies and materials that can be used in tissue engineering. One such strategy that can potentially advance tissue engineering is cell–cell communication. Gap junction intercellular communication is the most direct way of achieving such signaling. Gap junction communication through connexin-mediated junctions, in particular connexin 43 (Cx43), plays a major role bone development. Given the important role of Cx43 in controlling development and differentiation, especially in bone cells, controlling the expression of Cx43 may provide control over cell-to-cell communication and may help overcome some of the challenges in craniofacial tissue engineering. Following a review of gap junctions in bone cells, the ability to enhance cell–cell communication and osteogenic differentiation via control of gap junctions is discussed, as is the potential utility of this approach in craniofacial tissue engineering. PMID:18481782

Patterning vascular networks in vivo for tissue engineering applications.

PubMed

Chaturvedi, Ritika R; Stevens, Kelly R; Solorzano, Ricardo D; Schwartz, Robert E; Eyckmans, Jeroen; Baranski, Jan D; Stapleton, Sarah Chase; Bhatia, Sangeeta N; Chen, Christopher S

2015-05-01

The ultimate design of functionally therapeutic engineered tissues and organs will rely on our ability to engineer vasculature that can meet tissue-specific metabolic needs. We recently introduced an approach for patterning the formation of functional spatially organized vascular architectures within engineered tissues in vivo. Here, we now explore the design parameters of this approach and how they impact the vascularization of an engineered tissue construct after implantation. We used micropatterning techniques to organize endothelial cells (ECs) into geometrically defined "cords," which in turn acted as a template after implantation for the guided formation of patterned capillaries integrated with the host tissue. We demonstrated that the diameter of the cords before implantation impacts the location and density of the resultant capillary network. Inclusion of mural cells to the vascularization response appears primarily to impact the dynamics of vascularization. We established that clinically relevant endothelial sources such as induced pluripotent stem cell-derived ECs and human microvascular endothelial cells can drive vascularization within this system. Finally, we demonstrated the ability to control the juxtaposition of parenchyma with perfused vasculature by implanting cords containing a mixture of both a parenchymal cell type (hepatocytes) and ECs. These findings define important characteristics that will ultimately impact the design of vasculature structures that meet tissue-specific needs.

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.

A multi-scale controlled tissue engineering scaffold prepared by 3D printing and NFES technology

NASA Astrophysics Data System (ADS)

Yan, Feifei; Liu, Yuanyuan; Chen, Haiping; Zhang, Fuhua; Zheng, Lulu; Hu, Qingxi

2014-03-01

The current focus in the field of life science is the use of tissue engineering scaffolds to repair human organs, which has shown great potential in clinical applications. Extracellular matrix morphology and the performance and internal structure of natural organs are required to meet certain requirements. Therefore, integrating multiple processes can effectively overcome the limitations of the individual processes and can take into account the needs of scaffolds for the material, structure, mechanical properties and many other aspects. This study combined the biological 3D printing technology and the near-field electro-spinning (NFES) process to prepare a multi-scale controlled tissue engineering scaffold. While using 3D printing technology to directly prepare the macro-scaffold, the compositing NFES process to build tissue micro-morphology ultimately formed a tissue engineering scaffold which has the specific extracellular matrix structure. This scaffold not only takes into account the material, structure, performance and many other requirements, but also focuses on resolving the controllability problems in macro- and micro-forming which further aim to induce cell directed differentiation, reproduction and, ultimately, the formation of target tissue organs. It has in-depth immeasurable significance to build ideal scaffolds and further promote the application of tissue engineering.

Latest status of the clinical and industrial applications of cell sheet engineering and regenerative medicine.

PubMed

Egami, Mime; Haraguchi, Yuji; Shimizu, Tatsuya; Yamato, Masayuki; Okano, Teruo

2014-01-01

Cell sheet engineering, which allows tissue engineering to be realized without the use of biodegradable scaffolds as an original approach, using a temperature-responsive intelligent surface, has been applied in regenerative medicine for various tissues, and a number of clinical studies have been already performed for life-threatening diseases. By using the results and findings obtained from the initial clinical studies, additional investigative clinical studies in several tissues with cell sheet engineering are currently in preparation stage. For treating many patients effectively by cell sheet engineering, an automated system integrating cell culture, cell-sheet fabrication, and layering is essential, and the system should include an advanced three-dimensional suspension cell culture system and an in vitro bioreactor system to scale up the production of cultured cells and fabricate thicker vascularized tissues. In this paper, cell sheet engineering, its clinical application, and further the authors' challenge to develop innovative cell culture systems under newly legislated regulatory platform in Japan are summarized and discussed.

X-ray Phase Contrast Imaging of Calcified Tissue and Biomaterial Structure in Bioreactor Engineered Tissues

DOE Office of Scientific and Technical Information (OSTI.GOV)

Appel, Alyssa A.; Larson, Jeffery C.; Garson, III, Alfred B.

2014-11-04

Tissues engineered in bioreactor systems have been used clinically to replace damaged tissues and organs. In addition, these systems are under continued development for many tissue engineering applications. The ability to quantitatively assess material structure and tissue formation is critical for evaluating bioreactor efficacy and for preimplantation assessment of tissue quality. These techniques allow for the nondestructive and longitudinal monitoring of large engineered tissues within the bioreactor systems and will be essential for the translation of these strategies to viable clinical therapies. X-ray Phase Contrast (XPC) imaging techniques have shown tremendous promise for a number of biomedical applications owing tomore » their ability to provide image contrast based on multiple X-ray properties, including absorption, refraction, and scatter. In this research, mesenchymal stem cell-seeded alginate hydrogels were prepared and cultured under osteogenic conditions in a perfusion bioreactor. The constructs were imaged at various time points using XPC microcomputed tomography (µCT). Imaging was performed with systems using both synchrotron- and tube-based X-ray sources. XPC µCT allowed for simultaneous three-dimensional (3D) quantification of hydrogel size and mineralization, as well as spatial information on hydrogel structure and mineralization. Samples were processed for histological evaluation and XPC showed similar features to histology and quantitative analysis consistent with the histomorphometry. Furthermore, these results provide evidence of the significant potential of techniques based on XPC for noninvasive 3D imaging engineered tissues grown in bioreactors.« less

Microfabrication of Cell-Laden Hydrogels for Engineering Mineralized and Load Bearing Tissues.

PubMed

Li, Chia-Cheng; Kharaziha, Mahshid; Min, Christine; Maas, Richard; Nikkhah, Mehdi

2015-01-01

Microengineering technologies and advanced biomaterials have extensive applications in the field of regenerative medicine. In this chapter, we review the integration of microfabrication techniques and hydrogel-based biomaterials in the field of dental, bone, and cartilage tissue engineering. We primarily discuss the major features that make hydrogels attractive candidates to mimic extracellular matrix (ECM), and we consider the benefits of three-dimensional (3D) culture systems for tissue engineering applications. We then focus on the fundamental principles of microfabrication techniques including photolithography, soft lithography and bioprinting approaches. Lastly, we summarize recent research on microengineering cell-laden hydrogel constructs for dental, bone and cartilage regeneration, and discuss future applications of microfabrication techniques for load-bearing tissue engineering.

Tissue engineering applications of therapeutic cloning.

PubMed

Atala, Anthony; Koh, Chester J

2004-01-01

Few treatment options are available for patients suffering from diseased and injured organs because of a severe shortage of donor organs available for transplantation. 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 replacement therapy. 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. 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.

Pericyte-targeting drug delivery and tissue engineering.

PubMed

Kang, Eunah; Shin, Jong Wook

2016-01-01

Pericytes are contractile mural cells that wrap around the endothelial cells of capillaries and venules. Depending on the triggers by cellular signals, pericytes have specific functionality in tumor microenvironments, properties of potent stem cells, and plasticity in cellular pathology. These features of pericytes can be activated for the promotion or reduction of angiogenesis. Frontier studies have exploited pericyte-targeting drug delivery, using pericyte-specific peptides, small molecules, and DNA in tumor therapy. Moreover, the communication between pericytes and endothelial cells has been applied to the induction of vessel neoformation in tissue engineering. Pericytes may prove to be a novel target for tumor therapy and tissue engineering. The present paper specifically reviews pericyte-specific drug delivery and tissue engineering, allowing insight into the emerging research targeting pericytes.

The potential impact of bone tissue engineering in the clinic

PubMed Central

Mishra, Ruchi; Bishop, Tyler; Valerio, Ian L; Fisher, John P; Dean, David

2016-01-01

Bone tissue engineering (BTE) intends to restore structural support for movement and mineral homeostasis, and assist in hematopoiesis and the protective functions of bone in traumatic, degenerative, cancer, or congenital malformation. While much effort has been put into BTE, very little of this research has been translated to the clinic. In this review, we discuss current regenerative medicine and restorative strategies that utilize tissue engineering approaches to address bone defects within a clinical setting. These approaches involve the primary components of tissue engineering: cells, growth factors and biomaterials discussed briefly in light of their clinical relevance. This review also presents upcoming advanced approaches for BTE applications and suggests a probable workpath for translation from the laboratory to the clinic. PMID:27549369

Synthetic biodegradable functional polymers for tissue engineering: a brief review.

PubMed

BaoLin, Guo; Ma, Peter X

2014-04-01

Scaffolds play a crucial role in tissue engineering. Biodegradable polymers with great processing flexibility are the predominant scaffolding materials. Synthetic biodegradable polymers with well-defined structure and without immunological concerns associated with naturally derived polymers are widely used in tissue engineering. The synthetic biodegradable polymers that are widely used in tissue engineering, including polyesters, polyanhydrides, polyphosphazenes, polyurethane, and poly (glycerol sebacate) are summarized in this article. New developments in conducting polymers, photoresponsive polymers, amino-acid-based polymers, enzymatically degradable polymers, and peptide-activated polymers are also discussed. In addition to chemical functionalization, the scaffold designs that mimic the nano and micro features of the extracellular matrix (ECM) are presented as well, and composite and nanocomposite scaffolds are also reviewed.

76 FR 13631 - Food and Drug Administration Modernization Act of 1997: Modifications to the List of Recognized...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-14

... equipment. I. Tissue Engineering 15-25 ASTM F2312--10 Standard ASTM F2312-10. Terminology Relating to Tissue Engineered Medical Products. 15-26 ASTM F2211--04 Standard ASTM F2211-04. Classification for Tissue...

Liposomes in tissue engineering and regenerative medicine

PubMed Central

Monteiro, Nelson; Martins, Albino; Reis, Rui L.; Neves, Nuno M.

2014-01-01

Liposomes are vesicular structures made of lipids that are formed in aqueous solutions. Structurally, they resemble the lipid membrane of living cells. Therefore, they have been widely investigated, since the 1960s, as models to study the cell membrane, and as carriers for protection and/or delivery of bioactive agents. They have been used in different areas of research including vaccines, imaging, applications in cosmetics and tissue engineering. Tissue engineering is defined as a strategy for promoting the regeneration of tissues for the human body. This strategy may involve the coordinated application of defined cell types with structured biomaterial scaffolds to produce living structures. To create a new tissue, based on this strategy, a controlled stimulation of cultured cells is needed, through a systematic combination of bioactive agents and mechanical signals. In this review, we highlight the potential role of liposomes as a platform for the sustained and local delivery of bioactive agents for tissue engineering and regenerative medicine approaches. PMID:25401172

Bioprinting Cartilage Tissue from Mesenchymal Stem Cells and PEG Hydrogel.

PubMed

Gao, Guifang; Hubbell, Karen; Schilling, Arndt F; Dai, Guohao; Cui, Xiaofeng

2017-01-01

Bioprinting based on thermal inkjet printing is one of the most attractive enabling technologies for tissue engineering and regeneration. During the printing process, cells, scaffolds , and growth factors are rapidly deposited to the desired two-dimensional (2D) and three-dimensional (3D) locations. Ideally, the bioprinted tissues are able to mimic the native anatomic structures in order to restore the biological functions. In this study, a bioprinting platform for 3D cartilage tissue engineering was developed using a commercially available thermal inkjet printer with simultaneous photopolymerization . The engineered cartilage demonstrated native zonal organization, ideal extracellular matrix (ECM ) composition, and proper mechanical properties. Compared to the conventional tissue fabrication approach, which requires extended UV exposure, the viability of the printed cells with simultaneous photopolymerization was significantly higher. Printed neocartilage demonstrated excellent glycosaminoglycan (GAG) and collagen type II production, which was consistent with gene expression profile. Therefore, this platform is ideal for anatomic tissue engineering with accurate cell distribution and arrangement.

Image-guided tissue engineering of anatomically shaped implants via MRI and micro-CT using injection molding.

PubMed

Ballyns, Jeffery J; Gleghorn, Jason P; Niebrzydowski, Vicki; Rawlinson, Jeremy J; Potter, Hollis G; Maher, Suzanne A; Wright, Timothy M; Bonassar, Lawrence J

2008-07-01

This study demonstrates for the first time the development of engineered tissues based on anatomic geometries derived from widely used medical imaging modalities such as computed tomography (CT) and magnetic resonance imaging (MRI). Computer-aided design and tissue injection molding techniques have demonstrated the ability to generate living implants of complex geometry. Due to its complex geometry, the meniscus of the knee was used as an example of this technique's capabilities. MRI and microcomputed tomography (microCT) were used to design custom-printed molds that enabled the generation of anatomically shaped constructs that retained shape throughout 8 weeks of culture. Engineered constructs showed progressive tissue formation indicated by increases in extracellular matrix content and mechanical properties. The paradigm of interfacing tissue injection molding technology can be applied to other medical imaging techniques that render 3D models of anatomy, demonstrating the potential to apply the current technique to engineering of many tissues and organs.

In vivo outcomes of tissue-engineered osteochondral grafts.

PubMed

Bal, B Sonny; Rahaman, Mohamed N; Jayabalan, Prakash; Kuroki, Keiichi; Cockrell, Mary K; Yao, Jian Q; Cook, James L

2010-04-01

Tissue-engineered osteochondral grafts have been synthesized from a variety of materials, with some success at repairing chondral defects in animal models. We hypothesized that in tissue-engineered osteochondral grafts synthesized by bonding mesenchymal stem cell-loaded hydrogels to a porous material, the choice of the porous scaffold would affect graft healing to host bone, and the quality of cell restoration at the hyaline cartilage surface. Bone marrow-derived allogeneic mesenchymal stem cells were suspended in hydrogels that were attached to cylinders of porous tantalum metal, allograft bone, or a bioactive glass. The tissue-engineered osteochondral grafts, thus created were implanted into experimental defects in rabbit knees. Subchondral bone restoration, defect fill, bone ingrowth-implant integration, and articular tissue quality were compared between the three subchondral materials at 6 and 12 weeks. Bioactive glass and porous tantalum were superior to bone allograft in integrating to adjacent host bone, regenerating hyaline-like tissue at the graft surface, and expressing type II collagen in the articular cartilage.

Towards the design of 3D multiscale instructive tissue engineering constructs: Current approaches and trends.

PubMed

Oliveira, Sara M; Reis, Rui L; Mano, João F

2015-11-01

The design of 3D constructs with adequate properties to instruct and guide cells both in vitro and in vivo is one of the major focuses of tissue engineering. Successful tissue regeneration depends on the favorable crosstalk between the supporting structure, the cells and the host tissue so that a balanced matrix production and degradation are achieved. Herein, the major occurring events and players in normal and regenerative tissue are overviewed. These have been inspiring the selection or synthesis of instructive cues to include into the 3D constructs. We further highlight the importance of a multiscale perception of the range of features that can be included on the biomimetic structures. Lastly, we focus on the current and developing tissue-engineering approaches for the preparation of such 3D constructs: top-down, bottom-up and integrative. Bottom-up and integrative approaches present a higher potential for the design of tissue engineering devices with multiscale features and higher biochemical control than top-down strategies, and are the main focus of this review. Copyright © 2015 Elsevier Inc. All rights reserved.

Feasibility of autologous bone marrow mesenchymal stem cell-derived extracellular matrix scaffold for cartilage tissue engineering.

PubMed

Tang, Cheng; Xu, Yan; Jin, Chengzhe; Min, Byoung-Hyun; Li, Zhiyong; Pei, Xuan; Wang, Liming

2013-12-01

Extracellular matrix (ECM) materials are widely used in cartilage tissue engineering. However, the current ECM materials are unsatisfactory for clinical practice as most of them are derived from allogenous or xenogenous tissue. This study was designed to develop a novel autologous ECM scaffold for cartilage tissue engineering. The autologous bone marrow mesenchymal stem cell-derived ECM (aBMSC-dECM) membrane was collected and fabricated into a three-dimensional porous scaffold via cross-linking and freeze-drying techniques. Articular chondrocytes were seeded into the aBMSC-dECM scaffold and atelocollagen scaffold, respectively. An in vitro culture and an in vivo implantation in nude mice model were performed to evaluate the influence on engineered cartilage. The current results showed that the aBMSC-dECM scaffold had a good microstructure and biocompatibility. After 4 weeks in vitro culture, the engineered cartilage in the aBMSC-dECM scaffold group formed thicker cartilage tissue with more homogeneous structure and higher expressions of cartilaginous gene and protein compared with the atelocollagen scaffold group. Furthermore, the engineered cartilage based on the aBMSC-dECM scaffold showed better cartilage formation in terms of volume and homogeneity, cartilage matrix content, and compressive modulus after 3 weeks in vivo implantation. These results indicated that the aBMSC-dECM scaffold could be a successful novel candidate scaffold for cartilage tissue engineering. © 2013 Wiley Periodicals, Inc. and International Center for Artificial Organs and Transplantation.

Differential osteogenic activity of osteoprogenitor cells on HA and TCP/HA scaffold of tissue engineered bone.

PubMed

Ng, Angela M H; Tan, K K; Phang, M Y; Aziyati, O; Tan, G H; Isa, M R; Aminuddin, B S; Naseem, M; Fauziah, O; Ruszymah, B H I

2008-05-01

Biomaterial, an essential component of tissue engineering, serves as a scaffold for cell attachment, proliferation, and differentiation; provides the three dimensional (3D) structure and, in some applications, the mechanical strength required for the engineered tissue. Both synthetic and naturally occurring calcium phosphate based biomaterial have been used as bone fillers or bone extenders in orthopedic and reconstructive surgeries. This study aims to evaluate two popular calcium phosphate based biomaterial i.e., hydroxyapatite (HA) and tricalcium phosphate/hydroxyapatite (TCP/HA) granules as scaffold materials in bone tissue engineering. In our strategy for constructing tissue engineered bone, human osteoprogenitor cells derived from periosteum were incorporated with human plasma-derived fibrin and seeded onto HA or TCP/HA forming 3D tissue constructs and further maintained in osteogenic medium for 4 weeks to induce osteogenic differentiation. Constructs were subsequently implanted intramuscularly in nude mice for 8 weeks after which mice were euthanized and constructs harvested for evaluation. The differential cell response to the biomaterial (HA or TCP/HA) adopted as scaffold was illustrated by the histology of undecalcified constructs and evaluation using SEM and TEM. Both HA and TCP/HA constructs showed evidence of cell proliferation, calcium deposition, and collagen bundle formation albeit lesser in the former. Our findings demonstrated that TCP/HA is superior between the two in early bone formation and hence is the scaffold material of choice in bone tissue engineering. Copyright 2007 Wiley Periodicals, Inc.

A puzzle assembly strategy for fabrication of large engineered cartilage tissue constructs.

PubMed

Nover, Adam B; Jones, Brian K; Yu, William T; Donovan, Daniel S; Podolnick, Jeremy D; Cook, James L; Ateshian, Gerard A; Hung, Clark T

2016-03-21

Engineering of large articular cartilage tissue constructs remains a challenge as tissue growth is limited by nutrient diffusion. Here, a novel strategy is investigated, generating large constructs through the assembly of individually cultured, interlocking, smaller puzzle-shaped subunits. These constructs can be engineered consistently with more desirable mechanical and biochemical properties than larger constructs (~4-fold greater Young׳s modulus). A failure testing technique was developed to evaluate the physiologic functionality of constructs, which were cultured as individual subunits for 28 days, then assembled and cultured for an additional 21-35 days. Assembled puzzle constructs withstood large deformations (40-50% compressive strain) prior to failure. Their ability to withstand physiologic loads may be enhanced by increases in subunit strength and assembled culture time. A nude mouse model was utilized to show biocompatibility and fusion of assembled puzzle pieces in vivo. Overall, the technique offers a novel, effective approach to scaling up engineered tissues and may be combined with other techniques and/or applied to the engineering of other tissues. Future studies will aim to optimize this system in an effort to engineer and integrate robust subunits to fill large defects. Copyright © 2016 Elsevier Ltd. All rights reserved.

A Puzzle Assembly Strategy for Fabrication of Large Engineered Cartilage Tissue Constructs

PubMed Central

Nover, Adam B.; Jones, Brian K.; Yu, William T.; Donovan, Daniel S.; Podolnick, Jeremy D.; Cook, James L.; Ateshian, Gerard A.; Hung, Clark T.

2016-01-01

Engineering of large articular cartilage tissue constructs remains a challenge as tissue growth is limited by nutrient diffusion. Here, a novel strategy is investigated, generating large constructs through the assembly of individually cultured, interlocking, smaller puzzle-shaped subunits. These constructs can be engineered consistently with more desirable mechanical and biochemical properties than larger constructs (~4-fold greater Young's modulus). A failure testing technique was developed to evaluate the physiologic functionality of constructs, which were cultured as individual subunits for 28 days, then assembled and cultured for an additional 21-35 days. Assembled puzzle constructs withstood large deformations (40-50% compressive strain) prior to failure. Their ability to withstand physiologic loads may be enhanced by increases in subunit strength and assembled culture time. A nude mouse model was utilized to show biocompatibility and fusion of assembled puzzle pieces in vivo. Overall, the technique offers a novel, effective approach to scaling up engineered tissues and may be combined with other techniques and/or applied to the engineering of other tissues. Future studies will aim to optimize this system in an effort to engineer and integrate robust subunits to fill large defects. PMID:26895780

Raloxifene microsphere-embedded collagen/chitosan/β-tricalcium phosphate scaffold for effective bone tissue engineering.

PubMed

Zhang, Ming-Lei; Cheng, Ji; Xiao, Ye-Chen; Yin, Ruo-Feng; Feng, Xu

2017-02-25

Engineering novel scaffolds that can mimic the functional extracellular matrix (ECM) would be a great achievement in bone tissue engineering. This paper reports the fabrication of novel collagen/chitosan/β-tricalcium phosphate (CCTP) based tissue engineering scaffold. In order to improve the regeneration ability of scaffold, we have embedded raloxifene (RLX)-loaded PLGA microsphere in the CCTP scaffold. The average pore of scaffold was in the range of 150-200μm with ideal mechanical strength and swelling/degradation characteristics. The release rate of RLX from the microsphere (MS) embedded scaffold was gradual and controlled. Also a significantly enhanced cell proliferation was observed in RLX-MS exposed cell group suggesting that microsphere/scaffold could be an ideal biomaterial for bone tissue engineering. Specifically, RLX-MS showed a significantly higher Alizarin red staining indicating the higher mineralization capacity of this group. Furthermore, a high alkaline phosphatase (ALP) activity for RLX-MS exposed group after 15days incubation indicates the bone regeneration capacity of MC3T3-E1 cells. Overall, present study showed that RLX-loaded microsphere embedded scaffold has the promising potential for bone tissue engineering applications. Copyright © 2016. Published by Elsevier B.V.

Stem Cells and Scaffolds for Vascularizing Engineered Tissue Constructs

NASA Astrophysics Data System (ADS)

Luong, E.; Gerecht, S.

The clinical impact of tissue engineering depends upon our ability to direct cells to form tissues with characteristic structural and mechanical properties from the molecular level up to organized tissue. Induction and creation of functional vascular networks has been one of the main goals of tissue engineering either in vitro, for the transplantation of prevascularized constructs, or in vivo, for cellular organization within the implantation site. In most cases, tissue engineering attempts to recapitulate certain aspects of normal development in order to stimulate cell differentiation and functional tissue assembly. The induction of tissue growth generally involves the use of biodegradable and bioactive materials designed, ideally, to provide a mechanical, physical, and biochemical template for tissue regeneration. Human embryonic stem cells (hESCs), derived from the inner cell mass of a developing blastocyst, are capable of differentiating into all cell types of the body. Specifically, hESCs have the capability to differentiate and form blood vessels de novo in a process called vasculogenesis. Human ESC-derived endothelial progenitor cells (EPCs) and endothelial cells have substantial potential for microvessel formation, in vitro and in vivo. Human adult EPCs are being isolated to understand the fundamental biology of how these cells are regulated as a population and to explore whether these cells can be differentiated and reimplanted as a cellular therapy in order to arrest or even reverse damaged vasculature. This chapter focuses on advances made toward the generation and engineering of functional vascular tissue, focusing on both the scaffolds - the synthetic and biopolymer materials - and the cell sources - hESCs and hEPCs.

An update on the Application of Nanotechnology in Bone Tissue Engineering.

PubMed

Griffin, M F; Kalaskar, D M; Seifalian, A; Butler, P E

2016-01-01

Natural bone is a complex and hierarchical structure. Bone possesses an extracellular matrix that has a precise nano-sized environment to encourage osteoblasts to lay down bone by directing them through physical and chemical cues. For bone tissue regeneration, it is crucial for the scaffolds to mimic the native bone structure. Nanomaterials, with features on the nanoscale have shown the ability to provide the appropriate matrix environment to guide cell adhesion, migration and differentiation. This review summarises the new developments in bone tissue engineering using nanobiomaterials. The design and selection of fabrication methods and biomaterial types for bone tissue engineering will be reviewed. The interactions of cells with different nanostructured scaffolds will be discussed including nanocomposites, nanofibres and nanoparticles. Several composite nanomaterials have been able to mimic the architecture of natural bone. Bioceramics biomaterials have shown to be very useful biomaterials for bone tissue engineering as they have osteoconductive and osteoinductive properties. Nanofibrous scaffolds have the ability to provide the appropriate matrix environment as they can mimic the extracellular matrix structure of bone. Nanoparticles have been used to deliver bioactive molecules and label and track stem cells. Future studies to improve the application of nanomaterials for bone tissue engineering are needed.

Protein–Hydrogel Interactions in Tissue Engineering: Mechanisms and Applications

PubMed Central

Zustiak, Silviya P.; Wei, Yunqian

2013-01-01

Recent advances in our understanding of the sophistication of the cellular microenvironment and the dynamics of tissue remodeling during development, disease, and regeneration have increased our appreciation of the current challenges facing tissue engineering. As this appreciation advances, we are better equipped to approach problems in the biology and therapeutics of even more complex fields, such as stem cells and cancer. To aid in these studies, as well as the established areas of tissue engineering, including cardiovascular, musculoskeletal, and neural applications, biomaterials scientists have developed an extensive array of materials with specifically designed chemical, mechanical, and biological properties. Herein, we highlight an important topic within this area of biomaterials research, protein–hydrogel interactions. Due to inherent advantages of hydrated scaffolds for soft tissue engineering as well as specialized bioactivity of proteins and peptides, this field is well-posed to tackle major needs within emerging areas of tissue engineering. We provide an overview of the major modes of interactions between hydrogels and proteins (e.g., weak forces, covalent binding, affinity binding), examples of applications within growth factor delivery and three-dimensional scaffolds, and finally future directions within the area of hydrogel–protein interactions that will advance our ability to control the cell–biomaterial interface. PMID:23150926

Early fixation of cobalt-chromium based alloy surgical implants to bone using a tissue-engineering approach.

PubMed

Ogawa, Munehiro; Tohma, Yasuaki; Ohgushi, Hajime; Takakura, Yoshinori; Tanaka, Yasuhito

2012-01-01

To establish the methods of demonstrating early fixation of metal implants to bone, one side of a Cobalt-Chromium (CoCr) based alloy implant surface was seeded with rabbit marrow mesenchymal cells and the other side was left unseeded. The mesenchymal cells were further cultured in the presence of ascorbic acid, β-glycerophosphate and dexamethasone, resulting in the appearance of osteoblasts and bone matrix on the implant surface. Thus, we succeeded in generating tissue-engineered bone on one side of the CoCr implant. The CoCr implants were then implanted in rabbit bone defects. Three weeks after the implantation, evaluations of mechanical test, undecalcified histological section and electron microscope analysis were performed. Histological and electron microscope images of the tissue engineered surface exhibited abundant new bone formation. However, newly formed bone tissue was difficult to detect on the side without cell seeding. In the mechanical test, the mean values of pull-out forces were 77.15 N and 44.94 N for the tissue-engineered and non-cell-seeded surfaces, respectively. These findings indicate early bone fixation of the tissue-engineered CoCr surface just three weeks after implantation.

Early Fixation of Cobalt-Chromium Based Alloy Surgical Implants to Bone Using a Tissue-engineering Approach

PubMed Central

Ogawa, Munehiro; Tohma, Yasuaki; Ohgushi, Hajime; Takakura, Yoshinori; Tanaka, Yasuhito

2012-01-01

To establish the methods of demonstrating early fixation of metal implants to bone, one side of a Cobalt-Chromium (CoCr) based alloy implant surface was seeded with rabbit marrow mesenchymal cells and the other side was left unseeded. The mesenchymal cells were further cultured in the presence of ascorbic acid, β-glycerophosphate and dexamethasone, resulting in the appearance of osteoblasts and bone matrix on the implant surface. Thus, we succeeded in generating tissue-engineered bone on one side of the CoCr implant. The CoCr implants were then implanted in rabbit bone defects. Three weeks after the implantation, evaluations of mechanical test, undecalcified histological section and electron microscope analysis were performed. Histological and electron microscope images of the tissue engineered surface exhibited abundant new bone formation. However, newly formed bone tissue was difficult to detect on the side without cell seeding. In the mechanical test, the mean values of pull-out forces were 77.15 N and 44.94 N for the tissue-engineered and non-cell-seeded surfaces, respectively. These findings indicate early bone fixation of the tissue-engineered CoCr surface just three weeks after implantation. PMID:22754313

An integrated theoretical-experimental approach to accelerate translational tissue engineering.

PubMed

Coy, Rachel H; Evans, Owen R; Phillips, James B; Shipley, Rebecca J

2018-01-01

Implantable devices utilizing bioengineered tissue are increasingly showing promise as viable clinical solutions. The design of bioengineered constructs is currently directed according to the results of experiments that are used to test a wide range of different combinations and spatial arrangements of biomaterials, cells and chemical factors. There is an outstanding need to accelerate the design process and reduce financial costs, whilst minimizing the required number of animal-based experiments. These aims could be achieved through the incorporation of mathematical modelling as a preliminary design tool. Here we focus on tissue-engineered constructs for peripheral nerve repair, which are designed to aid nerve and blood vessel growth and repair after peripheral nerve injury. We offer insight into the role that mathematical modelling can play within tissue engineering, and motivate the use of modelling as a tool capable of improving and accelerating the design of nerve repair constructs in particular. Specific case studies are presented in order to illustrate the potential of mathematical modelling to direct construct design. Copyright © 2016 The Authors Journal of Tissue Engineering and Regenerative Medicine Published by John Wiley & Sons Ltd. Copyright © 2016 The Authors Journal of Tissue Engineering and Regenerative Medicine Published by John Wiley & Sons Ltd.

Using Polymeric Materials to Control Stem Cell Behavior for Tissue Regeneration

PubMed Central

Zhang, Nianli; Kohn, David H.

2017-01-01

Patients with organ failure often suffer from increased morbidity and decreased quality of life. Current strategies of treating organ failure have limitations, including shortage of donor organs, low efficiency of grafts, and immunological problems. Tissue engineering emerged about two decades ago as a strategy to restore organ function with a living, functional engineered substitute. However, the ability to engineer a functional organ substitute is limited by a limited understanding of the interactions between materials and cells that are required to yield functional tissue equivalents. Polymeric materials are one of the most promising classes of materials for use in tissue engineering due to their biodegradability, flexibility in processing and property design, and the potential to use polymer properties to control cell function. Stem cells offer potential in tissue engineering because of their unique capacity to self renew and differentiate into neurogenic, osteogenic, chondrogenic, myogenic lineages under appropriate stimuli from extracellular components. This review examines recent advances in stem cell-polymer interactions for tissue regeneration, specifically highlighting control of polymer properties to direct adhesion, proliferation, and differentiation of stem cells, and how biomaterials can be designed to provide some of the stimuli to cells that the natural extracellular matrix does. PMID:22457178

Gelatin Scaffolds with Controlled Pore Structure and Mechanical Property for Cartilage Tissue Engineering.

PubMed

Chen, Shangwu; Zhang, Qin; Nakamoto, Tomoko; Kawazoe, Naoki; Chen, Guoping

2016-03-01

Engineering of cartilage tissue in vitro using porous scaffolds and chondrocytes provides a promising approach for cartilage repair. However, nonuniform cell distribution and heterogeneous tissue formation together with weak mechanical property of in vitro engineered cartilage limit their clinical application. In this study, gelatin porous scaffolds with homogeneous and open pores were prepared using ice particulates and freeze-drying. The scaffolds were used to culture bovine articular chondrocytes to engineer cartilage tissue in vitro. The pore structure and mechanical property of gelatin scaffolds could be well controlled by using different ratios of ice particulates to gelatin solution and different concentrations of gelatin. Gelatin scaffolds prepared from ≥70% ice particulates enabled homogeneous seeding of bovine articular chondrocytes throughout the scaffolds and formation of homogeneous cartilage extracellular matrix. While soft scaffolds underwent cellular contraction, stiff scaffolds resisted cellular contraction and had significantly higher cell proliferation and synthesis of sulfated glycosaminoglycan. Compared with the gelatin scaffolds prepared without ice particulates, the gelatin scaffolds prepared with ice particulates facilitated formation of homogeneous cartilage tissue with significantly higher compressive modulus. The gelatin scaffolds with highly open pore structure and good mechanical property can be used to improve in vitro tissue-engineered cartilage.

Allogeneic versus autologous derived cell sources for use in engineered bone-ligament-bone grafts in sheep anterior cruciate ligament repair.

PubMed

Mahalingam, Vasudevan D; Behbahani-Nejad, Nilofar; Horine, Storm V; Olsen, Tyler J; Smietana, Michael J; Wojtys, Edward M; Wellik, Deneen M; Arruda, Ellen M; Larkin, Lisa M

2015-03-01

The use of autografts versus allografts for anterior cruciate ligament (ACL) reconstruction is controversial. The current popular options for ACL reconstruction are patellar tendon or hamstring autografts, yet advances in allograft technologies have made allogeneic grafts a favorable option for repair tissue. Despite this, the mismatched biomechanical properties and risk of osteoarthritis resulting from the current graft technologies have prompted the investigation of new tissue sources for ACL reconstruction. Previous work by our lab has demonstrated that tissue-engineered bone-ligament-bone (BLB) constructs generated from an allogeneic cell source develop structural and functional properties similar to those of native ACL and vascular and neural structures that exceed those of autologous patellar tendon grafts. In this study, we investigated the effectiveness of our tissue-engineered ligament constructs fabricated from autologous versus allogeneic cell sources. Our preliminary results demonstrate that 6 months postimplantation, our tissue-engineered auto- and allogeneic BLB grafts show similar histological and mechanical outcomes indicating that the autologous grafts are a viable option for ACL reconstruction. These data indicate that our tissue-engineered autologous ligament graft could be used in clinical situations where immune rejection and disease transmission may preclude allograft use.

Chm-1 gene-modified bone marrow mesenchymal stem cells maintain the chondrogenic phenotype of tissue-engineered cartilage.

PubMed

Chen, Zhuoyue; Wei, Jing; Zhu, Jun; Liu, Wei; Cui, Jihong; Li, Hongmin; Chen, Fulin

2016-05-05

Marrow mesenchymal stem cells (MSCs) can differentiate into specific phenotypes, including chondrocytes, and have been widely used for cartilage tissue engineering. However, cartilage grafts from MSCs exhibit phenotypic alternations after implantation, including matrix calcification and vascular ingrowth. We compared chondromodulin-1 (Chm-1) expression between chondrocytes and MSCs. We found that chondrocytes expressed a high level of Chm-1. We then adenovirally transduced MSCs with Chm-1 and applied modified cells to engineer cartilage in vivo. A gross inspection and histological observation indicated that the chondrogenic phenotype of the tissue-engineered cartilage graft was well maintained, and the stable expression of Chm-1 was detected by immunohistological staining in the cartilage graft derived from the Chm-1 gene-modified MSCs. Our findings defined an essential role for Chm-1 in maintaining chondrogenic phenotype and demonstrated that Chm-1 gene-modified MSCs may be used in cartilage tissue engineering.

Challenges in engineering large customized bone constructs.

PubMed

Forrestal, David P; Klein, Travis J; Woodruff, Maria A

2017-06-01

The ability to treat large tissue defects with customized, patient-specific scaffolds is one of the most exciting applications in the tissue engineering field. While an increasing number of modestly sized tissue engineering solutions are making the transition to clinical use, successfully scaling up to large scaffolds with customized geometry is proving to be a considerable challenge. Managing often conflicting requirements of cell placement, structural integrity, and a hydrodynamic environment supportive of cell culture throughout the entire thickness of the scaffold has driven the continued development of many techniques used in the production, culturing, and characterization of these scaffolds. This review explores a range of technologies and methods relevant to the design and manufacture of large, anatomically accurate tissue-engineered scaffolds with a focus on the interaction of manufactured scaffolds with the dynamic tissue culture fluid environment. Biotechnol. Bioeng. 2017;114: 1129-1139. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Tissue engineering, stem cells, cloning, and parthenogenesis: new paradigms for therapy

PubMed Central

Hipp, Jason; Atala, Anthony

2004-01-01

Patients suffering from diseased and injured organs may be treated with transplanted organs. However, there is a severe shortage of donor organs which is worsening yearly due to the aging population. Scientists in the field of tissue engineering apply the principles of cell transplantation, materials science, and bioengineering to construct biological substitutes that will restore and maintain normal function in diseased and injured tissues. Both therapeutic cloning (nucleus from a donor cell is transferred into an enucleated oocyte), and parthenogenesis (oocyte is activated and stimulated to divide), permit extraction of pluripotent embryonic stem cells, and offer a potentially limitless source of cells for tissue engineering applications. The stem cell field is also advancing rapidly, opening new options for therapy. The present article reviews recent progress in tissue engineering and describes applications of these new technologies that may offer novel therapies for patients with end-stage organ failure. PMID:15588286

Low-temperature deposition manufacturing: A novel and promising rapid prototyping technology for the fabrication of tissue-engineered scaffold.

PubMed

Liu, Wei; Wang, Daming; Huang, Jianghong; Wei, You; Xiong, Jianyi; Zhu, Weimin; Duan, Li; Chen, Jielin; Sun, Rong; Wang, Daping

2017-01-01

Developed in recent years, low-temperature deposition manufacturing (LDM) represents one of the most promising rapid prototyping technologies. It is not only based on rapid deposition manufacturing process but also combined with phase separation process. Besides the controlled macropore size, tissue-engineered scaffold fabricated by LDM has inter-connected micropores in the deposited lines. More importantly, it is a green manufacturing process that involves non-heating liquefying of materials. It has been employed to fabricate tissue-engineered scaffolds for bone, cartilage, blood vessel and nerve tissue regenerations. It is a promising technology in the fabrication of tissue-engineered scaffold similar to ideal scaffold and the design of complex organs. In the current paper, this novel LDM technology is introduced, and its control parameters, biomedical applications and challenges are included and discussed as well. Copyright © 2016 Elsevier B.V. All rights reserved.

Tissue engineering, stem cells, cloning, and parthenogenesis: new paradigms for therapy.

PubMed

Hipp, Jason; Atala, Anthony

2004-12-08

: BACKGROUND: Patients suffering from diseased and injured organs may be treated with transplanted organs. However, there is a severe shortage of donor organs which is worsening yearly due to the aging population. Scientists in the field of tissue engineering apply the principles of cell transplantation, materials science, and bioengineering to construct biological substitutes that will restore and maintain normal function in diseased and injured tissues. Both therapeutic cloning (nucleus from a donor cell is transferred into an enucleated oocyte), and parthenogenesis (oocyte is activated and stimulated to divide), permit extraction of pluripotent embryonic stem cells, and offer a potentially limitless source of cells for tissue engineering applications. The stem cell field is also advancing rapidly, opening new options for therapy. The present article reviews recent progress in tissue engineering and describes applications of these new technologies that may offer novel therapies for patients with end-stage organ failure.

The significance of cell-related challenges in the clinical application of tissue engineering.

PubMed

Almela, Thafar; Brook, Ian M; Moharamzadeh, Keyvan

2016-12-01

Tissue engineering is increasingly being recognized as a new approach that could alleviate the burden of tissue damage currently managed with transplants or synthetic devices. Making this novel approach available in the future for patients who would potentially benefit is largely dependent on understanding and addressing all those factors that impede the translation of this technology to the clinic. Cell-associated factors in particular raise many challenges, including those related to cell sources, up- and downstream techniques, preservation, and the creation of in vitro microenvironments that enable cells to grow and function as far as possible as they would in vivo. This article highlights the main confounding issues associated with cells in tissue engineering and how these issues may hinder the advancement of therapeutic tissue engineering. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 3157-3163, 2016. © 2016 Wiley Periodicals, Inc.

Biomaterial-mediated strategies targeting vascularization for bone repair.

PubMed

García, José R; García, Andrés J

2016-04-01

Repair of non-healing bone defects through tissue engineering strategies remains a challenging feat in the clinic due to the aversive microenvironment surrounding the injured tissue. The vascular damage that occurs following a bone injury causes extreme ischemia and a loss of circulating cells that contribute to regeneration. Tissue-engineered constructs aimed at regenerating the injured bone suffer from complications based on the slow progression of endogenous vascular repair and often fail at bridging the bone defect. To that end, various strategies have been explored to increase blood vessel regeneration within defects to facilitate both tissue-engineered and natural repair processes. Developments that induce robust vascularization will need to consolidate various parameters including optimization of embedded therapeutics, scaffold characteristics, and successful integration between the construct and the biological tissue. This review provides an overview of current strategies as well as new developments in engineering biomaterials to induce reparation of a functional vascular supply in the context of bone repair.

Dental pulp stem cells. Biology and use for periodontal tissue engineering.

PubMed

Ashri, Nahid Y; Ajlan, Sumaiah A; Aldahmash, Abdullah M

2015-12-01

Inflammatory periodontal disease is a major cause of loss of tooth-supporting structures. Novel approaches for regeneration of periodontal apparatus is an area of intensive research. Periodontal tissue engineering implies the use of appropriate regenerative cells, delivered through a suitable scaffold, and guided through signaling molecules. Dental pulp stem cells have been used in an increasing number of studies in dental tissue engineering. Those cells show mesenchymal (stromal) stem cell-like properties including self-renewal and multilineage differentiation potentials, aside from their relative accessibility and pleasant handling properties. The purpose of this article is to review the biological principles of periodontal tissue engineering, along with the challenges facing the development of a consistent and clinically relevant tissue regeneration platform. This article includes an updated review on dental pulp stem cells and their applications in periodontal regeneration, in combination with different scaffolds and growth factors.

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.

PCL-Based Composite Scaffold Matrices for Tissue Engineering Applications.

PubMed

Siddiqui, Nadeem; Asawa, Simran; Birru, Bhaskar; Baadhe, Ramaraju; Rao, Sreenivasa

2018-05-14

Biomaterial-based scaffolds are important cues in tissue engineering (TE) applications. Recent advances in TE have led to the development of suitable scaffold architecture for various tissue defects. In this narrative review on polycaprolactone (PCL), we have discussed in detail about the synthesis of PCL, various properties and most recent advances of using PCL and PCL blended with either natural or synthetic polymers and ceramic materials for TE applications. Further, various forms of PCL scaffolds such as porous, films and fibrous have been discussed along with the stem cells and their sources employed in various tissue repair strategies. Overall, the present review affords an insight into the properties and applications of PCL in various tissue engineering applications.

Nano-regenerative medicine towards clinical outcome of stem cell and tissue engineering in humans

PubMed Central

Arora, Pooja; Sindhu, Annu; Dilbaghi, Neeraj; Chaudhury, Ashok; Rajakumar, Govindasamy; Rahuman, Abdul Abdul

2012-01-01

Nanotechnology is a fast growing area of research that aims to create nanomaterials or nanostructures development in stem cell and tissue-based therapies. Concepts and discoveries from the fields of bio nano research provide exciting opportunities of using stem cells for regeneration of tissues and organs. The application of nanotechnology to stem-cell biology would be able to address the challenges of disease therapeutics. This review covers the potential of nanotechnology approaches towards regenerative medicine. Furthermore, it focuses on current aspects of stem- and tissue-cell engineering. The magnetic nanoparticles-based applications in stem-cell research open new frontiers in cell and tissue engineering. PMID:22260258

A tissue engineered human endometrial stroma that responds to cues for secretory differentiation, decidualization and menstruation

PubMed Central

Schutte, Stacey C.; Taylor, Robert N.

2012-01-01

Objective To show the responsiveness of a tissue engineered human endometrial stroma to combinations of hormones mimicking the secretory and menstrual phases of the cycle. Design In vitro experimental study Setting University uterine biology research laboratory Cells Telomerase immortalized human endometrial stromal cells Interventions The stromal cells were cultured in monolayers (2D) or encapsulated in a collagen I hydrogel (3D) to create a simplified tissue engineered stroma. The cells and tissues were exposed to hormone treatments mimicking early and late secretory phases, decidualization and steroid withdrawal conditions to recapitulate menstruation. Main Outcome Measure(s) Morphological and biochemical markers of decidualization and collagenase activity Result(s) The 3D tissue is capable of manifesting changes in morphology and biochemical markers of decidualization similar to 2D culture and characteristic of endometrial stroma in vivo. Unlike 2D culture, the 3D tissue responded to steroid withdrawal by increased collagenase activity and tissue breakdown. Conclusion(s) 3D tissue engineered endometrial stroma can mimic secretory and menstrual phases of the cycle and may be useful for studying uterine receptivity and menstruation in a physiological endocrine environment. PMID:22306710

The biomaterials conundrum in tissue engineering.

PubMed

Williams, David F

2014-04-01

The development of biomaterials for use in tissue engineering processes has not so far followed a scientifically valid pathway; there have been no properly constituted specifications for these biomaterials, whose choice has often been dictated by the perceived need to comply with prior FDA approval for use of the materials in nontissue engineering applications. This short essay discusses the difficulties that have resulted in this approach and provides both conceptual and practical solutions for the future, based on sound principles of biocompatibility and the need to use tissue engineering templates that replicate the niche of the target cells.

How Can Nanotechnology Help to Repair the Body? Advances in Cardiac, Skin, Bone, Cartilage and Nerve Tissue Regeneration

PubMed Central

Perán, Macarena; García, María Angel; Lopez-Ruiz, Elena; Jiménez, Gema; Marchal, Juan Antonio

2013-01-01

Nanotechnologists have become involved in regenerative medicine via creation of biomaterials and nanostructures with potential clinical implications. Their aim is to develop systems that can mimic, reinforce or even create in vivo tissue repair strategies. In fact, in the last decade, important advances in the field of tissue engineering, cell therapy and cell delivery have already been achieved. In this review, we will delve into the latest research advances and discuss whether cell and/or tissue repair devices are a possibility. Focusing on the application of nanotechnology in tissue engineering research, this review highlights recent advances in the application of nano-engineered scaffolds designed to replace or restore the followed tissues: (i) skin; (ii) cartilage; (iii) bone; (iv) nerve; and (v) cardiac. PMID:28809213

Induced Pluripotent Stem Cells and Periodontal Regeneration.

PubMed

Du, Mi; Duan, Xuejing; Yang, Pishan

Periodontitis is a chronic inflammatory disease which leads to destruction of both the soft and hard tissues of the periodontium. Tissue engineering is a therapeutic approach in regenerative medicine that aims to induce new functional tissue regeneration via the synergistic combination of cells, biomaterials, and/or growth factors. Advances in our understanding of the biology of stem cells, including embryonic stem cells and mesenchymal stem cells, have provided opportunities for periodontal tissue engineering. However, there remain a number of limitations affecting their therapeutic efficiency. Due to the considerable proliferation and differentiation capacities, recently described induced pluripotent stem cells (iPSCs) provide a new way for cell-based therapies for periodontal regeneration. This review outlines the latest status of periodontal tissue engineering and highlights the potential use of iPSCs in periodontal tissue regeneration.

Outlines on nanotechnologies applied to bladder tissue engineering.

PubMed

Alberti, C

2012-01-01

Tissue engineering technologies are more and more expanding as consequence of recent developments in the field of biomaterial science and nanotechnology research. An important issue in designing scaffold materials is that of recreating the ECM (extra-cellular matrix) functional features - particularly ECM-derived complex molecule signalling - to mimic its capability of directing cell-growth and neotissue morphogenesis. In this way the nanotechnology may offer intriguing chances, biomaterial nanoscale-based scaffold geometry behaving as nanomechanotransducer complex interacting with different cell nanosize proteins, especially with those of cell surface mechanoreceptors. To fabricate 3D-scaffold complex architectures, endowed with controlled geometry and functional properties, bottom-up approaches, based on molecular self-assembling of small building polymer units, are used, sometimes functionalizing them by incorporation of bioactive peptide sequences such as RDG (arginine - glycine - aspartic acid, a cell-integrin binding domain of fibronectin), whereas the top-down approaches are useful to fabricate micro/nanoscale structures, such as a microvasculature within an existing complex bioarchitecture. Synthetic polymer-based nanofibers, produced by electrospinning process, may be used to create fibrous scaffolds that can facilitate, given their nanostructured geometry and surface roughness, cell adhesion and growth. Also bladder tissue engineering may benefit by nanotechnology advances to achieve a better reliability of the bladder engineered tissue. Particularly, bladder smooth muscle cell adhesion to nanostructured polymeric surfaces is significantly enhanced in comparison with that to conventional biomaterials. Moreover nanostructured surfaces of bladder engineered tissue show a decreased calcium stone production. In a bladder tumor animal model, the dispersion of carbon nanofibers in a polymeric scaffold-based tissue engineered replacement neobladder, appears to inhibit a carcinogenic relapse in bladder prosthetic material. Facing the future, a full success of bladder tissue engineering will mainly depend on the progress of both biomaterial nanotechnologies and stem cell biology research.

Bone Marrow Mesenchymal Stem Cell-Based Engineered Cartilage Ameliorates Polyglycolic Acid/Polylactic Acid Scaffold-Induced Inflammation Through M2 Polarization of Macrophages in a Pig Model.

PubMed

Ding, Jinping; Chen, Bo; Lv, Tao; Liu, Xia; Fu, Xin; Wang, Qian; Yan, Li; Kang, Ning; Cao, Yilin; Xiao, Ran

2016-08-01

: The regeneration of tissue-engineered cartilage in an immunocompetent environment usually fails due to severe inflammation induced by the scaffold and their degradation products. In the present study, we compared the tissue remodeling and the inflammatory responses of engineered cartilage constructed with bone marrow mesenchymal stem cells (BMSCs), chondrocytes, or both and scaffold group in pigs. The cartilage-forming capacity of the constructs in vitro and in vivo was evaluated by histological, biochemical, and biomechanical analyses, and the inflammatory response was investigated by quantitative analysis of foreign body giant cells and macrophages. Our data revealed that BMSC-based engineered cartilage suppressed in vivo inflammation through the alteration of macrophage phenotype, resulting in better tissue survival compared with those regenerated with chondrocytes alone or in combination with BMSCs. To further confirm the macrophage phenotype, an in vitro coculture system established by engineered cartilage and macrophages was studied using immunofluorescence, enzyme-linked immunosorbent assay, and gene expression analysis. The results demonstrated that BMSC-based engineered cartilage promoted M2 polarization of macrophages with anti-inflammatory phenotypes including the upregulation of CD206, increased IL-10 synthesis, decreased IL-1β secretion, and alterations in gene expression indicative of M1 to M2 transition. It was suggested that BMSC-seeded constructs have the potential to ameliorate scaffold-induced inflammation and improve cartilaginous tissue regeneration through M2 polarization of macrophages. Finding a strategy that can prevent scaffold-induced inflammation is of utmost importance for the regeneration of tissue-engineered cartilage in an immunocompetent environment. This study demonstrated that bone marrow mesenchymal stem cell (BMSC)-based engineered cartilage could suppress inflammation by increasing M2 polarization of macrophages, resulting in better tissue survival in a pig model. Additionally, the effect of BMSC-based cartilage on the phenotype conversion of macrophages was further studied through an in vitro coculture system. This study could provide further support for the regeneration of cartilage engineering in immunocompetent animal models and provide new insight into the interaction of tissue-engineered cartilage and macrophages. ©AlphaMed Press.

Tissue engineering in periodontal tissue.

PubMed

Iwata, Takanori; Yamato, Masayuki; Ishikawa, Isao; Ando, Tomohiro; Okano, Teruo

2014-01-01

Periodontitis, a recognized disease worldwide, is bacterial infection-induced inflammation of the periodontal tissues that results in loss of alveolar bone. Once it occurs, damaged tissue cannot be restored to its original form, even if decontaminating treatments are performed. For more than half a century, studies have been conducted to investigate true periodontal regeneration. Periodontal regeneration is the complete reconstruction of the damaged attachment apparatus, which contains both hard tissue (alveolar bone and cementum) and soft tissue (periodontal ligament). Several treatments, including bone grafts, guided tissue regeneration with physical barriers for epithelial cells, and growth factors have been approved for clinical use; however, their indications and outcomes are limited. To overcome these limitations, the concept of "tissue engineering" was introduced. Combination treatment using cells, growth factors, and scaffolds, has been studied in experimental animal models, and some studies have been translated into clinical trials. In this review, we focus on recent progressive tissue engineering studies and discuss future perspectives on periodontal regeneration. Copyright © 2013 Wiley Periodicals, Inc.

Design and Fabrication of an MRI-Compatible, Autonomous Incubation System.

PubMed

Khalilzad-Sharghi, Vahid; Xu, Huihui

2015-10-01

Tissue engineers have long sought access to an autonomous, imaging-compatible tissue incubation system that, with minimum operator handling, can provide real-time visualization and quantification of cells, tissue constructs, and organs. This type of screening system, capable of operating noninvasively to validate tissue, can overcome current limitations like temperature shock, unsustainable cellular environments, sample contamination, and handling/stress. However, this type of system has been a major challenge, until now. Here, we describe the design, fabrication, and characterization of an innovative, autonomous incubation system that is compatible with a 9.4 T magnetic resonance imaging (MRI) scanner. Termed the e-incubator (patent pending; application number: 13/953,984), this microcontroller-based system is integrated into an MRI scanner and noninvasively screens cells and tissue cultures in an environment where temperature, pH, and media/gas handling are regulated. The 4-week study discussed herein details the continuous operation of the e-incubator for a tissue-engineered osteogenic construct, validated by LIVE/DEAD(®) cell assays and histology. The evolving MR quantitative parameters of the osteogenic construct were used as biomarkers for bone tissue engineering and to further validate the quality of the product noninvasively before harvesting. Importantly, the e-incubator reliably facilitates culturing cells and tissue constructs to create engineered tissues and/or investigate disease therapies.

Man as a living bioreactor: Long-term histological aspects of a mandibular replacement engineered in the patient's own body.

PubMed

Naujokat, H; Açil, Y; Gülses, A; Birkenfeld, F; Wiltfang, J

2018-05-26

In 2016, we reported the world's first reconstruction of a mandibular discontinuity defect using a custom-made bone transplant that had been prefabricated in the gastrocolic omentum using tissue engineering strategies. However, the tissue of an engineered human neomandible has not been evaluated histologically until now. The current study assessed the long-term histological characteristics of biopsies of the neomandible 9months after transplantation. Histological analysis showed an increased amount of vital mineralized bone tissue after 10months, in comparison to biopsies obtained earlier. The engineered bone covered the surface of the bone substitute material but also grew out typical structures of cancellous bone tissue without a core of BioOss. The amount of induced bone tissue was 32% in the biopsy. In addition, the soft tissue showed an alignment of the connective tissue fibres parallel to the trabecular bone. Increasing time and mechanical forces at the mandible led to an increased amount of mineralized tissue and remodelling of the connective tissue fibres after transplantation. Further research should focus on developing advanced scaffold materials, as the outer titanium mesh cage leads to complications. Copyright © 2018 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Directed 3D Cell Alignment and Elongation in Microengineered Hydrogels

DTIC Science & Technology

2010-01-01

Merok J, Vunjak- Novakovic G, Freed LE. Tissue engineering of functional cardiac muscle: molecular, structural, and electro- physiological studies. Am J...endothelial cells and smooth muscle cells. J Biomech 2004;37(4):531e9. [4] Vunjak- Novakovic G, Altman G, Horan R, Kaplan DL. Tissue engineering of...483e95. [9] Burdick JA, Vunjak- Novakovic G. Engineered microenvironments for controlled stem cell differentiation. Tissue Eng Part A 2009;15(2):205e19

Bone tissue engineering: a review in bone biomimetics and drug delivery strategies.

PubMed

Porter, Joshua R; Ruckh, Timothy T; Popat, Ketul C

2009-01-01

Critical-sized defects in bone, whether induced by primary tumor resection, trauma, or selective surgery have in many cases presented insurmountable challenges to the current gold standard treatment for bone repair. The primary purpose of a tissue-engineered scaffold is to use engineering principles to incite and promote the natural healing process of bone which does not occur in critical-sized defects. A synthetic bone scaffold must be biocompatible, biodegradable to allow native tissue integration, and mimic the multidimensional hierarchical structure of native bone. In addition to being physically and chemically biomimetic, an ideal scaffold is capable of eluting bioactive molecules (e.g., BMPs, TGF-betas, etc., to accelerate extracellular matrix production and tissue integration) or drugs (e.g., antibiotics, cisplatin, etc., to prevent undesired biological response such as sepsis or cancer recurrence) in a temporally and spatially controlled manner. Various biomaterials including ceramics, metals, polymers, and composites have been investigated for their potential as bone scaffold materials. However, due to their tunable physiochemical properties, biocompatibility, and controllable biodegradability, polymers have emerged as the principal material in bone tissue engineering. This article briefly reviews the physiological and anatomical characteristics of native bone, describes key technologies in mimicking the physical and chemical environment of bone using synthetic materials, and provides an overview of local drug delivery as it pertains to bone tissue engineering is included. (c) 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009.

Whyever bladder tissue engineering clinical applications still remain unusual even though many intriguing technological advances have been reached?

PubMed

Alberti, C

2016-01-01

To prevent problematic outcomes of bowel-based bladder reconstructive surgery, such as prosthetic tumors and systemic metabolic complications, research works, to either regenerate and strengthen failing organ or build organ replacement biosubstitute, have been turned, from 90s of the last century, to both regenerative medicine and tissue engineering.Various types of acellular matrices, naturally-derived materials, synthetic polymers have been used for either "unseeded" (cell free) or autologous "cell seeded" tissue engineering scaffolds. Different categories of cell sources - from autologous differentiated urothelial and smooth muscle cells to natural or laboratory procedure-derived stem cells - have been taken into consideration to reach the construction of suitable "cell seeded" templates. Current clinically validated bladder tissue engineering approaches essentially consist of augmentation cystoplasty in patients suffering from poorly compliant neuropathic bladder. No clinical applications of wholly tissue engineered neobladder have been carried out to radical-reconstructive surgical treatment of bladder malignancies or chronic inflammation-due vesical coarctation. Reliable reasons why bladder tissue engineering clinical applications so far remain unusual, particularly imply the risk of graft ischemia, hence its both fibrous contraction and even worse perforation. Therefore, the achievement of graft vascular network (vasculogenesis) could allow, together with the promotion of host surrounding vessel sprouting (angiogenesis), an effective graft blood supply, so avoiding the ischemia-related serious complications.

Effects of mechanical loading on human mesenchymal stem cells for cartilage tissue engineering.

PubMed

Choi, Jane Ru; Yong, Kar Wey; Choi, Jean Yu

2018-03-01

Today, articular cartilage damage is a major health problem, affecting people of all ages. The existing conventional articular cartilage repair techniques, such as autologous chondrocyte implantation (ACI), microfracture, and mosaicplasty, have many shortcomings which negatively affect their clinical outcomes. Therefore, it is essential to develop an alternative and efficient articular repair technique that can address those shortcomings. Cartilage tissue engineering, which aims to create a tissue-engineered cartilage derived from human mesenchymal stem cells (MSCs), shows great promise for improving articular cartilage defect therapy. However, the use of tissue-engineered cartilage for the clinical therapy of articular cartilage defect still remains challenging. Despite the importance of mechanical loading to create a functional cartilage has been well demonstrated, the specific type of mechanical loading and its optimal loading regime is still under investigation. This review summarizes the most recent advances in the effects of mechanical loading on human MSCs. First, the existing conventional articular repair techniques and their shortcomings are highlighted. The important parameters for the evaluation of the tissue-engineered cartilage, including chondrogenic and hypertrophic differentiation of human MSCs are briefly discussed. The influence of mechanical loading on human MSCs is subsequently reviewed and the possible mechanotransduction signaling is highlighted. The development of non-hypertrophic chondrogenesis in response to the changing mechanical microenvironment will aid in the establishment of a tissue-engineered cartilage for efficient articular cartilage repair. © 2017 Wiley Periodicals, Inc.

Microcomputed tomography characterization of neovascularization in bone tissue engineering applications.

PubMed

Young, Simon; Kretlow, James D; Nguyen, Charles; Bashoura, Alex G; Baggett, L Scott; Jansen, John A; Wong, Mark; Mikos, Antonios G

2008-09-01

Vasculogenesis and angiogenesis have been studied for decades using numerous in vitro and in vivo systems, fulfilling the need to elucidate the mechanisms involved in these processes and to test potential therapeutic agents that inhibit or promote neovascularization. Bone tissue engineering in particular has benefited from the application of proangiogenic strategies, considering the need for an adequate vascular supply during healing and the challenges associated with the vascularization of scaffolds implanted in vivo. Conventional methods of assessing the in vivo angiogenic response to tissue-engineered constructs tend to rely on a two-dimensional assessment of microvessel density within representative histological sections without elaboration of the true vascular tree. The introduction of microcomputed tomography (micro-CT) has recently allowed investigators to obtain a diverse range of high-resolution, three-dimensional characterization of structures, including renal, coronary, and hepatic vascular networks, as well as bone formation within healing defects. To date, few studies have utilized micro-CT to study the vascular response to an implanted tissue engineering scaffold. In this paper, conventional in vitro and in vivo models for studying angiogenesis will be discussed, followed by recent developments in the use of micro-CT for vessel imaging in bone tissue engineering research. A new study demonstrating the potential of contrast-enhanced micro-CT for the evaluation of in vivo neovascularization in bony defects is described, which offers significant potential in the evaluation of bone tissue engineering constructs.

Recent advances in gene-enhanced bone tissue engineering.

PubMed

Betz, Volker M; Kochanek, Stefan; Rammelt, Stefan; Müller, Peter E; Betz, Oliver B; Messmer, Carolin

2018-03-30

The loss of bone tissue represents a critical clinical condition that is frequently faced by surgeons. Substantial progress has been made in the area of bone research, providing insight into the biology of bone under physiological and pathological conditions, as well as tools for the stimulation of bone regeneration. The present review discusses recent advances in the field of gene-enhanced bone tissue engineering. Gene transfer strategies have emerged as highly effective tissue engineering approaches for supporting the repair of the musculoskeletal system. By contrast to treatment with recombinant proteins, genetically engineered cells can release growth factors at the site of injury over extended periods of time. Of particular interest are the expedited technologies that can be applied during a single surgical procedure in a cost-effective manner, allowing translation from bench to bedside. Several promising methods based on the intra-operative genetic manipulation of autologous cells or tissue fragments have been developed in preclinical studies. Moreover, gene therapy for bone regeneration has entered the clinical stage with clinical trials for the repair of alveolar bone. Current trends in gene-enhanced bone engineering are also discussed with respect to the movement of the field towards expedited, translational approaches. It is possible that gene-enhanced bone tissue engineering will become a clinical reality within the next few years. Copyright © 2018 John Wiley & Sons, Ltd.

Reducing the number of laboratory animals used in tissue engineering research by restricting the variety of animal models. Articular cartilage tissue engineering as a case study.

PubMed

de Vries, Rob B M; Buma, Pieter; Leenaars, Marlies; Ritskes-Hoitinga, Merel; Gordijn, Bert

2012-12-01

The use of laboratory animals in tissue engineering research is an important underexposed ethical issue. Several ethical questions may be raised about this use of animals. This article focuses on the possibilities of reducing the number of animals used. Given that there is considerable debate about the adequacy of the current animal models in tissue engineering research, we investigate whether it is possible to reduce the number of laboratory animals by selecting and using only those models that have greatest predictive value for future clinical application of the tissue engineered product. The field of articular cartilage tissue engineering is used as a case study. Based on a study of the scientific literature and interviews with leading experts in the field, an overview is provided of the animal models used and the advantages and disadvantages of each model, particularly in terms of extrapolation to the human situation. Starting from this overview, it is shown that, by skipping the small models and using only one large preclinical model, it is indeed possible to restrict the number of animal models, thereby reducing the number of laboratory animals used. Moreover, it is argued that the selection of animal models should become more evidence based and that researchers should seize more opportunities to choose or create characteristics in the animal models that increase their predictive value.

Engineered carbon (biochar) prepared by direct pyrolysis of Mg-accumulated tomato tissues: Characterization and phosphate removal potential

USDA-ARS?s Scientific Manuscript database

An innovative synthesis was developed to produce engineered biochar from magnesium (Mg) enriched tomato tissues through slow pyrolysis in a N2 environment. The resulting Mg-biochar composites showed excellent sorption ability to phosphate in aqueous solutions. The engineered biochar contained nanosc...

A review of evolution of electrospun tissue engineering scaffold: From two dimensions to three dimensions.

PubMed

Ngadiman, Nor Hasrul Akhmal; Noordin, M Y; Idris, Ani; Kurniawan, Denni

2017-07-01

The potential of electrospinning process to fabricate ultrafine fibers as building blocks for tissue engineering scaffolds is well recognized. The scaffold construct produced by electrospinning process depends on the quality of the fibers. In electrospinning, material selection and parameter setting are among many factors that contribute to the quality of the ultrafine fibers, which eventually determine the performance of the tissue engineering scaffolds. The major challenge of conventional electrospun scaffolds is the nature of electrospinning process which can only produce two-dimensional electrospun mats, hence limiting their applications. Researchers have started to focus on overcoming this limitation by combining electrospinning with other techniques to fabricate three-dimensional scaffold constructs. This article reviews various polymeric materials and their composites/blends that have been successfully electrospun for tissue engineering scaffolds, their mechanical properties, and the various parameters settings that influence the fiber morphology. This review also highlights the secondary processes to electrospinning that have been used to develop three-dimensional tissue engineering scaffolds as well as the steps undertaken to overcome electrospinning limitations.

Application of stem cells for cardiovascular grafts tissue engineering.

PubMed

Wu, Kaihong; Liu, Ying Long; Cui, Bin; Han, Zhongchao

2006-06-01

Congenital and acquired heart diseases are leading causes of morbidity and mortality world-wide. Currently, the synthetic materials or bioprosthetic replacement devices for cardiovascular surgery are imperfect and subject patients to one or more ongoing risks including thrombosis, limited durability and need for reoperations due to lack of growth in children and young adults. Suitable replacement grafts should have appropriate characteristics, including resistance to infection, low immunogenicity, good biocompatability and thromboresistance, with appropriate mechanical and physiological properties. Tissue engineering is a new scientific field aiming at fabrication of living, autologous grafts having structure or function properties that can be used to restore, maintain or improve tissue function. The use of autologous stem cells in cardiovascular tissue engineering is quite promising due to their capacity of self-renewal, high proliferation, and differentiation into specialized progeny. Progress has been made in engineering the various components of the cardiovascular system, including myocardial constructs, heart valves, and vascular patches or conduits with autologous stem cells. This paper will review the current achievements in stem cell-based cardiovascular grafts tissue engineering, with an emphasis on its clinical or possible clinical use in cardiovascular surgery.

A practical model for economic evaluation of tissue-engineered therapies.

PubMed

Tan, Tien-En; Peh, Gary S L; Finkelstein, Eric A; Mehta, Jodhbir S

2015-01-01

Tissue-engineered therapies are being developed across virtually all fields of medicine. Some of these therapies are already in clinical use, while others are still in clinical trials or the experimental phase. Most initial studies in the evaluation of new therapies focus on demonstration of clinical efficacy. However, cost considerations or economic viability are just as important. Many tissue-engineered therapies have failed to be impactful because of shortcomings in economic competitiveness, rather than clinical efficacy. Furthermore, such economic viability studies should be performed early in the process of development, before significant investment has been made. Cost-minimization analysis combined with sensitivity analysis is a useful model for the economic evaluation of new tissue-engineered therapies. The analysis can be performed early in the development process, and can provide valuable information to guide further investment and research. The utility of the model is illustrated with the practical real-world example of tissue-engineered constructs for corneal endothelial transplantation. The authors have declared no conflicts of interest for this article. © 2015 Wiley Periodicals, Inc.

The use of bone marrow stromal cells (bone marrow-derived multipotent mesenchymal stromal cells) for alveolar bone tissue engineering: basic science to clinical translation.

PubMed

Kagami, Hideaki; Agata, Hideki; Inoue, Minoru; Asahina, Izumi; Tojo, Arinobu; Yamashita, Naohide; Imai, Kohzoh

2014-06-01

Bone tissue engineering is a promising field of regenerative medicine in which cultured cells, scaffolds, and osteogenic inductive signals are used to regenerate bone. Human bone marrow stromal cells (BMSCs) are the most commonly used cell source for bone tissue engineering. Although it is known that cell culture and induction protocols significantly affect the in vivo bone forming ability of BMSCs, the responsible factors of clinical outcome are poorly understood. The results from recent studies using human BMSCs have shown that factors such as passage number and length of osteogenic induction significantly affect ectopic bone formation, although such differences hardly affected the alkaline phosphatase activity or gene expression of osteogenic markers. Application of basic fibroblast growth factor helped to maintain the in vivo osteogenic ability of BMSCs. Importantly, responsiveness of those factors should be tested under clinical circumstances to improve the bone tissue engineering further. In this review, clinical application of bone tissue engineering was reviewed with putative underlying mechanisms.

CRISPR/Cas9 Editing of Murine Induced Pluripotent Stem Cells for Engineering Inflammation-Resistant Tissues.

PubMed

Brunger, Jonathan M; Zutshi, Ananya; Willard, Vincent P; Gersbach, Charles A; Guilak, Farshid

2017-05-01

Proinflammatory cytokines such as interleukin-1 (IL-1) are found in elevated levels in diseased or injured tissues and promote rapid tissue degradation while preventing stem cell differentiation. This study was undertaken to engineer inflammation-resistant murine induced pluripotent stem cells (iPSCs) through deletion of the IL-1 signaling pathway and to demonstrate the utility of these cells for engineering replacements for diseased or damaged tissues. Targeted deletion of the IL-1 receptor type I (IL-1RI) gene in murine iPSCs was achieved using the RNA-guided, site-specific clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 genome engineering system. Clonal cell populations with homozygous and heterozygous deletions were isolated, and loss of receptor expression and cytokine signaling was confirmed by flow cytometry and transcriptional reporter assays, respectively. Cartilage was engineered from edited iPSCs and tested for its ability to resist IL-1-mediated degradation in gene expression, histologic, and biomechanical assays after a 3-day treatment with 1 ng/ml of IL-1α. Three of 41 clones isolated possessed the IL-1RI +/- genotype. Four clones possessed the IL-1RI -/- genotype, and flow cytometry confirmed loss of IL-1RI on the surface of these cells, which led to an absence of NF-κB transcription activation after IL-1α treatment. Cartilage engineered from homozygous null clones was resistant to cytokine-mediated tissue degradation. In contrast, cartilage derived from wild-type and heterozygous clones exhibited significant degradative responses, highlighting the need for complete IL-1 blockade. This work demonstrates proof-of-concept of the ability to engineer custom-designed stem cells that are immune to proinflammatory cytokines (i.e., IL-1) as a potential cell source for cartilage tissue engineering. © 2016, American College of Rheumatology.

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.

Poly(dopamine) coating to biodegradable polymers for bone tissue engineering.

PubMed

Tsai, Wei-Bor; Chen, Wen-Tung; Chien, Hsiu-Wen; Kuo, Wei-Hsuan; Wang, Meng-Jiy

2014-02-01

In this study, a technique based on poly(dopamine) deposition to promote cell adhesion was investigated for the application in bone tissue engineering. The adhesion and proliferation of rat osteoblasts were evaluated on poly(dopamine)-coated biodegradable polymer films, such as polycaprolactone, poly(l-lactide) and poly(lactic-co-glycolic acid), which are commonly used biodegradable polymers in tissue engineering. Cell adhesion was significantly increased to a plateau by merely 15 s of dopamine incubation, 2.2-4.0-folds of increase compared to the corresponding untreated substrates. Cell proliferation was also greatly enhanced by poly(dopamine) deposition, indicated by shortened cell doubling time. Mineralization was also increased on the poly(dopamine)-deposited surfaces. The potential of poly(dopamine) deposition in bone tissue engineering is demonstrated in this study.

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.

Advantages and challenges offered by biofunctional core-shell fiber systems for tissue engineering and drug delivery.

PubMed

Sperling, Laura E; Reis, Karina P; Pranke, Patricia; Wendorff, Joachim H

2016-08-01

Whereas highly porous scaffolds composed of electrospun nanofibers can mimick major features of the extracellular matrix in tissue engineering, they lack the ability to incorporate and release biocompounds (drugs, growth factors) safely in a controlled way. Here, electrospun core-shell fibers (core made from water and aqueous solutions of hydrophilic polymers and the shell from materials with well-defined release mechanisms) offer unique advantages in comparison with those that have helped make porous nanofibrillar scaffolds highly successful in tissue engineering. This review considers the preparation and biofunctionalization of such core-shell fibers as well as applications in various areas, including neural, vascular, cardiac, cartilage and bone tissue engineering, and touches on the topic of clinical trials. Copyright © 2016 Elsevier Ltd. All rights reserved.

A review on chitosan centred scaffolds and their applications in tissue engineering.

PubMed

Ahmed, Shakeel; Annu; Sheikh, Javed; Ali, Akbar

2018-05-03

The diversity and availability of biopolymer and increased clinical demand for safe scaffolds lead to an increased interest in fabricating scaffolds in order to achieve fruitful progress in tissue engineering. Due to biocompatibility, biodegradability, inherent antimicrobial character, chitosan has drawn ample consideration in recent years. Chitosan is a biopolymer obtained by de-acetylation of chitin extracted from shells of crustaceans and fungi. Due to the presence of reactive functionality in the molecular chain chitosan can be modified either chemically or physically to fabricate the tailor-made scaffolds having desired properties for tissue engineering centered applications. In this review chitosan, its properties and role either virgin, chemically or physically modified, 2D or 3D scaffolds for tissue engineering application have been highlighted. Copyright © 2017. Published by 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.

Fiber-reinforced scaffolds in soft tissue engineering

PubMed Central

Wang, Wei; Fan, Yubo; Wang, Xiumei; Watari, Fumio

2017-01-01

Abstract Soft tissue engineering has been developed as a new strategy for repairing damaged or diseased soft tissues and organs to overcome the limitations of current therapies. Since most of soft tissues in the human body are usually supported by collagen fibers to form a three-dimensional microstructure, fiber-reinforced scaffolds have the advantage to mimic the structure, mechanical and biological environment of natural soft tissues, which benefits for their regeneration and remodeling. This article reviews and discusses the latest research advances on design and manufacture of novel fiber-reinforced scaffolds for soft tissue repair and how fiber addition affects their structural characteristics, mechanical strength and biological activities in vitro and in vivo. In general, the concept of fiber-reinforced scaffolds with adjustable microstructures, mechanical properties and degradation rates can provide an effective platform and promising method for developing satisfactory biomechanically functional implantations for soft tissue engineering or regenerative medicine. PMID:28798872

An evaluation of Admedus' tissue engineering process-treated (ADAPT) bovine pericardium patch (CardioCel) for the repair of cardiac and vascular defects.

PubMed

Strange, Geoff; Brizard, Christian; Karl, Tom R; Neethling, Leon

2015-03-01

Tissue engineers have been seeking the 'Holy Grail' solution to calcification and cytotoxicity of implanted tissue for decades. Tissues with all of the desired qualities for surgical repair of congenital heart disease (CHD) are lacking. An anti-calcification tissue engineering process (ADAPT TEP) has been developed and applied to bovine pericardium (BP) tissue (CardioCel, AdmedusRegen Pty Ltd, Perth, WA, Australia) to eliminate cytotoxicity, improve resistance to acute and chronic inflammation, reduce calcification and facilitate controlled tissue remodeling. Clinical data in pediatric patients, and additional pre-market authorized prescriber data demonstrate that CardioCel performs extremely well in the short term and is safe and effective for a range of congenital heart deformations. These data are supported by animal studies which have shown no more than normal physiologic levels of calcification, with good durability, biocompatibility and controlled healing.

Engineering cellular fibers for musculoskeletal soft tissues using directed self-assembly.

PubMed

Schiele, Nathan R; Koppes, Ryan A; Chrisey, Douglas B; Corr, David T

2013-05-01

Engineering strategies guided by developmental biology may enhance and accelerate in vitro tissue formation for tissue engineering and regenerative medicine applications. In this study, we looked toward embryonic tendon development as a model system to guide our soft tissue engineering approach. To direct cellular self-assembly, we utilized laser micromachined, differentially adherent growth channels lined with fibronectin. The micromachined growth channels directed human dermal fibroblast cells to form single cellular fibers, without the need for a provisional three-dimensional extracellular matrix or scaffold to establish a fiber structure. Therefore, the resulting tissue structure and mechanical characteristics were determined solely by the cells. Due to the self-assembly nature of this approach, the growing fibers exhibit some key aspects of embryonic tendon development, such as high cellularity, the rapid formation (within 24 h) of a highly organized and aligned cellular structure, and the expression of cadherin-11 (indicating direct cell-to-cell adhesions). To provide a dynamic mechanical environment, we have also developed and characterized a method to apply precise cyclic tensile strain to the cellular fibers as they develop. After an initial period of cellular fiber formation (24 h postseeding), cyclic strain was applied for 48 h, in 8-h intervals, with tensile strain increasing from 0.7% to 1.0%, and at a frequency of 0.5 Hz. Dynamic loading dramatically increased cellular fiber mechanical properties with a nearly twofold increase in both the linear region stiffness and maximum load at failure, thereby demonstrating a mechanism for enhancing cellular fiber formation and mechanical properties. Tissue engineering strategies, designed to capture key aspects of embryonic development, may provide unique insight into accelerated maturation of engineered replacement tissue, and offer significant advances for regenerative medicine applications in tendon, ligament, and other fibrous soft tissues.

Engineering Pre-vascularized Scaffolds for Bone Regeneration.

PubMed

Barabaschi, Giada D G; Manoharan, Vijayan; Li, Qing; Bertassoni, Luiz E

2015-01-01

Survival of functional tissue constructs of clinically relevant size depends on the formation of an organized and uniformly distributed network of blood vessels and capillaries. The lack of such vasculature leads to spatio-temporal gradients in oxygen, nutrients and accumulation of waste products inside engineered tissue constructs resulting in negative biological events at the core of the scaffold. Unavailability of a well-defined vasculature also results in ineffective integration of scaffolds to the host vasculature upon implantation. Arguably, one of the greatest challenges in engineering clinically relevant bone substitutes, therefore, has been the development of vascularized bone scaffolds. Various approaches ranging from peptide and growth factor functionalized biomaterials to hyper-porous scaffolds have been proposed to address this problem with reasonable success. An emerging alternative to address this challenge has been the fabrication of pre-vascularized scaffolds by taking advantage of biomanufacturing techniques, such as soft- and photo-lithography or 3D bioprinting, and cell-based approaches, where functional capillaries are engineered in cell-laden scaffolds prior to implantation. These strategies seek to engineer pre-vascularized tissues in vitro, allowing for improved anastomosis with the host vasculature upon implantation, while also improving cell viability and tissue development in vitro. This book chapter provides an overview of recent methods to engineer pre-vascularized scaffolds for bone regeneration. We first review the development of functional blood capillaries in bony structures and discuss controlled delivery of growth factors, co-culture systems, and on-chip studies to engineer vascularized cell-laden biomaterials. Lastly, we review recent studies using microfabrication techniques and 3D printing to engineer pre-vascularized scaffolds for bone tissue engineering.

Noninvasive metabolic imaging of engineered 3D human adipose tissue in a perfusion bioreactor.

PubMed

Ward, Andrew; Quinn, Kyle P; Bellas, Evangelia; Georgakoudi, Irene; Kaplan, David L

2013-01-01

The efficacy and economy of most in vitro human models used in research is limited by the lack of a physiologically-relevant three-dimensional perfused environment and the inability to noninvasively quantify the structural and biochemical characteristics of the tissue. The goal of this project was to develop a perfusion bioreactor system compatible with two-photon imaging to noninvasively assess tissue engineered human adipose tissue structure and function in vitro. Three-dimensional (3D) vascularized human adipose tissues were engineered in vitro, before being introduced to a perfusion environment and tracked over time by automated quantification of endogenous markers of metabolism using two-photon excited fluorescence (TPEF). Depth-resolved image stacks were analyzed for redox ratio metabolic profiling and compared to prior analyses performed on 3D engineered adipose tissue in static culture. Traditional assessments with H&E staining were used to qualitatively measure extracellular matrix generation and cell density with respect to location within the tissue. The distribution of cells within the tissue and average cellular redox ratios were different between static and perfusion cultures, while the trends of decreased redox ratio and increased cellular proliferation with time in both static and perfusion cultures were similar. These results establish a basis for noninvasive optical tracking of tissue structure and function in vitro, which can be applied to future studies to assess tissue development or drug toxicity screening and disease progression.

Carbon nanotube scaffolds as emerging nanoplatform for myocardial tissue regeneration: A review of recent developments and therapeutic implications.

PubMed

Gorain, Bapi; Choudhury, Hira; Pandey, Manisha; Kesharwani, Prashant; Abeer, Muhammad Mustafa; Tekade, Rakesh Kumar; Hussain, Zahid

2018-08-01

Myocardial infarction (cardiac tissue death) is among the most prevalent causes of death among the cardiac patients due to the inability of self-repair in cardiac tissues. Myocardial tissue engineering is regarded as one of the most realistic strategies for repairing damaged cardiac tissue. However, hindrance in transduction of electric signals across the cardiomyocytes due to insulating properties of polymeric materials worsens the clinical viability of myocardial tissue engineering. Aligned and conductive scaffolds based on Carbon nanotubes (CNT) have gained remarkable recognition due to their exceptional attributes which provide synthetic but viable microenvironment for regeneration of engineered cardiomyocytes. This review presents an overview and critical analysis of pharmaceutical implications and therapeutic feasibility of CNT based scaffolds in improving the cardiac tissue regeneration and functionality. The expository analysis of the available evidence revealed that inclusion of single- or multi-walled CNT into fibrous, polymeric, and elastomeric scaffolds results in significant improvement in electrical stimulation and signal transduction through cardiomyocytes. Moreover, incorporation of CNT in engineering scaffolds showed a greater potential of augmenting cardiomyocyte proliferation, differentiation, and maturation and has improved synchronous beating of cardiomyocytes. Despite promising ability of CNT in promoting functionality of cardiomyocytes, their presence in scaffolds resulted in substantial improvement in mechanical properties and structural integrity. Conclusively, this review provides new insight into the remarkable potential of CNT aligned scaffolds in improving the functionality of engineered cardiac tissue and signifies their feasibility in cardiac tissue regenerative medicines and stem cell therapy. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Stem Cell-based Tissue Engineering Approaches for Musculoskeletal Regeneration

PubMed Central

Brown, Patrick T.; Handorf, Andrew M.; Jeon, Won Bae; Li, Wan-Ju

2014-01-01

The field of regenerative medicine and tissue engineering is an ever evolving field that holds promise in treating numerous musculoskeletal diseases and injuries. An important impetus in the development of the field was the discovery and implementation of stem cells. The utilization of mesenchymal stem cells, and later embryonic and induced pluripotent stem cells, opens new arenas for tissue engineering and presents the potential of developing stem cell-based therapies for disease treatment. Multipotent and pluripotent stem cells can produce various lineage tissues, and allow for derivation of a tissue that may be comprised of multiple cell types. As the field grows, the combination of biomaterial scaffolds and bioreactors provides methods to create an environment for stem cells that better represent their microenvironment for new tissue formation. As technologies for the fabrication of biomaterial scaffolds advance, the ability of scaffolds to modulate stem cell behavior advances as well. The composition of scaffolds could be of natural or synthetic materials and could be tailored to enhance cell self-renewal and/or direct cell fates. In addition to biomaterial scaffolds, studies of tissue development and cellular microenvironments have determined other factors, such as growth factors and oxygen tension, that are crucial to the regulation of stem cell activity. The overarching goal of stem cell-based tissue engineering research is to precisely control differentiation of stem cells in culture. In this article, we review current developments in tissue engineering, focusing on several stem cell sources, induction factors including growth factors, oxygen tension, biomaterials, and mechanical stimulation, and the internal and external regulatory mechanisms that govern proliferation and differentiation. PMID:23432679

Animal models for bone tissue engineering and modelling disease

PubMed Central

Griffin, Michelle

2018-01-01

ABSTRACT Tissue engineering and its clinical application, regenerative medicine, are instructing multiple approaches to aid in replacing bone loss after defects caused by trauma or cancer. In such cases, bone formation can be guided by engineered biodegradable and nonbiodegradable scaffolds with clearly defined architectural and mechanical properties informed by evidence-based research. With the ever-increasing expansion of bone tissue engineering and the pioneering research conducted to date, preclinical models are becoming a necessity to allow the engineered products to be translated to the clinic. In addition to creating smart bone scaffolds to mitigate bone loss, the field of tissue engineering and regenerative medicine is exploring methods to treat primary and secondary bone malignancies by creating models that mimic the clinical disease manifestation. This Review gives an overview of the preclinical testing in animal models used to evaluate bone regeneration concepts. Immunosuppressed rodent models have shown to be successful in mimicking bone malignancy via the implantation of human-derived cancer cells, whereas large animal models, including pigs, sheep and goats, are being used to provide an insight into bone formation and the effectiveness of scaffolds in induced tibial or femoral defects, providing clinically relevant similarity to human cases. Despite the recent progress, the successful translation of bone regeneration concepts from the bench to the bedside is rooted in the efforts of different research groups to standardise and validate the preclinical models for bone tissue engineering approaches. PMID:29685995

Image-guided tissue engineering

PubMed Central

Ballyns, Jeffrey J; Bonassar, Lawrence J

2009-01-01

Replication of anatomic shape is a significant challenge in developing implants for regenerative medicine. This has lead to significant interest in using medical imaging techniques such as magnetic resonance imaging and computed tomography to design tissue engineered constructs. Implementation of medical imaging and computer aided design in combination with technologies for rapid prototyping of living implants enables the generation of highly reproducible constructs with spatial resolution up to 25 μm. In this paper, we review the medical imaging modalities available and a paradigm for choosing a particular imaging technique. We also present fabrication techniques and methodologies for producing cellular engineered constructs. Finally, we comment on future challenges involved with image guided tissue engineering and efforts to generate engineered constructs ready for implantation. PMID:19583811

Bone tissue engineering with human mesenchymal stem cell sheets constructed using magnetite nanoparticles and magnetic force.

PubMed

Shimizu, Kazunori; Ito, Akira; Yoshida, Tatsuro; Yamada, Yoichi; Ueda, Minoru; Honda, Hiroyuki

2007-08-01

An in vitro reconstruction of three-dimensional (3D) tissues without the use of scaffolds may be an alternative strategy for tissue engineering. We have developed a novel tissue engineering strategy, termed magnetic force-based tissue engineering (Mag-TE), in which magnetite cationic liposomes (MCLs) with a positive charge at the liposomal surface, and magnetic force were used to construct 3D tissue without scaffolds. In this study, human mesenchymal stem cells (MSCs) magnetically labeled with MCLs were seeded onto an ultra-low attachment culture surface, and a magnet (4000 G) was placed on the reverse side. The MSCs formed multilayered sheet-like structures after a 24-h culture period. MSCs in the sheets constructed by Mag-TE maintained an in vitro ability to differentiate into osteoblasts, adipocytes, or chondrocytes after a 21-day culture period using each induction medium. Using an electromagnet, MSC sheets constructed by Mag-TE were harvested and transplanted into the bone defect in the crania of nude rats. Histological observation revealed that new bone surrounded by osteoblast-like cells was formed in the defect area 14 days after transplantation with MSC sheets, whereas no bone formation was observed in control rats without the transplant. These results indicated that Mag-TE could be used for the transplantation of MSC sheets using magnetite nanoparticles and magnetic force, providing novel methodology for bone tissue engineering.

The materials used in bone tissue engineering

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tereshchenko, V. P., E-mail: tervp@ngs.ru; Kirilova, I. A.; Sadovoy, M. A.

Bone tissue engineering looking for an alternative solution to the problem of skeletal injuries. The method is based on the creation of tissue engineered bone tissue equivalent with stem cells, osteogenic factors, and scaffolds - the carriers of these cells. For production of tissue engineered bone equivalent is advisable to create scaffolds similar in composition to natural extracellular matrix of the bone. This will provide optimal conditions for the cells, and produce favorable physico-mechanical properties of the final construction. This review article gives an analysis of the most promising materials for the manufacture of cell scaffolds. Biodegradable synthetic polymers aremore » the basis for the scaffold, but it alone cannot provide adequate physical and mechanical properties of the construction, and favorable conditions for the cells. Addition of natural polymers improves the strength characteristics and bioactivity of constructions. Of the inorganic compounds, to create cell scaffolds the most widely used calcium phosphates, which give the structure adequate stiffness and significantly increase its osteoinductive capacity. Signaling molecules do not affect the physico-mechanical properties of the scaffold, but beneficial effect is on the processes of adhesion, proliferation and differentiation of cells. Biodegradation of the materials will help to fulfill the main task of bone tissue engineering - the ability to replace synthetic construct by natural tissues that will restore the original anatomical integrity of the bone.« less

Future role of MR elastography in tissue engineering and regenerative medicine.

PubMed

Othman, Shadi F; Xu, Huihui; Mao, Jeremy J

2015-05-01

Tissue engineering (TE) has been introduced for more than 25 years without a boom in clinical trials. More than 70 TE-related start-up companies spent more than $600 million/year, with only two FDA-approved tissue-engineered products. Given the modest performance in clinically approved organs, TE is a tenaciously promising field. The TE community is advocating the application of clinically driven methodologies in large animal models enabling clinical translation. This challenge is hindered by the scarcity of tissue biopsies and the absence of standardized evaluation tools, but can be negated through non-invasive assessment of growth and integration, with reduced sample size and low cost. Solving this issue will speed the transition to cost-efficient clinical studies. In this paper we: (a) introduce magnetic resonance elastography to the tissue-engineering and regenerative medicine (TERM) community; (b) review recent MRE applications in TERM; and (c) discuss future directions of MRE in TERM. We have used MRE to study engineered tissues both in vitro and in vivo, where the mechanical properties of mesenchymally derived constructs were progressively monitored before and after tissues were implanted in mouse models. This study represents a stepping stone toward the applications of MRE in directing clinical trials with low cost and likely expediting the translation to more relevantly large animal models and clinical trials. Copyright © 2013 John Wiley & Sons, Ltd.

In vitro fabrication of a tissue engineered human cardiovascular patch for future use in cardiovascular surgery.

PubMed

Yang, Chao; Sodian, Ralf; Fu, Ping; Lüders, Cora; Lemke, Thees; Du, Jing; Hübler, Michael; Weng, Yuguo; Meyer, Rudolf; Hetzer, Roland

2006-01-01

One approach to tissue engineering has been the development of in vitro conditions for the fabrication of functional cardiovascular structures intended for implantation. In this experiment, we developed a pulsatile flow system that provides biochemical and biomechanical signals in order to regulate autologous, human patch-tissue development in vitro. We constructed a biodegradable patch scaffold from porous poly-4-hydroxy-butyrate (P4HB; pore size 80 to 150 microm). The scaffold was seeded with pediatric aortic cells. The cell-seeded patch constructs were placed in a self-developed bioreactor for 7 days to observe potential tissue formation under dynamic cell culture conditions. As a control, cell-seeded scaffolds were not conditioned in the bioreactor system. After maturation in vitro, the analysis of the tissue engineered constructs included biochemical, biomechanical, morphologic, and immunohistochemical examination. Macroscopically, all tissue engineered constructs were covered by cells. After conditioning in the bioreactor, the cells were mostly viable, had grown into the pores, and had formed tissue on the patch construct. Electron microscopy showed confluent smooth surfaces. Additionally, we demonstrated the capacity to generate collagen and elastin under in vitro pulsatile flow conditions in biochemical examination. Biomechanical testing showed mechanical properties of the tissue engineered human patch tissue without any statistical differences in strength or resistance to stretch between the static controls and the conditioned patches. Immunohistochemical examination stained positive for alpha smooth muscle actin, collagen type I, and fibronectin. There was minor tissue formation in the nonconditioned control samples. Porous P4HB may be used to fabricate a biodegradable patch scaffold. Human vascular cells attached themselves to the polymeric scaffold, and extracellular matrix formation was induced under controlled biomechanical and biodynamic stimuli in a self-developed pulsatile bioreactor system.

Tissue Engineering in der Hals-Nasen-Ohrenheilkunde, Kopf- und Halschirurgie

NASA Astrophysics Data System (ADS)

Bücheler, Markus; Bootz, Friedrich

Tissue Engineering ist eine Schlüsseltechnologie für den Gewebeersatz der Zukunft. Am Beispiel der Hals-Nasen-Ohrenheilkunde, Kopf- und Halschirurgie werden klinisch etablierte Gewebeersatzmethoden und aktuelle Entwicklungen des Tissue Engineering gegenübergestellt. Die Besonderheiten der zu ersetzenden Gewebe im Kopf- und Halsbereich erfordert vielfältige Ersatzverfahren. Im klinischen Alltag werden heute vor allem autogene Transplantate und Implantate für den Gewebeersatz verwendet [1]. In vitro hergestellte Gewebe werden abgesehen von Einzelanwendungen zur Zeit noch nicht am Patienten eingesetzt.

Protein-based hydrogels for tissue engineering

PubMed Central

Schloss, Ashley C.; Williams, Danielle M.; Regan, Lynne J.

2017-01-01

The tunable mechanical and structural properties of protein-based hydrogels make them excellent scaffolds for tissue engineering and repair. Moreover, using protein-based components provides the option to insert sequences associated with the promoting both cellular adhesion to the substrate and overall cell growth. Protein-based hydrogel components are appealing for their structural designability, specific biological functionality, and stimuli-responsiveness. Here we present highlights in the field of protein-based hydrogels for tissue engineering applications including design requirements, components, and gel types. PMID:27677513