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

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.

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.

Mesenchymal Stem Cells for Osteochondral Tissue Engineering

PubMed Central

Ng, Johnathan; Bernhard, Jonathan; Vunjak-Novakovic, Gordana

2017-01-01

Summary Mesenchymal stem cells (MSC) are of major interest to regenerative medicine, because of the ease of harvesting from a variety of sources (including bone marrow and fat aspirates) and ability to form a range of mesenchymal tissues, in vitro and in vivo. We focus here on the use of MSCs for engineering of cartilage, bone, and complex osteochondral tissue constructs, using protocols that replicate some aspects of the natural mesodermal development. For engineering of human bone, we discuss some of the current advances, and highlight the use of perfusion bioreactors for supporting anatomically exact human bone grafts. For engineering of human cartilage, we discuss limitations of current approaches, and highlight engineering of stratified, mechanically functional human cartilage interfaced with bone by mesenchymal condensation of MSCs. Taken together, the current advances enable engineering physiologically relevant bone, cartilage and osteochondral composites, and physiologically relevant studies of osteochondral development and disease. PMID:27236665

Quantitative Ultrasound for Nondestructive Characterization of Engineered Tissues and Biomaterials

PubMed Central

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

2015-01-01

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

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.

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.

Esophageal tissue engineering: Current status and perspectives.

PubMed

Poghosyan, T; Catry, J; Luong-Nguyen, M; Bruneval, P; Domet, T; Arakelian, L; Sfeir, R; Michaud, L; Vanneaux, V; Gottrand, F; Larghero, J; Cattan, P

2016-02-01

Tissue engineering, which consists of the combination and in vivo implantation of elements required for tissue remodeling toward a specific organ phenotype, could be an alternative for classical techniques of esophageal replacement. The current hybrid approach entails creation of an esophageal substitute composed of an acellular matrix and autologous epithelial and muscle cells provides the most successful results. Current research is based on the use of mesenchymal stem cells, whose potential for differentiation and proangioogenic, immune-modulator and anti-inflammatory properties are important assets. In the near future, esophageal substitutes could be constructed from acellular "intelligent matrices" that contain the molecules necessary for tissue regeneration; this should allow circumvention of the implantation step and still obtain standardized in vivo biological responses. At present, tissue engineering applications to esophageal replacement are limited to enlargement plasties with absorbable, non-cellular matrices. Nevertheless, the application of existing clinical techniques for replacement of other organs by tissue engineering in combination with a multiplication of translational research protocols for esophageal replacement in large animals should soon pave the way for health agencies to authorize clinical trials. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

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

Concise Review: Personalized Human Bone Grafts for Reconstructing Head and Face

PubMed Central

Bhumiratana, Sarindr

2012-01-01

Regeneration of normal shape, architecture, and function of craniofacial tissues following congenital abnormality, trauma, or surgical treatment presents special problems to tissue engineering. Because of the great variations in properties of these tissues, currently available treatment options fall short of adequate care. We propose that the engineering of personalized bone graft customized to the patient and the specific clinical condition would revolutionize the way we currently treat craniofacial defects and discuss some of the current and emerging treatment modalities. PMID:23197642

Platelet-Rich Blood Derivatives for Stem Cell-Based Tissue Engineering and Regeneration

PubMed Central

Kaushik, Gaurav; Leijten, Jeroen; Khademhosseini, Ali

2016-01-01

Platelet rich blood derivatives have been widely used in different fields of medicine and stem cell based tissue engineering. They represent natural cocktails of autologous growth factor, which could provide an alternative for recombinant protein based approaches. Platelet rich blood derivatives, such as platelet rich plasma, have consistently shown to potentiate stem cell proliferation, migration, and differentiation. Here, we review the spectrum of platelet rich blood derivatives, discuss their current applications in tissue engineering and regenerative medicine, reflect on their effect on stem cells, and highlight current translational challenges. PMID:27047733

Advances in Meniscal Tissue Engineering

PubMed Central

Longo, Umile Giuseppe; Loppini, Mattia; Forriol, Francisco; Romeo, Giovanni; Maffulli, Nicola; Denaro, Vincenzo

2012-01-01

Meniscal tears are the most common knee injuries and have a poor ability of healing. In the last few decades, several techniques have been increasingly used to optimize meniscal healing. Current research efforts of tissue engineering try to combine cell-based therapy, growth factors, gene therapy, and reabsorbable scaffolds to promote healing of meniscal defects. Preliminary studies did not allow to draw definitive conclusions on the use of these techniques for routine management of meniscal lesions. We performed a review of the available literature on current techniques of tissue engineering for the management of meniscal tears. PMID:25098366

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

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.

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

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.

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.

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

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.

Approaches to Neural Tissue Engineering Using Scaffolds for Drug Delivery

PubMed Central

Willerth, Stephanie M.; Sakiyama-Elbert, Shelly E.

2007-01-01

This review seeks to give an overview of the current approaches to drug delivery from scaffolds for neural tissue engineering applications. The challenges presented by attempting to replicate the three types of nervous tissue (brain, spinal cord, and peripheral nerve) are summarized. Potential scaffold materials (both synthetic and natural) and target drugs are discussed with the benefits and drawbacks given. Finally, common methods of drug delivery, including degradable/diffusion-based delivery systems, affinity-based delivery systems, immobilized drug delivery systems, and electrically controlled drug delivery systems, are examined and critiqued. Based on the current body of work, suggestions for future directions of research in the field of neural tissue engineering are presented. PMID:17482308

Tissue engineering: state of the art in oral rehabilitation

PubMed Central

SCHELLER, E. L.; KREBSBACH, P. H.; KOHN, D. H.

2009-01-01

SUMMARY More than 85% of the global population requires repair or replacement of a craniofacial structure. These defects range from simple tooth decay to radical oncologic craniofacial resection. Regeneration of oral and craniofacial tissues presents a formidable challenge that requires synthesis of basic science, clinical science and engineering technology. Identification of appropriate scaffolds, cell sources and spatial and temporal signals (the tissue engineering triad) is necessary to optimize development of a single tissue, hybrid organ or interface. Furthermore, combining the understanding of the interactions between molecules of the extracellular matrix and attached cells with an understanding of the gene expression needed to induce differentiation and tissue growth will provide the design basis for translating basic science into rationally developed components of this tissue engineering triad. Dental tissue engineers are interested in regeneration of teeth, oral mucosa, salivary glands, bone and periodontium. Many of these oral structures are hybrid tissues. For example, engineering the periodontium requires growth of alveolar bone, cementum and the periodontal ligament. Recapitulation of biological development of hybrid tissues and interfaces presents a challenge that exceeds that of engineering just a single tissue. Advances made in dental interface engineering will allow these tissues to serve as model systems for engineering other tissues or organs of the body. This review will begin by covering basic tissue engineering principles and strategic design of functional biomaterials. We will then explore the impact of biomaterials design on the status of craniofacial tissue engineering and current challenges and opportunities in dental tissue engineering. PMID:19228277

Tissue engineering: state of the art in oral rehabilitation.

PubMed

Scheller, E L; Krebsbach, P H; Kohn, D H

2009-05-01

More than 85% of the global population requires repair or replacement of a craniofacial structure. These defects range from simple tooth decay to radical oncologic craniofacial resection. Regeneration of oral and craniofacial tissues presents a formidable challenge that requires synthesis of basic science, clinical science and engineering technology. Identification of appropriate scaffolds, cell sources and spatial and temporal signals (the tissue engineering triad) is necessary to optimize development of a single tissue, hybrid organ or interface. Furthermore, combining the understanding of the interactions between molecules of the extracellular matrix and attached cells with an understanding of the gene expression needed to induce differentiation and tissue growth will provide the design basis for translating basic science into rationally developed components of this tissue engineering triad. Dental tissue engineers are interested in regeneration of teeth, oral mucosa, salivary glands, bone and periodontium. Many of these oral structures are hybrid tissues. For example, engineering the periodontium requires growth of alveolar bone, cementum and the periodontal ligament. Recapitulation of biological development of hybrid tissues and interfaces presents a challenge that exceeds that of engineering just a single tissue. Advances made in dental interface engineering will allow these tissues to serve as model systems for engineering other tissues or organs of the body. This review will begin by covering basic tissue engineering principles and strategic design of functional biomaterials. We will then explore the impact of biomaterials design on the status of craniofacial tissue engineering and current challenges and opportunities in dental tissue engineering.

Advanced Engineering Strategies for Periodontal Complex Regeneration.

PubMed

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

2016-01-18

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

Adipose-Derived Stem Cells in Functional Bone Tissue Engineering: Lessons from Bone Mechanobiology

PubMed Central

Bodle, Josephine C.; Hanson, Ariel D.

2011-01-01

This review aims to highlight the current and significant work in the use of adipose-derived stem cells (ASC) in functional bone tissue engineering framed through the bone mechanobiology perspective. Over a century of work on the principles of bone mechanosensitivity is now being applied to our understanding of bone development. We are just beginning to harness that potential using stem cells in bone tissue engineering. ASC are the primary focus of this review due to their abundance and relative ease of accessibility for autologous procedures. This article outlines the current knowledge base in bone mechanobiology to investigate how the knowledge from this area has been applied to the various stem cell-based approaches to engineering bone tissue constructs. Specific emphasis is placed on the use of human ASC for this application. PMID:21338267

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.

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.

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.

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

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.

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

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

NASA Astrophysics Data System (ADS)

Mercado, Karla Patricia E.

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

Articular cartilage tissue engineering with plasma-rich in growth factors and stem cells with nano scaffolds

NASA Astrophysics Data System (ADS)

Montaser, Laila M.; Abbassy, Hadeer A.; Fawzy, Sherin M.

2016-09-01

The ability to heal soft tissue injuries and regenerate cartilage is the Holy Grail of musculoskeletal medicine. Articular cartilage repair and regeneration is considered to be largely intractable due to the poor regenerative properties of this tissue. Due to their low self-repair ability, cartilage defects that result from joint injury, aging, or osteoarthritis, are the most often irreversible and are a major cause of joint pain and chronic disability. However, current methods do not perfectly restore hyaline cartilage and may lead to the apparition of fibro- or continue hypertrophic cartilage. The lack of efficient modalities of treatment has prompted research into tissue engineering combining stem cells, scaffold materials and environmental factors. The field of articular cartilage tissue engineering, which aims to repair, regenerate, and/or improve injured or diseased cartilage functionality, has evoked intense interest and holds great potential for improving cartilage therapy. Plasma-rich in growth factors (PRGF) and/or stem cells may be effective for tissue repair as well as cartilage regenerative processes. There is a great promise to advance current cartilage therapies toward achieving a consistently successful approach for addressing cartilage afflictions. Tissue engineering may be the best way to reach this objective via the use of stem cells, novel biologically inspired scaffolds and, emerging nanotechnology. In this paper, current and emergent approach in the field of cartilage tissue engineering is presented for specific application. In the next years, the development of new strategies using stem cells, in scaffolds, with supplementation of culture medium could improve the quality of new formed cartilage.

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.

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.

Regeneration of the anterior cruciate ligament: Current strategies in tissue engineering

PubMed Central

Nau, Thomas; Teuschl, Andreas

2015-01-01

Recent advancements in the field of musculoskeletal tissue engineering have raised an increasing interest in the regeneration of the anterior cruciate ligament (ACL). It is the aim of this article to review the current research efforts and highlight promising tissue engineering strategies. The four main components of tissue engineering also apply in several ACL regeneration research efforts. Scaffolds from biological materials, biodegradable polymers and composite materials are used. The main cell sources are mesenchymal stem cells and ACL fibroblasts. In addition, growth factors and mechanical stimuli are applied. So far, the regenerated ACL constructs have been tested in a few animal studies and the results are encouraging. The different strategies, from in vitro ACL regeneration in bioreactor systems to bio-enhanced repair and regeneration, are under constant development. We expect considerable progress in the near future that will result in a realistic option for ACL surgery soon. PMID:25621217

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.

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.

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

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.

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.

Mathematical modelling of skeletal repair.

PubMed

MacArthur, B D; Please, C P; Taylor, M; Oreffo, R O C

2004-01-23

Tissue engineering offers significant promise as a viable alternative to current clinical strategies for replacement of damaged tissue as a consequence of disease or trauma. Since mathematical modelling is a valuable tool in the analysis of complex systems, appropriate use of mathematical models has tremendous potential for advancing the understanding of the physical processes involved in such tissue reconstruction. In this review, the potential benefits, and limitations, of theoretical modelling in tissue engineering applications are examined with specific emphasis on tissue engineering of bone. A central tissue engineering approach is the in vivo implantation of a biomimetic scaffold seeded with an appropriate population of stem or progenitor cells. This review will therefore consider the theory behind a number of key factors affecting the success of such a strategy including: stem cell or progenitor population expansion and differentiation ex vivo; cell adhesion and migration, and the effective design of scaffolds; and delivery of nutrient to avascular structures. The focus will be on current work in this area, as well as on highlighting limitations and suggesting possible directions for future work to advance health-care for all.

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.

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

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

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.

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.

Using eddy currents for noninvasive in vivo pH monitoring for bone tissue engineering.

PubMed

Beck-Broichsitter, Benedicta E; Daschner, Frank; Christofzik, David W; Knöchel, Reinhard; Wiltfang, Jörg; Becker, Stephan T

2015-03-01

The metabolic processes that regulate bone healing and bone induction in tissue engineering models are not fully understood. Eddy current excitation is widely used in technical approaches and in the food industry. The aim of this study was to establish eddy current excitation for monitoring metabolic processes during heterotopic osteoinduction in vivo. Hydroxyapatite scaffolds were implanted into the musculus latissimus dorsi of six rats. Bone morphogenetic protein 2 (BMP-2) was applied 1 and 2 weeks after implantation. Weekly eddy current excitation measurements were performed. Additionally, invasive pH measurements were obtained from the scaffolds using fiber optic detection devices. Correlations between the eddy current measurements and the metabolic values were calculated. The eddy current measurements and pH values decreased significantly in the first 2 weeks of the study, followed by a steady increase and stabilization at higher levels towards the end of the study. The measurement curves and statistical evaluations indicated a significant correlation between the resonance frequency values of the eddy current excitation measurements and the observed pH levels (p = 0.0041). This innovative technique was capable of noninvasively monitoring metabolic processes in living tissues according to pH values, showing a direct correlation between eddy current excitation and pH in an in vivo tissue engineering model.

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.

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.

Orthopaedic regenerative tissue engineering en route to the holy grail: disequilibrium between the demand and the supply in the operating room.

PubMed

Cengiz, Ibrahim Fatih; Pereira, Hélder; de Girolamo, Laura; Cucchiarini, Magali; Espregueira-Mendes, João; Reis, Rui L; Oliveira, Joaquim Miguel

2018-05-22

Orthopaedic disorders are very frequent, globally found and often partially unresolved despite the substantial advances in science and medicine. Their surgical intervention is multifarious and the most favourable treatment is chosen by the orthopaedic surgeon on a case-by-case basis depending on a number of factors related with the patient and the lesion. Numerous regenerative tissue engineering strategies have been developed and studied extensively in laboratory through in vitro experiments and preclinical in vivo trials with various established animal models, while a small proportion of them reached the operating room. However, based on the available literature, the current strategies have not yet achieved to fully solve the clinical problems. Thus, the gold standards, if existing, remain unchanged in the clinics, notwithstanding the known limitations and drawbacks. Herein, the involvement of regenerative tissue engineering in the clinical orthopaedics is reviewed. The current challenges are indicated and discussed in order to describe the current disequilibrium between the needs and solutions made available in the operating room. Regenerative tissue engineering is a very dynamic field that has a high growth rate and a great openness and ability to incorporate new technologies with passion to edge towards the Holy Grail that is functional tissue regeneration. Thus, the future of clinical solutions making use of regenerative tissue engineering principles for the management of orthopaedic disorders is firmly supported by the clinical need.

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.

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.

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.

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

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

Articular cartilage: from formation to tissue engineering.

PubMed

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

2016-05-26

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

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

PubMed

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

2012-01-01

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

Current Concepts in Tissue Engineering: Skin and Wound.

PubMed

Tenenhaus, Mayer; Rennekampff, Hans-Oliver

2016-09-01

Pure regenerative healing with little to no donor morbidity remains an elusive goal for both surgeon and patient. The ability to engineer and promote the development of like tissue holds so much promise, and efforts in this direction are slowly but steadily advancing. Products selected and reviewed reflect historical precedence and importance and focus on current clinically available products in use. Emerging technologies we anticipate will further expand our therapeutic options are introduced. The topic of tissue engineering is incredibly broad in scope, and as such the authors have focused their review on that of constructs specifically designed for skin and wound healing. A review of pertinent and current clinically related literature is included. Products such as biosynthetics, biologics, cellular promoting factors, and commercially available matrices can be routinely found in most modern health care centers. Although to date no complete regenerative or direct identical soft-tissue replacement exists, currently available commercial components have proven beneficial in augmenting and improving some types of wound healing scenarios. Cost, directed specificity, biocompatibility, and bioburden tolerance are just some of the impending challenges to adoption. Quality of life and in fact the ability to sustain life is dependent on our most complex and remarkable organ, skin. Although pure regenerative healing and engineered soft-tissue constructs elude us, surgeons and health care providers are slowly gaining comfort and experience with concepts and strategies to improve the healing of wounds.

A Review of the Responses of Two- and Three-Dimensional Engineered Tissues to Electric Fields

PubMed Central

Hronik-Tupaj, Marie

2012-01-01

The application of external biophysical signals is one approach to tissue engineering that is explored less often than more traditional additions of exogenous biochemical and chemical factors to direct cell and tissue outcomes. The study of bioelectromagnetism and the field of electrotherapeutics have evolved over the years, and we review biocompatible electric stimulation devices and their successful application to tissue growth. Specifically, information on capacitively coupled alternating current, inductively coupled alternating current, and direct current devices is described. Cell and tissue responses from the application of these devices, including two- and three-dimensional in vitro studies and in vivo studies, are reviewed with regard to cell proliferation, adhesion, differentiation, morphology, and migration and tissue function. The current understanding of cellular mechanisms related to electric stimulation is detailed. The advantages of electric stimulation are compared with those pf other techniques, and areas in which electric fields are used as an adjuvant therapy for healing and regeneration are discussed. PMID:22046979

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.

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.

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.

3D bioprinting and the current applications in tissue engineering.

PubMed

Huang, Ying; Zhang, Xiao-Fei; Gao, Guifang; Yonezawa, Tomo; Cui, Xiaofeng

2017-08-01

Bioprinting as an enabling technology for tissue engineering possesses the promises to fabricate highly mimicked tissue or organs with digital control. As one of the biofabrication approaches, bioprinting has the advantages of high throughput and precise control of both scaffold and cells. Therefore, this technology is not only ideal for translational medicine but also for basic research applications. Bioprinting has already been widely applied to construct functional tissues such as vasculature, muscle, cartilage, and bone. In this review, the authors introduce the most popular techniques currently applied in bioprinting, as well as the various bioprinting processes. In addition, the composition of bioink including scaffolds and cells are described. Furthermore, the most current applications in organ and tissue bioprinting are introduced. The authors also discuss the challenges we are currently facing and the great potential of bioprinting. This technology has the capacity not only in complex tissue structure fabrication based on the converted medical images, but also as an efficient tool for drug discovery and preclinical testing. One of the most promising future advances of bioprinting is to develop a standard medical device with the capacity of treating patients directly on the repairing site, which requires the development of automation and robotic technology, as well as our further understanding of biomaterials and stem cell biology to integrate various printing mechanisms for multi-phasic tissue engineering. Copyright © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

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.

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

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.

Hydrogels for Engineering of Perfusable Vascular Networks

PubMed Central

Liu, Juan; Zheng, Huaiyuan; Poh, Patrina S. P.; Machens, Hans-Günther; Schilling, Arndt F.

2015-01-01

Hydrogels are commonly used biomaterials for tissue engineering. With their high-water content, good biocompatibility and biodegradability they resemble the natural extracellular environment and have been widely used as scaffolds for 3D cell culture and studies of cell biology. The possible size of such hydrogel constructs with embedded cells is limited by the cellular demand for oxygen and nutrients. For the fabrication of large and complex tissue constructs, vascular structures become necessary within the hydrogels to supply the encapsulated cells. In this review, we discuss the types of hydrogels that are currently used for the fabrication of constructs with embedded vascular networks, the key properties of hydrogels needed for this purpose and current techniques to engineer perfusable vascular structures into these hydrogels. We then discuss directions for future research aimed at engineering of vascularized tissue for implantation. PMID:26184185

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.

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

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.

[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.

Current Advancements and Strategies in Tissue Engineering for Wound Healing: A Comprehensive Review.

PubMed

Ho, Jasmine; Walsh, Claire; Yue, Dominic; Dardik, Alan; Cheema, Umber

2017-06-01

Significance: With an aging population leading to an increase in diabetes and associated cutaneous wounds, there is a pressing clinical need to improve wound-healing therapies. Recent Advances: Tissue engineering approaches for wound healing and skin regeneration have been developed over the past few decades. A review of current literature has identified common themes and strategies that are proving successful within the field: The delivery of cells, mainly mesenchymal stem cells, within scaffolds of the native matrix is one such strategy. We overview these approaches and give insights into mechanisms that aid wound healing in different clinical scenarios. Critical Issues: We discuss the importance of the biomimetic niche, and how recapitulating elements of the native microenvironment of cells can help direct cell behavior and fate. Future Directions: It is crucial that during the continued development of tissue engineering in wound repair, there is close collaboration between tissue engineers and clinicians to maintain the translational efficacy of this approach.

Current Advancements and Strategies in Tissue Engineering for Wound Healing: A Comprehensive Review

PubMed Central

Ho, Jasmine; Walsh, Claire; Yue, Dominic; Dardik, Alan; Cheema, Umber

2017-01-01

Significance: With an aging population leading to an increase in diabetes and associated cutaneous wounds, there is a pressing clinical need to improve wound-healing therapies. Recent Advances: Tissue engineering approaches for wound healing and skin regeneration have been developed over the past few decades. A review of current literature has identified common themes and strategies that are proving successful within the field: The delivery of cells, mainly mesenchymal stem cells, within scaffolds of the native matrix is one such strategy. We overview these approaches and give insights into mechanisms that aid wound healing in different clinical scenarios. Critical Issues: We discuss the importance of the biomimetic niche, and how recapitulating elements of the native microenvironment of cells can help direct cell behavior and fate. Future Directions: It is crucial that during the continued development of tissue engineering in wound repair, there is close collaboration between tissue engineers and clinicians to maintain the translational efficacy of this approach. PMID:28616360

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.

Micrometer scale guidance of mesenchymal stem cells to form structurally oriented large-scale tissue engineered cartilage.

PubMed

Chou, Chih-Ling; Rivera, Alexander L; Williams, Valencia; Welter, Jean F; Mansour, Joseph M; Drazba, Judith A; Sakai, Takao; Baskaran, Harihara

2017-09-15

Current clinical methods to treat articular cartilage lesions provide temporary relief of the symptoms but fail to permanently restore the damaged tissue. Tissue engineering, using mesenchymal stem cells (MSCs) combined with scaffolds and bioactive factors, is viewed as a promising method for repairing cartilage injuries. However, current tissue engineered constructs display inferior mechanical properties compared to native articular cartilage, which could be attributed to the lack of structural organization of the extracellular matrix (ECM) of these engineered constructs in comparison to the highly oriented structure of articular cartilage ECM. We previously showed that we can guide MSCs undergoing chondrogenesis to align using microscale guidance channels on the surface of a two-dimensional (2-D) collagen scaffold, which resulted in the deposition of aligned ECM within the channels and enhanced mechanical properties of the constructs. In this study, we developed a technique to roll 2-D collagen scaffolds containing MSCs within guidance channels in order to produce a large-scale, three-dimensional (3-D) tissue engineered cartilage constructs with enhanced mechanical properties compared to current constructs. After rolling the MSC-scaffold constructs into a 3-D cylindrical structure, the constructs were cultured for 21days under chondrogenic culture conditions. The microstructure architecture and mechanical properties of the constructs were evaluated using imaging and compressive testing. Histology and immunohistochemistry of the constructs showed extensive glycosaminoglycan (GAG) and collagen type II deposition. Second harmonic generation imaging and Picrosirius red staining indicated alignment of neo-collagen fibers within the guidance channels of the constructs. Mechanical testing indicated that constructs containing the guidance channels displayed enhanced compressive properties compared to control constructs without these channels. In conclusion, using a novel roll-up method, we have developed large scale MSC based tissue-engineered cartilage that shows microscale structural organization and enhanced compressive properties compared to current tissue engineered constructs. Tissue engineered cartilage constructs made with human mesenchymal stem cells (hMSCs), scaffolds and bioactive factors are a promising solution to treat cartilage defects. A major disadvantage of these constructs is their inferior mechanical properties compared to the native tissue, which is likely due to the lack of structural organization of the extracellular matrix of the engineered constructs. In this study, we developed three-dimensional (3-D) cartilage constructs from rectangular scaffold sheets containing hMSCs in micro-guidance channels and characterized their mechanical properties and metabolic requirements. The work led to a novel roll-up method to embed 2-D microscale structures in 3-D constructs. Further, micro-guidance channels incorporated within the 3-D cartilage constructs led to the production of aligned cell-produced matrix and enhanced mechanical function. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Overview on zein protein: a promising pharmaceutical excipient in drug delivery systems and tissue engineering.

PubMed

Labib, Gihan

2018-01-01

Natural pharmaceutical excipients have been applied extensively in the past decades owing to their safety and biocompatibility. Zein, a natural protein of plant origin offers great benefit over other synthetic polymers used in controlled drug and biomedical delivery systems. It was used in a variety of medical fields including pharmaceutical and biomedical drug targeting, vaccine, tissue engineering, and gene delivery. Being biodegradable and biocompatible, the current review focuses on the history and the medical application of zein as an attractive still promising biopolymer. Areas covered: The current review gives a broadscope on zein as a still promising protein excipient in different fields. Zein- based drug and biomedical delivery systems are discussed with special focus on current and potential application in controlled drug delivery systems, and tissue engineering. Expert opinion: Zein as a protein of natural origin can still be considered a promising polymer in the field of drug delivery systems as well as in tissue engineering. Although different researchers spotted light on zein application in different industrial fields extensively, the feasibility of its use in the field of drug delivery replenished by investigators in recent years has not yet been fully approached.

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.

Vascular tissue engineering: the next generation.

PubMed

Cleary, Muriel A; Geiger, Erik; Grady, Conor; Best, Cameron; Naito, Yuji; Breuer, Christopher

2012-07-01

It is the ultimate goal of tissue engineering: an autologous tissue engineered vascular graft (TEVG) that is immunologically compatible, nonthrombogenic, and can grow and remodel. Currently, native vessels are the preferred vascular conduit for procedures such as coronary artery bypass (CABG) or peripheral bypass surgery. However, in many cases these are damaged, have already been harvested, or are simply unusable. The use of synthetic conduits is severely limited in smaller diameter vessels due to increased incidence of thrombosis, infection, and graft failure. Current research has therefore energetically pursued the development of a TEVG that can incorporate into a patient's circulatory system, mimic the vasoreactivity and biomechanics of the native vasculature, and maintain long-term patency. Copyright © 2012. Published by Elsevier Ltd.

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.

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.

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.

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.

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.

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.

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

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.

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.

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

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

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.

Tissue engineering: current strategies and future directions.

PubMed

Olson, Jennifer L; Atala, Anthony; Yoo, James J

2011-04-01

Novel therapies resulting from regenerative medicine and tissue engineering technology may offer new hope for patients with injuries, end-stage organ failure, or other clinical issues. Currently, patients with diseased and injured organs are often treated with transplanted organs. However, there is a shortage of donor organs that is worsening yearly as the population ages and as the number of new cases of organ failure increases. Scientists in the field of regenerative medicine and tissue engineering 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 tissues. In addition, the stem cell field is a rapidly advancing part of regenerative medicine, and new discoveries in this field create new options for this type of therapy. For example, new types of stem cells, such as amniotic fluid and placental stem cells that can circumvent the ethical issues associated with embryonic stem cells, have been discovered. 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 clinical setting, indicating that regenerative medicine holds much promise for the future.

Biomaterials for Tissue Engineering

PubMed Central

Lee, Esther J.; Kasper, F. Kurtis; Mikos, Antonios G.

2013-01-01

Biomaterials serve as an integral component of tissue engineering. They are designed to provide architectural framework reminiscent of native extracellular matrix in order to encourage cell growth and eventual tissue regeneration. Bone and cartilage represent two distinct tissues with varying compositional and mechanical properties. Despite these differences, both meet at the osteochondral interface. This article presents an overview of current biomaterials employed in bone and cartilage applications, discusses some design considerations, and alludes to future prospects within this field of research. PMID:23820768

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.

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.

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

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

PubMed Central

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

2015-01-01

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

Temporomandibular disorders: a review of etiology, clinical management, and tissue engineering strategies.

PubMed

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

2013-01-01

Temporomandibular disorders (TMD) are a class of degenerative musculoskeletal conditions associated with morphologic and functional deformities that affect up to 25% of the population, but their etiology and progression are poorly understood and, as a result, treatment options are limited. In up to 70% of cases, TMD are accompanied by malpositioning of the temporomandibular joint (TMJ) disc, termed "internal derangement." Although the onset is not well characterized, correlations between internal derangement and osteoarthritic change have been identified. Because of the complex and unique nature of each TMD case, diagnosis requires patient-specific analysis accompanied by various diagnostic modalities. Likewise, treatment requires customized plans to address the specific characteristics of each patient's disease. In the mechanically demanding and biochemically active environment of the TMJ, therapeutic approaches that can restore joint functionality while responding to changes in the joint have become a necessity. One such approach, tissue engineering, which may be capable of integration and adaptation in the TMJ, carries significant potential for the development of repair and replacement tissues. The following review presents a synopsis of etiology, current treatment methods, and the future of tissue engineering for repairing and/or replacing diseased joint components, specifically the mandibular condyle and TMJ disc. An analysis of native tissue characterization to assist clinicians in identifying tissue engineering objectives and validation metrics for restoring healthy and functional structures of the TMJ is followed by a discussion of current trends in tissue engineering.

Current Advance and Future Prospects of Tissue Engineering Approach to Dentin/Pulp Regenerative Therapy

PubMed Central

Gong, Ting; Heng, Boon Chin; Lo, Edward Chin Man; Zhang, Chengfei

2016-01-01

Recent advances in biomaterial science and tissue engineering technology have greatly spurred the development of regenerative endodontics. This has led to a paradigm shift in endodontic treatment from simply filling the root canal systems with biologically inert materials to restoring the infected dental pulp with functional replacement tissues. Currently, cell transplantation has gained increasing attention as a scientifically valid method for dentin-pulp complex regeneration. This multidisciplinary approach which involves the interplay of three key elements of tissue engineering—stem cells, scaffolds, and signaling molecules—has produced an impressive number of favorable outcomes in preclinical animal studies. Nevertheless, many practical hurdles need to be overcome prior to its application in clinical settings. Apart from the potential health risks of immunological rejection and pathogenic transmission, the lack of a well-established banking system for the isolation and storage of dental-derived stem cells is the most pressing issue that awaits resolution and the properties of supportive scaffold materials vary across different studies and remain inconsistent. This review critically examines the classic triad of tissue engineering utilized in current regenerative endodontics and summarizes the possible techniques developed for dentin/pulp regeneration. PMID:27069484

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.

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

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.

The extracellular matrix: Structure, composition, age-related differences, tools for analysis and applications for tissue engineering.

PubMed

Kular, Jaspreet K; Basu, Shouvik; Sharma, Ram I

2014-01-01

The extracellular matrix is a structural support network made up of diverse proteins, sugars and other components. It influences a wide number of cellular processes including migration, wound healing and differentiation, all of which is of particular interest to researchers in the field of tissue engineering. Understanding the composition and structure of the extracellular matrix will aid in exploring the ways the extracellular matrix can be utilised in tissue engineering applications especially as a scaffold. This review summarises the current knowledge of the composition, structure and functions of the extracellular matrix and introduces the effect of ageing on extracellular matrix remodelling and its contribution to cellular functions. Additionally, the current analytical technologies to study the extracellular matrix and extracellular matrix-related cellular processes are also reviewed.

Vascular Mechanobiology: Towards Control of In Situ Regeneration

PubMed Central

van Haaften, Eline E.; Bouten, Carlijn V. C.; Kurniawan, Nicholas A.

2017-01-01

The paradigm of regenerative medicine has recently shifted from in vitro to in situ tissue engineering: implanting a cell-free, biodegradable, off-the-shelf available scaffold and inducing the development of functional tissue by utilizing the regenerative potential of the body itself. This approach offers a prospect of not only alleviating the clinical demand for autologous vessels but also circumventing the current challenges with synthetic grafts. In order to move towards a hypothesis-driven engineering approach, we review three crucial aspects that need to be taken into account when regenerating vessels: (1) the structure-function relation for attaining mechanical homeostasis of vascular tissues; (2) the environmental cues governing cell function; and (3) the available experimental platforms to test instructive scaffolds for in situ tissue engineering. The understanding of cellular responses to environmental cues leads to the development of computational models to predict tissue formation and maturation, which are validated using experimental platforms recapitulating the (patho)physiological micro-environment. With the current advances, a progressive shift is anticipated towards a rational and effective approach of building instructive scaffolds for in situ vascular tissue regeneration. PMID:28671618

Vascular Mechanobiology: Towards Control of In Situ Regeneration.

PubMed

van Haaften, Eline E; Bouten, Carlijn V C; Kurniawan, Nicholas A

2017-07-03

The paradigm of regenerative medicine has recently shifted from in vitro to in situ tissue engineering: implanting a cell-free, biodegradable, off-the-shelf available scaffold and inducing the development of functional tissue by utilizing the regenerative potential of the body itself. This approach offers a prospect of not only alleviating the clinical demand for autologous vessels but also circumventing the current challenges with synthetic grafts. In order to move towards a hypothesis-driven engineering approach, we review three crucial aspects that need to be taken into account when regenerating vessels: (1) the structure-function relation for attaining mechanical homeostasis of vascular tissues, (2) the environmental cues governing cell function, and (3) the available experimental platforms to test instructive scaffolds for in situ tissue engineering. The understanding of cellular responses to environmental cues leads to the development of computational models to predict tissue formation and maturation, which are validated using experimental platforms recapitulating the (patho)physiological micro-environment. With the current advances, a progressive shift is anticipated towards a rational and effective approach of building instructive scaffolds for in situ vascular tissue regeneration.

The Role of Bioreactors in Ligament and Tendon Tissue Engineering.

PubMed

Mace, James; Wheelton, Andy; Khan, Wasim S; Anand, Sanj

2016-01-01

Bioreactors are pivotal to the emerging field of tissue engineering. The formation of neotissue from pluripotent cell lineages potentially offers a source of tissue for clinical use without the significant donor site morbidity associated with many contemporary surgical reconstructive procedures. Modern bioreactor design is becoming increasingly complex to provide a both an expandable source of readily available pluripotent cells and to facilitate their controlled differentiation into a clinically applicable ligament or tendon like neotissue. This review presents the need for such a method, challenges in the processes to engineer neotissue and the current designs and results of modern bioreactors in the pursuit of engineered tendon and ligament.

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

PubMed

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

2004-08-09

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

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.

Engineered Heart Repair.

PubMed

Fujita, B; Zimmermann, W-H

2017-08-01

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

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.

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

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.

Educational Modules in Tissue Engineering Based on the "How People Learn" Framework

ERIC Educational Resources Information Center

Birol, Gulnur; Liu, Shu Q.; Smith, H. David; Hirsch, Penny

2006-01-01

This paper describes an educational package for use in tertiary level tissue engineering education. Current learning science principles and theory were employed in the design process of these educational tools. Each module started with a challenge statement designed to motivate students and consisted of laboratory exercises centered on the "How…

Creating biomaterials with spatially organized functionality.

PubMed

Chow, Lesley W; Fischer, Jacob F

2016-05-01

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

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.

Whole Organ Tissue Vascularization: Engineering the Tree to Develop the Fruits.

PubMed

Pellegata, Alessandro F; Tedeschi, Alfonso M; De Coppi, Paolo

2018-01-01

Tissue engineering aims to regenerate and recapitulate a tissue or organ that has lost its function. So far successful clinical translation has been limited to hollow organs in which rudimental vascularization can be achieved by inserting the graft into flaps of the omentum or muscle fascia. This technique used to stimulate vascularization of the graft takes advantage of angiogenesis from existing vascular networks. Vascularization of the engineered graft is a fundamental requirement in the process of engineering more complex organs, as it is crucial for the efficient delivery of nutrients and oxygen following in-vivo implantation. To achieve vascularization of the organ many different techniques have been investigated and exploited. The most promising results have been obtained by seeding endothelial cells directly into decellularized scaffolds, taking advantage of the channels remaining from the pre-existing vascular network. Currently, the main hurdle we need to overcome is achieving a fully functional vascular endothelium, stable over a long time period of time, which is engineered using a cell source that is clinically suitable and can generate, in vitro , a yield of cells suitable for the engineering of human sized organs. This review will give an overview of the approaches that have recently been investigated to address the issue of vascularization in the field of tissue engineering of whole organs, and will highlight the current caveats and hurdles that should be addressed in the future.

Tissue Engineered Skin and Wound Healing: Current Strategies and Future Directions.

PubMed

Bhardwaj, Nandana; Chouhan, Dimple; Mandal, Biman B

2017-01-01

The global volume of skin damage or injuries has major healthcare implications and, accounts for about half of the world's annual expenditure in the healthcare sector. In the last two decades, tissue-engineered skin constructs have shown great promise in the treatment of various skin-related disorders such as deep burns and wounds. The treatment methods for skin replacement and repair have evolved from utilization of autologous epidermal sheets to more complex bilayered cutaneous tissue engineered skin substitutes. However, inadequate vascularization, lack of flexibility in drug/growth factors loading and inability to reconstitute skin appendages such as hair follicles limits their utilization for restoration of normal skin anatomy on a routine basis. Recent advancements in cutting-edge technology from stem cell biology, nanotechnology, and various vascularization strategies have provided a tremendous springboard for researchers in developing and manipulating tissue engineered skin substitutes for improved skin regeneration and wound healing. This review summarizes the overview of skin tissue engineering and wound healing. Herein, developments and challenges of various available biomaterials, cell sources and in vitro skin models (full thickness and wound healing models) in tissue-engineered skin research are discussed. Furthermore, central to the discussion is the inclusion of various innovative strategies starting from stem cells, nanotechnology, vascularization strategies, microfluidics to three dimensional (3D) bioprinting based strategies for generation of complex skin mimics. The review then moves on to highlight the future prospects of advanced construction strategies of these bioengineered skin constructs and their contribution to wound healing and skin regeneration on current practice. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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.

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.

Engineering and commercialization of human-device interfaces, from bone to brain.

PubMed

Knothe Tate, Melissa L; Detamore, Michael; Capadona, Jeffrey R; Woolley, Andrew; Knothe, Ulf

2016-07-01

Cutting edge developments in engineering of tissues, implants and devices allow for guidance and control of specific physiological structure-function relationships. Yet the engineering of functionally appropriate human-device interfaces represents an intractable challenge in the field. This leading opinion review outlines a set of current approaches as well as hurdles to design of interfaces that modulate transfer of information, i.a. forces, electrical potentials, chemical gradients and haptotactic paths, between endogenous and engineered body parts or tissues. The compendium is designed to bridge across currently separated disciplines by highlighting specific commonalities between seemingly disparate systems, e.g. musculoskeletal and nervous systems. We focus on specific examples from our own laboratories, demonstrating that the seemingly disparate musculoskeletal and nervous systems share common paradigms which can be harnessed to inspire innovative interface design solutions. Functional barrier interfaces that control molecular and biophysical traffic between tissue compartments of joints are addressed in an example of the knee. Furthermore, we describe the engineering of gradients for interfaces between endogenous and engineered tissues as well as between electrodes that physically and electrochemically couple the nervous and musculoskeletal systems. Finally, to promote translation of newly developed technologies into products, protocols, and treatments that benefit the patients who need them most, regulatory and technical challenges and opportunities are addressed on hand from an example of an implant cum delivery device that can be used to heal soft and hard tissues, from brain to bone. Crown Copyright © 2016. Published by 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.

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.

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.

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.

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.

Nanotechnology in drug delivery and tissue engineering: from discovery to applications.

PubMed

Shi, Jinjun; Votruba, Alexander R; Farokhzad, Omid C; Langer, Robert

2010-09-08

The application of nanotechnology in medicine, referred to as nanomedicine, is offering numerous exciting possibilities in healthcare. Herein, we discuss two important aspects of nanomedicine, drug delivery and tissue engineering, highlighting the advances we have recently experienced, the challenges we are currently facing, and what we are likely to witness in the near future.

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

PubMed

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

2016-10-28

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

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

PubMed Central

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

2016-01-01

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

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.

[Mechanical strength and mechano-compatibility of tissue-engineered bones].

PubMed

Tanaka, Shigeo

2016-01-01

Current artificial bones made of metals and ceramics may be replaced around a decade after implantation due to its low durability, which is brought on by a large difference from the host bone in mechanical properties, i.e., low mechano-compatibility. On the other hand, tissue engineering could be a solution with regeneration of bone tissues from stem cells in vitro. However, there are still some problems to realize exactly the same mechanical properties as those of real bone. This paper introduces the technical background of bone tissue engineering and discusses possible methods for installation of mechano-compatibility into a regenerative bone. At the end, future directions toward the realization of ideal mechano-compatible regenerative bone are proposed.

The impact of simulated and real microgravity on bone cells and mesenchymal stem cells.

PubMed

Ulbrich, Claudia; Wehland, Markus; Pietsch, Jessica; Aleshcheva, Ganna; Wise, Petra; van Loon, Jack; Magnusson, Nils; Infanger, Manfred; Grosse, Jirka; Eilles, Christoph; Sundaresan, Alamelu; Grimm, Daniela

2014-01-01

How microgravity affects the biology of human cells and the formation of 3D cell cultures in real and simulated microgravity (r- and s-µg) is currently a hot topic in biomedicine. In r- and s-µg, various cell types were found to form 3D structures. This review will focus on the current knowledge of tissue engineering in space and on Earth using systems such as the random positioning machine (RPM), the 2D-clinostat, or the NASA-developed rotating wall vessel bioreactor (RWV) to create tissue from bone, tumor, and mesenchymal stem cells. To understand the development of 3D structures, in vitro experiments using s-µg devices can provide valuable information about modulations in signal-transduction, cell adhesion, or extracellular matrix induced by altered gravity conditions. These systems also facilitate the analysis of the impact of growth factors, hormones, or drugs on these tissue-like constructs. Progress has been made in bone tissue engineering using the RWV, and multicellular tumor spheroids (MCTS), formed in both r- and s-µg, have been reported and were analyzed in depth. Currently, these MCTS are available for drug testing and proteomic investigations. This review provides an overview of the influence of µg on the aforementioned cells and an outlook for future perspectives in tissue engineering.

The Impact of Simulated and Real Microgravity on Bone Cells and Mesenchymal Stem Cells

PubMed Central

Wehland, Markus; Pietsch, Jessica; Aleshcheva, Ganna; Wise, Petra; van Loon, Jack; Magnusson, Nils; Infanger, Manfred; Grosse, Jirka; Eilles, Christoph

2014-01-01

How microgravity affects the biology of human cells and the formation of 3D cell cultures in real and simulated microgravity (r- and s-µg) is currently a hot topic in biomedicine. In r- and s-µg, various cell types were found to form 3D structures. This review will focus on the current knowledge of tissue engineering in space and on Earth using systems such as the random positioning machine (RPM), the 2D-clinostat, or the NASA-developed rotating wall vessel bioreactor (RWV) to create tissue from bone, tumor, and mesenchymal stem cells. To understand the development of 3D structures, in vitro experiments using s-µg devices can provide valuable information about modulations in signal-transduction, cell adhesion, or extracellular matrix induced by altered gravity conditions. These systems also facilitate the analysis of the impact of growth factors, hormones, or drugs on these tissue-like constructs. Progress has been made in bone tissue engineering using the RWV, and multicellular tumor spheroids (MCTS), formed in both r- and s-µg, have been reported and were analyzed in depth. Currently, these MCTS are available for drug testing and proteomic investigations. This review provides an overview of the influence of µg on the aforementioned cells and an outlook for future perspectives in tissue engineering. PMID:25110709

Current strategies in multiphasic scaffold design for osteochondral tissue engineering: A review.

PubMed

Yousefi, Azizeh-Mitra; Hoque, Md Enamul; Prasad, Rangabhatala G S V; Uth, Nicholas

2015-07-01

The repair of osteochondral defects requires a tissue engineering approach that aims at mimicking the physiological properties and structure of two different tissues (cartilage and bone) using specifically designed scaffold-cell constructs. Biphasic and triphasic approaches utilize two or three different architectures, materials, or composites to produce a multilayered construct. This article gives an overview of some of the current strategies in multiphasic/gradient-based scaffold architectures and compositions for tissue engineering of osteochondral defects. In addition, the application of finite element analysis (FEA) in scaffold design and simulation of in vitro and in vivo cell growth outcomes has been briefly covered. FEA-based approaches can potentially be coupled with computer-assisted fabrication systems for controlled deposition and additive manufacturing of the simulated patterns. Finally, a summary of the existing challenges associated with the repair of osteochondral defects as well as some recommendations for future directions have been brought up in the concluding section of this article. © 2014 Wiley Periodicals, Inc.

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.

Soft tissue fillers for adipose tissue regeneration: From hydrogel development toward clinical applications.

PubMed

Van Nieuwenhove, I; Tytgat, L; Ryx, M; Blondeel, P; Stillaert, F; Thienpont, H; Ottevaere, H; Dubruel, P; Van Vlierberghe, S

2017-11-01

There is a clear and urgent clinical need to develop soft tissue fillers that outperform the materials currently used for adipose tissue reconstruction. Recently, extensive research has been performed within this field of adipose tissue engineering as the commercially available products and the currently existing techniques are concomitant with several disadvantages. Commercial products are highly expensive and associated with an imposing need for repeated injections. Lipofilling or free fat transfer has an unpredictable outcome with respect to cell survival and potential resorption of the fat grafts. Therefore, researchers are predominantly investigating two challenging adipose tissue engineering strategies: in situ injectable materials and porous 3D printed scaffolds. The present work provides an overview of current research encompassing synthetic, biopolymer-based and extracellular matrix-derived materials with a clear focus on emerging fabrication technologies and developments realized throughout the last decade. Moreover, clinical relevance of the most promising materials will be discussed, together with potential concerns associated with their application in the clinic. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

[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.

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.

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.

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.

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

3D Bioprinting for Engineering Complex Tissues

PubMed Central

Mandrycky, Christian; Wang, Zongjie; Kim, Keekyoung; Kim, Deok-Ho

2016-01-01

Bioprinting is a 3D fabrication technology used to precisely dispense cell-laden biomaterials for the construction of complex 3D functional living tissues or artificial organs. While still in its early stages, bioprinting strategies have demonstrated their potential use in regenerative medicine to generate a variety of transplantable tissues, including skin, cartilage, and bone. However, current bioprinting approaches still have technical challenges in terms of high-resolution cell deposition, controlled cell distributions, vascularization, and innervation within complex 3D tissues. While no one-size-fits-all approach to bioprinting has emerged, it remains an on-demand, versatile fabrication technique that may address the growing organ shortage as well as provide a high-throughput method for cell patterning at the micrometer scale for broad biomedical engineering applications. In this review, we introduce the basic principles, materials, integration strategies and applications of bioprinting. We also discuss the recent developments, current challenges and future prospects of 3D bioprinting for engineering complex tissues. Combined with recent advances in human pluripotent stem cell technologies, 3D-bioprinted tissue models could serve as an enabling platform for high-throughput predictive drug screening and more effective regenerative therapies. PMID:26724184

3D bioprinting for engineering complex tissues.

PubMed

Mandrycky, Christian; Wang, Zongjie; Kim, Keekyoung; Kim, Deok-Ho

2016-01-01

Bioprinting is a 3D fabrication technology used to precisely dispense cell-laden biomaterials for the construction of complex 3D functional living tissues or artificial organs. While still in its early stages, bioprinting strategies have demonstrated their potential use in regenerative medicine to generate a variety of transplantable tissues, including skin, cartilage, and bone. However, current bioprinting approaches still have technical challenges in terms of high-resolution cell deposition, controlled cell distributions, vascularization, and innervation within complex 3D tissues. While no one-size-fits-all approach to bioprinting has emerged, it remains an on-demand, versatile fabrication technique that may address the growing organ shortage as well as provide a high-throughput method for cell patterning at the micrometer scale for broad biomedical engineering applications. In this review, we introduce the basic principles, materials, integration strategies and applications of bioprinting. We also discuss the recent developments, current challenges and future prospects of 3D bioprinting for engineering complex tissues. Combined with recent advances in human pluripotent stem cell technologies, 3D-bioprinted tissue models could serve as an enabling platform for high-throughput predictive drug screening and more effective regenerative therapies. Copyright © 2015 Elsevier Inc. All rights reserved.

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.

Current progress in tissue engineering of heart valves: multiscale problems, multiscale solutions.

PubMed

Cheung, Daniel Y; Duan, Bin; Butcher, Jonathan T

2015-01-01

Heart valve disease is an increasingly prevalent and clinically serious condition. There are no clinically effective biological diagnostics or treatment strategies. The only recourse available is replacement with a prosthetic valve, but the inability of these devices to grow or respond biologically to their environments necessitates multiple resizing surgeries and life-long coagulation treatment, especially in children. Tissue engineering has a unique opportunity to impact heart valve disease by providing a living valve conduit, capable of growth and biological integration. This review will cover current tissue engineering strategies in fabricating heart valves and their progress towards the clinic, including molded scaffolds using naturally derived or synthetic polymers, decellularization, electrospinning, 3D bioprinting, hybrid techniques, and in vivo engineering. Whereas much progress has been made to create functional living heart valves, a clinically viable product is not yet realized. The next leap in engineered living heart valves will require a deeper understanding of how the natural multi-scale structural and biological heterogeneity of the tissue ensures its efficient function. Related, improved fabrication strategies must be developed that can replicate this de novo complexity, which is likely instructive for appropriate cell differentiation and remodeling whether seeded with autologous stem cells in vitro or endogenously recruited cells.

Current Progress in Tissue Engineering of Heart Valves: Multiscale Problems, Multiscale Solutions

PubMed Central

Cheung, Daniel Y; Duan, Bin; Butcher, Jonathan T.

2016-01-01

Introduction Heart valve disease is an increasingly prevalent and clinically serious condition. There are no clinically effective biological diagnostics or treatment strategies. The only recourse available is replacement with a prosthetic valve, but the inability of these devices to grow or respond biologically to their environments necessitates multiple resizing surgeries and life-long coagulation treatment, especially in children. Tissue engineering has a unique opportunity to impact heart valve disease by providing a living valve conduit, capable of growth and biological integration. Areas covered This review will cover current tissue engineering strategies in fabricating heart valves and their progress towards the clinic, including molded scaffolds using naturally-derived or synthetic polymers, decellularization, electrospinning, 3D bioprinting, hybrid techniques, and in vivo engineering. Expert opinion While much progress has been made to create functional living heart valves, a clinically viable product is not yet realized. The next leap in engineered living heart valves will require a deeper understanding of how the natural multi-scale structural and biological heterogeneity of the tissue ensures its efficient function. Related, improved fabrication strategies must be developed that can replicate this de novo complexity, which is likely instructive for appropriate cell differentiation and remodeling whether seeded with autologous stem cells in vitro or endogenously recruited cells. PMID:26027436

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.

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.

Tissue Engineering the Cornea: The Evolution of RAFT

PubMed Central

Levis, Hannah J.; Kureshi, Alvena K.; Massie, Isobel; Morgan, Louise; Vernon, Amanda J.; Daniels, Julie T.

2015-01-01

Corneal blindness affects over 10 million people worldwide and current treatment strategies often involve replacement of the defective layer with healthy tissue. Due to a worldwide donor cornea shortage and the absence of suitable biological scaffolds, recent research has focused on the development of tissue engineering techniques to create alternative therapies. This review will detail how we have refined the simple engineering technique of plastic compression of collagen to a process we now call Real Architecture for 3D Tissues (RAFT). The RAFT production process has been standardised, and steps have been taken to consider Good Manufacturing Practice compliance. The evolution of this process has allowed us to create biomimetic epithelial and endothelial tissue equivalents suitable for transplantation and ideal for studying cell-cell interactions in vitro. PMID:25809689

Recent tissue engineering-based advances for effective rAAV-mediated gene transfer in the musculoskeletal system.

PubMed

Rey-Rico, Ana; Cucchiarini, Magali

2016-04-01

Musculoskeletal tissues are diverse and significantly different in their ability to repair upon injury. Current treatments often fail to reproduce the natural functions of the native tissue, leading to an imperfect healing. Gene therapy might improve the repair of tissues by providing a temporarily and spatially defined expression of the therapeutic gene(s) at the site of the injury. Several gene transfer vehicles have been developed to modify various human cells and tissues from musculoskeletal system among which the non-pathogenic, effective, and relatively safe recombinant adeno-associated viral (rAAV) vectors that have emerged as the preferred gene delivery system to treat human disorders. Adapting tissue engineering platforms to gene transfer approaches mediated by rAAV vectors is an attractive tool to circumvent both the limitations of the current therapeutic options to promote an effective healing of the tissue and the natural obstacles from these clinically adapted vectors to achieve an efficient and durable gene expression of the therapeutic sequences within the lesions.

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

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.

Corneal Tissue Engineering: Recent Advances and Future Perspectives

PubMed Central

Ghezzi, Chiara E.; Rnjak-Kovacina, Jelena

2015-01-01

To address the growing need for corneal transplants two main approaches are being pursued: allogenic and synthetic materials. Allogenic tissue from human donors is currently the preferred choice; however, there is a worldwide shortage in donated corneal tissue. In addition, tissue rejection often limits the long-term success of this approach. Alternatively, synthetic homologs to donor corneal grafts are primarily considered temporary replacements until suitable donor tissue becomes available, as they result in a high incidence of graft failure. Tissue engineered cornea analogs would provide effective cornea tissue substitutes and alternatives to address the need to reduce animal testing of commercial products. Recent progress toward these needs is reviewed here, along with future perspectives. PMID:25434371

Cardiovascular Bio-Engineering: Current State of the Art.

PubMed

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

2017-04-01

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

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

NASA Astrophysics Data System (ADS)

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

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

The potential of nanofibers in tissue engineering and stem cell therapy.

PubMed

Gholizadeh-Ghaleh Aziz, Shiva; Gholizadeh-Ghaleh Aziz, Sara; Akbarzadeh, Abolfazl

2016-08-01

Electrospinning is a technique in which materials in solution are shaped into continuous nano- and micro-sized fibers. Combining stem cells with biomaterial scaffolds and nanofibers affords a favorable approach for bone tissue engineering, stem cell growth and transfer, ocular surface reconstruction, and treatment of congenital corneal diseases. This review seeks to describe the current examples of the use of scaffolds in stem cell therapy. Stem cells are classified as adult or embryonic stem (ES) cells, and the advantages and drawbacks of each group are detailed. The nanofibers and scaffolds are further classified in Tables I and II , which describe specific examples from the literature. Finally, the current applications of biomaterial scaffolds containing stem cells for tissue engineering applications are presented. Overall, this review seeks to give an overview of the biomaterials available for use in combination with stem cells, and the application of nanofibers in stem cell therapy.

Monitoring/Imaging and Regenerative Agents for Enhancing Tissue Engineering Characterization and Therapies.

PubMed

Santiesteban, Daniela Y; Kubelick, Kelsey; Dhada, Kabir S; Dumani, Diego; Suggs, Laura; Emelianov, Stanislav

2016-03-01

The past three decades have seen numerous advances in tissue engineering and regenerative medicine (TERM) therapies. However, despite the successes there is still much to be done before TERM therapies become commonplace in clinic. One of the main obstacles is the lack of knowledge regarding complex tissue engineering processes. Imaging strategies, in conjunction with exogenous contrast agents, can aid in this endeavor by assessing in vivo therapeutic progress. The ability to uncover real-time treatment progress will help shed light on the complex tissue engineering processes and lead to development of improved, adaptive treatments. More importantly, the utilized exogenous contrast agents can double as therapeutic agents. Proper use of these Monitoring/Imaging and Regenerative Agents (MIRAs) can help increase TERM therapy successes and allow for clinical translation. While other fields have exploited similar particles for combining diagnostics and therapy, MIRA research is still in its beginning stages with much of the current research being focused on imaging or therapeutic applications, separately. Advancing MIRA research will have numerous impacts on achieving clinical translations of TERM therapies. Therefore, it is our goal to highlight current MIRA progress and suggest future research that can lead to effective TERM treatments.

Emerging Perspectives in Scaffold for Tissue Engineering in Oral Surgery.

PubMed

Ceccarelli, Gabriele; Presta, Rossella; Benedetti, Laura; Cusella De Angelis, Maria Gabriella; Lupi, Saturnino Marco; Rodriguez Y Baena, Ruggero

2017-01-01

Bone regeneration is currently one of the most important and challenging tissue engineering approaches in regenerative medicine. Bone regeneration is a promising approach in dentistry and is considered an ideal clinical strategy in treating diseases, injuries, and defects of the maxillofacial region. Advances in tissue engineering have resulted in the development of innovative scaffold designs, complemented by the progress made in cell-based therapies. In vitro bone regeneration can be achieved by the combination of stem cells, scaffolds, and bioactive factors. The biomimetic approach to create an ideal bone substitute provides strategies for developing combined scaffolds composed of adult stem cells with mesenchymal phenotype and different organic biomaterials (such as collagen and hyaluronic acid derivatives) or inorganic biomaterials such as manufactured polymers (polyglycolic acid (PGA), polylactic acid (PLA), and polycaprolactone). This review focuses on different biomaterials currently used in dentistry as scaffolds for bone regeneration in treating bone defects or in surgical techniques, such as sinus lift, horizontal and vertical bone grafts, or socket preservation. Our review would be of particular interest to medical and surgical researchers at the interface of cell biology, materials science, and tissue engineering, as well as industry-related manufacturers and researchers in healthcare, prosthetics, and 3D printing, too.

Controlled Positioning of Cells in Biomaterials—Approaches Towards 3D Tissue Printing

PubMed Central

Wüst, Silke; Müller, Ralph; Hofmann, Sandra

2011-01-01

Current tissue engineering techniques have various drawbacks: they often incorporate uncontrolled and imprecise scaffold geometries, whereas the current conventional cell seeding techniques result mostly in random cell placement rather than uniform cell distribution. For the successful reconstruction of deficient tissue, new material engineering approaches have to be considered to overcome current limitations. An emerging method to produce complex biological products including cells or extracellular matrices in a controlled manner is a process called bioprinting or biofabrication, which effectively uses principles of rapid prototyping combined with cell-loaded biomaterials, typically hydrogels. 3D tissue printing is an approach to manufacture functional tissue layer-by-layer that could be transplanted in vivo after production. This method is especially advantageous for stem cells since a controlled environment can be created to influence cell growth and differentiation. Using printed tissue for biotechnological and pharmacological needs like in vitro drug-testing may lead to a revolution in the pharmaceutical industry since animal models could be partially replaced by biofabricated tissues mimicking human physiology and pathology. This would not only be a major advancement concerning rising ethical issues but would also have a measureable impact on economical aspects in this industry of today, where animal studies are very labor-intensive and therefore costly. In this review, current controlled material and cell positioning techniques are introduced highlighting approaches towards 3D tissue printing. PMID:24956301

Controlled Positioning of Cells in Biomaterials-Approaches Towards 3D Tissue Printing.

PubMed

Wüst, Silke; Müller, Ralph; Hofmann, Sandra

2011-08-04

Current tissue engineering techniques have various drawbacks: they often incorporate uncontrolled and imprecise scaffold geometries, whereas the current conventional cell seeding techniques result mostly in random cell placement rather than uniform cell distribution. For the successful reconstruction of deficient tissue, new material engineering approaches have to be considered to overcome current limitations. An emerging method to produce complex biological products including cells or extracellular matrices in a controlled manner is a process called bioprinting or biofabrication, which effectively uses principles of rapid prototyping combined with cell-loaded biomaterials, typically hydrogels. 3D tissue printing is an approach to manufacture functional tissue layer-by-layer that could be transplanted in vivo after production. This method is especially advantageous for stem cells since a controlled environment can be created to influence cell growth and differentiation. Using printed tissue for biotechnological and pharmacological needs like in vitro drug-testing may lead to a revolution in the pharmaceutical industry since animal models could be partially replaced by biofabricated tissues mimicking human physiology and pathology. This would not only be a major advancement concerning rising ethical issues but would also have a measureable impact on economical aspects in this industry of today, where animal studies are very labor-intensive and therefore costly. In this review, current controlled material and cell positioning techniques are introduced highlighting approaches towards 3D tissue printing.

Biomimetic Materials and Fabrication Approaches for Bone Tissue Engineering.

PubMed

Kim, Hwan D; Amirthalingam, Sivashanmugam; Kim, Seunghyun L; Lee, Seunghun S; Rangasamy, Jayakumar; Hwang, Nathaniel S

2017-12-01

Various strategies have been explored to overcome critically sized bone defects via bone tissue engineering approaches that incorporate biomimetic scaffolds. Biomimetic scaffolds may provide a novel platform for phenotypically stable tissue formation and stem cell differentiation. In recent years, osteoinductive and inorganic biomimetic scaffold materials have been optimized to offer an osteo-friendly microenvironment for the osteogenic commitment of stem cells. Furthermore, scaffold structures with a microarchitecture design similar to native bone tissue are necessary for successful bone tissue regeneration. For this reason, various methods for fabricating 3D porous structures have been developed. Innovative techniques, such as 3D printing methods, are currently being utilized for optimal host stem cell infiltration, vascularization, nutrient transfer, and stem cell differentiation. In this progress report, biomimetic materials and fabrication approaches that are currently being utilized for biomimetic scaffold design are reviewed. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

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.

Current and future regenerative medicine — Principles, concepts, and therapeutic use of stem cell therapy and tissue engineering in equine medicine

PubMed Central

Koch, Thomas G.; Berg, Lise C.; Betts, Dean H.

2009-01-01

This paper provides a bird’s-eye perspective of the general principles of stem-cell therapy and tissue engineering; it relates comparative knowledge in this area to the current and future status of equine regenerative medicine. The understanding of equine stem cell biology, biofactors, and scaffolds, and their potential therapeutic use in horses are rudimentary at present. Mesenchymal stem cell isolation has been proclaimed from several equine tissues in the past few years. Based on the criteria of the International Society for Cellular Therapy, most of these cells are more correctly referred to as multipotent mesenchymal stromal cells, unless there is proof that they exhibit the fundamental in vivo characteristics of pluripotency and the ability to self-renew. That said, these cells from various tissues hold great promise for therapeutic use in horses. The 3 components of tissue engineering — cells, biological factors, and biomaterials — are increasingly being applied in equine medicine, fuelled by better scaffolds and increased understanding of individual biofactors and cell sources. The effectiveness of stem cell-based therapies and most tissue engineering concepts has not been demonstrated sufficiently in controlled clinical trials in equine patients to be regarded as evidence-based medicine. In the meantime, the medical mantra “do no harm” should prevail, and the application of stem cell-based therapies in the horse should be done critically and cautiously, and treatment outcomes (good and bad) should be recorded and reported. Stem cell and tissue engineering research in the horse has exciting comparative and equine specific perspectives that most likely will benefit the health of horses and humans. Controlled, well-designed studies are needed to move this new equine research field forward. PMID:19412395

A Review of Current Regenerative Medicine Strategies that Utilize Nanotechnology to Treat Cartilage Damage

PubMed Central

Kumar, R.; Griffin, M.; Butler, P.E.

2016-01-01

Background: Cartilage is an important tissue found in a variety of anatomical locations. Damage to cartilage is particularly detrimental, owing to its intrinsically poor healing capacity. Current reconstructive options for cartilage repair are limited, and alternative approaches are required. Biomaterial science and Tissue engineering are multidisciplinary areas of research that integrate biological and engineering principles for the purpose of restoring premorbid tissue function. Biomaterial science traditionally focuses on the replacement of diseased or damaged tissue with implants. Conversely, tissue engineering utilizes porous biomimetic scaffolds, containing cells and bioactive molecules, to regenerate functional tissue. However, both paradigms feature several disadvantages. Faced with the increasing clinical burden of cartilage defects, attention has shifted towards the incorporation of Nanotechnology into these areas of regenerative medicine. Methods: Searches were conducted on Pubmed using the terms “cartilage”, “reconstruction”, “nanotechnology”, “nanomaterials”, “tissue engineering” and “biomaterials”. Abstracts were examined to identify articles of relevance, and further papers were obtained from the citations within. Results: The content of 96 articles was ultimately reviewed. The literature yielded no studies that have progressed beyond in vitro and in vivo experimentation. Several limitations to the use of nanomaterials to reconstruct damaged cartilage were identified in both the tissue engineering and biomaterial fields. Conclusion: Nanomaterials have unique physicochemical properties that interact with biological systems in novel ways, potentially opening new avenues for the advancement of constructs used to repair cartilage. However, research into these technologies is in its infancy, and clinical translation remains elusive. PMID:28217211

Design of electrical stimulation bioreactors for cardiac tissue engineering.

PubMed

Tandon, N; Marsano, A; Cannizzaro, C; Voldman, J; Vunjak-Novakovic, G

2008-01-01

Electrical stimulation has been shown to improve functional assembly of cardiomyocytes in vitro for cardiac tissue engineering. Carbon electrodes were found in past studies to have the best current injection characteristics. The goal of this study was to develop rational experimental design principles for the electrodes and stimulation regime, in particular electrode configuration, electrode ageing, and stimulation amplitude. Carbon rod electrodes were compared via electrochemical impedance spectroscopy (EIS) and we identified a safety range of 0 to 8 V/cm by comparing excitation thresholds and maximum capture rates for neonatal rat cardiomyocytes cultured with electrical stimulation. We conclude with recommendations for studies involving carbon electrodes for cardiac tissue engineering.

Recent Advances in Biohybrid Materials for Tissue Engineering and Regenerative Medicine

NASA Astrophysics Data System (ADS)

Wan, Ying; Li, Xing; Wang, Shenqi

2016-07-01

Biohybrid materials play an important role in tissue engineering, artificial organs and regenerative medicine due to their regulation of cell function through specific cell-matrix interactions involving integrins, mostly those of fibroblasts and myofibroblasts, and ligands on the matrix surface, which have become current research focus. In this paper, recent progress of biohybrid materials, mainly including main types of biohybrid materials, rapid prototype (RP) technique for construction of 3D biohybrid materials, was reviewed in detail; moreover, their applications in tissue engineering, artificial organs and regenerative medicine were also reviewed in detail. At last, we address the challenges biohybrid materials may face.

Cartilage tissue engineering: recent advances and perspectives from gene regulation/therapy.

PubMed

Li, Kuei-Chang; Hu, Yu-Chen

2015-05-01

Diseases in articular cartilages affect millions of people. Despite the relatively simple biochemical and cellular composition of articular cartilages, the self-repair ability of cartilage is limited. Successful cartilage tissue engineering requires intricately coordinated interactions between matrerials, cells, biological factors, and phycial/mechanical factors, and still faces a multitude of challenges. This article presents an overview of the cartilage biology, current treatments, recent advances in the materials, biological factors, and cells used in cartilage tissue engineering/regeneration, with strong emphasis on the perspectives of gene regulation (e.g., microRNA) and gene therapy. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Convergence of regenerative medicine and synthetic biology to develop standardized and validated models of human diseases with clinical relevance.

PubMed

Hutmacher, Dietmar Werner; Holzapfel, Boris Michael; De-Juan-Pardo, Elena Maria; Pereira, Brooke Anne; Ellem, Stuart John; Loessner, Daniela; Risbridger, Gail Petuna

2015-12-01

In order to progress beyond currently available medical devices and implants, the concept of tissue engineering has moved into the centre of biomedical research worldwide. The aim of this approach is not to replace damaged tissue with an implant or device but rather to prompt the patient's own tissue to enact a regenerative response by using a tissue-engineered construct to assemble new functional and healthy tissue. More recently, it has been suggested that the combination of Synthetic Biology and translational tissue-engineering techniques could enhance the field of personalized medicine, not only from a regenerative medicine perspective, but also to provide frontier technologies for building and transforming the research landscape in the field of in vitro and in vivo disease models. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

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.

Advances in Skin Regeneration Using Tissue Engineering.

PubMed

Vig, Komal; Chaudhari, Atul; Tripathi, Shweta; Dixit, Saurabh; Sahu, Rajnish; Pillai, Shreekumar; Dennis, Vida A; Singh, Shree R

2017-04-07

Tissue engineered skin substitutes for wound healing have evolved tremendously over the last couple of years. New advances have been made toward developing skin substitutes made up of artificial and natural materials. Engineered skin substitutes are developed from acellular materials or can be synthesized from autologous, allograft, xenogenic, or synthetic sources. Each of these engineered skin substitutes has their advantages and disadvantages. However, to this date, a complete functional skin substitute is not available, and research is continuing to develop a competent full thickness skin substitute product that can vascularize rapidly. There is also a need to redesign the currently available substitutes to make them user friendly, commercially affordable, and viable with longer shelf life. The present review focuses on providing an overview of advances in the field of tissue engineered skin substitute development, the availability of various types, and their application.

Generation and Assessment of Functional Biomaterial Scaffolds for Applications in Cardiovascular Tissue Engineering and Regenerative Medicine

PubMed Central

Hinderer, Svenja; Brauchle, Eva

2015-01-01

Current clinically applicable tissue and organ replacement therapies are limited in the field of cardiovascular regenerative medicine. The available options do not regenerate damaged tissues and organs, and, in the majority of the cases, show insufficient restoration of tissue function. To date, anticoagulant drug‐free heart valve replacements or growing valves for pediatric patients, hemocompatible and thrombus‐free vascular substitutes that are smaller than 6 mm, and stem cell‐recruiting delivery systems that induce myocardial regeneration are still only visions of researchers and medical professionals worldwide and far from being the standard of clinical treatment. The design of functional off‐the‐shelf biomaterials as well as automatable and up‐scalable biomaterial processing methods are the focus of current research endeavors and of great interest for fields of tissue engineering and regenerative medicine. Here, various approaches that aim to overcome the current limitations are reviewed, focusing on biomaterials design and generation methods for myocardium, heart valves, and blood vessels. Furthermore, novel contact‐ and marker‐free biomaterial and extracellular matrix assessment methods are highlighted. PMID:25778713

Biofunctionalized Plants as Diverse Biomaterials for Human Cell Culture.

PubMed

Fontana, Gianluca; Gershlak, Joshua; Adamski, Michal; Lee, Jae-Sung; Matsumoto, Shion; Le, Hau D; Binder, Bernard; Wirth, John; Gaudette, Glenn; Murphy, William L

2017-04-01

The commercial success of tissue engineering products requires efficacy, cost effectiveness, and the possibility of scaleup. Advances in tissue engineering require increased sophistication in the design of biomaterials, often challenging the current manufacturing techniques. Interestingly, several of the properties that are desirable for biomaterial design are embodied in the structure and function of plants. This study demonstrates that decellularized plant tissues can be used as adaptable scaffolds for culture of human cells. With simple biofunctionalization technique, it is possible to enable adhesion of human cells on a diverse set of plant tissues. The elevated hydrophilicity and excellent water transport abilities of plant tissues allow cell expansion over prolonged periods of culture. Moreover, cells are able to conform to the microstructure of the plant frameworks, resulting in cell alignment and pattern registration. In conclusion, the current study shows that it is feasible to use plant tissues as an alternative feedstock of scaffolds for mammalian cells. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Towards artificial tissue models: past, present, and future of 3D bioprinting.

PubMed

Arslan-Yildiz, Ahu; El Assal, Rami; Chen, Pu; Guven, Sinan; Inci, Fatih; Demirci, Utkan

2016-03-01

Regenerative medicine and tissue engineering have seen unprecedented growth in the past decade, driving the field of artificial tissue models towards a revolution in future medicine. Major progress has been achieved through the development of innovative biomanufacturing strategies to pattern and assemble cells and extracellular matrix (ECM) in three-dimensions (3D) to create functional tissue constructs. Bioprinting has emerged as a promising 3D biomanufacturing technology, enabling precise control over spatial and temporal distribution of cells and ECM. Bioprinting technology can be used to engineer artificial tissues and organs by producing scaffolds with controlled spatial heterogeneity of physical properties, cellular composition, and ECM organization. This innovative approach is increasingly utilized in biomedicine, and has potential to create artificial functional constructs for drug screening and toxicology research, as well as tissue and organ transplantation. Herein, we review the recent advances in bioprinting technologies and discuss current markets, approaches, and biomedical applications. We also present current challenges and provide future directions for bioprinting research.

Bioactive Glass and Glass-Ceramic Scaffolds for Bone Tissue Engineering

PubMed Central

Gerhardt, Lutz-Christian; Boccaccini, Aldo R.

2010-01-01

Traditionally, bioactive glasses have been used to fill and restore bone defects. More recently, this category of biomaterials has become an emerging research field for bone tissue engineering applications. Here, we review and discuss current knowledge on porous bone tissue engineering scaffolds on the basis of melt-derived bioactive silicate glass compositions and relevant composite structures. Starting with an excerpt on the history of bioactive glasses, as well as on fundamental requirements for bone tissue engineering scaffolds, a detailed overview on recent developments of bioactive glass and glass-ceramic scaffolds will be given, including a summary of common fabrication methods and a discussion on the microstructural-mechanical properties of scaffolds in relation to human bone (structure-property and structure-function relationship). In addition, ion release effects of bioactive glasses concerning osteogenic and angiogenic responses are addressed. Finally, areas of future research are highlighted in this review. PMID:28883315

Chondrogenesis and cartilage tissue engineering: the longer road to technology development.

PubMed

Mahmoudifar, Nastaran; Doran, Pauline M

2012-03-01

Joint injury and disease are painful and debilitating conditions affecting a substantial proportion of the population. The idea that damaged cartilage in articulating joints might be replaced seamlessly with tissue-engineered cartilage is of obvious commercial interest because the market for such treatments is large. Recently, a wealth of new information about the complex biology of chondrogenesis and cartilage has emerged from stem cell research, including increasing evidence of the role of physical stimuli in directing differentiation. The challenge for the next generation of tissue engineers is to identify the key elements in this new body of knowledge that can be applied to overcome current limitations affecting cartilage synthesis in vitro. Here we review the status of cartilage tissue engineering and examine the contribution of stem cell research to technology development for cartilage production. Copyright © 2011 Elsevier Ltd. All rights reserved.

Influence of nanomaterials on stem cell differentiation: designing an appropriate nanobiointerface

PubMed Central

Ilie, Ioana; Ilie, Razvan; Mocan, Teodora; Bartos, Dana; Mocan, Lucian

2012-01-01

During the last decade, due to advances in functionalization chemistry, novel nanobiomaterials with applications in tissue engineering and regenerative medicine have been developed. These novel materials with their unique physical and chemical properties are bioactive hierarchical structures that hold great promise for future development of human tissues. Thus, various nanomaterials are currently being intensively explored in the directed differentiation of stem cells, the design of novel bioactive scaffolds, and new research avenues towards tissue regeneration. This paper illustrates the latest achievements in the applications of nanotechnology in tissue engineering in the field of regenerative medicine. PMID:22619557

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

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

Silk fibroin in tissue engineering.

PubMed

Kasoju, Naresh; Bora, Utpal

2012-07-01

Tissue engineering (TE) is a multidisciplinary field that aims at the in vitro engineering of tissues and organs by integrating science and technology of cells, materials and biochemical factors. Mimicking the natural extracellular matrix is one of the critical and challenging technological barriers, for which scaffold engineering has become a prime focus of research within the field of TE. Amongst the variety of materials tested, silk fibroin (SF) is increasingly being recognized as a promising material for scaffold fabrication. Ease of processing, excellent biocompatibility, remarkable mechanical properties and tailorable degradability of SF has been explored for fabrication of various articles such as films, porous matrices, hydrogels, nonwoven mats, etc., and has been investigated for use in various TE applications, including bone, tendon, ligament, cartilage, skin, liver, trachea, nerve, cornea, eardrum, dental, bladder, etc. The current review extensively covers the progress made in the SF-based in vitro engineering and regeneration of various human tissues and identifies opportunities for further development of this field. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Advances in Tissue Engineering Techniques for Articular Cartilage Repair

PubMed Central

Haleem, AM; Chu, CR

2010-01-01

The limited repair potential of human articular cartilage contributes to development of debilitating osteoarthritis and remains a great clinical challenge. This has led to evolution of cartilage treatment strategies from palliative to either reconstructive or reparative methods in an attempt to delay or “bridge the gap” to joint replacement. Further development of tissue engineering-based cartilage repair methods have been pursued to provide a more functional biological tissue. Currently, tissue engineering of articular cartilage has three cornerstones; a cell population capable of proliferation and differentiation into mature chondrocytes, a scaffold that can host these cells, provide a suitable environment for cellular functioning and serve as a sustained-release delivery vehicle of chondrogenic growth factors and thirdly, signaling molecules and growth factors that stimulate the cellular response and the production of a hyaline extracellular matrix (ECM). The aim of this review is to summarize advances in each of these three fields of tissue engineering with specific relevance to surgical techniques and technical notes. PMID:29430164

Biomaterials and cells for neural tissue engineering: Current choices.

PubMed

Sensharma, Prerana; Madhumathi, G; Jayant, Rahul D; Jaiswal, Amit K

2017-08-01

The treatment of nerve injuries has taken a new dimension with the development of tissue engineering techniques. Prior to tissue engineering, suturing and surgery were the only options for effective treatment. With the advent of tissue engineering, it is now possible to design a scaffold that matches the exact biological and mechanical properties of the tissue. This has led to substantial reduction in the complications posed by surgeries and suturing to the patients. New synthetic and natural polymers are being applied to test their efficiency in generating an ideal scaffold. Along with these, cells and growth factors are also being incorporated to increase the efficiency of a scaffold. Efforts are being made to devise a scaffold that is biodegradable, biocompatible, conducting and immunologically inert. The ultimate goal is to exactly mimic the extracellular matrix in our body, and to elicit a combination of biochemical, topographical and electrical cues via various polymers, cells and growth factors, using which nerve regeneration can efficiently occur. Copyright © 2017 Elsevier B.V. All rights reserved.

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

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

PubMed

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

2017-12-01

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

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.

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

Messenger RNA Delivery for Tissue Engineering and Regenerative Medicine Applications.

PubMed

Patel, Siddharth; Athirasala, Avathamsa; Menezes, Paula P; Ashwanikumar, N; Zou, Ting; Sahay, Gaurav; Bertassoni, Luiz E

2018-06-07

The ability to control cellular processes and precisely direct cellular reprogramming has revolutionized regenerative medicine. Recent advances in in vitro transcribed (IVT) mRNA technology with chemical modifications have led to development of methods that control spatiotemporal gene expression. Additionally, there is a current thrust toward the development of safe, integration-free approaches to gene therapy for translational purposes. In this review, we describe strategies of synthetic IVT mRNA modifications and nonviral technologies for intracellular delivery. We provide insights into the current tissue engineering approaches that use a hydrogel scaffold with genetic material. Furthermore, we discuss the transformative potential of novel mRNA formulations that when embedded in hydrogels can trigger controlled genetic manipulation to regenerate tissues and organs in vitro and in vivo. The role of mRNA delivery in vascularization, cytoprotection, and Cas9-mediated xenotransplantation is additionally highlighted. Harmonizing mRNA delivery vehicle interactions with polymeric scaffolds can be used to present genetic cues that lead to precise command over cellular reprogramming, differentiation, and secretome activity of stem cells-an ultimate goal for tissue engineering.

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.

Harnessing the power of macrophages/monocytes for enhanced bone tissue engineering.

PubMed

Dong, Lei; Wang, Chunming

2013-06-01

Bone tissue engineering has attracted considerable attention as a promising treatment modality for severe bone degeneration. The pressing need for more sophisticated and fully functional bone substitutes has spurred a refocus on the development of bone constructs in a way more comparable to the physiological process. Current research is increasingly revealing the central roles of macrophages/monocytes in regulating bone development and repair, so we propose that these immunocytes can play a similar pivotal role in directing engineered bone regeneration. Accordingly, we discuss two possible strategies to exemplify how the distinctive power of macrophages/monocytes--particularly their cytokine-secretion ability and chemotactic response to foreign materials--can be harnessed to enhance the performance of bone tissue engineering applications. Copyright © 2013 Elsevier Ltd. All rights reserved.

Tissue Engineering and Regenerative Repair in Wound Healing

PubMed Central

Hu, Michael S.; Maan, Zeshaan N.; Wu, Jen-Chieh; Rennert, Robert C.; Hong, Wan Xing; Lai, Tiffany S.; Cheung, Alexander T. M.; Walmsley, Graham G.; Chung, Michael T.; McArdle, Adrian; Longaker, Michael T.; Lorenz, H. Peter

2014-01-01

Wound healing is a highly evolved defense mechanism against infection and further injury. It is a complex process involving multiple cell types and biological pathways. Mammalian adult cutaneous wound healing is mediated by a fibroproliferative response leading to scar formation. In contrast, early to mid-gestational fetal cutaneous wound healing is more akin to regeneration and occurs without scar formation. This early observation has led to extensive research seeking to unlock the mechanism underlying fetal scarless regenerative repair. Building upon recent advances in biomaterials and stem cell applications, tissue engineering approaches are working towards a recapitulation of this phenomenon. In this review, we describe the elements that distinguish fetal scarless and adult scarring wound healing, and discuss current trends in tissue engineering aimed at achieving scarless tissue regeneration. PMID:24788648

Muscle Tissue Engineering Using Gingival Mesenchymal Stem Cells Encapsulated in Alginate Hydrogels Containing Multiple Growth Factors.

PubMed

Ansari, Sahar; Chen, Chider; Xu, Xingtian; Annabi, Nasim; Zadeh, Homayoun H; Wu, Benjamin M; Khademhosseini, Ali; Shi, Songtao; Moshaverinia, Alireza

2016-06-01

Repair and regeneration of muscle tissue following traumatic injuries or muscle diseases often presents a challenging clinical situation. If a significant amount of tissue is lost the native regenerative potential of skeletal muscle will not be able to grow to fill the defect site completely. Dental-derived mesenchymal stem cells (MSCs) in combination with appropriate scaffold material, present an advantageous alternative therapeutic option for muscle tissue engineering in comparison to current treatment modalities available. To date, there has been no report on application of gingival mesenchymal stem cells (GMSCs) in three-dimensional scaffolds for muscle tissue engineering. The objectives of the current study were to develop an injectable 3D RGD-coupled alginate scaffold with multiple growth factor delivery capacity for encapsulating GMSCs, and to evaluate the capacity of encapsulated GMSCs to differentiate into myogenic tissue in vitro and in vivo where encapsulated GMSCs were transplanted subcutaneously into immunocompromised mice. The results demonstrate that after 4 weeks of differentiation in vitro, GMSCs as well as the positive control human bone marrow mesenchymal stem cells (hBMMSCs) exhibited muscle cell-like morphology with high levels of mRNA expression for gene markers related to muscle regeneration (MyoD, Myf5, and MyoG) via qPCR measurement. Our quantitative PCR analyzes revealed that the stiffness of the RGD-coupled alginate regulates the myogenic differentiation of encapsulated GMSCs. Histological and immunohistochemical/fluorescence staining for protein markers specific for myogenic tissue confirmed muscle regeneration in subcutaneous transplantation in our in vivo animal model. GMSCs showed significantly greater capacity for myogenic regeneration in comparison to hBMMSCs (p < 0.05). Altogether, our findings confirmed that GMSCs encapsulated in RGD-modified alginate hydrogel with multiple growth factor delivery capacity is a promising candidate for muscle tissue engineering.

Design of Electrical Stimulation Bioreactors for Cardiac Tissue Engineering

PubMed Central

Tandon, N.; Marsano, A.; Cannizzaro, C.; Voldman, J.; Vunjak-Novakovic, G.

2009-01-01

Electrical stimulation has been shown to improve functional assembly of cardiomyocytes in vitro for cardiac tissue engineering. Carbon electrodes were found in past studies to have the best current injection characteristics. The goal of this study was to develop rational experimental design principles for the electrodes and stimulation regime, in particular electrode configuration, electrode ageing, and stimulation amplitude. Carbon rod electrodes were compared via electrochemical impedance spectroscopy (EIS) and we identified a safety range of 0 to 8 V/cm by comparing excitation thresholds and maximum capture rates for neonatal rat cardiomyocytes cultured with electrical stimulation. We conclude with recommendations for studies involving carbon electrodes for cardiac tissue engineering. PMID:19163486

Poly (lactic acid)-based biomaterials for orthopaedic regenerative engineering.

PubMed

Narayanan, Ganesh; Vernekar, Varadraj N; Kuyinu, Emmanuel L; Laurencin, Cato T

2016-12-15

Regenerative engineering converges tissue engineering, advanced materials science, stem cell science, and developmental biology to regenerate complex tissues such as whole limbs. Regenerative engineering scaffolds provide mechanical support and nanoscale control over architecture, topography, and biochemical cues to influence cellular outcome. In this regard, poly (lactic acid) (PLA)-based biomaterials may be considered as a gold standard for many orthopaedic regenerative engineering applications because of their versatility in fabrication, biodegradability, and compatibility with biomolecules and cells. Here we discuss recent developments in PLA-based biomaterials with respect to processability and current applications in the clinical and research settings for bone, ligament, meniscus, and cartilage regeneration. Copyright © 2016 Elsevier B.V. All rights reserved.

Emerging Perspectives in Scaffold for Tissue Engineering in Oral Surgery

PubMed Central

Presta, Rossella

2017-01-01

Bone regeneration is currently one of the most important and challenging tissue engineering approaches in regenerative medicine. Bone regeneration is a promising approach in dentistry and is considered an ideal clinical strategy in treating diseases, injuries, and defects of the maxillofacial region. Advances in tissue engineering have resulted in the development of innovative scaffold designs, complemented by the progress made in cell-based therapies. In vitro bone regeneration can be achieved by the combination of stem cells, scaffolds, and bioactive factors. The biomimetic approach to create an ideal bone substitute provides strategies for developing combined scaffolds composed of adult stem cells with mesenchymal phenotype and different organic biomaterials (such as collagen and hyaluronic acid derivatives) or inorganic biomaterials such as manufactured polymers (polyglycolic acid (PGA), polylactic acid (PLA), and polycaprolactone). This review focuses on different biomaterials currently used in dentistry as scaffolds for bone regeneration in treating bone defects or in surgical techniques, such as sinus lift, horizontal and vertical bone grafts, or socket preservation. Our review would be of particular interest to medical and surgical researchers at the interface of cell biology, materials science, and tissue engineering, as well as industry-related manufacturers and researchers in healthcare, prosthetics, and 3D printing, too. PMID:28337223

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.

Are synthetic scaffolds suitable for the development of clinical tissue-engineered tubular organs?

PubMed

Del Gaudio, Costantino; Baiguera, Silvia; Ajalloueian, Fatemeh; Bianco, Alessandra; Macchiarini, Paolo

2014-07-01

Transplantation of tissues and organs is currently the only available treatment for patients with end-stage diseases. However, its feasibility is limited by the chronic shortage of suitable donors, the need for life-long immunosuppression, and by socioeconomical and religious concerns. Recently, tissue engineering has garnered interest as a means to generate cell-seeded three-dimensional scaffolds that could replace diseased organs without requiring immunosuppression. Using a regenerative approach, scaffolds made by synthetic, nonimmunogenic, and biocompatible materials have been developed and successfully clinically implanted. This strategy, based on a viable and ready-to-use bioengineered scaffold, able to promote novel tissue formation, favoring cell adhesion and proliferation, could become a reliable alternative to allotransplatation in the next future. In this article, tissue-engineered synthetic substitutes for tubular organs (such as trachea, esophagus, bile ducts, and bowel) are reviewed, including a discussion on their morphological and functional properties. © 2013 Wiley Periodicals, Inc.

Design and optimization of a novel bio-loom to weave melt-spun absorbable polymers for bone tissue engineering.

PubMed

Gilmore, Jordon; Burg, Timothy; Groff, Richard E; Burg, Karen J L

2017-08-01

Bone graft procedures are currently among the most common surgical procedures performed worldwide, but due to high risk of complication and lack of viable donor tissue, there exists a need to develop alternatives for bone defect healing. Tissue engineering, for example, combining biocompatible scaffolds with mesenchymal stem cells to achieve new bone growth, is a possible solution. Recent work has highlighted the potential for woven polymer meshes to serve as bone tissue engineering scaffolds; since, scaffolds can be iteratively designed by adjusting weave settings, material types, and mesh parameters. However, there are a number of material and system challenges preventing the implementation of such a tissue engineering strategy. Fiber compliance, tensile strength, brittleness, cross-sectional geometry, and size present specific challenges for using traditional textile weaving methods. In the current work, two potential scaffold materials, melt-spun poly-l-lactide, and poly-l-lactide-co-ε-caprolactone, were investigated. An automated bio-loom was engineered and built to weave these materials. The bio-loom was used to successfully demonstrate the weaving of these difficult-to-handle fiber types into various mesh configurations and material combinations. The dobby-loom design, adapted with an air jet weft placement system, warp tension control system, and automated collection spool, provides minimal damage to the polymer fibers while overcoming the physical constraints presented by the inherent material structure. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1342-1351, 2017. © 2016 Wiley Periodicals, Inc.

Clinical applications of decellularized extracellular matrices for tissue engineering and regenerative medicine.

PubMed

Parmaksiz, Mahmut; Dogan, Arin; Odabas, Sedat; Elçin, A Eser; Elçin, Y Murat

2016-03-17

Decellularization is the process of removing the cellular components from tissues or organs. It is a promising technology for obtaining a biomaterial with a highly preserved extracellular matrix (ECM), which may also act as a biological scaffold for tissue engineering and regenerative therapies. Decellularized products are gaining clinical importance and market space due to their ease of standardized production, constant availability for grafting and mechanical or biochemical superiority against competing clinical options, yielding clinical results ahead of the ones with autografts in some applications. Current drawbacks and limitations of traditional treatments and clinical applications can be overcome by using decellularized or acellular matrices. Several companies are leading the market with versatile acellular products designed for diverse use in the reconstruction of tissues and organs. This review describes ECM-based decellularized and acellular products that are currently in use for different branches of clinic.

In vitro plant tissue culture: means for production of biological active compounds.

PubMed

Espinosa-Leal, Claudia A; Puente-Garza, César A; García-Lara, Silverio

2018-05-07

Plant tissue culture as an important tool for the continuous production of active compounds including secondary metabolites and engineered molecules. Novel methods (gene editing, abiotic stress) can improve the technique. Humans have a long history of reliance on plants for a supply of food, shelter and, most importantly, medicine. Current-day pharmaceuticals are typically based on plant-derived metabolites, with new products being discovered constantly. Nevertheless, the consistent and uniform supply of plant pharmaceuticals has often been compromised. One alternative for the production of important plant active compounds is in vitro plant tissue culture, as it assures independence from geographical conditions by eliminating the need to rely on wild plants. Plant transformation also allows the further use of plants for the production of engineered compounds, such as vaccines and multiple pharmaceuticals. This review summarizes the important bioactive compounds currently produced by plant tissue culture and the fundamental methods and plants employed for their production.

Colloidal gas aphron foams: A novel approach to a hydrogel based tissue engineered myocardial patch

NASA Astrophysics Data System (ADS)

Johnson, Elizabeth Edna

Cardiovascular disease currently affects an estimated 58 million Americans and is the leading cause of death in the US. Over 2.3 million Americans are currently living with heart failure a leading cause of which is acute myocardial infarction, during which a part of the heart muscle is damaged beyond repair. There is a great need to develop treatments for damaged heart tissue. One potential therapy involves replacement of nonfunctioning scar tissue with a patch of healthy, functioning tissue. A tissue engineered cardiac patch would be ideal for such an application. Tissue engineering techniques require the use of porous scaffolds, which serve as a 3-D template for initial cell attachment and grow-th leading to tissue formation. The scaffold must also have mechanical properties closely matching those of the tissues at the site of implantation. Our research presents a new approach to meet these design requirements. A unique interaction between poly(vinyl alcohol) and amino acids has been discovered by our lab, resulting in the production of novel gels. These unique synthetic hydrogels along with one natural hydrogel, alginate (derived from brown seaweed), have been coupled with a new approach to tissue scaffold fabrication using solid colloidal gas aphrons (CGAs). CGAs are colloidal foams containing uniform bubbles with diameters on the order of micrometers. Upon solidification the GCAs form a porous, 3-D network suitable for a tissue scaffold. The project encompasses four specific aims: (I) characterize hydrogel formation mechanism, (II) use colloidal gas aphrons to produce hydrogel scaffolds, (III) chemically and physically characterize scaffold materials and (IV) optimize and evaluate scaffold biocompatibility.

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.

Supporting Biomaterials for Articular Cartilage Repair

PubMed Central

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

2012-01-01

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

Tissue Engineering of the Urethra: A Systematic Review and Meta-analysis of Preclinical and Clinical Studies.

PubMed

Versteegden, Luuk R M; de Jonge, Paul K J D; IntHout, Joanna; van Kuppevelt, Toin H; Oosterwijk, Egbert; Feitz, Wout F J; de Vries, Rob B M; Daamen, Willeke F

2017-10-01

Urethra repair by tissue engineering has been extensively studied in laboratory animals and patients, but is not routinely used in clinical practice. To systematically investigate preclinical and clinical evidence of the efficacy of tissue engineering for urethra repair in order to stimulate translation of preclinical studies to the clinic. A systematic search strategy was applied in PubMed and EMBASE. Studies were independently screened for relevance by two reviewers, resulting in 80 preclinical and 23 clinical studies of which 63 and 13 were selected for meta-analysis to assess side effects, functionality, and study completion. Analyses for preclinical and clinical studies were performed separately. Full circumferential and inlay procedures were assessed independently. Evaluated parameters included seeding of cells and type of biomaterial. Meta-analysis revealed that cell seeding significantly reduced the probability of encountering side effects in preclinical studies. Remarkably though, cells were only sparsely used in the clinic (4/23 studies) and showed no significant reduction of side effects. ln 21 out of 23 clinical studies, decellularized templates were used, while in preclinical studies other biomaterials showed promising outcomes as well. No direct comparison to current clinical practice could be made due to the limited number of randomized controlled studies. Due to a lack of controlled (pre)clinical studies, the efficacy of tissue engineering for urethra repair could not be determined. Meta-analysis outcome measures were similar to current treatment options described in literature. Surprisingly, it appeared that favorable preclinical results, that is inclusion of cells, were not translated to the clinic. Improved (pre)clinical study designs may enhance clinical translation. We reviewed all available literature on urethral tissue engineering to assess the efficacy in preclinical and clinical studies. We show that improvements to (pre)clinical study design is required to improve clinical translation of tissue engineering technologies. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

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.

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.

Skin Bioprinting: Impending Reality or Fantasy?

PubMed

Ng, Wei Long; Wang, Shuai; Yeong, Wai Yee; Naing, May Win

2016-09-01

Bioprinting provides a fully automated and advanced platform that facilitates the simultaneous and highly specific deposition of multiple types of skin cells and biomaterials, a process that is lacking in conventional skin tissue-engineering approaches. Here, we provide a realistic, current overview of skin bioprinting, distinguishing facts from myths. We present an in-depth analysis of both current skin bioprinting works and the cellular and matrix components of native human skin. We also highlight current limitations and achievements, followed by design considerations and a future outlook for skin bioprinting. The potential of bioprinting with converging opportunities in biology, material, and computational design will eventually facilitate the fabrication of improved tissue-engineered (TE) skin constructs, making bioprinting skin an impending reality. Copyright © 2016 Elsevier Ltd. All rights reserved.

Scaffolds for peripheral nerve repair and reconstruction.

PubMed

Yi, Sheng; Xu, Lai; Gu, Xiaosong

2018-06-02

Trauma-associated peripheral nerve defect is a widespread clinical problem. Autologous nerve grafting, the current gold standard technique for the treatment of peripheral nerve injury, has many internal disadvantages. Emerging studies showed that tissue engineered nerve graft is an effective substitute to autologous nerves. Tissue engineered nerve graft is generally composed of neural scaffolds and incorporating cells and molecules. A variety of biomaterials have been used to construct neural scaffolds, the main component of tissue engineered nerve graft. Synthetic polymers (e.g. silicone, polyglycolic acid, and poly(lactic-co-glycolic acid)) and natural materials (e.g. chitosan, silk fibroin, and extracellular matrix components) are commonly used along or together to build neural scaffolds. Many other materials, including the extracellular matrix, glass fabrics, ceramics, and metallic materials, have also been used to construct neural scaffolds. These biomaterials are fabricated to create specific structures and surface features. Seeding supporting cells and/or incorporating neurotrophic factors to neural scaffolds further improve restoration effects. Preliminary studies demonstrate that clinical applications of these neural scaffolds achieve satisfactory functional recovery. Therefore, tissue engineered nerve graft provides a good alternative to autologous nerve graft and represents a promising frontier in neural tissue engineering. Copyright © 2018 Elsevier Inc. All rights reserved.

[Using of cell biocomposite material in tissue engineering of the urinary bladder].

PubMed

Glybochko, P V; Olefir, Yu V; Alyaev, Yu G; Butnaru, D V; Bezrukov, E A; Chaplenko, A A; Zharikova, T M

2017-06-01

In a systematic review, to present an overview of the current situation in the field of tissue engineering of urinary bladder related to the use of cell lines pre-cultured on matrices. The selection of eligible publications was conducted according to the method described in the article Glybochko P.V. et al. "Tissue engineering of urinary bladder using acellular matrix." At the final stage, studies investigating the application of matrices with human and animal cell lines were analyzed. Contemporary approaches to using cell-based tissue engineering of the bladder were analyzed, including the formation of 3D structures from several types of cells, cell layers and genetic modification of injected cells. The most commonly used cell lines are urothelial cells, mesenchymal stem cells and fibroblasts. The safety and efficacy of any types of composite cell structures used in the cell-based bladder tissue engineering has not been proven sufficiently to warrant clinical studies of their usefulness. The results of cystoplasty of rat bladder are almost impossible to extrapolate to humans; besides, it is difficult to predict possible side effects. For the transition to clinical trials, additional studies on relevant animal models are needed.

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.

Materials from Mussel-Inspired Chemistry for Cell and Tissue Engineering Applications.

PubMed

Madhurakkat Perikamana, Sajeesh Kumar; Lee, Jinkyu; Lee, Yu Bin; Shin, Young Min; Lee, Esther J; Mikos, Antonios G; Shin, Heungsoo

2015-09-14

Current advances in biomaterial fabrication techniques have broadened their application in different realms of biomedical engineering, spanning from drug delivery to tissue engineering. The success of biomaterials depends highly on the ability to modulate cell and tissue responses, including cell adhesion, as well as induction of repair and immune processes. Thus, most recent approaches in the field have concentrated on functionalizing biomaterials with different biomolecules intended to evoke cell- and tissue-specific reactions. Marine mussels produce mussel adhesive proteins (MAPs), which help them strongly attach to different surfaces, even under wet conditions in the ocean. Inspired by mussel adhesiveness, scientists discovered that dopamine undergoes self-polymerization at alkaline conditions. This reaction provides a universal coating for metals, polymers, and ceramics, regardless of their chemical and physical properties. Furthermore, this polymerized layer is enriched with catechol groups that enable immobilization of primary amine or thiol-based biomolecules via a simple dipping process. Herein, this review explores the versatile surface modification techniques that have recently been exploited in tissue engineering and summarizes polydopamine polymerization mechanisms, coating process parameters, and effects on substrate properties. A brief discussion of polydopamine-based reactions in the context of engineering various tissue types, including bone, blood vessels, cartilage, nerves, and muscle, is also provided.

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

PubMed

Zhang, Shichao; Xing, Malcolm; Li, Bingyun

2018-06-01

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

Enhancement of keratinocyte performance in the production of tissue-engineered skin using a low-calcium medium.

PubMed

Hernon, Catherine A; Harrison, Caroline A; Thornton, Daniel J A; MacNeil, Sheila

2007-01-01

The success of laboratory-expanded autologous keratinocytes for the treatment of severe burn injuries is often compromised by their lack of dermal remnants and failure to establish a secure dermo-epidermal junction on the wound bed. We have developed a tissue-engineered skin substitute for in vivo use, based on a sterilized donor human dermis seeded with autologous keratinocytes and fibroblasts. However, culture rates are currently too slow for clinical use in acute burns. Our aim in this study was to increase the rate of production of tissue-engineered skin. Two approaches were explored: one using a commercial low-calcium media and the other supplementing well-established media for keratinocyte culture with the calcium-chelating agent ethylene glutamine tetra-acetic acid (EGTA). Using commercial low-calcium media for both the initial cell culture and subsequent culture of tissue-engineered skin did not produce tissue suitable for clinical use. However, it was possible to enhance the initial proliferation of keratinocytes and to increase their horizontal migration in tissue-engineered skin by supplementing established culture medium with 0.04 mM EGTA without sacrificing epidermal attachment and differentiation. Enhancement of keratinocyte migration with EGTA was also maximal in the absence of fibroblasts or basement membrane.

[Tissue engineering of urinary bladder using acellular matrix].

PubMed

Glybochko, P V; Olefir, Yu V; Alyaev, Yu G; Butnaru, D V; Bezrukov, E A; Chaplenko, A A; Zharikova, T M

2017-04-01

Tissue engineering has become a new promising strategy for repairing damaged organs of the urinary system, including the bladder. The basic idea of tissue engineering is to integrate cellular technology and advanced bio-compatible materials to replace or repair tissues and organs. of the study is the objective reflection of the current trends and advances in tissue engineering of the bladder using acellular matrix through a systematic search of preclinical and clinical studies of interest. Relevant studies, including those on methods of tissue engineering of urinary bladder, was retrieved from multiple databases, including Scopus, Web of Science, PubMed, Embase. The reference lists of the retrieved review articles were analyzed for the presence of the missing relevant publications. In addition, a manual search for registered clinical trials was conducted in clinicaltrials.gov. Following the above search strategy, a total of 77 eligible studies were selected for further analysis. Studies differed in the types of animal models, supporting structures, cells and growth factors. Among those, studies using cell-free matrix were selected for a more detailed analysis. Partial restoration of urothelium layer was observed in most studies where acellular grafts were used for cystoplasty, but no the growth of the muscle layer was observed. This is the main reason why cellular structures are more commonly used in clinical practice.

Dental Pulp and Dentin Tissue Engineering and Regeneration – Advancement and Challenge

PubMed Central

Huang, George T.-J.

2012-01-01

Hard tissue is difficult to repair especially dental structures. Tooth enamel is incapable of self-repairing whereas dentin and cememtum can regenerate with limited capacity. Enamel and dentin are commonly under the attack by caries. Extensive forms of caries destroy enamel and dentin and can lead to dental pulp infection. Entire pulp amputation followed by the pulp space disinfection and filled with an artificial rubber-like material is employed to treat the infection --commonly known as root canal or endodontic therapy. Regeneration of dentin relies on having vital pulps; however, regeneration of pulp tissue has been difficult as the tissue is encased in dentin without collateral blood supply except from the root apical end. With the advent of modern tissue engineering concept and the discovery of dental stem cells, regeneration of pulp and dentin has been tested. This article will review the recent endeavor on pulp and dentin tissue engineering and regeneration. The prospective outcome of the current advancement and challenge in this line of research will be discussed. PMID:21196351

Tissue-engineered cartilage: the crossroads of biomaterials, cells and stimulating factors.

PubMed

Bhardwaj, Nandana; Devi, Dipali; Mandal, Biman B

2015-02-01

Damage to cartilage represents one of the most challenging tasks of musculoskeletal therapeutics due to its limited propensity for healing and regenerative capabilities. Lack of current treatments to restore cartilage tissue function has prompted research in this rapidly emerging field of tissue regeneration of functional cartilage tissue substitutes. The development of cartilaginous tissue largely depends on the combination of appropriate biomaterials, cell source, and stimulating factors. Over the years, various biomaterials have been utilized for cartilage repair, but outcomes are far from achieving native cartilage architecture and function. This highlights the need for exploration of suitable biomaterials and stimulating factors for cartilage regeneration. With these perspectives, we aim to present an overview of cartilage tissue engineering with recent progress, development, and major steps taken toward the generation of functional cartilage tissue. In this review, we have discussed the advances and problems in tissue engineering of cartilage with strong emphasis on the utilization of natural polymeric biomaterials, various cell sources, and stimulating factors such as biophysical stimuli, mechanical stimuli, dynamic culture, and growth factors used so far in cartilage regeneration. Finally, we have focused on clinical trials, recent innovations, and future prospects related to cartilage engineering. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Recent advances in hydrogels for cartilage tissue engineering.

PubMed

Vega, S L; Kwon, M Y; Burdick, J A

2017-01-30

Articular cartilage is a load-bearing tissue that lines the surface of bones in diarthrodial joints. Unfortunately, this avascular tissue has a limited capacity for intrinsic repair. Treatment options for articular cartilage defects include microfracture and arthroplasty; however, these strategies fail to generate tissue that adequately restores damaged cartilage. Limitations of current treatments for cartilage defects have prompted the field of cartilage tissue engineering, which seeks to integrate engineering and biological principles to promote the growth of new cartilage to replace damaged tissue. To date, a wide range of scaffolds and cell sources have emerged with a focus on recapitulating the microenvironments present during development or in adult tissue, in order to induce the formation of cartilaginous constructs with biochemical and mechanical properties of native tissue. Hydrogels have emerged as a promising scaffold due to the wide range of possible properties and the ability to entrap cells within the material. Towards improving cartilage repair, hydrogel design has advanced in recent years to improve their utility. Some of these advances include the development of improved network crosslinking (e.g. double-networks), new techniques to process hydrogels (e.g. 3D printing) and better incorporation of biological signals (e.g. controlled release). This review summarises these innovative approaches to engineer hydrogels towards cartilage repair, with an eye towards eventual clinical translation.

Generation and Assessment of Functional Biomaterial Scaffolds for Applications in Cardiovascular Tissue Engineering and Regenerative Medicine.

PubMed

Hinderer, Svenja; Brauchle, Eva; Schenke-Layland, Katja

2015-11-18

Current clinically applicable tissue and organ replacement therapies are limited in the field of cardiovascular regenerative medicine. The available options do not regenerate damaged tissues and organs, and, in the majority of the cases, show insufficient restoration of tissue function. To date, anticoagulant drug-free heart valve replacements or growing valves for pediatric patients, hemocompatible and thrombus-free vascular substitutes that are smaller than 6 mm, and stem cell-recruiting delivery systems that induce myocardial regeneration are still only visions of researchers and medical professionals worldwide and far from being the standard of clinical treatment. The design of functional off-the-shelf biomaterials as well as automatable and up-scalable biomaterial processing methods are the focus of current research endeavors and of great interest for fields of tissue engineering and regenerative medicine. Here, various approaches that aim to overcome the current limitations are reviewed, focusing on biomaterials design and generation methods for myocardium, heart valves, and blood vessels. Furthermore, novel contact- and marker-free biomaterial and extracellular matrix assessment methods are highlighted. © 2015 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Tissue Engineering Strategies for Myocardial Regeneration: Acellular Versus Cellular Scaffolds?

PubMed

Domenech, Maribella; Polo-Corrales, Lilliana; Ramirez-Vick, Jaime E; Freytes, Donald O

2016-12-01

Heart disease remains one of the leading causes of death in industrialized nations with myocardial infarction (MI) contributing to at least one fifth of the reported deaths. The hypoxic environment eventually leads to cellular death and scar tissue formation. The scar tissue that forms is not mechanically functional and often leads to myocardial remodeling and eventual heart failure. Tissue engineering and regenerative medicine principles provide an alternative approach to restoring myocardial function by designing constructs that will restore the mechanical function of the heart. In this review, we will describe the cellular events that take place after an MI and describe current treatments. We will also describe how biomaterials, alone or in combination with a cellular component, have been used to engineer suitable myocardium replacement constructs and how new advanced culture systems will be required to achieve clinical success.

Spatial regulation of controlled bioactive factor delivery for bone tissue engineering

PubMed Central

Samorezov, Julia E.; Alsberg, Eben

2015-01-01

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

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

PubMed

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

2015-10-01

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

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

PubMed Central

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

2015-01-01

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

Tissue Engineering Strategies for the Tendon/ligament-to-bone insertion

PubMed Central

Smith, Lester; Xia, Younan; Galatz, Leesa M.; Genin, Guy M.; Thomopoulos, Stavros

2012-01-01

Injuries to connective tissues are painful and disabling and result in costly medical expenses. These injuries often require re-attachment of an unmineralized connective tissue to bone. The uninjured tendon/ligament-to-bone insertion (enthesis) is a functionally graded material that exhibits a gradual transition from soft tissue (i.e., tendon or ligament) to hard tissue (i.e., mineralized bone) through a fibrocartilaginous transition region. This transition is believed to facilitate force transmission between the two dissimilar tissues by ameliorating potentially damaging interfacial stress concentrations. The transition region is impaired or lost upon tendon/ligament injury and is not regenerated following surgical repair or natural healing, exposing the tissue to risk of re-injury. The need to regenerate a robust tendon-to-bone insertion has led a number of tissue engineering repair strategies. This review treats the tendon-to-bone insertion site as a tissue structure whose primary role is mechanical and discusses current and emerging strategies for engineering the tendon/ligament-to-bone insertion in this context. The focus lies on strategies for producing mechanical structures that can guide and subsequently sustain a graded tissue structure and the associated cell populations. PMID:22185608

Tissue-engineering strategies for the tendon/ligament-to-bone insertion.

PubMed

Smith, Lester; Xia, Younan; Galatz, Leesa M; Genin, Guy M; Thomopoulos, Stavros

2012-01-01

Injuries to connective tissues are painful and disabling and result in costly medical expenses. These injuries often require reattachment of an unmineralized connective tissue to bone. The uninjured tendon/ligament-to-bone insertion (enthesis) is a functionally graded material that exhibits a gradual transition from soft tissue (i.e., tendon or ligament) to hard tissue (i.e., mineralized bone) through a fibrocartilaginous transition region. This transition is believed to facilitate force transmission between the two dissimilar tissues by ameliorating potentially damaging interfacial stress concentrations. The transition region is impaired or lost upon tendon/ligament injury and is not regenerated following surgical repair or natural healing, exposing the tissue to risk of reinjury. The need to regenerate a robust tendon-to-bone insertion has led a number of tissue engineering repair strategies. This review treats the tendon-to-bone insertion site as a tissue structure whose primary role is mechanical and discusses current and emerging strategies for engineering the tendon/ligament-to-bone insertion in this context. The focus lies on strategies for producing mechanical structures that can guide and subsequently sustain a graded tissue structure and the associated cell populations.

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.

Non-invasive Assessments of Adipose Tissue Metabolism In Vitro.

PubMed

Abbott, Rosalyn D; Borowsky, Francis E; Quinn, Kyle P; Bernstein, David L; Georgakoudi, Irene; Kaplan, David L

2016-03-01

Adipose tissue engineering is a diverse area of research where the developed tissues can be used to study normal adipose tissue functions, create disease models in vitro, and replace soft tissue defects in vivo. Increasing attention has been focused on the highly specialized metabolic pathways that regulate energy storage and release in adipose tissues which affect local and systemic outcomes. Non-invasive, dynamic measurement systems are useful to track these metabolic pathways in the same tissue model over time to evaluate long term cell growth, differentiation, and development within tissue engineering constructs. This approach reduces costs and time in comparison to more traditional destructive methods such as biochemical and immunochemistry assays and proteomics assessments. Towards this goal, this review will focus on important metabolic functions of adipose tissues and strategies to evaluate them with non-invasive in vitro methods. Current non-invasive methods, such as measuring key metabolic markers and endogenous contrast imaging will be explored.

Non-invasive assessments of adipose tissue metabolism in vitro

PubMed Central

Abbott, Rosalyn D.; Borowsky, Francis E.; Quinn, Kyle P.; Bernstein, David L.; Georgakoudi, Irene; Kaplan, David L.

2015-01-01

Adipose tissue engineering is a diverse area of research where the developed tissues can be used to study normal adipose tissue functions, create disease models in vitro, and replace soft tissue defects in vivo. Increasing attention has been focused on the highly specialized metabolic pathways that regulate energy storage and release in adipose tissues which affect local and systemic outcomes. Non-invasive, dynamic measurement systems are useful to track these metabolic pathways in the same tissue model over time to evaluate long term cell growth, differentiation, and development within tissue engineering constructs. This approach reduces costs and time in comparison to more traditional destructive methods such as biochemical and immunochemistry assays and proteomics assessments. Towards this goal, this review will focus on important metabolic functions of adipose tissues and strategies to evaluate them with noninvasive in vitro methods. Current non-invasive methods, such as measuring key metabolic markers and endogenous contrast imaging will be explored. PMID:26399988

Engineering craniofacial structures: facing the challenge.

PubMed

Zaky, S H; Cancedda, R

2009-12-01

The human innate regenerative ability is known to be limited by the intensity of the insult together with the availability of progenitor cells, which may cause certain irreparable damage. It is only recently that the paradigm of tissue engineering found its way to the treatment of irreversibly affected body structures with the challenge of reconstructing the lost part. In the current review, we underline recent trials that target engineering of human craniofacial structures, mainly bone, cartilage, and teeth. We analyze the applied engineering strategies relative to the selection of cell types to lay down a specific targeted tissue, together with their association with an escorting scaffold for a particular engineered site, and discuss their necessity to be sustained by growth factors. Challenges and expectations for facial skeletal engineering are discussed in the context of future treatment.

Engineering organs.

PubMed

Atala, Anthony

2009-10-01

Applications of regenerative medicine technology may offer novel therapies for patients with injuries, end-stage organ failure, or other clinical problems. Currently, patients suffering from diseased and injured organs can be treated with transplanted organs. However, there is a severe shortage of donor organs that is worsening yearly as the population ages and new cases of organ failure increase. Scientists in the field of regenerative medicine and tissue engineering are now applying the principles of cell transplantation, material science, and bioengineering to construct biological substitutes that will restore and maintain normal function in diseased and injured tissues. The stem cell field is also advancing rapidly, opening new avenues for this type of therapy. For example, therapeutic cloning and cellular reprogramming may one day provide a potentially limitless source of cells for tissue engineering applications. Although stem cells are still in the research phase, some therapies arising from tissue engineering endeavors have already entered the clinical setting successfully, indicating the promise regenerative medicine holds for the future.

Using Acellular Bioactive Extracellular Matrix Scaffolds to Enhance Endogenous Cardiac Repair

PubMed Central

Svystonyuk, Daniyil A.; Mewhort, Holly E. M.; Fedak, Paul W. M.

2018-01-01

An inability to recover lost cardiac muscle following acute ischemic injury remains the biggest shortcoming of current therapies to prevent heart failure. As compared to standard medical and surgical treatments, tissue engineering strategies offer the promise of improved heart function by inducing regeneration of functional heart muscle. Tissue engineering approaches that use stem cells and genetic manipulation have shown promise in preclinical studies but have also been challenged by numerous critical barriers preventing effective clinical translational. We believe that surgical intervention using acellular bioactive ECM scaffolds may yield similar therapeutic benefits with minimal translational hurdles. In this review, we outline the limitations of cellular-based tissue engineering strategies and the advantages of using acellular biomaterials with bioinductive properties. We highlight key anatomic targets enriched with cellular niches that can be uniquely activated using bioactive scaffold therapy. Finally, we review the evolving cardiovascular tissue engineering landscape and provide critical insights into the potential therapeutic benefits of acellular scaffold therapy. PMID:29696148

Bladder tissue engineering through nanotechnology.

PubMed

Harrington, Daniel A; Sharma, Arun K; Erickson, Bradley A; Cheng, Earl Y

2008-08-01

The field of tissue engineering has developed in phases: initially researchers searched for "inert" biomaterials to act solely as replacement structures in the body. Then, they explored biodegradable scaffolds--both naturally derived and synthetic--for the temporary support of growing tissues. Now, a third phase of tissue engineering has developed, through the subcategory of "regenerative medicine." This renewed focus toward control over tissue morphology and cell phenotype requires proportional advances in scaffold design. Discoveries in nanotechnology have driven both our understanding of cell-substrate interactions, and our ability to influence them. By operating at the size regime of proteins themselves, nanotechnology gives us the opportunity to directly speak the language of cells, through reliable, repeatable creation of nanoscale features. Understanding the synthesis of nanoscale materials, via "top-down" and "bottom-up" strategies, allows researchers to assess the capabilities and limits inherent in both techniques. Urology research as a whole, and bladder regeneration in particular, are well-positioned to benefit from such advances, since our present technology has yet to reach the end goal of functional bladder restoration. In this article, we discuss the current applications of nanoscale materials to bladder tissue engineering, and encourage researchers to explore these interdisciplinary technologies now, or risk playing catch-up in the future.

Tissue engineering strategies applied in the regeneration of the human intervertebral disk.

PubMed

Silva-Correia, Joana; Correia, Sandra I; Oliveira, Joaquim M; Reis, Rui L

2013-12-01

Low back pain (LBP) is one of the most common painful conditions that lead to work absenteeism, medical visits, and hospitalization. The majority of cases showing signs of LBP are due to age-related degenerative changes in the intervertebral disk (IVD), which are, in fact, associated with multiple spine pathologies. Traditional and more conservative procedures/clinical approaches only treat the symptoms of disease and not the underlying pathology, thus limiting their long-term efficiency. In the last few years, research and development of new approaches aiming to substitute the nucleus pulposus and annulus fibrosus tissue and stimulate its regeneration has been conducted. Regeneration of the damaged IVD using tissue engineering strategies appears particularly promising in pre-clinical studies. Meanwhile, surgical techniques must be adapted to this new approach in order to be as minimally invasive as possible, reducing recovering time and side effects associated to traditional surgeries. In this review, the current knowledge on IVD, its associated pathologies and current surgical procedures are summarized. Furthermore, it also provides a succinct and up-to-date overview on regenerative medicine research, especially on the newest tissue engineering strategies for IVD regeneration. © 2013.

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

Building a Roadmap for the Biomaterials Science and Technology to Serve Military Needs

DTIC Science & Technology

2005-08-01

Accessed July 2004. 22 N.A. Peppas. 1997. Hydrogels and drug delivery . Current Opinion in Colloid and Interface Science 2(5):531-537. 24 R. Langer. 2001...researchers engaged in a workshop structured around the key topics of wound care, drug delivery , tissue engineering/restoration and sensors and...the workshop and a well- constructed final report. The focus areas of the report are Far Forward Wound Care, Tissue Engineering, Drug Delivery

Hydrogels for precision meniscus tissue engineering: a comprehensive review.

PubMed

Rey-Rico, Ana; Cucchiarini, Magali; Madry, Henning

The meniscus plays a pivotal role to preserve the knee joint homeostasis. Lesions to the meniscus are frequent, have a reduced ability to heal, and may induce tibiofemoral osteoarthritis. Current reconstructive therapeutic options mainly focus on the treatment of lesions in the peripheral vascularized region. In contrast, few approaches are capable of stimulating repair of damaged meniscal tissue in the central, avascular portion. Tissue engineering approaches are of high interest to repair or replace damaged meniscus tissue in this area. Hydrogel-based biomaterials are of special interest for meniscus repair as its inner part contains relatively high proportions of proteoglycans which are responsible for the viscoelastic compressive properties and hydration grade. Hydrogels exhibiting high water content and providing a specific three-dimensional (3D) microenvironment may be engineered to precisely resemble this topographical composition of the meniscal tissue. Different polymers of both natural and synthetic origins have been manipulated to produce hydrogels hosting relevant cell populations for meniscus regeneration and provide platforms for meniscus tissue replacement. So far, these compounds have been employed to design controlled delivery systems of bioactive molecules involved in meniscal reparative processes or to host genetically modified cells as a means to enhance meniscus repair. This review describes the most recent advances on the use of hydrogels as platforms for precision meniscus tissue engineering.

Wireless Passive Stimulation of Engineered Cardiac Tissues.

PubMed

Liu, Shiyi; Navaei, Ali; Meng, Xueling; Nikkhah, Mehdi; Chae, Junseok

2017-07-28

We present a battery-free radio frequency (RF) microwave activated wireless stimulator, 25 × 42 × 1.6 mm 3 on a flexible substrate, featuring high current delivery, up to 60 mA, to stimulate engineered cardiac tissues. An external antenna shines 2.4 GHz microwave, which is modulated by an inverted pulse to directly control the stimulating waveform, to the wireless passive stimulator. The stimulator is equipped with an on-board antenna, multistage diode multipliers, and a control transistor. Rat cardiomyocytes, seeded on electrically conductive gelatin-based hydrogels, demonstrate synchronous contractions and Ca 2+ transients immediately upon stimulation. Notably, the stimulator output voltage and current profiles match the tissue contraction frequency within 0.5-2 Hz. Overall, our results indicate the promising potential of the proposed wireless passive stimulator for cardiac stimulation and therapy by induction of precisely controlled and synchronous contractions.

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

Engineered hybrid cardiac patches with multifunctional electronics for online monitoring and regulation of tissue function

PubMed Central

Feiner, Ron; Engel, Leeya; Fleischer, Sharon; Malki, Maayan; Gal, Idan; Shapira, Assaf; Shacham-Diamand, Yosi; Dvir, Tal

2016-01-01

In cardiac tissue engineering approaches to treat myocardial infarction, cardiac cells are seeded within three-dimensional porous scaffolds to create functional cardiac patches. However, current cardiac patches do not allow for online monitoring and reporting of engineered-tissue performance, and do not interfere to deliver signals for patch activation or to enable its integration with the host. Here, we report an engineered cardiac patch that integrates cardiac cells with flexible, free-standing electronics and a 3D nanocomposite scaffold. The patch exhibited robust electronic properties, enabling the recording of cellular electrical activities and the on-demand provision of electrical stimulation for synchronizing cell contraction. We also show that electroactive polymers containing biological factors can be deposited on designated electrodes to release drugs in the patch microenvironment on-demand. We expect that the integration of complex electronics within cardiac patches will eventually provide therapeutic control and regulation of cardiac function. PMID:26974408

Engineered hybrid cardiac patches with multifunctional electronics for online monitoring and regulation of tissue function.

PubMed

Feiner, Ron; Engel, Leeya; Fleischer, Sharon; Malki, Maayan; Gal, Idan; Shapira, Assaf; Shacham-Diamand, Yosi; Dvir, Tal

2016-06-01

In cardiac tissue engineering approaches to treat myocardial infarction, cardiac cells are seeded within three-dimensional porous scaffolds to create functional cardiac patches. However, current cardiac patches do not allow for online monitoring and reporting of engineered-tissue performance, and do not interfere to deliver signals for patch activation or to enable its integration with the host. Here, we report an engineered cardiac patch that integrates cardiac cells with flexible, freestanding electronics and a 3D nanocomposite scaffold. The patch exhibited robust electronic properties, enabling the recording of cellular electrical activities and the on-demand provision of electrical stimulation for synchronizing cell contraction. We also show that electroactive polymers containing biological factors can be deposited on designated electrodes to release drugs in the patch microenvironment on demand. We expect that the integration of complex electronics within cardiac patches will eventually provide therapeutic control and regulation of cardiac function.

Factors Affecting the Longevity and Strength in an In Vitro Model of the Bone–Ligament Interface

PubMed Central

Paxton, Jennifer Z.; Donnelly, Kenneth; Keatch, Robert P.; Grover, Liam M.

2010-01-01

The interfaces between musculoskeletal tissues with contrasting moduli are morphologically and biochemically adapted to allow the transmission of force with minimal injury. Current methods of tissue engineering ligaments and tendons do not include the interface and this may limit the future clinical success of engineered musculoskeletal tissues. This study aimed to use solid brushite cement anchors to engineer intact ligaments from bone-to-bone, creating a functional musculoskeletal interface in vitro. We show here that modifying anchor shape and cement composition can alter both the longevity and the strength of an in vitro model of the bone–ligament interface: with values reaching 23 days and 21.6 kPa, respectively. These results validate the use of brushite bone cement to engineer the bone–ligament interface in vitro and raise the potential for future use in ligament replacement surgery. PMID:20431953

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

PubMed Central

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

2016-01-01

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

Reconstruction of structure and function in tissue engineering of solid organs: Toward simulation of natural development based on decellularization.

PubMed

Zheng, Chen-Xi; Sui, Bing-Dong; Hu, Cheng-Hu; Qiu, Xin-Yu; Zhao, Pan; Jin, Yan

2018-04-27

Failure of solid organs, such as the heart, liver, and kidney, remains a major cause of the world's mortality due to critical shortage of donor organs. Tissue engineering, which uses elements including cells, scaffolds, and growth factors to fabricate functional organs in vitro, is a promising strategy to mitigate the scarcity of transplantable organs. Within recent years, different construction strategies that guide the combination of tissue engineering elements have been applied in solid organ tissue engineering and have achieved much progress. Most attractively, construction strategy based on whole-organ decellularization has become a popular and promising approach, because the overall structure of extracellular matrix can be well preserved. However, despite the preservation of whole structure, the current constructs derived from decellularization-based strategy still perform partial functions of solid organs, due to several challenges, including preservation of functional extracellular matrix structure, implementation of functional recellularization, formation of functional vascular network, and realization of long-term functional integration. This review overviews the status quo of solid organ tissue engineering, including both advances and challenges. We have also put forward a few techniques with potential to solve the challenges, mainly focusing on decellularization-based construction strategy. We propose that the primary concept for constructing tissue-engineered solid organs is fabricating functional organs based on intact structure via simulating the natural development and regeneration processes. Copyright © 2018 John Wiley & Sons, Ltd.

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.

Developing research competencies through a project-based tissue-engineering module in the biomedical engineering undergraduate curriculum.

PubMed

Wallen, M; Pandit, A

2009-05-01

In addressing the task of developing an undergraduate module in the field of tissue engineering, the greatest challenge lies in managing to capture what is a growing and rapidly changing field. Acknowledging the call for the development of greater critical thinking and interpersonal skills among the next generation of engineers as well as encouraging students to engage actively with the dynamic nature of research in the field, the module was developed to include both project-based and cooperative-learning experiences. These learning activities include developing hypotheses for the application of newly introduced laboratory procedures, a collaborative mock grant submission, and debates on ethical issues in which students are assigned roles as various stakeholders. Feedback from module evaluations has indicated that, while students find the expectations challenging, they are able to gain an advanced insight into a dynamic field. More importantly, students develop research competencies by engaging in activities that require them to link current research directions with their own development of hypotheses for future tissue-engineering applications.

Tissue engineering, stem cells and cloning: current concepts and changing trends.

PubMed

Atala, Anthony

2005-07-01

Organ damage or loss can occur from congenital disorders, cancer, trauma, infection, inflammation, iatrogenic injuries or other conditions and often necessitates reconstruction or replacement. Replacement may take the form of organ transplant. At present, there is a severe shortage of donor organs that is worsening with the aging of the population. Tissue engineering follows the principles of cell transplantation, materials science and engineering towards the development of biological substitutes that can restore and maintain normal tissue function. Therapeutic cloning involves the introduction of a nucleus from a donor cell into an enucleated oocyte to generate embryonic stem cell lines whose genetic material is identical to that of its source. These autologous stem cells have the potential to become almost any type of cell in the adult body, and thus would be useful in tissue and organ replacement applications. This paper reviews recent advances in stem cell research and regenerative medicine, and describes the clinical applications of these technologies as novel therapies for tissue or organ loss.

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

PubMed Central

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

2016-01-01

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

Current concepts: tissue engineering and regenerative medicine applications in the ankle joint

PubMed Central

Correia, S. I.; Pereira, H.; Silva-Correia, J.; Van Dijk, C. N.; Espregueira-Mendes, J.; Oliveira, J. M.; Reis, R. L.

2014-01-01

Tissue engineering and regenerative medicine (TERM) has caused a revolution in present and future trends of medicine and surgery. In different tissues, advanced TERM approaches bring new therapeutic possibilities in general population as well as in young patients and high-level athletes, improving restoration of biological functions and rehabilitation. The mainstream components required to obtain a functional regeneration of tissues may include biodegradable scaffolds, drugs or growth factors and different cell types (either autologous or heterologous) that can be cultured in bioreactor systems (in vitro) prior to implantation into the patient. Particularly in the ankle, which is subject to many different injuries (e.g. acute, chronic, traumatic and degenerative), there is still no definitive and feasible answer to ‘conventional’ methods. This review aims to provide current concepts of TERM applications to ankle injuries under preclinical and/or clinical research applied to skin, tendon, bone and cartilage problems. A particular attention has been given to biomaterial design and scaffold processing with potential use in osteochondral ankle lesions. PMID:24352667

Current concepts: tissue engineering and regenerative medicine applications in the ankle joint.

PubMed

Correia, S I; Pereira, H; Silva-Correia, J; Van Dijk, C N; Espregueira-Mendes, J; Oliveira, J M; Reis, R L

2014-03-06

Tissue engineering and regenerative medicine (TERM) has caused a revolution in present and future trends of medicine and surgery. In different tissues, advanced TERM approaches bring new therapeutic possibilities in general population as well as in young patients and high-level athletes, improving restoration of biological functions and rehabilitation. The mainstream components required to obtain a functional regeneration of tissues may include biodegradable scaffolds, drugs or growth factors and different cell types (either autologous or heterologous) that can be cultured in bioreactor systems (in vitro) prior to implantation into the patient. Particularly in the ankle, which is subject to many different injuries (e.g. acute, chronic, traumatic and degenerative), there is still no definitive and feasible answer to 'conventional' methods. This review aims to provide current concepts of TERM applications to ankle injuries under preclinical and/or clinical research applied to skin, tendon, bone and cartilage problems. A particular attention has been given to biomaterial design and scaffold processing with potential use in osteochondral ankle lesions.

Periodontal tissue engineering strategies based on nonoral stem cells.

PubMed

Requicha, João Filipe; Viegas, Carlos Alberto; Muñoz, Fernando; Reis, Rui Luís; Gomes, Manuela Estima

2014-01-01

Periodontal disease is an inflammatory disease which constitutes an important health problem in humans due to its enormous prevalence and life threatening implications on systemic health. Routine standard periodontal treatments include gingival flaps, root planning, application of growth/differentiation factors or filler materials and guided tissue regeneration. However, these treatments have come short on achieving regeneration ad integrum of the periodontium, mainly due to the presence of tissues from different embryonic origins and their complex interactions along the regenerative process. Tissue engineering (TE) aims to regenerate damaged tissue by providing the repair site with a suitable scaffold seeded with sufficient undifferentiated cells and, thus, constitutes a valuable alternative to current therapies for the treatment of periodontal defects. Stem cells from oral and dental origin are known to have potential to regenerate these tissues. Nevertheless, harvesting cells from these sites implies a significant local tissue morbidity and low cell yield, as compared to other anatomical sources of adult multipotent stem cells. This manuscript reviews studies describing the use of non-oral stem cells in tissue engineering strategies, highlighting the importance and potential of these alternative stem cells sources in the development of advanced therapies for periodontal regeneration. Copyright © 2013 Wiley Periodicals, Inc.

Engineering stromal-epithelial interactions in vitro for ...

EPA Pesticide Factsheets

Background: Crosstalk between epithelial and stromal cells drives the morphogenesis of ectodermal organs during development and promotes normal mature adult epithelial tissue function. Epithelial-mesenchymal interactions (EMIs) have been examined using mammalian models, ex vivo tissue recombination, and in vitro co-cultures. Although these approaches have elucidated signaling mechanisms underlying morphogenetic processes and adult mammalian epithelial tissue function, they are limited by the availability of human tissue, low throughput, and human developmental or physiological relevance. Objectives: Bioengineering strategies to promote EMIs using human epithelial and mesenchymal cells have enabled the development of human in vitro models of adult epidermal and glandular tissues. In this review, we describe recent bioengineered models of human epithelial tissue and organs that can instruct the design of organotypic models of human developmental processes.Methods: We reviewed current bioengineering literature and here describe how bioengineered EMIs have enabled the development of human in vitro epithelial tissue models.Discussion: Engineered models to promote EMIs have recapitulated the architecture, phenotype, and function of adult human epithelial tissue, and similar engineering principles could be used to develop models of developmental morphogenesis. We describe how bioengineering strategies including bioprinting and spheroid culture could be implemented to

Critical review on the physical and mechanical factors involved in tissue engineering of cartilage.

PubMed

Gaut, Carrie; Sugaya, Kiminobu

2015-01-01

Articular cartilage defects often progress to osteoarthritis, which negatively impacts quality of life for millions of people worldwide and leads to high healthcare expenditures. Tissue engineering approaches to osteoarthritis have concentrated on proliferation and differentiation of stem cells by activation and suppression of signaling pathways, and by using a variety of scaffolding techniques. Recent studies indicate a key role of environmental factors in the differentiation of mesenchymal stem cells to mature cartilage-producing chondrocytes. Therapeutic approaches that consider environmental regulation could optimize chondrogenesis protocols for regeneration of articular cartilage. This review focuses on the effect of scaffold structure and composition, mechanical stress and hypoxia in modulating mesenchymal stem cell fate and the current use of these environmental factors in tissue engineering research.

Nanotechnology in bone tissue engineering.

PubMed

Walmsley, Graham G; McArdle, Adrian; Tevlin, Ruth; Momeni, Arash; Atashroo, David; Hu, Michael S; Feroze, Abdullah H; Wong, Victor W; Lorenz, Peter H; Longaker, Michael T; Wan, Derrick C

2015-07-01

Nanotechnology represents a major frontier with potential to significantly advance the field of bone tissue engineering. Current limitations in regenerative strategies include impaired cellular proliferation and differentiation, insufficient mechanical strength of scaffolds, and inadequate production of extrinsic factors necessary for efficient osteogenesis. Here we review several major areas of research in nanotechnology with potential implications in bone regeneration: 1) nanoparticle-based methods for delivery of bioactive molecules, growth factors, and genetic material, 2) nanoparticle-mediated cell labeling and targeting, and 3) nano-based scaffold construction and modification to enhance physicochemical interactions, biocompatibility, mechanical stability, and cellular attachment/survival. As these technologies continue to evolve, ultimate translation to the clinical environment may allow for improved therapeutic outcomes in patients with large bone deficits and osteodegenerative diseases. Traditionally, the reconstruction of bony defects has relied on the use of bone grafts. With advances in nanotechnology, there has been significant development of synthetic biomaterials. In this article, the authors provided a comprehensive review on current research in nanoparticle-based therapies for bone tissue engineering, which should be useful reading for clinicians as well as researchers in this field. Copyright © 2015 Elsevier Inc. All rights reserved.

Current Status of Tissue-Engineered Scaffolds for Rotator Cuff Repair.

PubMed

Chainani, Abby; Little, Dianne

2016-06-01

Rotator cuff tears continue to be at significant risk for re-tear or for failure to heal after surgical repair despite the use of a variety of surgical techniques and augmentation devices. Therefore, there is a need for functionalized scaffold strategies to provide sustained mechanical augmentation during the critical first 12-weeks following repair, and to enhance the healing potential of the repaired tendon and tendon-bone interface. Tissue engineered approaches that combine the use of scaffolds, cells, and bioactive molecules towards promising new solutions for rotator cuff repair are reviewed. The ideal scaffold should have adequate initial mechanical properties, be slowly degrading or non-degradable, have non-toxic degradation products, enhance cell growth, infiltration and differentiation, promote regeneration of the tendon-bone interface, be biocompatible and have excellent suture retention and handling properties. Scaffolds that closely match the inhomogeneity and non-linearity of the native rotator cuff may significantly advance the field. While substantial pre-clinical work remains to be done, continued progress in overcoming current tissue engineering challenges should allow for successful clinical translation.

Current Status of Tissue-Engineered Scaffolds for Rotator Cuff Repair

PubMed Central

Chainani, Abby; Little, Dianne

2015-01-01

Rotator cuff tears continue to be at significant risk for re-tear or for failure to heal after surgical repair despite the use of a variety of surgical techniques and augmentation devices. Therefore, there is a need for functionalized scaffold strategies to provide sustained mechanical augmentation during the critical first 12-weeks following repair, and to enhance the healing potential of the repaired tendon and tendon-bone interface. Tissue engineered approaches that combine the use of scaffolds, cells, and bioactive molecules towards promising new solutions for rotator cuff repair are reviewed. The ideal scaffold should have adequate initial mechanical properties, be slowly degrading or non-degradable, have non-toxic degradation products, enhance cell growth, infiltration and differentiation, promote regeneration of the tendon-bone interface, be biocompatible and have excellent suture retention and handling properties. Scaffolds that closely match the inhomogeneity and non-linearity of the native rotator cuff may significantly advance the field. While substantial pre-clinical work remains to be done, continued progress in overcoming current tissue engineering challenges should allow for successful clinical translation. PMID:27346922

Potential of Bioactive Glasses for Cardiac and Pulmonary Tissue Engineering

PubMed Central

Hamzehlou, Sepideh

2017-01-01

Repair and regeneration of disorders affecting cardiac and pulmonary tissues through tissue-engineering-based approaches is currently of particular interest. On this matter, different families of bioactive glasses (BGs) have recently been given much consideration with respect to treating refractory diseases of these tissues, such as myocardial infarction. The inherent properties of BGs, including their ability to bond to hard and soft tissues, to stimulate angiogenesis, and to elicit antimicrobial effects, along with their excellent biocompatibility, support these newly proposed strategies. Moreover, BGs can also act as a bioactive reinforcing phase to finely tune the mechanical properties of polymer-based constructs used to repair the damaged cardiac and pulmonary tissues. In the present study, we evaluated the potential of different forms of BGs, alone or in combination with other materials (e.g., polymers), in regards to repair and regenerate injured tissues of cardiac and pulmonary systems. PMID:29244726

Periodontics--tissue engineering and the future.

PubMed

Douglass, Gordon L

2005-03-01

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

Skin bioprinting: a novel approach for creating artificial skin from synthetic and natural building blocks.

PubMed

Augustine, Robin

2018-05-12

Significant progress has been made over the past few decades in the development of in vitro-engineered substitutes that mimic human skin, either as grafts for the replacement of lost skin, or for the establishment of in vitro human skin models. Tissue engineering has been developing as a novel strategy by employing the recent advances in various fields such as polymer engineering, bioengineering, stem cell research and nanomedicine. Recently, an advancement of 3D printing technology referred as bioprinting was exploited to make cell loaded scaffolds to produce constructs which are more matching with the native tissue. Bioprinting facilitates the simultaneous and highly specific deposition of multiple types of skin cells and biomaterials, a process that is lacking in conventional skin tissue-engineering approaches. Bioprinted skin substitutes or equivalents containing dermal and epidermal components offer a promising approach in skin bioengineering. Various materials including synthetic and natural biopolymers and cells with or without signalling molecules like growth factors are being utilized to produce functional skin constructs. This technology emerging as a novel strategy to overcome the current bottle-necks in skin tissue engineering such as poor vascularization, absence of hair follicles and sweat glands in the construct.

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

78 FR 71625 - Government-Owned Inventions; Availability for Licensing

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-29

...-specific glycan engineering method to conjugate the antibody to the small molecule drug auristatin F. The... results in enhanced sensitivity of cancer cells to chemotherapy treatment and in healthy tissues reduces... tissue associated with the use of anthracycline chemotherapy. The current invention builds on the NIH's...

Genetic engineering of mesenchymal stem cells and its application in human disease therapy.

PubMed

Hodgkinson, Conrad P; Gomez, José A; Mirotsou, Maria; Dzau, Victor J

2010-11-01

The use of stem cells for tissue regeneration and repair is advancing both at the bench and bedside. Stem cells isolated from bone marrow are currently being tested for their therapeutic potential in a variety of clinical conditions including cardiovascular injury, kidney failure, cancer, and neurological and bone disorders. Despite the advantages, stem cell therapy is still limited by low survival, engraftment, and homing to damage area as well as inefficiencies in differentiating into fully functional tissues. Genetic engineering of mesenchymal stem cells is being explored as a means to circumvent some of these problems. This review presents the current understanding of the use of genetically engineered mesenchymal stem cells in human disease therapy with emphasis on genetic modifications aimed to improve survival, homing, angiogenesis, and heart function after myocardial infarction. Advancements in other disease areas are also discussed.

Fabrication of functional PLGA-based electrospun scaffolds and their applications in biomedical engineering.

PubMed

Zhao, Wen; Li, Jiaojiao; Jin, Kaixiang; Liu, Wenlong; Qiu, Xuefeng; Li, Chenrui

2016-02-01

Electrospun PLGA-based scaffolds have been applied extensively in biomedical engineering, such as tissue engineering and drug delivery system. Due to lack of the recognition sites on cells, hydropholicity and single-function, the applications of PLGA fibrous scaffolds are limited. In order to tackle these issues, many works have been done to obtain functional PLGA-based scaffolds, including surface modifications, the fabrication of PLGA-based composite scaffolds and drug-loaded scaffolds. The functional PLGA-based scaffolds have significantly improved cell adhesion, attachment and proliferation. Moreover, the current study has summarized the applications of functional PLGA-based scaffolds in wound dressing, vascular and bone tissue engineering area as well as drug delivery system. Copyright © 2015 Elsevier B.V. All rights reserved.

Development of decellularized scaffolds for stem cell-driven tissue engineering.

PubMed

Rana, Deepti; Zreiqat, Hala; Benkirane-Jessel, Nadia; Ramakrishna, Seeram; Ramalingam, Murugan

2017-04-01

Organ transplantation is an effective treatment for chronic organ dysfunctioning conditions. However, a dearth of available donor organs for transplantation leads to the death of numerous patients waiting for a suitable organ donor. The potential of decellularized scaffolds, derived from native tissues or organs in the form of scaffolds has been evolved as a promising approach in tissue-regenerative medicine for translating functional organ replacements. In recent years, donor organs, such as heart, liver, lung and kidneys, have been reported to provide acellular extracellular matrix (ECM)-based scaffolds through the process called 'decellularization' and proved to show the potential of recellularization with selected cell populations, particularly with stem cells. In fact, decellularized stem cell matrix (DSCM) has also emerged as a potent biological scaffold for controlling stem cell fate and function during tissue organization. Despite the proven potential of decellularized scaffolds in tissue engineering, the molecular mechanism responsible for stem cell interactions with decellularized scaffolds is still unclear. Stem cells interact with, and respond to, various signals/cues emanating from their ECM. The ability to harness the regenerative potential of stem cells via decellularized ECM-based scaffolds has promising implications for tissue-regenerative medicine. Keeping these points in view, this article reviews the current status of decellularized scaffolds for stem cells, with particular focus on: (a) concept and various methods of decellularization; (b) interaction of stem cells with decellularized scaffolds; (c) current recellularization strategies, with associated challenges; and (iv) applications of the decellularized scaffolds in stem cell-driven tissue engineering and regenerative medicine. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Functionalized α-Helical Peptide Hydrogels for Neural Tissue Engineering

PubMed Central

2015-01-01

Trauma to the central and peripheral nervous systems often lead to serious morbidity. Current surgical methods for repairing or replacing such damage have limitations. Tissue engineering offers a potential alternative. Here we show that functionalized α-helical-peptide hydrogels can be used to induce attachment, migration, proliferation and differentiation of murine embryonic neural stem cells (NSCs). Specifically, compared with undecorated gels, those functionalized with Arg-Gly-Asp-Ser (RGDS) peptides increase the proliferative activity of NSCs; promote their directional migration; induce differentiation, with increased expression of microtubule-associated protein-2, and a low expression of glial fibrillary acidic protein; and lead to the formation of larger neurospheres. Electrophysiological measurements from NSCs grown in RGDS-decorated gels indicate developmental progress toward mature neuron-like behavior. Our data indicate that these functional peptide hydrogels may go some way toward overcoming the limitations of current approaches to nerve-tissue repair. PMID:26240838

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

PubMed

Duan, Bin

2017-01-01

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

Mesenchymal Stem Cell-Mediated Functional Tooth Regeneration in Swine

PubMed Central

Fang, Dianji; Yamaza, Takayoshi; Seo, Byoung-Moo; Zhang, Chunmei; Liu, He; Gronthos, Stan; Wang, Cun-Yu; Shi, Songtao; Wang, Songlin

2006-01-01

Mesenchymal stem cell-mediated tissue regeneration is a promising approach for regenerative medicine for a wide range of applications. Here we report a new population of stem cells isolated from the root apical papilla of human teeth (SCAP, stem cells from apical papilla). Using a minipig model, we transplanted both human SCAP and periodontal ligament stem cells (PDLSCs) to generate a root/periodontal complex capable of supporting a porcelain crown, resulting in normal tooth function. This work integrates a stem cell-mediated tissue regeneration strategy, engineered materials for structure, and current dental crown technologies. This hybridized tissue engineering approach led to recovery of tooth strength and appearance. PMID:17183711

The knee meniscus: structure-function, pathophysiology, current repair techniques, and prospects for regeneration

PubMed Central

Makris, Eleftherios A.; Hadidi, Pasha; Athanasiou, Kyriacos A.

2011-01-01

Extensive scientific investigations in recent decades have established the anatomical, biomechanical, and functional importance that the meniscus holds within the knee joint. As a vital part of the joint, it acts to prevent the deterioration and degeneration of articular cartilage, and the onset and development of osteoarthritis. For this reason, research into meniscus repair has been the recipient of particular interest from the orthopedic and bioengineering communities. Current repair techniques are only effective in treating lesions located in the peripheral vascularized region of the meniscus. Healing lesions found in the inner avascular region, which functions under a highly demanding mechanical environment, is considered to be a significant challenge. An adequate treatment approach has yet to be established, though many attempts have been undertaken. The current primary method for treatment is partial meniscectomy, which commonly results in the progressive development of osteoarthritis. This drawback has shifted research interest towards the fields of biomaterials and bioengineering, where it is hoped that meniscal deterioration can be tackled with the help of tissue engineering. So far, different approaches and strategies have contributed to the in vitro generation of meniscus constructs, which are capable of restoring meniscal lesions to some extent, both functionally as well as anatomically. The selection of the appropriate cell source (autologous, allogeneic, or xenogeneic cells, or stem cells) is undoubtedly regarded as key to successful meniscal tissue engineering. Furthermore, a large variation of scaffolds for tissue engineering have been proposed and produced in experimental and clinical studies, although a few problems with these (e.g., byproducts of degradation, stress shielding) have shifted research interest towards new strategies (e.g., scaffoldless approaches, self-assembly). A large number of different chemical (e.g., TGF-β1, C-ABC) and mechanical stimuli (e.g., direct compression, hydrostatic pressure) have also been investigated, both in terms of encouraging functional tissue formation, as well as in differentiating stem cells. Even though the problems accompanying meniscus tissue engineering research are considerable, we are undoubtedly in the dawn of a new era, whereby recent advances in biology, engineering, and medicine are leading to the successful treatment of meniscal lesions. PMID:21764438

Strategic Design and Fabrication of Engineered Scaffolds for Articular Cartilage Repair

PubMed Central

Izadifar, Zohreh; Chen, Xiongbiao; Kulyk, William

2012-01-01

Damage to articular cartilage can eventually lead to osteoarthritis (OA), a debilitating, degenerative joint disease that affects millions of people around the world. The limited natural healing ability of cartilage and the limitations of currently available therapies make treatment of cartilage defects a challenging clinical issue. Hopes have been raised for the repair of articular cartilage with the help of supportive structures, called scaffolds, created through tissue engineering (TE). Over the past two decades, different designs and fabrication techniques have been investigated for developing TE scaffolds suitable for the construction of transplantable artificial cartilage tissue substitutes. Advances in fabrication technologies now enable the strategic design of scaffolds with complex, biomimetic structures and properties. In particular, scaffolds with hybrid and/or biomimetic zonal designs have recently been developed for cartilage tissue engineering applications. This paper reviews critical aspects of the design of engineered scaffolds for articular cartilage repair as well as the available advanced fabrication techniques. In addition, recent studies on the design of hybrid and zonal scaffolds for use in cartilage tissue repair are highlighted. PMID:24955748

Nanoparticles-Based Systems for Osteochondral Tissue Engineering.

PubMed

Oliveira, Isabel; Vieira, Sílvia; Oliveira, J Miguel; Reis, Rui L

2018-01-01

Osteochondral lesions represent one of the major causes of disabilities in the world. These defects are due to degenerative or inflammatory arthritis, but both affect the articular cartilage and the underlying subchondral bone. Defects from trauma or degenerative pathology frequently cause severe pain, joint deformity, and loss of joint motion. Osteochondral defects are a significant challenge in orthopedic surgery, due to the cartilage complexity and unique structure, as well as its exposure to high pressure and motion. Although there are treatments routinely performed in the clinical practice, they present several limitations. Tissue engineering can be a suitable alternative for osteochondral defects since bone and cartilage engineering had experienced a notable advance over the years. Allied with nanotechnology, osteochondral tissue engineering (OCTE) can be leveled up, being possible to create advanced structures similar to the OC tissue. In this chapter, the current strategies using nanoparticles-based systems are overviewed. The results of the studies herein considered confirm that advanced nanomaterials will undoubtedly play a crucial role in the design of strategies for treatment of osteochondral defects in the near future.

Isolation and Purification of Satellite Cells for Skeletal Muscle Tissue Engineering

PubMed Central

Syverud, Brian C; Lee, Jonah D; VanDusen, Keith W; Larkin, Lisa M

2015-01-01

Engineered skeletal muscle holds promise as a source of graft tissue for the repair of traumatic injuries such as volumetric muscle loss. The resident skeletal muscle stem cell, the satellite cell, has been identified as an ideal progenitor for tissue engineering due to its role as an essential player in the potent skeletal muscle regeneration mechanism. A significant challenge facing tissue engineers, however, is the isolation of sufficiently large satellite cell populations with high purity. The two common isolation techniques, single fiber explant culture and enzymatic dissociation, can yield either a highly pure satellite cell population or a suitably large number or cells but fail to do both simultaneously. As a result, it is often necessary to use a purification technique such as pre-plating or cell sorting to enrich the satellite cell population post-isolation. Furthermore, the absence of complex chemical and biophysical cues influencing the in vivo satellite cell “niche” complicates the culture of isolated satellite cells. Techniques under investigation to maximize myogenic proliferation and differentiation in vitro are described in this article, along with current methods for isolating and purifying satellite cells. PMID:26413555

Biomimetic tissue-engineered anterior cruciate ligament replacement

PubMed Central

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

2007-01-01

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

Decellularized Tissue and Cell-Derived Extracellular Matrices as Scaffolds for Orthopaedic Tissue Engineering

PubMed Central

Cheng, Christina W.; Solorio, Loran D.; Alsberg, Eben

2014-01-01

The reconstruction of musculoskeletal defects is a constant challenge for orthopaedic surgeons. Musculoskeletal injuries such as fractures, chondral lesions, infections and tumor debulking can often lead to large tissue voids requiring reconstruction with tissue grafts. Autografts are currently the gold standard in orthopaedic tissue reconstruction; however, there is a limit to the amount of tissue that can be harvested before compromising the donor site. Tissue engineering strategies using allogeneic or xenogeneic decellularized bone, cartilage, skeletal muscle, tendon and ligament have emerged as promising potential alternative treatment. The extracellular matrix provides a natural scaffold for cell attachment, proliferation and differentiation. Decellularization of in vitro cell-derived matrices can also enable the generation of autologous constructs from tissue specific cells or progenitor cells. Although decellularized bone tissue is widely used clinically in orthopaedic applications, the exciting potential of decellularized cartilage, skeletal muscle, tendon and ligament cell-derived matrices has only recently begun to be explored for ultimate translation to the orthopaedic clinic. PMID:24417915

Trends in the development of microfluidic cell biochips for in vitro hepatotoxicity.

PubMed

Baudoin, Régis; Corlu, Anne; Griscom, Laurent; Legallais, Cécile; Leclerc, Eric

2007-06-01

Current developments in the technological fields of liver tissue engineering, bioengineering, biomechanics, microfabrication and microfluidics have lead to highly complex and pertinent new tools called "cell biochips" for in vitro toxicology. The purpose of "cell biochips" is to mimic organ tissues in vitro in order to partially reduce the amount of in vivo testing. These "cell biochips" consist of microchambers containing engineered tissue and living cell cultures interconnected by a microfluidic network, which allows the control of microfluidic flows for dynamic cultures, by continuous feeding of nutrients to cultured cells and waste removal. Cell biochips also allow the control of physiological contact times of diluted molecules with the tissues and cells, for rapid testing of sample preparations or specific addressing. Cell biochips can be situated between in vitro and in vivo testing. These types of systems can enhance functionality of cells by mimicking the tissue architecture complexities when compared to in vitro analysis but at the same time present a more rapid and simple process when compared to in vivo testing procedures. In this paper, we first introduce the concepts of microfluidic and biochip systems based on recent progress in microfabrication techniques used to mimic liver tissue in vitro. This includes progress and understanding in biomaterials science (cell culture substrate), biomechanics (dynamic cultures conditions) and biology (tissue engineering). The development of new "cell biochips" for chronic toxicology analysis of engineered tissues can be achieved through the combination of these research domains. Combining these advanced research domains, we then present "cell biochips" that allow liver chronic toxicity analysis in vitro on engineered tissues. An extension of the "cell biochip" idea has also allowed "organ interactions on chip", which can be considered as a first step towards the replacement of animal testing using a combined liver/lung organ model.

Adipose-derived stem cells and periodontal tissue engineering.

PubMed

Tobita, Morikuni; Mizuno, Hiroshi

2013-01-01

Innovative developments in the multidisciplinary field of tissue engineering have yielded various implementation strategies and the possibility of functional tissue regeneration. Technologic advances in the combination of stem cells, biomaterials, and growth factors have created unique opportunities to fabricate tissues in vivo and in vitro. The therapeutic potential of human multipotent mesenchymal stem cells (MSCs), which are harvested from bone marrow and adipose tissue, has generated increasing interest in a wide variety of biomedical disciplines. These cells can differentiate into a variety of tissue types, including bone, cartilage, fat, and nerve tissue. Adipose-derived stem cells have some advantages compared with other sources of stem cells, most notably that a large number of cells can be easily and quickly isolated from adipose tissue. In current clinical therapy for periodontal tissue regeneration, several methods have been developed and applied either alone or in combination, such as enamel matrix proteins, guided tissue regeneration, autologous/allogeneic/xenogeneic bone grafts, and growth factors. However, there are various limitations and shortcomings for periodontal tissue regeneration using current methods. Recently, periodontal tissue regeneration using MSCs has been examined in some animal models. This method has potential in the regeneration of functional periodontal tissues because the various secreted growth factors from MSCs might not only promote the regeneration of periodontal tissue but also encourage neovascularization of the damaged tissues. Adipose-derived stem cells are especially effective for neovascularization compared with other MSC sources. In this review, the possibility and potential of adipose-derived stem cells for regenerative medicine are introduced. Of particular interest, periodontal tissue regeneration with adipose-derived stem cells is discussed.

Translational Applications of Tissue Engineering in Cardiovascular Medicine.

PubMed

Dogan, Arin; Elcin, A Eser; Elcin, Y Murat

2017-03-26

Cardiovascular diseases are the leading cause of global deaths. The current paradigm in medicine seeks novel approaches for the treatment of progressive or end-stage diseases. The organ transplantation option is limited in availability, and unfortunately, a significant number of patients are lost while waiting for donor organs. Animal studies have shown that upon myocardial infarction, it is possible to stop adverse remodeling in its tracks and reverse with tissue engineering methods. Regaining the myocardium function and avoiding further deterioration towards heart failure can benefit millions of people with a significantly lesser burden on healthcare systems worldwide. The advent of induced pluripotent stem cells brings the unique advantage of testing candidate drug molecules on organ-on-chip systems, which mimics human heart in vitro. Biomimetic three-dimensional constructs that contain disease-specific or normal cardiomyocytes derived from human induced pluripotent stem cells are a useful tool for screening drug molecules and studying dosage, mode of action and cardio-toxicity. Tissue engineering approach aims to develop the treatments for heart valve deficiency, ischemic heart disease and a wide range of vascular diseases. Translational research seeks to improve the patient's quality of life, progressing towards developing cures, rather than treatments. To this end, researchers are working on tissue engineered heart valves, blood vessels, cardiac patches, and injectable biomaterials, hence developing new ways for engineering bio-artificial organs or tissue parts that the body will adopt as its own. In this review, we summarize translational methods for cardiovascular tissue engineering and present useful tables on pre-clinical and clinical applications. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Functional Attachment of Soft Tissues to Bone: Development, Healing, and Tissue Engineering

PubMed Central

Lu, Helen H.; Thomopoulos, Stavros

2014-01-01

Connective tissues such as tendons or ligaments attach to bone across a multitissue interface with spatial gradients in composition, structure, and mechanical properties. These gradients minimize stress concentrations and mediate load transfer between the soft and hard tissues. Given the high incidence of tendon and ligament injuries and the lack of integrative solutions for their repair, interface regeneration remains a significant clinical challenge. This review begins with a description of the developmental processes and the resultant structure-function relationships that translate into the functional grading necessary for stress transfer between soft tissue and bone. It then discusses the interface healing response, with a focus on the influence of mechanical loading and the role of cell-cell interactions. The review continues with a description of current efforts in interface tissue engineering, highlighting key strategies for the regeneration of the soft tissue–to-bone interface, and concludes with a summary of challenges and future directions. PMID:23642244

Development of Scaffold-Free Elastic Cartilaginous Constructs with Structural Similarities to Auricular Cartilage

PubMed Central

Giardini-Rosa, Renata; Joazeiro, Paulo P.; Thomas, Kathryn; Collavino, Kristina; Weber, Joanna

2014-01-01

External ear reconstruction with autologous cartilage still remains one of the most difficult problems in the fields of plastic and reconstructive surgery. As the absence of tissue vascularization limits the ability to stimulate new tissue growth, relatively few surgical approaches are currently available (alloplastic implants or sculpted autologous cartilage grafts) to repair or reconstruct the auricle (or pinna) as a result of traumatic loss or congenital absence (e.g., microtia). Alternatively, tissue engineering can offer the potential to grow autogenous cartilage suitable for implantation. While tissue-engineered auricle cartilage constructs can be created, a substantial number of cells are required to generate sufficient quantities of tissue for reconstruction. Similarly, as routine cell expansion can elicit negative effects on chondrocyte function, we have developed an approach to generate large-sized engineered auricle constructs (≥3 cm2) directly from a small population of donor cells (20,000–40,000 cells/construct). Using rabbit donor cells, the developed bioreactor-cultivated constructs adopted structural-like characteristics similar to native auricular cartilage, including the development of distinct cartilaginous and perichondrium-like regions. Both alterations in media composition and seeding density had profound effects on the formation of engineered elastic tissue constructs in terms of cellularity, extracellular matrix accumulation, and tissue structure. Higher seeding densities and media containing sodium bicarbonate produced tissue constructs that were closer to the native tissue in terms of structure and composition. Future studies will be aimed at improving the accumulation of specific tissue constituents and determining the clinical effectiveness of this approach using a reconstructive animal model. PMID:24124666

Development of scaffold-free elastic cartilaginous constructs with structural similarities to auricular cartilage.

PubMed

Giardini-Rosa, Renata; Joazeiro, Paulo P; Thomas, Kathryn; Collavino, Kristina; Weber, Joanna; Waldman, Stephen D

2014-03-01

External ear reconstruction with autologous cartilage still remains one of the most difficult problems in the fields of plastic and reconstructive surgery. As the absence of tissue vascularization limits the ability to stimulate new tissue growth, relatively few surgical approaches are currently available (alloplastic implants or sculpted autologous cartilage grafts) to repair or reconstruct the auricle (or pinna) as a result of traumatic loss or congenital absence (e.g., microtia). Alternatively, tissue engineering can offer the potential to grow autogenous cartilage suitable for implantation. While tissue-engineered auricle cartilage constructs can be created, a substantial number of cells are required to generate sufficient quantities of tissue for reconstruction. Similarly, as routine cell expansion can elicit negative effects on chondrocyte function, we have developed an approach to generate large-sized engineered auricle constructs (≥3 cm(2)) directly from a small population of donor cells (20,000-40,000 cells/construct). Using rabbit donor cells, the developed bioreactor-cultivated constructs adopted structural-like characteristics similar to native auricular cartilage, including the development of distinct cartilaginous and perichondrium-like regions. Both alterations in media composition and seeding density had profound effects on the formation of engineered elastic tissue constructs in terms of cellularity, extracellular matrix accumulation, and tissue structure. Higher seeding densities and media containing sodium bicarbonate produced tissue constructs that were closer to the native tissue in terms of structure and composition. Future studies will be aimed at improving the accumulation of specific tissue constituents and determining the clinical effectiveness of this approach using a reconstructive animal model.

Tissue-Engineering Approaches to Restore Kidney Function.

PubMed

Katari, Ravi; Edgar, Lauren; Wong, Theresa; Boey, Angela; Mancone, Sarah; Igel, Daniel; Callese, Tyler; Voigt, Marcia; Tamburrini, Riccardo; Zambon, Joao Paulo; Perin, Laura; Orlando, Giuseppe

2015-10-01

Kidney transplantation for the treatment of chronic kidney disease has established outcome and quality of life. However, its implementation is severely limited by a chronic shortage of donor organs; consequently, most candidates remain on dialysis and on the waiting list while accruing further morbidity and mortality. Furthermore, those patients that do receive kidney transplants are committed to a life-long regimen of immunosuppressive drugs that also carry significant adverse risk profiles. The disciplines of tissue engineering and regenerative medicine have the potential to produce alternative therapies which circumvent the obstacles posed by organ shortage and immunorejection. This review paper describes some of the most promising tissue-engineering solutions currently under investigation for the treatment of acute and chronic kidney diseases. The various stem cell therapies, whole embryo transplantation, and bioengineering with ECM scaffolds are outlined and summarized.

Engineering Approaches Toward Deconstructing and Controlling the Stem Cell Environment

PubMed Central

Edalat, Faramarz; Bae, Hojae; Manoucheri, Sam; Cha, Jae Min; Khademhosseini, Ali

2012-01-01

Stem cell-based therapeutics have become a vital component in tissue engineering and regenerative medicine. The microenvironment within which stem cells reside, i.e. the niche, plays a crucial role in regulating stem cell self-renewal and differentiation. However, current biological techniques lack the means to recapitulate the complexity of this microenvironment. Nano- and microengineered materials offer innovative methods to: (1) deconstruct the stem cell niche to understand the effects of individual elements; (2) construct complex tissue-like structures resembling the niche to better predict and control cellular processes; and (3) transplant stem cells or activate endogenous stem cell populations for regeneration of aged or diseased tissues. Here, we highlight some of the latest advances in this field and discuss future applications and directions of the use of nano- and microtechnologies for stem cell engineering. PMID:22101755

Vascular tissue engineering: towards the next generation vascular grafts.

PubMed

Naito, Yuji; Shinoka, Toshiharu; Duncan, Daniel; Hibino, Narutoshi; Solomon, Daniel; Cleary, Muriel; Rathore, Animesh; Fein, Corey; Church, Spencer; Breuer, Christopher

2011-04-30

The application of tissue engineering technology to cardiovascular surgery holds great promise for improving outcomes in patients with cardiovascular diseases. Currently used synthetic vascular grafts have several limitations including thrombogenicity, increased risk of infection, and lack of growth potential. We have completed the first clinical trial evaluating the feasibility of using tissue engineered vascular grafts (TEVG) created by seeding autologous bone marrow-derived mononuclear cells (BM-MNC) onto biodegradable tubular scaffolds. Despite an excellent safety profile, data from the clinical trial suggest that the primary graft related complication of the TEVG is stenosis, affecting approximately 16% of grafts within the first seven years after implantation. Continued investigation into the cellular and molecular mechanisms underlying vascular neotissue formation will improve our basic understanding and provide insights that will enable the rationale design of second generation TEVG. Published by Elsevier B.V.

Two-photon excitation based photochemistry and neural imaging

NASA Astrophysics Data System (ADS)

Hatch, Kevin Andrew

Two-photon microscopy is a fluorescence imaging technique which provides distinct advantages in three-dimensional cellular and molecular imaging. The benefits of this technology may extend beyond imaging capabilities through exploitation of the quantum processes responsible for fluorescent events. This study utilized a two-photon microscope to investigate a synthetic photoreactive collagen peptidomimetic, which may serve as a potential material for tissue engineering using the techniques of two-photon photolysis and two-photon polymerization. The combination of these techniques could potentially be used to produce a scaffold for the vascularization of engineered three-dimensional tissues in vitro to address the current limitations of tissue engineering. Additionally, two-photon microscopy was used to observe the effects of the application of the neurotransmitter dopamine to the mushroom body neural structures of Drosophila melanogaster to investigate dopamine's connection to cognitive degeneration.

Engineering approaches toward deconstructing and controlling the stem cell environment.

PubMed

Edalat, Faramarz; Bae, Hojae; Manoucheri, Sam; Cha, Jae Min; Khademhosseini, Ali

2012-06-01

Stem cell-based therapeutics have become a vital component in tissue engineering and regenerative medicine. The microenvironment within which stem cells reside, i.e., the niche, plays a crucial role in regulating stem cell self-renewal and differentiation. However, current biological techniques lack the means to recapitulate the complexity of this microenvironment. Nano- and microengineered materials offer innovative methods to (1) deconstruct the stem cell niche to understand the effects of individual elements; (2) construct complex tissue-like structures resembling the niche to better predict and control cellular processes; and (3) transplant stem cells or activate endogenous stem cell populations for regeneration of aged or diseased tissues. In this article, we highlight some of the latest advances in this field and discuss future applications and directions of the use of nano- and microtechnologies for stem cell engineering.

3D printing of functional biomaterials for tissue engineering.

PubMed

Zhu, Wei; Ma, Xuanyi; Gou, Maling; Mei, Deqing; Zhang, Kang; Chen, Shaochen

2016-08-01

3D printing is emerging as a powerful tool for tissue engineering by enabling 3D cell culture within complex 3D biomimetic architectures. This review discusses the prevailing 3D printing techniques and their most recent applications in building tissue constructs. The work associated with relatively well-known inkjet and extrusion-based bioprinting is presented with the latest advances in the fields. Emphasis is put on introducing two relatively new light-assisted bioprinting techniques, including digital light processing (DLP)-based bioprinting and laser based two photon polymerization (TPP) bioprinting. 3D bioprinting of vasculature network is particularly discussed for its foremost significance in maintaining tissue viability and promoting functional maturation. Limitations to current bioprinting approaches, as well as future directions of bioprinting functional tissues are also discussed. Copyright © 2016 Elsevier Ltd. All rights reserved.

Tissue Equivalents Based on Cell-Seeded Biodegradable Microfluidic Constructs

PubMed Central

Borenstein, Jeffrey T.; Megley, Katie; Wall, Kimberly; Pritchard, Eleanor M.; Truong, David; Kaplan, David L.; Tao, Sarah L.; Herman, Ira M.

2010-01-01

One of the principal challenges in the field of tissue engineering and regenerative medicine is the formation of functional microvascular networks capable of sustaining tissue constructs. Complex tissues and vital organs require a means to support oxygen and nutrient transport during the development of constructs both prior to and after host integration, and current approaches have not demonstrated robust solutions to this challenge. Here, we present a technology platform encompassing the design, construction, cell seeding and functional evaluation of tissue equivalents for wound healing and other clinical applications. These tissue equivalents are comprised of biodegradable microfluidic scaffolds lined with microvascular cells and designed to replicate microenvironmental cues necessary to generate and sustain cell populations to replace dermal and/or epidermal tissues lost due to trauma or disease. Initial results demonstrate that these biodegradable microfluidic devices promote cell adherence and support basic cell functions. These systems represent a promising pathway towards highly integrated three-dimensional engineered tissue constructs for a wide range of clinical applications.

Novel strategy to engineer trachea cartilage graft with marrow mesenchymal stem cell macroaggregate and hydrolyzable scaffold.

PubMed

Liu, Liangqi; Wu, Wei; Tuo, Xiaoye; Geng, Wenxin; Zhao, Jie; Wei, Jing; Yan, Xingrong; Yang, Wei; Li, Liwen; Chen, Fulin

2010-05-01

Limited donor sites of cartilage and dedifferentiation of chondrocytes during expansion, low tissue reconstruction efficiency, and uncontrollable immune reactions to foreign materials are the main obstacles to overcome before cartilage tissue engineering can be widely used in the clinic. In the current study, we developed a novel strategy to fabricate tissue-engineered trachea cartilage grafts using marrow mesenchymal stem cell (MSC) macroaggregates and hydrolyzable scaffold of polylactic acid-polyglycolic acid copolymer (PLGA). Rabbit MSCs were continuously cultured to prepare macroaggregates in sheet form. The macroaggregates were studied for their potential for chondrogenesis. The macroaggregates were wrapped against the PLGA scaffold to make a tubular composite. The composites were incubated in spinner flasks for 4 weeks to fabricate trachea cartilage grafts. Histological observation and polymerase chain reaction array showed that MSC macroaggregates could obtain the optimal chondrogenic capacity under the induction of transforming growth factor-beta. Engineered trachea cartilage consisted of evenly spaced lacunae embedded in a matrix rich in proteoglycans. PLGA scaffold degraded totally during in vitro incubation and the engineered cartilage graft was composed of autologous tissue. Based on this novel, MSC macroaggregate and hydrolyzable scaffold composite strategy, ready-to-implant autologous trachea cartilage grafts could be successfully fabricated. The strategy also had the advantages of high efficiency in cell seeding and tissue regeneration, and could possibly be used in future in vivo experiments.

Bioreactor-induced mesenchymal progenitor cell differentiation and elastic fiber assembly in engineered vascular tissues.

PubMed

Lin, Shigang; Mequanint, Kibret

2017-09-01

In vitro maturation of engineered vascular tissues (EVT) requires the appropriate incorporation of smooth muscle cells (SMC) and extracellular matrix (ECM) components similar to native arteries. To this end, the aim of the current study was to fabricate 4mm inner diameter vascular tissues using mesenchymal progenitor cells seeded into tubular scaffolds. A dual-pump bioreactor operating either in perfusion or pulsatile perfusion mode was used to generate physiological-like stimuli to promote progenitor cell differentiation, extracellular elastin production, and tissue maturation. Our data demonstrated that pulsatile forces and perfusion of 3D tubular constructs from both the lumenal and ablumenal sides with culture media significantly improved tissue assembly, effectively inducing mesenchymal progenitor cell differentiation to SMCs with contemporaneous elastin production. With bioreactor cultivation, progenitor cells differentiated toward smooth muscle lineage characterized by the expression of smooth muscle (SM)-specific markers smooth muscle alpha actin (SM-α-actin) and smooth muscle myosin heavy chain (SM-MHC). More importantly, pulsatile perfusion bioreactor cultivation enhanced the synthesis of tropoelastin and its extracellular cross-linking into elastic fiber compared with static culture controls. Taken together, the current study demonstrated progenitor cell differentiation and vascular tissue assembly, and provides insights into elastin synthesis and assembly to fibers. Incorporation of elastin into engineered vascular tissues represents a critical design goal for both mechanical and biological functions. In the present study, we seeded porous tubular scaffolds with multipotent mesenchymal progenitor cells and cultured in dual-pump pulsatile perfusion bioreactor. Physiological-like stimuli generated by bioreactor not only induced mesenchymal progenitor cell differentiation to vascular smooth muscle lineage but also actively promoted elastin synthesis and fiber assembly. Gene expression and protein synthesis analyses coupled with histological and immunofluorescence staining revealed that elastin-containing vascular tissues were fabricated. More importantly, co-localization and co-immunoprecipitation experiments demonstrated that elastin and fibrillin-1 were abundant throughout the cross-section of the tissue constructs suggesting a process of elastin protein crosslinking. This study paves a way forward to engineer elastin-containing functional vascular substitutes from multipotent progenitor cells in a bioreactor. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Athymic Rat Model for Evaluation of Engineered Anterior Cruciate Ligament Grafts

PubMed Central

Leong, Natalie L.; Kabir, Nima; Arshi, Armin; Nazemi, Azadeh; Wu, Ben M.; McAllister, David R.; Petrigliano, Frank A.

2015-01-01

Anterior cruciate ligament (ACL) rupture is a common ligamentous injury that often requires surgery because the ACL does not heal well without intervention. Current treatment strategies include ligament reconstruction with either autograft or allograft, which each have their associated limitations. Thus, there is interest in designing a tissue-engineered graft for use in ACL reconstruction. We describe the fabrication of an electrospun polymer graft for use in ACL tissue engineering. This polycaprolactone graft is biocompatible, biodegradable, porous, and is comprised of aligned fibers. Because an animal model is necessary to evaluate such a graft, this paper describes an intra-articular athymic rat model of ACL reconstruction that can be used to evaluate engineered grafts, including those seeded with xenogeneic cells. Representative histology and biomechanical testing results at 16 weeks postoperatively are presented, with grafts tested immediately post-implantation and contralateral native ACLs serving as controls. The present study provides a reproducible animal model with which to evaluate tissue engineered ACL grafts, and demonstrates the potential of a regenerative medicine approach to treatment of ACL rupture. PMID:25867958

Biomaterial design for specific cellular interactions: Role of surface functionalization and geometric features

NASA Astrophysics Data System (ADS)

Kolhar, Poornima

The areas of drug delivery and tissue engineering have experienced extraordinary growth in recent years with the application of engineering principles and their potential to support and improve the field of medicine. The tremendous progress in nanotechnology and biotechnology has lead to this explosion of research and development in biomedical applications. Biomaterials can now be engineered at a nanoscale and their specific interactions with the biological tissues can be modulated. Various design parameters are being established and researched for design of drug-delivery carriers and scaffolds to be implanted into humans. Nanoparticles made from versatile biomaterial can deliver both small-molecule drugs and various classes of bio-macromolecules, such as proteins and oligonucleotides. Similarly in the field of tissue engineering, current approaches emphasize nanoscale control of cell behavior by mimicking the natural extracellular matrix (ECM) unlike, traditional scaffolds. Drug delivery and tissue engineering are closely connected fields and both of these applications require materials with exceptional physical, chemical, biological, and biomechanical properties to provide superior therapy. In the current study the surface functionalization and the geometric features of the biomaterials has been explored. In particular, a synthetic surface for culture of human embryonic stem cells has been developed, demonstrating the importance of surface functionalization in maintaining the pluripotency of hESCs. In the second study, the geometric features of the drug delivery carriers are investigated and the polymeric nanoneedles mediated cellular permeabilization and direct cytoplasmic delivery is reported. In the third study, the combined effect of surface functionalization and geometric modification of carriers for vascular targeting is enunciated. These studies illustrate how the biomaterials can be designed to achieve various cellular behaviors and control the interactions with cells in vivo .

Craniofacial Tissue Engineering by Stem Cells

PubMed Central

Mao, J.J.; Giannobile, W.V.; Helms, J.A.; Hollister, S.J.; Krebsbach, P.H.; Longaker, M.T.; Shi, S.

2008-01-01

Craniofacial tissue engineering promises the regeneration or de novo formation of dental, oral, and craniofacial structures lost to congenital anomalies, trauma, and diseases. Virtually all craniofacial structures are derivatives of mesenchymal cells. Mesenchymal stem cells are the offspring of mesenchymal cells following asymmetrical division, and reside in various craniofacial structures in the adult. Cells with characteristics of adult stem cells have been isolated from the dental pulp, the deciduous tooth, and the periodontium. Several craniofacial structures—such as the mandibular condyle, calvarial bone, cranial suture, and subcutaneous adipose tissue—have been engineered from mesenchymal stem cells, growth factor, and/or gene therapy approaches. As a departure from the reliance of current clinical practice on durable materials such as amalgam, composites, and metallic alloys, biological therapies utilize mesenchymal stem cells, delivered or internally recruited, to generate craniofacial structures in temporary scaffolding biomaterials. Craniofacial tissue engineering is likely to be realized in the foreseeable future, and represents an opportunity that dentistry cannot afford to miss. PMID:17062735

Engineering hydrogels as extracellular matrix mimics

PubMed Central

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

2010-01-01

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

Application of xanthan gum as polysaccharide in tissue engineering: A review.

PubMed

Kumar, Anuj; Rao, Kummara Madhusudana; Han, Sung Soo

2018-01-15

Xanthan gum is a microbial high molecular weight exo-polysaccharide produced by Xanthomonas bacteria (a Gram-negative bacteria genus that exhibits several different species) and it has widely been used as an additive in various industrial and biomedical applications such as food and food packaging, cosmetics, water-based paints, toiletries, petroleum, oil-recovery, construction and building materials, and drug delivery. Recently, it has shown great potential in issue engineering applications and a variety of modification methods have been employed to modify xanthan gum as polysaccharide for this purpose. However, xanthan gum-based biomaterials need further modification for several targeted applications due to some disadvantages (e.g., processing and mechanical performance of xanthan gum), where modified xanthan gum will be well suited for tissue engineering products. In this review, the current scenario of the use of xanthan gum for various tissue engineering applications, including its origin, structure, properties, modification, and processing for the preparation of the hydrogels and/or the scaffolds is precisely reviewed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Tubular organ epithelialisation

PubMed Central

Saksena, Rhea; Gao, Chuanyu; Wicox, Mathew; de Mel, Achala

2016-01-01

Hollow, tubular organs including oesophagus, trachea, stomach, intestine, bladder and urethra may require repair or replacement due to disease. Current treatment is considered an unmet clinical need, and tissue engineering strategies aim to overcome these by fabricating synthetic constructs as tissue replacements. Smart, functionalised synthetic materials can act as a scaffold base of an organ and multiple cell types, including stem cells can be used to repopulate these scaffolds to replace or repair the damaged or diseased organs. Epithelial cells have not yet completely shown to have efficacious cell–scaffold interactions or good functionality in artificial organs, thus limiting the success of tissue-engineered grafts. Epithelial cells play an essential part of respective organs to maintain their function. Without successful epithelialisation, hollow organs are liable to stenosis, collapse, extensive fibrosis and infection that limit patency. It is clear that the source of cells and physicochemical properties of scaffolds determine the successful epithelialisation. This article presents a review of tissue engineering studies on oesophagus, trachea, stomach, small intestine, bladder and urethral constructs conducted to actualise epithelialised grafts. PMID:28228931

Biomimetic and bioactive nanofibrous scaffolds from electrospun composite nanofibers

PubMed Central

Zhang, YZ; Su, B; Venugopal, J; Ramakrishna, S; Lim, CT

2007-01-01

Electrospinning is an enabling technology that can architecturally (in terms of geometry, morphology or topography) and biochemically fabricate engineered cellular scaffolds that mimic the native extracellular matrix (ECM). This is especially important and forms one of the essential paradigms in the area of tissue engineering. While biomimesis of the physical dimensions of native ECM’s major constituents (eg, collagen) is no longer a fabrication-related challenge in tissue engineering research, conveying bioactivity to electrospun nanofibrous structures will determine the efficiency of utilizing electrospun nanofibers for regenerating biologically functional tissues. This can certainly be achieved through developing composite nanofibers. This article gives a brief overview on the current development and application status of employing electrospun composite nanofibers for constructing biomimetic and bioactive tissue scaffolds. Considering that composites consist of at least two material components and phases, this review details three different configurations of nanofibrous composite structures by using hybridizing basic binary material systems as example. These are components blended composite nanofiber, core-shell structured composite nanofiber, and nanofibrous mingled structure. PMID:18203429

Learning from real and tissue-engineered jellyfish: How to design and build a muscle-powered pump at intermediate Reynolds numbers

NASA Astrophysics Data System (ADS)

Nawroth, Janna; Lee, Hyungsuk; Feinberg, Adam; Ripplinger, Crystal; McCain, Megan; Grosberg, Anna; Dabiri, John; Parker, Kit

2012-11-01

Tissue-engineered devices promise to advance medical implants, aquatic robots and experimental platforms for tissue-fluid interactions. The design, fabrication and systematic improvement of tissue constructs, however, is challenging because of the complex interactions of living cell, synthetic materials and their fluid environments. In a proof of concept study we have tissue-engineered a construct that mimics the swimming of a juvenile jellyfish, a simple model system for muscle-powered pumps at intermediate Reynolds numbers with quantifiable fluid dynamics and morphological properties. Optimally designed constructs achieved jellyfish-like swimming and generated biomimetic propulsion and feeding currents. Focusing on the fluid interactions, we discuss failed and successful designs and the lessons learned in the process. The main challenges were (1) to derive a body shape and deformation suitable for effective fluid transport under physiological fluid conditions, (2) to understand the mechanical properties of muscle and bell matrix and device a design capable of the desired deformation, (3) to establish adequate 3D kinematics of power and recovery stroke, and (4) to evaluate the performance of the design.

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

PubMed

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

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

Stem Cells for Skeletal Muscle Tissue Engineering.

PubMed

Pantelic, Molly N; Larkin, Lisa M

2018-04-19

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

Scaffold-based Anti-infection Strategies in Bone Repair

PubMed Central

Johnson, Christopher T.; García, Andrés J.

2014-01-01

Bone fractures and non-union defects often require surgical intervention where biomaterials are used to correct the defect, and approximately 10% of these procedures are compromised by bacterial infection. Currently, treatment options are limited to sustained, high doses of antibiotics and surgical debridement of affected tissue, leaving a significant, unmet need for the development of therapies to combat device-associated biofilm and infections. Engineering implants to prevent infection is a desirable material characteristic. Tissue engineered scaffolds for bone repair provide a means to both regenerate bone and serve as a base for adding antimicrobial agents. Incorporating anti-infection properties into regenerative medicine therapies could improve clinical outcomes and reduce the morbidity and mortality associated with biomaterial implant-associated infections. This review focuses on current animal models and technologies available to assess bone repair in the context of infection, antimicrobial agents to fight infection, the current state of antimicrobial scaffolds, and future directions in the field. PMID:25476163

Challenges in Bio-fabrication of Organoid Cultures.

PubMed

Peng, Weijie; Datta, Pallab; Wu, Yang; Dey, Madhuri; Ayan, Bugra; Dababneh, Amer; Ozbolat, Ibrahim T

2018-06-01

Three-dimensional (3D) organoids have shown advantages in cell culture over traditional two-dimensional (2D) culture, and have great potential in various applications of tissue engineering. However, there are limitations in current organoid fabrication technologies, such as uncontrolled size, poor reproductively, and inadequate complexity of organoids. In this chapter, we present the existing techniques and discuss the major challenges for 3D organoid biofabrication. Future perspectives on organoid bioprinting are also discussed, where bioprinting technologies are expected to make a major contribution in organoid fabrication, such as realizing mass production and constructing complex heterotypic tissues, and thus further advance the translational application of organoids in tissue engineering and regenerative medicine as well drug testing and pharmaceutics.

Silk fibroin as biomaterial for bone tissue engineering.

PubMed

Melke, Johanna; Midha, Swati; Ghosh, Sourabh; Ito, Keita; Hofmann, Sandra

2016-02-01

Silk fibroin (SF) is a fibrous protein which is produced mainly by silkworms and spiders. Its unique mechanical properties, tunable biodegradation rate and the ability to support the differentiation of mesenchymal stem cells along the osteogenic lineage, have made SF a favorable scaffold material for bone tissue engineering. SF can be processed into various scaffold forms, combined synergistically with other biomaterials to form composites and chemically modified, which provides an impressive toolbox and allows SF scaffolds to be tailored to specific applications. This review discusses and summarizes recent advancements in processing SF, focusing on different fabrication and functionalization methods and their application to grow bone tissue in vitro and in vivo. Potential areas for future research, current challenges, uncertainties and gaps in knowledge are highlighted. Silk fibroin is a natural biomaterial with remarkable biomedical and mechanical properties which make it favorable for a broad range of bone tissue engineering applications. It can be processed into different scaffold forms, combined synergistically with other biomaterials to form composites and chemically modified which provides a unique toolbox and allows silk fibroin scaffolds to be tailored to specific applications. This review discusses and summarizes recent advancements in processing silk fibroin, focusing on different fabrication and functionalization methods and their application to grow bone tissue in vitro and in vivo. Potential areas for future research, current challenges, uncertainties and gaps in knowledge are highlighted. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Three-Dimensional Printing Articular Cartilage: Recapitulating the Complexity of Native Tissue.

PubMed

Guo, Ting; Lembong, Josephine; Zhang, Lijie Grace; Fisher, John P

2017-06-01

In the past few decades, the field of tissue engineering combined with rapid prototyping (RP) techniques has been successful in creating biological substitutes that mimic tissues. Its applications in regenerative medicine have drawn efforts in research from various scientific fields, diagnostics, and clinical translation to therapies. While some areas of therapeutics are well developed, such as skin replacement, many others such as cartilage repair can still greatly benefit from tissue engineering and RP due to the low success and/or inefficiency of current existing, often surgical treatments. Through fabrication of complex scaffolds and development of advanced materials, RP provides a new avenue for cartilage repair. Computer-aided design and three-dimensional (3D) printing allow the fabrication of modeled cartilage scaffolds for repair and regeneration of damaged cartilage tissues. Specifically, the various processes of 3D printing will be discussed in details, both cellular and acellular techniques, covering the different materials, geometries, and operational printing conditions for the development of tissue-engineered articular cartilage. Finally, we conclude with some insights on future applications and challenges related to this technology, especially using 3D printing techniques to recapitulate the complexity of native structure for advanced cartilage regeneration.

Proresolving Nanomedicines Activate Bone Regeneration in Periodontitis

PubMed Central

Hasturk, H.; Kantarci, A.; Freire, M.O.; Nguyen, D.; Dalli, J.; Serhan, C.N.

2015-01-01

Therapies to reverse tissue damage from osteolytic inflammatory diseases are limited by the inability of current tissue-engineering procedures to restore lost hard and soft tissues. There is a critical need for new therapeutics in regeneration. In addition to scaffolds, cells, and soluble mediators necessary for tissue engineering, control of endogenous inflammation is an absolute requirement for success. Although significant progress has been made in understanding natural resolution of inflammation pathways to limit uncontrolled inflammation in disease, harnessing the biomimetic properties of proresolving lipid mediators has not been demonstrated. Here, we report the use of nano-proresolving medicines (NPRM) containing a novel lipoxin analog (benzo-lipoxin A4, bLXA4) to promote regeneration of hard and soft tissues irreversibly lost to periodontitis in the Hanford miniature pig. In this proof-of-principle experiment, NPRM-bLXA4 dramatically reduced inflammatory cell infiltrate into chronic periodontal disease sites treated surgically and dramatically increased new bone formation and regeneration of the periodontal organ. These findings indicate that NPRM-bLXA4 is a mimetic of endogenous resolving mechanisms with potent bioactions that offers a new therapeutic tissue-engineering approach for the treatment of chronic osteolytic inflammatory diseases. PMID:25389003

Tissue engineering in urothelium regeneration.

PubMed

Vaegler, Martin; Maurer, Sabine; Toomey, Patricia; Amend, Bastian; Sievert, Karl-Dietrich

2015-03-01

The development of therapeutic treatments to regenerate urothelium, manufacture tissue equivalents or neourethras for in-vivo application is a significant challenge in the field of tissue engineering. Many studies have focused on urethral defects that, in most cases, inadequately address current therapies. This article reviews the primary tissue engineering strategies aimed at the clinical requirements for urothelium regeneration while concentrating on promising investigations in the use of grafts, cellular preparations, as well as seeded or unseeded natural and synthetic materials. Despite significant progress being made in the development of scaffolds and matrices, buccal mucosa transplants have not been replaced. Recently, graft tissues appear to have an advantage over the use of matrices. These therapies depend on cell isolation and propagation in vitro that require, not only substantial laboratory resources, but also subsequent surgical implant procedures. The choice of the correct cell source is crucial when determining an in-vivo application because of the risks of tissue changes and abnormalities that may result in donor site morbidity. Addressing an appropriately-designed animal model and relevant regulatory issues is of fundamental importance for the principal investigators when a therapy using cellular components has been developed for clinical use. Copyright © 2014 Elsevier B.V. All rights reserved.

Proresolving nanomedicines activate bone regeneration in periodontitis.

PubMed

Van Dyke, T E; Hasturk, H; Kantarci, A; Freire, M O; Nguyen, D; Dalli, J; Serhan, C N

2015-01-01

Therapies to reverse tissue damage from osteolytic inflammatory diseases are limited by the inability of current tissue-engineering procedures to restore lost hard and soft tissues. There is a critical need for new therapeutics in regeneration. In addition to scaffolds, cells, and soluble mediators necessary for tissue engineering, control of endogenous inflammation is an absolute requirement for success. Although significant progress has been made in understanding natural resolution of inflammation pathways to limit uncontrolled inflammation in disease, harnessing the biomimetic properties of proresolving lipid mediators has not been demonstrated. Here, we report the use of nano-proresolving medicines (NPRM) containing a novel lipoxin analog (benzo-lipoxin A4, bLXA4) to promote regeneration of hard and soft tissues irreversibly lost to periodontitis in the Hanford miniature pig. In this proof-of-principle experiment, NPRM-bLXA4 dramatically reduced inflammatory cell infiltrate into chronic periodontal disease sites treated surgically and dramatically increased new bone formation and regeneration of the periodontal organ. These findings indicate that NPRM-bLXA4 is a mimetic of endogenous resolving mechanisms with potent bioactions that offers a new therapeutic tissue-engineering approach for the treatment of chronic osteolytic inflammatory diseases. © International & American Associations for Dental Research 2014.

Scaffolds containing chitosan/carboxymethyl cellulose/mesoporous wollastonite for bone tissue engineering.

PubMed

Sainitya, R; Sriram, M; Kalyanaraman, V; Dhivya, S; Saravanan, S; Vairamani, M; Sastry, T P; Selvamurugan, N

2015-09-01

Scaffold based bone tissue engineering utilizes a variety of biopolymers in different combinations aiming to deliver optimal properties required for bone regeneration. In the current study, we fabricated bio-composite scaffolds containing chitosan (CS), carboxymethylcellulose (CMC) with varied concentrations of mesoporous wollastonite (m-WS) particles by the freeze drying method. The CS/CMC/m-WS scaffolds were characterized by the SEM, EDS and FT-IR studies. Addition of m-WS particles had no effect on altering the porosity of the scaffolds. m-WS particles at 0.5% concentration in the CS/CMC scaffolds showed significant improvement in the bio-mineralization and protein adsorption properties. Addition of m-WS particles in the CS/CMC scaffolds significantly reduced their swelling and degradation properties. The CS/CMC/m-WS scaffolds also showed cyto-friendly nature to human osteoblastic cells. The osteogenic potential of CS/CMC/m-WS scaffolds was confirmed by calcium deposition and expression of an osteoblast specific microRNA, pre-mir-15b. Thus, the current investigations support the use of CS/CMC/m-WS scaffolds for bone tissue engineering applications. Copyright © 2015 Elsevier B.V. All rights reserved.

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

PubMed

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

2015-07-22

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

Multiphasic Scaffolds for Periodontal Tissue Engineering

PubMed Central

Ivanovski, S.; Vaquette, C.; Gronthos, S.; Hutmacher, D.W.; Bartold, P.M.

2014-01-01

For a successful clinical outcome, periodontal regeneration requires the coordinated response of multiple soft and hard tissues (periodontal ligament, gingiva, cementum, and bone) during the wound-healing process. Tissue-engineered constructs for regeneration of the periodontium must be of a complex 3-dimensional shape and adequate size and demonstrate biomechanical stability over time. A critical requirement is the ability to promote the formation of functional periodontal attachment between regenerated alveolar bone, and newly formed cementum on the root surface. This review outlines the current advances in multiphasic scaffold fabrication and how these scaffolds can be combined with cell- and growth factor–based approaches to form tissue-engineered constructs capable of recapitulating the complex temporal and spatial wound-healing events that will lead to predictable periodontal regeneration. This can be achieved through a variety of approaches, with promising strategies characterized by the use of scaffolds that can deliver and stabilize cells capable of cementogenesis onto the root surface, provide biomechanical cues that encourage perpendicular alignment of periodontal fibers to the root surface, and provide osteogenic cues and appropriate space to facilitate bone regeneration. Progress on the development of multiphasic constructs for periodontal tissue engineering is in the early stages of development, and these constructs need to be tested in large animal models and, ultimately, human clinical trials. PMID:25139362

Multiphasic scaffolds for periodontal tissue engineering.

PubMed

Ivanovski, S; Vaquette, C; Gronthos, S; Hutmacher, D W; Bartold, P M

2014-12-01

For a successful clinical outcome, periodontal regeneration requires the coordinated response of multiple soft and hard tissues (periodontal ligament, gingiva, cementum, and bone) during the wound-healing process. Tissue-engineered constructs for regeneration of the periodontium must be of a complex 3-dimensional shape and adequate size and demonstrate biomechanical stability over time. A critical requirement is the ability to promote the formation of functional periodontal attachment between regenerated alveolar bone, and newly formed cementum on the root surface. This review outlines the current advances in multiphasic scaffold fabrication and how these scaffolds can be combined with cell- and growth factor-based approaches to form tissue-engineered constructs capable of recapitulating the complex temporal and spatial wound-healing events that will lead to predictable periodontal regeneration. This can be achieved through a variety of approaches, with promising strategies characterized by the use of scaffolds that can deliver and stabilize cells capable of cementogenesis onto the root surface, provide biomechanical cues that encourage perpendicular alignment of periodontal fibers to the root surface, and provide osteogenic cues and appropriate space to facilitate bone regeneration. Progress on the development of multiphasic constructs for periodontal tissue engineering is in the early stages of development, and these constructs need to be tested in large animal models and, ultimately, human clinical trials. © International & American Associations for Dental Research.

Development and characterization of decellularized human nasoseptal cartilage matrix for use in tissue engineering.

PubMed

Graham, M Elise; Gratzer, Paul F; Bezuhly, Michael; Hong, Paul

2016-10-01

Reconstruction of cartilage defects in the head and neck can require harvesting of autologous cartilage grafts, which can be associated with donor site morbidity. To overcome this limitation, tissue-engineering approaches may be used to generate cartilage grafts. The objective of this study was to decellularize and characterize human nasoseptal cartilage with the aim of generating a biological scaffold for cartilage tissue engineering. Laboratory study using nasoseptal cartilage. Remnant human nasoseptal cartilage specimens were collected and subjected to a novel decellularization treatment. The decellularization process involved several cycles of enzymatic detergent treatments. For characterization, decellularized and fresh (control) specimens underwent histological, biochemical, and mechanical analyses. Scanning electron microscopy and biocompatibility assay were also performed. The decellularization process had minimal effect on glycosaminoglycan content of the cartilage extracellular matrix. Deoxyribonucleic acid (DNA) analysis revealed the near-complete removal of genomic DNA from decellularized tissues. The effectiveness of the decellularization process was also confirmed on histological and scanning electron microscopic analyses. Mechanical testing results showed that the structural integrity of the decellularized tissue was maintained, and biocompatibility was confirmed. Overall, the current decellularization treatment resulted in significant reduction of genetic/cellular material with preservation of the underlying extracellular matrix structure. This decellularized material may serve as a potential scaffold for cartilage tissue engineering. N/A. Laryngoscope, 126:2226-2231, 2016. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

Ocular surface reconstruction with a tissue-engineered nasal mucosal epithelial cell sheet for the treatment of severe ocular surface diseases.

PubMed

Kobayashi, Masakazu; Nakamura, Takahiro; Yasuda, Makoto; Hata, Yuiko; Okura, Shoki; Iwamoto, Miyu; Nagata, Maho; Fullwood, Nigel J; Koizumi, Noriko; Hisa, Yasuo; Kinoshita, Shigeru

2015-01-01

Severe ocular surface diseases (OSDs) with severe dry eye can be devastating and are currently some of the most challenging eye disorders to treat. To investigate the feasibility of using an autologous tissue-engineered cultivated nasal mucosal epithelial cell sheet (CNMES) for ocular surface reconstruction, we developed a novel technique for the culture of nasal mucosal epithelial cells expanded ex vivo from biopsy-derived human nasal mucosal tissues. After the protocol, the CNMESs had 4-5 layers of stratified, well-differentiated cells, and we successfully generated cultured epithelial sheets, including numerous goblet cells. Immunohistochemistry confirmed the presence of keratins 3, 4, and 13; mucins 1, 16, and 5AC; cell junction and basement membrane assembly proteins; and stem/progenitor cell marker p75 in the CNMESs. We then transplanted the CNMESs onto the ocular surfaces of rabbits and confirmed the survival of this tissue, including the goblet cells, up to 2 weeks. The present report describes an attempt to overcome the problems of treating severe OSDs with the most severe dry eye by treating them using tissue-engineered CNMESs to supply functional goblet cells and to stabilize and reconstruct the ocular surface. The present study is a first step toward assessing the use of tissue-engineered goblet-cell transplantation of nonocular surface origin for ocular surface reconstruction. ©AlphaMed Press.

Reconstruction of thin fluorophore-filled capillaries in thick scattering medium using fluorescence diffuse optical tomography within the diffusion approximation

NASA Astrophysics Data System (ADS)

Desrochers, Johanne; Vermette, Patrick; Fontaine, Réjean; Bérubé-Lauzière, Yves

2009-02-01

Current efforts in tissue engineering target the growth of 3D volumes of tissue cultures in bioreactor conditions. Fluorescence optical tomography has the potential to monitor cells viability and tissue growth non-destructively directly within the bioreactor via bio-molecular fluorescent labelling strategies. We currently work on developing the imaging instrumentation for tissue cultures in bioreactor conditions. Previously, we localized in 3D thin fluorescent-labelled capillaries in a cylindrically shaped bioreactor phantom containing a diffusive medium with our time-of-flight localization technique. Here, we present our first reconstruction results of the spatial distribution of fluorophore concentrations for labelled capillaries embedded in a bioreactor phantom.

Human Urine Derived Stem Cells in Combination with β-TCP Can Be Applied for Bone Regeneration.

PubMed

Guan, Junjie; Zhang, Jieyuan; Li, Haiyan; Zhu, Zhenzhong; Guo, Shangchun; Niu, Xin; Wang, Yang; Zhang, Changqing

2015-01-01

Bone tissue engineering requires highly proliferative stem cells that are easy to isolate. Human urine stem cells (USCs) are abundant and can be easily harvested without using an invasive procedure. In addition, in our previous studies, USCs have been proved to be able to differentiate into osteoblasts, chondrocytes, and adipocytes. Therefore, USCs may have great potential and advantages to be applied as a cell source for tissue engineering. However, there are no published studies that describe the interactions between USCs and biomaterials and applications of USCs for bone tissue engineering. Therefore, the objective of the present study was to evaluate the interactions between USCs with a typical bone tissue engineering scaffold, beta-Tricalcium Phosphate (β-TCP), and to determine whether the USCs seeded onto β-TCP scaffold can promote bone regeneration in a segmental femoral defect of rats. Primary USCs were isolated from urine and seeded on β-TCP scaffolds. Results showed that USCs remained viable and proliferated within β-TCP. The osteogenic differentiation of USCs within the scaffolds was demonstrated by increased alkaline phosphatase activity and calcium content. Furthermore, β-TCP with adherent USCs (USCs/β-TCP) were implanted in a 6-mm critical size femoral defect of rats for 12 weeks. Bone regeneration was determined using X-ray, micro-CT, and histologic analyses. Results further demonstrated that USCs in the scaffolds could enhance new bone formation, which spanned bone defects in 5 out of 11 rats while β-TCP scaffold alone induced modest bone formation. The current study indicated that the USCs can be used as a cell source for bone tissue engineering as they are compatible with bone tissue engineering scaffolds and can stimulate the regeneration of bone in a critical size bone defect.

Novel surgical techniques, regenerative medicine, tissue engineering and innovative immunosuppression in kidney transplantation.

PubMed

Nowacki, Maciej; Nazarewski, Łukasz; Kloskowski, Tomasz; Tyloch, Dominik; Pokrywczyńska, Marta; Pietkun, Katarzyna; Jundziłł, Arkadiusz; Tyloch, Janusz; Habib, Samy L; Drewa, Tomasz

2016-10-01

On the 60 th anniversary of the first successfully performed renal transplantation, we summarize the historical, current and potential future status of kidney transplantation. We discuss three different aspects with a potential significant influence on kidney transplantation progress: the development of surgical techniques, the influence of regenerative medicine and tissue engineering, and changes in immunosuppression. We evaluate the standard open surgical procedures with modern techniques and compare them to less invasive videoscopic as well as robotic techniques. The role of tissue engineering and regenerative medicine as a potential method for future kidney regeneration or replacement and the interesting search for novel solutions in the field of immunosuppression will be discussed. After 60 years since the first successfully performed kidney transplantation, we can conclude that the greatest achievements are associated with the development of surgical techniques and with planned systemic immunosuppression.

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

PubMed

Benny, Paula; Raghunath, Michael

2017-01-01

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

Novel surgical techniques, regenerative medicine, tissue engineering and innovative immunosuppression in kidney transplantation

PubMed Central

Nowacki, Maciej; Nazarewski, Łukasz; Tyloch, Dominik; Pokrywczyńska, Marta; Pietkun, Katarzyna; Jundziłł, Arkadiusz; Tyloch, Janusz; Habib, Samy L.; Drewa, Tomasz

2016-01-01

On the 60th anniversary of the first successfully performed renal transplantation, we summarize the historical, current and potential future status of kidney transplantation. We discuss three different aspects with a potential significant influence on kidney transplantation progress: the development of surgical techniques, the influence of regenerative medicine and tissue engineering, and changes in immunosuppression. We evaluate the standard open surgical procedures with modern techniques and compare them to less invasive videoscopic as well as robotic techniques. The role of tissue engineering and regenerative medicine as a potential method for future kidney regeneration or replacement and the interesting search for novel solutions in the field of immunosuppression will be discussed. After 60 years since the first successfully performed kidney transplantation, we can conclude that the greatest achievements are associated with the development of surgical techniques and with planned systemic immunosuppression. PMID:27695507

Matrices and scaffolds for drug delivery in dental, oral and craniofacial tissue engineering☆

PubMed Central

Moioli, Eduardo K.; Clark, Paul A.; Xin, Xuejun; Lal, Shan; Mao, Jeremy J.

2010-01-01

Current treatments for diseases and trauma of dental, oral and craniofacial (DOC) structures rely on durable materials such as amalgam and synthetic materials, or autologous tissue grafts. A paradigm shift has taken place to utilize tissue engineering and drug delivery approaches towards the regeneration of these structures. Several prototypes of DOC structures have been regenerated such as temporomandibular joint (TMJ) condyle, cranial sutures, tooth structures and periodontium components. However, many challenges remain when taking in consideration the high demand for esthetics of DOC structures, the complex environment and yet minimal scar formation in the oral cavity, and the need for accommodating multiple tissue phenotypes. This review highlights recent advances in the regeneration of DOC structures, including the tooth, periodontium, TMJ, cranial sutures and implant dentistry, with specific emphasis on controlled release of signaling cues for stem cells, biomaterial matrices and scaffolds, and integrated tissue engineering approaches. PMID:17499385

Regenerative endodontics: a state of the art.

PubMed

Bansal, Rashmi; Bansal, Rajesh

2011-01-01

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

Preclinical and clinical data for the use of mesenchymal stem cells in articular cartilage tissue engineering.

PubMed

Tang, Quen Oak; Carasco, Clare Francesca; Gamie, Zakareya; Korres, Nectarios; Mantalaris, Athanasios; Tsiridis, Eleftherios

2012-10-01

With an ageing population, the prevalence of osteoarthritis (OA) has increased. Mesenchymal Stem Cells (MSCs) have been proposed to be an attractive alternative candidate in the tissue engineering of articular cartilage primarily due to its abundant source, reduced cartilage donor site morbidity, and strong capacity for proliferation and potential to differentiate toward a chondrogenic phenotype. A current overview of human, in vivo, and in vitro evidence on the use of MSCs in cartilage tissue engineering. We demonstrate robust evidence that MSCs have the potential to regenerate articular cartilage. We also identify the complexity of designing a suitable preclinical model and the challenges in considering its clinical application such as type of MSC, scaffold, culture construct and the method by which growth factors are delivered. Of great interest is further characterization of the factors that may prevent MSC-derived chondrocytes to undergo premature hypertrophy and to understand what enables the terminal developmental pathway for permanent hyaline cartilage regeneration. Despite this, there is an abundance of evidence suggesting that MSCs are a desirable cell source and will have significant impact in tissue engineering of cartilage in the future.

Mandibular Tissue Engineering: Past, Present, Future.

PubMed

Konopnicki, Sandra; Troulis, Maria J

2015-12-01

Almost 2 decades ago, the senior author's (M.T.J.) first article was with our mentor, Dr Leonard B. Kaban, a review article titled "Distraction Osteogenesis: Past, Present, Future." In 1998, many thought it would be impossible to have a remotely activated, small, curvilinear distractor that could be placed using endoscopic techniques. Currently, a U.S. patent for a curvilinear automated device and endoscopic techniques for minimally invasive access for jaw reconstruction exist. With minimally invasive access for jaw reconstruction, the burden to decrease donor site morbidity has increased. Distraction osteogenesis (DO) is an in vivo form of tissue engineering. The DO technique eliminates a donor site, is less invasive, requires a shorter operative time than usual procedures, and can be used for multiple reconstruction applications. Tissue engineering could further reduce morbidity and cost and increase treatment availability. The purpose of the present report was to review our experience with tissue engineering of bone: the past, present, and our vision for the future. The present report serves as a tribute to our mentor and acknowledges Dr Kaban for his incessant tutelage, guidance, wisdom, and boundless vision. Copyright © 2015 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Organ Bioprinting: Are We There Yet?

PubMed

Gao, Guifang; Huang, Ying; Schilling, Arndt F; Hubbell, Karen; Cui, Xiaofeng

2018-01-01

About 15 years ago, bioprinting was coined as one of the ultimate solutions to engineer vascularized tissues, which was impossible to accomplish using the conventional tissue fabrication approaches. With the advances of 3D-printing technology during the past decades, one may expect 3D bioprinting being developed as much as 3D printing. Unfortunately, this is not the case. The printing principles of bioprinting are dramatically different from those applied in industrialized 3D printing, as they have to take the living components into account. While the conventional 3D-printing technologies are actually applied for biological or biomedical applications, true 3D bioprinting involving direct printing of cells and other biological substances for tissue reconstruction is still in its infancy. In this progress report, the current status of bioprinting in academia and industry is subjectively evaluated. The progress made is acknowledged, and the existing bottlenecks in bioprinting are discussed. Recent breakthroughs from a variety of associated fields, including mechanical engineering, robotic engineering, computing engineering, chemistry, material science, cellular biology, molecular biology, system control, and medicine may overcome some of these current bottlenecks. For this to happen, a convergence of these areas into a systemic research area "3D bioprinting" is needed to develop bioprinting as a viable approach for creating fully functional organs for standard clinical diagnosis and treatment including transplantation. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

PubMed

Lott, David G

2014-10-01

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

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

PubMed

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

2015-02-01

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

Long-Term Morphological and Microarchitectural Stability of Tissue-Engineered, Patient-Specific Auricles In Vivo

PubMed Central

Cohen, Benjamin Peter; Hooper, Rachel C.; Puetzer, Jennifer L.; Nordberg, Rachel; Asanbe, Ope; Hernandez, Karina A.; Spector, Jason A.

2016-01-01

Current techniques for autologous auricular reconstruction produce substandard ear morphologies with high levels of donor-site morbidity, whereas alloplastic implants demonstrate poor biocompatibility. Tissue engineering, in combination with noninvasive digital photogrammetry and computer-assisted design/computer-aided manufacturing technology, offers an alternative method of auricular reconstruction. Using this method, patient-specific ears composed of collagen scaffolds and auricular chondrocytes have generated auricular cartilage with great fidelity following 3 months of subcutaneous implantation, however, this short time frame may not portend long-term tissue stability. We hypothesized that constructs developed using this technique would undergo continued auricular cartilage maturation without degradation during long-term (6 month) implantation. Full-sized, juvenile human ear constructs were injection molded from high-density collagen hydrogels encapsulating juvenile bovine auricular chondrocytes and implanted subcutaneously on the backs of nude rats for 6 months. Upon explantation, constructs retained overall patient morphology and displayed no evidence of tissue necrosis. Limited contraction occurred in vivo, however, no significant change in size was observed beyond 1 month. Constructs at 6 months showed distinct auricular cartilage microstructure, featuring a self-assembled perichondrial layer, a proteoglycan-rich bulk, and rounded cellular lacunae. Verhoeff's staining also revealed a developing elastin network comparable to native tissue. Biochemical measurements for DNA, glycosaminoglycan, and hydroxyproline content and mechanical properties of aggregate modulus and hydraulic permeability showed engineered tissue to be similar to native cartilage at 6 months. Patient-specific auricular constructs demonstrated long-term stability and increased cartilage tissue development during extended implantation, and offer a potential tissue-engineered solution for the future of auricular reconstructions. PMID:26847742

Current and emerging applications of 3D printing in medicine.

PubMed

Liaw, Chya-Yan; Guvendiren, Murat

2017-06-07

Three-dimensional (3D) printing enables the production of anatomically matched and patient-specific devices and constructs with high tunability and complexity. It also allows on-demand fabrication with high productivity in a cost-effective manner. As a result, 3D printing has become a leading manufacturing technique in healthcare and medicine for a wide range of applications including dentistry, tissue engineering and regenerative medicine, engineered tissue models, medical devices, anatomical models and drug formulation. Today, 3D printing is widely adopted by the healthcare industry and academia. It provides commercially available medical products and a platform for emerging research areas including tissue and organ printing. In this review, our goal is to discuss the current and emerging applications of 3D printing in medicine. A brief summary on additive manufacturing technologies and available printable materials is also given. The technological and regulatory barriers that are slowing down the full implementation of 3D printing in the medical field are also discussed.

Repair and tissue engineering techniques for articular cartilage

PubMed Central

Makris, Eleftherios A.; Gomoll, Andreas H.; Malizos, Konstantinos N.; Hu, Jerry C.; Athanasiou, Kyriacos A.

2015-01-01

Chondral and osteochondral lesions due to injury or other pathology commonly result in the development of osteoarthritis, eventually leading to progressive total joint destruction. Although current progress suggests that biologic agents can delay the advancement of deterioration, such drugs are incapable of promoting tissue restoration. The limited ability of articular cartilage to regenerate renders joint arthroplasty an unavoidable surgical intervention. This Review describes current, widely used clinical repair techniques for resurfacing articular cartilage defects; short-term and long-term clinical outcomes of these techniques are discussed. Also reviewed is a developmental pipeline of regenerative biological products that over the next decade could revolutionize joint care by functionally healing articular cartilage. These products include cell-based and cell-free materials such as autologous and allogeneic cell-based approaches and multipotent and pluripotent stem-cell-based techniques. Central to these efforts is the prominent role that tissue engineering has in translating biological technology into clinical products; therefore, concomitant regulatory processes are also discussed. PMID:25247412

Repair and tissue engineering techniques for articular cartilage.

PubMed

Makris, Eleftherios A; Gomoll, Andreas H; Malizos, Konstantinos N; Hu, Jerry C; Athanasiou, Kyriacos A

2015-01-01

Chondral and osteochondral lesions due to injury or other pathology commonly result in the development of osteoarthritis, eventually leading to progressive total joint destruction. Although current progress suggests that biologic agents can delay the advancement of deterioration, such drugs are incapable of promoting tissue restoration. The limited ability of articular cartilage to regenerate renders joint arthroplasty an unavoidable surgical intervention. This Review describes current, widely used clinical repair techniques for resurfacing articular cartilage defects; short-term and long-term clinical outcomes of these techniques are discussed. Also reviewed is a developmental pipeline of acellular and cellular regenerative products and techniques that could revolutionize joint care over the next decade by promoting the development of functional articular cartilage. Acellular products typically consist of collagen or hyaluronic-acid-based materials, whereas cellular techniques use either primary cells or stem cells, with or without scaffolds. Central to these efforts is the prominent role that tissue engineering has in translating biological technology into clinical products; therefore, concomitant regulatory processes are also discussed.

Electrospinning of Chitosan-Based Solutions for Tissue Engineering and Regenerative Medicine

PubMed Central

Qasim, Saad B.; Khurshid, Zohaib; Shah, Altaf H.; Husain, Shehriar; Rehman, Ihtesham Ur

2018-01-01

Electrospinning has been used for decades to generate nano-fibres via an electrically charged jet of polymer solution. This process is established on a spinning technique, using electrostatic forces to produce fine fibres from polymer solutions. Amongst, the electrospinning of available biopolymers (silk, cellulose, collagen, gelatine and hyaluronic acid), chitosan (CH) has shown a favourable outcome for tissue regeneration applications. The aim of the current review is to assess the current literature about electrospinning chitosan and its composite formulations for creating fibres in combination with other natural polymers to be employed in tissue engineering. In addition, various polymers blended with chitosan for electrospinning have been discussed in terms of their potential biomedical applications. The review shows that evidence exists in support of the favourable properties and biocompatibility of chitosan electrospun composite biomaterials for a range of applications. However, further research and in vivo studies are required to translate these materials from the laboratory to clinical applications. PMID:29385727

Stem cell technology for tendon regeneration: current status, challenges, and future research directions

PubMed Central

Lui, Pauline Po Yee

2015-01-01

Tendon injuries are a common cause of physical disability. They present a clinical challenge to orthopedic surgeons because injured tendons respond poorly to current treatments without tissue regeneration and the time required for rehabilitation is long. New treatment options are required. Stem cell-based therapies offer great potential to promote tendon regeneration due to their high proliferative, synthetic, and immunomodulatory activities as well as their potential to differentiate to the target cell types and undergo genetic modification. In this review, I first recapped the challenges of tendon repair by reviewing the anatomy of tendon. Next, I discussed the advantages and limitations of using different types of stem cells compared to terminally differentiated cells for tendon tissue engineering. The safety and efficacy of application of stem cells and their modified counterparts for tendon tissue engineering were then summarized after a systematic literature search in PubMed. The challenges and future research directions to enhance, optimize, and standardize stem cell-based therapies for augmenting tendon repair were then discussed. PMID:26715856

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

PubMed

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

2014-02-28

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

An overview of inverted colloidal crystal systems for tissue engineering.

PubMed

João, Carlos Filipe C; Vasconcelos, Joana Marta; Silva, Jorge Carvalho; Borges, João Paulo

2014-10-01

Scaffolding is at the heart of tissue engineering but the number of techniques available for turning biomaterials into scaffolds displaying the features required for a tissue engineering application is somewhat limited. Inverted colloidal crystals (ICCs) are inverse replicas of an ordered array of monodisperse colloidal particles, which organize themselves in packed long-range crystals. The literature on ICC systems has grown enormously in the past 20 years, driven by the need to find organized macroporous structures. Although replicating the structure of packed colloidal crystals (CCs) into solid structures has produced a wide range of advanced materials (e.g., photonic crystals, catalysts, and membranes) only in recent years have ICCs been evaluated as devices for medical/pharmaceutical and tissue engineering applications. The geometry, size, pore density, and interconnectivity are features of the scaffold that strongly affect the cell environment with consequences on cell adhesion, proliferation, and differentiation. ICC scaffolds are highly geometrically ordered structures with increased porosity and connectivity, which enhances oxygen and nutrient diffusion, providing optimum cellular development. In comparison to other types of scaffolds, ICCs have three major unique features: the isotropic three-dimensional environment, comprising highly uniform and size-controllable pores, and the presence of windows connecting adjacent pores. Thus far, this is the only technique that guarantees these features with a long-range order, between a few nanometers and thousands of micrometers. In this review, we present the current development status of ICC scaffolds for tissue engineering applications.

Nanotechnology in Drug Delivery and Tissue Engineering: From Discovery to Applications

PubMed Central

Shi, Jinjun; Votruba, Alexander R.; Farokhzad, Omid C.; Langer, Robert

2010-01-01

The application of nanotechnology in medicine, referred to as nanomedicine, is offering numerous exciting possibilities in healthcare. Herein, we discuss two important aspects of nanomedicine—drug delivery and tissue engineering—highlighting the advances we have recently experienced, the challenges we are currently facing, and what we are likely to witness in the near future. PMID:20726522

Enhanced Intracellular Delivery and Tissue Retention of Nanoparticles by Mussel-Inspired Surface Chemistry.

PubMed

Chen, Kai; Xu, Xiaoqiu; Guo, Jiawei; Zhang, Xuelin; Han, Songling; Wang, Ruibing; Li, Xiaohui; Zhang, Jianxiang

2015-11-09

Nanomaterials have been broadly studied for intracellular delivery of diverse compounds for diagnosis or therapy. Currently it remains challenging for discovering new biomolecules that can prominently enhance cellular internalization and tissue retention of nanoparticles (NPs). Herein we report for the first time that a mussel-inspired engineering approach may notably promote cellular uptake and tissue retention of NPs. In this strategy, the catechol moiety is covalently anchored onto biodegradable NPs. Thus, fabricated NPs can be more effectively internalized by sensitive and multidrug resistant tumor cells, as well as some normal cells, resulting in remarkably potentiated in vitro activity when an antitumor drug is packaged. Moreover, the newly engineered NPs afford increased tissue retention post local or oral delivery. This biomimetic approach is promising for creating functional nanomaterials for drug delivery, vaccination, and cell therapy.

Crosslinkable hydrogels derived from cartilage, meniscus, and tendon tissue.

PubMed

Visser, Jetze; Levett, Peter A; te Moller, Nikae C R; Besems, Jeremy; Boere, Kristel W M; van Rijen, Mattie H P; de Grauw, Janny C; Dhert, Wouter J A; van Weeren, P René; Malda, Jos

2015-04-01

Decellularized tissues have proven to be versatile matrices for the engineering of tissues and organs. These matrices usually consist of collagens, matrix-specific proteins, and a set of largely undefined growth factors and signaling molecules. Although several decellularized tissues have found their way to clinical applications, their use in the engineering of cartilage tissue has only been explored to a limited extent. We set out to generate hydrogels from several tissue-derived matrices, as hydrogels are the current preferred cell carriers for cartilage repair. Equine cartilage, meniscus, and tendon tissue was harvested, decellularized, enzymatically digested, and functionalized with methacrylamide groups. After photo-cross-linking, these tissue digests were mechanically characterized. Next, gelatin methacrylamide (GelMA) hydrogel was functionalized with these methacrylated tissue digests. Equine chondrocytes and mesenchymal stromal cells (MSCs) (both from three donors) were encapsulated and cultured in vitro up to 6 weeks. Gene expression (COL1A1, COL2A1, ACAN, MMP-3, MMP-13, and MMP-14), cartilage-specific matrix formation, and hydrogel stiffness were analyzed after culture. The cartilage, meniscus, and tendon digests were successfully photo-cross-linked into hydrogels. The addition of the tissue-derived matrices to GelMA affected chondrogenic differentiation of MSCs, although no consequent improvement was demonstrated. For chondrocytes, the tissue-derived matrix gels performed worse compared to GelMA alone. This work demonstrates for the first time that native tissues can be processed into crosslinkable hydrogels for the engineering of tissues. Moreover, the differentiation of encapsulated cells can be influenced in these stable, decellularized matrix hydrogels.

Tissue Engineering Approaches in the Design of Healthy and Pathological In Vitro Tissue Models

PubMed Central

Caddeo, Silvia; Boffito, Monica; Sartori, Susanna

2017-01-01

In the tissue engineering (TE) paradigm, engineering and life sciences tools are combined to develop bioartificial substitutes for organs and tissues, which can in turn be applied in regenerative medicine, pharmaceutical, diagnostic, and basic research to elucidate fundamental aspects of cell functions in vivo or to identify mechanisms involved in aging processes and disease onset and progression. The complex three-dimensional (3D) microenvironment in which cells are organized in vivo allows the interaction between different cell types and between cells and the extracellular matrix, the composition of which varies as a function of the tissue, the degree of maturation, and health conditions. In this context, 3D in vitro models can more realistically reproduce a tissue or organ than two-dimensional (2D) models. Moreover, they can overcome the limitations of animal models and reduce the need for in vivo tests, according to the “3Rs” guiding principles for a more ethical research. The design of 3D engineered tissue models is currently in its development stage, showing high potential in overcoming the limitations of already available models. However, many issues are still opened, concerning the identification of the optimal scaffold-forming materials, cell source and biofabrication technology, and the best cell culture conditions (biochemical and physical cues) to finely replicate the native tissue and the surrounding environment. In the near future, 3D tissue-engineered models are expected to become useful tools in the preliminary testing and screening of drugs and therapies and in the investigation of the molecular mechanisms underpinning disease onset and progression. In this review, the application of TE principles to the design of in vitro 3D models will be surveyed, with a focus on the strengths and weaknesses of this emerging approach. In addition, a brief overview on the development of in vitro models of healthy and pathological bone, heart, pancreas, and liver will be presented. PMID:28798911

Tissue Engineering Approaches in the Design of Healthy and Pathological In Vitro Tissue Models.

PubMed

Caddeo, Silvia; Boffito, Monica; Sartori, Susanna

2017-01-01

In the tissue engineering (TE) paradigm, engineering and life sciences tools are combined to develop bioartificial substitutes for organs and tissues, which can in turn be applied in regenerative medicine, pharmaceutical, diagnostic, and basic research to elucidate fundamental aspects of cell functions in vivo or to identify mechanisms involved in aging processes and disease onset and progression. The complex three-dimensional (3D) microenvironment in which cells are organized in vivo allows the interaction between different cell types and between cells and the extracellular matrix, the composition of which varies as a function of the tissue, the degree of maturation, and health conditions. In this context, 3D in vitro models can more realistically reproduce a tissue or organ than two-dimensional (2D) models. Moreover, they can overcome the limitations of animal models and reduce the need for in vivo tests, according to the "3Rs" guiding principles for a more ethical research. The design of 3D engineered tissue models is currently in its development stage, showing high potential in overcoming the limitations of already available models. However, many issues are still opened, concerning the identification of the optimal scaffold-forming materials, cell source and biofabrication technology, and the best cell culture conditions (biochemical and physical cues) to finely replicate the native tissue and the surrounding environment. In the near future, 3D tissue-engineered models are expected to become useful tools in the preliminary testing and screening of drugs and therapies and in the investigation of the molecular mechanisms underpinning disease onset and progression. In this review, the application of TE principles to the design of in vitro 3D models will be surveyed, with a focus on the strengths and weaknesses of this emerging approach. In addition, a brief overview on the development of in vitro models of healthy and pathological bone, heart, pancreas, and liver will be presented.

Multiscale Characterization of Engineered Cardiac Tissue Architecture.

PubMed

Drew, Nancy K; Johnsen, Nicholas E; Core, Jason Q; Grosberg, Anna

2016-11-01

In a properly contracting cardiac muscle, many different subcellular structures are organized into an intricate architecture. While it has been observed that this organization is altered in pathological conditions, the relationship between length-scales and architecture has not been properly explored. In this work, we utilize a variety of architecture metrics to quantify organization and consistency of single structures over multiple scales, from subcellular to tissue scale as well as correlation of organization of multiple structures. Specifically, as the best way to characterize cardiac tissues, we chose the orientational and co-orientational order parameters (COOPs). Similarly, neonatal rat ventricular myocytes were selected for their consistent architectural behavior. The engineered cells and tissues were stained for four architectural structures: actin, tubulin, sarcomeric z-lines, and nuclei. We applied the orientational metrics to cardiac cells of various shapes, isotropic cardiac tissues, and anisotropic globally aligned tissues. With these novel tools, we discovered: (1) the relationship between cellular shape and consistency of self-assembly; (2) the length-scales at which unguided tissues self-organize; and (3) the correlation or lack thereof between organization of actin fibrils, sarcomeric z-lines, tubulin fibrils, and nuclei. All of these together elucidate some of the current mysteries in the relationship between force production and architecture, while raising more questions about the effect of guidance cues on self-assembly function. These types of metrics are the future of quantitative tissue engineering in cardiovascular biomechanics.

Three-Dimensional Optical Mapping of Nanoparticle Distribution in Intact Tissues.

PubMed

Sindhwani, Shrey; Syed, Abdullah Muhammad; Wilhelm, Stefan; Glancy, Dylan R; Chen, Yih Yang; Dobosz, Michael; Chan, Warren C W

2016-05-24

The role of tissue architecture in mediating nanoparticle transport, targeting, and biological effects is unknown due to the lack of tools for imaging nanomaterials in whole organs. Here, we developed a rapid optical mapping technique to image nanomaterials in intact organs ex vivo and in three-dimensions (3D). We engineered a high-throughput electrophoretic flow device to simultaneously transform up to 48 tissues into optically transparent structures, allowing subcellular imaging of nanomaterials more than 1 mm deep into tissues which is 25-fold greater than current techniques. A key finding is that nanomaterials can be retained in the processed tissue by chemical cross-linking of surface adsorbed serum proteins to the tissue matrix, which enables nanomaterials to be imaged with respect to cells, blood vessels, and other structures. We developed a computational algorithm to analyze and quantitatively map nanomaterial distribution. This method can be universally applied to visualize the distribution and interactions of materials in whole tissues and animals including such applications as the imaging of nanomaterials, tissue engineered constructs, and biosensors within their intact biological environment.

Methods for Incorporating Oxygen-Generating Biomaterials into Cell Culture and Microcapsule Systems.

PubMed

McQuilling, John Patrick; Opara, Emmanuel C

2017-01-01

A major obstacle to long-term performance of tissue construct implants in regenerative medicine is the inherent hypoxia to which cells in the engineered construct are exposed prior to vascularization of the implant. Various approaches are currently being designed to address this problem. An emerging area of interest on this issue is the use of peroxide-based materials to generate oxygen during the critical period of extended hypoxia that occurs from the time cells are in culture waiting to be used in tissue engineering devices through the immediate post-implant period. In this chapter we provide protocols that we have developed for using these chemical oxygen generators in cell culture and tissue constructs as illustrated by pancreatic islet cell microencapsulation.

In vitro corrosion and cytocompatibility properties of nano-whisker hydroxyapatite coating on magnesium alloy for bone tissue engineering applications.

PubMed

Yang, Huawei; Yan, Xueyu; Ling, Min; Xiong, Zuquan; Ou, Caiwen; Lu, Wei

2015-03-17

We report here the successful fabrication of nano-whisker hydroxyapatite (nHA) coatings on Mg alloy by using a simple one-step hydrothermal process in aqueous solution. The nHA coating shows uniform structure and high crystallinity. Results indicate that nHA coating is promising for improving the in vitro corrosion and cytocompatibility properties of Mg-based implants and devices for bone tissue engineering. In addition, the simple hydrothermal deposition method used in the current study is also applicable to substrates with complex shapes or surface geometries.

A Review of Cellularization Strategies for Tissue Engineering of Whole Organs

PubMed Central

Scarritt, Michelle E.; Pashos, Nicholas C.; Bunnell, Bruce A.

2015-01-01

With the advent of whole organ decellularization, extracellular matrix scaffolds suitable for organ engineering were generated from numerous tissues, including the heart, lung, liver, kidney, and pancreas, for use as alternatives to traditional organ transplantation. Biomedical researchers now face the challenge of adequately and efficiently recellularizing these organ scaffolds. Herein, an overview of whole organ decellularization and a thorough review of the current literature for whole organ recellularization are presented. The cell types, delivery methods, and bioreactors employed for recellularization are discussed along with commercial and clinical considerations, such as immunogenicity, biocompatibility, and Food and Drug Administartion regulation. PMID:25870857

In Vitro Corrosion and Cytocompatibility Properties of Nano-Whisker Hydroxyapatite Coating on Magnesium Alloy for Bone Tissue Engineering Applications

PubMed Central

Yang, Huawei; Yan, Xueyu; Ling, Min; Xiong, Zuquan; Ou, Caiwen; Lu, Wei

2015-01-01

We report here the successful fabrication of nano-whisker hydroxyapatite (nHA) coatings on Mg alloy by using a simple one-step hydrothermal process in aqueous solution. The nHA coating shows uniform structure and high crystallinity. Results indicate that nHA coating is promising for improving the in vitro corrosion and cytocompatibility properties of Mg-based implants and devices for bone tissue engineering. In addition, the simple hydrothermal deposition method used in the current study is also applicable to substrates with complex shapes or surface geometries. PMID:25789500

Printing of Three-Dimensional Tissue Analogs for Regenerative Medicine

PubMed Central

Lee, Vivian K.; Dai, Guohao

2016-01-01

3-D cell printing, which can accurately deposit cells, biomaterial scaffolds and growth factors in precisely defined spatial patterns to form biomimetic tissue structures, has emerged as a powerful enabling technology to create live tissue and organ structures for drug discovery and tissue engineering applications. Unlike traditional 3-D printing that uses metals, plastics and polymers as the printing materials, cell printing has to be compatible with living cells and biological matrix. It is also required that the printing process preserves the biological functions of the cells and extracellular matrix, and to mimic the cell-matrix architectures and mechanical properties of the native tissues. Therefore, there are significant challenges in order to translate the technologies of traditional 3-D printing to cell printing, and ultimately achieve functional outcomes in the printed tissues. So it is essential to develop new technologies specially designed for cell printing and in-depth basic research in the bioprinted tissues, such as developing novel biomaterials specifically for cell printing applications, understanding the complex cell-matrix remodeling for the desired mechanical properties and functional outcomes, establishing proper vascular perfusion in bioprinted tissues, etc. In recent years, many exciting research progresses have been made in the 3-D cell printing technology and its application in engineering live tissue constructs. This review paper summarized the current development in 3-D cell printing technologies; focus on the outcomes of the live printed tissues and their potential applications in drug discovery and regenerative medicine. Current challenges and limitations are highlighted, and future directions of 3-D cell printing technology are also discussed. PMID:27066784

Systematic Review to Compare Urothelium Differentiation with Urethral Epithelium Differentiation in Fetal Development, as a Basis for Tissue Engineering of the Male Urethra.

PubMed

de Graaf, Petra; van der Linde, E Martine; Rosier, Peter F W M; Izeta, Ander; Sievert, Karl-Dietrich; Bosch, J L H Ruud; de Kort, Laetitia M O

2017-06-01

Tissue-engineered (TE) urethra is desirable in men with urethral disease (stricture or hypospadias) and shortage of local tissue. Although ideally a TE graft would contain urethral epithelium cells, currently, bladder epithelium (urothelium) is widely used, but morphologically different. Understanding the differences and similarities of urothelium and urethral epithelium could help design a protocol for in vitro generation of urethral epithelium to be used in TE grafts for the urethra. To understand the development toward urethral epithelium or urothelium to improve TE of the urethra. A literature search was done following PRISMA guidelines. Articles describing urethral epithelium and bladder urothelium development in laboratory animals and humans were selected. Twenty-nine studies on development of urethral epithelium and 29 studies on development of urothelium were included. Both tissue linings derive from endoderm and although adult urothelium and urethral epithelium are characterized by different gene expression profiles, the signaling pathways underlying their development are similar, including Shh, BMP, Wnt, and FGF. The progenitor of the urothelium and the urethral epithelium is the early fetal urogenital sinus (UGS). The urethral plate and the urothelium are both formed from the p63+ cells of the UGS. Keratin 20 and uroplakins are exclusively expressed in urothelium, not in the urethral epithelium. Further research has to be done on unique markers for the urethral epithelium. This review has summarized the current knowledge about embryonic development of urothelium versus urethral epithelium and especially focuses on the influencing factors that are potentially specific for the eventual morphological differences of both cell linings, to be a basis for developmental or tissue engineering of urethral tissue.

[Reconstruction of penile function with tissue engineering techniques].

PubMed

Song, Lu-jie; Pan, Lian-jun; Xu, Yue-min

2007-04-01

Tissue engineering techniques, with their potential applied value for penile reconstruction, are of special interest for andrologists. The purpose of this review is to appraise the recent development and publications in this field. In the past few years, great efforts have been made to develop corpus cavernosum tissues by combining smooth muscle and endothelial cells seeded on biodegradable polyglycolic acid polymer (PGA) or acellular corporal collagen matrices scaffolds. Animal experiment demonstrated that the engineered corpus cavernosum achieved adequate structural and functional parameters. Engineered cartilage rods as an alternative for the current clinical standard of semirigid or inflatable penile implants could be created by seeding chondrocyte cylindrical PGA. A series of studies showed that, compared to commercially available silicone implants, the engineered rods were flexible, elastic and stable. Besides, a variety of decellularized biological materials have been used as grafts not only for substitution of tunica albuginea but also for penile enhancement, with promising results. For treating erectile dysfunction, a new approach to recovering erectile function by cell-based therapy could be the injection of functional cells into corpus cavernosum, which seemed to be promising when combined with cell manipulation by gene therapy prior to cell transfer.

Recent advancements in carbon nanofiber and carbon nanotube applications in drug delivery and tissue engineering.

PubMed

Stout, David A

2015-01-01

Since the discovery and synthesis of carbon nanotubes (CNTs) and carbon nanofibers (CNFs) over a decade ago, researchers have envisioned and discovered new potential applications for these materials. CNTs and CNFs have rapidly become a platform technology for a variety of uses, including biomedical applications due to their mechanical, electrical, thermal, optical and structural properties. CNTs and CNFs are also advantageous due to their ability to be produced in many different shapes and sizes. Since their discovery, of the many imaginable applications, CNTs and CNFs have gained a significant amount of attention and therapeutic potential in tissue engineering and drug delivery applications. In recent years, CNTs and CNFs have made significant contributions in designing new strategies for, delivery of pharmaceuticals, genes and molecular probes into cells, stem cell therapies and assisting in tissue regeneration. Furthermore, it is widely expressed that these materials will significantly contribute to the next generation of health care technologies in treating diseases and contributing to tissue growth. Hence, this review seeks to explore the recent advancements, current status and limitations of CNTs and CNFs for drug delivery and tissue engineering applications.

Applications of Microscale Technologies for Regenerative Dentistry

PubMed Central

Hacking, S.A.; Khademhosseini, A.

2009-01-01

While widespread advances in tissue engineering have occurred over the past decade, many challenges remain in the context of tissue engineering and regeneration of the tooth. For example, although tooth development is the result of repeated temporal and spatial interactions between cells of ectoderm and mesoderm origin, most current tooth engineering systems cannot recreate such developmental processes. In this regard, microscale approaches that spatially pattern and support the development of different cell types in close proximity can be used to regulate the cellular microenvironment and, as such, are promising approaches for tooth development. Microscale technologies also present alternatives to conventional tissue engineering approaches in terms of scaffolds and the ability to direct stem cells. Furthermore, microscale techniques can be used to miniaturize many in vitro techniques and to facilitate high-throughput experimentation. In this review, we discuss the emerging microscale technologies for the in vitro evaluation of dental cells, dental tissue engineering, and tooth regeneration. Abbreviations: AS, adult stem cell; BMP, bone morphogenic protein; ECM, extracellular matrix; ES, embryonic stem cell; HA, hydroxyapatite; FGF-2, fibroblast growth factor; iPS, inducible pleuripotent stem cell; IGF-1, insulin-like growth factor; PDGF, platelet-derived growth factor; PDMS, poly(dimethylsiloxane); PGA, polyglycolate; PGS, polyglycerol sebacate; PLGA, poly-L-lactate-co-glycolate; PLL, poly-L-lactate; RGD, Arg-Gly-Asp attachment site; TCP, tricalcium phosphate; TGF-β, transforming growth factor beta; and VEGF, vascular endothelial growth factor. PMID:19493883

Geometric modeling of space-optimal unit-cell-based tissue engineering scaffolds

NASA Astrophysics Data System (ADS)

Rajagopalan, Srinivasan; Lu, Lichun; Yaszemski, Michael J.; Robb, Richard A.

2005-04-01

Tissue engineering involves regenerating damaged or malfunctioning organs using cells, biomolecules, and synthetic or natural scaffolds. Based on their intended roles, scaffolds can be injected as space-fillers or be preformed and implanted to provide mechanical support. Preformed scaffolds are biomimetic "trellis-like" structures which, on implantation and integration, act as tissue/organ surrogates. Customized, computer controlled, and reproducible preformed scaffolds can be fabricated using Computer Aided Design (CAD) techniques and rapid prototyping devices. A curved, monolithic construct with minimal surface area constitutes an efficient substrate geometry that promotes cell attachment, migration and proliferation. However, current CAD approaches do not provide such a biomorphic construct. We address this critical issue by presenting one of the very first physical realizations of minimal surfaces towards the construction of efficient unit-cell based tissue engineering scaffolds. Mask programmability, and optimal packing density of triply periodic minimal surfaces are used to construct the optimal pore geometry. Budgeted polygonization, and progressive minimal surface refinement facilitate the machinability of these surfaces. The efficient stress distributions, as deduced from the Finite Element simulations, favor the use of these scaffolds for orthopedic applications.

3D printing for clinical application in otorhinolaryngology.

PubMed

Zhong, Nongping; Zhao, Xia

2017-12-01

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

On the nature of biomaterials.

PubMed

Williams, David F

2009-10-01

The situations in which biomaterials are currently used are vastly different to those of just a decade ago. Although implantable medical devices are still immensely important, medical technologies now encompass a range of drug and gene delivery systems, tissue engineering and cell therapies, organ printing and cell patterning, nanotechnology based imaging and diagnostic systems and microelectronic devices. These technologies still encompass metals, ceramics and synthetic polymers, but also biopolymers, self assembled systems, nanoparticles, carbon nanotubes and quantum dots. These changes imply that our original concepts of biomaterials and our expectations of their performance also have to change. This Leading Opinion Paper addresses these issues. It concludes that many substances which hitherto we may not have thought of as biomaterials should now be considered as such so that, alongside the traditional structural biomaterials, we have substances that have been engineered to perform functions within health care where their performance is directly controlled by interactions with tissues and tissue components. These include engineered tissues, cells, organs and even viruses. This essay develops the arguments for a radically different definition of a biomaterial.

Implantation of In Vitro Tissue Engineered Muscle Repair Constructs and Bladder Acellular Matrices Partially Restore In Vivo Skeletal Muscle Function in a Rat Model of Volumetric Muscle Loss Injury

PubMed Central

Corona, Benjamin T.; Ward, Catherine L.; Baker, Hannah B.; Walters, Thomas J.

2014-01-01

The frank loss of a large volume of skeletal muscle (i.e., volumetric muscle loss [VML]) can lead to functional debilitation and presents a significant problem to civilian and military medicine. Current clinical treatment for VML involves the use of free muscle flaps and physical rehabilitation; however, neither are effective in promoting regeneration of skeletal muscle to replace the tissue that was lost. Toward this end, skeletal muscle tissue engineering therapies have recently shown great promise in offering an unprecedented treatment option for VML. In the current study, we further extend our recent progress (Machingal et al., 2011, Tissue Eng; Corona et al., 2012, Tissue Eng) in the development of tissue engineered muscle repair (TEMR) constructs (i.e., muscle-derived cells [MDCs] seeded on a bladder acellular matrix (BAM) preconditioned with uniaxial mechanical strain) for the treatment of VML. TEMR constructs were implanted into a VML defect in a tibialis anterior (TA) muscle of Lewis rats and observed up to 12 weeks postinjury. The salient findings of the study were (1) TEMR constructs exhibited a highly variable capacity to restore in vivo function of injured TA muscles, wherein TEMR-positive responders (n=6) promoted an ≈61% improvement, but negative responders (n=7) resulted in no improvement compared to nonrepaired controls, (2) TEMR-positive and -negative responders exhibited differential immune responses that may underlie these variant responses, (3) BAM scaffolds (n=7) without cells promoted an ≈26% functional improvement compared to uninjured muscles, (4) TEMR-positive responders promoted muscle fiber regeneration within the initial defect area, while BAM scaffolds did so only sparingly. These findings indicate that TEMR constructs can improve the in vivo functional capacity of the injured musculature at least, in part, by promoting generation of functional skeletal muscle fibers. In short, the degree of functional recovery observed following TEMR implantation (BAM+MDCs) was 2.3×-fold greater than that observed following implantation of BAM alone. As such, this finding further underscores the potential benefits of including a cellular component in the tissue engineering strategy for VML injury. PMID:24066899

Automated and Adaptable Quantification of Cellular Alignment from Microscopic Images for Tissue Engineering Applications

PubMed Central

Xu, Feng; Beyazoglu, Turker; Hefner, Evan; Gurkan, Umut Atakan

2011-01-01

Cellular alignment plays a critical role in functional, physical, and biological characteristics of many tissue types, such as muscle, tendon, nerve, and cornea. Current efforts toward regeneration of these tissues include replicating the cellular microenvironment by developing biomaterials that facilitate cellular alignment. To assess the functional effectiveness of the engineered microenvironments, one essential criterion is quantification of cellular alignment. Therefore, there is a need for rapid, accurate, and adaptable methodologies to quantify cellular alignment for tissue engineering applications. To address this need, we developed an automated method, binarization-based extraction of alignment score (BEAS), to determine cell orientation distribution in a wide variety of microscopic images. This method combines a sequenced application of median and band-pass filters, locally adaptive thresholding approaches and image processing techniques. Cellular alignment score is obtained by applying a robust scoring algorithm to the orientation distribution. We validated the BEAS method by comparing the results with the existing approaches reported in literature (i.e., manual, radial fast Fourier transform-radial sum, and gradient based approaches). Validation results indicated that the BEAS method resulted in statistically comparable alignment scores with the manual method (coefficient of determination R2=0.92). Therefore, the BEAS method introduced in this study could enable accurate, convenient, and adaptable evaluation of engineered tissue constructs and biomaterials in terms of cellular alignment and organization. PMID:21370940

Development of an Indirect Stereolithography Technology for Scaffold Fabrication with a Wide Range of Biomaterial Selectivity

PubMed Central

Kang, Hyun-Wook

2012-01-01

Tissue engineering, which is the study of generating biological substitutes to restore or replace tissues or organs, has the potential to meet current needs for organ transplantation and medical interventions. Various approaches have been attempted to apply three-dimensional (3D) solid freeform fabrication technologies to tissue engineering for scaffold fabrication. Among these, the stereolithography (SL) technology not only has the highest resolution, but also offers quick fabrication. However, a lack of suitable biomaterials is a barrier to applying the SL technology to tissue engineering. In this study, an indirect SL method that combines the SL technology and a sacrificial molding process was developed to address this challenge. A sacrificial mold with an inverse porous shape was fabricated from an alkali-soluble photopolymer by the SL technology. A sacrificial molding process was then developed for scaffold construction using a variety of biomaterials. The results indicated a wide range of biomaterial selectivity and a high resolution. Achievable minimum pore and strut sizes were as large as 50 and 65 μm, respectively. This technology can also be used to fabricate three-dimensional organ shapes, and combined with traditional fabrication methods to construct a new type of scaffold with a dual-pore size. Cytotoxicity tests, as well as nuclear magnetic resonance and gel permeation chromatography analyses, showed that this technology has great potential for tissue engineering applications. PMID:22443315

Tissue-Engineered Autologous Grafts for Facial Bone Reconstruction

PubMed Central

Bhumiratana, Sarindr; Bernhard, Jonathan C.; Alfi, David M.; Yeager, Keith; Eton, Ryan E.; Bova, Jonathan; Shah, Forum; Gimble, Jeffrey M.; Lopez, Mandi J.; Eisig, Sidney B.; Vunjak-Novakovic, Gordana

2016-01-01

Facial deformities require precise reconstruction of the appearance and function of the original tissue. The current standard of care—the use of bone harvested from another region in the body—has major limitations, including pain and comorbidities associated with surgery. We have engineered one of the most geometrically complex facial bones by using autologous stromal/stem cells, without bone morphogenic proteins, using native bovine bone matrix and a perfusion bioreactor for the growth and transport of living grafts. The ramus-condyle unit (RCU), the most eminent load-bearing bone in the skull, was reconstructed using an image-guided personalized approach in skeletally mature Yucatan minipigs (human-scale preclinical model). We used clinically approved decellularized bovine trabecular bone as a scaffolding material, and crafted it into an anatomically correct shape using image-guided micromilling, to fit the defect. Autologous adipose-derived stromal/stem cells were seeded into the scaffold and cultured in perfusion for 3 weeks in a specialized bioreactor to form immature bone tissue. Six months after implantation, the engineered grafts maintained their anatomical structure, integrated with native tissues, and generated greater volume of new bone and greater vascular infiltration than either non-seeded anatomical scaffolds or untreated defects. This translational study demonstrates feasibility of facial bone reconstruction using autologous, anatomically shaped, living grafts formed in vitro, and presents a platform for personalized bone tissue engineering. PMID:27306665

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

PubMed

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

2015-03-01

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

A tissue engineering approach for prenatal closure of myelomeningocele: comparison of gelatin sponge and microsphere scaffolds and bioactive protein coatings.

PubMed

Watanabe, Miho; Li, Hiaying; Roybal, Jessica; Santore, Matthew; Radu, Antonetta; Jo, Jun-Ichiro; Kaneko, Michio; Tabata, Yasuhiko; Flake, Alan

2011-04-01

Myelomeningocele (MMC) is a common and devastating malformation. As an alternative to fetal surgical repair, tissue engineering has the potential to provide a less invasive approach for tissue coverage applicable at an earlier stage of gestation. We have previously evaluated the use of gelatin hydrogel composites composed of gelatin sponges and sheets as a platform for tissue coverage of the MMC defect in the retinoic acid induced fetal rat model of MMC. In the current study, we compare our previous composite with gelatin microspheres as a scaffold for tissue ingrowth and cellular adhesion within the amniotic fluid environment. We also examine the relative efficacy of various bioactive protein coatings on the adhesion of amniotic fluid cells to the construct within the amniotic cavity. We conclude from this study that gelatin microspheres are as effective as gelatin sponges as a scaffold for cellular ingrowth and amniotic fluid cell adhesion and that collagen type I and fibronectin coatings enhance amniotic fluid cell adhesion to the gelatin-based scaffolds. These findings support the potential for the development of a tissue-engineered injectable scaffold that could be applied by ultrasound-guided injection, much earlier and less invasively than sponge or sheet-based composites.

A versatile modular bioreactor platform for Tissue Engineering.

PubMed

Schuerlein, Sebastian; Schwarz, Thomas; Krziminski, Steffan; Gätzner, Sabine; Hoppensack, Anke; Schwedhelm, Ivo; Schweinlin, Matthias; Walles, Heike; Hansmann, Jan

2017-02-01

Tissue Engineering (TE) bears potential to overcome the persistent shortage of donor organs in transplantation medicine. Additionally, TE products are applied as human test systems in pharmaceutical research to close the gap between animal testing and the administration of drugs to human subjects in clinical trials. However, generating a tissue requires complex culture conditions provided by bioreactors. Currently, the translation of TE technologies into clinical and industrial applications is limited due to a wide range of different tissue-specific, non-disposable bioreactor systems. To ensure a high level of standardization, a suitable cost-effectiveness, and a safe graft production, a generic modular bioreactor platform was developed. Functional modules provide robust control of culture processes, e.g. medium transport, gas exchange, heating, or trapping of floating air bubbles. Characterization revealed improved performance of the modules in comparison to traditional cell culture equipment such as incubators, or peristaltic pumps. By combining the modules, a broad range of culture conditions can be achieved. The novel bioreactor platform allows using disposable components and facilitates tissue culture in closed fluidic systems. By sustaining native carotid arteries, engineering a blood vessel, and generating intestinal tissue models according to a previously published protocol the feasibility and performance of the bioreactor platform was demonstrated. © 2017 The Authors. Biotechnology Journal published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Preparation and characterization of novel functionalized multiwalled carbon nanotubes/chitosan/β-Glycerophosphate scaffolds for bone tissue engineering.

PubMed

Gholizadeh, Shayan; Moztarzadeh, Fathollah; Haghighipour, Nooshin; Ghazizadeh, Leila; Baghbani, Fatemeh; Shokrgozar, Mohammad Ali; Allahyari, Zahra

2017-04-01

A major limitation in current tissue engineering scaffolds is that some of the most important characteristics of the intended tissue are ignored. As piezoelectricity and high mechanical strength are two of the most important characteristics of the bone tissue, carbon nanotubes are getting a lot of attention as a bone tissue scaffold component in recent years. In the present study, composite scaffolds comprised of functionalized Multiwalled Carbon Nanotubes (f-MWCNT), medium molecular weight chitosan and β-Glycerophosphate were fabricated and characterized. Biodegradability and mechanical tests indicate that while increasing f-MWCNT content can improve electrical conductivity and mechanical properties, there are some limitations for these increases, such as a decrease in mechanical properties and biodegradability in 1w/v% content of f-MWCNTs. Also, MTT cytotoxicity assay was conducted for the scaffolds and no significant cytotoxicity was observed. Increasing f-MWCNT content led to higher alkaline Phosphatase activity. The overall results show that composites with f-MWCNT content between 0.1w/v% and 0.5w/v% are the most suitable for bone tissue engineering application. Additionally, Preliminary cell electrical tests proved the efficiency of the prepared scaffolds for cell electrical applications. Copyright © 2017 Elsevier B.V. All rights reserved.

The Application of Ultrasound in 3D Bio-Printing.

PubMed

Zhou, Yufeng

2016-05-05

Three-dimensional (3D) bioprinting is an emerging and promising technology in tissue engineering to construct tissues and organs for implantation. Alignment of self-assembly cell spheroids that are used as bioink could be very accurate after droplet ejection from bioprinter. Complex and heterogeneous tissue structures could be built using rapid additive manufacture technology and multiple cell lines. Effective vascularization in the engineered tissue samples is critical in any clinical application. In this review paper, the current technologies and processing steps (such as printing, preparation of bioink, cross-linking, tissue fusion and maturation) in 3D bio-printing are introduced, and their specifications are compared with each other. In addition, the application of ultrasound in this novel field is also introduced. Cells experience acoustic radiation force in ultrasound standing wave field (USWF) and then accumulate at the pressure node at low acoustic pressure. Formation of cell spheroids by this method is within minutes with uniform size and homogeneous cell distribution. Neovessel formation from USWF-induced endothelial cell spheroids is significant. Low-intensity ultrasound could enhance the proliferation and differentiation of stem cells. Its use is at low cost and compatible with current bioreactor. In summary, ultrasound application in 3D bio-printing may solve some challenges and enhance the outcomes.

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

NASA Astrophysics Data System (ADS)

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

2018-02-01

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

Naturally Engineered Maturation of Cardiomyocytes

PubMed Central

Scuderi, Gaetano J.; Butcher, Jonathan

2017-01-01

Ischemic heart disease remains one of the most prominent causes of mortalities worldwide with heart transplantation being the gold-standard treatment option. However, due to the major limitations associated with heart transplants, such as an inadequate supply and heart rejection, there remains a significant clinical need for a viable cardiac regenerative therapy to restore native myocardial function. Over the course of the previous several decades, researchers have made prominent advances in the field of cardiac regeneration with the creation of in vitro human pluripotent stem cell-derived cardiomyocyte tissue engineered constructs. However, these engineered constructs exhibit a functionally immature, disorganized, fetal-like phenotype that is not equivalent physiologically to native adult cardiac tissue. Due to this major limitation, many recent studies have investigated approaches to improve pluripotent stem cell-derived cardiomyocyte maturation to close this large functionality gap between engineered and native cardiac tissue. This review integrates the natural developmental mechanisms of cardiomyocyte structural and functional maturation. The variety of ways researchers have attempted to improve cardiomyocyte maturation in vitro by mimicking natural development, known as natural engineering, is readily discussed. The main focus of this review involves the synergistic role of electrical and mechanical stimulation, extracellular matrix interactions, and non-cardiomyocyte interactions in facilitating cardiomyocyte maturation. Overall, even with these current natural engineering approaches, pluripotent stem cell-derived cardiomyocytes within three-dimensional engineered heart tissue still remain mostly within the early to late fetal stages of cardiomyocyte maturity. Therefore, although the end goal is to achieve adult phenotypic maturity, more emphasis must be placed on elucidating how the in vivo fetal microenvironment drives cardiomyocyte maturation. This information can then be utilized to develop natural engineering approaches that can emulate this fetal microenvironment and thus make prominent progress in pluripotent stem cell-derived maturity toward a more clinically relevant model for cardiac regeneration. PMID:28529939

The Hyaluronic Acid Fillers: Current Understanding of the Tissue Device Interface.

PubMed

Greene, Jacqueline J; Sidle, Douglas M

2015-11-01

The article is a detailed update regarding cosmetic injectable fillers, specifically focusing on hyaluronic acid fillers. Hyaluronic acid-injectable fillers are used extensively for soft tissue volumizing and contouring. Many different hyaluronic acid-injectable fillers are available on the market and differ in terms of hyaluronic acid concentration, particle size, cross-linking density, requisite needle size, duration, stiffness, hydration, presence of lidocaine, type of cross-linking technology, and cost. Hyaluronic acid is a natural component of many soft tissues, is identical across species minimizing immunogenicity has been linked to wound healing and skin regeneration, and is currently actively being studied for tissue engineering purposes. The biomechanical and biochemical effects of HA on the local microenvironment of the injected site are key to its success as a soft tissue filler. Knowledge of the tissue-device interface will help guide the facial practitioner and lead to optimal outcomes for patients. Copyright © 2015 Elsevier Inc. All rights reserved.

In vitro activation of the neuro-transduction mechanism in sensitive organotypic human skin model.

PubMed

Martorina, Francesca; Casale, Costantino; Urciuolo, Francesco; Netti, Paolo A; Imparato, Giorgia

2017-01-01

Recent advances in tissue engineering have encouraged researchers to endeavor the production of fully functional three-dimensional (3D) thick human tissues in vitro. Here, we report the fabrication of a fully innervated human skin tissue in vitro that recapitulates and replicates skin sensory function. Previous attempts to innervate in vitro 3D skin models did not demonstrate an effective functionality of the nerve network. In our approach, we initially engineer functional human skin tissue based on fibroblast-generated dermis and differentiated epidermis; then, we promote rat dorsal root ganglion (DRG) neurons axon ingrowth in the de-novo developed tissue. Neurofilaments network infiltrates the entire native dermis extracellular matrix (ECM), as demonstrated by immunofluorescence and second harmonic generation (SHG) imaging. To prove sensing functionality of the tissue, we use topical applications of capsaicin, an agonist of transient receptor protein-vanilloid 1 (TRPV1) channel, and quantify calcium currents resulting from variations of Ca ++ concentration in DRG neurons innervating our model. Calcium currents generation demonstrates functional cross-talking between dermis and epidermis compartments. Moreover, through a computational fluid dynamic (CFD) analysis, we set fluid dynamic conditions for a non-planar skin equivalent growth, as proof of potential application in creating skin grafts tailored on-demand for in vivo wound shape. Copyright © 2016 Elsevier Ltd. All rights reserved.

Icariin: does it have an osteoinductive potential for bone tissue engineering?

PubMed

Zhang, Xin; Liu, Tie; Huang, Yuanliang; Wismeijer, Daniel; Liu, Yuelian

2014-04-01

Traditional Chinese medicines have been recommended for bone regeneration and repair for thousands of years. Currently, the Herba Epimedii and its multi-component formulation are the attractive native herbs for the treatment of osteoporosis. Icariin, a typical flavonol glycoside, is considered to be the main active ingredient of the Herba Epimedii from which icariin has been successfully extracted. Most interestingly, it has been reported that icariin can be delivered locally by biomaterials and that it has an osteoinductive potential for bone tissue engineering. This review focuses on the performance of icariin in bone tissue engineering and on blending the information from icariin with the current knowledge relevant to molecular mechanisms and signal pathways. The osteoinductive potential of icariin could be attributed to its multiple functions in the musculoskeletal system which is involved in the regulation of multiple signaling pathways in anti-osteoporosis, osteogenesis, anti-osteoclastogenesis, chondrogenesis, angiogenesis, and anti-inflammation. The osteoinductive potential and the low price of icariin make it a very attractive candidate as a substitute of osteoinductive protein-bone morphogenetic proteins (BMPs), or as a promoter for enhancing the therapeutic effects of BMPs. However, the effectiveness of the local delivery of icariin needs to be investigated further. Copyright © 2013 John Wiley & Sons, Ltd.

Regenerative Engineering and Bionic Limbs.

PubMed

James, Roshan; Laurencin, Cato T

2015-03-01

Amputations of the upper extremity are severely debilitating, current treatments support very basic limb movement, and patients undergo extensive physiotherapy and psychological counselling. There is no prosthesis that allows the amputees near-normal function. With increasing number of amputees due to injuries sustained in accidents, natural calamities and international conflicts, there is a growing requirement for novel strategies and new discoveries. Advances have been made in technological, material and in prosthesis integration where researchers are now exploring artificial prosthesis that integrate with the residual tissues and function based on signal impulses received from the residual nerves. Efforts are focused on challenging experts in different disciplines to integrate ideas and technologies to allow for the regeneration of injured tissues, recording on tissue signals and feed-back to facilitate responsive movements and gradations of muscle force. A fully functional replacement and regenerative or integrated prosthesis will rely on interface of biological process with robotic systems to allow individual control of movement such as at the elbow, forearm, digits and thumb in the upper extremity. Regenerative engineering focused on the regeneration of complex tissue and organ systems will be realized by the cross-fertilization of advances over the past thirty years in the fields of tissue engineering, nanotechnology, stem cell science, and developmental biology. The convergence of toolboxes crated within each discipline will allow interdisciplinary teams from engineering, science, and medicine to realize new strategies, mergers of disparate technologies, such as biophysics, smart bionics, and the healing power of the mind. Tackling the clinical challenges, interfacing the biological process with bionic technologies, engineering biological control of the electronic systems, and feed-back will be the important goals in regenerative engineering over the next two decades.

Regenerative Engineering and Bionic Limbs

PubMed Central

James, Roshan; Laurencin, Cato T.

2015-01-01

Amputations of the upper extremity are severely debilitating, current treatments support very basic limb movement, and patients undergo extensive physiotherapy and psychological counselling. There is no prosthesis that allows the amputees near-normal function. With increasing number of amputees due to injuries sustained in accidents, natural calamities and international conflicts, there is a growing requirement for novel strategies and new discoveries. Advances have been made in technological, material and in prosthesis integration where researchers are now exploring artificial prosthesis that integrate with the residual tissues and function based on signal impulses received from the residual nerves. Efforts are focused on challenging experts in different disciplines to integrate ideas and technologies to allow for the regeneration of injured tissues, recording on tissue signals and feed-back to facilitate responsive movements and gradations of muscle force. A fully functional replacement and regenerative or integrated prosthesis will rely on interface of biological process with robotic systems to allow individual control of movement such as at the elbow, forearm, digits and thumb in the upper extremity. Regenerative engineering focused on the regeneration of complex tissue and organ systems will be realized by the cross-fertilization of advances over the past thirty years in the fields of tissue engineering, nanotechnology, stem cell science, and developmental biology. The convergence of toolboxes crated within each discipline will allow interdisciplinary teams from engineering, science, and medicine to realize new strategies, mergers of disparate technologies, such as biophysics, smart bionics, and the healing power of the mind. Tackling the clinical challenges, interfacing the biological process with bionic technologies, engineering biological control of the electronic systems, and feed-back will be the important goals in regenerative engineering over the next two decades. PMID:25983525

A Clinical, Biological, and Biomaterials Perspective into Tendon Injuries and Regeneration

PubMed Central

Walden, Grace; Liao, Xin; Donell, Simon; Raxworthy, Mike J.; Riley, Graham P.

2017-01-01

Tendon injury is common and debilitating, and it is associated with long-term pain and ineffective healing. It is estimated to afflict 25% of the adult population and is often a career-ending disease in athletes and racehorses. Tendon injury is associated with high morbidity, pain, and long-term suffering for the patient. Due to the low cellularity and vascularity of tendon tissue, once damage has occurred, the repair process is slow and inefficient, resulting in mechanically, structurally, and functionally inferior tissue. Current treatment options focus on pain management, often being palliative and temporary and ending in reduced function. Most treatments available do not address the underlying cause of the disease and, as such, are often ineffective with variable results. The need for an advanced therapeutic that addresses the underlying pathology is evident. Tissue engineering and regenerative medicine is an emerging field that is aimed at stimulating the body's own repair system to produce de novo tissue through the use of factors such as cells, proteins, and genes that are delivered by a biomaterial scaffold. Successful tissue engineering strategies for tendon regeneration should be built on a foundation of understanding of the molecular and cellular composition of healthy compared with damaged tendon, and the inherent differences seen in the tissue after disease. This article presents a comprehensive clinical, biological, and biomaterials insight into tendon tissue engineering and regeneration toward more advanced therapeutics. PMID:27596929

Regenerative medicine as applied to solid organ transplantation: current status and future challenges

PubMed Central

Orlando, Giuseppe; Baptista, Pedro; Birchall, Martin; De Coppi, Paolo; Farney, Alan; Guimaraes-Souza, Nadia K.; Opara, Emmanuel; Rogers, Jeffrey; Seliktar, Dror; Shapira-Schweitzer, Keren; Stratta, Robert J.; Atala, Anthony; Wood, Kathryn J.; Soker, Shay

2013-01-01

Summary In the last two decades, regenerative medicine has shown the potential for “bench-to-bedside” translational research in specific clinical settings. Progress made in cell and stem cell biology, material sciences and tissue engineering enabled researchers to develop cutting-edge technology which has lead to the creation of nonmodular tissue constructs such as skin, bladders, vessels and upper airways. In all cases, autologous cells were seeded on either artificial or natural supporting scaffolds. However, such constructs were implanted without the reconstruction of the vascular supply, and the nutrients and oxygen were supplied by diffusion from adjacent tissues. Engineering of modular organs (namely, organs organized in functioning units referred to as modules and requiring the reconstruction of the vascular supply) is more complex and challenging. Models of functioning hearts and livers have been engineered using “natural tissue” scaffolds and efforts are underway to produce kidneys, pancreata and small intestine. Creation of custom-made bioengineered organs, where the cellular component is exquisitely autologous and have an internal vascular network, will theoretically overcome the two major hurdles in transplantation, namely the shortage of organs and the toxicity deriving from lifelong immuno-suppression. This review describes recent advances in the engineering of several key tissues and organs. PMID:21062367

Overcoming scarring in the urethra: Challenges for tissue engineering.

PubMed

Simsek, Abdulmuttalip; Aldamanhori, Reem; Chapple, Christopher R; MacNeil, Sheila

2018-04-01

Urethral stricture disease is increasingly common occurring in about 1% of males over the age of 55. The stricture tissue is rich in myofibroblasts and multi-nucleated giant cells which are thought to be related to stricture formation and collagen synthesis. An increase in collagen is associated with the loss of the normal vasculature of the normal urethra. The actual incidence differs based on worldwide populations, geography, and income. The stricture aetiology, location, length and patient's age and comorbidity are important in deciding the course of treatment. In this review we aim to summarise the existing knowledge of the aetiology of urethral strictures, review current treatment regimens, and present the challenges of using tissue-engineered buccal mucosa (TEBM) to repair scarring of the urethra. In asking this question we are also mindful that recurrent fibrosis occurs in other tissues-how can we learn from these other pathologies?

3D bioprinting for reconstructive surgery: Principles, applications and challenges.

PubMed

Jessop, Zita M; Al-Sabah, Ayesha; Gardiner, Matthew D; Combellack, Emman; Hawkins, Karl; Whitaker, Iain S

2017-09-01

Despite the increasing laboratory research in the growing field of 3D bioprinting, there are few reports of successful translation into surgical practice. This review outlines the principles of 3D bioprinting including software and hardware processes, biocompatible technological platforms and suitable bioinks. The advantages of 3D bioprinting over traditional tissue engineering techniques in assembling cells, biomaterials and biomolecules in a spatially controlled manner to reproduce native tissue macro-, micro- and nanoarchitectures are discussed, together with an overview of current progress in bioprinting tissue types relevant for plastic and reconstructive surgery. If successful, this platform technology has the potential to biomanufacture autologous tissue for reconstruction, obviating the need for donor sites or immunosuppression. The biological, technological and regulatory challenges are highlighted, with strategies to overcome these challenges by using an integrated approach from the fields of engineering, biomaterial science, cell biology and reconstructive microsurgery. Copyright © 2017. Published by Elsevier Ltd.

A radiopaque electrospun scaffold for engineering fibrous musculoskeletal tissues: Scaffold characterization and in vivo applications.

PubMed

Martin, John T; Milby, Andrew H; Ikuta, Kensuke; Poudel, Subash; Pfeifer, Christian G; Elliott, Dawn M; Smith, Harvey E; Mauck, Robert L

2015-10-01

Tissue engineering strategies have emerged in response to the growing prevalence of chronic musculoskeletal conditions, with many of these regenerative methods currently being evaluated in translational animal models. Engineered replacements for fibrous tissues such as the meniscus, annulus fibrosus, tendons, and ligaments are subjected to challenging physiologic loads, and are difficult to track in vivo using standard techniques. The diagnosis and treatment of musculoskeletal conditions depends heavily on radiographic assessment, and a number of currently available implants utilize radiopaque markers to facilitate in vivo imaging. In this study, we developed a nanofibrous scaffold in which individual fibers included radiopaque nanoparticles. Inclusion of radiopaque particles increased the tensile modulus of the scaffold and imparted radiation attenuation within the range of cortical bone. When scaffolds were seeded with bovine mesenchymal stem cells in vitro, there was no change in cell proliferation and no evidence of promiscuous conversion to an osteogenic phenotype. Scaffolds were implanted ex vivo in a model of a meniscal tear in a bovine joint and in vivo in a model of total disc replacement in the rat coccygeal spine (tail), and were visualized via fluoroscopy and microcomputed tomography. In the disc replacement model, histological analysis at 4 weeks showed that the scaffold was biocompatible and supported the deposition of fibrous tissue in vivo. Nanofibrous scaffolds that include radiopaque nanoparticles provide a biocompatible template with sufficient radiopacity for in vivo visualization in both small and large animal models. This radiopacity may facilitate image-guided implantation and non-invasive long-term evaluation of scaffold location and performance. The healing capacity of fibrous musculoskeletal tissues is limited, and injury or degeneration of these tissues compromises the standard of living of millions in the US. Tissue engineering repair strategies for the intervertebral disc, meniscus, tendon and ligament have progressed from in vitro to in vivo evaluation using a variety of animal models, and the clinical application of these technologies is imminent. The composition of most scaffold materials however does not allow for visualization by methods available to clinicians (e.g., radiography), and thus it is not possible to assess their performance in situ. In this work, we describe a radiopaque nanofibrous scaffold that can be visualized radiographically in both small and large animal models and serve as a framework for the development of an engineered fibrous tissue. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Future potentials for using osteogenic stem cells and biomaterials in orthopedics.

PubMed

Oreffo, R O; Triffitt, J T

1999-08-01

Ideal skeletal reconstruction depends on regeneration of normal tissues that result from initiation of progenitor cell activity. However, knowledge of the origins and phenotypic characteristics of these progenitors and the controlling factors that govern bone formation and remodeling to give a functional skeleton adequate for physiological needs is limited. Practical methods are currently being investigated to amplify in in vitro culture the appropriate autologous cells to aid skeletal healing and reconstruction. Recent advances in the fields of biomaterials, biomimetics, and tissue engineering have focused attention on the potentials for clinical application. Current cell therapy procedures include the use of tissue-cultured skin cells for treatment of burns and ulcers, and in orthopedics, the use of cultured cartilage cells for articular defects. As mimicry of natural tissues is the goal, a fuller understanding of the development, structures, and functions of normal tissues is necessary. Practically all tissues are capable of being repaired by tissue engineering principles. Basic requirements include a scaffold conducive to cell attachment and maintenance of cell function, together with a rich source of progenitor cells. In the latter respect, bone is a special case and there is a vast potential for regeneration from cells with stem cell characteristics. The development of osteoblasts, chondroblasts, adipoblasts, myoblasts, and fibroblasts results from colonies derived from such single cells. They may thus, theoretically, be useful for regeneration of all tissues that this variety of cells comprise: bone, cartilage, fat, muscle, tendons, and ligaments. Also relevant to tissue reconstruction is the field of genetic engineering, which as a principal step in gene therapy would be the introduction of a functional specific human DNA into cells of a patient with a genetic disease that affects mainly a particular tissue or organ. Such a situation is pertinent to osteogenesis imperfecta, for example, where in more severely affected individuals any improvements in long bone quality would be beneficial to the patient. In conclusion, the potentials for using osteogenic stem cells and biomaterials in orthopedics for skeletal healing is immense, and work in this area is likely to expand significantly in the future.

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

PubMed

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

2017-01-01

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

Biomaterials and scaffolds in reparative medicine

NASA Technical Reports Server (NTRS)

Chaikof, Elliot L.; Matthew, Howard; Kohn, Joachim; Mikos, Antonios G.; Prestwich, Glenn D.; Yip, Christopher M.; McIntire, L. V. (Principal Investigator)

2002-01-01

Most approaches currently pursued or contemplated within the framework of reparative medicine, including cell-based therapies, artificial organs, and engineered living tissues, are dependent on our ability to synthesize or otherwise generate novel materials, fabricate or assemble materials into appropriate 2-D and 3-D forms, and precisely tailor material-related physical and biological properties so as to achieve a desired clinical response. This paper summarizes the scientific and technological opportunities within the fields of biomaterials science and molecular engineering that will likely establish new enabling technologies for cellular and molecular therapies directed at the repair, replacement, or reconstruction of diseased or damaged organs and tissues.

Tissue Engineering of the Corneal Endothelium: A Review of Carrier Materials

PubMed Central

Teichmann, Juliane; Valtink, Monika; Nitschke, Mirko; Gramm, Stefan; Funk, Richard H.W.; Engelmann, Katrin; Werner, Carsten

2013-01-01

Functional impairment of the human corneal endothelium can lead to corneal blindness. In order to meet the high demand for transplants with an appropriate human corneal endothelial cell density as a prerequisite for corneal function, several tissue engineering techniques have been developed to generate transplantable endothelial cell sheets. These approaches range from the use of natural membranes, biological polymers and biosynthetic material compositions, to completely synthetic materials as matrices for corneal endothelial cell sheet generation. This review gives an overview about currently used materials for the generation of transplantable corneal endothelial cell sheets with a special focus on thermo-responsive polymer coatings. PMID:24956190

Nondestructive measurement of esophageal biaxial mechanical properties utilizing sonometry

NASA Astrophysics Data System (ADS)

Aho, Johnathon M.; Qiang, Bo; Wigle, Dennis A.; Tschumperlin, Daniel J.; Urban, Matthew W.

2016-07-01

Malignant esophageal pathology typically requires resection of the esophagus and reconstruction to restore foregut continuity. Reconstruction options are limited and morbid. The esophagus represents a useful target for tissue engineering strategies based on relative simplicity in comparison to other organs. The ideal tissue engineered conduit would have sufficient and ideally matched mechanical tolerances to native esophageal tissue. Current methods for mechanical testing of esophageal tissues both in vivo and ex vivo are typically destructive, alter tissue conformation, ignore anisotropy, or are not able to be performed in fluid media. The aim of this study was to investigate biomechanical properties of swine esophageal tissues through nondestructive testing utilizing sonometry ex vivo. This method allows for biomechanical determination of tissue properties, particularly longitudinal and circumferential moduli and strain energy functions. The relative contribution of mucosal-submucosal layers and muscular layers are compared to composite esophagi. Swine thoracic esophageal tissues (n  =  15) were tested by pressure loading using a continuous pressure pump system to generate stress. Preconditioning of tissue was performed by pressure loading with the pump system and pre-straining the tissue to in vivo length before data was recorded. Sonometry using piezocrystals was utilized to determine longitudinal and circumferential strain on five composite esophagi. Similarly, five mucosa-submucosal and five muscular layers from thoracic esophagi were tested independently. This work on esophageal tissues is consistent with reported uniaxial and biaxial mechanical testing and reported results using strain energy theory and also provides high resolution displacements, preserves native architectural structure and allows assessment of biomechanical properties in fluid media. This method may be of use to characterize mechanical properties of tissue engineered esophageal constructs.

Integration of technologies for hepatic tissue engineering.

PubMed

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

2007-01-01

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

Engineering Bi-Layer Nanofibrous Conduits for Peripheral Nerve Regeneration

PubMed Central

Zhu, Yiqian; Wang, Aijun; Patel, Shyam; Kurpinski, Kyle; Diao, Edward; Bao, Xuan; Kwong, George; Young, William L.

2011-01-01

Trauma injuries often cause peripheral nerve damage and disability. A goal in neural tissue engineering is to develop synthetic nerve conduits for peripheral nerve regeneration having therapeutic efficacy comparable to that of autografts. Nanofibrous conduits with aligned nanofibers have been shown to promote nerve regeneration, but current fabrication methods rely on rolling a fibrous sheet into the shape of a conduit, which results in a graft with inconsistent size and a discontinuous joint or seam. In addition, the long-term effects of nanofibrous nerve conduits, in comparison with autografts, are still unknown. Here we developed a novel one-step electrospinning process and, for the first time, fabricated a seamless bi-layer nanofibrous nerve conduit: the luminal layer having longitudinally aligned nanofibers to promote nerve regeneration, and the outer layer having randomly organized nanofibers for mechanical support. Long-term in vivo studies demonstrated that bi-layer aligned nanofibrous nerve conduits were superior to random nanofibrous conduits and had comparable therapeutic effects to autografts for nerve regeneration. In summary, we showed that the engineered nanostructure had a significant impact on neural tissue regeneration in situ. The results from this study will also lead to the scalable fabrication of engineered nanofibrous nerve conduits with designed nanostructure. This technology platform can be combined with drug delivery and cell therapies for tissue engineering. PMID:21501089

Tissue engineering on the nanoscale: lessons from the heart.

PubMed

Fleischer, Sharon; Dvir, Tal

2013-08-01

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

Juvenile Swine Surgical Alveolar Cleft Model to Test Novel Autologous Stem Cell Therapies

PubMed Central

Caballero, Montserrat; Morse, Justin C.; Halevi, Alexandra E.; Emodi, Omri; Pharaon, Michael R.; Wood, Jeyhan S.

2015-01-01

Reconstruction of craniofacial congenital bone defects has historically relied on autologous bone grafts. Engineered bone using mesenchymal stem cells from the umbilical cord on electrospun nanomicrofiber scaffolds offers an alternative to current treatments. This preclinical study presents the development of a juvenile swine model with a surgically created maxillary cleft defect for future testing of tissue-engineered implants for bone generation. Five-week-old pigs (n=6) underwent surgically created maxillary (alveolar) defects to determine critical-sized defect and the quality of treatment outcomes with rib, iliac crest cancellous bone, and tissue-engineered scaffolds. Pigs were sacrificed at 1 month. Computed tomography scans were obtained at days 0 and 30, at the time of euthanasia. Histological evaluation was performed on newly formed bone within the surgical defect. A 1 cm surgically created defect healed with no treatment, the 2 cm defect did not heal. A subsequently created 1.7 cm defect, physiologically similar to a congenitally occurring alveolar cleft in humans, from the central incisor to the canine, similarly did not heal. Rib graft treatment did not incorporate into adjacent normal bone; cancellous bone and the tissue-engineered graft healed the critical-sized defect. This work establishes a juvenile swine alveolar cleft model with critical-sized defect approaching 1.7 cm. Both cancellous bone and tissue engineered graft generated bridging bone formation in the surgically created alveolar cleft defect. PMID:25837453

Periosteum tissue engineering in an orthotopic in vivo platform.

PubMed

Baldwin, J G; Wagner, F; Martine, L C; Holzapfel, B M; Theodoropoulos, C; Bas, O; Savi, F M; Werner, C; De-Juan-Pardo, E M; Hutmacher, D W

2017-03-01

The periosteum plays a critical role in bone homeostasis and regeneration. It contains a vascular component that provides vital blood supply to the cortical bone and an osteogenic niche that acts as a source of bone-forming cells. Periosteal grafts have shown promise in the regeneration of critical size defects, however their limited availability restricts their widespread clinical application. Only a small number of tissue-engineered periosteum constructs (TEPCs) have been reported in the literature. A current challenge in the development of appropriate TEPCs is a lack of pre-clinical models in which they can reliably be evaluated. In this study, we present a novel periosteum tissue engineering concept utilizing a multiphasic scaffold design in combination with different human cell types for periosteal regeneration in an orthotopic in vivo platform. Human endothelial and bone marrow mesenchymal stem cells (BM-MSCs) were used to mirror both the vascular and osteogenic niche respectively. Immunohistochemistry showed that the BM-MSCs maintained their undifferentiated phenotype. The human endothelial cells developed into mature vessels and connected to host vasculature. The addition of an in vitro engineered endothelial network increased vascularization in comparison to cell-free constructs. Altogether, the results showed that the human TEPC (hTEPC) successfully recapitulated the osteogenic and vascular niche of native periosteum, and that the presented orthotopic xenograft model provides a suitable in vivo environment for evaluating scaffold-based tissue engineering concepts exploiting human cells. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

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

PubMed Central

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

2018-01-01

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

A versatile modular bioreactor platform for Tissue Engineering

PubMed Central

Schuerlein, Sebastian; Schwarz, Thomas; Krziminski, Steffan; Gätzner, Sabine; Hoppensack, Anke; Schwedhelm, Ivo; Schweinlin, Matthias; Walles, Heike

2016-01-01

Abstract Tissue Engineering (TE) bears potential to overcome the persistent shortage of donor organs in transplantation medicine. Additionally, TE products are applied as human test systems in pharmaceutical research to close the gap between animal testing and the administration of drugs to human subjects in clinical trials. However, generating a tissue requires complex culture conditions provided by bioreactors. Currently, the translation of TE technologies into clinical and industrial applications is limited due to a wide range of different tissue‐specific, non‐disposable bioreactor systems. To ensure a high level of standardization, a suitable cost‐effectiveness, and a safe graft production, a generic modular bioreactor platform was developed. Functional modules provide robust control of culture processes, e.g. medium transport, gas exchange, heating, or trapping of floating air bubbles. Characterization revealed improved performance of the modules in comparison to traditional cell culture equipment such as incubators, or peristaltic pumps. By combining the modules, a broad range of culture conditions can be achieved. The novel bioreactor platform allows using disposable components and facilitates tissue culture in closed fluidic systems. By sustaining native carotid arteries, engineering a blood vessel, and generating intestinal tissue models according to a previously published protocol the feasibility and performance of the bioreactor platform was demonstrated. PMID:27492568

Electrically polarized PLLA nanofibers as neural tissue engineering scaffolds with improved neuritogenesis.

PubMed

Barroca, Nathalie; Marote, Ana; Vieira, Sandra I; Almeida, Abílio; Fernandes, Maria H V; Vilarinho, Paula M; da Cruz E Silva, Odete A B

2018-07-01

Tissue engineering is evolving towards the production of smart platforms exhibiting stimulatory cues to guide tissue regeneration. This work explores the benefits of electrical polarization to produce more efficient neural tissue engineering platforms. Poly (l-lactic) acid (PLLA)-based scaffolds were prepared as solvent cast films and electrospun aligned nanofibers, and electrically polarized by an in-lab built corona poling device. The characterization of the platforms by thermally stimulated depolarization currents reveals a polarization of 60 × 10 -10 C cm -2 that is stable on poled electrospun nanofibers for up to 6 months. Further in vitro studies using neuroblastoma cells reveals that platforms' polarization potentiates Retinoic Acid-induced neuronal differentiation. Additionally, in differentiating embryonic cortical neurons, poled aligned nanofibers further increased neurite outgrowth by 30% (+70 μm) over non-poled aligned nanofibers, and by 50% (+100 μm) over control conditions. Therefore, the synergy of topographical cues and electrical polarization of poled aligned nanofibers places them as promising biocompatible and bioactive platforms for neural tissue regeneration. Given their long lasting induced polarization, these PLLA poled nanofibrous scaffolds can be envisaged as therapeutic devices of long shelf life for neural repair applications. Copyright © 2018 Elsevier B.V. All rights reserved.

A Review of Injectable Polymeric Hydrogel Systems for Application in Bone Tissue Engineering.

PubMed

Kondiah, Pariksha J; Choonara, Yahya E; Kondiah, Pierre P D; Marimuthu, Thashree; Kumar, Pradeep; du Toit, Lisa C; Pillay, Viness

2016-11-21

Biodegradable, stimuli-responsive polymers are essential platforms in the field of drug delivery and injectable biomaterials for application of bone tissue engineering. Various thermo-responsive hydrogels display water-based homogenous properties to encapsulate, manipulate and transfer its contents to the surrounding tissue, in the least invasive manner. The success of bioengineered injectable tissue modified delivery systems depends significantly on their chemical, physical and biological properties. Irrespective of shape and defect geometry, injectable therapy has an unparalleled advantage in which intricate therapy sites can be effortlessly targeted with minimally invasive procedures. Using material testing, it was found that properties of stimuli-responsive hydrogel systems enhance cellular responses and cell distribution at any site prior to the transitional phase leading to gelation. The substantially hydrated nature allows significant simulation of the extracellular matrix (ECM), due to its similar structural properties. Significant current research strategies have been identified and reported to date by various institutions, with particular attention to thermo-responsive hydrogel delivery systems, and their pertinent focus for bone tissue engineering. Research on future perspective studies which have been proposed for evaluation, have also been reported in this review, directing considerable attention to the modification of delivering natural and synthetic polymers, to improve their biocompatibility and mechanical properties.

Microcracks induce osteoblast alignment and maturation on hydroxyapatite scaffolds

NASA Astrophysics Data System (ADS)

Shu, Yutian

Physiological bone tissue is a mineral/collagen composite with a hierarchical structure. The features in bone, such as mineral crystals, fibers, and pores can range from the nanometer to the centimeter in size. Currently available bone tissue scaffolds primarily address the chemical composition, pore size, and pore size distribution. While these design parameters are extensively investigated for mimicking bone function and inducing bone regeneration, little is known about microcracks, which is a prevalent feature found in fractured bone in vivo and associated with fracture healing and repair. Since the purpose of bone tissue engineering scaffold is to enhance bone regeneration, the coincidence of microcracks and bone densification should not be neglected but rather be considered as a potential parameter in bone tissue engineering scaffold design. The purpose of this study is to test the hypothesis that microcracks enhance bone healing. In vitro studies were designed to investigate the osteoblast (bone forming cells) response to microcracks in dense (94%) hydroxyapatite substrates. Microcracks were introduced using a well-established Vickers indentation technique. The results of our study showed that microcracks induced osteoblast alignment, enhanced osteoblast attachment and more rapid maturation. These findings may provide insight into fracture healing mechanism(s) as well as improve the design of bone tissue engineering orthopedic scaffolds for more rapid bone regeneration.

Advances in Application of Mechanical Stimuli in Bioreactors for Cartilage Tissue Engineering.

PubMed

Li, Ke; Zhang, Chunqiu; Qiu, Lulu; Gao, Lilan; Zhang, Xizheng

2017-08-01

Articular cartilage (AC) is the weight-bearing tissue in diarthroses. It lacks the capacity for self-healing once there are injuries or diseases due to its avascularity. With the development of tissue engineering, repairing cartilage defects through transplantation of engineered cartilage that closely matches properties of native cartilage has become a new option for curing cartilage diseases. The main hurdle for clinical application of engineered cartilage is how to develop functional cartilage constructs for mass production in a credible way. Recently, impressive hyaline cartilage that may have the potential to provide capabilities for treating large cartilage lesions in the future has been produced in laboratories. The key to functional cartilage construction in vitro is to identify appropriate mechanical stimuli. First, they should ensure the function of metabolism because mechanical stimuli play the role of blood vessels in the metabolism of AC, for example, acquiring nutrition and removing wastes. Second, they should mimic the movement of synovial joints and produce phenotypically correct tissues to achieve the adaptive development between the micro- and macrostructure and function. In this article, we divide mechanical stimuli into three types according to forces transmitted by different media in bioreactors, namely forces transmitted through the liquid medium, solid medium, or other media, then we review and summarize the research status of bioreactors for cartilage tissue engineering (CTE), mainly focusing on the effects of diverse mechanical stimuli on engineered cartilage. Based on current researches, there are several motion patterns in knee joints; but compression, tension, shear, fluid shear, or hydrostatic pressure each only partially reflects the mechanical condition in vivo. In this study, we propose that rolling-sliding-compression load consists of various stimuli that will represent better mechanical environment in CTE. In addition, engineers often ignore the importance of biochemical factors to the growth and development of engineered cartilage. In our point of view, only by fully considering synergistic effects of mechanical and biochemical factors can we find appropriate culture conditions for functional cartilage constructs. Once again, rolling-sliding-compression load under appropriate biochemical conditions may be conductive to realize the adaptive development between the structure and function of engineered cartilage in vitro.

Engineering complex tissues.

PubMed

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

2012-11-14

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

Tubular Tissues and Organs of Human Body--Challenges in Regenerative Medicine.

PubMed

Góra, Aleksander; Pliszka, Damian; Mukherjee, Shayanti; Ramakrishna, Seeram

2016-01-01

Tissue engineering of tubular organs such as the blood vessel, trachea gastrointestinal tract, urinary tract are of the great interest due to the high amount of surgeries performed annually on those organs. Development in tissue engineering in recent years and promising results, showed need to investigate more complex constructs that need to be designed in special manner. Stent technology remain the most widely used procedure to restore functions of tubular tissues after cancer treatment, or after organ removal due to traumatic accidents. Tubular structures like blood vessels, intestines, and trachea have to work in specific environment at the boundary of the liquids, solids or air and surrounding tissues and ensure suitable separation between them. This brings additional challenges in tissue engineering science in order to construct complete organs by using combinations of various cells along with the support material systems. Here we give a comprehensive review of the tubular structures of the human body, in perspective of the current methods of treatment and progress in regenerative medicine that aims to develop fully functioning organs of tubular shape. Extensive analysis of the available literature has been done focusing on materials and methods of creations of such organs. This work describes the attempts to incorporate growth factors and drugs within the scaffolds to ensure localized drug release and enhance vascularization of the organ by attracting blood vessels to the site of implantation.

Design Approaches to Myocardial and Vascular Tissue Engineering.

PubMed

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

2017-06-21

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

3D Printing and Biofabrication for Load Bearing Tissue Engineering.

PubMed

Jeong, Claire G; Atala, Anthony

2015-01-01

Cell-based direct biofabrication and 3D bioprinting is becoming a dominant technological platform and is suggested as a new paradigm for twenty-first century tissue engineering. These techniques may be our next step in surpassing the hurdles and limitations of conventional scaffold-based tissue engineering, and may offer the industrial potential of tissue engineered products especially for load bearing tissues. Here we present a topically focused review regarding the fundamental concepts, state of the art, and perspectives of this new technology and field of biofabrication and 3D bioprinting, specifically focused on tissue engineering of load bearing tissues such as bone, cartilage, osteochondral and dental tissue engineering.

Evaluation of Soft Tissue Coverage over Porous Polymethylmethacrylate Space Maintainers Within Nonhealing Alveolar Bone Defects

PubMed Central

Kretlow, James D.; Shi, Meng; Young, Simon; Spicer, Patrick P.; Demian, Nagi; Jansen, John A.; Wong, Mark E.; Kasper, F. Kurtis

2010-01-01

Current treatment of traumatic craniofacial injuries often involves early free tissue transfer, even if the recipient site is contaminated or lacks soft tissue coverage. There are no current tissue engineering strategies to definitively regenerate tissues in such an environment at an early time point. For a tissue engineering approach to be employed in the treatment of such injuries, a two-stage approach could potentially be used. The present study describes methods for fabrication, characterization, and processing of porous polymethylmethacrylate (PMMA) space maintainers for temporary retention of space in bony craniofacial defects. Carboxymethylcellulose hydrogels were used as a porogen. Implants with controlled porosity and pore interconnectivity were fabricated by varying the ratio of hydrogel:polymer and the amount of carboxymethylcellulose within the hydrogel. The in vivo tissue response to the implants was observed by implanting solid, low-porosity, and high-porosity implants (n = 6) within a nonhealing rabbit mandibular defect that included an oral mucosal defect to allow open communication between the oral cavity and the mandibular defect. Oral mucosal wound healing was observed after 12 weeks and was complete in 3/6 defects filled with solid PMMA implants and 5/6 defects filled with either a low- or high-porosity PMMA implant. The tissue response around and within the pores of the two formulations of porous implants tested in vivo was characterized, with the low-porosity implants surrounded by a minimal but well-formed fibrous capsule in contrast to the high-porosity implants, which were surrounded and invaded by almost exclusively inflammatory tissue. On the basis of these results, PMMA implants with limited porosity hold promise for temporary implantation and space maintenance within clean/contaminated bone defects. PMID:20524844

Current status of tissue engineering applied to bladder reconstruction in humans.

PubMed

Gasanz, C; Raventós, C; Morote, J

2018-01-11

Bladder reconstruction is performed to replace or expand the bladder. The intestine is used in standard clinical practice for tissue in this procedure. The complications of bladder reconstruction range from those of intestinal resection to those resulting from the continuous contact of urine with tissue not prepared for this contact. In this article, we describe and classify the various biomaterials and cell cultures used in bladder tissue engineering and reviews the studies performed with humans. We conducted a review of literature published in the PubMed database between 1950 and 2017, following the principles of the PRISM declaration. Numerous in vitro and animal model studies have been conducted, but only 18 experiments have been performed with humans, with a total of 169 patients. The current evidence suggests that an acellular matrix, a synthetic polymer with urothelial and autologous smooth muscle cells attached in vitro or stem cells would be the most practical approach for experimental bladder reconstruction. Bladder replacement or expansion without using intestinal tissue is still a challenge, despite progress in the manufacture of biomaterials and the development of cell therapy. Well-designed studies with large numbers of patients and long follow-up times are needed to establish an effective clinical translation and standardisation of the check-up functional tests. Copyright © 2017 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Tissue engineering for clinical applications.

PubMed

Bhatia, Sujata K

2010-12-01

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

Bioprinting for vascular and vascularized tissue biofabrication.

PubMed

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

2017-03-15

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

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

PubMed

Stylios, George; Wan, Taoyu; Giannoudis, Peter

2007-03-01

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

Quantitative monitoring of lipid accumulation over time in cultured adipocytes as function of culture conditions: toward controlled adipose tissue engineering.

PubMed

Or-Tzadikario, Shira; Sopher, Ran; Gefen, Amit

2010-10-01

Adipose tissue engineering is investigated for native fat substitutes and wound healing model systems. Research and clinical applications of bioartificial fat require a quantitative and objective method to continuously measure adipogenesis in living cultures as opposed to currently used culture-destructive techniques that stain lipid droplet (LD) accumulation. To allow standardization, automatic quantification of LD size is further needed, but currently LD size is measured mostly manually. We developed an image processing-based method that does not require staining to monitor adipose cell maturation in vitro nondestructively using optical micrographs taken consecutively during culturing. We employed our method to monitor LD accumulation in 3T3-L1 and mesenchymal stem cells over 37 days. For each cell type, percentage of lipid area, number of droplets per cell, and droplet diameter were obtained every 2-3 days. In 3T3-L1 cultures, high insulin concentration (10 microg/mL) yielded a significantly different (p < 0.01) time course of all three outcome measures. In mesenchymal stem cell cultures, high fetal bovine serum concentration (12.5%) produced significantly more lipid area (p < 0.01). Our method was able to successfully characterize time courses and extents of adipogenesis and is useful for a wide range of applications testing the effects of biochemical, mechanical, and thermal stimulations in tissue engineering of bioartificial fat constructs.

Trends in the design of nerve guidance channels in peripheral nerve tissue engineering.

PubMed

Chiono, Valeria; Tonda-Turo, Chiara

2015-08-01

The current trend of peripheral nerve tissue engineering is the design of advanced nerve guidance channels (NGCs) acting as physical guidance for regeneration of nerves across lesions. NGCs should present multifunctional properties aiming to direct the sprouting of axons from the proximal nerve end, to concentrate growth factors secreted by the injured nerve ends, and to reduce the ingrowth of scar tissue into the injury site. A critical aspect in the design of NGCs is conferring them the ability to provide topographic, chemotactic and haptotactic cues that lead to functional nerve regeneration thus increasing the axon growth rate and avoiding or minimizing end-organ (e.g. muscle) atrophy. The present work reviews the recent state of the art in NGCs engineering and defines the external guide and internal fillers structural and compositional requirements that should be satisfied to improve nerve regeneration, especially in the case of large gaps (>2 cm). Techniques for NGCs fabrication were described highlighting the innovative approaches direct to enhance the regeneration of axon stumps compared to current clinical treatments. Furthermore, the possibility to apply stem cells as internal cues to the NGCs was discussed focusing on scaffold properties necessary to ensure cell survival. Finally, the optimized features for NGCs design were summarized showing as multifunctional cues are needed to produce NGCs having improved results in clinics. Copyright © 2015 Elsevier Ltd. All rights reserved.

A gold nanoparticle coated porcine cholecyst-derived bioscaffold for cardiac tissue engineering.

PubMed

Nair, Reshma S; Ameer, Jimna Mohamed; Alison, Malcolm R; Anilkumar, Thapasimuthu V

2017-09-01

Extracellular matrices of xenogeneic origin have been extensively used for biomedical applications, despite the possibility of heterogeneity in structure. Surface modification of biologically derived biomaterials using nanoparticles is an emerging strategy for improving topographical homogeneity when employing these scaffolds for sophisticated tissue engineering applications. Recently, as a tissue engineering scaffold, cholecyst derived extracellular matrix (C-ECM) has been shown to have several advantages over extracellular matrices derived from other organs such as jejunum and urinary bladder. This study explored the possibility of adding gold nanoparticles, which have a large surface area to volume ratio on C-ECM for achieving homogeneity in surface architecture, a requirement for cardiac tissue engineering. In the current study, gold nanoparticles (AuNPs) were synthesized and functionalised for conjugating with a porcine cholecystic extracellular matrix scaffold. The conjugation of nanoparticles to C-ECM was achieved by 1-ethyl-3-(3-dimethyl aminopropyl)-carbodiimide/N-hydroxysuccinimide chemistry and further characterized by Fourier transform infrared spectroscopy, environmental scanning electron microscopy, energy dispersive X-ray spectroscopy and thermogravimetric analysis. The physical properties of the modified scaffold were similar to the original C-ECM. Biological properties were evaluated by using H9c2 cells, a cardiomyoblast cell line commonly used for cellular and molecular studies of cardiac cells. The modified scaffold was found to be a suitable substrate for the growth and proliferation of the cardiomyoblasts. Further, the non-cytotoxic nature of the modified scaffold was established by direct contact cytotoxicity testing and live/dead staining. Thus, the modified C-ECM appears to be a potential biomaterial for cardiac tissue engineering. Copyright © 2017 Elsevier B.V. All rights reserved.

An Overview of Recent Patents on Musculoskeletal Interface Tissue Engineering

PubMed Central

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

2018-01-01

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

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

PubMed Central

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

2013-01-01

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

Three-dimensional bioprinting of stem-cell derived tissues for human regenerative medicine.

PubMed

Skeldon, Gregor; Lucendo-Villarin, Baltasar; Shu, Wenmiao

2018-07-05

Stem cell technology in regenerative medicine has the potential to provide an unlimited supply of cells for drug testing, medical transplantation and academic research. In order to engineer a realistic tissue model using stem cells as an alternative to human tissue, it is essential to create artificial stem cell microenvironment or niches. Three-dimensional (3D) bioprinting is a promising tissue engineering field that offers new opportunities to precisely place stem cells within their niches layer-by-layer. This review covers bioprinting technologies, the current development of 'bio-inks' and how bioprinting has already been applied to stem-cell culture, as well as their applications for human regenerative medicine. The key considerations for bioink properties such as stiffness, stability and biodegradation, biocompatibility and printability are highlighted. Bioprinting of both adult and pluriopotent stem cells for various types of artificial tissues from liver to brain has been reviewed. 3D bioprinting of stem-cell derived tissues for human regenerative medicine is an exciting emerging area that represents opportunities for new research, industries and products as well as future challenges in clinical translation.This article is part of the theme issue 'Designer human tissue: coming to a lab near you'. © 2018 The Author(s).

Introduction to tissue engineering and application for cartilage engineering.

PubMed

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

2010-01-01

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

An approach to architecture 3D scaffold with interconnective microchannel networks inducing angiogenesis for tissue engineering.

PubMed

Sun, Jiaoxia; Wang, Yuanliang; Qian, Zhiyong; Hu, Chenbo

2011-11-01

The angiogenesis of 3D scaffold is one of the major current limitations in clinical practice tissue engineering. The new strategy of construction 3D scaffold with microchannel circulation network may improve angiogenesis. In this study, 3D poly(D: ,L: -lactic acid) scaffolds with controllable microchannel structures were fabricated using sacrificial sugar structures. Melt drawing sugar-fiber network produced by a modified filament spiral winding method was used to form the microchannel with adjustable diameters and porosity. This fabrication process was rapid, inexpensive, and highly scalable. The porosity, microchannel diameter, interconnectivity and surface topographies of the scaffold were characterized by scanning electron microscopy. Mechanical properties were evaluated by compression tests. The mean porosity values of the scaffolds were in the 65-78% and the scaffold exhibited microchannel structure with diameter in the 100-200 μm range. The results showed that the scaffolds exhibited an adequate porosity, interconnective microchannel network, and mechanical properties. The cell culture studies with endothelial cells (ECs) demonstrated that the scaffold allowed cells to proliferate and penetrate into the volume of the entire scaffold. Overall, these findings suggest that the fabrication process offers significant advantages and flexibility in generating a variety of non-cytotoxic tissue engineering scaffolds with controllable distributions of porosity and physical properties that could provide the necessary physical cues for ECs and further improve angiogenesis for tissue engineering.

Fibrin glue in ophthalmology

PubMed Central

Panda, Anita; Kumar, Sandeep; Kumar, Abhiyan; Bansal, Raseena; Bhartiya, Shibal

2009-01-01

Suturing is a time consuming task in ophthalmology and suture induced irritation and redness are frequent problems. Postoperative wound infection and corneal graft rejection are examples of possible suture related complications. To prevent these complications, ophthalmic surgeons are switching to sutureless surgery. A number of recent developments have established tissue adhesives like cyanoacrylate glue and fibrin glue as attractive alternatives to sutures. A possible and promising new application for tissue adhesives is to provide a platform for tissue engineering. Currently, tissue glue is being used for conjunctival closure following pterygium and strabismus surgery, forniceal reconstruction surgery, amniotic membrane transplantation, lamellar corneal grafting, closure of corneal perforations and descematoceles, management of conjunctival wound leaks after trabeculectomy, lid surgery, adnexal surgery and as a hemostat to minimise bleeding. The purpose of this review is to discuss the currently available information on fibrin glue. PMID:19700876

Tissue engineering therapy for cardiovascular disease.

PubMed

Nugent, Helen M; Edelman, Elazer R

2003-05-30

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

Engineering Complex Tissues

PubMed Central

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

2010-01-01

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

Rational design of nanofiber scaffolds for orthopedic tissue repair and regeneration

PubMed Central

Ma, Bing; Xie, Jingwei; Jiang, Jiang; Shuler, Franklin D; Bartlett, David E

2013-01-01

This article reviews recent significant advances in the design of nanofiber scaffolds for orthopedic tissue repair and regeneration. It begins with a brief introduction on the limitations of current approaches for orthopedic tissue repair and regeneration. It then illustrates that rationally designed scaffolds made up of electrospun nanofibers could be a promising solution to overcome the problems that current approaches encounter. The article also discusses the intriguing properties of electrospun nanofibers, including control of composition, structures, orders, alignments and mechanical properties, use as carriers for topical drug and/or gene sustained delivery, and serving as substrates for the regulation of cell behaviors, which could benefit musculoskeletal tissue repair and regeneration. It further highlights a few of the many recent applications of electrospun nanofiber scaffolds in repairing and regenerating various orthopedic tissues. Finally, the article concludes with perspectives on the challenges and future directions for better design, fabrication and utilization of nanofiber scaffolds for orthopedic tissue engineering. PMID:23987110

Current advances and future perspectives in extrusion-based bioprinting.

PubMed

Ozbolat, Ibrahim T; Hospodiuk, Monika

2016-01-01

Extrusion-based bioprinting (EBB) is a rapidly growing technology that has made substantial progress during the last decade. It has great versatility in printing various biologics, including cells, tissues, tissue constructs, organ modules and microfluidic devices, in applications from basic research and pharmaceutics to clinics. Despite the great benefits and flexibility in printing a wide range of bioinks, including tissue spheroids, tissue strands, cell pellets, decellularized matrix components, micro-carriers and cell-laden hydrogels, the technology currently faces several limitations and challenges. These include impediments to organ fabrication, the limited resolution of printed features, the need for advanced bioprinting solutions to transition the technology bench to bedside, the necessity of new bioink development for rapid, safe and sustainable delivery of cells in a biomimetically organized microenvironment, and regulatory concerns to transform the technology into a product. This paper, presenting a first-time comprehensive review of EBB, discusses the current advancements in EBB technology and highlights future directions to transform the technology to generate viable end products for tissue engineering and regenerative medicine. Copyright © 2015 Elsevier Ltd. All rights reserved.

Micropatterned nanostructures: a bioengineered approach to mass-produce functional myocardial grafts.

PubMed

Serpooshan, Vahid; Mahmoudi, Morteza

2015-02-13

Cell-based therapies are a recently established path for treating a wide range of human disease. Tissue engineering of contractile heart muscle for replacement therapy is among the most exciting and important of these efforts. However, current in vitro techniques of cultivating functional mature cardiac grafts have only been moderately successful due to the poor capability of traditional two-dimensional cell culture systems to recapitulate necessary in vivo conditions. In this issue, Kiefer et al introduce a laser-patterned nanostructured substrate (Al/Al2O3 nanowires) for efficient maintenance of oriented human cardiomyocytes, with great potential to open new roads to mass-production of contractile myocardial grafts for cardiovascular tissue engineering.

New cell engineering approaches for cartilage regenerative medicine.

PubMed

Cucchiarini, Magali

2017-01-01

Articular cartilage injuries have an inadequate aptitude to reproduce the original structure and functions of this highly specialized tissue. As most of the currently available options also do not lead to the restoration of the original hyaline cartilage, novel treatments are critically needed to address this global problems in the clinics. Gene therapy combined with tissue engineering approaches offers effective tools capable of enhancing cartilage repair experimentally, especially those based on the controlled delivery of the highly effective, clinically adapted recombinant adeno-associated viral (rAAV) vectors. This work presents an overview of the most recent evidence showing the benefits of using rAAV vectors and biocompatible materials for the elaboration of adapted treatments against cartilage injuries.

Micropatterned nanostructures: a bioengineered approach to mass-produce functional myocardial grafts

NASA Astrophysics Data System (ADS)

Serpooshan, Vahid; Mahmoudi, Morteza

2015-02-01

Cell-based therapies are a recently established path for treating a wide range of human disease. Tissue engineering of contractile heart muscle for replacement therapy is among the most exciting and important of these efforts. However, current in vitro techniques of cultivating functional mature cardiac grafts have only been moderately successful due to the poor capability of traditional two-dimensional cell culture systems to recapitulate necessary in vivo conditions. In this issue, Kiefer et al [1] introduce a laser-patterned nanostructured substrate (Al/Al2O3 nanowires) for efficient maintenance of oriented human cardiomyocytes, with great potential to open new roads to mass-production of contractile myocardial grafts for cardiovascular tissue engineering.

Advances in combining gene therapy with cell and tissue engineering-based approaches to enhance healing of the meniscus

PubMed Central

Cucchiarini, M.; McNulty, A.L.; Mauck, R.L.; Setton, L.A.; Guilak, F.; Madry, H.

2017-01-01

SUMMARY Meniscal lesions are common problems in orthopaedic surgery and sports medicine, and injury or loss of the meniscus accelerates the onset of knee osteoarthritis. Despite a variety of therapeutic options in the clinics, there is a critical need for improved treatments to enhance meniscal repair. In this regard, combining gene-, cell-, and tissue engineering-based approaches is an attractive strategy to generate novel, effective therapies to treat meniscal lesions. In the present work, we provide an overview of the tools currently available to improve meniscal repair and discuss the progress and remaining challenges for potential future translation in patients. PMID:27063441

The past, present and future of ligament regenerative engineering

PubMed Central

Mengsteab, Paulos Y; Nair, Lakshmi S; Laurencin, Cato T

2016-01-01

Regenerative engineering has been defined as the convergence of Advanced Materials Sciences, Stem Cell Sciences, Physics, Developmental Biology and Clinical Translation for the regeneration of complex tissues and organ systems. Anterior cruciate ligament (ACL) reconstruction necessitates the regeneration of bone, ligament and their interface to achieve superior clinical results. In the past, the ACL has been repaired with the use of autologous and allogeneic grafts, which have their respective drawbacks. Currently, investigations on the use of biodegradable matrices to achieve knee stability and permit tissue regeneration are making promising advancements. In the future, utilizing regenerative biology cues to induce an endogenous regenerative response may aid the enhancement of clinical ACL reconstruction outcomes. PMID:27879170

The past, present and future of ligament regenerative engineering.

PubMed

Mengsteab, Paulos Y; Nair, Lakshmi S; Laurencin, Cato T

2016-12-01

Regenerative engineering has been defined as the convergence of Advanced Materials Sciences, Stem Cell Sciences, Physics, Developmental Biology and Clinical Translation for the regeneration of complex tissues and organ systems. Anterior cruciate ligament (ACL) reconstruction necessitates the regeneration of bone, ligament and their interface to achieve superior clinical results. In the past, the ACL has been repaired with the use of autologous and allogeneic grafts, which have their respective drawbacks. Currently, investigations on the use of biodegradable matrices to achieve knee stability and permit tissue regeneration are making promising advancements. In the future, utilizing regenerative biology cues to induce an endogenous regenerative response may aid the enhancement of clinical ACL reconstruction outcomes.

Effects of Epidermal Growth Factor-Loaded Mucoadhesive Films on Wounded Oral Tissue Rafts

PubMed Central

Ramineni, Sandeep K.; Fowler, Craig B.; Fisher, Paul D.; Cunningham, Larry L.; Puleo, David A.

2015-01-01

Current treatments for traumatic oral mucosal wounds include the gold standard of autologous tissue and alternative tissue engineered grafts. While use of autografts has disadvantages of minimal availability of oral keratinized tissue, second surgery, and donor site discomfort, tissue engineered grafts are limited by their unavailability as off-the-shelf products owing to their fabrication time of 4–8 weeks. Hence, the current work aimed to develop a potentially cost-effective, readily available device capable of enhancing native mucosal regeneration. Considering the key role of epidermal growth factor (EGF) in promoting mucosal wound regeneration and the advantages of mucoadhesive delivery systems, mucoadhesive films composed of polyvinylpyrrolidone and carboxymethylcellulose were developed to provide sustained release of EGF for minimum of 6 hours. Bioactivity of released EGF supernatants was then confirmed by its ability to promote proliferation of BALB/3T3 fibroblasts. Efficacy of the developed system was then investigated in vitro using buccal tissues (ORL 300-FT) as a potential replacement for small animal studies. Although the mucoadhesive films achieved their desired role of delivering bioactive EGF in a sustained manner, treatment with EGF, irrespective of its release from the films or solubilized in medium, caused a hyperparakeratotic response from in vitro tissues with distinguishable histological features including thickening of the spinous layer, intra- and intercellular edema, and pyknotic nuclei. These significant morphological changes were associated with no improvements in wound closure. These observations raise questions about the potential of using in vitro tissues as a wound healing model and substitute for small animal studies. The mucoadhesive delivery system developed, however, with its potential for sustained release of bioactive growth factors and small molecules, may be loaded with other desired compounds, with or without EGF, to accelerate the process of wound healing. PMID:25729882

Three-Dimensional Bioprinting: Toward the Era of Manufacturing Human Organs as Spare Parts for Healthcare and Medicine^.

PubMed

Mir, Tanveer Ahmad; Nakamura, Makoto

2017-06-01

Three-dimensional (3D) printing technology has been used in industrial worlds for decades. Three-dimensional bioprinting has recently received an increasing attention across the globe among researchers, academicians, students, and even the ordinary people. This emerging technique has a great potential to engineer highly organized functional bioconstructs with complex geometries and tailored components for engineering bioartificial tissues/organs for widespread applications, including transplantation, therapeutic investigation, drug development, bioassay, and disease modeling. Although many specialized 3D printers have been developed and applied to print various types of 3D tissue constructs, bioprinting technologies still have several technical challenges, including high resolution distribution of cells, controlled deposition of bioinks, suitable bioink materials, maturation of cells, and effective vascularization and innervation within engineered complex structures. In this brief review, we discuss about bioprinting approach, current limitations, and possibility of future advancements for producing engineered bioconstructs and bioartificial organs with desired functionalities.

Perfusion-decellularization of human ear grafts enables ECM-based scaffolds for auricular vascularized composite tissue engineering.

PubMed

Duisit, Jérôme; Amiel, Hadrien; Wüthrich, Tsering; Taddeo, Adriano; Dedriche, Adeline; Destoop, Vincent; Pardoen, Thomas; Bouzin, Caroline; Joris, Virginie; Magee, Derek; Vögelin, Esther; Harriman, David; Dessy, Chantal; Orlando, Giuseppe; Behets, Catherine; Rieben, Robert; Gianello, Pierre; Lengelé, Benoît

2018-06-01

Human ear reconstruction is recognized as the emblematic enterprise in tissue engineering. Up to now, it has failed to reach human applications requiring appropriate tissue complexity along with an accessible vascular tree. We hereby propose a new method to process human auricles in order to provide a poorly immunogenic, complex and vascularized ear graft scaffold. 12 human ears with their vascular pedicles were procured. Perfusion-decellularization was applied using a SDS/polar solvent protocol. Cell and antigen removal was examined by histology and DNA was quantified. Preservation of the extracellular matrix (ECM) was assessed by conventional and 3D-histology, proteins and cytokines quantifications. Biocompatibility was assessed by implantation in rats for up to 60 days. Adipose-derived stem cells seeding was conducted on scaffold samples and with human aortic endothelial cells whole graft seeding in a perfusion-bioreactor. Histology confirmed cell and antigen clearance. DNA reduction was 97.3%. ECM structure and composition were preserved. Implanted scaffolds were tolerated in vivo, with acceptable inflammation, remodeling, and anti-donor antibody formation. Seeding experiments demonstrated cell engraftment and viability. Vascularized and complex auricular scaffolds can be obtained from human source to provide a platform for further functional auricular tissue engineered constructs, hence providing an ideal road to the vascularized composite tissue engineering approach. The ear is emblematic in the biofabrication of tissues and organs. Current regenerative medicine strategies, with matrix from donor tissues or 3D-printed, didn't reach any application for reconstruction, because critically missing a vascular tree for perfusion and transplantation. We previously described the production of vascularized and cell-compatible scaffolds, from porcine ear grafts. In this study, we ---- applied findings directly to human auricles harvested from postmortem donors, providing a perfusable matrix that retains the ear's original complexity and hosts new viable cells after seeding. This approach unlocks the ability to achieve an auricular tissue engineering approach, associated with possible clinical translation. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

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

PubMed

Fleischer, Sharon; Feiner, Ron; Dvir, Tal

2017-04-01

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

Emergence of Scaffold-free Approaches for Tissue Engineering Musculoskeletal Cartilages

PubMed Central

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

2014-01-01

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

Imaging Strategies for Tissue Engineering Applications

PubMed Central

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

2015-01-01

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

Current opinion on auricular reconstruction.

PubMed

Sivayoham, Eason; Woolford, Tim J

2012-08-01

To review the current practice in the field of auricular reconstruction and to highlight the recent advances reported in the medical literature. The majority of surgeons who perform auricular reconstruction continue to employ the well-established techniques developed by Brent and Nagata. Surgery takes between two and four stages, with the initial stage being construction of a framework of autogenous rib cartilage which is implanted into a subcutaneous pocket. Several modifications of these techniques have been reported. More recently, synthetic frameworks have been employed instead of autogenous rib cartilage. For this procedure, the implant is generally covered with a temporoparietal flap and a skin graft at the first stage of surgery. Tissue engineering is a rapidly developing field, and there have been several articles related to the field of auricular reconstruction. These show great potential to offer a solution to the challenge associated with construction of a viable autogenous cartilage framework, whilst avoiding donor-site morbidity. This article gives an overview of the current practice in the field of auricular reconstruction and summarizes the recent surgical developments and relevant tissue engineering research.

Programmable Hydrogel Ionic Circuits for Biologically Matched Electronic Interfaces.

PubMed

Zhao, Siwei; Tseng, Peter; Grasman, Jonathan; Wang, Yu; Li, Wenyi; Napier, Bradley; Yavuz, Burcin; Chen, Ying; Howell, Laurel; Rincon, Javier; Omenetto, Fiorenzo G; Kaplan, David L

2018-06-01

The increased need for wearable and implantable medical devices has driven the demand for electronics that interface with living systems. Current bioelectronic systems have not fully resolved mismatches between engineered circuits and biological systems, including the resulting pain and damage to biological tissues. Here, salt/poly(ethylene glycol) (PEG) aqueous two-phase systems are utilized to generate programmable hydrogel ionic circuits. High-conductivity salt-solution patterns are stably encapsulated within PEG hydrogel matrices using salt/PEG phase separation, which route ionic current with high resolution and enable localized delivery of electrical stimulation. This strategy allows designer electronics that match biological systems, including transparency, stretchability, complete aqueous-based connective interface, distribution of ionic electrical signals between engineered and biological systems, and avoidance of tissue damage from electrical stimulation. The potential of such systems is demonstrated by generating light-emitting diode (LED)-based displays, skin-mounted electronics, and stimulators that deliver localized current to in vitro neuron cultures and muscles in vivo with reduced adverse effects. Such electronic platforms may form the basis of future biointegrated electronic systems. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Current Treatment Limitations in Age-Related Macular Degeneration and Future Approaches Based on Cell Therapy and Tissue Engineering

PubMed Central

Fernández-Robredo, P.; Sancho, A.; Johnen, S.; Recalde, S.; Gama, N.; Thumann, G.; Groll, J.; García-Layana, A.

2014-01-01

Age-related macular degeneration (AMD) is the leading cause of blindness in the Western world. With an ageing population, it is anticipated that the number of AMD cases will increase dramatically, making a solution to this debilitating disease an urgent requirement for the socioeconomic future of the European Union and worldwide. The present paper reviews the limitations of the current therapies as well as the socioeconomic impact of the AMD. There is currently no cure available for AMD, and even palliative treatments are rare. Treatment options show several side effects, are of high cost, and only treat the consequence, not the cause of the pathology. For that reason, many options involving cell therapy mainly based on retinal and iris pigment epithelium cells as well as stem cells are being tested. Moreover, tissue engineering strategies to design and manufacture scaffolds to mimic Bruch's membrane are very diverse and under investigation. Both alternative therapies are aimed to prevent and/or cure AMD and are reviewed herein. PMID:24672707

Advances in bionanomaterials for bone tissue engineering.

PubMed

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

2013-01-01

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

Biomechanics and mechanobiology in functional tissue engineering.

PubMed

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

2014-06-27

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

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.

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.

Electrospinning of Biocompatible Nanofibers

NASA Astrophysics Data System (ADS)

Coughlin, Andrew J.; Queen, Hailey A.; McCullen, Seth D.; Krause, Wendy E.

2006-03-01

Artificial scaffolds for growing cells can have a wide range of applications including wound coverings, supports in tissue cultures, drug delivery, and organ and tissue transplantation. Tissue engineering is a promising field which may resolve current problems with transplantation, such as rejection by the immune system and scarcity of donors. One approach to tissue engineering utilizes a biodegradable scaffold onto which cells are seeded and cultured, and ideally develop into functional tissue. The scaffold acts as an artificial extracellular matrix (ECM). Because a typical ECM contains collagen fibers with diameters of 50-500 nm, electrostatic spinning (electrospinning) was used to mimic the size and structure of these fibers. Electrospinning is a novel way of spinning a nonwoven web of fibers on the order of 100 nm, much like the web of collagen in an ECM. We are investigating the ability of several biocompatible polymers (e.g., chitosan and polyvinyl alcohol) to form defect-free nanofiber webs and are studying the influence of the zero shear rate viscosity, molecular weight, entanglement concentration, relaxation time, and solvent on the resulting fiber size and morphology.

Parthenogenesis-derived Multipotent Stem Cells Adapted for Tissue Engineering Applications

PubMed Central

Koh, Chester J.; Delo, Dawn M.; Lee, Jang Won; Siddiqui, M. Minhaj; Lanza, Robert P.; Soker, Shay; Yoo, James J.; Atala, Anthony

2009-01-01

Embryonic stem cells are envisioned as a viable source of pluripotent cells for use in regenerative medicine applications when donor tissue is not available. However, most current harvest techniques for embryonic stem cells require the destruction of embryos, which has led to significant political and ethical limitations on their usage. Parthenogenesis, the process by which an egg can develop into an embryo in the absence of sperm, may be a potential source of embryonic stem cells that may avoid some of the political and ethical concerns surrounding embryonic stem cells. Here we provide the technical aspects of embryonic stem cell isolation and expansion from the parthenogenetic activation of oocytes. These cells were characterized for their stem-cell properties. In addition, these cells were induced to differentiate to the myogenic, osteogenic, adipogenic, and endothelial lineages, and were able to form muscle-like and bony-like tissue in vivo. Furthermore, parthenogenetic stem cells were able to integrate into injured muscle tissue. Together, these results demonstrate that parthenogenetic stem cells can be successfully isolated and utilized for various tissue engineering applications. PMID:18799133

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.

Silk: a potential medium for tissue engineering.

PubMed

Sobajo, Cassandra; Behzad, Farhad; Yuan, Xue-Feng; Bayat, Ardeshir

2008-01-01

Human skin is a complex bilayered organ that serves as a protective barrier against the environment. The loss of integrity of skin by traumatic experiences such as burns and ulcers may result in considerable disability or ultimately death. Therefore, in skin injuries, adequate dermal substitutes are among primary care targets, aimed at replacing the structural and functional properties of native skin. To date, there are very few single application tissue-engineered dermal constructs fulfilling this criterion. Silk produced by the domestic silkworm, Bombyx mori, has a long history of use in medicine. It has recently been increasingly investigated as a promising biomaterial for dermal constructs. Silk contains 2 fibrous proteins, sericin and fibroin. Each one exhibits unique mechanical and biological properties. Comprehensive review of randomized-controlled trials investigating current dermal constructs and the structures and properties of silk-based constructs on wound healing. This review revealed that silk-fibroin is regarded as the most promising biomaterial, providing options for the construction of tissue-engineered skin. The research available indicates that silk fibroin is a suitable biomaterial scaffold for the provision of adequate dermal constructs.

New paradigms in internal architecture design and freeform fabrication of tissue engineering porous scaffolds.

PubMed

Yoo, Dongjin

2012-07-01

Advanced additive manufacture (AM) techniques are now being developed to fabricate scaffolds with controlled internal pore architectures in the field of tissue engineering. In general, these techniques use a hybrid method which combines computer-aided design (CAD) with computer-aided manufacturing (CAM) tools to design and fabricate complicated three-dimensional (3D) scaffold models. The mathematical descriptions of micro-architectures along with the macro-structures of the 3D scaffold models are limited by current CAD technologies as well as by the difficulty of transferring the designed digital models to standard formats for fabrication. To overcome these difficulties, we have developed an efficient internal pore architecture design system based on triply periodic minimal surface (TPMS) unit cell libraries and associated computational methods to assemble TPMS unit cells into an entire scaffold model. In addition, we have developed a process planning technique based on TPMS internal architecture pattern of unit cells to generate tool paths for freeform fabrication of tissue engineering porous scaffolds. Copyright © 2012 IPEM. Published by Elsevier Ltd. All rights reserved.

Design and characterization of a biodegradable composite scaffold for ligament tissue engineering.

PubMed

Hayami, James W S; Surrao, Denver C; Waldman, Stephen D; Amsden, Brian G

2010-03-15

Herein we report on the development and characterization of a biodegradable composite scaffold for ligament tissue engineering based on the fundamental morphological features of the native ligament. An aligned fibrous component was used to mimic the fibrous collagen network and a hydrogel component to mimic the proteoglycan-water matrix of the ligament. The composite scaffold was constructed from cell-adherent, base-etched, electrospun poly(epsilon-caprolactone-co-D,L-lactide) (PCLDLLA) fibers embedded in a noncell-adherent photocrosslinked N-methacrylated glycol chitosan (MGC) hydrogel seeded with primary ligament fibroblasts. Base etching improved cellular adhesion to the PCLDLLA material. Cells within the MGC hydrogel remained viable (72 +/- 4%) during the 4-week culture period. Immunohistochemistry staining revealed ligament ECM markers collagen type I, collagen type III, and decorin organizing and accumulating along the PCLDLLA fibers within the composite scaffolds. On the basis of these results, it was determined that the composite scaffold design was a viable alternative to the current approaches used for ligament tissue engineering and merits further study. (c) 2009 Wiley Periodicals, Inc.

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.

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

PubMed

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

2009-08-01

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

New approaches to increase intestinal length: Methods used for intestinal regeneration and bioengineering

PubMed Central

Shirafkan, Ali; Montalbano, Mauro; McGuire, Joshua; Rastellini, Cristiana; Cicalese, Luca

2016-01-01

Inadequate absorptive surface area poses a great challenge to the patients suffering a variety of intestinal diseases causing short bowel syndrome. To date, these patients are managed with total parenteral nutrition or intestinal transplantation. However, these carry significant morbidity and mortality. Currently, by emergence of tissue engineering, anticipations to utilize an alternative method to increase the intestinal absorptive surface area are increasing. In this paper, we will review the improvements made over time in attempting elongating the intestine with surgical techniques as well as using intestinal bioengineering. Performing sequential intestinal lengthening was the preliminary method applied in humans. However, these methods did not reach widespread use and has limited outcome. Subsequent experimental methods were developed utilizing scaffolds to regenerate intestinal tissue and organoids unit from the intestinal epithelium. Stem cells also have been studied and applied in all types of tissue engineering. Biomaterials were utilized as a structural support for naive cells to produce bio-engineered tissue that can achieve a near-normal anatomical structure. A promising novel approach is the elongation of the intestine with an acellular biologic scaffold to generate a neo-formed intestinal tissue that showed, for the first time, evidence of absorption in vivo. In the large intestine, studies are more focused on regeneration and engineering of sphincters and will be briefly reviewed. From the review of the existing literature, it can be concluded that significant progress has been achieved in these experimental methods but that these now need to be fully translated into a pre-clinical and clinical experimentation to become a future viable therapeutic option. PMID:27011901

An update-tissue engineered nerve grafts for the repair of peripheral nerve injuries.

PubMed

Patel, Nitesh P; Lyon, Kristopher A; Huang, Jason H

2018-05-01

Peripheral nerve injuries (PNI) are caused by a range of etiologies and result in a broad spectrum of disability. While nerve autografts are the current gold standard for the reconstruction of extensive nerve damage, the limited supply of autologous nerve and complications associated with harvesting nerve from a second surgical site has driven groups from multiple disciplines, including biomedical engineering, neurosurgery, plastic surgery, and orthopedic surgery, to develop a suitable or superior alternative to autografting. Over the last couple of decades, various types of scaffolds, such as acellular nerve grafts (ANGs), nerve guidance conduits, and non-nervous tissues, have been filled with Schwann cells, stem cells, and/or neurotrophic factors to develop tissue engineered nerve grafts (TENGs). Although these have shown promising effects on peripheral nerve regeneration in experimental models, the autograft has remained the gold standard for large nerve gaps. This review provides a discussion of recent advances in the development of TENGs and their efficacy in experimental models. Specifically, TENGs have been enhanced via incorporation of genetically engineered cells, methods to improve stem cell survival and differentiation, optimized delivery of neurotrophic factors via drug delivery systems (DDS), co-administration of platelet-rich plasma (PRP), and pretreatment with chondroitinase ABC (Ch-ABC). Other notable advancements include conduits that have been bioengineered to mimic native nerve structure via cell-derived extracellular matrix (ECM) deposition, and the development of transplantable living nervous tissue constructs from rat and human dorsal root ganglia (DRG) neurons. Grafts composed of non-nervous tissues, such as vein, artery, and muscle, will be briefly discussed.

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

Methodology of citrate-based biomaterial development and application

NASA Astrophysics Data System (ADS)

Tran, M. Richard

Biomaterials play central roles in modern strategies of regenerative medicine and tissue engineering. Attempts to find tissue-engineered solutions to cure various injuries or diseases have led to an enormous increase in the number of polymeric biomaterials over the past decade. The breadth of new materials arises from the multiplicity of anatomical locations, cell types, and mode of application, which all place application-specific requirements on the biomaterial. Unfortunately, many of the currently available biodegradable polymers are limited in their versatility to meet the wide range of requirements for tissue engineering. Therefore, a methodology of biomaterial development, which is able to address a broad spectrum of requirements, would be beneficial to the biomaterial field. This work presents a methodology of citrate-based biomaterial design and application to meet the multifaceted needs of tissue engineering. We hypothesize that (1) citric acid, a non-toxic metabolic product of the body (Krebs Cycle), can be exploited as a universal multifunctional monomer and reacted with various diols to produce a new class of soft biodegradable elastomers with the flexibility to tune the material properties of the resulting material to meet a wide range of requirements; (2) the newly developed citrate-based polymers can be used as platform biomaterials for the design of novel tissue engineering scaffolding; and (3) microengineering approaches in the form thin scaffold sheets, microchannels, and a new porogen design can be used to generate complex cell-cell and cell-microenvironment interactions to mimic tissue complexity and architecture. To test these hypotheses, we first developed a methodology of citrate-based biomaterial development through the synthesis and characterization of a family of in situ crosslinkable and urethane-doped elastomers, which are synthesized using simple, cost-effective strategies and offer a variety methods to tailor the material properties to meet the needs of a particular application. Next, we introduced a new porogen generation technique, and showed the potential application of the newly developed materials through the fabrication and characterization of scaffold sheets, multiphasic small diameter vascular grafts, and multichanneled nerve guides. Finally, the in vivo applications of citrate-based materials are exemplified through the evaluation of peripheral nerve regeneration using multichanneled guides and the ability to assist in injection-based endoscopic mucosal resection therapy. The results presented in this work show that citric acid can be utilized as a cornerstone in the development of novel biodegradable materials, and combined with microengineering approaches to produce the next generation of tissue engineering scaffolding. These enabling new biomaterials and scaffolding strategies should address many of the existing challenges in tissue engineering and advance the field as a whole.

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.

Recent advancements in regenerative dentistry: A review.

PubMed

Amrollahi, Pouya; Shah, Brinda; Seifi, Amir; Tayebi, Lobat

2016-12-01

Although human mouth benefits from remarkable mechanical properties, it is very susceptible to traumatic damages, exposure to microbial attacks, and congenital maladies. Since the human dentition plays a crucial role in mastication, phonation and esthetics, finding promising and more efficient strategies to reestablish its functionality in the event of disruption has been important. Dating back to antiquity, conventional dentistry has been offering evacuation, restoration, and replacement of the diseased dental tissue. However, due to the limited ability and short lifespan of traditional restorative solutions, scientists have taken advantage of current advancements in medicine to create better solutions for the oral health field and have coined it "regenerative dentistry." This new field takes advantage of the recent innovations in stem cell research, cellular and molecular biology, tissue engineering, and materials science etc. In this review, the recently known resources and approaches used for regeneration of dental and oral tissues were evaluated using the databases of Scopus and Web of Science. Scientists have used a wide range of biomaterials and scaffolds (artificial and natural), genes (with viral and non-viral vectors), stem cells (isolated from deciduous teeth, dental pulp, periodontal ligament, adipose tissue, salivary glands, and dental follicle) and growth factors (used for stimulating cell differentiation) in order to apply tissue engineering approaches to dentistry. Although they have been successful in preclinical and clinical partial regeneration of dental tissues, whole-tooth engineering still seems to be far-fetched, unless certain shortcomings are addressed. Copyright © 2016 Elsevier B.V. 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.

The application of multiple biophysical cues to engineer functional neocartilage for treatment of osteoarthritis. Part I: cellular response.

PubMed

Brady, Mariea A; Waldman, Stephen D; Ethier, C Ross

2015-02-01

Osteoarthritis (OA) is a complex disease of the joint for which current treatments are unsatisfactory, thus motivating development of tissue engineering (TE)-based therapies. To date, TE strategies have had some success, developing replacement tissue constructs with biochemical properties approaching that of native cartilage. However, poor biomechanical properties and limited postimplantation integration with surrounding tissue are major shortcomings that need to be addressed. Functional tissue engineering strategies that apply physiologically relevant biophysical cues provide a platform to improve TE constructs before implantation. In the previous decade, new experimental and theoretical findings in cartilage biomechanics and electromechanics have emerged, resulting in an increased understanding of the complex interplay of multiple biophysical cues in the extracellular matrix of the tissue. The effect of biophysical stimulation on cartilage, and the resulting chondrocyte-mediated biosynthesis, remodeling, degradation, and repair, has, therefore, been extensively explored by the TE community. This article compares and contrasts the cellular response of chondrocytes to multiple biophysical stimuli, and may be read in conjunction with its companion paper that compares and contrasts the subsequent intracellular signal transduction cascades. Mechanical, magnetic, and electrical stimuli promote proliferation, differentiation, and maturation of chondrocytes within established dose parameters or "biological windows." This knowledge will provide a framework for ongoing studies incorporating multiple biophysical cues in TE functional neocartilage for treatment of OA.

Three-Dimensional Scaffolds for Tissue Engineering Applications: Role of Porosity and Pore Size

PubMed Central

Loh, Qiu Li

2013-01-01

Tissue engineering applications commonly encompass the use of three-dimensional (3D) scaffolds to provide a suitable microenvironment for the incorporation of cells or growth factors to regenerate damaged tissues or organs. These scaffolds serve to mimic the actual in vivo microenvironment where cells interact and behave according to the mechanical cues obtained from the surrounding 3D environment. Hence, the material properties of the scaffolds are vital in determining cellular response and fate. These 3D scaffolds are generally highly porous with interconnected pore networks to facilitate nutrient and oxygen diffusion and waste removal. This review focuses on the various fabrication techniques (e.g., conventional and rapid prototyping methods) that have been employed to fabricate 3D scaffolds of different pore sizes and porosity. The different pore size and porosity measurement methods will also be discussed. Scaffolds with graded porosity have also been studied for their ability to better represent the actual in vivo situation where cells are exposed to layers of different tissues with varying properties. In addition, the ability of pore size and porosity of scaffolds to direct cellular responses and alter the mechanical properties of scaffolds will be reviewed, followed by a look at nature's own scaffold, the extracellular matrix. Overall, the limitations of current scaffold fabrication approaches for tissue engineering applications and some novel and promising alternatives will be highlighted. PMID:23672709

Surface Entrapment of Fibronectin on Electrospun PLGA Scaffolds for Periodontal Tissue Engineering

PubMed Central

Gritsch, Kerstin; Salles, Vincent; Attik, Ghania N.; Grosgogeat, Brigitte

2014-01-01

Abstract Nowadays, the challenge in the tissue engineering field consists in the development of biomaterials designed to regenerate ad integrum damaged tissues. Despite the current use of bioresorbable polyesters such as poly(l-lactide) (PLA), poly(d,l-lactide-co-glycolide) (PLGA), and poly-ɛ-caprolactone in soft tissue regeneration researches, their hydrophobic properties negatively influence the cell adhesion. Here, to overcome it, we have developed a fibronectin (FN)-functionalized electrospun PLGA scaffold for periodontal ligament regeneration. Functionalization of electrospun PLGA scaffolds was performed by alkaline hydrolysis (0.1 or 0.01 M NaOH). Then, hydrolyzed scaffolds were coated by simple deposition of an FN layer (10 μg/mL). FN coating was evidenced by X-ray photoelectron analysis. A decrease of contact angle and greater cell adhesion to hydrolyzed, FN-coated PLGA scaffolds were noticed. Suitable degradation behavior without pH variations was observed for all samples up to 28 days. All treated materials presented strong shrinkage, fiber orientation loss, and collapsed fibers. However, functionalization process using 0.01 M NaOH concentration resulted in unchanged scaffold porosity, preserved chemical composition, and similar mechanical properties compared with untreated scaffolds. The proposed simplified method to functionalize electrospun PLGA fibers is an efficient route to make polyester scaffolds more biocompatible and shows potential for tissue engineering. PMID:24940563

Stem Cell Extracellular Vesicles: Extended Messages of Regeneration

PubMed Central

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

2017-01-01

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

Infused polymers for cell sheet release

NASA Astrophysics Data System (ADS)

Juthani, Nidhi; Howell, Caitlin; Ledoux, Haylea; Sotiri, Irini; Kelso, Susan; Kovalenko, Yevgen; Tajik, Amanda; Vu, Thy L.; Lin, Jennifer J.; Sutton, Amy; Aizenberg, Joanna

2016-05-01

Tissue engineering using whole, intact cell sheets has shown promise in many cell-based therapies. However, current systems for the growth and release of these sheets can be expensive to purchase or difficult to fabricate, hindering their widespread use. Here, we describe a new approach to cell sheet release surfaces based on silicone oil-infused polydimethylsiloxane. By coating the surfaces with a layer of fibronectin (FN), we were able to grow mesenchymal stem cells to densities comparable to those of tissue culture polystyrene controls (TCPS). Simple introduction of oil underneath an edge of the sheet caused it to separate from the substrate. Characterization of sheets post-transfer showed that they retain their FN layer and morphology, remain highly viable, and are able to grow and proliferate normally after transfer. We expect that this method of cell sheet growth and detachment may be useful for low-cost, flexible, and customizable production of cellular layers for tissue engineering.

Infused polymers for cell sheet release

PubMed Central

Juthani, Nidhi; Howell, Caitlin; Ledoux, Haylea; Sotiri, Irini; Kelso, Susan; Kovalenko, Yevgen; Tajik, Amanda; Vu, Thy L.; Lin, Jennifer J.; Sutton, Amy; Aizenberg, Joanna

2016-01-01

Tissue engineering using whole, intact cell sheets has shown promise in many cell-based therapies. However, current systems for the growth and release of these sheets can be expensive to purchase or difficult to fabricate, hindering their widespread use. Here, we describe a new approach to cell sheet release surfaces based on silicone oil-infused polydimethylsiloxane. By coating the surfaces with a layer of fibronectin (FN), we were able to grow mesenchymal stem cells to densities comparable to those of tissue culture polystyrene controls (TCPS). Simple introduction of oil underneath an edge of the sheet caused it to separate from the substrate. Characterization of sheets post-transfer showed that they retain their FN layer and morphology, remain highly viable, and are able to grow and proliferate normally after transfer. We expect that this method of cell sheet growth and detachment may be useful for low-cost, flexible, and customizable production of cellular layers for tissue engineering. PMID:27189419

Infused polymers for cell sheet release.

PubMed

Juthani, Nidhi; Howell, Caitlin; Ledoux, Haylea; Sotiri, Irini; Kelso, Susan; Kovalenko, Yevgen; Tajik, Amanda; Vu, Thy L; Lin, Jennifer J; Sutton, Amy; Aizenberg, Joanna

2016-05-18

Tissue engineering using whole, intact cell sheets has shown promise in many cell-based therapies. However, current systems for the growth and release of these sheets can be expensive to purchase or difficult to fabricate, hindering their widespread use. Here, we describe a new approach to cell sheet release surfaces based on silicone oil-infused polydimethylsiloxane. By coating the surfaces with a layer of fibronectin (FN), we were able to grow mesenchymal stem cells to densities comparable to those of tissue culture polystyrene controls (TCPS). Simple introduction of oil underneath an edge of the sheet caused it to separate from the substrate. Characterization of sheets post-transfer showed that they retain their FN layer and morphology, remain highly viable, and are able to grow and proliferate normally after transfer. We expect that this method of cell sheet growth and detachment may be useful for low-cost, flexible, and customizable production of cellular layers for tissue engineering.

Electrospinning polymer blends for biomimetic scaffolds for ACL tissue engineering

NASA Astrophysics Data System (ADS)

Garcia, Vanessa Lizeth

The anterior cruciate ligament (ACL) rupture is one of the most common knee injuries. Current ACL reconstructive strategies consist of using an autograft or an allograft to replace the ligament. However, limitations have led researchers to create tissue engineered grafts, known as scaffolds, through electrospinning. Scaffolds made of natural and synthetic polymer blends have the potential to promote cell adhesion while having strong mechanical properties. However, enzymes found in the knee are known to degrade tissues and affect the healing of intra-articular injuries. Results suggest that the natural polymers used in this study modify the thermal properties and tensile strength of the synthetic polymers when blended. Scanning electron microscopy display bead-free and enzyme biodegradability of the fibers. Raman spectroscopy confirms the presence of the natural and synthetic polymers in the scaffolds while, amino acid analysis present the types of amino acids and their concentrations found in the natural polymers.

Accelerated wound healing in a diabetic rat model using decellularized dermal matrix and human umbilical cord perivascular cells

PubMed Central

Milan, P. Brouki; Lotfibakhshaiesh, N.; Joghataie, M.T.; Ai, J.; Pazouki, A.; Kaplan, D.L.; kargozar, S.; Amini, N.; Hamblin, M.R.; Mozafari, M.; Samadikuchaksaraei, A.

2016-01-01

There is an unmet clinical need for novel wound healing strategies to treat full thickness skin defects, especially in diabetic patients. We hypothesized that a scaffold could perform dual roles of a biomechanical support and a favorable biochemical environment for stem cells. Human umbilical cord perivascular cells (HUCPVCs) have been recently reported as a type of mesenchymal stem cell that can accelerate early wound healing in skin defects. However, there are only a limited number of studies that have incorporated these cells into natural scaffolds for dermal tissue engineering. The aim of the present study was to promote angiogenesis and accelerate wound healing by using HUCPVCs and decellularized dermal matrix (DDM) in a rat model of diabetic wounds. The DDM scaffolds were prepared from harvested human skin samples and histological, ultrastructural, molecular and mechanical assessments were carried out. In comparison with the control (without any treatment) and DDM alone group, full thickness excisional wounds treated with HUCPVCs-loaded DDM scaffolds demonstrated an accelerated wound closure rate, faster re-epithelization, more granulation tissue formation and decreased collagen deposition. Furthermore, immunofluorescence analysis showed that the VEGFR-2 expression and vascular density in the HUCPVCs-loaded DDM scaffold treated group were also significantly higher than the other groups at 7 days post implantation. Since the rates of angiogenesis, re-epithelization and formation of granulation tissue are directly correlated with full thickness wound healing in patients, the proposed HUCPVCs-loaded DDM scaffolds may fulfil a role neglected by current treatment strategies. This pre-clinical proof-of-concept study warrants further clinical evaluation. Statement of Significance The aim of the present study was to design a novel tissue-engineered system to promote angiogenesis, re-epithelization and granulation of skin tissue using human umbilical cord perivascular stem cells and decellularized dermal matrix natural scaffolds in rat diabetic wound models. The authors of this research article have been working on stem cells and tissue engineering scaffolds for years. According to our knowledge, there is a lack of an efficient system for the treatment of skin defects using tissue engineering strategy. Since the rates of angiogenesis, re-epithelization and granulation tissue are directly correlated with full thickness wound healing, the proposed HUCPVCs-loaded DDM scaffolds perfectly fills the niche neglected by current treatment strategies. This pre-clinical study demonstrates the proof-of-concept that necessitates clinical evaluations. PMID:27591919

Accelerated wound healing in a diabetic rat model using decellularized dermal matrix and human umbilical cord perivascular cells.

PubMed

Milan, P Brouki; Lotfibakhshaiesh, N; Joghataie, M T; Ai, J; Pazouki, A; Kaplan, D L; Kargozar, S; Amini, N; Hamblin, M R; Mozafari, M; Samadikuchaksaraei, A

2016-11-01

There is an unmet clinical need for novel wound healing strategies to treat full thickness skin defects, especially in diabetic patients. We hypothesized that a scaffold could perform dual roles of a biomechanical support and a favorable biochemical environment for stem cells. Human umbilical cord perivascular cells (HUCPVCs) have been recently reported as a type of mesenchymal stem cell that can accelerate early wound healing in skin defects. However, there are only a limited number of studies that have incorporated these cells into natural scaffolds for dermal tissue engineering. The aim of the present study was to promote angiogenesis and accelerate wound healing by using HUCPVCs and decellularized dermal matrix (DDM) in a rat model of diabetic wounds. The DDM scaffolds were prepared from harvested human skin samples and histological, ultrastructural, molecular and mechanical assessments were carried out. In comparison with the control (without any treatment) and DDM alone group, full thickness excisional wounds treated with HUCPVCs-loaded DDM scaffolds demonstrated an accelerated wound closure rate, faster re-epithelization, more granulation tissue formation and decreased collagen deposition. Furthermore, immunofluorescence analysis showed that the VEGFR-2 expression and vascular density in the HUCPVCs-loaded DDM scaffold treated group were also significantly higher than the other groups at 7days post implantation. Since the rates of angiogenesis, re-epithelization and formation of granulation tissue are directly correlated with full thickness wound healing in patients, the proposed HUCPVCs-loaded DDM scaffolds may fulfil a role neglected by current treatment strategies. This pre-clinical proof-of-concept study warrants further clinical evaluation. The aim of the present study was to design a novel tissue-engineered system to promote angiogenesis, re-epithelization and granulation of skin tissue using human umbilical cord perivascular stem cells and decellularized dermal matrix natural scaffolds in rat diabetic wound models. The authors of this research article have been working on stem cells and tissue engineering scaffolds for years. According to our knowledge, there is a lack of an efficient system for the treatment of skin defects using tissue engineering strategy. Since the rates of angiogenesis, re-epithelization and granulation tissue are directly correlated with full thickness wound healing, the proposed HUCPVCs-loaded DDM scaffolds perfectly fills the niche neglected by current treatment strategies. This pre-clinical study demonstrates the proof-of-concept that necessitates clinical evaluations. Copyright © 2016. Published by Elsevier Ltd.

Practical Modeling Concepts for Connective Tissue Stem Cell and Progenitor Compartment Kinetics

PubMed Central

2003-01-01

Stem cell activation and development is central to skeletal development, maintenance, and repair, as it is for all tissues. However, an integrated model of stem cell proliferation, differentiation, and transit between functional compartments has yet to evolve. In this paper, the authors review current concepts in stem cell biology and progenitor cell growth and differentiation kinetics in the context of bone formation. A cell-based modeling strategy is developed and offered as a tool for conceptual and quantitative exploration of the key kinetic variables and possible organizational hierarchies in bone tissue development and remodeling, as well as in tissue engineering strategies for bone repair. PMID:12975533

Application of laser scanning confocal microscopy in the soft tissue exquisite structure for 3D scan

PubMed Central

Zhang, Zhaoqiang; Ibrahim, Mohamed; Fu, Yang; Wu, Xujia; Ren, Fei; Chen, Lei

2018-01-01

Three-dimensional (3D) printing is a new developing technology for printing individualized materials swiftly and precisely in the field of biological medicine (especially tissue-engineered materials). Prior to printing, it is necessary to scan the structure of the natural biological tissue, then construct the 3D printing digital model through optimizing the scanned data. By searching the literatures, magazines at home and abroad, this article reviewed the current status, main processes and matters needing attention of confocal laser scanning microscope (LSCM) in the application of soft tissue fine structure 3D scanning, empathizing the significance of LSCM in this field. PMID:29755838

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

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

The Tissue-Engineered Vascular Graft—Past, Present, and Future

PubMed Central

Pashneh-Tala, Samand; MacNeil, Sheila

2016-01-01

Cardiovascular disease is the leading cause of death worldwide, with this trend predicted to continue for the foreseeable future. Common disorders are associated with the stenosis or occlusion of blood vessels. The preferred treatment for the long-term revascularization of occluded vessels is surgery utilizing vascular grafts, such as coronary artery bypass grafting and peripheral artery bypass grafting. Currently, autologous vessels such as the saphenous vein and internal thoracic artery represent the gold standard grafts for small-diameter vessels (<6 mm), outperforming synthetic alternatives. However, these vessels are of limited availability, require invasive harvest, and are often unsuitable for use. To address this, the development of a tissue-engineered vascular graft (TEVG) has been rigorously pursued. This article reviews the current state of the art of TEVGs. The various approaches being explored to generate TEVGs are described, including scaffold-based methods (using synthetic and natural polymers), the use of decellularized natural matrices, and tissue self-assembly processes, with the results of various in vivo studies, including clinical trials, highlighted. A discussion of the key areas for further investigation, including graft cell source, mechanical properties, hemodynamics, integration, and assessment in animal models, is then presented. PMID:26447530

Bioprinting for Neural Tissue Engineering.

PubMed

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

2018-01-01

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

A novel porous scaffold fabrication technique for epithelial and endothelial tissue engineering.

PubMed

McHugh, Kevin J; Tao, Sarah L; Saint-Geniez, Magali

2013-07-01

Porous scaffolds have the ability to minimize transport barriers for both two- (2D) and three-dimensional tissue engineering. However, current porous scaffolds may be non-ideal for 2D tissues such as epithelium due to inherent fabrication-based characteristics. While 2D tissues require porosity to support molecular transport, pores must be small enough to prevent cell migration into the scaffold in order to avoid non-epithelial tissue architecture and compromised function. Though electrospun meshes are the most popular porous scaffolds used today, their heterogeneous pore size and intense topography may be poorly-suited for epithelium. Porous scaffolds produced using other methods have similar unavoidable limitations, frequently involving insufficient pore resolution and control, which make them incompatible with 2D tissues. In addition, many of these techniques require an entirely new round of process development in order to change material or pore size. Herein we describe "pore casting," a fabrication method that produces flat scaffolds with deterministic pore shape, size, and location that can be easily altered to accommodate new materials or pore dimensions. As proof-of-concept, pore-cast poly(ε-caprolactone) (PCL) scaffolds were fabricated and compared to electrospun PCL in vitro using canine kidney epithelium, human colon epithelium, and human umbilical vein endothelium. All cell types demonstrated improved morphology and function on pore-cast scaffolds, likely due to reduced topography and universally small pore size. These results suggest that pore casting is an attractive option for creating 2D tissue engineering scaffolds, especially when the application may benefit from well-controlled pore size or architecture.