Concept Of Tissue Engineering Research Articles

SH15 THE EVOLUTION OF BREAST RECONSTRUCTION

Mastectomy is frequently used in the treatment and prophylaxis of malignant breast disease, thus reconstruction of the breast has become a significant part of the management of breast cancer. With advances in anatomical knowledge, surgical techniques and prostheses, a multitude of options for reconstruction have surfaced. These options have provided improvements in cosmetic outcome, operative recovery and operative morbidity. Attempts at achieving optimal breast reconstruction has progressed greatly from the transfer of a lipoma in 1895, to the current use of free tissue transfer. Autologous reconstruction has evolved such that the reconstructive surgeon can choose from pedicled transfer of rectus abdominis, to the free transfer of gracilis. Implant based techniques have come far since the initial use of paraffin injections in 1889, to the current use of tissue expanders and saline implants. Endoscopic techniques have recently gained popularity, offering patients minimized operative morbidity, reduced hospital stay and reduced scar formation. As the search for optimal breast reconstruction continues, the concept of tissue engineering offers yet another pathway to achieving near normal anatomy for the patient. Human mesenchymal stem cells differentiated into adipocytes have successfully been grown into pre‐defined shapes using cell‐scaffold constructs, or hydro‐gels, however generating an adequate blood supply to sustain an adipose unit of clinically significant size remains a challenge. This paper serves to acknowledge the significant contributions made by our predecessors to the art of breast reconstruction, as well as offer an insight to the prospects for its future.

Modeling fluid flow through irregular scaffolds for perfusion bioreactors

Direct perfusion of 3D tissue engineered constructs is known to enhance osteogenesis, which can be partly attributed to enhanced nutrient and waste transport. In addition flow mediated shear stresses are known to upregulate osteogenic differentiation and mineralization. A quantification of the hydrodynamic environment is therefore crucial to interpret and compare results of in vitro bioreactor experiments. This study aims to deal with the pitfalls of numerical model preparation of highly complex 3D bone scaffold structures and aims to provide more accurate wall shear stress (WSS) estimates. microCT imaging techniques were used to reconstruct the geometry of both a titanium (Ti) and a hydroxyapatite scaffold, starting from 430 images with a resolution of 8 microm. To tackle the tradeoff between model size and mesh resolution we selected two concentric regions of interest (cubes with a volume of 1 and 3.375 mm(3), respectively) for both scaffolds. A flow guidance in front of the real inlet surface of the scaffold was designed to mimic realistic inlet conditions. With a flow rate of 0.04 mL/min perfused through a 5 mm diameter scaffold at an inlet velocity of 33.95 microm/s we obtained average WSSs of 1.10 and 1.46 mPa for the 1 mm(3) and the 3.375 mm(3) model of the hydroxyapatite scaffold compared to 1.40 and 1.95 mPa for the 1 mm(3) model and the 3.375 mm(3) model of the Ti scaffold, showing the important influence of the scaffold micro-architecture heterogeneity and the proximity of boundaries. To assess that influence we selected cubic portions, of which the WSS data were analyzed, with the same size and the same location within both 1 and 3.375 mm(3) cubic models. Varying the size of the inner portions simultaneously in both model selections gives a quantification of the sensitivity to boundary neighborhood. This methodology allows to get more insight in the complex concept of tissue engineering and will likely help to understand and eventually improve the fluid-mechanical aspects.

Tissue engineering in endodontics

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

The Orthodontist's Role in 21st Century Periodontic-Prosthodontic Therapy

Often orthodontists can be of considerable assistance in periodontal and prosthodontic treatment. The orthodontists' principle periodontal objective with so-called facilitative care is to reduce or prevent excessive periodontal surgery by establishing a physiologic alveolar crestal topography. This can be done by recognizing the effect of orthodontic tooth movement (OTM) on the alveloar topography and engineering the desired contour with selective force gradients in concert with minor periodontal surgery.With this synergistic orchestration between specials the prosthetic foundation is more stable, the esthetic contour of the gingiva is improved and, most important, unnecessary removal of alveolar bone is avoided because pathologic contours due to tooth malalignment are eliminated prior to osseous surgery. Case studies are integrated herein with emerging 21st century concepts of periodontal tissue engineering

Liver tissue engineering: The future of liver therapeutics

The applications derived from the concept of tissue engineering have spurred significant interest in the field of regenerative medicine as novel, next generation therapies. Due to a lack of treatment modalities for patients suffering from many forms of liver diseases, recent studies have touted that engineering hepatic tissues de novo in culture may be a viable method to address this therapeutic void. Liver tissue engineering is a new and emerging field in which a functional liver system is created in vivo using isolated hepatocytes and/or other cells types to treat acute and chronic liver diseases. Under circumstances in which a small, but functional liver tissue system could be engineered to provide the equivalent biological function proportional to a few percent of a normal, well-functioning liver, it would be possible to correct many disease phenotypes as a result of various forms of inherited metabolic deficiencies. Alternatively, hepatic tissues can be engineered rapidly to produce therapeutic effects allowing this approach to become an effective modality in the treatment of acute liver failure. Strategies to achieve high levels of hepatocyte survival and the development of methods to engineer a functional liver system in vivo will be discussed in this review.

Cell therapy for bone regeneration—Bench to bedside

The concept of bone tissue engineering, which began in the early 1980s, has seen tremendous growth in the numbers of research studies. One of the key areas of research has been in the field of mesenchymal stem cells, where the challenge is to produce the perfect tissue-engineered bone construct. This practical review summarizes basic and applied state-of-the-art research in the area of mesenchymal stem cells, and highlights the important translational research that has already been initiated. The topics that will be covered include the sources of stem cells in use, scaffolds, gene therapy, clinical applications in nonunions, tumors, osteonecrosis, revision arthroplasties, and spine fusion. Although significant challenges remain, there exists an exceptional opportunity to translate basic research in mesenchymal stem cell technologies into viable clinical treatments for bone regeneration.

Herzgewebe aus embryonalen Stammzellen

Embryonic stem cells can give rise to all somatic cells, making them an attractive cell source for tissue engineering applications. The propensity of cells to form tissue-like structures in a culture dish has been well documented. We and others made use of this intrinsic property to generate bioartificial heart muscle. First proof-of-concept studies involved immature heart cells mainly from fetal chicken, neonatal rats and mice. They eventually provided evidence that force-generating heart muscle can be engineered in vitro. Recently, the focus shifted to the application of stem cells to eventually enable the generation of human heart muscle and reach following long-term goals: (1) development of a simplified in vitro model of heart muscle development; (2) generation of a human test-bed for drug screening and development; (3) allocation of surrogate heart tissue to myocardial repair applications. This overview will provide the background for cell-based myocardial repair, introduce the main myocardial tissue engineering concepts, discuss the use of embryonic and non-embryonic stem cells, and lays out the potential direct and indirect therapeutic use of human tissue engineered myocardium.

Crossing Frontiers in Biomaterials and Regenerative Medicine

From 28 May–1 June 2008, the 8th World Biomaterials Congress (WBC) was held in Amsterdam, The Netherlands. The meeting attracted 3052 participants from 82 countries, which has made this congress the largest meeting ever held in the field of biomaterials and regenerative medicine. More than 650 oral and 1500 poster contributions [1] were presented in 108 scientific sessions, divided into nine parallel sessions, including 48 dedicated symposia that had been proposed by international leaders in the field. The symposia each contained an invited keynote, providing expert opinions on current developments in biomaterials research. Historically, research in the field of biomaterials has focused on the optimization of materials by increasing their compatibility with living tissue. In the last two decades, however, this focus has gradually shifted from conventional materials science and engineering towards an integrated approach involving material scientists as well as biologists and clinicians of various disciplines. Clearly, a major paradigm shift occurred around the early 1990s. At that time, research efforts were increasingly aimed at improving and replacing biological functions, including the concept of tissue engineering, by combining the three key elements of tissue engineering: cells, biologically active molecules and carrier materials called scaffolds or matrices. By the subsequent convergence of stem cell research with tissue engineering during the early 2000s, the even broader field of regenerative medicine emerged, which focuses in general on the replacement or regeneration of human cells, tissue or organs in order to restore or establish normal function. The papers that were presented at the WBC clearly illustrated the current trend in biomaterials research that focuses on regenerative approaches through careful design of functional materials. The five plenary lecturers provided the attendees of the WBC meeting with a clear and inspiring update of the latest developments in regenerative medicine. It is highly significant that although the five plenary speakers represent the combined fields of materials science, chemical engineering and polymer chemistry, all based their presentations on the translational aspects from ‘bench to bedside’. This awareness of patient needs and the requirement to build multidisciplinary research consortia represents a major focus of this field, and is in marked contrast to the biomaterial science of the past decades, when material and life scientists tended to be preoccupied with the exciting developments within their own disciplines. This multiand interdisciplinary approach as a scientific philosophy as well as the progress which it is expected to bring lay behind the theme chosen for the WBC, namely ‘Crossing Frontiers in Biomaterials and Regenerative Medicine’, and was exemplified by the research activity of the plenary speakers.

Current Concepts in Meniscus Tissue Engineering

After partial or total meniscus resection, cartilage degeneration can be observed in many knee joints, frequently culminating in osteoarthritic changes. Therefore, a meniscus preserving therapy should be performed whenever possible. However, despite improved surgical techniques and new treatment strategies, meniscal tissue resection cannot always be avoided. Currently, only few treatment options are available after total meniscectomy, a dissatisfying situation considering that many patients presenting with meniscal injuries are young patients. Transplantation of allogenous menisci has been valuable only in particular cases and does not seem to prevent degenerative changes in the affected knee joint. Because of the unsatisfactory clinical progression after resection of meniscal tissue, new tissue engineering concepts are eagerly sought after. A first step towards a meniscus replacement therapy has been achieved with the development of a collagen meniscus implant (CMI), which has recently been approved for clinical application in Europe. This review will give a short overview about actual meniscus replacement therapies. Current experimental research concepts for meniscus tissue engineering and new perspectives for clinical treatment strategies will also be presented. Additionally, we will report about successful experimental application of new scaffolds and scaffolding materials, the use of different cell types and gene therapy approaches.

Spatial and temporal patterns of bone formation in ectopically pre-fabricated, autologous cell-based engineered bone flaps in rabbits.

Biological substitutes for autologous bone flaps could be generated by combining flap pre-fabrication and bone tissue engineering concepts. Here, we investigated the pattern of neotissue formation within large pre-fabricated engineered bone flaps in rabbits. Bone marrow stromal cells from 12 New Zealand White rabbits were expanded and uniformly seeded in porous hydroxyapatite scaffolds (tapered cylinders, 10–20 mm diameter, 30 mm height) using a perfusion bioreactor. Autologous cell-scaffold constructs were wrapped in a panniculus carnosus flap, covered by a semipermeable membrane and ectopically implanted. Histological analysis, substantiated by magnetic resonance imaging (MRI) and micro-computerized tomography scans, indicated three distinct zones: an outer one, including bone tissue; a middle zone, formed by fibrous connective tissue; and a central zone, essentially necrotic. The depths of connective tissue and of bone ingrowth were consistent at different construct diameters and significantly increased from respectively 3.1 ± 0.7 mm and 1.0 ± 0.4 mm at 8 weeks to 3.7± 0.6 mm and 1.4 ± 0.6 mm at 12 weeks. Bone formation was found at a maximum depth of 1.8 mm after 12 weeks. Our findings indicate the feasibility of ectopic pre-fabrication of large cell-based engineered bone flaps and prompt for the implementation of strategies to improve construct vascularization, in order to possibly accelerate bone formation towards the core of the grafts.

Applicability of cord blood‐derived unrestricted somatic stem cells in tissue engineering concepts

Cell-based tissue engineering concepts are becoming an important therapeutic alternative in the treatment of traumatic or chronic skeletal diseases. Here, we have evaluated cord blood-derived unrestricted somatic stem cells (USSCs) for use in bone and cartilage repair strategies. This type of somatic stem cell can be generated from cord blood with a current rate of 29% and we have documented excellent proliferation potential to high passage numbers. The cells have an initial population doubling time of 39 h, which slightly decreased with increasing passage number, but cells maintained their proliferation abilities up to passage 23. Cells clearly differentiated towards chondrogenic, adipogenic and osteogenic lineage as shown by reverse transcription-polymerase chain reaction as well as by histological, biochemical and immunohistochemical stains. Differentiation potential of USSCs was observed at passage 6, passage 15 and passage 21. In addition, USSCs showed increased secretion of vascular endothelial growth factor (VEGF) during osteogenic differentiation, as well as expression of key markers of angiogenesis such as vascular endothelial growth factor receptor-2 and platelet/endothelial cell adhesion molecule. USSCs when transplanted into a bone defect might support the repair process not only by pure remineralization but also by installation of angiogenic environment.

Stem cell-derived cardiac patches: A tissue engineering approach to cardiac healing

The role of adult stem cells in cardiac homeostasis and repair has been addressed by several studies and the possibility that resident or circulating progenitors could be transplanted into the damaged myocardium envisaged as a new perspective for the treatment of cardiac diseases. So far, few protocols based on the injection of cells into the injured site demonstrated the complexity of a cell-based approach to cardiac repair, suggesting the adoption of tissue engineering concepts to setup more suitable procedures. In the present study, a functional comparison between mesenchymal (MSC) vs. cardiac progenitor cells (CPC) is given by culturing them on biocompatible and bioerodible synthetic scaffolds. In such conditions, both cell types showed multipotential capacity and, when tested for their ability to grow on polymeric scaffolds of PLLA, PLGA and PCL produced by Pressure Assisted Mycrosyringe (PAM), expressed functional adhesion proteins, while preserving their multipotential capacity on 2D polymers. Interestingly, on 3D scaffolds with controlled tridimensional geometry, CPC were prompted to express the cardiac phenotype and formed a quasi-tissue on PLLA polymeric matrix, while MSC preserved their undifferentiated features. Such results demonstrate the feasibility of in vitro stem cell-derived cardiac patches and suggest that it is possible to obtain 3D bio-constructs with different degrees of induction to be used in cardiac tissue healing. Further investigations will be necessary to assess the activity of MSC- and CPC-based patches in vivo.

Regenerative medicine: enabling technologies for clinical translation

Tissue engineering and regenerative medicine has emerged as an innovative scientific field that focuses on development of new approaches to repairing cells, tissues and organs for clinical applications. Recent advances in this field have offered new therapeutic opportunities that facilitate the restoration and maintenance of normal tissue function. Consistent with the goals of tissue engineering and regenerative medicine, we have followed a strategy that has shown to be effective clinically. This approach involves the use of biocompatible matrices either with or without cells. The matrices are either used as cell delivery vehicles or as scaffolds to promote and enhance tissue regeneration. When cells are used, donor tissue is dissociated into individual cells, which are expanded in culture, attached to a support matrix, and reimplanted into recipient for recovery of tissue function.Over the past years, research investigations have been actively pursued in various tissue systems using tissue engineering and regenerative medicine concepts and technologies. Although these tissues have shown their potential applicability experimentally, only a limited number of tissues have been successfully engineered for clinical use to date. This is due to various obstacles encountered in the tissue building process. The progress toward clinical translation, current challenges hampering organ development and potential solutions to overcome technical hurdles will be discussed.

QS444. Cell Guidance: A New Concept for Tissue Engineering Using SDF-1 to Induce Site Directed Homing of Mesenchymal Stem Cells

Objective of Study: Cell guidance is a new tissue engineering concept aimed at total in vivo tissue engineering without the need for cell seeding. Conventional approaches which rely on seeding of cells within a scaffold to mimic cellular structure and recreate a functional tissue equivalent in vitro or in vivo are limited by donor site morbidity from harvesting of cells. SDF-1 is a chemokine previously shown to be vital in stem and progenitor cell recruitment for tissue repair after injury. This study was performed to investigate use of SDF-1 to induce homing of mesenchymal stem cells (MSCs) in order to demonstrate the feasibility of in vivo tissue engineering without the need for prior cell seeding before implantation of scaffolds.

Novel method of preparing hydroxyapatite foams

Porous scaffolds are considered a key strategy in the concept of bone tissue engineering. Hydroxyapatite, which is a bioceramic has been used as a popular scaffold material due to its bioactive and osteoconductive properties. A combination of slurry-dipping and electrospraying has been used as a new foam fabrication method to produce porous and interconnected foam structures. The combined method has shown to overcome the shortcomings of the individual methods and it has produced open pores in the desired range of 100-350 microm. The porosity which was determined by calculation and microtomography was between 84% and 88%. Reduced cracks and thicker struts were observed in the microstructure, pointing to improved mechanical properties.

Histological and biomechanical properties of regenerated articular cartilage using chondrogenic bone marrow stromal cells with a PLGA scaffold in vivo

The properties of regenerated cartilage using bone marrow-derived mesenchymal stem cells (MSCs) and poly lactic-co-glycolic acid (PLGA) scaffold composites pretreated with TGF-beta3 were investigated and compared to the non-TGF-beta3 treated MSCs/PLGA composites in a rabbit model. We prepared MSCs/PLGA scaffold composites and pretreated it with TGF-beta3 for 3 weeks prior to transplantation. Then, composites were transplanted to the osteochondral defect in the rabbit knee. After 12 weeks of transplantation, 10 of the 12 rabbits in which TGF-beta3 pretreated MSCs/PLGA scaffold composites were transplanted showed cartilaginous regeneration. In gross morphology, regenerated cartilage showed smooth, flush, and transparent features. In indentation test, this had about 80% of Young's modulus of normal articular cartilage. Histological examination demonstrated hyaline like cartilage structures with glycosaminoglycan and type II collagen expression. Histological scores were not statistically different to the normal articular cartilage. These results showed improvement of cartilage regeneration compared to the non-TGF-beta3 pretreated MSCs/PLGA scaffold composite transplanted group. Thus, we have successfully regenerated improved hyaline-like cartilage and determined the feasibility of treating damaged articular cartilage using MSCs/PLGA scaffold composite pretreated with TGF-beta3. Also, we suggest this treatment modality as another concept of cartilage tissue engineering.

Odontogenic differentiation of adipose-derived stem cells for tooth regeneration: necessity, possibility, and strategy

Tooth regeneration using tissue engineering concepts is a promising biological approach to solving problems of tooth loss in elderly patients. The seeding cells, however, for tooth regeneration such as odontoblasts from dental germ, stem cells from dental pulp and deciduous teeth, and ectomesenchymal cells from the first branchial arch are difficult, even impossible to harvest in clinic. Bone marrow mesenchymal stem cells have odontogenic capacity, but their differentiation abilities significantly decrease with the increasing age of the donors. Therefore, the cells mentioned above are not practical in the clinical application of tooth regeneration in the old. Adipose derived stem cells have many clinical advantages over bone marrow mesenchymal stem cells, and their differentiation potential can be maintained with aging. Here we propose the hypothesis that adipose derived stem cells could be induced into odontogenic lineage and might be used as suitable seeding cells for tooth regeneration to replace the lost tooth of elderly patients.

Cardiac Tissue Engineering: A Clinical Perspective

Engineered myocardium may be used to repair myocardial defects. Although not clinically applicable yet, initial studies in rodents have demonstrated the feasibility of tissue engineering based myocardial repair in vivo. In order for restorative treatment to evolve into a functional treatment modality, tissue engineers have to generate human myocardium of sufficient size and with relevant contractile function to replace/repair myocardial defects. This requires the identification of a scalable and ideally autologous cardiomyocyte source as well as the development of strategies to overcome size limitations. We will further address pivotal issues pertaining to the allocation of suitable human cells for myocardial tissue engineering and discuss the translation of present myocardial tissue engineering concepts into preclinical, as well as clinical, trials.

Adult mesenchymal stem cells and impaction grafting: a new clinical paradigm shift

The demographic challenges of an increasingly aging population emphasize the need for innovative approaches to skeletal reconstruction to augment and repair skeletal tissue lost as a consequence of implant loosening, trauma, degeneration or in situations involving revision surgery requiring bone stock. These clinical imperatives to augment skeletal tissue loss have brought mesenchymal stem cells to the fore in combination with the emerging discipline of tissue engineering. To date, impaction bone grafting for revision hip surgery is a recognized technique to reconstitute bone utilizing morselized allograft to provide a good mechanical scaffold, although with little osteoinductive biological potential. This review details laboratory and clinical examples of a paradigm shift in the application of mesenchymal stem cells with allograft to produce a living composite using the principles of tissue engineering. This step change creates a composite that offers a biological and mechanical advantage over the current gold standard of allograft alone. This translation of tissue engineering concepts into clinical practice offers enormous input into the field of bone regeneration and has implications for translation and future change in skeletal orthopedic practice in an increasingly aging population.

11th International Dental Congress on Modern Pain Control The Essential Role of Dental Anesthesiology in the 21st Century Safe and Comfortable Dentistry 4th–7th October, 2006

11th International Dental Congress on Modern Pain Control The Essential Role of Dental Anesthesiology in the 21st Century Safe and Comfortable Dentistry 4th–7th October, 2006