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Review: tissue engineering of the urinary bladder: considering structure-function relationships and the role of mechanotransduction.

A variety of conditions encountered in urology result in bladder dysfunction and the need for bioengineered tissue substitutes. Traditionally, a number of synthetic materials and natural matrices have been used in experimental and clinical settings. However, the production of functional bladder tissue replacements remains elusive. The urinary bladder sustains considerable structural deformation during its normal function and represents an ideal model tissue in which to study the effects of biomechanical simulation on tissue morphogenesis, differentiation, and function. However, the actual role of mechanical forces within the bladder has received little attention. A strategy in which in vitro-generated tissue constructs are conditioned by exposure to the same mechanical forces as they would encounter in vivo could potentially be used both in the development of functional tissue replacements and to further study the role of biomechanical signalling. The purpose of this review is to examine the role and structure-function relationship of the urinary bladder and, through consultation of the literature available on mechanotransduction and tissue engineering of alternative tissues, to determine the factors that need to be considered when biomechanically engineering a functional bladder.

Animals↗

Cartilage and bone regeneration using gene-enhanced tissue engineering.

Joint cartilage injury remains a major problem in orthopaedics with more than 500,000 cartilage repair procedures performed yearly in the United States at a cost of hundreds of millions of dollars. No consistently reliable means to regenerate joint cartilage currently exists. The technologies of gene therapy and tissue engineering were combined using a retroviral vector to stably introduce the human bone morphogenic protein-7 complementary deoxyribonucleic acid into periosteal-derived rabbit mesenchymal stem cells. Bone morphogenic protein-7 secreting gene modified cells subsequently were expanded in monolayer culture, seeded onto polyglycolic acid grafts, implanted into a rabbit knee osteochondral defect model, and evaluated for bone and cartilage repair after 4, 8, and 12 weeks. The grafts containing bone morphogenic protein-7 gene modified cells consistently showed complete or near complete bone and articular cartilage regeneration at 8 and 12 weeks whereas the grafts from the control groups had poor repair as judged by macroscopic, histologic, and immunohistologic criteria. This is the first report of articular cartilage regeneration using a combined gene therapy and tissue engineering approach.

Animals↗

Donor cell fate in tissue engineering for articular cartilage repair.

Articular cartilage repair is a clinical challenge because of its limited intrinsic healing potential. Considerable research has focused on tissue engineering and transplantation of viable chondrogenic cells to enhance cartilage regeneration. However, the question remains: do transplanted allogenic cells survive in the repair with time? This study assessed donor cell fate after transplantation of male New Zealand White rabbit perichondrium cell and polylactic acid constructs into osteochondral defects created in the medial femoral condyles of female New Zealand White rabbits. Repair tissue was harvested at 0, 1, 2, 3, 7, and 28 days after implantation and was evaluated for cell viability and total cell number using confocal microscopic analysis. The number of donor cells in each sample was estimated using quantitative polymerase chain reaction targeting a gender-specific gene present on the Y-chromosome, the sex-determining region Y gene, and a control deoxyribonucleic acid present in male and female cell deoxyribonucleic acid, the matrix metalloproteinase-1 gene promoter. Average cell viability was found to be 87% or more at all times. Donor cells were present in repair tissue for 28 days after implantation. However, the number of donor cells declined from approximately 1 million at Time 0 to approximately 140,000 at 28 days. This decline in donor cells was accompanied by a significant influx of host cells into the repair tissue. This study shows that the sex-determining region Y gene is a valuable marker for tracking the fate of transplanted allogenic cells in tissue engineering.

Animals↗

Challenges in tissue engineering.

Almost 30 years have passed since a term 'tissue engineering' was created to represent a new concept that focuses on regeneration of neotissues from cells with the support of biomaterials and growth factors. This interdisciplinary engineering has attracted much attention as a new therapeutic means that may overcome the drawbacks involved in the current artificial organs and organ transplantation that have been also aiming at replacing lost or severely damaged tissues or organs. However, the tissues regenerated by this tissue engineering and widely applied to patients are still very limited, including skin, bone, cartilage, capillary and periodontal tissues. What are the reasons for such slow advances in clinical applications of tissue engineering? This article gives the brief overview on the current tissue engineering, covering the fundamentals and applications. The fundamentals of tissue engineering involve the cell sources, scaffolds for cell expansion and differentiation and carriers for growth factors. Animal and human trials are the major part of the applications. Based on these results, some critical problems to be resolved for the advances of tissue engineering are addressed from the engineering point of view, emphasizing the close collaboration between medical doctors and biomaterials scientists.

Animals↗

Novel biodegradable films and scaffolds of chitosan blended with poly(3-hydroxybutyrate).

In order to develop a novel biomaterial, films of chitosan blended with poly(3-hydroxybutyrate) (PHB) were prepared by an emulsion blending technique and their properties were characterized. Scanning electron microscopy (SEM) showed that PHB microspheres were formed and were entrapped in chitosan matrices, which made the film surface rough. With increasing PHB content, the roughness of the film surface increased, while the swelling capability of the films decreased. In a wet state, the blended films exhibited a lower elastic modulus, a higher elongation-at-break and a higher tensile strength compared with chitosan films. Cell-culture experiments revealed that the blended films had better cytocompatibility than chitosan films. To explore the potential application of the blended material in tissue engineering, the porous blended scaffolds were fabricated and their pore morphology was observed by SEM. The results revealed that not only pore structure but also pore wall morphology of the blended scaffolds could be controlled by selecting the parameters of the fabrication process. These advantageous properties indicate that the blended chitosan/PHB material is promising for tissue engineering applications.

Absorbable Implants↗

Application of engineering principles in management of spinal cord injured patients.

Engineering services currently being used for spine stabilization, respiratory assist, and pressure sore prevention are discussed as well as devices under development for bowel and bladder control, reduction of contractural deformities and spasticity, and electrical stimulation of paralyzed muscles. Concepts and devices for improved function are divided into categories of: orthotic devices; environmental control systems; mobility systems; page-turning devices. A wide range of engineering devices are available but strict attention must be given to medical rationale for their use.

Biomedical Engineering↗

University of Wyoming, College of Engineering, undergraduate design project: star tracer.

The University of Wyoming received funding in the spring of 2002 from the National Science Foundation Division of Bioengineering and Environmental Systems in order to complete undergraduate design projects. One design project that was chosen by the College of Engineering involved partnering with the College of Education. The College of Education's Special Education Department needed some visual teaching aids to be redesigned and then built. Two undergraduate students were hired throughout the summer of 2002 under NSF REU funding in order to develop thirty new teaching devices. These devices were going to be used to educate middle school students about the effects of possessing a learning disability. The teaching aids are specifically designed for simulating the affects of dyslexia. The new teaching aids required improved transportability and durability, quicker setup time, and a lighter weight. Throughout the summer, the teaching aids were redesigned and built by an undergraduate student team from the College of Engineering, and have since provided many benefits for the state of Wyoming.

Biomedical Engineering↗

Engineering approaches to the evaluation of cardiac function in future.

The present and future impact of engineering technology on observing and evaluating cardiac function is discussed, with particular reference to the development of cardiac measurements. Several new topics in cardiac imaging, manometers, and blood flow velocity measurements are briefly reviewed. The effectiveness of cardiac models in the evaluation of cardiac function is emphasized, although there are many unsolved basic problems concerning muscle mechanics of the heart. Overall, comprehensive studies in cooperation with clinical cardiology, cardiac physiology, and engineering are necessary to accelerate further progress in the evaluation of cardiac function.

Biomedical Engineering↗

[Clinical engineering. Rationale for implementing the technology in hospitals].

A new clinical engineering service was started in the Hospital General de México, almost 5 years ago, with the technical assistance of Universidad Autonoma Metropolitana and financial support of Patronato del Hospital General de Mexico, A.C. The purpose of such service is to improve all aspects of medical device management in the hospital, i.e., selection, acquisition, installation, quality control, use and maintenance. The project also includes education, research and development related to health care technology. Interesting results have been obtained in each of the areas of clinical engineering, even during the early stages. They are herein presented to the medical community.

Biomedical Engineering↗

Establishing a protocol to quantify leaflet fibroblast responses to physiologic flow through a viable heart valve.

Mechanical stresses are thought to affect the metabolism of a variety of cell types. Little quantitative data exist regarding heart valve leaflet fibroblast activity after dynamic loading. The goal of this study was to examine leaflet fibroblast function and differentiation in response to flow through an intact valve. This requires the development of a flow system capable of reproducing the valve's native environment, as well as assay protocols to analyze cellular viability and protein and collagen synthesis. As a tool to expose viable tissue valves to physiologic flow, a sterilizable pulsatile flow system has been developed to recreate the dynamic flow environment of the aortic valve while preventing contamination from room air. Physiologic flow conditions [frequency 70 bpm, aortic pressure 129/82 mmHg (systolic/diastolic), cardiac output 2.3 L/min] were sustained for 71 hr without microbiologic contamination. Analytic tools for assessment of fibroblast function include a viability assay, which demonstrated that leaflet viability decreases after prolonged exposure to antibiotics. Proline incorporation studies revealed that 11 times more protein is retained by leaflet tissue than is released into the medium, and 27% of this protein is collagen. Polyacrylamide gel electrophoresis clearly resolved collagen Types I and III from both prepared standards as well as leaflet extracts. In ongoing work, the sterile flow loop will be used to expose fresh porcine aortic valves to defined flow conditions, and the viability and protein/collagen biosynthetic activity of leaflet fibroblasts in response to flow will be quantified. These experiments will provide a baseline by which to design and evaluate future tissue engineered substitutes.

Animals↗

Future directions in biomaterial implants and tissue engineering.

Over the last 50 years, we have gained much knowledge about biomaterial implants by incorporating the fields of basic biologic science and engineering science. Future implant developments will have a significant impact on facial cosmetic and reconstructive surgical therapy.

Biocompatible Materials↗

Adipose tissue engineering: the future of breast and soft tissue reconstruction following tumor resection.

Reconstructive surgeons have always been at the forefront of medical technology. The history of reconstructive surgery began with ablative surgery, which was followed by tissue and organ transplantation, leading to contemporary tissue reconstruction. The field of reconstructive surgery is poised at the next stage of its evolution, namely tissue regeneration. The field of tissue engineering has largely defined this evolutionary leap. One active area of investigation is the development of tissue engineering strategies for adipose tissue. Bioengineers, life scientists, and reconstructive surgeons are synergistically coupling expertise in areas such as cell culture technology, tissue transfer, cell differentiation, angiogenesis, computer modeling, and polymer chemistry to regenerate adipose tissue de novo for breast replacement and soft-tissue augmentation following tumor resection. This work presents the current state of the art in adipose tissue engineering, as well the clinically translatable strategies currently under development. Semin. Surg. Oncol. 19:302-311, 2000.

Adipose Tissue↗

Computer-assisted ankle joint arthroplasty using bio-engineered autografts.

Bio-engineered cartilage has made substantial progress over the last years. Preciously few cases, however, are known where patients were actually able to benefit from these developments. In orthopaedic surgery, there are two major obstacles between in-vitro cartilage engineering and its clinical application: successful integration of an autologuous graft into a joint and the high cost of individually manufactured implants. Computer Assisted Surgery techniques can potentially address both issues at once by simplifying the therapy, allowing pre-fabrication of bone grafts according to a shape model, individual operation planning based on CT images and providing optimal accuracy during the intervention. A pilot study was conducted for the ankle joint, comprising a simplified rotational symmetric bone surface model, a dedicated planning software and a complete cycle of treatment on one cadaveric human foot. The outcome was analysed using CT and MRI images; the post-operative CT was further segmented and registered with the implant shape to prove the feasibility of computer assisted arthroplasty using bio-engineered autografts.

Ankle Joint↗

From neural chip and engineered biomolecules to bioelectronic devices: an overview.

At the first C.E.C. Workshop, in Brussels on 28-29 November 1991, attended by over 70 leading European scientists and industrialists, bioelectronics was defined as 'the use of biological materials and biological architectures for information processing systems and new devices'. At the end of the Frankfurt Workshop, bioelectronics, specifically bio-molecular electronics, was described as 'the research and development of bio-inspired (i.e. self-assembly) inorganic and organic materials and of bio-inspired (i.e. massive parallelism) hardware architectures for the implementation of new information processing systems, sensors and actuators, and for molecular manufacturing down to the atomic scale'. The subject of this overview is to summarize some of the most significant progress in bio-molecular electronics from neural VLSI networks and bio-molecular engineering. As an example of one possible route, emphasis is placed on the results recently obtained within this laboratory.

Biofilms↗