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PubMed1998

Tissue engineering of skin.

The skin plays a crucial role in protecting the integrity of the body's internal milieu. The loss of this largest organ is incompatible with sustained life. In reconstructive surgery or burn management, substitution of the skin is often necessary. In addition to traditional approaches such as split- or full-thickness skin grafts, tissue flaps and free-tissue transfers, skin bioengineering in vitro or in vivo has been developing over the past decades. It applies the principles and methods of both engineering and life sciences toward the development of substitutes to restore and maintain skin structure and function. Currently, these methods are valuable alternatives or complements to other techniques in reconstructive surgery. This review article deals with the evolution and current approaches to the development of in vitro and in vivo epidermis and dermis.

Biomedical Engineering↗
PubMedDate not supplied

Food safety: risk assessment methodology and decision-making criteria.

As our scientific technology grows, risk assessment methods become more complex and, therefore, open to greater scientific debate. Risk assessment has always been a part of the regulatory notification and approval process for foods. However, the methodologies applied to risk assessment and decision-making have become diverse, dependent on a number of features, including the areas of the world in which one operates, the need to use cumulative risk assessment for pesticides and other ingredients or alternative risk assessment considerations for evaluating nontraditional or bioengineered foods. Diverse institutional structures within a single federal regulatory authority may tend to lead to diversity in risk outcomes that creates policy decisions that complicate and confuse the risk management process. On top of this challenge, decisions become more complicated by the need to examine beneficial factors of foods rather than the adverse effects of foods and food additives. Foods are a complex mixture of ingredients. Regulatory groups recognize the need to use new approaches for evaluating the safety and risks associated with foods and food additives, and to do so in a timely manner. The United States Food and Drug Administration (US FDA) in its need to ensure standards of "reasonable certainty of no harm" continues to explore alternative means to be responsive to petitioners as well as continue to examine scientifically validated means, e.g., quantitative structure-activity relationship (QSAR), and computer-assisted programs, within the approval process to assist in the evaluation of risks. Another means to improve the risk management process would include the cumulative risk assessment of pesticides that will, no doubt, be the beginning of more intensive efforts to understand cumulative exposures and the inherent risks from multiple pathways of exposure. The passage of the Food Quality Protection Act (FQPA) resulted in developing additional risk assessment methodologies and approaches to assess the potential for multiple exposures and risks. Addressing the international criteria used in decision-making related to foods safety assessment has resulted in acceptable intake values for food ingredients for carcinogens and noncarcinogens that, in general, tend to be more stringent in the United States compared to Europe. Clearly, the need for harmonization of risk assessment criteria and the impact of the decision process on regulatory approvals and safety assessment is a future need for the continued assurances of food safety. The topics presented in this paper are based on a symposium held in November 2002 at the annual meeting of the American College of Toxicology.

Animals↗
PubMed1999

Editorial

Remarkable advances have occurred in wound healing during the past decade in both basic wound biology, as well as applied research into novel treatments of chronic wounds. Newly developed therapies have included the use of growth factors to enhance wound epithelialization, and the use of bioengineered dressings, including skin substitutes. These advances were recently highlighted in the December 1998 JCMS supplement on Wound Care. The lead article in this current issue of JCMS focuses on potential mechanisms to establish quantifiable end points during wound healing, and speculates on the potential relevance to the development of novel therapies. Palenske and Morhenn have found that measurement of skin capacitance is a useful tool in determining endpoints in wound healing. While our ultimate goal in wound healing is to completely re-epithelialize and heal a wound, sometimes interventions are less successful. In evaluating wound healing agents in preclinical or early clinical studies, surrogate markers may be necessary. Skin capacitance may serve as such a marker. In our Point Counterpoint Section, Drs Goldhar and Gratton address the controversial issue of whether dermatologists should promote treatment products. There are strong opinions on both sides of this question, and these two practitioners have concisely addressed the respective sides of this issue. The Grand Rounds Section features an article by Bergman and co-authors in which they describe a case of crusted scabies in association with HTLV-1. Dermatologists are frequently faced with individuals with generalized pruritic eruptions, where scabies is frequently in the differential diagnosis. Indeed, scabies is quite common worldwide. However, crusted scabies, or Norwegian scabies, is much less common, and one clearly has to consider immune deficiencies. This report highlights the association of crusted scabies with immune deficiency. In our CME sections of this issue, we have two important articles. The first, by Dr. Sherri Bale, is a continuation of our Genetic Studies in skin disease research, and the article reviews the area of mapping of hereditary skin disease by focusing on the gene for pseudoxanthoma elasticum. In our day-to- day clinical practice, we frequently discuss the clinical diseases we see in terms of prognosis that is often based on our own individual experience. Evidence based prognostic modelling may provide a very important technique to more accurately assess our patients' outcomes. Drs. Kantor and Margolis review the models and enhance our understanding of these techniques. In this issue of the Journal we introduce a new section of structured book reviews. Two books, Morphologic Diagnosis of Skin Disease and Handbook of Dermatology for Primary Care are reviewed. The structured review provides a concise analysis of these books to allow readers to determine application of these publications to their needs. I hope that each and every one of our readers had a very happy holiday season and I wish you the best for the new year.

Journal Article↗
PubMed2002

Using living skin equivalents for diabetic foot ulceration.

Diabetic foot ulcers are a major clinical challenge with enormous socioeconomic consequence. All advances in the understanding and management of this problem are eagerly received by wound specialists. The development of bioengineered skin--living skin equivalent--is an interesting event that could be significant in the management of lower extremity wounds such as the diabetic foot ulcer.

Journal Article↗
PubMed2002

Skin grafting of venous ulcers: a review of its current role.

As a therapeutic option, grafting of venous ulcers has not been very successfully received despite the different types of grafting methods. Currently, there are only a few controlled randomized trials offering clear guidance to clinicians. The development of artificially bioengineered skin constructs has led to a renewed interest in wound bed preparation, and preliminary successes suggest that the role of skin grafting could be studied in the current context.

Journal Article↗
PubMed2006

Cutaneous tissue engineering and lower extremity wounds (part 2).

In a previous article, this group described the principles involved in the development of bioengineered skin equivalents that held out much promise. This article has examined some of the uses of such products in treating venous ulcers, diabetic foot ulcers, and skin diseases leaving skin wounds. Data encouraging the use of such products in certain indications are available. The costs of using such products are also appreciated.

Humans↗
PubMed2001

Immunotherapy: on the edge between experimental and clinical oncology.

Cancer immunotherapy is still largely confined to the laboratory bench and experimental animal models. Yet the field is rapidly moving forward and some immunological tools are now entering into clinical use. The first and perhaps best example of such progress is given by bioengineered humanized monoclonal antibodies of which some have been already approved for therapy in B-cell lymphoma and breast cancer. Unexpectedly, another remarkable form of immunotherapy has turned out to derive from T-cell adoptive therapy associated with allogeneic bone marrow transplantation. Its benefits render such an approach the first choice therapy for a large number of hematological malignancies and it is now being adapted also for treatment of advanced solid tumors. Finally, harnessing the immune system against the autologous tumor remains the most ambitious but still distant design for immunotherapy. Recent technical advances and a better understanding of the immune system in cancer patients should concur in defining the best strategy for active immunotherapy in clinical oncology.

Antibodies, Monoclonal↗
PubMed1997

Pulmonary perspective: immunology in diagnosis and treatment of lung cancer.

The combination of the limits encountered with current therapies and the increased knowledge of immunology have opened perspectives for the use of immunomodulators in the management of lung cancer patients. Both humoral and cellular immunity are now evaluated in diagnosis and treatment of cancer. Monoclonal antibodies (MoAbs) against tumour-associated antigens are now tested with various imaging techniques to improve detection and staging of lung cancer. MoAbs are also used in therapeutic clinical trials as: 1) mediators of immune effector function; 2) carriers of cytotoxic agents; 3) agents to block tumour growth factor; or 4) anti-idiotype vaccines. Immune effector cells, such as natural killer (NK) cells, T- and B-lymphocytes, macrophages, dendritic cells and neutrophils, are present either within or around tumours and are likely to play a role in cancer. These cells, either alone or with cytokines, could provide new efficient therapeutic approaches, particularly if immunosuppression is involved in tumour progression. In this context, most recent studies using immune cells and molecular bioengineering, could provide additional antitumoral effects. Finally, the discovery of several tumour rejection antigens has revived the dream of designing tumour vaccines and active specific immunotherapy.

Antibodies, Monoclonal↗
PubMed2004

Production of Se-methylselenocysteine in transgenic plants expressing selenocysteine methyltransferase.

BACKGROUND: It has become increasingly evident that dietary Se plays a significant role in reducing the incidence of lung, colorectal and prostate cancer in humans. Different forms of Se vary in their chemopreventative efficacy, with Se-methylselenocysteine being one of the most potent. Interestingly, the Se accumulating plant Astragalus bisulcatus (Two-grooved poison vetch) contains up to 0.6% of its shoot dry weight as Se-methylselenocysteine. The ability of this Se accumulator to biosynthesize Se-methylselenocysteine provides a critical metabolic shunt that prevents selenocysteine and selenomethionine from entering the protein biosynthetic machinery. Such a metabolic shunt has been proposed to be vital for Se tolerance in A. bisulcatus. Utilization of this mechanism in other plants may provide a possible avenue for the genetic engineering of Se tolerance in plants ideally suited for the phytoremediation of Se contaminated land. Here, we describe the overexpression of a selenocysteine methyltransferase from A. bisulcatus to engineer Se-methylselenocysteine metabolism in the Se non-accumulator Arabidopsis thaliana (Thale cress). RESULTS: By over producing the A. bisulcatus enzyme selenocysteine methyltransferase in A. thaliana, we have introduced a novel biosynthetic ability that allows the non-accumulator to accumulate Se-methylselenocysteine and gamma-glutamylmethylselenocysteine in shoots. The biosynthesis of Se-methylselenocysteine in A. thaliana also confers significantly increased selenite tolerance and foliar Se accumulation. CONCLUSION: These results demonstrate the feasibility of developing transgenic plant-based production of Se-methylselenocysteine, as well as bioengineering selenite resistance in plants. Selenite resistance is the first step in engineering plants that are resistant to selenate, the predominant form of Se in the environment.

Arabidopsis↗
PubMed2006

Biotech and biomaterials research to reduce the caries epidemic.

The goal of this workshop is to develop a consensus within the biomaterials/bioengineering community for a research agenda focused on creating technologies that will address the current dental caries pandemic. The workshop will bring together expertise from academia, industry, and the NIH institutes in the areas of oral biofilm microbiology and innovative biomaterials. The rationale for the workshop is that science and technology have not produced sufficient practical tools for public health practitioners and the private delivery system to address the pandemic in dental caries that exists for children and adults from families with low incomes and for numerous ethnic minority and racial groups. Moreover, it is unclear whether the barriers are remediable bioengineering and technical problems or fundamental science questions. Nevertheless, the obligation to address the gap between scientific research and practical application is especially relevant today. The U.S. and state governments bear the majority of the cost of trying to control this pandemic through Medicaid, the Public Health Service, Indian Health Service and other similar programs. These costs continue to escalate as continued applications of existing technology are unlikely to markedly reduce disparities. The mainstays of caries prevention, topical and systemic fluorides and pit and fissure sealants, are technologies developed in the 1950s and 1960s.

Journal Article↗
PubMed2004

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

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

Journal Article↗
PubMed2006

Biomechanics and anterior cruciate ligament reconstruction.

For years, bioengineers and orthopaedic surgeons have applied the principles of mechanics to gain valuable information about the complex function of the anterior cruciate ligament (ACL). The results of these investigations have provided scientific data for surgeons to improve methods of ACL reconstruction and postoperative rehabilitation. This review paper will present specific examples of how the field of biomechanics has impacted the evolution of ACL research. The anatomy and biomechanics of the ACL as well as the discovery of new tools in ACL-related biomechanical study are first introduced. Some important factors affecting the surgical outcome of ACL reconstruction, including graft selection, tunnel placement, initial graft tension, graft fixation, graft tunnel motion and healing, are then discussed. The scientific basis for the new surgical procedure, i.e., anatomic double bundle ACL reconstruction, designed to regain rotatory stability of the knee, is presented. To conclude, the future role of biomechanics in gaining valuable in-vivo data that can further advance the understanding of the ACL and ACL graft function in order to improve the patient outcome following ACL reconstruction is suggested.

Journal Article↗
PubMed2006

Fast, cheap and somewhat in control.

Efforts to manipulate living organisms have raised the question of whether engineering principles of hierarchy, abstraction and design can be applied to biological systems. Here, we consider the practical challenges to controlling living organisms that must be surmounted, or at least managed, if synthetic biology and cellular bioengineering are to be productive.

Animals↗
PubMed2005

Cardiac systems biology.

As more detailed molecular information accumulates on the biology of the heart and other complex systems in health and disease, the need for new integrative analyses and tools is growing. Systems biology and bioengineering seek to use high-throughput technologies and integrative computational analysis to construct networks of the interactions between molecular components in the system, to develop systems models of their functionally integrated biological properties, and to incorporate these systems models into structurally integrated multi-scale models for predicting clinical phenotypes. This review gives examples of recent applications using these approaches to elucidate the electromechanical function of the heart in aging and disease.

Aging↗
PubMed1997

An autosomal dominant form of familial persistent hyperinsulinemic hypoglycemia of infancy, not linked to the sulfonylurea receptor locus.

Persistent hyperinsulinemic hypoglycemia of infancy (PHHI), a rare disorder due to defective negative feedback regulation of insulin secretion by low glucose levels, is often familial. Most cases are recessively inherited, and mutations of the sulfonylurea receptor gene (SUR) or the closely linked KIR6.2 gene have been found in several families. Both of these genes encode components of the potassium channels responsible for glucose-regulated insulin release. However, in some families recessive PHHI is not linked to the SUR-KIR6.2 locus, suggesting genetic heterogeneity. We report here a French Canadian kindred with hypoglycemia in five first cousins. All five patients had documented hypoglycemia, and all responded well to diazoxide. In two, inappropriately elevated insulin levels during hypoglycemia were documented. This familial clustering strongly suggests the existence of an autosomal dominant form of PHHI. By preliminary linkage analysis, we tested the possibility of a dominant negative SUR or KIR6.2 mutant. The insulin (INS) and glucokinase (GCK) genes were also tested as additional candidates. Microsatellite markers closely linked to each gene were used, and large negative Lod scores were obtained at the known recombination fractions between all three genes studied and the corresponding marker. We conclude that mutation of a gene other than SUR or KIR6.2 is responsible for the dominant PHHI in this family, and this gene cannot be INS or GCK. We propose that a genome-wide search for this gene is important for elucidating this rare disorder and, more importantly, for determining its potential impact on understanding noninsulin-dependent diabetes mellitus and on the effort to develop bioengineered beta-cells for transplantation.

ATP-Binding Cassette Transporters↗
PubMed2006

Silken toolkits: biomechanics of silk fibers spun by the orb web spider Argiope argentata (Fabricius 1775).

Orb-weaving spiders spin five fibrous silks from differentiated glands that contain unique sets of proteins. Despite diverse ecological functions, the mechanical properties of most of these silks are not well characterized. Here, we quantify the mechanical performance of this toolkit of silks for the silver garden spider Argiope argentata. Four silks exhibit viscoelastic behaviour typical of polymers, but differ statistically from each other by up to 250% in performance, giving each silk a distinctive suite of material properties. Major ampullate silk is 50% stronger than other fibers, but also less extensible. Aciniform silk is almost twice as tough as other silks because of high strength and extensibility. Capture spiral silk, coated with aqueous glue, is an order of magnitude stretchier than other silks. Dynamic mechanical properties are qualitatively similar, but quantitatively vary by up to 300% among silks. Storage moduli are initially nearly constant and increase after fiber yield, whereas loss tangents reach maxima of 0.1-0.2 at the yield. The remarkable mechanical diversity of Argiope argentata silks probably results in part from the different molecular structures of fibers and can be related to the specific ecological role of each silk. Our study indicates substantial potential to customize the mechanics of bioengineered silks.

Animals↗
PubMed1991

Non-invasive diagnosis and prophylaxis in orthopaedics.

In this paper some ten years of work in bioengineering is described. The central theme is non-invasive diagnosis and prophylaxis. This theme is exemplified in several interrelated sections of work which are described. The work is categorized into: modest beginnings, hip and knee vibration papers, deep venous thrombosis and cavitation in human joints. The philosophy is straightforward--to benefit patients by making harmless measurement.

Biomechanical Phenomena↗
PubMed2005

Bone marrow cell-seeded biodegradable polymeric scaffold enhances angiogenesis and improves function of the infarcted heart.

BACKGROUND: The present study examined whether a bioengineered polyglycolic acid cloth (PGAC) impregnated with bone marrow cells (BMC) improved the function and angiogenesis of the infarcted heart. METHODS AND RESULTS: The coronary artery was ligated in Lewis rats and the infarcted area was covered with a PGAC in group 1 (n=8), with a PGAC containing basic-fibroblast growth factor (b-FGF) in group 2 (n=11) and a PGAC containing b-FGF and freshly isolated BMC in group 3 (n=10). In addition, BMC derived from transgenic mice expressing green fluorescent protein (GFP)-BMC were seeded into a PGAC, which was sutured over the infarcted area of C57BL/6 mice (n=5). In the rat study, developed and systolic pressures, dp/dt max and dp/dt min) were the highest in group 3, as were the capillary density in the PGAC and infarcted area. In the mouse study, there were few GFP-BMC in the PGAC, but none in the infarcted area. CONCLUSIONS: A PGAC with BMC improved cardiac function by inducing angiogenesis without migration of BMC. Freshly isolated BMC work as angiogenic inducers and a PGAC is useful as a "drug delivery system".

Absorbable Implants↗