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Ethical considerations in bioengineering research.

Biomedical science and engineering have made rapid advancements in the field of medicine over the past few decades. New ethical problems arising from this technology are influencing biomedical research more and more. It is disturbing that bioengineering professionals have had relatively little contact with moral and legal theory in light of these developments and particularly since they represent the forefront of new medical innovations. The objective of this communication is to introduce the study of bioethics and the use of principlism when examining bioengineering problems and dilemmas. Specific examples derived from actual proceedings, such as the Baltimore case, will alert scientists to the importance of misconduct in academic society. Cases will be used to illustrate how tools learned in this presentation are applied to analyze bioethical issues. New technology has a large social impact and is setting the standard of care for treatment. The health care system continually relies on researchers to produce improvements in patient therapy. Society will increasingly expect scientists to be morally responsible for the research they perform and uphold those virtues that ensure good ethical conduct.

Biomedical Engineering↗

Symbiosis: nursing and the bioengineer.

At this time, bioinstrumentation is the product of the possible as modified by what is practical. The bioengineer offers both the possible and the practical from an engineering and ideal model. The nurse, in contrast, speaks to the ideal possible from a confining practical clinical model. Symbiosis of nursing and bioengineering will combine the important attributes of each discipline for the betterment of patient care. In truth, the machine becomes an instrument of humanity.

Biomedical Engineering↗

Bioengineering principles of hydrotherapy.

Hydrotherapy is based on several important bioengineering principles that permit the design and development of aquatic exercise devices, techniques and programs. These principles involve several forces (buoyancy, drag, inertia), hydrostatic pressure and the specific heat of water. By acquiring a knowledge of these bioengineering principles, an individualized exercise program can be prescribed that will enhance physical fitness which is associated with desirable psychological changes.

Biomechanical Phenomena↗

A voyage of reprogrammable metabolic bioengineering reshapes plant defense: from editing tools to synthetic systems.

Metabolic bioengineering has emerged as a transformative approach for reshaping plant defense by targeting intrinsic biosynthetic pathways to enhance immunity in modern agriculture. Moving beyond proof-of-concept metabolomics to broad-spectrum programmable pathway engineering addresses gaps in plant rational design and optimizes resilience in response to diverse environmental cues. This review aims to comprehensively highlight the transition of innovative approaches to phenolics, alkaloids, flavonoids, terpenoids, and benzoxazinoids, inferring adaptive reprogramming that mediates the growth-defense balance and functions as molecular sentinels in plants. Furthermore, decoding the volatile metabolome reveals a dynamic signaling interface that influences defense responses and stress-induced plant-microbe interactions, with the shikimate, jasmonate, and salicylate pathways functioning as central hubs for microbial deterrence and priming immune memory. Recent developments in multi-scalar genome-editing strategies, including CRISPR-driven combinatorial edits, enzyme orthogonalization, fluxomics, and spatially resolved multi-omics, reconfigure central and specialized metabolic fluxes toward improved defense function and regulation. Additionally, emerging tools, such as WUSCHEL2 and BABY BOOM transcriptional modules, and artificial engineering strategies integrating deep learning model-driven predictions facilitate rapid development of synthetic genetic circuits and support a predictive engineering of plants. Moreover, Mass spectrometry imaging (MSI) in spatial metabolomics enables to obtain structures and locations of unidentified endogenous metabolites within cells and tissues. Overall, this review emphasizes a diverse array of primary and secondary metabolites, spanning molecular concepts to recent advances in plant immune mechanisms. It also illustrates new frontiers in programmable metabolic engineering that accelerate the understanding of plant-microbe-metabolite cross-talks, offering strategies to improve plant resistance and advance sustainable agricultural solutions.

metabolic bioengineering↗

Novel chemicals from plants via bioengineering. An overview.

Novel chemicals were traditionally extracted from medicinal plants or produced synthetically. However, new development in the field of bioengineering has allowed production of novel products from plants such as edible and industrial oils as well as specific chemicals which could be used as foods with remedial effects.

Bioreactors↗

Bioengineering aspects of heart valve replacement.

Biomedical engineering inputs have been important in the design, development and testing of substitute heart valves as well as in the pre- and post-operative management of patients with cardiac valve disease. This paper is a review of heart valve replacement whose goal is the enhancement of future bioengineering contributions. We review the approach to the patient with valvular heart disease, and the sources of early and late postoperative pathology with emphasis on complications of the prostheses used. Major significant problem areas relate to the noninvasive evaluation of cardiovascular function (both before and after surgery), device design, hemodynamics, and the need for thromboresistant and durable materials.

Biomedical Engineering↗

1992 ALZA Distinguished Lecture: bioengineering and vascular biology.

The vascular system is naturally dynamic; fluid mechanics and mass transfer are closely integrated with blood and vascular cell function. We are beginning to understand how local wall shear stress and strain modulate endothelial cell metabolism at the gene level. This knowledge may help explain the focal nature of many vascular pathologies, including atherosclerosis. Understanding mechanical control of gene regulation at the level of specific promoter elements and transcription factors involved will lead to development of novel constructs for localized delivery of specific gene products in regions of high or low shear stress or strain in the vascular system. In addition, recent research has shown how local fluid mechanics can alter receptor specificity in cell-to-cell and cell-to-matrix protein adhesion and aggregation. Knowledge of the specific molecular sequences involved in cell-to-cell recognition will allow development of targeted therapeutics, with applications in thrombosis, inflammation, cancer metastasis, and sickle-cell anemia. Bioengineers are uniquely qualified to be leaders in this field, because advances require a synthesis of cell and molecular biology with systems analysis, transport phenomena, and quantitative modeling. Rapid progress in tissue engineering applications will require this new kind of biomedical engineer, which represents both a challenge and an opportunity for our profession.

Biomedical Engineering↗

Bioengineering problems connected with the use of conventional and unconventional raw materials in fermentation. A review.

Some bioengineering problems connected with the use of conventional and unconventional raw materials in fermentation research and industry are reviewed. They include the effect of the physical state of different substrates (solid, liquid, gaseous) and considerations of physico-chemical processes, especially the identification of limiting steps. A new concept of classification of fermentors with respect to the macromixing properties is suggested and its applicability for different substrates is considered.

Bacteria↗

In Haughton's footsteps: mathematical insights into bioengineering and rehabilitation.

Four attempts are outlined which the author has made to develop mathematical models for topics encountered in bioengineering and rehabilitation. The first is autoregulation in the kidney, for which a nonlinear oscillator model is derived, based on observations of flow noise made by Erol Basar. The second is a nonlinear observer based on the theory of automatic control, developed to study patterns of spastic torque in paralysed legs via the pendulum test. The third is a design study of a skeletal muscle reflex arc involving the muscle spindle dynamics and invoking a principle of optimum stability. The final topic is an attempt to lay the groundwork for a mathematical theory of the cross-bridge or sliding filament mechanism of muscular contraction.

Biomedical Engineering↗

Protection against the co-operative toxicity of nitric oxide and oxygen free radicals by overexpression of antioxidant enzymes in bioengineered insulin-producing RINm5F cells.

AIMS/HYPOTHESIS: The importance of different antioxidative enzymes for the defence of insulin-producing cells against the toxicity of nitric oxide (NO) was characterised in bioengineered RINm5F cells. METHODS: RINm5F insulin-producing cells stably overexpressing glutathione peroxidase (GPX), catalase (CAT) or Cu/Zn superoxide dismutase (SOD) were exposed to S-nitroso-N-acetyl-D,L-penicillamine (SNAP), sodium nitroprusside (SNP) and 3 morpholinosydnonimine (SIN-1), which generate both NO and reactive oxygen species, and to the polyamine/ NO, complex DETA/NO which generates NO alone. The viability of the cells was tested by the MTT assay. RESULTS: Overexpression of antioxidant enzymes provided significant protection against the toxicity of SNAP, SNP and SIN-1, with an individual specificity related to their chemical characteristics, but was without effect upon the toxicity of DETA/NO. Cells overexpressing GPX were well protected against SNP and SNAP, while CAT was most effective against SIN-1. SOD overexpression provided less protection against the toxicity of SNAP and SNP than overexpression of GPX but was more effective in protecting against SIN-1. Co-incubation of cells with NO donors and hydrogen peroxide or hypoxanthine and xanthine oxidase showed an overadditive synergism of toxicity. CONCLUSION/INTERPRETATION: The results emphasise the importance of a synergism between NO and reactive oxygen species for pancreatic beta-cell death. Such a synergism has also been observed after exposure of beta cells to cytokines. The component of the toxicity that is mediated by oxygen radicals can be suppressed effectively through overexpression of CAT, GPX or SOD or both.

Animals↗

Bioengineered emulsans from Acinetobacter calcoaceticusRAG-1 transposon mutants.

Transposon mutants of Acinetobacter calcoaceticus strain RAG-1 were studied in an effort to control fatty acid (FA) substitution patterns of emulsan, a bioemulsifier secreted by the organism. The disrupted genes, involved in the biosynthetic pathways of biotin, histidine, cysteine or purines, influenced the level and types of FAs incorporated into emulsan. The structural variants of emulsan generated by the transposon mutants were characterized for yield, FA content, molecular weight, and emulsification behavior when grown on a series of FAs of different chain lengths from C11 to C18. Yields of emulsan from the transposon mutants were found to be lower than the parent strain and depended on the type of FA used to supplement the growth medium. Mutants 13D (His-) and 52D (Cys-) grown on LB plus C16 or C14, respectively, exhibited enhanced emulsifying activity compared to A. calcoaceticus RAG-1. The presence and composition of long chain FAs on the polysaccharide backbone influenced emulsification behavior: particularly a high mole percentage of C16 (48%) and C18 (42%). The results provide important insight into the bioengineering of bioemulsifier-producing microorganisms and provide a path towards highly tailored novel amphipathic structures to utilize as biodegradable in environmental, biomedical, and personal care applications.

Acinetobacter calcoaceticus↗

Quantitation of putative glycoprotein X in bioengineered pseudorabies vaccine virus culture medium by ELISA.

An enzyme-linked immunosorbent assay has been developed for the detection and quantitation of putative pseudorabies glycoprotein X (gX) in bulk bioengineered PRV delta gX delta tk-1 pseudorabies vaccine virus culture medium supernatants. The assay has a dynamic range of 0.2-25 ng, with a best linear region of 0.4-12.5 ng (correlation coefficient = 0.99) which permits 1 ppm discrimination for gX.

Antigens, Viral↗

Antibodies to foot-and-mouth disease virus infection associated (VIA) antigen: use of a bioengineered VIA protein as antigen in an ELISA.

An enzyme-linked immunosorbent assay (ELISA) to detect antibodies to foot-and-mouth disease (FMD) virus infection associated (VIA) antigen (viral RNA polymerase) in cattle sera, was developed using a bioengineered VIA (BioVIA) protein antigen. Compared with the classical immunodiffusion test, with viral RNA polymerase purified from infected cell cultures as antigen, this ELISA was more sensitive. However, depending on the cattle population examined, sera with antibodies to viral RNA polymerase, probably due to infection with other picornaviruses, were detected. Despite these observations, the ELISA using BioVIA provided a rapid answer as to whether or not FMD virus circulated in a given herd of cattle. The main advantage of this ELISA is its absolute safety, since in no step of the antigen production was infectious or uninfectious FMD virus involved. The test can therefore be performed under normal laboratory conditions and no isolation units are needed as they are for the immunodiffusion test.

Animals↗

A scientist's view of bioengineering.

So, to summarize: my themes in this lecture have been: 1. Bioengineering is a many-splendoured thing. 2. There are few differences in principle between scientists and engineers, and they need to work together and respect one another's special contribution. 3. The Department of Health has done much to enhance your career structure and prospects recently; now you have to help us to polish your image even further. 4. There is urgent need for collaboration amongst all parties if we are to counter some potentially deleterious effects of the recent NHS reforms on the work of clinical scientists and engineers. Finally, I wanted to thank you for admitting me, just a little way, into the magical world of biological engineering. Life has become infinitely more exciting since you did so, and I owe you all a considerable debt of gratitude.

Biomedical Engineering↗

Novel treatment strategy for leg and sternal wound complications after coronary artery bypass graft surgery: bioengineered Apligraf.

PURPOSE: To demonstrate that bioengineered Apligraf improves time to wound healing in sternal and leg wound complications after coronary artery bypass surgery. DESCRIPTION: Between 1998 and 2001, 1,550 patients underwent coronary artery bypass surgery utilizing saphenous vein. In 45 (2.9%) of 1,550 patients, leg wound complications developed (group A); and in 15 (0.9%) of 1,550 patients, sternal wound complications developed (group B). Apligraf was utilized as the primary treatment for 30 (66%) of 45 leg wounds and for 9 (60%) of 15 sternal wounds. Traditional wound care included debridement and daily wet-to-dry dressings. EVALUATION: Time to wound healing ranged from 26 to 72 days (mean, 46) for Apligraf group A and from 34 to 120 days (mean, 84) for traditional wound care group A. The time to wound healing ranged from 21 to 80 days (mean, 39) for Apligraf group B, and from 36 to 110 days (mean, 62) for traditional care group B. Apligraf treatment was simpler, with less time and resource utilization than traditional wound care. CONCLUSIONS: Apligraf significantly improves time to wound healing in patients with leg and sternal wound complications and offers an attractive new treatment alternative to traditional wound care.

Aged↗

Cryoprotectant permeability parameters for cells used in a bioengineered human corneal equivalent and applications for cryopreservation.

A human corneal equivalent is being developed with applications in pharmaceutical testing and biomedical research, but the distribution of this engineered tissue, depends on successful cryopreservation. Cryopreservation of tissues depends on the presence of cryoprotectants, their addition and removal, and exposure to conditions during freezing and thawing, all of which depend on cellular membrane permeabilities to water and cryoprotectant. This study defines the permeability properties that define the rate of water and cryoprotectant movement across the plasma membrane of isolated human corneal endothelial, keratocyte, and epithelial cells. Cells were transferred from isotonic conditions (300 mosm/kg) to 0.5, 1, or 2 M dimethyl sulfoxide and propylene glycol solutions at constant temperature, and cell volumes monitored using an electronic particle counter. Histograms describing cell volume changes over time after cryoprotectant exposure allowed calculation of hydraulic conductivity (Lp), cryoprotectant permeability (Ps), and the reflection coefficient (sigma). Experimental values for Lp and Ps at 4, 13, 22, and 37 degrees C were used to determine the Arrhenius activation energy (Ea). Defining the permeability parameters and temperature dependencies allows simulation of responses of human corneal cells to addition and removal of cryoprotectants and to freezing conditions, allowing amount of supercooling, intracellular electrolyte concentration, and intracellular cryoprotectant concentration to be calculated. Simulations also show that the constituent cells in the bioengineered cornea respond differently to addition and removal of cryoprotectants and to freezing. This study has defined the requirements during cryopreservation for the corneal cells; future work will define the matrix requirements which will allow the development of a cryopreservation protocol.

Cell Membrane Permeability↗

Biodegradable polymer with collagen microsponge serves as a new bioengineered cardiovascular prosthesis.

OBJECTIVE: Biodegradable materials with autologous cell seeding have attracted much interest as potential cardiovascular grafts. However, pretreatment of these materials requires a complicated and invasive procedure that carries the risk of infection. To avoid these problems, we sought to develop a biodegradable graft material containing collagen microsponge that would permit the regeneration of autologous vessel tissue. The ability of this material to accelerate in situ cellularization with autologous endothelial and smooth muscle cells was tested with and without precellularization. METHODS: Poly(lactic-co-glycolic acid) as a biodegradable scaffold was compounded with collagen microsponge to form a vascular patch material. These poly(lactic-co-glycolic acid)-collagen patches with (n = 10) or without (n = 10) autologous vessel cellularization were used to patch the canine pulmonary artery trunk. Histologic and biochemical assessments were performed 2 and 6 months after the implantation. RESULTS: There was no thrombus formation in either group, and the poly(lactic-co-glycolic acid) scaffold was almost completely absorbed in both groups. Histologic results showed the formation of an endothelial cell monolayer, a parallel alignment of smooth muscle cells, and reconstructed vessel wall with elastin and collagen fibers. The cellular and extracellular components in the patch had increased to levels similar to those in native tissue at 6 months. CONCLUSIONS: The poly(lactic-co-glycolic acid)-collagen microsponge patch with and without precellularization showed good histologic findings and durability. This patch shows promise as a bioengineered material for promoting in situ cellularization and the regeneration of autologous tissue in cardiovascular surgery.

Animals↗

Bioengineering and physicochemical optimization of ergothioneine production by Aspergillus oryzae.

Ergothioneine (EGT) is a bioactive, rare variant of histidine with many applications in the medical, pharmaceutical, and food fields. Therefore, we aimed to investigate in this study the impact of genomic and physicochemical factors on EGT production by the industrial filamentous fungus Aspergillus oryzae. Firstly, to facilitate efficient EGT production, we analyzed the subcellular localization of the three EGT biosynthetic enzymes present in A. oryzae. During screening for the most potent producer of EGT among bioengineered transformants, the strain EgtACO overexpressing both AoegtA and AoegtC showed promising EGT production in DPY medium. Five days of incubation was the optimum period, and CZYP medium was the optimum medium for EGT production. Co-cultivation with the nisin Z-producing Lactococcus lactis JCM 7638 yielded EGT production equivalent to that of the EgtACO strain alone. Having broad-spectrum antimicrobial activity without suppressing growth of the EgtACO strain suggested that bacteriocin may help reduce the risk of contamination during long-term cultivation. Moreover, supplementing the production medium with L-methionine or zinc sulfate improved EGT production (1468.5 or 1565 mg/L, respectively). Furthermore, repeated inoculation of the producer strain EgtACO and incubation in blue light were the optimum conditions for EGT production (1895 mg/L). Finally, we achieved cost-effective EGT production using A. oryzae strain EgtACO under the optimal culture conditions using agricultural wastes: potato peel and sweet potato peel (293 and 308 mg/L, respectively).

Aspergillus oryzae↗