Translational bioengineering strategies for peripheral nerve regeneration:opportunities,challenges,and novel concepts

Peripheral nerve injuries remain a challenging problem in need of better treatment strategies.Despite best efforts at surgical reconstruction and postoperative rehabilitation,patients are often left with persistent,debilitating motor and sensory deficits.There are currently no therapeutic strategies proven to enhance the regenerative process in humans.A clinical need exists for the development of technologies to promote nerve regeneration and improve functional outcomes.Recent advances in the fields of tissue engineering and nanotechnology have enabled biomaterial scaffolds to modulate the host response to tissue repair through tailored mechanical,chemical,and conductive cues.New bioengineered approaches have enabled targeted,sustained delivery of protein therapeutics with the capacity to unlock the clinical potential of a myriad of neurotrophic growth factors that have demonstrated promise in enhancing regenerative outcomes.As such,further exploration of combinatory strategies leveraging these technological advances may offer a pathway towards clinically translatable solutions to advance the care of patients with peripheral nerve injuries.This review first presents the various emerging bioengineering strategies that can be applied for the management of nerve gap injuries.We cover the rationale and limitations for their use as an alternative to autografts,focusing on the approaches to increase the number of regenerating axons crossing the repair site,and facilitating their growth towards the distal stump.We also discuss the emerging growth factor-based therapeutic strategies designed to improve functional outcomes in a multimodal fashion,by accelerating axonal growth,improving the distal regenerative environment,and preventing end-organs atrophy.

Bioengineering liver tissue by repopulation of decellularised scaffolds

Liver transplantation is the only curative therapy for end stage liver disease,but is limited by the organ shortage,and is associated with the adverse consequences of immunosuppression.Repopulation of decellularised whole organ scaffolds with appropriate cells of recipient origin offers a theoretically attractive solution,allowing reliable and timely organ sourcing without the need for immunosuppression.Decellularisation methodologies vary widely but seek to address the conflicting objectives of removing the cellular component of tissues whilst keeping the 3D structure of the extra-cellular matrix intact,as well as retaining the instructive cell fate determining biochemicals contained therein.Liver scaffold recellularisation has progressed from small rodent in vitro studies to large animal in vivo perfusion models,using a wide range of cell types including primary cells,cell lines,foetal stem cells,and induced pluripotent stem cells.Within these models,a limited but measurable degree of physiologically significant hepatocyte function has been reported with demonstrable ammonia metabolism in vivo.Biliary repopulation and function have been restricted by challenges relating to the culture and propagations of cholangiocytes,though advances in organoid culture may help address this.Hepatic vasculature repopulation has enabled sustainable blood perfusion in vivo,but with cell types that would limit clinical applications,and which have not been shown to have the specific functions of liver sinusoidal endothelial cells.Minority cell groups such as Kupffer cells and stellate cells have not been repopulated.Bioengineering by repopulation of decellularised scaffolds has significantly progressed,but there remain significant experimental challenges to be addressed before therapeutic applications may be envisaged.

Bioengineering models of female reproduction

The female reproductive system consists of the ovaries,the female gonads,and the reproductive tract organs of the fallopian tubes,uterus,cervix,and vagina.It functions to provide hormonal support and anatomical structure for the production of new offspring.A number of endogenous and exogenous factors can impact female reproductive health and fertility,including genetic vulnerability,medications,environmental exposures,age,nutrition,and diseases.To date,due to the ethical concerns of using human subjects in biomedical research,the majority of studies use in vivo animal models and 2D cell/tissue culture models to study female reproduction.However,the complexity and species difference of the female reproductive system in humans make it difficult to compare to those of animals.Moreover,the monolayered cells cultured on flat plastics or glass lose their 3D architecture as well as the physical and/or biochemical contacts with other cells in vivo.Further,all reproductive organs do not work alone but interconnect with each other and also with non-reproductive organs to support female reproductive,endocrine,and systemic health.These facts suggest that there is an urgent and unmet need to develop representative,effective,and efficient in vitro models for studying human female reproduction.The prodigious advancements of bioengineering(e.g.,biomaterials,3D printing,and organ-on-a-chip)allow us to study female reproduction in an entirely new way.Here,we review recent advances that use bioengineering methods to study female reproduction,including the bioengineering models of the ovary,fallopian tube,uterus,embryo implantation,placenta,and reproductive disease.

Fractional Order Proportional Integral Derivative Controller Design and Simulation for Bioengineering Systems

This paper deals with the study of fractional order system tuning method based on Factional Order Proportional Integral Derivative( FOPID) controller in allusion to the nonlinear characteristics and fractional order mathematical model of bioengineering systems. The main contents include the design of FOPID controller and the simulation for bioengineering systems. The simulation results show that the tuning method of fractional order system based on the FOPID controller outperforms the fractional order system based on Fractional Order Proportional Integral( FOPI) controller. As it can enhance control character and improve the robustness of the system.

Genetic Bioengineering in the Achievement of Algae Biofuels and High-Value Bio-products

The dependence to fossil fuels has increased the amount of greenhouse gases in the atmosphere.That is why,the production of renewable and sustainable biofuels has gained a long-term importance for both scientific and political necessities.In this context,algae are promising in terms of alternative biofuels resources.For this reason,intensive scientific researches have been carried out in recent years on providing optimum efficiency in this regard.Bioengineering is a discipline that applies engineering principles of design and analysis to biological systems and biomedical technologies.Examples of bioengineering research include bacteria or microalgae engineered to produce valuable bioactive chemicals.Microalgae by target gene modification may serve as a promising source for the production of biofuels and bio-based chemicals.A lot of research has been carried out by applying microalgae genomic editing technique with the aim to produce numerous biotechnological products.Some successful previously reported research and production activities are still underway in this area.However,in order to produce the desired products efficiently with manipulated microalgae biorefinery,there is a need to overcome the problem of low biomass production despite high production costs.The aim of this work is to give special attention to the rich potential content of microalgae and to provide information on algal genetic manipulations to increase products by bioengineering methods.

Environmental Cultural Landscape Characteristics of Agricultural Vocational Colleges: A Case Study of Bioengineering Branch of Yangling Vocation and Technical College and Doucun Farm

Based on the overall planning of environmental cultural construction of Yangling Vocational & Technical College and the college–enterprise co-construction of Doucun Farm, this paper combined environmental cultural reformation inside and outside the college and reform of off-campus teaching experiment farm in view of outstanding agricultural characteristics of the bioengineering branch, with environmental health preservation as the fundamental goal and "health-preserving agriculture" as the link. In addition, four major characteristic landscape frameworks of "point, line, surface, and body" were established, and the effective construction approaches of health-preserving environmental cultural landscapes in vocational colleges were explored.

The present and the prospect of bioengineering cornea

Corneal blindness represents one of the world’s three major causes of blindness,and the fundamental problem of corneal transplantation is a severe shortage of donor tissues worldwide,resulting in approximately 1.5 million new cases of blindness annually.To address the growing need for corneal transplants two main approaches are being pursued:allogenic and bioengineering cornea.Bioengineering corneas are constructed by naturally generating an extracellular matrix(ECM)component as the scaffold structure with or without corneal cells.It is well established that the scaffold structure directs the fate of cells,therefore,the fabrication of the correct scaffold structure components could produce an ideal corneal substitute,able to mimic the native corneal function.Another key factor in the construction of tissue engineering cornea is seed cells.However,unlike the epithelium and stroma cells,human cornea endothelium cells(HCECs)are notorious for having a limited proliferative capacity in vivo because of the mitotic block at the G1 phase of the cell cycle due to“contact-inhibition”.This review will focus on the main concepts of recent progress towards the scaffold and seed cells,especially endothelial cells for bioengineering cornea,along with future perspectives.

Relevance of Protein Content within the Renal Scaffold for Kidney Bioengineering and Regeneration

Chronic kidney disease is currently a major public health problem around the world. Although hemodialysis increases survival of patients with end-stage renal disease, kidney transplantation remains the only potentially curative treatment. However, transplantation as a therapeutic option is limited by availability of suitable donor organs. This situation highlights the urgent need to find new and potentially inexhaustible sources of transplantable organs. Perfusion decellularizarion of whole organs is a novel approach to organ engineering and regeneration. In the present research, we used a continuous perfusion decellularization protocol to eliminate cellular componet of kidney and evaluated residual scaffold components after decellularizarion process by proteomics analysis. Our proteomic data show that this protocol results in incomplete removal of cellular proteins. However, unlike other authors, we assume that proteins retained within decellularized kidney scaffold could be the basis for specific homing and celular differentation in the recellularization process.

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

Inadequate absorptive surface area poses a great challenge to the patients suffering a variety of in-testinal 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 neoformed 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.

Upcycling electroplating sludge into bioengineering-enabled highly stable dual-site Fe-Ni_(2)P@C electrocatalysts for efficient oxygen evolution

The advancement of bimetallic catalysts holds significant promise for the innovation of oxygen evolution reaction(OER)catalysts.Drawing from adsorbate evolution mechanism(AEM)and lattice oxygen oxidation mechanism(LOM),the incorporation of dual active sites has the potential to foster novel OER pathways,such as the coupled oxygen evolution mechanism(COM),which can surpass the limitations of OER and elevate catalytic performance.In this study,uniformly distributed Fe/Ni dual-site Fe-Ni_(2)P@C electrocatalysts are crafted by upcycling metals in electroplating sludge via an eco-friendly and sustainable microbial engineering technique.Our findings indicate that a substantial number of defects emerge at the Ni2P crystal during the OER process,laying the groundwork for lattice oxygen involvement.Moreover,the displacement of Ni/Fe in the crystal lattice intensifies the asymmetry of the electronic structure at the metal active sites,facilitating the deprotonation process.This research introduces an innovative paradigm for the synthesis of effective and robust transition metal-based OER catalysts,with implications for sustainable energy generation technologies.

Bioengineering extracellular vesicles as novel nanocarriers towards brain disorders

Despite noteworthy technological progress and promising preclinical trials,brain disorders are still the leading causes of death globally.Extracellular vesicles(EVs),nano-/micro-sized membrane vesicles carrying bioactive molecules,are involved in cellular communication.Based on their unique properties,including superior biocompatibility,non-immunogenicity,and blood-brain barrier(BBB)penetration,EVs can shield their cargos from immune clearance and transport them to specific site,which have attracted increasing interests as novel nanocarriers for brain disorders.However,considering the limitations of native EVs,such as poor encapsulation efficiency,inadequate targeting capability,uncontrolled drug release,and limited production,researchers bioengineer EVs to fully exploit the clinical potential.Herein,this review initially describes the basic properties,biogenesis,and uptake process of EVs from different subtypes.Then,we highlight the application of EVs derived from different sources for personalized therapy and novel strategies to construct bioengineered EVs for enhanced diagnosis and treatment of brain disorders.Besides,it also presents a systematic comparison between EVs and other brain-targeted nanocarriers.Finally,existing challenges and future perspectives of EVs have been discussed,hoping to bolster the research from benchtop to bedside.

Treatment of spinal cord injury with biomaterials and stem cell therapy in non-human primates and humans

Spinal cord injury results in the loss of sensory,motor,and autonomic functions,which almost always produces permanent physical disability.Thus,in the search for more effective treatments than those already applied for years,which are not entirely efficient,researches have been able to demonstrate the potential of biological strategies using biomaterials to tissue manufacturing through bioengineering and stem cell therapy as a neuroregenerative approach,seeking to promote neuronal recovery after spinal cord injury.Each of these strategies has been developed and meticulously evaluated in several animal models with the aim of analyzing the potential of interventions for neuronal repair and,consequently,boosting functional recovery.Although the majority of experimental research has been conducted in rodents,there is increasing recognition of the importance,and need,of evaluating the safety and efficacy of these interventions in non-human primates before moving to clinical trials involving therapies potentially promising in humans.This article is a literature review from databases(PubMed,Science Direct,Elsevier,Scielo,Redalyc,Cochrane,and NCBI)from 10 years ago to date,using keywords(spinal cord injury,cell therapy,non-human primates,humans,and bioengineering in spinal cord injury).From 110 retrieved articles,after two selection rounds based on inclusion and exclusion criteria,21 articles were analyzed.Thus,this review arises from the need to recognize the experimental therapeutic advances applied in non-human primates and even humans,aimed at deepening these strategies and identifying the advantages and influence of the results on extrapolation for clinical applicability in humans.

Enhanced extracellular production of alpha-lactalbumin from Bacillus subtilis through signal peptide and promoter screening

Alpha-lactalbumin(α-LA)is a major whey protein found in breast milk and plays a crucial role in the growth and development of infants.In this study,Bacillus subtilis RIK1285 harboring AprE signal peptide(SP)was selected as the original strain for the production ofα-LA.It was found thatα-LA was identified in the pellet after ultrasonic disruption and centrifugation instead of in the fermentation supernatant.The original strain most likely only producedα-LA intracellular,but not extracellular.To improve the expression and secretion ofα-LA in RIK1285,a library of 173 homologous SPs from the B.subtilis 168 genome was fused with target LALBA gene in the pBE-S vector and expressed extracellularly in RIK1285.SP YjcN was determined to be the best signal peptide.Bands in supernatant were observed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and purified by nickel column to calculate the highest yield signal peptide.In addition,different promoters(P_(aprE),P_(43),and P_(glv))were compared and applied.The results indicated that the strain RIK1285-pBE-P_(glv)-YjcN-LALBA had the highestα-LA yield,reaching 122.04μg/mL.This study demonstrates successful expression and secretion of humanα-LA in B.subtilis and establishes a foundation for simulating breast milk for infant formulas and developing bioengineered milk.

Bioengineering of nano metal-organic frameworks for cancer immunotherapy

Immunotherapy techniques,such as immune checkpoint inhibitors,chimeric antigen receptor(CAR)T cell therapies and cancer vaccines,have been burgeoning with great success,particularly for specific cancer types.However,side effects with fatal risks,dysfunction in tumor microenvironment and low immune response rates remain the bottlenecks in immunotherapy.Nano metal-organic frameworks(nMOFs),with an accurate structure and a narrow size distribution,are emerging as a solution to these problems.In addition to their function of temporospatial delivery,a large library of their compositions,together with flexibility in chemical interaction and inherent immune efficacy,offers opportunities for various designs of nMOFs for immunotherapy.In this review,we overview state-of-the-art research on nMOFs-based immunotherapies as well as their combination with other therapies.We demonstrate that nMOFs are predominantly customized for vaccine delivery or tumor-microenvironment modulation.Finally,a prospect of nMOFs in cancer immunotherapy will be discussed.

Durable endothelium-mimicking coating for surface bioengineering cardiovascular stents

Mimicking the nitric oxide(NO)-release and glycocalyx functions of native vascular endothelium on cardiovascular stent surfaces has been demonstrated to reduce in-stent restenosis(ISR)effectively.However,the practical performance of such an endothelium-mimicking surfaces is strictly limited by the durability of both NO release and bioactivity of the glycocalyx component.Herein,we present a mussel-inspired amine-bearing adhesive coating able to firmly tether the NO-generating species(e.g.,Cu-DOTA coordination complex)and glycocalyx-like component(e.g.,heparin)to create a durable endothelium-mimicking surface.The stent surface was firstly coated with polydopamine(pDA),followed by a surface chemical cross-link with polyamine(pAM)to form a durable pAMDA coating.Using a stepwise grafting strategy,Cu-DOTA and heparin were covalently grafted on the pAMDA-coated stent based on carbodiimide chemistry.Owing to both the high chemical stability of the pAMDA coating and covalent immobilization manner of the molecules,this proposed strategy could provide 62.4%bioactivity retention ratio of heparin,meanwhile persistently generate NO at physiological level from 5.9±0.3 to 4.8±0.4×10^(-10) mol cm^(-2) min^(-1) in 1 month.As a result,the functionalized vascular stent showed long-term endothelium-mimicking physiological effects on inhibition of thrombosis,inflammation,and intimal hyperplasia,enhanced re-endothelialization,and hence efficiently reduced ISR.

Bioengineering protection mechanism of city rock slope and its laboratory test

Based on the features of rock slope bioengineering protection,the ecology protection mechanism of the urban rock slope was discussed with the mechanics effect of plants and rock slope,and the reinforcement action mechanism of rock slope by plant root system was analyzed as well.Then,the corresponding mechanical model was proposed,from which the formula to calculate the increased shearing strength of the root system-earth compound body was derived.Moreover,the side slope rainfall interception,the runoff lagging,the soil antiseepage,and the soil layer consolidating effect were studied,respectively.Furthermore,the indoor model experiment of urban crag rock slope ecology protection was designed and completed,in which various grasses to plant in slope with different angles,solid earth forms,and the different strengthening earth mechanism were studied.Finally,the present method was applied in an engineering project,from which the antiwashing behavior of three kind of grasses(i.e.,the Bahiagrass,the tall fescue,and the Bermudagrass)planted in the slope with an angle of 38°,48°,and 58°,respectively,and different strengthening structures(i.e.,the diamond wire netting,the geocell and the threedimensional network)were obtained.The application results also show that the effect of geocell structure is the best one followed by the three-dimensional net and the diamond wire net.The antiwashing capability per unit area has a critical slope angle of about 25°.The reinforcing effect of Bermudagrass is better than the Bahiagrass and tall fescue.

Impact of Forestry Interventions on Groundwater Recharge and Sediment Control in the Ganga River Basin

Water related services of natural infrastructure will help to combat the risk of water crisis, and nature-based solutions involve the management of ecosystems to mimic or optimize the natural processes for the provision and regulation of water. Forested areas provide environmental stability and supply a high proportion of the world’s accessible freshwater for domestic, agricultural, industrial and ecological needs. The present work on “Forestry Interventions for Ganga” to rejuvenate the river is one of the steps toward the Ganga River rejuvenation programme in the country. The consequences of forestry interventions for Ganga will be determined on the basis of water quantity and water quality in the Ganga River. The study conservatively estimated the water savings and sedimentation reduction of the riverscape management in the Ganga basin using the Soil Conservation Service Curve Number (SCS-CN) & GEC, 2015 and Trimble, 1999 & CWC, 2019 methodologies, respectively. Forestry plantations and soil and moisture conservation measures devised in the programme to rejuvenate the Ganga River are expected to increase water recharge and decrease sedimentation load by 231.011 MCM·yr-1 and 1119.6 cubic m·yr-1 or 395.20 tons·yr-1, respectively, in delineated riverscape area of 83,946 km2 in Ganga basin due to these interventions. The role of trees and forests in improving hydrologic cycles, soil infiltration and ground water recharge in Ganga basin seems to be the reason for this change. Forest plantations and other bioengineering techniques can help to keep rivers perennial, increase precipitation, prevent soil erosion and mitigate floods, drought & climate change. The bioengineering techniques could be a feasible tool to enhance rivers’ self-purification as well as to make river perennial. The results will give momentum to the National Mission of Clean Ganga (NMCG) and its Namami Gange programme including other important rivers in the country and provide inputs in understanding the linkages among forest structure, function, and streamflow.

Translational research and innovation in modern transplant practice:Paradigms from Greece and around the world

The continuous clinical and technological advances,together with the social,health and economic challenges that the global population faces,have created an environment where the evolution of the field of transplantation is essentially necessary.The goal of this special issue is to provide a picture of the current status of transplantation in Greece as well as in many other countries in Europe and around the world.Authors from Greece and several other countries provide us with valuable insight into their respective areas of transplant expertise,with a main focus on the field of translational research and innovation.The papers that are part of this Special Issue“Translational Research and Innovation and the current status of Transplantation in Greece”have presented innovative and meaningful approaches in modern transplant research and practice.They provide us with a clear overview of the current landscape in transplantation,including liver transplantation in the context of a major pandemic,the evolution of living donor kidney transplantation or the evolution of the effect of hepatitis C virus infection in transplantation,while at the same time explore more recent challenges,such as the issue of frailty in the transplant candidate and the changes brought by newer treatments,such as immunotherapy,in transplant oncology.Additionally,they offer us a glimpse of the effect that technological innovations,such as virtual reality,can have on transplantation,both in terms of clinical and educational aspects.Just as critical is the fact that this Special Issue emphasizes the multidisciplinary,collaborative efforts currently taking place that link transplant research and innovation with other cutting-edge disciplines such as bioengineering,advanced information technology and artificial intelligence.In this Special Issue,in addition to the clinical and research evolution of the field of transplantation,we are witnessing the importance of interdisciplinary collaboration in medicine.

3D printing of functional bioengineered constructs for neural regeneration: a review

Three-dimensional(3D)printing technology has opened a new paradigm to controllably and reproducibly fabricate bioengineered neural constructs for potential applications in repairing injured nervous tissues or producing in vitro nervous tissue models.However,the complexity of nervous tissues poses great challenges to 3D-printed bioengineered analogues,which should possess diverse architectural/chemical/electrical functionalities to resemble the native growth microenvironments for functional neural regeneration.In this work,we provide a state-of-the-art review of the latest development of 3D printing for bioengineered neural constructs.Various 3D printing techniques for neural tissue-engineered scaffolds or living cell-laden constructs are summarized and compared in terms of their unique advantages.We highlight the advanced strategies by integrating topographical,biochemical and electroactive cues inside 3D-printed neural constructs to replicate in vivo-like microenvironment for functional neural regeneration.The typical applications of 3D-printed bioengineered constructs for in vivo repair of injured nervous tissues,bio-electronics interfacing with native nervous system,neural-on-chips as well as brain-like tissue models are demonstrated.The challenges and future outlook associated with 3D printing for functional neural constructs in various categories are discussed.

Transitioning of renal transplant pathology from allograft to xenograft and tissue engineering pathology:Are we prepared?

Currently,the most feasible and widely practiced option for patients with endstage organ failure is the transplantation of part of or whole organs,either from deceased or living donors.However,organ shortage has posed and is still posing a big challenge in this field.Newer options being explored are xenografts and engineered/bioengineered tissues/organs.Already small steps have been taken in this direction and sooner or later,these will become a norm in this field.However,these developments will pose different challenges for the diagnosis and management of problems as compared with traditional allografts.The approach to pathologic diagnosis of dysfunction in these settings will likely be significantly different.Thus,there is a need to increase awareness and prepare transplant diagnosticians to meet this future challenge in the field of xenotransplantation/regenerative medicine.This review will focus on the current status of transplant pathology and how it will be changed in the future with the emerging scenario of routine xenotransplantation.