Orbital fractures are a frequent and serious problem for practicing ophthalmologists. The complexity of the pathology is explained by the combined nature of the injuries(often associated with craniofacial injuries), m...Orbital fractures are a frequent and serious problem for practicing ophthalmologists. The complexity of the pathology is explained by the combined nature of the injuries(often associated with craniofacial injuries), multistage treatments, results that are often unsatisfactory, and a wide range of complaints about functional and cosmetic limitations. Over the years, significant progress has been made in the field of orbital reconstruction,allowing the transition from traditional methods using simple materials to innovative bioengineering solutions.This evolution has been driven by advances in surgical technologies, imaging techniques, and biomaterials aimed at optimizing the restoration of the shape and function of the orbital region. Traditional approaches are based on the use of autologous tissues such as bone grafts and muscle flaps, which provide biocompatibility and natural integration, but have limitations in terms of customization and accessibility. The advent of patient-specific implants and 3D printing technology has revolutionized the reconstruction of the orbit, allowing implants to be precisely adapted to a patient's anatomy. Biocompatible materials, such as porous polyethylene, titanium, and silicone, have become the basis for orbital reconstruction, ensuring durability and compatibility while minimizing long-term complications. Bioengineered solutions hold promise for further advancements in orbital reconstruction. We searched Pub Med, Cyberleninka, and other verified databases for published articles on orbital reconstruction reported in the literature between 1960 and January 2024. In this article, we consider the advantages and disadvantages of each category of reconstruction materials and provide up-to-date information on the methods for modifying their properties using modern processing technologies.展开更多
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 producin...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.展开更多
End stage liver diseases (ESLD) represent a major, neglected global public health crisis which requires an urgent action towards fnding a proper cure. Orthotro-pic liver transplantation has been the only definitive ...End stage liver diseases (ESLD) represent a major, neglected global public health crisis which requires an urgent action towards fnding a proper cure. Orthotro-pic liver transplantation has been the only definitive treatment modality for ESLD. However, shortage of donor organs, timely unavailability, post-surgery related complications and financial burden on the patients li-mits the number of patients receiving the transplants. Since last two decades cell-based therapies have revolu-tionized the feld of organ/tissue regeneration. However providing an alternative organ source to address the donor liver shortage still poses potential challenges. The developments made in this direction provide useful futuristic approaches, which could be translated into preclinical and clinical settings targeting appropriate applications in specific disease conditions. Earlier studies have demonstrated the applicability of this particular approach to generate functional organ in rodent system by connecting them with portal and hepatic circulatory networks. However, such strategy requires very high level of surgical expertise and also poses the technical and financial questions towards its future applicability. Hence, alternative sites for generating secondary organs are being tested in several types of disease conditions. Among different sites, omentum has been proved to be more appropriate site for implanting several kinds of functional tissue constructs without eliciting much immunological response. Hence, omentum may be con-sidered as better site for transplanting humanized bio-engineered ex vivo generated livers, thereby creating a secondary organ at intra-omental site. However, the expertise for generating such bioengineered organs are limited and only very few centres are involved for inve-stigating the potential use of such implants in clinical practice due to gap between the clinical transplant surgeons and basic scientists working on the concept evolution. Herein we discuss the recent advances and challenges to create functional secondary organs thr-ough intra-omental transplantation of ex vivo genera-ted bioengineered humanized livers and their further application in the management of ESLD as a supportive bridge for organ transplantation.展开更多
In January of 2010 we will launch Bioengineered Bugs,the first international peerreviewed journal of its kind to focus on genetic engineering which involves the generation of recombinant strains(from higher plants and...In January of 2010 we will launch Bioengineered Bugs,the first international peerreviewed journal of its kind to focus on genetic engineering which involves the generation of recombinant strains(from higher plants and animals to bacteria,fungi and viruses)and their metabolic products for beneficial applications in food,medicine,industry,environment and bio-defense.Bioengineered Bugs boasts an impressive international Editorial Board,including展开更多
Bioengineered materials are used as a substitute in many fields of medicine,especially in plastic surgery and in burns.In ophthalmic plastic surgery they can be used for covering large tissue defects or as a tarsal pl...Bioengineered materials are used as a substitute in many fields of medicine,especially in plastic surgery and in burns.In ophthalmic plastic surgery they can be used for covering large tissue defects or as a tarsal plate substitute,in cases when it is not possible to use conventional surgical techniques.We have searched PubMed and Web of Science scientific databases.We can generally categorize skin substitutes by the type of tissue used-we distinguish autografts,allografts,and xenografts.There are also completely synthetic substitutes.The aim of our article was to summarize the current state of knowledge and to sum up all the clinical applications of bioengineered materials in the periocular region.There are only a few scientific articles about this topic and lack of prospective randomized studies aimed on use of bioengineered materials in periocular region.Nevertheless,there are many articles describing successful case reports or case reports series.According to literature,bioengineered materials are the most commonly used in big traumas or large surgical defects,especially in oculoplastic tumour surgery.Bioengineered dermal substitutes are not frequently used in the periocular region.Dermal substitutes are useful,when it is not possible to close the defect with any other conventional surgical technique.展开更多
Extracellular vesicles(EVs)-based cell-free therapy,particularly stem cell-derived extracellular vesicles(SC-EVs),offers new insights into treating a series of neurological disorders and becomes a promising candidate ...Extracellular vesicles(EVs)-based cell-free therapy,particularly stem cell-derived extracellular vesicles(SC-EVs),offers new insights into treating a series of neurological disorders and becomes a promising candidate for alternative stem cell regenerative therapy.Currently,SC-EVs are considered direct therapeutic agents by themselves and/or dynamic delivery systems as they have a similar regenerative capacity of stem cells to promote neurogenesis and can easily load many functional small molecules to recipient cells in the central nervous system.Meanwhile,as non-living entities,SC-EVs avoid the uncontrollability and manufacturability limitations of live stem cell products in vivo(e.g.,low survival rate,immune response,and tumorigenicity)and in vitro(e.g.,restricted sources,complex preparation processes,poor quality control,low storage,shipping instability,and ethical controversy)by strict quality control system.Moreover,SC-EVs can be engineered or designed to enhance further overall yield,increase bioactivity,improve targeting,and extend their half-life.Here,this review provides an overview on the biological properties of SC-EVs,and the current progress in the strategies of native or bioengineered SC-EVs for nerve injury repairing is presented.Then we further summarize the challenges of recent research and perspectives for successful clinical application to advance SC-EVs from bench to bedside in neurological diseases.展开更多
AIM To develop appropriate humanized three-dimensional ex-vivo model system for drug testing. METHODS Bioengineered humanized livers were developed in this study using human hepatic stem cells repopulation within the ...AIM To develop appropriate humanized three-dimensional ex-vivo model system for drug testing. METHODS Bioengineered humanized livers were developed in this study using human hepatic stem cells repopulation within the acellularized liver scaffolds which mimics with the natural organ anatomy and physiology. Six cytochrome P-450 probes were used to enable efficient identification of drug metabolism in bioengineered humanized livers. The drug metabolism study in bioengineered livers was evaluated to identify the absorption, distribution, metabolism, excretion and toxicity responses.RESULTS The bioengineered humanized livers showed cellular and molecular characteristics of human livers. The bioengineered liver showed three-dimensional natural architecture with intact vasculature and extra-cellular matrix. Human hepatic cells were engrafted similar to the human liver. Drug metabolism studies provided a suitable platform alternative to available ex-vivo and in vivo models for identifying cellular and molecular dynamics of pharmacological drugs.CONCLUSION The present study paves a way towards the development of suitable humanized preclinical model systems for pharmacological testing. This approach may reduce the cost and time duration of preclinical drug testing and further overcomes on the anatomical and physiological variations in xenogeneic systems.展开更多
In recent years,increasing attention has been paid to bioengineered bacteria as vectors for the treatment of allergic diseases.The methods for preparing bioengineered bacteria that can express exogenous genes are impr...In recent years,increasing attention has been paid to bioengineered bacteria as vectors for the treatment of allergic diseases.The methods for preparing bioengineered bacteria that can express exogenous genes are improving.Research has focused mainly on application of bioengineered bacteria expressing recombinant allergens,hypoallergenic derivatives of allergens,T-cell epitope derivatives,cytokines,or as mucosal adjuvants to enhance immunotherapy effects.This strategy offers new ideas for the treatment of allergic diseases.This review summarizes recent advances in use of live bioengineered bacteria in allergic diseases as well as the challenges of using microorganisms(or their components)in immunotherapy.展开更多
Drug-metabolizing enzymes, transporters, and nuclear receptors are essential for the absorption, distribution, metabolism, and excretion(ADME) of drugs and xenobiotics. MicroRNAs participate in the regulation of ADME ...Drug-metabolizing enzymes, transporters, and nuclear receptors are essential for the absorption, distribution, metabolism, and excretion(ADME) of drugs and xenobiotics. MicroRNAs participate in the regulation of ADME gene expression via imperfect complementary Watson–Crick base pairings with target transcripts. We have previously reported that Cytochrome P450 3A4(CYP3A4) and ATP-binding cassette sub-family G member 2(ABCG2) are regulated by miR-27b-3p and miR-328-3p,respectively. Here we employed our newly established RNA bioengineering technology to produce bioengineered RNA agents(BERA), namely BERA/miR-27b-3p and BERA/miR-328-3p, via fermentation. When introduced into human cells, BERA/miR-27b-3p and BERA/miR-328-3p were selectively processed to target miRNAs and thus knock down CYP3A4 and ABCG2 mRNA and their protein levels,respectively, as compared to cells treated with vehicle or control RNA. Consequently, BERA/miR-27b-3p led to a lower midazolam 10-hydroxylase activity, indicating the reduction of CYP3A4 activity. Likewise,BERA/miR-328-3p treatment elevated the intracellular accumulation of anticancer drug mitoxantrone, a classic substrate of ABCG2, hence sensitized the cells to chemotherapy. The results indicate that biologic miRNA agents made by RNA biotechnology may be applied to research on miRNA functions in the regulation of drug metabolism and disposition that could provide insights into the development of more effective therapies.展开更多
MicroRNAs(miRNAs or miRs)are small noncoding RNAs derived from genome to control target gene expression.Recently we have developed a novel platform permitting high-yield production of bioengineered miRNA agents(BERA)....MicroRNAs(miRNAs or miRs)are small noncoding RNAs derived from genome to control target gene expression.Recently we have developed a novel platform permitting high-yield production of bioengineered miRNA agents(BERA).This study is to produce and utilize novel fully-humanized BERA/miR-3’28-3p molecule(hBERA/miR-3’28)to delineate the role of miR-328-3p in controlling nutrient uptake essential for cell metabolism.We first demonstrated successful high-level expression of hBERA/miR-328 in bacteria and purification to high degree of homogeneity(>98%).Biologic miR-328-3p prodrug was selectively processed to miR-328-3p to suppress the growth of highly-proliferative human osteosarcoma(OS)cells.Besides glucose transporter protein type 1,gene symbol solute carrier family 2 member 1(GUJTHSLC2A1),we identified and verified large neutral amino acid transporter 1,gene symbol solute carrier family 7 member 5(LPAT1/SLC7A5)as a direct target for miR-3’28-3p.While reduction of LAT1 protein levels by miR-3’28-3p did not alter homeostasis of amino acids within OS cells,suppression of GLUT1 led to a significantly lower glucose uptake and decline in intracellular levels of glucose and glycolytic metabolite lactate.Moreover,combination treatment with hBERA/miR-3’28 and cisplatin or doxorubicin exerted a strong synergism in the inhibition of OS cell proliferation.These findings support the utility of novel bioengineered RNA molecules and establish an important role of miR-328-3p in the control of nutrient transport and homeostasis behind cancer metabolism.展开更多
Immunotherapy is emerging as a powerful tool for combating many human diseases.However,the application of this life-saving treatment in serious brain diseases,including glioma,is greatly restricted.The major obstacle ...Immunotherapy is emerging as a powerful tool for combating many human diseases.However,the application of this life-saving treatment in serious brain diseases,including glioma,is greatly restricted.The major obstacle is the lack of effective technologies for transporting therapeutic agents across the blood-brain barrier(BBB)and achieving targeted delivery to specific cells once across the BBB.Ferritin,an iron storage protein,traverses the BBB via receptor-mediated transcytosis by binding to transferrin receptor 1(TfR1)overexpressed on BBB endothelial cells.Here,we developed bioengineered ferritin nanoparticles as drug delivery carriers that enable the targeted delivery of a small-molecule immunomodulator to achieve enhanced immunotherapeutic efficacy in an orthotopic glioma-bearing mouse model.We fused different glioma-targeting moieties on self-assembled ferritin nanoparticles via genetic engineering,and RGE fusion protein nanoparticles(RGE-HFn NPs)were identified as the best candidate.Furthermore,RGE-HFn NPs encapsulating a stimulator of interferon genes(STING)agonist(SR717@RGE-HFn NPs)maintained stable self-assembled structure and targeting properties even after traversing the BBB.In the glioma-bearing mouse model,SR717@RGE-HFn NPs elicited a potent local innate immune response in the tumor microenvironment,resulting in significant tumor growth inhibition and prolonged survival.Overall,this biomimetic brain delivery platform offers new opportunities to overcome the BBB and provides a promising approach for brain drug delivery and immunotherapy in patients with glioma.展开更多
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 selec...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.展开更多
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 fo...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.展开更多
In the context of emerging engineering disciplines,a hybrid teaching reform for the Bioengineering Downstream Technology course,based on ideological and political education and online open courses,is being carried out...In the context of emerging engineering disciplines,a hybrid teaching reform for the Bioengineering Downstream Technology course,based on ideological and political education and online open courses,is being carried out.This reform focuses on aspects such as“building a professional teacher team for ideological and political education,scientifically designing the ideological and political teaching system,innovating classroom teaching methods,and improving both formative and summative evaluation systems.”The“Craftsmanship in Education and Cultivating Soul and Roots”small private online course hybrid teaching reform for the Bioengineering Downstream Technology online open course provides a replicable model for the comprehensive implementation of ideological and political education in engineering courses and offers a reference for advancing ideological and political education and hybrid teaching reform in new engineering disciplines.展开更多
With the understanding of microRNA(miRNA or miR) functions in tumor initiation,progression,and metastasis,efforts are underway to develop new miRNA-based therapies.Very recently,we demonstrated effectiveness of a nove...With the understanding of microRNA(miRNA or miR) functions in tumor initiation,progression,and metastasis,efforts are underway to develop new miRNA-based therapies.Very recently,we demonstrated effectiveness of a novel humanized bioengineered miR-124-3 p prodrug in controlling spontaneous lung metastasis in mouse models.This study was to investigate the molecular and cellular mechanisms by which miR-124-3 p controls tumor metastasis.Proteomics study identified a set of proteins selectively and significantly downregulated by bioengineered miR-124-3 p in A549 cells,which were assembled into multiple cellular components critical for metastatic potential.Among them,plectin(PLEC) was verified as a new direct target for miR-124-3 p that links cytoskeleton components and junctions.In miR-124-3 p-treated lung cancer and osteosarcoma cells,protein levels of vimentin,talin 1(TLN1),integrin beta-1(ITGB1),IQ motif containing GTPase activating protein 1(IQGAP1),cadherin2 or N-cadherin(CDH2),and junctional adhesion molecule A(F11 R or JAMA or JAM1) decreased,causing remodeling of cytoskeletons and disruption of cell-cell junctions.Furthermore,miR-124-3 p sharply suppressed the formation of focal adhesion plaques,leading to reduced cell adhesion capacity.Additionally,efficacy and safety of biologic miR-124-3 p therapy was established in an aggressive experimental metastasis mouse model in vivo.These results connect miR-124-3 p-PLEC signaling to other elements in the control of cytoskeleton,cell junctions,and adhesion essential for cancer cell invasion and extravasation towards metastasis,and support the promise of miR-124 therapy.展开更多
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...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.展开更多
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,de...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.展开更多
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 provisi...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<sup>-1</sup> and 1119.6 cubic m·yr<sup>-1</sup> or 395.20 tons·yr<sup>-1</sup>, respectively, in delineated riverscape area of 83,946 km<sup>2</sup> 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.展开更多
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 w...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.展开更多
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 transplantati...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.展开更多
文摘Orbital fractures are a frequent and serious problem for practicing ophthalmologists. The complexity of the pathology is explained by the combined nature of the injuries(often associated with craniofacial injuries), multistage treatments, results that are often unsatisfactory, and a wide range of complaints about functional and cosmetic limitations. Over the years, significant progress has been made in the field of orbital reconstruction,allowing the transition from traditional methods using simple materials to innovative bioengineering solutions.This evolution has been driven by advances in surgical technologies, imaging techniques, and biomaterials aimed at optimizing the restoration of the shape and function of the orbital region. Traditional approaches are based on the use of autologous tissues such as bone grafts and muscle flaps, which provide biocompatibility and natural integration, but have limitations in terms of customization and accessibility. The advent of patient-specific implants and 3D printing technology has revolutionized the reconstruction of the orbit, allowing implants to be precisely adapted to a patient's anatomy. Biocompatible materials, such as porous polyethylene, titanium, and silicone, have become the basis for orbital reconstruction, ensuring durability and compatibility while minimizing long-term complications. Bioengineered solutions hold promise for further advancements in orbital reconstruction. We searched Pub Med, Cyberleninka, and other verified databases for published articles on orbital reconstruction reported in the literature between 1960 and January 2024. In this article, we consider the advantages and disadvantages of each category of reconstruction materials and provide up-to-date information on the methods for modifying their properties using modern processing technologies.
基金financially supported by the National Natural Science Foundation of China (52125501)OPEN Project (BHJ17C019)+4 种基金the Key Research Project of Shaanxi Province (2021LLRH-08)the Program for Innovation Team of Shaanxi Province (2023-CX-TD-17)the Natural Science Basic Research Program of Shaanxi Province (2023-JCQN-0543)the China Postdoctoral Science Foundation (2021M702597)the Fundamental Research Funds for the Central Universities
文摘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.
文摘End stage liver diseases (ESLD) represent a major, neglected global public health crisis which requires an urgent action towards fnding a proper cure. Orthotro-pic liver transplantation has been the only definitive treatment modality for ESLD. However, shortage of donor organs, timely unavailability, post-surgery related complications and financial burden on the patients li-mits the number of patients receiving the transplants. Since last two decades cell-based therapies have revolu-tionized the feld of organ/tissue regeneration. However providing an alternative organ source to address the donor liver shortage still poses potential challenges. The developments made in this direction provide useful futuristic approaches, which could be translated into preclinical and clinical settings targeting appropriate applications in specific disease conditions. Earlier studies have demonstrated the applicability of this particular approach to generate functional organ in rodent system by connecting them with portal and hepatic circulatory networks. However, such strategy requires very high level of surgical expertise and also poses the technical and financial questions towards its future applicability. Hence, alternative sites for generating secondary organs are being tested in several types of disease conditions. Among different sites, omentum has been proved to be more appropriate site for implanting several kinds of functional tissue constructs without eliciting much immunological response. Hence, omentum may be con-sidered as better site for transplanting humanized bio-engineered ex vivo generated livers, thereby creating a secondary organ at intra-omental site. However, the expertise for generating such bioengineered organs are limited and only very few centres are involved for inve-stigating the potential use of such implants in clinical practice due to gap between the clinical transplant surgeons and basic scientists working on the concept evolution. Herein we discuss the recent advances and challenges to create functional secondary organs thr-ough intra-omental transplantation of ex vivo genera-ted bioengineered humanized livers and their further application in the management of ESLD as a supportive bridge for organ transplantation.
文摘In January of 2010 we will launch Bioengineered Bugs,the first international peerreviewed journal of its kind to focus on genetic engineering which involves the generation of recombinant strains(from higher plants and animals to bacteria,fungi and viruses)and their metabolic products for beneficial applications in food,medicine,industry,environment and bio-defense.Bioengineered Bugs boasts an impressive international Editorial Board,including
文摘Bioengineered materials are used as a substitute in many fields of medicine,especially in plastic surgery and in burns.In ophthalmic plastic surgery they can be used for covering large tissue defects or as a tarsal plate substitute,in cases when it is not possible to use conventional surgical techniques.We have searched PubMed and Web of Science scientific databases.We can generally categorize skin substitutes by the type of tissue used-we distinguish autografts,allografts,and xenografts.There are also completely synthetic substitutes.The aim of our article was to summarize the current state of knowledge and to sum up all the clinical applications of bioengineered materials in the periocular region.There are only a few scientific articles about this topic and lack of prospective randomized studies aimed on use of bioengineered materials in periocular region.Nevertheless,there are many articles describing successful case reports or case reports series.According to literature,bioengineered materials are the most commonly used in big traumas or large surgical defects,especially in oculoplastic tumour surgery.Bioengineered dermal substitutes are not frequently used in the periocular region.Dermal substitutes are useful,when it is not possible to close the defect with any other conventional surgical technique.
基金financial support received from the Program of the China National Health Commission and National Medical Products Administration(NMPA)under Grant No.CMR-20161129-1003(to JL)The National Nature Science Foundation of China under Grant No.82072953(to LW)+2 种基金The Liaoning Province Excellent Talent Program Project under Grant No.XLYC1902031(to JL)Top young talents of Liaoning Provincial Government under Grant No.XLYC1907009(to LW)Dalian Outstanding Young Talents Project under Grant No.2021RJ12(to LW)。
文摘Extracellular vesicles(EVs)-based cell-free therapy,particularly stem cell-derived extracellular vesicles(SC-EVs),offers new insights into treating a series of neurological disorders and becomes a promising candidate for alternative stem cell regenerative therapy.Currently,SC-EVs are considered direct therapeutic agents by themselves and/or dynamic delivery systems as they have a similar regenerative capacity of stem cells to promote neurogenesis and can easily load many functional small molecules to recipient cells in the central nervous system.Meanwhile,as non-living entities,SC-EVs avoid the uncontrollability and manufacturability limitations of live stem cell products in vivo(e.g.,low survival rate,immune response,and tumorigenicity)and in vitro(e.g.,restricted sources,complex preparation processes,poor quality control,low storage,shipping instability,and ethical controversy)by strict quality control system.Moreover,SC-EVs can be engineered or designed to enhance further overall yield,increase bioactivity,improve targeting,and extend their half-life.Here,this review provides an overview on the biological properties of SC-EVs,and the current progress in the strategies of native or bioengineered SC-EVs for nerve injury repairing is presented.Then we further summarize the challenges of recent research and perspectives for successful clinical application to advance SC-EVs from bench to bedside in neurological diseases.
文摘AIM To develop appropriate humanized three-dimensional ex-vivo model system for drug testing. METHODS Bioengineered humanized livers were developed in this study using human hepatic stem cells repopulation within the acellularized liver scaffolds which mimics with the natural organ anatomy and physiology. Six cytochrome P-450 probes were used to enable efficient identification of drug metabolism in bioengineered humanized livers. The drug metabolism study in bioengineered livers was evaluated to identify the absorption, distribution, metabolism, excretion and toxicity responses.RESULTS The bioengineered humanized livers showed cellular and molecular characteristics of human livers. The bioengineered liver showed three-dimensional natural architecture with intact vasculature and extra-cellular matrix. Human hepatic cells were engrafted similar to the human liver. Drug metabolism studies provided a suitable platform alternative to available ex-vivo and in vivo models for identifying cellular and molecular dynamics of pharmacological drugs.CONCLUSION The present study paves a way towards the development of suitable humanized preclinical model systems for pharmacological testing. This approach may reduce the cost and time duration of preclinical drug testing and further overcomes on the anatomical and physiological variations in xenogeneic systems.
基金supported by the Nanjing Incubation Program for National Clinical Research Center(No.2019060001)the key project of Social Development in Jiangsu Province(No.BE2020632)+1 种基金National Natural Science Foundation of China(No.82073446)Medicine and Health Technology Innovation Project of Chinese Academy of Medical Sciences(No.2016-I2M-1-005)。
文摘In recent years,increasing attention has been paid to bioengineered bacteria as vectors for the treatment of allergic diseases.The methods for preparing bioengineered bacteria that can express exogenous genes are improving.Research has focused mainly on application of bioengineered bacteria expressing recombinant allergens,hypoallergenic derivatives of allergens,T-cell epitope derivatives,cytokines,or as mucosal adjuvants to enhance immunotherapy effects.This strategy offers new ideas for the treatment of allergic diseases.This review summarizes recent advances in use of live bioengineered bacteria in allergic diseases as well as the challenges of using microorganisms(or their components)in immunotherapy.
基金supported in part by the National Institutes of Health [Grant No. R01GM113888 (Aiming Yu), USA]supported by Visiting Scholar Programs from China Scholarship Council (201608440507, USA) Guangzhou Medical University+2 种基金National Natural Science Foundation of China (81603191, China)Natural Science Foundation of Guangdong Province (2015A030310153, China)supported by the 3102018zy053 from Fundamental Research Funds for the Central Universities (China)funded by the UC Davis Comprehensive Cancer Center Support Grant (CCSG) awarded by the National Cancer Institute (Grant No. P30CA093373, USA)
文摘Drug-metabolizing enzymes, transporters, and nuclear receptors are essential for the absorption, distribution, metabolism, and excretion(ADME) of drugs and xenobiotics. MicroRNAs participate in the regulation of ADME gene expression via imperfect complementary Watson–Crick base pairings with target transcripts. We have previously reported that Cytochrome P450 3A4(CYP3A4) and ATP-binding cassette sub-family G member 2(ABCG2) are regulated by miR-27b-3p and miR-328-3p,respectively. Here we employed our newly established RNA bioengineering technology to produce bioengineered RNA agents(BERA), namely BERA/miR-27b-3p and BERA/miR-328-3p, via fermentation. When introduced into human cells, BERA/miR-27b-3p and BERA/miR-328-3p were selectively processed to target miRNAs and thus knock down CYP3A4 and ABCG2 mRNA and their protein levels,respectively, as compared to cells treated with vehicle or control RNA. Consequently, BERA/miR-27b-3p led to a lower midazolam 10-hydroxylase activity, indicating the reduction of CYP3A4 activity. Likewise,BERA/miR-328-3p treatment elevated the intracellular accumulation of anticancer drug mitoxantrone, a classic substrate of ABCG2, hence sensitized the cells to chemotherapy. The results indicate that biologic miRNA agents made by RNA biotechnology may be applied to research on miRNA functions in the regulation of drug metabolism and disposition that could provide insights into the development of more effective therapies.
基金supported by Hubei Province Scientific and Technological Innovation Key Project(No.2019ACA136,China)supported by National Institute of General Medical Sciences grant(No.R01GM113888)+3 种基金National Cancer Institute grant(No.R01CA225958)National Institutes of Health(USA)supported by a fellowship from the Chinese Scholarship Council(No.201706270162,China)funded by the UC Davis Comprehensive Cancer Center Support Grant awarded by the National Cancer Institute grant(P30CA093373,USA).
文摘MicroRNAs(miRNAs or miRs)are small noncoding RNAs derived from genome to control target gene expression.Recently we have developed a novel platform permitting high-yield production of bioengineered miRNA agents(BERA).This study is to produce and utilize novel fully-humanized BERA/miR-3’28-3p molecule(hBERA/miR-3’28)to delineate the role of miR-328-3p in controlling nutrient uptake essential for cell metabolism.We first demonstrated successful high-level expression of hBERA/miR-328 in bacteria and purification to high degree of homogeneity(>98%).Biologic miR-328-3p prodrug was selectively processed to miR-328-3p to suppress the growth of highly-proliferative human osteosarcoma(OS)cells.Besides glucose transporter protein type 1,gene symbol solute carrier family 2 member 1(GUJTHSLC2A1),we identified and verified large neutral amino acid transporter 1,gene symbol solute carrier family 7 member 5(LPAT1/SLC7A5)as a direct target for miR-3’28-3p.While reduction of LAT1 protein levels by miR-3’28-3p did not alter homeostasis of amino acids within OS cells,suppression of GLUT1 led to a significantly lower glucose uptake and decline in intracellular levels of glucose and glycolytic metabolite lactate.Moreover,combination treatment with hBERA/miR-3’28 and cisplatin or doxorubicin exerted a strong synergism in the inhibition of OS cell proliferation.These findings support the utility of novel bioengineered RNA molecules and establish an important role of miR-328-3p in the control of nutrient transport and homeostasis behind cancer metabolism.
基金funded by the Interdisciplinary Program of Shanghai Jiao Tong University(project number ZH2018ZDA36(19X190020006))Shanghai Jiao Tong University Scientific and Technological Innovation Funds(2019TPA10)+1 种基金the Foundation of National Facility for Translational Medicine(Shanghai)(TMSK-2020-008).X.X.acknowledges support from the National Science Foundation(2001606)the Gustavus and Louise Pfeiffer Research Foundation Award.We greatly thank Xiyun Yan(Institute of Biophysics,CAS)for her generous gift of the pET-HFn plasmid.We also thank Kelong Fan(Institute of Biophysics,CAS)for his professional suggestions on protein purification.
文摘Immunotherapy is emerging as a powerful tool for combating many human diseases.However,the application of this life-saving treatment in serious brain diseases,including glioma,is greatly restricted.The major obstacle is the lack of effective technologies for transporting therapeutic agents across the blood-brain barrier(BBB)and achieving targeted delivery to specific cells once across the BBB.Ferritin,an iron storage protein,traverses the BBB via receptor-mediated transcytosis by binding to transferrin receptor 1(TfR1)overexpressed on BBB endothelial cells.Here,we developed bioengineered ferritin nanoparticles as drug delivery carriers that enable the targeted delivery of a small-molecule immunomodulator to achieve enhanced immunotherapeutic efficacy in an orthotopic glioma-bearing mouse model.We fused different glioma-targeting moieties on self-assembled ferritin nanoparticles via genetic engineering,and RGE fusion protein nanoparticles(RGE-HFn NPs)were identified as the best candidate.Furthermore,RGE-HFn NPs encapsulating a stimulator of interferon genes(STING)agonist(SR717@RGE-HFn NPs)maintained stable self-assembled structure and targeting properties even after traversing the BBB.In the glioma-bearing mouse model,SR717@RGE-HFn NPs elicited a potent local innate immune response in the tumor microenvironment,resulting in significant tumor growth inhibition and prolonged survival.Overall,this biomimetic brain delivery platform offers new opportunities to overcome the BBB and provides a promising approach for brain drug delivery and immunotherapy in patients with glioma.
基金This work was funded by National Natural Science Foundation of China(32272279)the Key R&D project of Qingdao Science and Technology Plan(22-3-3-hygg-29-hy).
文摘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.
文摘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.
基金Guangdong Province Undergraduate Online Open Course Guidance Committee Research Project(2022ZXKC462)Foshan Philosophy and Social Science Planning Project(2024-GJ 037)+4 种基金Provincial First-Class Undergraduate Courses of Guangdong Provincial Education Department(Guangdong Education Gaohan[2022]No.10)Innovation Project of Guangdong Graduate Education(2022JGXM129,2022JGXM128,2023ANLK-080)Foshan University Curriculum Ideological and Political Teaching Reform and Practice Demonstration Project in 2023Quality Engineering Project of Foshan University in 2023Collaborative Education Project of the Ministry of Education in 2023(230703232312141)。
文摘In the context of emerging engineering disciplines,a hybrid teaching reform for the Bioengineering Downstream Technology course,based on ideological and political education and online open courses,is being carried out.This reform focuses on aspects such as“building a professional teacher team for ideological and political education,scientifically designing the ideological and political teaching system,innovating classroom teaching methods,and improving both formative and summative evaluation systems.”The“Craftsmanship in Education and Cultivating Soul and Roots”small private online course hybrid teaching reform for the Bioengineering Downstream Technology online open course provides a replicable model for the comprehensive implementation of ideological and political education in engineering courses and offers a reference for advancing ideological and political education and hybrid teaching reform in new engineering disciplines.
基金supported by the National Cancer Institute (No. R01CA225958 to Ai-Ming Yu, USA)National Institutes of Health+3 种基金supported by Hubei Province Scientific and Technological Innovation Key Project (No. 2019ACA136, China)Hubei Province Medical Leader Talent Project (No. LJ20200405, China)supported by a fellowship from the Chinese Scholarship Council (No. 201906270202, China)the Mouse Biology and Molecular Pharmacology Shared Resources funded by the UC Davis Comprehensive Cancer Center Support Grant awarded by the National Cancer Institute (No. P30CA093373, USA), National Institutes of Health。
文摘With the understanding of microRNA(miRNA or miR) functions in tumor initiation,progression,and metastasis,efforts are underway to develop new miRNA-based therapies.Very recently,we demonstrated effectiveness of a novel humanized bioengineered miR-124-3 p prodrug in controlling spontaneous lung metastasis in mouse models.This study was to investigate the molecular and cellular mechanisms by which miR-124-3 p controls tumor metastasis.Proteomics study identified a set of proteins selectively and significantly downregulated by bioengineered miR-124-3 p in A549 cells,which were assembled into multiple cellular components critical for metastatic potential.Among them,plectin(PLEC) was verified as a new direct target for miR-124-3 p that links cytoskeleton components and junctions.In miR-124-3 p-treated lung cancer and osteosarcoma cells,protein levels of vimentin,talin 1(TLN1),integrin beta-1(ITGB1),IQ motif containing GTPase activating protein 1(IQGAP1),cadherin2 or N-cadherin(CDH2),and junctional adhesion molecule A(F11 R or JAMA or JAM1) decreased,causing remodeling of cytoskeletons and disruption of cell-cell junctions.Furthermore,miR-124-3 p sharply suppressed the formation of focal adhesion plaques,leading to reduced cell adhesion capacity.Additionally,efficacy and safety of biologic miR-124-3 p therapy was established in an aggressive experimental metastasis mouse model in vivo.These results connect miR-124-3 p-PLEC signaling to other elements in the control of cytoskeleton,cell junctions,and adhesion essential for cancer cell invasion and extravasation towards metastasis,and support the promise of miR-124 therapy.
文摘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.
基金supported by The Plastic Surgery Foundation Research Pilot Grant,No.627383(to KAS).
文摘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.
文摘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<sup>-1</sup> and 1119.6 cubic m·yr<sup>-1</sup> or 395.20 tons·yr<sup>-1</sup>, respectively, in delineated riverscape area of 83,946 km<sup>2</sup> 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.
文摘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.
文摘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.