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Regenerative engineering and bionic limbs

Rare Metals 2015年第3期34卷 143-155页

作者： Roshan James cato t.laurencin Institute for Regenerative Engineering University of Connecticut Health Center Raymond and Beverly Sackler Center for Biological Physical and Engineering SciencesUniversity of Connecticut Health Center Department of Orthopaedic Surgery University of Connecticut Health Center Connecticut Institute for Clinical and translational Science Department of Chemical Materials and Biomolecular EngineeringUniversity of Connecticut

Amputations of the upper extremity are severely debilitating, current treatments support very basic limb movement, and patients undergo extensive physiotherapy and psychological counseling. there is no prosthesis that allows the amputees near normal function. With increasing number of amputees due to injuries sustained in accidents, natural calamities, and international conflicts, there is a growing requirement for novel strategies and new discov- eries. Advances have been made in technological, material, and in prosthesis integration where researchers are now exploring artificial prosthesis that integrate with the residual tissues and function based on signal impulses received from the residual nerves. Efforts are focused on challenging experts in different disciplines to integrate ideas and tech- nologies to allow for the regeneration of injured tissues,recording on tissue signals and feedback to facilitate responsive movements and gradations of muscle force. A fully functional replacement and regenerative or integrated prosthesis will rely on interface of biological process with robotic systems to allow individual control of movement such as at the elbow, forearm, digits, and thumb in the upper extremity. Regenerative engineering focused on the regen- eration of complex tissue and organ systems will be realized by the cross-fertilization of advances over the past 30 years in the fields of tissue engineering, nanotechnology, stem cell science, and developmental biology. the convergence of toolboxes crated within each discipline will allow interdis- ciplinary teams from engineering, science, and medicine to realize new strategies, mergers of disparate technologies, such as biophysics, smart bionics, and the healing power of the mind. tackling the clinical challenges, interfacing the biological process with bionic technologies, engineering biological control of the electronic systems, and feedback will be the important goals in regenerative engineering over the next two decades.

关键词： Bionic Electrical stimulation Regenerativeengineering Muscle Nerve Prosthetic

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the Quest toward limb regeneration:a regenerative engineering approach

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Regenerative Biomaterials 2016年第2期3卷 123-125页

作者： cato t.laurencin Lakshmi S.Nair Department of Orthopaedic Surgery Institute for Regenerative EngineeringRaymond and Beverly Sackler Center for BiomedicalBiologicalPhysical and Engineering SciencesUniversity of Connecticut HealthFarmingtonCT 06030USA Department of Biomedical Engineering University of ConnecticutStorrsCT 06269USA Department of Materials Science and Engineering University of ConnecticutStorrsCT 06269USA Department of Chemical and Biomolecular Engineering University of ConnecticutStorrsCT 06269USA Department of Craniofacial Sciences School of Dental MedicineUniversity of Connecticut HealthFarmingtonCT 06030USA.

the Holy Grail to address the clinical grand challenge of human limb loss is to develop innovative strategies to regrow the amputated limb.the remarkable advances in the scientific understanding of regeneration,stem cell science,material science and engineering,physics and novel surgical approaches in the past few decades have provided a regenerative tool box to face this grand challenge and address the limitations of human wound healing.Here we discuss the convergence approach put forward by the field of Regenerative Engineering to use the regenerative tool box to design and develop novel translational strategies to limb regeneration.

关键词： regenerative engineering limb regeneration stem cells advanced biomaterial science clinical translation

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Nanofiber–microsphere (nano-micro) matrices for bone regenerative engineering: a convergence approach toward matrix design

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Regenerative Biomaterials 2014年第1期1卷 3-9页

作者： Clarke Nelson Yusuf Khan cato t.laurencin Raymond and Beverly Sackler Center for Biomedical BiologicalPhysical and Engineering SciencesInstitute for Regenerative EngineeringUniversity of Connecticut Health CenterFarmingtonCT 06030USA Department of Orthopaedic Surgery University of Connecticut Health CenterFarmingtonCT 06030USA Department of Materials Science and Engineering University of ConnecticutStorrsCT 06269USA Department of Chemical and Biomolecular Engineering University of ConnecticutStorrsCT 06269USA

Bone is an essential organ for health and quality of life.Due to current shortfalls in therapy for bone tissue engineering,scientists have sought the application of synthetic materials as bone graft substitutes.As a composite organic/inorganic material with significant extra cellular matrix(ECM),one way to improve bone graft substitutes may be to engineer a synthetic matrix that is influenced by the physical appearance of natural ECM networks.In this work,the authors evaluate composite,hybrid scaffolds for bone tissue engineering based on composite ceramic/polymer microsphere scaffolds with synthetic ECM-mimetic networks in their pore spaces.Using thermally induced phase separation,nanoscale fibers were deposited in the pore spaces of structurally sound microsphere-based scaffold with a density proportionate to the initial polymer concentration.Porosimetry and mechanical testing indicated no significant changes in overall pore characteristics or mechanical integrity as a result of the fiber deposition process.these scaffolds displayed adequate mechanical integrity on the scale of human trabecular bone and supported the adhesion and proliferation of cultured mouse calvarial osteoblasts.Drawing from natural cues,these scaffolds may represent a new avenue forward for advanced bone tissue engineering scaffolds.

关键词： nanobiomaterials bioceramics medical device bone

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Enhancing the Surface Properties of a Bioengineered Anterior Cruciate Ligament Matrix for Use with Point-of-Care Stem Cell therapy

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Engineering 2021年第2期7卷 153-161页

作者： Xiaohua Yu Paulos Y.Mengsteab Ganesh Narayanan Lakshmi S.Nair cato t.laurencin Connecticut Convergence Institute for translation in Regenerative Engineering University of Connecticut HealthFarmingtonCT 06030USA Raymond and Beverly Sackler Center for Biological Physical and Engineering SciencesUniversity of Connecticut HealthFarmingtonCT 06030USA Department of Orthopedic Surgery University of Connecticut HealthFarmingtonCT 06030USA Department of Biomedical Engineering University of ConnecticutStorrsCT 06269USA Department of Materials Science and Engineering University of ConnecticutStorrsCT 06269USA Department of Chemical and Biomolecular Engineering University of ConnecticutStorrsCT 06269USA Department of Reconstructive Sciences University of Connecticut HealthFarmingtonCT 06030USA

We have previously developed a poly(L-lactic)acid(PLLA)bioengineered anterior cruciate ligament(ACL)matrix that has demonstrated enhanced healing when seeded with primary ACL cells prior to implantation in a rabbit model,as compared with the matrix alone.this suggests that improving cell adhesion on the matrix may beneficially affect the healing response and long-term performance of the bioengineered ACL matrix.One regenerative engineering approach involves enhancing the surface properties of the matrix to support cell adhesion and growth in combination with point-of-care stem cell therapy.Herein,we studied the cell adhesion properties of PLLA braided microfiber matrices enhanced through the physical adsorption of fibronectin and air plasma treatment.We evaluated the kinetics and binding efficiency of fibronectin onto matrices at three time points and three fibronectin concentrations.Incubating the matrix for 120 min in a solution of 25 lgmL1 fibronectin achieved the greatest binding efficiency to the matrix and cellular adhesion.Exposing the matrices to air plasma treatment for 5 min before fibronectin adsorption significantly enhanced the cell adhesion of rabbit bone marrow-derived mesenchymal stem cells(R-BMMSCs)24 h post cell seeding.Finally,cellular proliferation was monitored for up to 21 d,the matrices were exposed to air plasma treatment,and fibronectin adsorption was found to result in enhanced cell number.these findings suggest that exposure to air plasma treatment and fibronectin adsorption enhances the cellular adhesion of PLLA braided microfiber matrices and may improve the clinical efficacy of the matrix in combination with point-of-care stem cell therapies.

关键词： Anterior cruciate ligament Ligament Poly(L-lactic)acid plasma treatment Fibronectin Stem cells Adhesion

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BME 2.0: Engineering the Future of Medicine

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Biomedical Engineering Frontiers 2023年第1期4卷 217-227页

作者： Michael I.Miller Andrew O.Brightman Frederick H.Epstein KJane Grande-Allen Jordan J.Green Eileen Haase cato t.laurencin Elizabeth Logsdon Feilim Mac Gabhann Brenda Ogle Chun Wang George R.Wodicka Raimond L.Winslow Department of Biomedical Engineering Johns Hopkins UniversityBaltimoreMDUSA Weldon School of Biomedical Engineering Purdue UniversityWest LafayetteINUSA Biomedical Engineering University of VirginiaCharlottesvilleVAUSA Department of Bioengineering Rice UniversityHoustonTXUSA Department of Biomolecular Engineering and Department of Orthopaedic Surgery University of ConnecticuttStorrsCTUSA Department of Biomedical Engineering University of Minnesota-Twin CitiesMinneapolisMNUSA

If the 20th century was the age of mapping and controlling the external world,the 21st century is the biomedical age of mapping and controlling the biological internal world.the biomedical age is bringing new technological breakthroughs for sensing and controlling human biomolecules,cells,tissues,and organs,which underpin new frontiers in the biomedical discovery,data,biomanufacturing,and translational sciences.this article reviews what we believe will be the next wave of biomedical engineering(BME)education in support of the biomedical age,what we have termed BME 2.0.BME 2.0 was announced on October 122017 at BMES 49(https://www.***.jhu.edu/news-events/news/miller-opens-2017-bmes-annual-meeting-with-vision-for-new-bme-era/).We present several principles upon which we believe the BME 2.0 curriculum should be constructed,and from these principles,we describe what view as the foundations that form the next generations of curricula in support of the BME enterprise.the core principles of BME 2.0 education are(a)educate students bilingually,from day 1,in the languages of modern molecular biology and the analytical modeling of complex biological systems;(b)prepare every student to be a biomedical data scientist;(c)build a unique BME community for discovery and innovation via a vertically integrated and convergent learning environment spanning the university and hospital systems;(d)champion an educational culture of inclusive excellence;and(e)codify in the curriculum ongoing discoveries at the frontiers of the discipline,thus ensuring BME 2.0 as a launchpad for training the future leaders of the biotechnology marketplaces.We envision that the BME 2.0 education is the path for providing every student with the training to lead in this new era of engineering the future of medicine in the 21st century.

关键词： organs education frontier

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Erratum to “BME 2.0: Engineering the Future of Medicine”

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Biomedical Engineering Frontiers 2023年第1期4卷 29-29页

作者： Michael I.Miller Andrew O.Brightman Frederick H.Epstein K.Jane Grande-Allen Jordan J.Green Eileen Haase cato t.laurencin Elizabeth Logsdon Feilim Mac Gabhann Brenda Ogle Chun Wang George R.Wodicka Raimond L.Winslow Department of Biomedical Engineering Johns Hopkins UniversityBaltimoreMDUSA Weldon School of Biomedical Engineering Purdue UniversityWest LafayetteINUSA Biomedical Engineering University of VirginiaCharlottesvilleVAUSA Department of Bioengineering Rice UniversityHoustonTXUSA Department of Biomolecular Engineering and Department of Orthopaedic Surgery University of ConnecticuttStorrsCTUSA Department of Biomedical Engineering University of Minnesota-Twin CitiesMinneapolisMNUSA

In the article“BME 2.0:Engineering the Future of Medicine”[1],the competing interests statement was inadvertently omitted by the publisher from the published version of the article.this has now been corrected in the... 详细信息

关键词： HtML BME text

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Nanocomposites and bone regeneration

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Frontiers of Materials Science 2011年第4期5卷 342-357页

作者： Roshan JAMES Meng DENG cato t. laurencin Sangamesh G. KUMBAR Institute for Regenerative Engineering University of Connecticut Health Center Farmington CT 06030 USA New England Musculoskeletal Institute University of Connecticut Health Center Farmington CT 06030 USA Department of Orthopaedic Surgery University of Connecticut Health Center Farmington CT 06030 USA Department of Chemical Materials and Biomolecular Engineering University of Connecticut Storrs CT 06269 USA

this manuscript focuses on bone repair/regeneration using tissue engineering strategies, and highlights nanobiotechnology developments leading to novel nanocomposite systems. About 6.5 million fractures occur annually in USA, and about 550,000 of these individual cases required the application of a bone graft. Autogenous and allogenous bone have been most widely used for bone graft based therapies; however, there are significant problems such as donor shortage and risk of infection. Alternatives using synthetic and natural biomaterials have been developed, and some are commercially available for clinical applications requiring bone grafts. However, it remains a great challenge to design an ideal synthetic graft that very closely mimics the bone tissue structurally, and can modulate the desired function in osteoblast and progenitor cell populations. Nanobiomaterials, specifically nanocomposites composed of hydroxyapatite （HA） and/or collagen are extremely promising graft substitutes. the biocomposites can be fabricated to mimic the material composition of native bone tissue, and additionally, when using nano-HA （reduced grain size）, one mimics the structural arrangement of native bone. A good understanding of bone biology and structure is critical to development of bone mimicking graft substitutes. HA and collagen exhibit excellent osteoconductive properties which can further modulate the regenerative/ healing process following fracture injury. Combining with other polymeric biomaterials will reinforce the mechanical properties thus making the novel nano-HA based composites comparable to human bone. We report on recent studies using nanocomposites that have been fabricated as particles and nanofibers for regeneration of segmental bone defects. the research in nanocomposites, highlight a pivotal role in the future development of an ideal orthopaedic implant device, however further significant advancements are necessary to achieve clinical use.

关键词： bone graft substitute nanocomposite hydroxyapatite collagen nanofiber,biomimetic nanobiomaterial osteogenic segmental defect tibia defect

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Regenerative Engineering for Knee Osteoarthritis treatment： Biomaterials and Cell-Based technologies

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Engineering 2017年第1期3卷 16-27页

作者： Jorge L. Escobar Ivirico Maumita Bhattacharjee Emmanuel Kuyinu Lakshmi S. Nair cato t. laurencin Institute for Regenerative Engineering University of Connecticut Health Center Farrnington CT 06030 USA Raymond and Beverly Sackler Center for Biomedical Biological Physical and Engineering Sciences University of Connecticut Health Center Farmington CT 06030 USA Department of Orthopaedic Surgery University of Connecticut Health Center Farmington CT 06030 USA Department of Biomedical Engineering School of Engineering University of Connecticut Storrs CT 06269 USA Department of Materials Science and Engineering School of Engineering University of Connecticut Storrs CT 06269 USA Institute of Materials Science University of Connecticut Storrs CT 06269 USA Department of Craniofacial Sciences School of Dental Medicine University of Connecticut Health Center Farmington CF 06030 USA Department of Chemical and Biomolecular Engineering School of Engineering University of Connecticut Storrs CT 06269 USA

膝关节骨性关节炎(OA)是世界上最常见的关节炎,其发病率逐年上升。不断上涨的治疗费用给患者带来了经济负担。膝关节OA治疗的两个早期干预目标是减轻膝关节的疼痛和关节软骨的损害。目前用于治疗膝关节OA的方法虽取得了一定疗效,但仍没... 详细信息

膝关节骨性关节炎(OA)是世界上最常见的关节炎,其发病率逐年上升。不断上涨的治疗费用给患者带来了经济负担。膝关节OA治疗的两个早期干预目标是减轻膝关节的疼痛和关节软骨的损害。目前用于治疗膝关节OA的方法虽取得了一定疗效,但仍没有一种方法可达到全膝关节置换术(tKA)的治疗效果。tKA主要应用于治疗末期膝关节OA,其缺点是有手术侵入性和手术费用昂贵。因而,应该重视创新性的再生技术,以推迟甚至消除患者对tKA的需求。一些基于生物材料和细胞的疗法目前正处于发展阶段,并已在临床前和临床研究方面取得了初步进展。单独或联合应用先进的生物材料和干细胞治疗膝关节OA可减轻疼痛,使损害的关节软骨再生。在此综述中,我们讨论了膝关节OA疼痛和软骨损害的发病机制,并探讨了该病的最新治疗策略及其局限性。

关键词：膝关节骨性关节炎骨关节炎疼痛间充质干细胞生物材料再生工程

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Improving QoS Using Mobility-Based Optimized Multipath Routing Protocol in MANEt

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Computer Systems Science & Engineering 2023年第7期46卷 1169-1181页

作者： S.J.Sangeetha t.Rajendran Department of Computer Science Periyar UniversitySalem636011India PG and Research Department of Computer Science Government Arts and Science CollegeKangeyam638108India

Mobile Ad-hoc Networks(MANEts)connect numerous nodes to communicate data from the sender node to the target node.Due to the lack of an infrastructure network,mobile nodes communicate through wireless without an access *** does not have a centralized controller and has a dynamic network topology,which increases link failure and energy consumption resulting in excessive path delay,loss of Quality of service(QoS),and reduced throughput during data communication.Congestion is a significant problem when the QoS of the link carrying the data is degraded.Routing is one of the vital challenges of MANEt due to the very dynamic and distributed nature of MANEt.this article introduces a Mobility-Based Optimized Multipath Routing Protocol(MBOMRP)and an Efficient Reliable Link-State transmission(ERLSt)algorithm to overcome these problems.the proposed Mobility-Based Optimized Multipath Routing Protocol(MBOMRP)is utilized for route discovery and maintenance to efficiently avoid traffic and sleeping nodes.ERLSt algorithm is used for efficient data transmission to increase QoS measurement parameters like throughput,Packet Delivery Ratio(PDR),and minimize the latency performance.the proposed MBOMRP-ERLSt algorithm improves data communication network lifetime,avoids link failures,and provides efficient results compared with previous algorithms.

关键词： MANEt QoS link failure improve data communication avoid traffic network lifetime MBOMRP-ERLSt

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基于G-蛋白偶联受体激酶2抑制剂治疗心力衰竭的合理药物设计（英文）

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中国药理学与毒理学杂志 2017年第10期31卷 945-946页

作者： John J tESMER Helen V WALDSCHMIDt Marie C cato Renee BOULEY Osvaldo CRUZ-RODRIGUEZ Scott D LARSEN University of Michigan Life Sciences Institute Ann ArborMichigan 48109 USA Department of Biological Sciences Purdue UniversityWest Lafayette Indiana 47907 USA University of Michigan Valteich Medicinal Chemistry Core Ann ArborMichigan 48109 USA

G protein-coupled receptors(GPCRs)convert extracellular stimuli in the form of hormones,odorants and light into profound changes in cell homeostasis.their timely desensitization is critical for cells to rapidly respond to changes in their environment and to avoid damage from sustained signaling.Seven GPCR kinases(GRKs)phosphorylate and regulate the activity of most of the^800 GPCRs in the human genome.Although GRKs normally play an adaptive role,in conditions such as chronic heart failure they are overexpressed and linked to disease progression.GRK2 and GRK5 have thus become important targets for the treatment of heart failure and pathological cardiac hypertrophy,respectively.Our lab has determined atomic structures representing all three vertebrate GRK subfamilies,and is now in the midst of a campaign to develop selective inhibitors of these enzymes using structure-based rational design.We have identified the FDA approved drug paroxetine as a selective GRK2 inhibitor,determined the crystal structure of the GRK2·paroxetine complex and,in collaboration with the Koch lab,showed that the drug improves contractility in myocytes and,most impressively,recovery in postmyocardial infarcted mice.Since then,we have identified additional chemical scaffolds that exhibit even higher potency and/or selectivity for GRK5.Using a"hybrid"inhibitor design approach we have generated GRK selective chemical probes that exhibit improved potency and stability and are able to increase inotropy and dampen the hypertrophic response in cardiomyocytes and small animal models.Structural analysis has revealed the molecular basis for selectivity and potency in many of these compounds,allowing for the design of future generations of GRK chemical probes.

关键词： herat failure GPCR GPCR kinase paroxetine drug design X-ray crystallography

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