Knee osteoarthritis （OA） is the most common form of arthritis worldwide. The incidence of this disease is rising and its treatment poses an economic burden. Two early targets of knee OA treatment include the predomi...Knee osteoarthritis （OA） is the most common form of arthritis worldwide. The incidence of this disease is rising and its treatment poses an economic burden. Two early targets of knee OA treatment include the predominant symptom of pain, and cartilage damage in the knee joint. Current treatments have been beneficial in treating the disease but none is as effective as total knee arthroplasty （TKA）. However, while TKA is an end-stage solution of the disease, it is an invasive and expensive procedure, Therefore, innovative regenerative engineering strategies should be established as these could defer or annul the need for a TKA. Several biomaterial and cell-based therapies are currently in development and have shown early promise in both preclinical and clinical studies. The use of advanced biomaterials and stem cells independently or in conjunction to treat knee OA could potentially reduce pain and regenerate fo- cal articular cartilage damage. In this review, we discuss the pathogenesis of pain and cartilage damage in knee OA and explore novel treatment options currently being studied, along with some of their limitations.展开更多
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...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.展开更多
For over a decade,regenerative engineering has been defined as the convergence of advanced materials sciences,stem cell sciences,physics,developmental biology,and clinical translation for the regeneration of complex t...For over a decade,regenerative engineering has been defined as the convergence of advanced materials sciences,stem cell sciences,physics,developmental biology,and clinical translation for the regeneration of complex tissues.Recently,the field has made major strides because of new efforts made possible by the utilization of another growing field:artificial intelligence.However,there is currently no term to describe the use of artificial intelligence for regenerative engineering.Therefore,we hereby present a new term,“Regenerative Engineering AI”,which cohesively describes the interweaving of artificial intelligence into the framework of regenerative engineering rather than using it merely as a tool.As the first to define the term,regenerative engineering AI is the interdisciplinary integration of artificial intelligence and machine learning within the fundamental core of regenerative engineering to advance its principles and goals.It represents the subsequent synergetic relationship between the two that allow for multiplex solutions toward human limb regeneration in a manner different from individual fields and artificial intelligence alone.Establishing such a term creates a unique and unified space to consolidate the work of growing fields into one coherent discipline under a common goal and language,fostering interdisciplinary collaboration and promoting focused research and innovation.展开更多
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 c...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.展开更多
A variety of engineered scaffolds have been created for tissue engineering using polymers,ceramics and their composites.Biomimicry has been adopted for majority of the three-dimensional(3D)scaffold design both in term...A variety of engineered scaffolds have been created for tissue engineering using polymers,ceramics and their composites.Biomimicry has been adopted for majority of the three-dimensional(3D)scaffold design both in terms of physicochemical properties,as well as bioactivity for superior tissue regeneration.Scaffolds fabricated via salt leaching,particle sintering,hydrogels and lithography have been successful in promoting cell growth in vitro and tissue regeneration in vivo.Scaffold systems derived from decellularization of whole organs or tissues has been popular due to their assured biocompatibility and bioactivity.Traditional scaffold fabrication techniques often failed to create intricate structures with greater resolution,not reproducible and involved multiple steps.The 3D printing technology overcome several limitations of the traditional techniques and made it easier to adopt several thermoplastics and hydrogels to create micro-nanostructured scaffolds and devices for tissue engineering and drug delivery.This review highlights scaffold fabrication methodologies with a focus on optimizing scaffold performance through the matrix pores,bioactivity and degradation rate to enable tissue regeneration.Review highlights few examples of bioactive scaffold mediated nerve,muscle,tendon/ligament and bone regeneration.Regardless of the efforts required for optimization,a shift in 3D scaffold uses from the laboratory into everyday life is expected in the near future as some of the methods discussed in this review become more streamlined.展开更多
Inhalation-administrated drugs remain an interesting possibility of addressing pulmonary diseases.Direct drug delivery to the lungs allows one to obtain high concentration in the site of action with limited systemic d...Inhalation-administrated drugs remain an interesting possibility of addressing pulmonary diseases.Direct drug delivery to the lungs allows one to obtain high concentration in the site of action with limited systemic distribution,leading to a more effective therapy with reduced required doses and side effects.On the other hand,there are several difficulties in obtaining a formulation that would meet all the criteria related to physicochemical,aerodynamic and biological properties,which is the reason why only very few of the investigated systems can reach the clinical trial phase and proceed to everyday use as a result.Therefore,we focused on powders consisting of polysaccharides,lipids,proteins or natural and synthetic polymers in the form of microparticles that are delivered by inhalation to the lungs as drug carriers.We summarized the most common trends in research today to provide the best dry powders in the right fraction for inhalation that would be able to release the drug before being removed by natural mechanisms.This review article addresses the most common manufacturing methods with novel modifications,pros and cons of different materials,drug loading capacities with release profiles,and biological properties such as cytocompatibility,bactericidal or anticancer properties.展开更多
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 c...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.展开更多
Bone defects affect millions of people annually,making bone tissue of particular interest for developing treatments.Current strategies for healing suffer drawbacks.Regenerative engineering seeks to achieve effi cient ...Bone defects affect millions of people annually,making bone tissue of particular interest for developing treatments.Current strategies for healing suffer drawbacks.Regenerative engineering seeks to achieve effi cient bone regeneration by utilizing synthetic bone grafts to evade these drawbacks.One material that offers such benefits is a class of functional graphenic material,known as Phosphate Graphenes.While many of our studies have focused on Calcium Phosphate Graphene,magnesium is also osteogenic.Therefore,in this study,we utilized regenerative engineering techniques to incorporate Magnesium Phosphate Graphene(MgPG)into poly(lactic-co-glycolic acid)(PLGA)to fabricate composite microsphere-based matrices as a potential synthetic bone graft.Employing different amounts of MgPG within PLGA matrices,we studied the effect of MgPG on the morphological,structural,physical and biological characteristics.MgPG-containing matrices demonstratedgreat mechanical strength,hydrophilicity and degradability without compromising matrix morphology.Because MgPG is a graphene oxide derivative with magnesium and phosphate ions capable of supporting bone healing as inducerons,we next evaluated the cytocompatibility and osteogenic potential of these PLGA/MgPG composite matrices.MgPG matrices demonstrated high cell viability and proliferation of MC3T3-E1 cells as well as increased osteogenic activity reported by alkaline phosphatase activity,calcium deposition and gene expression of Col1a1,osteocalcin,bone sialoprotein and Sp7.Lastly,we investigated the gene expression profile of markers/targets of the canonicalβ-catenin dependent Wnt signaling pathway with and without inhibitor DKK1 to understand the potential underlying mechanism behind the enhanced osteogenic potential of MgPG.In response to MgPG,gene expression ofβ-catenin increased,while protein expression of BMP-2 and WISP-1 also increased.These results suggest the influence of MgPG on the Wnt pathway in relation to osteogenic differentiation.With further study,MgPG matrices may provide practical solutions to the problem of effectively regenerating critical-sized bone defects,which remains a challenge in orthopaedics.展开更多
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...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.展开更多
文摘Knee osteoarthritis （OA） is the most common form of arthritis worldwide. The incidence of this disease is rising and its treatment poses an economic burden. Two early targets of knee OA treatment include the predominant symptom of pain, and cartilage damage in the knee joint. Current treatments have been beneficial in treating the disease but none is as effective as total knee arthroplasty （TKA）. However, while TKA is an end-stage solution of the disease, it is an invasive and expensive procedure, Therefore, innovative regenerative engineering strategies should be established as these could defer or annul the need for a TKA. Several biomaterial and cell-based therapies are currently in development and have shown early promise in both preclinical and clinical studies. The use of advanced biomaterials and stem cells independently or in conjunction to treat knee OA could potentially reduce pain and regenerate fo- cal articular cartilage damage. In this review, we discuss the pathogenesis of pain and cartilage damage in knee OA and explore novel treatment options currently being studied, along with some of their limitations.
基金funding from the Raymond and Beverly Sackler Center for Biomedical,Biological,Physical and Engineering Sciencesthe funding from National Science Foundation Award(Nos.IIP-1311907,IIP-1355327 and EFRI-1332329)+2 种基金the Presidential Faculty Fellowship Award from President William Clintonthe Presidential Award for Excellence in Science,Mathematics,and Engineering Mentorship from President Barack Obamathe NIH Director’s Pioneer Award(No.1DP1AR068147-01)
文摘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.
文摘For over a decade,regenerative engineering has been defined as the convergence of advanced materials sciences,stem cell sciences,physics,developmental biology,and clinical translation for the regeneration of complex tissues.Recently,the field has made major strides because of new efforts made possible by the utilization of another growing field:artificial intelligence.However,there is currently no term to describe the use of artificial intelligence for regenerative engineering.Therefore,we hereby present a new term,“Regenerative Engineering AI”,which cohesively describes the interweaving of artificial intelligence into the framework of regenerative engineering rather than using it merely as a tool.As the first to define the term,regenerative engineering AI is the interdisciplinary integration of artificial intelligence and machine learning within the fundamental core of regenerative engineering to advance its principles and goals.It represents the subsequent synergetic relationship between the two that allow for multiplex solutions toward human limb regeneration in a manner different from individual fields and artificial intelligence alone.Establishing such a term creates a unique and unified space to consolidate the work of growing fields into one coherent discipline under a common goal and language,fostering interdisciplinary collaboration and promoting focused research and innovation.
基金This work was supported by the Department of Defense for their sponsorship through grant DAMD W81XWH11-10262 and funding from the Raymond and Beverly Sackler Center for Biomedical,Biological,Physical and Engineering Sciences.
文摘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.
基金Authors also acknowledge funding from the National Institute of Health-5R03NS058595the Connecticut Regenerative Medicine Research Fund-15-RMBUCHC-08+2 种基金the National Science Foundation(Award Numbers IIP-1311907,IIP-1355327EFRI-1332329)the Department of Defense(OR120140).
文摘A variety of engineered scaffolds have been created for tissue engineering using polymers,ceramics and their composites.Biomimicry has been adopted for majority of the three-dimensional(3D)scaffold design both in terms of physicochemical properties,as well as bioactivity for superior tissue regeneration.Scaffolds fabricated via salt leaching,particle sintering,hydrogels and lithography have been successful in promoting cell growth in vitro and tissue regeneration in vivo.Scaffold systems derived from decellularization of whole organs or tissues has been popular due to their assured biocompatibility and bioactivity.Traditional scaffold fabrication techniques often failed to create intricate structures with greater resolution,not reproducible and involved multiple steps.The 3D printing technology overcome several limitations of the traditional techniques and made it easier to adopt several thermoplastics and hydrogels to create micro-nanostructured scaffolds and devices for tissue engineering and drug delivery.This review highlights scaffold fabrication methodologies with a focus on optimizing scaffold performance through the matrix pores,bioactivity and degradation rate to enable tissue regeneration.Review highlights few examples of bioactive scaffold mediated nerve,muscle,tendon/ligament and bone regeneration.Regardless of the efforts required for optimization,a shift in 3D scaffold uses from the laboratory into everyday life is expected in the near future as some of the methods discussed in this review become more streamlined.
基金funded by DHHS/NIH/NIAMS entitled,Regenerative Engineering of Complex Musculoskeletal Tissue and Joints(Grant No.:DP1AR068147 and NSF/EFRI Grant No:1332329)funded by Imam Abdulrahman Bin Faisal University,Dammam 34212,Saudi Arabia.
文摘Inhalation-administrated drugs remain an interesting possibility of addressing pulmonary diseases.Direct drug delivery to the lungs allows one to obtain high concentration in the site of action with limited systemic distribution,leading to a more effective therapy with reduced required doses and side effects.On the other hand,there are several difficulties in obtaining a formulation that would meet all the criteria related to physicochemical,aerodynamic and biological properties,which is the reason why only very few of the investigated systems can reach the clinical trial phase and proceed to everyday use as a result.Therefore,we focused on powders consisting of polysaccharides,lipids,proteins or natural and synthetic polymers in the form of microparticles that are delivered by inhalation to the lungs as drug carriers.We summarized the most common trends in research today to provide the best dry powders in the right fraction for inhalation that would be able to release the drug before being removed by natural mechanisms.This review article addresses the most common manufacturing methods with novel modifications,pros and cons of different materials,drug loading capacities with release profiles,and biological properties such as cytocompatibility,bactericidal or anticancer properties.
基金This work was supported by the NIH Director’s Pioneer Award,1DP1AR068147,R21-AR062771,R01-AR063698funding from Raymond and Beverly Sackler Center for Biomedical,Biological,Physical and Engineering Sciences.C.T.L.was the recipient of the Presidential Faculty Fellowship Award from President William Clinton and the Presidential Award for Excellence in Science,Mathematics,and Engineering Mentorship and the National Medial of Technology and Innovation from President Barack Obama.
文摘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.
基金supported by the National Institutes of Health T32(AR079114)National Science Foundation Emerging Frontiers in Research and Innovation-BioFlex(1332329)grants.Additionally,figures were created with BioRender.com.
文摘Bone defects affect millions of people annually,making bone tissue of particular interest for developing treatments.Current strategies for healing suffer drawbacks.Regenerative engineering seeks to achieve effi cient bone regeneration by utilizing synthetic bone grafts to evade these drawbacks.One material that offers such benefits is a class of functional graphenic material,known as Phosphate Graphenes.While many of our studies have focused on Calcium Phosphate Graphene,magnesium is also osteogenic.Therefore,in this study,we utilized regenerative engineering techniques to incorporate Magnesium Phosphate Graphene(MgPG)into poly(lactic-co-glycolic acid)(PLGA)to fabricate composite microsphere-based matrices as a potential synthetic bone graft.Employing different amounts of MgPG within PLGA matrices,we studied the effect of MgPG on the morphological,structural,physical and biological characteristics.MgPG-containing matrices demonstratedgreat mechanical strength,hydrophilicity and degradability without compromising matrix morphology.Because MgPG is a graphene oxide derivative with magnesium and phosphate ions capable of supporting bone healing as inducerons,we next evaluated the cytocompatibility and osteogenic potential of these PLGA/MgPG composite matrices.MgPG matrices demonstrated high cell viability and proliferation of MC3T3-E1 cells as well as increased osteogenic activity reported by alkaline phosphatase activity,calcium deposition and gene expression of Col1a1,osteocalcin,bone sialoprotein and Sp7.Lastly,we investigated the gene expression profile of markers/targets of the canonicalβ-catenin dependent Wnt signaling pathway with and without inhibitor DKK1 to understand the potential underlying mechanism behind the enhanced osteogenic potential of MgPG.In response to MgPG,gene expression ofβ-catenin increased,while protein expression of BMP-2 and WISP-1 also increased.These results suggest the influence of MgPG on the Wnt pathway in relation to osteogenic differentiation.With further study,MgPG matrices may provide practical solutions to the problem of effectively regenerating critical-sized bone defects,which remains a challenge in orthopaedics.
文摘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.
