A series of multiblock copolymers of PLLA\|PEG(PLE) with high molecular weight were synthesized by coupling PLLA\|PEG\|PLLA triblock copolymers with succinic anhydride in the presence of ( N,N\| dimethylamino) pyridin...A series of multiblock copolymers of PLLA\|PEG(PLE) with high molecular weight were synthesized by coupling PLLA\|PEG\|PLLA triblock copolymers with succinic anhydride in the presence of ( N,N\| dimethylamino) pyridine(DMAP) and dicyclohexylcarbodimide (DCC).The results of the viscometry measurement,GPC and 1H\|NMR,elucidated that multiblock PLE copolymers with high content of short PEG segments( M n=2000) had been successfully obtained.The crystallinity of the copolymers was investigated by X\|ray diffraction.Mechanical testing showed that multiblock copolymers had relatively high tensile strength and large elongation.In a word,the measurements showed that the multiblock PLE copolymers had high content of short PEG segments( M n=2000),high molecular weight( M w～100,000),excellent hydrophilicity and mechanical properties.The results of cells cultured on the multiblock PLE copolymer indicated that it might be suitable to be utilized as cell scaffold for tissue engineering.展开更多
Spinal cord injury usually leads to permanent disability, which could cause a huge financial problem to the patient. Up to now there is no effective method to treat this disease. The key of the treatment is to enable ...Spinal cord injury usually leads to permanent disability, which could cause a huge financial problem to the patient. Up to now there is no effective method to treat this disease. The key of the treatment is to enable the damage zone axonal regeneration and luckily it could go through the damage zone; last a connection can be established with the target neurons. This study attempts to combine stem cell, material science and genetic modification technology together, by preparing two genes modified adipose-derived stem cells and inducing them into neuron direction; then by compositing them on the silk fibroin/chitosan scaffold and implanting them into the spinal cord injury model, seed cells can have features of neuron cells. At the same time, it could stably express the brain-derived neurotrophic factor and neurotrophin-3, both of which could produce synergistic effects, which have a positive effect on the recovery of spinal cord. The spinal cord scaffold bridges the broken end of the spinal cord and isolates with the surrounding environment, which could avoid a scar effect on the nerve regeneration and provide three-dimensional space for the seed cell growth, and at last we hope to provide a new treatment for spinal cord injury with the tissue engineering technique.展开更多
A tooth is a complex biological organ and consists of multiple tissues including the enamel, dentin, cementum and pulp. Tooth loss is the most common organ failure. Can a tooth be regenerated？ Can adult stem cells be...A tooth is a complex biological organ and consists of multiple tissues including the enamel, dentin, cementum and pulp. Tooth loss is the most common organ failure. Can a tooth be regenerated？ Can adult stem cells be orchestrated to regenerate tooth structures such as the enamel, dentin, cementum and dental pulp, or even an entire tooth？ If not, what are the therapeutically viable sources of stem cells for tooth regeneration？ Do stem cells necessarily need to be taken out of the body, and manipulated ex vivo before they are transplanted for tooth regeneration？ How can regenerated teeth be economically competitive with dental implants？ Would it be possible to make regenerated teeth affordable by a large segment of the population worldwide？ This review article explores existing and visionary approaches that address some of the above-mentioned questions. Tooth regeneration represents a revolution in stomatology as a shift in the paradigm from repair to regeneration： repair is by metal or artificial materials whereas regeneration is by biological restoration. Tooth regeneration is an extension of the concepts in the broad field of regenerative medicine to restore a tissue defect to its original form and function by biological substitutes.展开更多
Many studies have shown that bio-scaffolds have important value for promoting axonal regeneration of injured spinal cord.Indeed,cell transplantation and bio-scaffold implantation are considered to be effective methods...Many studies have shown that bio-scaffolds have important value for promoting axonal regeneration of injured spinal cord.Indeed,cell transplantation and bio-scaffold implantation are considered to be effective methods for neural regeneration.This study was designed to fabricate a type of three-dimensional collagen/silk fibroin scaffold (3D-CF) with cavities that simulate the anatomy of normal spinal cord.This scaffold allows cell growth in vitro and in vivo.To observe the effects of combined transplantation of neural stem cells (NSCs) and 3D-CF on the repair of spinal cord injury.Forty Sprague-Dawley rats were divided into four groups: sham (only laminectomy was performed),spinal cord injury (transection injury of T10 spinal cord without any transplantation),3D-CF (3D scaffold was transplanted into the local injured cavity),and 3D-CF + NSCs (3D scaffold co-cultured with NSCs was transplanted into the local injured cavity.Neuroelectrophysiology,imaging,hematoxylin-eosin staining,argentaffin staining,immunofluorescence staining,and western blot assay were performed.Apart from the sham group,neurological scores were significantly higher in the 3D-CF + NSCs group compared with other groups.Moreover,latency of the 3D-CF + NSCs group was significantly reduced,while the amplitude was significantly increased in motor evoked potential tests.The results of magnetic resonance imaging and diffusion tensor imaging showed that both spinal cord continuity and the filling of injury cavity were the best in the 3D-CF + NSCs group.Moreover,regenerative axons were abundant and glial scarring was reduced in the 3D-CF + NSCs group compared with other groups.These results confirm that implantation of 3D-CF combined with NSCs can promote the repair of injured spinal cord.This study was approved by the Institutional Animal Care and Use Committee of People’s Armed Police Force Medical Center in 2017 (approval No.2017-0007.2).展开更多
An appropriate cell microenvironment is key to tissue engineering and regenerative medicine.Revealing the factors that influence the cell microenvironment is a fundamental research topic in the fields of cell biology,...An appropriate cell microenvironment is key to tissue engineering and regenerative medicine.Revealing the factors that influence the cell microenvironment is a fundamental research topic in the fields of cell biology,biomaterials,tissue engineering,and regenerative medicine.The cell microenvironment consists of not only its surrounding cells and soluble factors,but also its extracellular matrix(ECM)or nearby external biomaterials in tissue engineering and regeneration.This review focuses on six aspects of bioma-terial-related cell microenvironments:①chemical composition of materials,②material dimensions and architecture,③material-controlled cell geometry,④effects of material charges on cells,⑤matrix stiff-ness and biomechanical microenvironment,and⑥surface modification of materials.The present chal-lenges in tissue engineering are also mentioned,and eight perspectives are predicted.展开更多
Hydrophilic bone morphogenetic protein 2(BMP2)is easily degraded and difficult to load onto hydrophobic carrier materials,which limits the application of polyester materials in bone tissue engineering.Based on soybean...Hydrophilic bone morphogenetic protein 2(BMP2)is easily degraded and difficult to load onto hydrophobic carrier materials,which limits the application of polyester materials in bone tissue engineering.Based on soybean-lecithin as an adjuvant biosurfactant,we designed a novel cell-free-scaffold of polymer of poly(ε-caprolactone)and poly(lactide-co-glycolide)-co-polyetherimide with abundant entrapped and continuously released BMP2 for in vivo stem cell-capture and in situ osteogenic induction,avoiding the use of exogenous cells.The optimized bioactive osteo-polyester scaffold(BOPSC),i.e.SBMP-10SC,had a high BMP2 entrapment efficiency of 95.35%.Due to its higher porosity of 83.42%,higher water uptake ratio of 850%,and sustained BMP2 release with polymer degradation,BOPSCs were demonstrated to support excellent in vitro capture,proliferation,migration and osteogenic differentiation of mouse adipose derived mesenchymal stem cells(mADSCs),and performed much better than traditional BMP-10SCs with unmodified BMP2 and single polyester scaffolds(10SCs).Furthermore,in vivo capture and migration of stem cells and differentiation into osteoblasts was observed in mice implanted with BOPSCs without exogenous cells,which enabled allogeneic bone formation with a high bone mineral density and ratios of new bone volume to existing tissue volume after 6 months.The BOPSC is an advanced 3D cell-free platform with sustained BMP2 supply for in situ stem cell capture and osteoinduction in bone tissue engineering with potential for clinical translation.展开更多
Because the inhibition of Nogo proteins can promote neurite growth and nerve cell differentiation, a cell-scaffold complex seeded with Nogo receptor （NgR）-silenced neural stem cells and Schwann cells may be able to ...Because the inhibition of Nogo proteins can promote neurite growth and nerve cell differentiation, a cell-scaffold complex seeded with Nogo receptor （NgR）-silenced neural stem cells and Schwann cells may be able to improve the microenvironment for spinal cord injury repair. Previous studies have found that mild hypothermia helps to attenuate secondary damage in the spinal cord and exerts a neuroprotective effect. Here, we constructed a cell-scaffold complex consisting of a poly（D,L-lactide-co-glycolic acid） （PLGA） scaffold seeded with NgR-silenced neural stem cells and Schwann cells, and determined the effects of mild hypothermia combined with the cell-scaffold complexes on the spinal cord hemi-transection injury in the T9 segment in rats. Compared with the PLGA group and the NgR-silencing cells ＋ PLGA group, hindlimb motor function and nerve electrophysiological function were dearly improved, pathological changes in the injured spinal cord were attenuated, and the number of surviving cells and nerve fibers were increased in the group treated with the NgR-silenced cell scaffold ＋ mild hypothermia at 34℃ for 6 hours. Furthermore, fewer pathological changes to the injured spinal cord and more surviving cells and nerve fibers were found after mild hypothermia therapy than in injuries not treated with mild hypothermia. These experimental results indicate that mild hypothermia combined with NgR gene-silenced cells in a PLGA scaffold may be an effective therapy for treating spinal cord injury.展开更多
Bone tissue engineering (BTE) is a rapidly developing strategy for repairing critical-sized bone defects to address the unmet need for bone augmentation and skeletal repair. Effective therapies for bone regeneration p...Bone tissue engineering (BTE) is a rapidly developing strategy for repairing critical-sized bone defects to address the unmet need for bone augmentation and skeletal repair. Effective therapies for bone regeneration primarily require the coordinated combination of innovative scaffolds, seed cells, and biological factors. However, current techniques in bone tissue engineering have not yet reached valid translation into clinical applications because of several limitations, such as weaker osteogenic differentiation, inadequate vascularization of scaffolds, and inefficient growth factor delivery. Therefore, further standardized protocols and innovative measures are required to overcome these shortcomings and facilitate the clinical application of these techniques to enhance bone regeneration. Given the deficiency of comprehensive studies in the development in BTE, our review systematically introduces the new types of biomimetic and bifunctional scaffolds. We describe the cell sources, biology of seed cells, growth factors, vascular development, and the interactions of relevant molecules. Furthermore, we discuss the challenges and perspectives that may propel the direction of future clinical delivery in bone regeneration.展开更多
Collagen scaffolds possess a three-dimensional porous structure that provides sufficient space for cell growth and proliferation,the passage of nutrients and oxygen,and the discharge of metabolites.In this study,a por...Collagen scaffolds possess a three-dimensional porous structure that provides sufficient space for cell growth and proliferation,the passage of nutrients and oxygen,and the discharge of metabolites.In this study,a porous collagen scaffold with axially-aligned luminal conduits was prepared.In vitro biocompatibility analysis of the collagen scaffold revealed that it enhances the activity of neural stem cells and promotes cell extension,without affecting cell differentiation.The collagen scaffold loaded with neural stem cells improved the hindlimb motor function in the rat model of T8 complete transection and promoted nerve regeneration.The collagen scaffold was completely degraded in vivo within 5 weeks of implantation,exhibiting good biodegradability.Rectal temperature,C-reactive protein expression and CD68 staining demonstrated that rats with spinal cord injury that underwent implantation of the collagen scaffold had no notable inflammatory reaction.These findings suggest that this novel collagen scaffold is a good carrier for neural stem cell transplantation,thereby enhancing spinal cord repair following injury.This study was approved by the Animal Ethics Committee of Nanjing Drum Tower Hospital(the Affiliated Hospital of Nanjing University Medical School),China(approval No.2019AE02005)on June 15,2019.展开更多
文摘A series of multiblock copolymers of PLLA\|PEG(PLE) with high molecular weight were synthesized by coupling PLLA\|PEG\|PLLA triblock copolymers with succinic anhydride in the presence of ( N,N\| dimethylamino) pyridine(DMAP) and dicyclohexylcarbodimide (DCC).The results of the viscometry measurement,GPC and 1H\|NMR,elucidated that multiblock PLE copolymers with high content of short PEG segments( M n=2000) had been successfully obtained.The crystallinity of the copolymers was investigated by X\|ray diffraction.Mechanical testing showed that multiblock copolymers had relatively high tensile strength and large elongation.In a word,the measurements showed that the multiblock PLE copolymers had high content of short PEG segments( M n=2000),high molecular weight( M w～100,000),excellent hydrophilicity and mechanical properties.The results of cells cultured on the multiblock PLE copolymer indicated that it might be suitable to be utilized as cell scaffold for tissue engineering.
文摘Spinal cord injury usually leads to permanent disability, which could cause a huge financial problem to the patient. Up to now there is no effective method to treat this disease. The key of the treatment is to enable the damage zone axonal regeneration and luckily it could go through the damage zone; last a connection can be established with the target neurons. This study attempts to combine stem cell, material science and genetic modification technology together, by preparing two genes modified adipose-derived stem cells and inducing them into neuron direction; then by compositing them on the silk fibroin/chitosan scaffold and implanting them into the spinal cord injury model, seed cells can have features of neuron cells. At the same time, it could stably express the brain-derived neurotrophic factor and neurotrophin-3, both of which could produce synergistic effects, which have a positive effect on the recovery of spinal cord. The spinal cord scaffold bridges the broken end of the spinal cord and isolates with the surrounding environment, which could avoid a scar effect on the nerve regeneration and provide three-dimensional space for the seed cell growth, and at last we hope to provide a new treatment for spinal cord injury with the tissue engineering technique.
基金supported by RC2DE020767 from the National Institute of Dental and Craniofacial Research (NIDCR), the National Institutes of Health (NIH)
文摘A tooth is a complex biological organ and consists of multiple tissues including the enamel, dentin, cementum and pulp. Tooth loss is the most common organ failure. Can a tooth be regenerated？ Can adult stem cells be orchestrated to regenerate tooth structures such as the enamel, dentin, cementum and dental pulp, or even an entire tooth？ If not, what are the therapeutically viable sources of stem cells for tooth regeneration？ Do stem cells necessarily need to be taken out of the body, and manipulated ex vivo before they are transplanted for tooth regeneration？ How can regenerated teeth be economically competitive with dental implants？ Would it be possible to make regenerated teeth affordable by a large segment of the population worldwide？ This review article explores existing and visionary approaches that address some of the above-mentioned questions. Tooth regeneration represents a revolution in stomatology as a shift in the paradigm from repair to regeneration： repair is by metal or artificial materials whereas regeneration is by biological restoration. Tooth regeneration is an extension of the concepts in the broad field of regenerative medicine to restore a tissue defect to its original form and function by biological substitutes.
基金supported by the National Natural Science Foundation of China,No.11672332(to XYC)the National Key Research and Development Plan of China,No.2016YFC1101500(to SZ)
文摘Many studies have shown that bio-scaffolds have important value for promoting axonal regeneration of injured spinal cord.Indeed,cell transplantation and bio-scaffold implantation are considered to be effective methods for neural regeneration.This study was designed to fabricate a type of three-dimensional collagen/silk fibroin scaffold (3D-CF) with cavities that simulate the anatomy of normal spinal cord.This scaffold allows cell growth in vitro and in vivo.To observe the effects of combined transplantation of neural stem cells (NSCs) and 3D-CF on the repair of spinal cord injury.Forty Sprague-Dawley rats were divided into four groups: sham (only laminectomy was performed),spinal cord injury (transection injury of T10 spinal cord without any transplantation),3D-CF (3D scaffold was transplanted into the local injured cavity),and 3D-CF + NSCs (3D scaffold co-cultured with NSCs was transplanted into the local injured cavity.Neuroelectrophysiology,imaging,hematoxylin-eosin staining,argentaffin staining,immunofluorescence staining,and western blot assay were performed.Apart from the sham group,neurological scores were significantly higher in the 3D-CF + NSCs group compared with other groups.Moreover,latency of the 3D-CF + NSCs group was significantly reduced,while the amplitude was significantly increased in motor evoked potential tests.The results of magnetic resonance imaging and diffusion tensor imaging showed that both spinal cord continuity and the filling of injury cavity were the best in the 3D-CF + NSCs group.Moreover,regenerative axons were abundant and glial scarring was reduced in the 3D-CF + NSCs group compared with other groups.These results confirm that implantation of 3D-CF combined with NSCs can promote the repair of injured spinal cord.This study was approved by the Institutional Animal Care and Use Committee of People’s Armed Police Force Medical Center in 2017 (approval No.2017-0007.2).
基金the financial support from the National Natural Science Foundation of China (21961160721 and 52130302)the National Key Research and Development Program of China(2016YFC1100300)
文摘An appropriate cell microenvironment is key to tissue engineering and regenerative medicine.Revealing the factors that influence the cell microenvironment is a fundamental research topic in the fields of cell biology,biomaterials,tissue engineering,and regenerative medicine.The cell microenvironment consists of not only its surrounding cells and soluble factors,but also its extracellular matrix(ECM)or nearby external biomaterials in tissue engineering and regeneration.This review focuses on six aspects of bioma-terial-related cell microenvironments:①chemical composition of materials,②material dimensions and architecture,③material-controlled cell geometry,④effects of material charges on cells,⑤matrix stiff-ness and biomechanical microenvironment,and⑥surface modification of materials.The present chal-lenges in tissue engineering are also mentioned,and eight perspectives are predicted.
基金Grants from National Natural Science Foundation of China(Grant Nos.31900950,31670991 and 52072210)National Key Research and Development Project of China(Grant No.2018YFA0900100).
文摘Hydrophilic bone morphogenetic protein 2(BMP2)is easily degraded and difficult to load onto hydrophobic carrier materials,which limits the application of polyester materials in bone tissue engineering.Based on soybean-lecithin as an adjuvant biosurfactant,we designed a novel cell-free-scaffold of polymer of poly(ε-caprolactone)and poly(lactide-co-glycolide)-co-polyetherimide with abundant entrapped and continuously released BMP2 for in vivo stem cell-capture and in situ osteogenic induction,avoiding the use of exogenous cells.The optimized bioactive osteo-polyester scaffold(BOPSC),i.e.SBMP-10SC,had a high BMP2 entrapment efficiency of 95.35%.Due to its higher porosity of 83.42%,higher water uptake ratio of 850%,and sustained BMP2 release with polymer degradation,BOPSCs were demonstrated to support excellent in vitro capture,proliferation,migration and osteogenic differentiation of mouse adipose derived mesenchymal stem cells(mADSCs),and performed much better than traditional BMP-10SCs with unmodified BMP2 and single polyester scaffolds(10SCs).Furthermore,in vivo capture and migration of stem cells and differentiation into osteoblasts was observed in mice implanted with BOPSCs without exogenous cells,which enabled allogeneic bone formation with a high bone mineral density and ratios of new bone volume to existing tissue volume after 6 months.The BOPSC is an advanced 3D cell-free platform with sustained BMP2 supply for in situ stem cell capture and osteoinduction in bone tissue engineering with potential for clinical translation.
基金supported by a grant from the Application Basis and Front Technology Projects of Tianjin(Science and Technology Foundation of Tianjin),No.12JCYBJC18000
文摘Because the inhibition of Nogo proteins can promote neurite growth and nerve cell differentiation, a cell-scaffold complex seeded with Nogo receptor （NgR）-silenced neural stem cells and Schwann cells may be able to improve the microenvironment for spinal cord injury repair. Previous studies have found that mild hypothermia helps to attenuate secondary damage in the spinal cord and exerts a neuroprotective effect. Here, we constructed a cell-scaffold complex consisting of a poly（D,L-lactide-co-glycolic acid） （PLGA） scaffold seeded with NgR-silenced neural stem cells and Schwann cells, and determined the effects of mild hypothermia combined with the cell-scaffold complexes on the spinal cord hemi-transection injury in the T9 segment in rats. Compared with the PLGA group and the NgR-silencing cells ＋ PLGA group, hindlimb motor function and nerve electrophysiological function were dearly improved, pathological changes in the injured spinal cord were attenuated, and the number of surviving cells and nerve fibers were increased in the group treated with the NgR-silenced cell scaffold ＋ mild hypothermia at 34℃ for 6 hours. Furthermore, fewer pathological changes to the injured spinal cord and more surviving cells and nerve fibers were found after mild hypothermia therapy than in injuries not treated with mild hypothermia. These experimental results indicate that mild hypothermia combined with NgR gene-silenced cells in a PLGA scaffold may be an effective therapy for treating spinal cord injury.
基金the National Natural Science Foundation of China (Nos.51673029,81330043,and 81071499)Beijing Talent Fund (No.2016000021223ZK34)another fund (No.PXM2018_026275_000001).
文摘Bone tissue engineering (BTE) is a rapidly developing strategy for repairing critical-sized bone defects to address the unmet need for bone augmentation and skeletal repair. Effective therapies for bone regeneration primarily require the coordinated combination of innovative scaffolds, seed cells, and biological factors. However, current techniques in bone tissue engineering have not yet reached valid translation into clinical applications because of several limitations, such as weaker osteogenic differentiation, inadequate vascularization of scaffolds, and inefficient growth factor delivery. Therefore, further standardized protocols and innovative measures are required to overcome these shortcomings and facilitate the clinical application of these techniques to enhance bone regeneration. Given the deficiency of comprehensive studies in the development in BTE, our review systematically introduces the new types of biomimetic and bifunctional scaffolds. We describe the cell sources, biology of seed cells, growth factors, vascular development, and the interactions of relevant molecules. Furthermore, we discuss the challenges and perspectives that may propel the direction of future clinical delivery in bone regeneration.
基金supported by the National Key Research and Development Program of China,No.2017YFA0104304(to NG)the National Natural Science Foundation of China,Nos.81571213(to BW),81800583(to YYX),81601539(to DM)+2 种基金the Nanjing Medical Science and Technique Development Foundation of China,Nos.QRX17006(to BW),QRX17057(to DM)the Key Project Supported by Medical Science and Technology Development Foundation,Nanjing Department of Health and the Nanjing Medical Science and Innovation Platform of China,No.ZDX16005(to BW)Chongqing Yuzhong District Science and Technology Commission Project of China,No.20140112(to YYC).
文摘Collagen scaffolds possess a three-dimensional porous structure that provides sufficient space for cell growth and proliferation,the passage of nutrients and oxygen,and the discharge of metabolites.In this study,a porous collagen scaffold with axially-aligned luminal conduits was prepared.In vitro biocompatibility analysis of the collagen scaffold revealed that it enhances the activity of neural stem cells and promotes cell extension,without affecting cell differentiation.The collagen scaffold loaded with neural stem cells improved the hindlimb motor function in the rat model of T8 complete transection and promoted nerve regeneration.The collagen scaffold was completely degraded in vivo within 5 weeks of implantation,exhibiting good biodegradability.Rectal temperature,C-reactive protein expression and CD68 staining demonstrated that rats with spinal cord injury that underwent implantation of the collagen scaffold had no notable inflammatory reaction.These findings suggest that this novel collagen scaffold is a good carrier for neural stem cell transplantation,thereby enhancing spinal cord repair following injury.This study was approved by the Animal Ethics Committee of Nanjing Drum Tower Hospital(the Affiliated Hospital of Nanjing University Medical School),China(approval No.2019AE02005)on June 15,2019.
