The Experts below are selected from a list of 17667 Experts worldwide ranked by ideXlab platform

Bing Chen - One of the best experts on this subject based on the ideXlab platform.

  • a functional Scaffold to promote the migration and neuronal differentiation of neural stem progenitor cells for spinal cord injury repair
    Biomaterials, 2020
    Co-Authors: Bai Xu, Zhifeng Xiao, Bing Chen, Bin Yang, Qi Zhang, Yannan Zhao
    Abstract:

    Abstract After spinal cord injury (SCI), endogenous neural/progenitor stem cells (NSPCs) were activated in neural tissue adjacent to the injured segment, but few cells migrated to the injury epicenter and differentiated into neurons. N-cadherin regulates mechanical adhesion between NSPCs, and also drives NSPCs migration and promotes NSPCs differentiation. In this study, linearly ordered Collagen Scaffold (LOCS) was modified with N-cadherin through a two-step cross-linking between thiol and amino group. The results indicated that N-cadherin modification improved the adhesion of NSPCs on Collagen Scaffold and increased the differentiation into neurons. When LOCS-Ncad was transplanted into complete transected rat spinal cords, more NSPCs migrated to the lesion center and more newborn neurons appeared within the injury site. Furthermore, rats transplanted with LOCS-Ncad showed significantly improved locomotor recovery compared with the rats without implants. Collectively, our results suggest that LOCS-Ncad may be a promising treatment option to facilitate SCI repair by recruiting endogenous NSPCs to the lesion center and promoting neuronal differentiation.

  • controlled release of Collagen binding sdf 1α from the Collagen Scaffold promoted tendon regeneration in a rat achilles tendon defect model
    Biomaterials, 2018
    Co-Authors: Jie Sun, Bing Chen, Qin Shi, Xianglin Hou, Chenchen Mou, Wen Zhang, Yan Zhuang, Jiajia Shi, Yanyan Chen, Jianwu Dai
    Abstract:

    Abstract It had been demonstrated that stromal cell-derived factor-1α (SDF-1α) could promote in situ tendon regeneration by recruiting endogenous cells. However, native SDF-1α diffuses too fast in vivo , reducing its local concentration and efficacy. In this study, we prepared a recombinant SDF-1α containing a Collagen-binding domain (CBD-SDF-1α) and developed a functional Collagen Scaffold by tethering CBD-SDF-1α on the Collagen Scaffold for in situ tendon regeneration. CBD-SDF-1α could induce the migration of mesenchymal stem cells, dermal fibroblasts and Achilles tendon fibroblasts in vitro , and achieve controlled release from the Collagen Scaffold. In a rat Achilles tendon defect model, the functional Scaffold could increase the recruitment of CXCR4 positive fibroblast-like cells and the deposition of Tenascin-C at 7 days after implantation. After 4 and 12 weeks, the functional Collagen Scaffold could promote the expression of type I Collagen, increase the diameters of Collagen fibrils and improve the mechanical properties of regenerated tendons. Hence, the functional Scaffold increased the efficacy of tendon regeneration by controlling release of SDF-1α, enhancing the recruitment of fibroblast-like cells and providing instructive microenvironment and mechanical support for tendon regeneration. Therefore, CBD-SDF-1α-modified Collagen Scaffold could serve as a practical application for tendon regeneration.

  • human placenta derived mesenchymal stem cells loaded on linear ordered Collagen Scaffold improves functional recovery after completely transected spinal cord injury in canine
    Science China-life Sciences, 2018
    Co-Authors: Sufang Han, Zhifeng Xiao, Bing Chen, Jin Han, Bin Wang, Caixia Fan, Huan Zhao, Zhixue Qiu, Xin Mei, Huilin Yang
    Abstract:

    Traumatic spinal cord injury (SCI) is a major challenge in the clinic. In this study, we sought to examine the synergistic effects of linear ordered Collagen Scaffold (LOCS) and human placenta-derived mesenchymal stem cells (hPMSCs) when transplanted into completely transected beagle dogs. After 36 weeks observation, we found that LOCS+hPMSCs implants promoted better hindlimb locomotor recovery than was observed in the non-treatment (control) group and LOCS group. Histological analysis showed that the regenerated tissue after treatment was well integrated with the host tissue, and dramatically reduced the volume of cystic and chondroitin sulfate proteoglycans (CSPGs) expression. Furthermore, the LOCS+hPMSCs group also showed more neuron-specific βIII-tubulin (Tuj-1)- and NeuN-positive neurons in the lesion area, as well as axonal regeneration, remyelination and synapse formation in the lesion site. Additionally, dogs in the LOCS+hPMSCs group experienced enhanced sprouting of both ascending (CGRP-positive) sensory fibers and descending (5-HT- and TH-positive) motor fibers at the lesion area. All these data together suggested that the combined treatment had beneficial effects on neuronal regeneration and functional improvement in a canine complete transection model. Therefore, LOCS+hPMSCs implantation holds a great promise for bridging the nerve defect and may be clinically useful in the near future.

  • the neuronal differentiation microenvironment is essential for spinal cord injury repair
    Organogenesis, 2017
    Co-Authors: Yannan Zhao, Zhifeng Xiao, Bing Chen
    Abstract:

    Spinal cord injury (SCI) often leads to substantial disability due to loss of motor function and sensation below the lesion. Neural stem cells (NSCs) are a promising strategy for SCI repair. However, NSCs rarely differentiate into neurons; they mostly differentiate into astrocytes because of the adverse microenvironment present after SCI. We have shown that myelin-associated inhibitors (MAIs) inhibited neuronal differentiation of NSCs. Given that MAIs activate epidermal growth factor receptor (EGFR) signaling, we used a Collagen Scaffold-tethered anti-EGFR antibody to attenuate the inhibitory effects of MAIs and create a neuronal differentiation microenvironment for SCI repair. The Collagen Scaffold modified with anti-EGFR antibody prevented the inhibition of NSC neuronal differentiation by myelin. After transplantation into completely transected SCI animals, the Scaffold-linked antibodies induced production of nascent neurons from endogenous and transplanted NSCs, which rebuilt the neuronal relay by forming connections with each other or host neurons to transmit electrophysiological signals and promote functional recovery. Thus, a Scaffold-based strategy for rebuilding the neuronal differentiation microenvironment could be useful for SCI repair.

  • Functionalized Collagen Scaffold implantation and cAMP administration collectively facilitate spinal cord regeneration.
    Acta Biomaterialia, 2016
    Co-Authors: Jin Han, Yannan Zhao, Wenyong Ding, Jianshu Wei, Sufang Han, Xianping Shang, Bin Wang, Bing Chen
    Abstract:

    Abstract Previous studies have demonstrated that several mechanisms, including numerous inhibitory molecules, weak neurotrophic stimulation and deficient intrinsic regenerative responses, collectively contribute to the failure of mature spinal cord axon regeneration. Thus, combinatorial therapies targeting multiple mechanisms have attracted much attention. In the present study, a porous Collagen Scaffold was used to support neuronal attachment and bridge axonal regeneration. The Scaffold was specifically functionalized using neutralizing proteins (CBD-EphA4LBD, CBD-PlexinB1LBD and NEP1-40) and Collagen-binding neurotrophic factors (CBD-BDNF and CBD-NT3) to simultaneously antagonize myelin inhibitory molecules (ephrinB3, Sema4D and Nogo) and exert neurotrophic protection and stimulation. Cerebellar granular neurons cultured on the functionalized Collagen Scaffold promoted neurite outgrowth in the presence of myelin. Furthermore, a full combinatorial treatment comprising functionalized Scaffold implantation and cAMP administration was developed to evaluate the synergistic repair ability in a rat T10 complete removal spinal cord injury model. The results showed that full combinatorial therapy exhibited the greatest advantage in reducing the volume of cavitation, facilitating axonal regeneration, and promoting neuronal generation. The newborn neurons generated in the lesion area could form the neuronal relay and enhance the locomotion recovery after severe spinal cord injury. Statement of Significance A porous Collagen Scaffold was specifically functionalized with neutralizing proteins and neurotrophic factors to antagonize the myelin inhibitory molecules and exert neurotrophic protection and stimulation for spinal cord regeneration. Cerebellar granular neurons seeded on the functionalized Collagen Scaffold showed enhanced neurite outgrowth ability in vitro. The functionalized Scaffold implantation combined with cAMP administration exhibited synergistic repair ability for rat T10 complete spinal cord transection injury.

Yannan Zhao - One of the best experts on this subject based on the ideXlab platform.

  • a functional Scaffold to promote the migration and neuronal differentiation of neural stem progenitor cells for spinal cord injury repair
    Biomaterials, 2020
    Co-Authors: Bai Xu, Zhifeng Xiao, Bing Chen, Bin Yang, Qi Zhang, Yannan Zhao
    Abstract:

    Abstract After spinal cord injury (SCI), endogenous neural/progenitor stem cells (NSPCs) were activated in neural tissue adjacent to the injured segment, but few cells migrated to the injury epicenter and differentiated into neurons. N-cadherin regulates mechanical adhesion between NSPCs, and also drives NSPCs migration and promotes NSPCs differentiation. In this study, linearly ordered Collagen Scaffold (LOCS) was modified with N-cadherin through a two-step cross-linking between thiol and amino group. The results indicated that N-cadherin modification improved the adhesion of NSPCs on Collagen Scaffold and increased the differentiation into neurons. When LOCS-Ncad was transplanted into complete transected rat spinal cords, more NSPCs migrated to the lesion center and more newborn neurons appeared within the injury site. Furthermore, rats transplanted with LOCS-Ncad showed significantly improved locomotor recovery compared with the rats without implants. Collectively, our results suggest that LOCS-Ncad may be a promising treatment option to facilitate SCI repair by recruiting endogenous NSPCs to the lesion center and promoting neuronal differentiation.

  • Collagen Scaffold combined with human umbilical cord derived mesenchymal stem cells promote functional recovery after scar resection in rats with chronic spinal cord injury
    Journal of Tissue Engineering and Regenerative Medicine, 2018
    Co-Authors: Nuo Wang, Yannan Zhao, Zhifeng Xiao, Bin Wang, Jianwu Dai
    Abstract:

    Effective therapeutic strategies for treating chronic spinal cord injury (SCI) are currently unavailable. Scar tissue in the lesion area is a main inhibitory factor for axonal regeneration and repair of chronic SCI. In this study, scar tissue was surgically resected from adult rats with 12 week chronic SCI and then Collagen Scaffold (NeuroRegen Scaffold; NRS) and human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) were implanted into the resected cavity to repair chronic SCI. The results demonstrated that the locomotor function of rats was not affected by surgical scar resection, indicating its safety in treating chronic SCI. Implanting NRS and hUC-MSCs promoted locomotion in rats and improved cortical motor- and somatosensory-evoked potentials. Furthermore, implanting NRS and hUC-MSCs promoted neurofilament- and β-tubulin-III-positive neural regeneration and remyelination, elicited β-tubulin-III-positive neuron production in the lesion area and blocked astrocyte growth outside the lesion area. In conclusion, implanting NRS in combination with hUC-MSCs provided a beneficial microenvironment for neural regeneration, showing significant therapeutic effects for chronic SCI.

  • the neuronal differentiation microenvironment is essential for spinal cord injury repair
    Organogenesis, 2017
    Co-Authors: Yannan Zhao, Zhifeng Xiao, Bing Chen
    Abstract:

    Spinal cord injury (SCI) often leads to substantial disability due to loss of motor function and sensation below the lesion. Neural stem cells (NSCs) are a promising strategy for SCI repair. However, NSCs rarely differentiate into neurons; they mostly differentiate into astrocytes because of the adverse microenvironment present after SCI. We have shown that myelin-associated inhibitors (MAIs) inhibited neuronal differentiation of NSCs. Given that MAIs activate epidermal growth factor receptor (EGFR) signaling, we used a Collagen Scaffold-tethered anti-EGFR antibody to attenuate the inhibitory effects of MAIs and create a neuronal differentiation microenvironment for SCI repair. The Collagen Scaffold modified with anti-EGFR antibody prevented the inhibition of NSC neuronal differentiation by myelin. After transplantation into completely transected SCI animals, the Scaffold-linked antibodies induced production of nascent neurons from endogenous and transplanted NSCs, which rebuilt the neuronal relay by forming connections with each other or host neurons to transmit electrophysiological signals and promote functional recovery. Thus, a Scaffold-based strategy for rebuilding the neuronal differentiation microenvironment could be useful for SCI repair.

  • a modified Collagen Scaffold facilitates endogenous neurogenesis for acute spinal cord injury repair
    Acta Biomaterialia, 2017
    Co-Authors: Caixia Fan, Yannan Zhao, Zhifeng Xiao, Sufang Han, Bin Wang, Hui Liang, Nuo Wang, Sumei Liu, Weiwei Xue, Jianwu Dai
    Abstract:

    Abstract Due to irreversible neuronal loss and glial scar deposition, spinal cord injury (SCI) ultimately results in permanent neurological dysfunction. Neuronal regeneration of neural stem cells (NSCs) residing in the spinal cord could be an ideal strategy for replenishing the lost neurons and restore function. However, many myelin-associated inhibitors in the SCI microenvironment limit the ability of spinal cord NSCs to regenerate into neurons. Here, a linearly ordered Collagen Scaffold was used to prevent scar deposition, guide nerve regeneration and carry drugs to neutralize the inhibitory molecules. A Collagen-binding EGFR antibody Fab fragment, CBD-Fab, was constructed to neutralize the myelin inhibitory molecules, which was demonstrated to promote neuronal differentiation and neurite outgrowth under myelin in vitro. This fragment could also specifically bind to the Collagen and undergo sustained release from Collagen Scaffold. Then, the Scaffolds modified with CBD-Fab were transplanted into an acute rat SCI model. The robust neurogenesis of endogenous injury-activated NSCs was observed, and these NSCs could not only differentiate into neurons but further mature into functional neurons to reconnect the injured gap. The results indicated that the modified Collagen Scaffold could be an ideal candidate for spinal cord regeneration after acute SCI. Statements of Significance A linearly ordered Collagen Scaffold was specifically modified with Collagen-binding EGFR antibody, allowed for sustained release of this EGFR neutralizing factor, to block the myelin associated inhibitory molecules and guide spinal cord regeneration along its linear fibers. Dorsal root ganglion neurons and neural stem cells induced by CBD-Fab exhibited enhanced neurite outgrowth and neuronal differentiation rate under myelin in vitro. Transplantation of the modified Collagen Scaffold with moderate EGFR neutralizing proteins showed greatest advantage on endogenous neurogenesis of injury-activated neural stem cells for acute spinal cord injury repair.

  • Functionalized Collagen Scaffold implantation and cAMP administration collectively facilitate spinal cord regeneration.
    Acta Biomaterialia, 2016
    Co-Authors: Jin Han, Yannan Zhao, Wenyong Ding, Jianshu Wei, Sufang Han, Xianping Shang, Bin Wang, Bing Chen
    Abstract:

    Abstract Previous studies have demonstrated that several mechanisms, including numerous inhibitory molecules, weak neurotrophic stimulation and deficient intrinsic regenerative responses, collectively contribute to the failure of mature spinal cord axon regeneration. Thus, combinatorial therapies targeting multiple mechanisms have attracted much attention. In the present study, a porous Collagen Scaffold was used to support neuronal attachment and bridge axonal regeneration. The Scaffold was specifically functionalized using neutralizing proteins (CBD-EphA4LBD, CBD-PlexinB1LBD and NEP1-40) and Collagen-binding neurotrophic factors (CBD-BDNF and CBD-NT3) to simultaneously antagonize myelin inhibitory molecules (ephrinB3, Sema4D and Nogo) and exert neurotrophic protection and stimulation. Cerebellar granular neurons cultured on the functionalized Collagen Scaffold promoted neurite outgrowth in the presence of myelin. Furthermore, a full combinatorial treatment comprising functionalized Scaffold implantation and cAMP administration was developed to evaluate the synergistic repair ability in a rat T10 complete removal spinal cord injury model. The results showed that full combinatorial therapy exhibited the greatest advantage in reducing the volume of cavitation, facilitating axonal regeneration, and promoting neuronal generation. The newborn neurons generated in the lesion area could form the neuronal relay and enhance the locomotion recovery after severe spinal cord injury. Statement of Significance A porous Collagen Scaffold was specifically functionalized with neutralizing proteins and neurotrophic factors to antagonize the myelin inhibitory molecules and exert neurotrophic protection and stimulation for spinal cord regeneration. Cerebellar granular neurons seeded on the functionalized Collagen Scaffold showed enhanced neurite outgrowth ability in vitro. The functionalized Scaffold implantation combined with cAMP administration exhibited synergistic repair ability for rat T10 complete spinal cord transection injury.

Zhifeng Xiao - One of the best experts on this subject based on the ideXlab platform.

  • a functional Scaffold to promote the migration and neuronal differentiation of neural stem progenitor cells for spinal cord injury repair
    Biomaterials, 2020
    Co-Authors: Bai Xu, Zhifeng Xiao, Bing Chen, Bin Yang, Qi Zhang, Yannan Zhao
    Abstract:

    Abstract After spinal cord injury (SCI), endogenous neural/progenitor stem cells (NSPCs) were activated in neural tissue adjacent to the injured segment, but few cells migrated to the injury epicenter and differentiated into neurons. N-cadherin regulates mechanical adhesion between NSPCs, and also drives NSPCs migration and promotes NSPCs differentiation. In this study, linearly ordered Collagen Scaffold (LOCS) was modified with N-cadherin through a two-step cross-linking between thiol and amino group. The results indicated that N-cadherin modification improved the adhesion of NSPCs on Collagen Scaffold and increased the differentiation into neurons. When LOCS-Ncad was transplanted into complete transected rat spinal cords, more NSPCs migrated to the lesion center and more newborn neurons appeared within the injury site. Furthermore, rats transplanted with LOCS-Ncad showed significantly improved locomotor recovery compared with the rats without implants. Collectively, our results suggest that LOCS-Ncad may be a promising treatment option to facilitate SCI repair by recruiting endogenous NSPCs to the lesion center and promoting neuronal differentiation.

  • Collagen Scaffold combined with human umbilical cord derived mesenchymal stem cells promote functional recovery after scar resection in rats with chronic spinal cord injury
    Journal of Tissue Engineering and Regenerative Medicine, 2018
    Co-Authors: Nuo Wang, Yannan Zhao, Zhifeng Xiao, Bin Wang, Jianwu Dai
    Abstract:

    Effective therapeutic strategies for treating chronic spinal cord injury (SCI) are currently unavailable. Scar tissue in the lesion area is a main inhibitory factor for axonal regeneration and repair of chronic SCI. In this study, scar tissue was surgically resected from adult rats with 12 week chronic SCI and then Collagen Scaffold (NeuroRegen Scaffold; NRS) and human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) were implanted into the resected cavity to repair chronic SCI. The results demonstrated that the locomotor function of rats was not affected by surgical scar resection, indicating its safety in treating chronic SCI. Implanting NRS and hUC-MSCs promoted locomotion in rats and improved cortical motor- and somatosensory-evoked potentials. Furthermore, implanting NRS and hUC-MSCs promoted neurofilament- and β-tubulin-III-positive neural regeneration and remyelination, elicited β-tubulin-III-positive neuron production in the lesion area and blocked astrocyte growth outside the lesion area. In conclusion, implanting NRS in combination with hUC-MSCs provided a beneficial microenvironment for neural regeneration, showing significant therapeutic effects for chronic SCI.

  • human placenta derived mesenchymal stem cells loaded on linear ordered Collagen Scaffold improves functional recovery after completely transected spinal cord injury in canine
    Science China-life Sciences, 2018
    Co-Authors: Sufang Han, Zhifeng Xiao, Bing Chen, Jin Han, Bin Wang, Caixia Fan, Huan Zhao, Zhixue Qiu, Xin Mei, Huilin Yang
    Abstract:

    Traumatic spinal cord injury (SCI) is a major challenge in the clinic. In this study, we sought to examine the synergistic effects of linear ordered Collagen Scaffold (LOCS) and human placenta-derived mesenchymal stem cells (hPMSCs) when transplanted into completely transected beagle dogs. After 36 weeks observation, we found that LOCS+hPMSCs implants promoted better hindlimb locomotor recovery than was observed in the non-treatment (control) group and LOCS group. Histological analysis showed that the regenerated tissue after treatment was well integrated with the host tissue, and dramatically reduced the volume of cystic and chondroitin sulfate proteoglycans (CSPGs) expression. Furthermore, the LOCS+hPMSCs group also showed more neuron-specific βIII-tubulin (Tuj-1)- and NeuN-positive neurons in the lesion area, as well as axonal regeneration, remyelination and synapse formation in the lesion site. Additionally, dogs in the LOCS+hPMSCs group experienced enhanced sprouting of both ascending (CGRP-positive) sensory fibers and descending (5-HT- and TH-positive) motor fibers at the lesion area. All these data together suggested that the combined treatment had beneficial effects on neuronal regeneration and functional improvement in a canine complete transection model. Therefore, LOCS+hPMSCs implantation holds a great promise for bridging the nerve defect and may be clinically useful in the near future.

  • the neuronal differentiation microenvironment is essential for spinal cord injury repair
    Organogenesis, 2017
    Co-Authors: Yannan Zhao, Zhifeng Xiao, Bing Chen
    Abstract:

    Spinal cord injury (SCI) often leads to substantial disability due to loss of motor function and sensation below the lesion. Neural stem cells (NSCs) are a promising strategy for SCI repair. However, NSCs rarely differentiate into neurons; they mostly differentiate into astrocytes because of the adverse microenvironment present after SCI. We have shown that myelin-associated inhibitors (MAIs) inhibited neuronal differentiation of NSCs. Given that MAIs activate epidermal growth factor receptor (EGFR) signaling, we used a Collagen Scaffold-tethered anti-EGFR antibody to attenuate the inhibitory effects of MAIs and create a neuronal differentiation microenvironment for SCI repair. The Collagen Scaffold modified with anti-EGFR antibody prevented the inhibition of NSC neuronal differentiation by myelin. After transplantation into completely transected SCI animals, the Scaffold-linked antibodies induced production of nascent neurons from endogenous and transplanted NSCs, which rebuilt the neuronal relay by forming connections with each other or host neurons to transmit electrophysiological signals and promote functional recovery. Thus, a Scaffold-based strategy for rebuilding the neuronal differentiation microenvironment could be useful for SCI repair.

  • a modified Collagen Scaffold facilitates endogenous neurogenesis for acute spinal cord injury repair
    Acta Biomaterialia, 2017
    Co-Authors: Caixia Fan, Yannan Zhao, Zhifeng Xiao, Sufang Han, Bin Wang, Hui Liang, Nuo Wang, Sumei Liu, Weiwei Xue, Jianwu Dai
    Abstract:

    Abstract Due to irreversible neuronal loss and glial scar deposition, spinal cord injury (SCI) ultimately results in permanent neurological dysfunction. Neuronal regeneration of neural stem cells (NSCs) residing in the spinal cord could be an ideal strategy for replenishing the lost neurons and restore function. However, many myelin-associated inhibitors in the SCI microenvironment limit the ability of spinal cord NSCs to regenerate into neurons. Here, a linearly ordered Collagen Scaffold was used to prevent scar deposition, guide nerve regeneration and carry drugs to neutralize the inhibitory molecules. A Collagen-binding EGFR antibody Fab fragment, CBD-Fab, was constructed to neutralize the myelin inhibitory molecules, which was demonstrated to promote neuronal differentiation and neurite outgrowth under myelin in vitro. This fragment could also specifically bind to the Collagen and undergo sustained release from Collagen Scaffold. Then, the Scaffolds modified with CBD-Fab were transplanted into an acute rat SCI model. The robust neurogenesis of endogenous injury-activated NSCs was observed, and these NSCs could not only differentiate into neurons but further mature into functional neurons to reconnect the injured gap. The results indicated that the modified Collagen Scaffold could be an ideal candidate for spinal cord regeneration after acute SCI. Statements of Significance A linearly ordered Collagen Scaffold was specifically modified with Collagen-binding EGFR antibody, allowed for sustained release of this EGFR neutralizing factor, to block the myelin associated inhibitory molecules and guide spinal cord regeneration along its linear fibers. Dorsal root ganglion neurons and neural stem cells induced by CBD-Fab exhibited enhanced neurite outgrowth and neuronal differentiation rate under myelin in vitro. Transplantation of the modified Collagen Scaffold with moderate EGFR neutralizing proteins showed greatest advantage on endogenous neurogenesis of injury-activated neural stem cells for acute spinal cord injury repair.

Jianwu Dai - One of the best experts on this subject based on the ideXlab platform.

  • controlled release of Collagen binding sdf 1α from the Collagen Scaffold promoted tendon regeneration in a rat achilles tendon defect model
    Biomaterials, 2018
    Co-Authors: Jie Sun, Bing Chen, Qin Shi, Xianglin Hou, Chenchen Mou, Wen Zhang, Yan Zhuang, Jiajia Shi, Yanyan Chen, Jianwu Dai
    Abstract:

    Abstract It had been demonstrated that stromal cell-derived factor-1α (SDF-1α) could promote in situ tendon regeneration by recruiting endogenous cells. However, native SDF-1α diffuses too fast in vivo , reducing its local concentration and efficacy. In this study, we prepared a recombinant SDF-1α containing a Collagen-binding domain (CBD-SDF-1α) and developed a functional Collagen Scaffold by tethering CBD-SDF-1α on the Collagen Scaffold for in situ tendon regeneration. CBD-SDF-1α could induce the migration of mesenchymal stem cells, dermal fibroblasts and Achilles tendon fibroblasts in vitro , and achieve controlled release from the Collagen Scaffold. In a rat Achilles tendon defect model, the functional Scaffold could increase the recruitment of CXCR4 positive fibroblast-like cells and the deposition of Tenascin-C at 7 days after implantation. After 4 and 12 weeks, the functional Collagen Scaffold could promote the expression of type I Collagen, increase the diameters of Collagen fibrils and improve the mechanical properties of regenerated tendons. Hence, the functional Scaffold increased the efficacy of tendon regeneration by controlling release of SDF-1α, enhancing the recruitment of fibroblast-like cells and providing instructive microenvironment and mechanical support for tendon regeneration. Therefore, CBD-SDF-1α-modified Collagen Scaffold could serve as a practical application for tendon regeneration.

  • promotion of neurological recovery in rat spinal cord injury by mesenchymal stem cells loaded on nerve guided Collagen Scaffold through increasing alternatively activated macrophage polarization
    Journal of Tissue Engineering and Regenerative Medicine, 2018
    Co-Authors: Zhan Peng, Wei Gao, Bing Yue, Jie Jiang, Jianwu Dai, Liang Chen, Qin Shi
    Abstract:

    Mesenchymal stem cells (MSCs) are characterized by multidifferentiation and immunoregulatory potential and have been used in the treatment of spinal cord injury (SCI), but direct transplantation may limit effectiveness due to their quick diffusion. The role of macrophages in healing is being increasingly recognized because of their ability to polarize into pro- and anti-inflammatory phenotypes. In the present study, nerve-guide Collagen Scaffold (CS) combined with rat MSCs was developed. After CS was confirmed to minimize MSC distribution in vivo by positron emission tomography (PET) imaging, the repair capacity of combined implantation of CS and MSCs and the effect on classically activated macrophage/alternatively activated macrophage (M2) polarization was assessed in a hemisected SCI rat model. In vivo studies showed that, compared to the control group, the rats in the combined implantation group exhibited more significant recovery of nerve function evidenced by the 21-point Basso-Beattie-Bresnahan score and footprint analysis. Morphological staining showed less macrophage infiltration, apoptosis and glial fibrillary acidic protein, and more neurofilaments, and the fibres were guided to grow through the implant. More M2 were observed in the combined implantation group. The data suggest that the combined implantation could support MSCs to play a protective role of SCI, not only through inhibiting chronic scar formation and providing linear guidance for the nerve, but also benefitting M2 polarization to form an anti-inflammatory environment. Thus, the combination of biomaterial and MSCs might be a prominent therapeutic treatment for SCI. Copyright © 2016 John Wiley & Sons, Ltd.

  • Collagen Scaffold combined with human umbilical cord derived mesenchymal stem cells promote functional recovery after scar resection in rats with chronic spinal cord injury
    Journal of Tissue Engineering and Regenerative Medicine, 2018
    Co-Authors: Nuo Wang, Yannan Zhao, Zhifeng Xiao, Bin Wang, Jianwu Dai
    Abstract:

    Effective therapeutic strategies for treating chronic spinal cord injury (SCI) are currently unavailable. Scar tissue in the lesion area is a main inhibitory factor for axonal regeneration and repair of chronic SCI. In this study, scar tissue was surgically resected from adult rats with 12 week chronic SCI and then Collagen Scaffold (NeuroRegen Scaffold; NRS) and human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) were implanted into the resected cavity to repair chronic SCI. The results demonstrated that the locomotor function of rats was not affected by surgical scar resection, indicating its safety in treating chronic SCI. Implanting NRS and hUC-MSCs promoted locomotion in rats and improved cortical motor- and somatosensory-evoked potentials. Furthermore, implanting NRS and hUC-MSCs promoted neurofilament- and β-tubulin-III-positive neural regeneration and remyelination, elicited β-tubulin-III-positive neuron production in the lesion area and blocked astrocyte growth outside the lesion area. In conclusion, implanting NRS in combination with hUC-MSCs provided a beneficial microenvironment for neural regeneration, showing significant therapeutic effects for chronic SCI.

  • a modified Collagen Scaffold facilitates endogenous neurogenesis for acute spinal cord injury repair
    Acta Biomaterialia, 2017
    Co-Authors: Caixia Fan, Yannan Zhao, Zhifeng Xiao, Sufang Han, Bin Wang, Hui Liang, Nuo Wang, Sumei Liu, Weiwei Xue, Jianwu Dai
    Abstract:

    Abstract Due to irreversible neuronal loss and glial scar deposition, spinal cord injury (SCI) ultimately results in permanent neurological dysfunction. Neuronal regeneration of neural stem cells (NSCs) residing in the spinal cord could be an ideal strategy for replenishing the lost neurons and restore function. However, many myelin-associated inhibitors in the SCI microenvironment limit the ability of spinal cord NSCs to regenerate into neurons. Here, a linearly ordered Collagen Scaffold was used to prevent scar deposition, guide nerve regeneration and carry drugs to neutralize the inhibitory molecules. A Collagen-binding EGFR antibody Fab fragment, CBD-Fab, was constructed to neutralize the myelin inhibitory molecules, which was demonstrated to promote neuronal differentiation and neurite outgrowth under myelin in vitro. This fragment could also specifically bind to the Collagen and undergo sustained release from Collagen Scaffold. Then, the Scaffolds modified with CBD-Fab were transplanted into an acute rat SCI model. The robust neurogenesis of endogenous injury-activated NSCs was observed, and these NSCs could not only differentiate into neurons but further mature into functional neurons to reconnect the injured gap. The results indicated that the modified Collagen Scaffold could be an ideal candidate for spinal cord regeneration after acute SCI. Statements of Significance A linearly ordered Collagen Scaffold was specifically modified with Collagen-binding EGFR antibody, allowed for sustained release of this EGFR neutralizing factor, to block the myelin associated inhibitory molecules and guide spinal cord regeneration along its linear fibers. Dorsal root ganglion neurons and neural stem cells induced by CBD-Fab exhibited enhanced neurite outgrowth and neuronal differentiation rate under myelin in vitro. Transplantation of the modified Collagen Scaffold with moderate EGFR neutralizing proteins showed greatest advantage on endogenous neurogenesis of injury-activated neural stem cells for acute spinal cord injury repair.

  • urethral tissue regeneration using Collagen Scaffold modified with Collagen binding vegf in a beagle model
    Biomaterials, 2015
    Co-Authors: Weisheng Jia, Yannan Zhao, Bing Chen, He Tang, Xianglin Hou, Wei Chen, Chunying Shi, Feng Zhou, Shengquan Huang, Jianwu Dai
    Abstract:

    Extensive urethral defects have a serious impact on quality of life, and treatment is challenging. A shortage of material for reconstruction is a key limitation. Improving the properties of biomaterials and making them suitable for urethral reconstruction will be helpful. Previously, we constructed a fusion protein, Collagen-binding VEGF (CBD-VEGF), which can bind to Collagen Scaffold, stimulate cell proliferation, and promote angiogenesis and tissue regeneration. We proposed that CBD-VEGF could improve the performance of Collagen in reconstruction of extensive urethral defects. Our results showed that Collagen Scaffolds modified with CBD-VEGF could promote urethral tissue regeneration and improve the function of the neo-urethra in a beagle extensive urethral defect model. Thus, modifying biomaterials with bioactive factors provides an alternative strategy for the production of suitable biomaterials for urethral reconstruction.

Brendan A C Harley - One of the best experts on this subject based on the ideXlab platform.

  • glycosaminoglycan content of a mineralized Collagen Scaffold promotes mesenchymal stem cell secretion of factors to modulate angiogenesis and monocyte differentiation
    Materialia, 2021
    Co-Authors: Marley J Dewey, Vasiliki Kolliopoulos, Mai T Ngo, Brendan A C Harley
    Abstract:

    Abstract Effective design of biomaterials to aid regenerative repair of craniomaxillofacial (CMF) bone defects requires approaches that modulate the complex interplay between exogenously added progenitor cells and cells in the wound microenvironment, such as osteoblasts, osteoclasts, endothelial cells, and immune cells. We are exploring the role of the glycosaminoglycan (GAG) content in a class of mineralized Collagen Scaffolds recently shown to promote osteogenesis and healing of craniofacial bone defects. We previously showed that incorporating chondroitin-6-sulfate or heparin improved mineral deposition by seeded human mesenchymal stem cells (hMSCs). Here, we examine the effect of varying Scaffold GAG content on hMSC behavior, and their ability to modulate osteoclastogenesis, vasculogenesis, and the immune response. We report the role of hMSC-conditioned media produced in Scaffolds containing chondroitin-6-sulfate (CS6), chondroitin-4-sulfate (CS4), or heparin (Heparin) GAGs on endothelial tube formation and monocyte differentiation. Notably, endogenous production by hMSCs within Heparin Scaffolds most significantly inhibits osteoclastogenesis via secreted osteoprotegerin (OPG), while the secretome generated by CS6 Scaffolds reduced pro-inflammatory immune response and increased endothelial tube formation. All conditioned media down-regulated many pro- and anti-inflammatory cytokines, such as IL6, IL-1β, and CCL18 and CCL17 respectively. Together, these findings demonstrate that modifying mineralized Collagen Scaffold GAG content can both directly (hMSC activity) and indirectly (production of secreted factors) influence overall osteogenic potential and mineral biosynthesis as well as angiogenic potential and monocyte differentiation towards osteoclastic and macrophage lineages. Scaffold GAG content is therefore a powerful stimulus to modulate reciprocal signaling between multiple cell populations within the bone healing microenvironment.

  • glycosaminoglycan content of a mineralized Collagen Scaffold promotes mesenchymal stem cell secretion of factors to modulate angiogenesis and monocyte differentiation
    bioRxiv, 2021
    Co-Authors: Marley J Dewey, Vasiliki Kolliopoulos, Mai T Ngo, Brendan A C Harley
    Abstract:

    Effective design of biomaterials to aid regenerative repair of craniomaxillofacial (CMF) bone defects requires approaches that modulate the complex interplay between exogenously added progenitor cells and cells in the wound microenvironment, such as osteoblasts, osteoclasts, endothelial cells, and immune cells. We are exploring the role of the glycosaminoglycan (GAG) content in a class of mineralized Collagen Scaffolds recently shown to promote osteogenesis and healing of craniofacial bone defects. We previously showed that incorporating chondroitin-6-sulfate or heparin improved mineral deposition by seeded human mesenchymal stem cells (hMSCs). However, improved healing requires angiogenic processes as well as an immune response. Here, we examine the effect of varying Scaffold GAG content on hMSC behavior, specifically with regards to their ability to act as endogenous factories of biomolecules that modulate processes associated with osteoclastogenesis, vasculogenesis, and the immune response. We report the role of hMSC-conditioned media produced in mineralized Scaffolds containing chondroitin-6-sulfate (CS6), chondroitin-4-sulfate (CS4), or heparin (Heparin) GAGs on biomarkers of endothelial tube formation and monocyte differentiation towards macrophage and osteoclast lineages. Notably, endogenous production by hMSCs within Heparin Scaffolds most significantly inhibits osteoclastogenesis via secreted osteoprotegerin (OPG), while the secretome generated by CS6 Scaffolds reduced pro-inflammatory immune response and increased endothelial tube formation. Modulation of endogenous factor production by seeded hMSCs via Scaffold GAG content is sufficient to down-regulate many pro- and anti-inflammatory cytokines, such as IL6, IL-1{beta}, and CCL18 and CCL17 respectively. Together, these findings demonstrate that modifying mineralized Collagen Scaffold GAG content can both directly (hMSC activity) and indirectly (endogenous production of secreted factors) influence overall osteogenic potential and mineral biosynthesis as well as angiogenic potential and monocyte differentiation towards osteoclastic and macrophage lineages. Scaffold GAG content is therefore a powerful stimulus to modulate reciprocal signaling between multiple cell populations within the bone healing microenvironment.

  • inclusion of a 3d printed hyperelastic bone mesh improves mechanical and osteogenic performance of a mineralized Collagen Scaffold
    Acta Biomaterialia, 2021
    Co-Authors: Marley J Dewey, Andrey V Nosatov, Kiran Subedi, Ramille N Shah, Adam E Jakus, Brendan A C Harley
    Abstract:

    Regenerative repair of craniomaxillofacial bone injuries is challenging due to both the large size and irregular shape of many defects. Mineralized Collagen Scaffolds have previously been shown to be a promising biomaterial implant to accelerate craniofacial bone regeneration in vivo. Here we describe inclusion of a 3D-printed polymer or ceramic-based mesh into a mineralized Collagen Scaffold to improve mechanical and biological activity. Mineralized Collagen Scaffolds were reinforced with 3D-printed Fluffy-PLG (ultraporous polylactide-co-glycolide co-polymer) or Hyperelastic Bone (90wt% calcium phosphate in PLG) meshes. We show degradation byproducts and acidic release from the printed structures have limited negative impact on the viability of mesenchymal stem cells. Further, inclusion of a mesh formed from Hyperelastic Bone generates a reinforced composite with significantly improved mechanical performance (elastic modulus, push-out strength). Composites formed from the mineralized Collagen Scaffold and either Hyperelastic Bone or Fluffy-PLG reinforcement both supported human bone-marrow derived mesenchymal stem cell osteogenesis and new bone formation. This was observed by increased mineral formation in Fluffy-PLG composites and increased cell viability and upregulation of RUNX2, Osterix, and COL1A2 genes in both composites. Strikingly, composites reinforced with Hyperelastic Bone mesh elicited significantly increased secretion of osteoprotegerin, a soluble glycoprotein and endogenous inhibitor of osteoclast activity. These results suggest that architectured meshes can be integrated into Collagen Scaffolds to boost mechanical performance and actively instruct cell processes that aid osteogenicity; specifically, secretion of a factor crucial to inhibiting osteoclast-mediated bone resorption. Future work will focus on further adapting the polymer mesh architecture to confer improved shape-fitting capacity as well as to investigate the role of polymer reinforcement on MSC-osteoclast interactions as a means to increase regenerative potential.

  • inclusion of a 3d printed hyperelastic bone mesh improves mechanical and osteogenic performance of a mineralized Collagen Scaffold
    Social Science Research Network, 2020
    Co-Authors: Marley J Dewey, Andrey V Nosatov, Kiran Subedi, Ramille N Shah, Adam E Jakus, Brendan A C Harley
    Abstract:

    Regenerative repair of craniomaxillofacial bone injuries is challenging due to both the large size and irregular shape of many defects. Mineralized Collagen Scaffolds have previously been shown to be a promising biomaterial implant to accelerate craniofacial bone regeneration in vivo . Here we describe inclusion of a 3D-printed polymer or ceramic-based mesh into a mineralized Collagen Scaffold to improve mechanical and biological activity. Mineralized Collagen Scaffolds were reinforced with 3D-printed Fluffy-PLG (ultraporous polylactide-co-glycolide co-polymer) or Hyperelastic Bone (90wt% calcium phosphate in PLG) meshes. We show degradation byproducts and acidic release from the printed structures have limited negative impact on the viability of mesenchymal stem cells. Further, inclusion of a mesh formed from Hyperelastic Bone generates a reinforced composite with significantly improved mechanical performance (elastic modulus, push-out strength). Composites formed from the mineralized Collagen Scaffold and either Hyperelastic Bone or Fluffy-PLG reinforcement both supported human bone-marrow derived mesenchymal stem cell osteogenesis and new bone formation. Strikingly, composites reinforced with Hyperelastic Bone mesh elicited significantly increased secretion of osteoprotegerin, a soluble glycoprotein and endogenous inhibitor of osteoclast activity. These results suggest that architectured meshes can be integrated into Collagen Scaffolds to boost mechanical performance and actively instruct cell processes that aid osteogenicity; specifically, secretion of a factor crucial to inhibiting osteoclast-mediated bone resorption. Future work will focus on further adapting the polymer mesh architecture to confer improved shape-fitting capacity as well as to investigate the role of polymer reinforcement on MSC-osteoclast interactions as a means to increase regenerative potential.

  • shape fitting Collagen pla composite promotes osteogenic differentiation of porcine adipose stem cells
    Journal of The Mechanical Behavior of Biomedical Materials, 2019
    Co-Authors: Marley J Dewey, Eileen M Johnson, Daniel W Weisgerber, Matthew B Wheeler, Brendan A C Harley
    Abstract:

    Craniomaxillofacial bone defects can occur as a result of congenital, post-oncologic, and high-energy impact conditions. The scale and irregularity of such defects motivate new biomaterials to promote regeneration of the damaged bone. We have recently described a mineralized Collagen Scaffold capable of instructing stem cell osteogenic differentiation and new bone infill in the absence of traditional osteogenic supplements. Herein, we report the integration of a millimeter-scale reinforcing poly (lactic acid) frame fabricated via 3D-printing into the mineralized Collagen Scaffold with micron-scale porosity to form a multi-scale mineralized Collagen-PLA composite. We describe modifications to the PLA frame design to increase the compressive strength (Young's Modulus, ultimate stress and strain) of the composite. A critical challenge beyond increasing the compressive strength of the Collagen Scaffold is addressing challenges inherent with the irregularity of clinical defects. As a result, we examined the potential for modifying the frame architecture to render the composite with increased compressive strength in one axis or radial compressibility and shape-fitting capacity in an orthogonal axis. A library of mineralized Collagen-PLA composites was mechanically characterized via compression testing and push-out test to describe mechanical performance and shape-fitting capacity. We also report in vitro comparison of the bioactivity of porcine adipose derived stem cells in the mineralized Collagen-PLA composite versus the mineralized Collagen Scaffold via metabolic activity, gene expression, and functional matrix synthesis. The results suggest that incorporation of the PLA reinforcing frame does not negatively influence the osteoinductive nature of the mineralized Collagen Scaffold. Together, these findings suggest a strategy to address often competing bioactivity, mechanical strength, and shape-fitting design requirements for biomaterials for craniomaxillofacial bone regeneration.