Design Of Microstructure Biomaterials And Microenvironments For Nerve Guidance

Nerve induction is fundamental to support,reconstruct,regenerate or replace damaged nerve tissue or organ,which has great importance in neuroengineering and regenerative medicine.Currently,nerve tissue engineering mainly focuses on biomaterials with electrical conductivity,topological morphology,and controllable microenvironment functions.Meanwhile,exploring the effect of the extracellular matrix on neural tissue is also of great importance.So far,researchers have developed a variety of new biological materials for tissue engineering,including carbon materials,photonic crystals,and organ chips.We designed some neural tissue engineering materials and fabricated microenvironment systems to combine the physical and chemical properties of biomaterials with organ-on-a-chip technology.We applied them to neural tissue engineering,including neural stem cell growth regulation,bionic spinal cord,brain organoid development regulation and other applications.The specific research content and methods are as follows:1)A poly dopamine-functionalized carbon microfibrous scaffold accelerates the development of neural stem cells.We aimed to develop an electrically conductive and adherent 3D scaffold and examined the effects on nerve stem cell development by combining poly dopamine(PDA)functionalization and electrical stimulation with 3D structures.Compared to the untreated carbon fiber(CF)group,the PDA-mediated collection of electrically conductive and viscous microfiber webs improved the adhesion,organization,and intercellular coupling of NCSs.The presence of PDA resulted in a significantly increased proliferation of NSCs and expression of Ki-67.Representative 3D reconstructions of confocal microscope images demonstrated that NSCs could quickly grew into the interior of the PDA-CF but only accumulated across the surface of the CF scaffold.The expression of vinculin by NSCs was also significantly enhanced in NSCs grown on PDA-CF compared to those grown on CF.2)Ordered carbon inverse-opal scaffolds based on bionic transpiration for biomimetic spinal.We proposed a new conception of the biomimetic spinal scaffolds by ordered carbon inverse-opal scaffolds based on bionic transpiration.This spinal mimicry material was inspired by plant transpiration and formed by self-assembly colloidal crystals in capillaries after the solvent evaporating.Compared with the current spinal scaffolds,the strategy for the formation were low fabrication cost,time-effective,and not restricted by complex operation.Combining the effects of internal-external interconnected structure with the characteristics of electrical stimulation with 3D structures,our bionic scaffolds significantly promoted neuroregeneration and neural network formation so that acute spinal cord injury could be regenerated and repaired.3)Human brain organoid polarized guidance based on a thin layer chip for the revealing of neurulation.We aimed to model the reproducible topographic organization and maturation of cerebral organoids by combining engineering methods with organ-on-chips.By mimicking the neural plate formation process in vivo,a low-cost PDMS chip was designed with a microspace to simulate a narrow environment.The expression of dorsal forebrain marker PAX6 indicated that the brain organoids are endowed with regional polarity by the PDMS chip.Besides,the organoids in the chip increased wrinkles compared to the control group.This work suggests that our organ chips successfully guide the polarization development and maturation of brain organoids.This thesis was mainly focused on the realization of neural guidance by microstructure materials and microenvironment control.Through the design and development of carbon materials,photonic crystal materials and organ-on-chips were adopted to guide the neural tissue plasticity in neural development.Neural applications such as the induction of neural stem cell growth,the preparation of transplantable spinal cord stents,and the development and regulation of brain organoids in the frontier hot areas of neural engineering provide a means and platform for the treatment of central nervous system diseases.