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Biomimetic 3D-printed scaffolds for spinal cord injury repair.

ABSTRACT: Current methods for bioprinting functional tissue lack appropriate biofabrication techniques to build complex 3D microarchitectures essential for guiding cell growth and promoting tissue maturation1. 3D printing of central nervous system (CNS) structures has not been accomplished, possibly owing to the complexity of CNS architecture. Here, we report the use of a microscale continuous projection printing method (?CPP) to create a complex CNS structure for regenerative medicine applications in the spinal cord. ?CPP can print 3D biomimetic hydrogel scaffolds tailored to the dimensions of the rodent spinal cord in 1.6?s and is scalable to human spinal cord sizes and lesion geometries. We tested the ability of µCPP 3D-printed scaffolds loaded with neural progenitor cells (NPCs) to support axon regeneration and form new 'neural relays' across sites of complete spinal cord injury in vivo in rodents1,2. We find that injured host axons regenerate into 3D biomimetic scaffolds and synapse onto NPCs implanted into the device and that implanted NPCs in turn extend axons out of the scaffold and into the host spinal cord below the injury to restore synaptic transmission and significantly improve functional outcomes. Thus, 3D biomimetic scaffolds offer a means of enhancing CNS regeneration through precision medicine.

SUBMITTER: Koffler J

PROVIDER: S-EPMC6559945 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Biomimetic 3D-printed scaffolds for spinal cord injury repair.

Koffler Jacob J Zhu Wei W Qu Xin X Platoshyn Oleksandr O Dulin Jennifer N JN Brock John J Graham Lori L Lu Paul P Sakamoto Jeff J Marsala Martin M Chen Shaochen S Tuszynski Mark H MH

Nature medicine 20190114 2

Current methods for bioprinting functional tissue lack appropriate biofabrication techniques to build complex 3D microarchitectures essential for guiding cell growth and promoting tissue maturation<sup>1</sup>. 3D printing of central nervous system (CNS) structures has not been accomplished, possibly owing to the complexity of CNS architecture. Here, we report the use of a microscale continuous projection printing method (μCPP) to create a complex CNS structure for regenerative medicine applicat ...[more]

PMID: 30643285

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Project description:In clinical trials, new scaffolds for regeneration after spinal cord injury (SCI) should reflect the importance of a mechanically optimised, hydrated environment. Composite scaffolds of nonwovens, self-assembling peptides (SAPs) and hydrogels offer the ability to mimic native spinal cord tissue, promote aligned tissue regeneration and tailor mechanical properties. This work studies the effects of an aligned electrospun nonwoven of P11-8-enriched poly(ε-caprolactone) (PCL) fibres, integrated with a photo-crosslinked hydrogel of glycidylmethacrylated collagen (collagen-GMA), on neurite extension. Mechanical properties of collagen-GMA hydrogel in compression and shear were recorded, along with cell viability. Collagen-GMA hydrogels showed J-shaped stress-strain curves in compression, mimicking native spinal cord tissue. For hydrogels prepared with a 0.8-1.1 wt.% collagen-GMA concentration, strain at break values were 68 ± 1-81 ± 1% (±SE); maximum stress values were 128 ± 9-311 ± 18 kPa (±SE); and maximum force values were 1.0 ± 0.1-2.5 ± 0.1 N (±SE). These values closely mimicked the compression values for feline and porcine tissue in the literature, especially those for 0.8 wt.%. Complex shear modulus values fell in the range 345-2588 Pa, with the lower modulus hydrogels in the range optimal for neural cell survival and growth. Collagen-GMA hydrogel provided an environment for homogenous and three-dimensional cell encapsulation, and high cell viability of 84 ± 2%. Combination of the aligned PCL/P11-8 electrospun nonwoven and collagen-GMA hydrogel retained fibre alignment and pore structure, respectively, and promoted aligned neurite extension of PC12 cells. Thus, it is possible to conclude that scaffolds with mechanical properties that both closely mimic native spinal cord tissue and are optimal for neural cells can be produced, which also promote aligned tissue regeneration when the benefits of hydrogels and electrospun nonwovens are combined.

Project description:BACKGROUND:Spinal cord injury (SCI) is a severe medical condition affecting the hand and locomotor function. New medical technologies, including various wearable devices, as well as rehabilitation treatments are being developed to enhance hand function in patients with SCI. As three-dimensional (3D) printing has the advantage of being able to produce low-cost personalized devices, there is a growing appeal to apply this technology to rehabilitation equipment in conjunction with scientific advances. In this study, we proposed a novel 3D-printed hand orthosis that is controlled by electromyography (EMG) signals. The orthosis was designed to aid the grasping function for patients with cervical SCI. We applied this hand exoskeleton system to individuals with tetraplegia due to SCI and validated its effectiveness. METHODS:The 3D architecture of the device was designed using computer-aided design software and printed with a polylactic acid filament. The dynamic hand orthosis enhanced the tenodesis grip to provide sufficient grasping function. The root mean square of the EMG signal was used as the input for controlling the device. Ten subjects with hand weakness due to chronic cervical SCI were enrolled in this study, and their hand function was assessed before and after wearing the orthosis. The Toronto Rehabilitation Institute Hand Function Test (TRI-HFT) was used as the primary outcome measure. Furthermore, improvements in functional independence in daily living and device usability were evaluated. RESULTS:The newly developed orthosis improved hand function of subjects, as determined using the TRI-HFT (p < 0.05). Furthermore, participants obtained immediate functionality on eating after wearing the orthosis. Moreover, most participants were satisfied with the device as determined by the usability test. There were no side effects associated with the experiment. CONCLUSIONS:The 3D-printed myoelectric hand orthosis was intuitive, easy to use, and showed positive effects in its ability to handle objects encountered in daily life. This study proved that combining simple EMG-based control strategies and 3D printing techniques was feasible and promising in rehabilitation engineering. TRIAL REGISTRATION:Clinical Research Information Service (CRiS), Republic of Korea. KCT0003995. Registered 2 May 2019 - Retrospectively registered.

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Biomimetic 3D-printed scaffolds for spinal cord injury repair.

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Biomimetic 3D-printed scaffolds for spinal cord injury repair.

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