A conductive supramolecular hydrogel creates ideal endogenous niches to promote spinal cord injury repair
Source abstract
Abstract
The current effective method for treatment of spinal cord injury (SCI) is to reconstruct the biological microenvironment by filling the injured cavity area and increasing neuronal differentiation of neural stem cells (NSCs) to repair SCI. However, the method is characterized by several challenges including irregular wounds, and mechanical and electrical mismatch of the material-tissue interface. In the current study, a unique and facile agarose/gelatin/polypyrrole (Aga/Gel/PPy, AGP3) hydrogel with similar conductivity and modulus as the spinal cord was developed by altering the concentration of Aga and PPy. The gelation occurred through non-covalent interactions, and the physically crosslinked features made the AGP3 hydrogels injectable. In vitro cultures showed that AGP3 hydrogel exhibited excellent biocompatibility, and promoted differentiation of NSCs toward neurons whereas it inhibited over-proliferation of astrocytes. The in vivo implanted AGP3 hydrogel completely covered the tissue defects and reduced injured cavity areas. In vivo studies further showed that the AGP3 hydrogel provided a biocompatible microenvironment for promoting endogenous neurogenesis rather than glial fibrosis formation, resulting in significant functional recovery. RNA sequencing analysis further indicated that AGP3 hydrogel significantly modulated expression of neurogenesis-related genes through intracellular Ca2+ signaling cascades. Overall, this supramolecular strategy produces AGP3 hydrogel that can be used as favorable biomaterials for SCI repair by filling the cavity and imitating the physiological properties of the spinal cord.
Source: openalex_inverted_index · Quality: baseline
Research context
OpenAlex topics: Nerve injury and regeneration · Spinal Cord Injury Research · Neurogenesis and neuroplasticity mechanisms
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
References (72)
Show source-provided references
1. Restoring the sense of touch using a sensorimotor demultiplexing neural interface10.1016/j.cell.2020.03.054 ↗
2. Transplanting neural progenitor cells to restore connectivity after spinal cord injury10.1038/s41583-020-0314-2 ↗
3. Spinal-cord injury: spurring regrowth10.1038/d41586-017-07550-9 ↗
4. Multi-target approaches to CNS repair: olfactory mucosa-derived cells and heparan sulfates10.1038/s41582-020-0311-0 ↗
5. A bioactive injectable self-healing anti-inflammatory hydrogel with ultralong extracellular vesicles release synergistically enhances motor functional recovery of spinal cord injury
6. A latent lineage potential in resident neural stem cells enables spinal cord repair10.1126/science.abb8795 ↗
7. Soft conducting polymer hydrogels cross-linked and doped by tannic acid for spinal cord injury repair10.1021/acsnano.8b04609 ↗
8. Effective modulation of CNS inhibitory microenvironment using bioinspired hybrid-nanoscaffold-based therapeutic interventions
9. An injectable hydrogel enhances tissue repair after spinal cord injury by promoting extracellular matrix remodeling10.1038/s41467-017-00583-8 ↗
10. Spinal cord repair: advances in biology and technology10.1038/s41591-019-0475-6 ↗
11. Advances in engineering hydrogels10.1126/science.aaf3627 ↗
12. An adhesive hydrogel with "Load-Sharing" effect as tissue bandages for drug and cell delivery10.1002/adma.202001628 ↗
13. Portraits of communication in neuronal networks10.1038/s41583-018-0094-0 ↗
14. Brain-controlled modulation of spinal circuits improves recovery from spinal cord injury10.1038/s41467-018-05282-6 ↗
15. Cell-laden electroconductive hydrogel simulating nerve matrix to deliver electrical cues and promote neurogenesis10.1021/acsami.9b05520 ↗
16. Biofunctionalized PEDOT-coated microfibers for the treatment of spinal cord injury10.1016/j.biomaterials.2016.02.037 ↗
17. Black-phosphorus-incorporated hydrogel as a conductive and biodegradable platform for enhancement of the neural differentiation of mesenchymal stem cells
18. Regenerative rehabilitation with conductive biomaterials for spinal cord injury
19. Conductive scaffolds for cardiac and neuronal tissue engineering: governing factors and mechanisms10.1002/adfm.201901369 ↗
20. Injectable and tunable gelatin hydrogels enhance stem cell retention and improve cutaneous wound healing10.1002/adfm.201606619 ↗
21. A self-doping conductive polymer hydrogel that can restore electrical impulse propagation at myocardial infarct to prevent cardiac arrhythmia and preserve ventricular function10.1016/j.biomaterials.2019.119672 ↗
22. Physical double-network hydrogel adhesives with rapid shape adaptability, fast self-healing, antioxidant and NIR/pH stimulus-responsiveness for multidrug-resistant bacterial infection and removable wound dressing
23. Antibacterial and anti-inflammatory pH-responsive tannic acid-carboxylated agarose composite hydrogels for wound healing10.1021/acsami.6b10491 ↗
24. Time controlled protein release from layer-by-layer assembled multilayer functionalized agarose hydrogels10.1002/adfm.200901172 ↗
25. Controlling spatiotemporal mechanics of supramolecular hydrogel networks with highly branched cucurbit[8]uril polyrotaxanes10.1002/adfm.201702994 ↗
26. A macroporous hydrogel dressing with enhanced antibacterial and anti-inflammatory capabilities for accelerated wound healing
27. Rheological properties of aqueous agarose-gelatin gels10.1111/j.1745-4603.1980.tb00325.x ↗
28. Paintable and rapidly bondable conductive hydrogels as therapeutic cardiac patches10.1002/adma.201704235 ↗
29. Supramolecular metallo-bioadhesive for minimally invasive use10.1002/adma.201602606 ↗
30. 3D particle-free printing of biocompatible conductive hydrogel platforms for neuron growth and electrophysiological recording
31. An injectable, self-healing, electroconductive extracellular matrix-based hydrogel for enhancing tissue repair after traumatic spinal cord injury
32. 3D spatiotemporal mechanical microenvironment: a hydrogel-based platform for guiding stem cell fate10.1002/adma.201705911 ↗
33. Functional supramolecular polymers for biomedical applications10.1002/adma.201402975 ↗
34. Supramolecular hydrogels with tunable chirality for promising biomedical applications10.1021/acs.accounts.0c00012 ↗
35. An injectable, self-healing hydrogel to repair the central nervous system10.1002/adma.201500762 ↗
36. Directing induced pluripotent stem cell derived neural stem cell fate with a three-dimensional biomimetic hydrogel for spinal cord injury repair10.1021/acsami.8b05293 ↗
37. The influence of hydrogel modulus on the proliferation and differentiation of encapsulated neural stem cells10.1016/j.biomaterials.2009.05.050 ↗
38. Two-dimensional-germanium phosphide-reinforced conductive and biodegradable hydrogel scaffolds enhance spinal cord injury repair10.1002/adfm.202104440 ↗
39. Computer modelling of spinal cord stimulation and its contribution to therapeutic efficacy10.1038/sj.sc.3100717 ↗
40. An injectable and self-healing hydrogel with controlled release of curcumin to repair spinal cord injury
41. Injectable nanoreinforced shape-memory hydrogel system for regenerating spinal cord tissue from traumatic injury10.1021/acsami.8b08929 ↗
42. When bio meets technology: biohybrid neural interfaces10.1002/adma.201903182 ↗
43. Spinal cord injury scarring and inflammation: therapies targeting glial and inflammatory responses10.1007/s13311-018-0631-6 ↗
44. Bioinspired hydrogel electrospun fibers for spinal cord regeneration
45. Microenvironment-responsive immunoregulatory electrospun fibers for promoting nerve function recovery10.1038/s41467-020-18265-3 ↗
46. Interaction of reactive astrocytes with type I collagen induces astrocytic scar formation through the integrin-N-cadherin pathway after spinal cord injury10.1038/nm.4354 ↗
47. Biomaterials. Electronic dura mater for long-term multimodal neural interfaces10.1126/science.1260318 ↗
48. Glial interfaces: advanced materials and devices to uncover the role of astroglial cells in brain function and dysfunction10.1002/adhm.202001268 ↗
49. Foreign body responses in mouse central nervous system mimic natural wound responses and alter biomaterial functions10.1038/s41467-020-19906-3 ↗
50. Materials for flexible bioelectronic systems as chronic neural interfaces10.1038/s41563-020-0679-7 ↗
51. Three-dimensional conductive scaffolds as neural prostheses based on carbon nanotubes and polypyrrole10.1021/acsami.8b16462 ↗
52. An NT-3-releasing bioscaffold supports the formation of TrkC-modified neural stem cell-derived neural network tissue with efficacy in repairing spinal cord injury
53. Long-distance growth and connectivity of neural stem cells after severe spinal cord injury10.1016/j.cell.2012.08.020 ↗
54. Microenvironment-responsive immunoregulatory electrospun fibers for promoting nerve function recovery10.1038/s41467-020-18265-3 ↗
55. Highly permeable DNA supramolecular hydrogel promotes neurogenesis and functional recovery after completely transected spinal cord injury10.1002/adma.202102428 ↗
56. Different functional bio-scaffolds share similar neurological mechanism to promote locomotor recovery of canines with complete spinal cord injury10.1016/j.biomaterials.2019.119230 ↗
57. cAMP response element-binding protein (CREB): a possible signaling molecule link in the pathophysiology of Schizophrenia10.3389/fnmol.2018.00255 ↗
58. A conductive dual-network hydrogel composed of oxidized dextran and hyaluronic-hydrazide as BDNF delivery systems for potential spinal cord injury repair10.1016/j.ijbiomac.2020.11.206 ↗
59. An anti-inflammatory peptide and brain-derived neurotrophic factor-modified hyaluronan-methylcellulose hydrogel promotes nerve regeneration in rats with spinal cord injury10.2147/IJN.S187854 ↗
60. Small molecules combined with collagen hydrogel direct neurogenesis and migration of neural stem cells after spinal cord injury10.1016/j.biomaterials.2020.120479 ↗
61. A functional scaffold to promote the migration and neuronal differentiation of neural stem/progenitor cells for spinal cord injury repair10.1016/j.biomaterials.2020.119941 ↗
62. Biomimetic 3D-printed scaffolds for spinal cord injury repair10.1038/s41591-018-0296-z ↗
63. Combinatorial therapies after spinal cord injury: how can biomaterials help?10.1002/adhm.201601130 ↗
64. Biomaterials used in stem cell therapy for spinal cord injury10.1016/j.pmatsci.2019.02.002 ↗
65. Anisotropic scaffolds for peripheral nerve and spinal cord regeneration
66. Wang · 2021
67. Biomimicking fiber platform with tunable stiffness to study mechanotransduction reveals stiffness enhances oligodendrocyte differentiation but impedes myelination through YAP-dependent regulation10.1002/smll.202003656 ↗
68. Accelerating bioelectric functional development of neural stem cells by graphene coupling: implications for neural interfacing with conductive materials10.1016/j.biomaterials.2016.08.019 ↗
69. Anisotropic alginate hydrogels promote axonal growth across chronic spinal cord transections after scar removal10.1021/acsbiomaterials.9b01802 ↗
70. Injured adult neurons regress to an embryonic transcriptional growth state10.1038/s41586-020-2200-5 ↗
71. Restoring cellular energetics promotes axonal regeneration and functional recovery after spinal cord injury10.1016/j.cmet.2020.02.002 ↗
72. Glial metabolic rewiring promotes axon regeneration and functional recovery in the central nervous system10.1016/j.cmet.2020.08.015 ↗