An injectable hydrogel enhances tissue repair after spinal cord injury by promoting extracellular matrix remodeling

Abstract

The cystic cavity that develops following injuries to brain or spinal cord is a major obstacle for tissue repair in central nervous system (CNS). Here we report that injection of imidazole-poly(organophosphazenes) (I-5), a hydrogel with thermosensitive sol–gel transition behavior, almost completely eliminates cystic cavities in a clinically relevant rat spinal cord injury model. Cystic cavities are bridged by fibronectin-rich extracellular matrix. The fibrotic extracellular matrix remodeling is mediated by matrix metalloproteinase-9 expressed in macrophages within the fibrotic extracellular matrix. A poly(organophosphazenes) hydrogel lacking the imidazole moiety, which physically interacts with macrophages via histamine receptors, exhibits substantially diminished bridging effects. I-5 injection improves coordinated locomotion, and this functional recovery is accompanied by preservation of myelinated white matter and motor neurons and an increase in axonal reinnervation of the lumbar motor neurons. Our study demonstrates that dynamic interactions between inflammatory cells and injectable biomaterials can induce beneficial extracellular matrix remodeling to stimulate tissue repair following CNS injuries.

<p>An anti-inflammatory peptide and brain-derived neurotrophic factor-modified hyaluronan-methylcellulose hydrogel promotes nerve regeneration in rats with spinal cord injury</p>

“…[11][12][13] Biomaterial-based hydrogels have shown potential promise in restoring connectivity and function after SCI as drug delivery systems, by regulating microenvironment and by providing favorable substrates and paths for axonal regeneration. 31 Among these hydrogels, HAMC has been shown to be a flexible, localized drug delivery platform for several different therapeutic proteins in a sustained manner releasing at the injury site and supporting axonal extension across the lesion. In this study, a HAMC hydrogel was modified with the anti-inflammatory peptide KAFAK and BDNF and injected into a lesion region to suppress inflammation, promote the survival of existing neurons, and enhance axonal regeneration.…”

Evidence of superdiffusive nanoscale motion in anionic polymeric hydrogels: Analysis of PGSE- NMR data and comparison with drug release properties

“…[1][2][3] Although waterinsoluble due to strong physical or chemical cross-linking, hydrogels may retain large amounts of water, thus providing a versatile matrix with tissue-like mechanical properties. [4] Thanks to these features, hydrogels have found applications in the area of tissue engineering, [5] biosensors, [6,7] chemical analysis, [8] agriculture, [9] and drug delivery. [10][11][12][13][14][15] The latter application involves the use of hydrogels to deliver pharmaceuticals into the body, where they can be subsequently released in a controlled way.…”

Placenta mesenchymal stem cells differentiation toward neuronal-like cells on nanofibrous scaffold

“…25 Moreover, scaffold transplantation supported tissue repair by reducing the cavity size at the lesion site. 26 This work was expected to study appropriate stem cell and biomaterial interactions for neural tissue engineering. To date, numerous stem cells have been studied for neurological disorders, such as ESCs 5,27,28 and MSCs.…”