Abstract
Advanced cell therapies require robust delivery materials and silk is a promising contender with a long clinical track record. Our aim was to optimise self-assembling silk hydrogels as a mesenchymal stem cell (MSC)-support matrix that would allow future minimally invasive brain application. We used sonication energy to programme the transition of silk (1–5% w/v) secondary structure from a random coil to a stable β-sheet configuration. This allowed fine tuning of self-assembling silk hydrogels to achieve space conformity in the absence of any silk hydrogel swelling and to support uniform cell distribution as well as cell viability. Embedded cells underwent significant proliferation over 14 days in vitro, with the best proliferation achieved with 2% w/v hydrogels. Embedded MSCs showed significantly better viability in vitro after injection through a 30G needle when the gels were in the pre-gelled versus post-gelled state. Silk hydrogels (4% w/v) with physical characteristics matching brain tissue were visualised in preliminary in vivo experiments to exhibit good space conformity in an ischemic cavity (intraluminal thread middle cerebral artery occlusion model) in adult male Sprague-Dawley rats (n = 3). This study informs on optimal MSC-hydrogel matrix conditions for minimally invasive application as a platform for future experiments targeting brain repair.
Highlights
Cell-based therapy, especially the use of stem cells, is one of the main approaches that successfully promotes neurorestoration of function and improves outcomes such as angiogenesis, neuroprotection, immune response and modulated inflammation in experimental models[1]
Emerging evidence suggests that extracellular matrix (ECM) tissue specificity is important for obtaining the desired treatment outcome[21], so ECM extracts from tumours or tissues that are unrelated to the brain are likely to require further optimisation
Silk self-assembly was initiated by sonication energy (Fig. 1a) and the visible kinetics of silk nanocrystal formation was monitored by light scattering (Fig. 1b)
Summary
Cell-based therapy, especially the use of stem cells, is one of the main approaches that successfully promotes neurorestoration of function and improves outcomes such as angiogenesis, neuroprotection, immune response and modulated inflammation in experimental models[1]. One key issue hindering the translation of cell therapies to the clinic is the lack of suitable cell delivery technologies that can support cell survival and provide transplanted cells with the necessary cues to perform their intended restorative functions such as trophic factor production[3,4] These support and cueing functions are normally provided by the extracellular matrix (ECM), which is critical for the storage and presentation of growth and signalling factors and the provision of cell adhesion sites to guide and promote proliferation and survival. Basement membrane and tunica propria ECM isolated from porcine urinary bladder is emerging as an interesting alternative to existing ECM preparations[19,20] All these systems have shown promise for brain repair, but these materials continue to show limitations. The development of biomimetic hydrogels (e.g. peptides, peptoids) and biohybrid hydrogel systems is promising, these systems still require significant research efforts to yield self-assembling hydrogels with sufficiently robust mechanical properties, in vivo biocompatibility and the desired performance[12,23]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
