Hydrogels Derivatized With Cationic Moieties or Functional Peptides as Efficient Supports for Neural Stem Cells

Abstract

The increasing incidence of neurodegenerative diseases such as Alzheimer's or Parkinson's disease represents a significant burden for patients and national health systems. The conditions are primarily caused by the death of neurons and other neural cell types. One important aim of current stem cell research is to find a way to replace the lost cells. In this perspective, neural stem cells (NSCs) have been considered as a promising tool in the field of regenerative medicine. The behavior of NSCs is modulated by environmental influences, for example hormones, growth factors, cytokines, and extracellular matrix molecules or biomechanics. These factors can be studied by using well-defined hydrogels, which are polymeric networks of synthetic or natural origin with the ability to swell in water. These gels can be modified with a variety of molecules and optimized with regard to their mechanical properties to mimic the natural extracellular environment. In particular modifications applying distinct units such as functional domains and peptides can modulate the development of NSCs with regard to proliferation, differentiation and migration. One well-known peptide sequence that affects the behavior of NSCs is the integrin recognition sequence RGD that has originally been derived from fibronectin. In the present review we provide an overview concerning the applications of modified hydrogels with an emphasis on synthetic hydrogels based on poly(acrylamides), as modified with either cationic moieties or the peptide sequence RGD. This knowledge might be used in tissue engineering and regenerative medicine for the therapy of spinal cord injuries, neurodegenerative diseases and traumata.

Substrate-bound and soluble domains of tenascin-C regulate differentiation, proliferation and migration of neural stem and progenitor cells

“…The use of single domains instead of the total protein has many advantages for regenerative medicine due to controllable effects. In order to create the best possible natural environment in vitro , hydrogels were often used ( Caliari and Burdick, 2016 ; Glotzbach et al, 2020 ). These matrices can be tailored regarding stiffness, charge and biodegradability and can thereby mimic the in vivo setting of the cells ( Huebsch et al, 2010 ; Wade and Burdick, 2012 ; Stamm et al, 2022 ).…”

Cell-binding peptides on the material surface guide stem cell fate of adhesion, proliferation and differentiation

“…The development of synthetic ECM protein-derived peptides that mimic the biological and biochemical functions of natural ECMs should be beneficial for academic and clinical application. 1,[81][82][83][84][85][86] Peptides derived from or inspired by specific ECM proteins can work as agonists of each ECM protein receptor. Considering that most ECM proteins influence cell adhesion via integrin receptors, many peptides have been developed that bind to specific integrin receptors.…”

“…Various peptide sequences derived from mainly ECM protein molecules, which are used for coating or grafting on dishes, scaffolds, hydrogels, implants or nanofibers for adhesion, proliferation or differentiation of stem cells and their differentiated cells, are summarized in Tables S1, 1,72,87-114 S2 86,88,94,98,105 S3 83,97,98,108,[115][116][117][118][119][120][121][122][123][124] and S4 (ESI †). 86,100,101,110,[125][126][127][128][129][130][131][132][133][134][135][136] The peptides derived from growth factors are also summarized in Table S5 (ESI †). 105,[137][138][139][140][141][142][143][144] 2.…”

“…Various peptide sequences derived from mainly ECM protein molecules, which are used for coating or grafting on dishes, scaffolds, hydrogels, implants or nanofibers for adhesion, proliferation or differentiation of stem cells and their differentiated cells, are summarized in Tables S1, 1,72,87–114 S2 86,88,94,98,105 S3 83,97,98,108,115–124 and S4 (ESI†). 86,100,101,110,125–136 The peptides derived from growth factors are also summarized in Table S5 (ESI†). 105,137–144…”