Physical and biological regulation of neuron regenerative growth and network formation on recombinant dragline silks

Abstract

Recombinant spider silks produced in transgenic goat milk were studied as cell culture matrices for neuronal growth. Major ampullate spidroin 1 (MaSp1) supported neuronal growth, axon extension and network connectivity, with cell morphology comparable to the gold standard poly-lysine. In addition, neurons growing on MaSp1 films had increased neural cell adhesion molecule (NCAM) expression at both mRNA and protein levels. The results indicate that MaSp1 films present useful surface charge and substrate stiffness to support the growth of primary rat cortical neurons. Moreover, a putative neuron-specific surface binding sequence GRGGL within MaSp1 may contribute to the biological regulation of neuron growth. These findings indicate that MaSp1 could regulate neuron growth through its physical and biological features. This dual regulation mode of MaSp1 could provide an alternative strategy for generating functional silk materials for neural tissue engineering.

Three-dimensional hyaluronic acid hydrogel-based models for in vitro human iPSC-derived NPC culture and differentiation

“…33,34 Moreover, many studies have demonstrated that nerve-related cells could sense and respond to mechanical cues from the culture substrate. 35-37 Softer substrates have been found to promote the neuronal maturation and differentiation, 38,39 as well as neurite outgrowth and axon specification, 40 whereas astrocytes spread less and adhered poorly to softer gels. 41,42 Another study showed that neuronal cultures were more adherent to stiff gels and neurite length had no stiffness preference.…”

Intracellular Pathways Involved in Bone Regeneration Triggered by Recombinant Silk–Silica Chimeras

“…As such, improved insight into key features of these biomaterials that modulate the biological outcomes would be useful . Silk fibroin is useful as biomaterial due to its biocompatibility and outstanding mechanical and physical properties, as well as due to the potential for fine‐tuning properties through bioengineered sequence modification to incorporate diverse functional domains . Organic–inorganic biomaterial systems, such as silk–silica materials, provide suitable systems for the study of tissue regeneration.…”

Predicting rates of in vivo degradation of recombinant spider silk proteins

“…Numerous studies have analysed the biodegradation behaviour of B. mori silk fibroin in vivo (Cao and Wang, 2009), whereas the in vivo degradation rates of recombinant spider silks have not been studied exhaustively. Recombinant spider silk proteins have great potential for utility in a range of applications for biomedical needs, such as the regulation of neuron regenerative growth, bone regeneration, and drug and gene delivery as demonstrated mostly in vitro (Altman et al, 2003;An et al, 2015;Plowright et al, 2016;Spiess et al, 2010;Yigit et al, 2014). The initial degradation of implanted silk fibres, possibly due to macrophage endocytosis, has been demonstrated (Fredriksson et al, 2009).…”

“…Spider silk motifs and their structure–function relationships have been a focus of research for almost two decades, due to the outstanding mechanical and biophysical properties of these proteins (An et al, ; Ebrahimi et al, ; Tokareva et al, ). The potential for functionalized recombinant spider silks for biomedical applications such as regulation/induction of neuron growth and network formation, drug/gene delivery and bone regeneration has also been evaluated in vitro (An et al, ; Plowright et al, ; Spiess et al . , ; Yigit et al .…”