Resistance to Degradation of Silk Fibroin Hydrogels Exposed to Neuroinflammatory Environments

Abstract

Central nervous system (CNS) diseases represent an extreme burden with significant social and economic costs. A common link in most brain pathologies is the appearance of inflammatory components that can jeopardize the stability of the implanted biomaterials and the effectiveness of therapies. Different silk fibroin scaffolds have been used in applications related to CNS disorders. Although some studies have analyzed the degradability of silk fibroin in non-cerebral tissues (almost exclusively upon non-inflammatory conditions), the stability of silk hydrogel scaffolds in the inflammatory nervous system has not been studied in depth. In this study, the stability of silk fibroin hydrogels exposed to different neuroinflammatory contexts has been explored using an in vitro microglial cell culture and two in vivo pathological models of cerebral stroke and Alzheimer’s disease. This biomaterial was relatively stable and did not show signs of extensive degradation across time after implantation and during two weeks of in vivo analysis. This finding contrasted with the rapid degradation observed under the same in vivo conditions for other natural materials such as collagen. Our results support the suitability of silk fibroin hydrogels for intracerebral applications and highlight the potentiality of this vehicle for the release of molecules and cells for acute and chronic treatments in cerebral pathologies.

Permselectivity of Silk Fibroin Hydrogels for Advanced Drug Delivery Neurotherapies

“…Previously, we have found a marked resistance of SF hydrogels to degradation in saline solutions. 10 Under these pseudophysiological conditions (PBS) and along 7 days of analysis, we found that the SF hydrogel weight, and the secondary structure (βsheet content) quantified by ATR-FTIR, remained constant, and both parameters were only impaired by enzymatic digestion (proteinase K). This result agrees with previous observations, where the deswelling ratio of SF hydrogels (inferred from the analysis of weight) in PBS was negligible, 38 suggesting that the mechanism driving the delivery of molecules from pure SF hydrogels in PBS is unlikely to be due to progressive matrix erosion or changes in secondary structure.…”

“…At a confluence of approximately 80%, BV2 cells were polarized toward a proinflammatory phenotype using Escherichia coli O111:B4 lipopolysaccharide (LPS, Sigma-Aldrich, L3024) at 100 ng/mL, following the procedure described by Yonesi and colleagues. 10 Cells were divided into different groups: −LPS −TGF-β-1, +LPS − TGF-β-1, +LPS + TGF-β-1 (recombinant TGF-β-1 was used at 10 ng/ mL), and +LPS + TGF-β-1 released from SF hydrogels at two concentrations (2 and 6%) with two different release time periods (0−1 and 3−7 d). The control media (−LPS − TGF-β-1, +LPS − TGF-β-1, and +LPS + TGF-β-1) were composed of DMEM supplemented with 2% FBS, 1% P/S, and 2 mM l-Gln.…”

“…Silk fibroin (SF) is a prominent biomaterial that can be used for pharmacological administration because of two specific properties: poor immunogenicity and high stability with in vivo resistance to degradation even under inflammatory conditions. 10 In the context of the CNS, the limited but theoretically controllable degradability of SF can be exploited where either short 11 or extended 12 drug delivery times are required. Previous studies illustrate a wide range of possibilities of using SF in formats such as nanoparticles, films, fibers, microspheres, and hydrogels 13 to gradually deliver small 14 and large 15 molecules in various tissues.…”

Progress in Wound-Healing Products Based on Natural Compounds, Stem Cells, and MicroRNA-Based Biopolymers in the European, USA, and Asian Markets: Opportunities, Barriers, and Regulatory Issues

“…However, the specific requirements vary based on the classification of the woundhealing product. A real case is represented by silk fibroin, a 100% biocompatible natural protein, totally free of any dangerous particle/molecule, with intrinsic antioxidant and reparative properties [146][147][148]. A clear candidate for natural polymer-based class I woundcare products.…”

Progress in Wound Healing Products Based on Natural Compounds, Stem Cells and MicroRNA-Based Biopolymers in the European, USA, and Asian Markets: Opportunities, Barriers, and Regulatory Issues

“…However, the specific requirements vary based on the classification of the wound healing product. A real case is represented by silk fibroin, a 100% biocompatible natural protein, totally free of any dangerous particle/molecule, with intrinsic antioxidant and reparative properties [104] [105]. A clear candidate for natural polymer-based class I wound care products.…”