Methacrylated Silk Fibroin Hydrogels: pH as a Tool to Control Functionality

Abstract

The last decade has witnessed significant progress in the development of photosensitive polymers for in situ polymerization and 3D printing applications. Light-mediated sol−gel transitions have immense potential for tissue engineering applications as cell-laden materials can be crosslinked within minutes under mild environmental conditions. Silk fibroin (SF) is extensively explored in regenerative medicine applications due to its ease of modification and exceptional mechanical properties along with cytocompatibility. To efficiently design SF materials, the in vivo assembly of SF proteins must be considered. During SF biosynthesis, changes in pH, water content, and metal ion concentrations throughout the silkworm gland divisions drive the transition from liquid silk to its fiber form. Herein, we study the effect of the glycidyl-methacrylate-modified SF (SilkMA) solution pH on the properties and secondary structure of SilkMA hydrogels by testing formulations prepared at pH 5, 7, and 8. Our results demonstrate an influence of the prepolymer solution pH on the hydrogel rheological properties, compressive modulus, optical transmittance, and network swellability. The hydrogel pH did not affect the in vitro viability and morphology of human dermal fibroblasts. This work demonstrates the utility of the solution pH to tailor the SilkMA conformational structure development toward utility and function and shows the need to strictly control the pH to reduce batch-to-batch variability and ensure reproducibility.

Photocurable GelMA Adhesives for Corneal Perforations

“…The viscoelastic properties of GelMA bioadhesives were studied via oscillatory rheometry. Storage (G’) and loss (G’’) modulus represent the elastic and reversible response of the material and the viscous and irreversible rearrangement of its polymeric structure, respectively [ 58 , 59 ]. As shown in Figure 6 a,b, a positive correlation between G’ and the polymer concentration was observed.…”

Photocurable antimicrobial silk‐based hydrogels for corneal repair

“…In particular, SF membranes have been widely explored for corneal and retinal reconstruction due to their permeability and high transparency (90.6%) 24–26 . However, most studies concerning SF hydrogels are based on the protein self‐assembly into β‐sheet‐rich networks 27 . Despite providing strength to the hydrogels through physical crosslinking, these β‐sheet structures decrease the optical clarity and elasticity of the gels since the crystals block long‐range molecular displacements.…”

“…Despite providing strength to the hydrogels through physical crosslinking, these β‐sheet structures decrease the optical clarity and elasticity of the gels since the crystals block long‐range molecular displacements. Furthermore, the clinical application of these materials is limited due to the long gelation times and harsh environmental conditions used to induce β‐sheet formation (e.g., low pH, vortexing, or methanol treatments) 27 . Thus, chemically modifying SF via the addition of methacrylate side groups allows for the covalent crosslinking of SF hydrogels via photocrosslinking.…”

“…[24][25][26] However, most studies concerning SF hydrogels are based on the protein self-assembly into β-sheet-rich networks. 27 Despite providing strength to the hydrogels through physical crosslinking, these β-sheet structures decrease the optical clarity and elasticity of the gels since the crystals block long-range molecular displacements.…”

“…Furthermore, the clinical application of these materials is limited due to the long gelation times and harsh environmental conditions used to induce β-sheet formation (e.g., low pH, vortexing, or methanol treatments). 27 Thus, chemically modifying SF via the addition of methacrylate side groups allows for the covalent crosslinking of SF hydrogels via photocrosslinking. This provides increased mechanical strength but also allows for greater control of the in situ cross-linking kinetics.…”