Physical Interactions Strengthen Chemical Gelatin Methacryloyl Gels

Abstract

Chemically cross-linkable gelatin methacryloyl (GM) derivatives are getting increasing attention regarding biomedical applications. Thus, thorough investigations are needed to achieve full understanding and control of the physico-chemical behavior of these promising biomaterials. We previously introduced gelatin methacryloyl acetyl (GMA) derivatives, which can be used to control physical network formation (solution viscosity, sol-gel transition) independently from chemical cross-linking by variation of the methacryloyl-to-acetyl ratio. It is known that temperature dependent physical network formation significantly influences the mechanical properties of chemically cross-linked GM hydrogels. We investigated the temperature sensitivity of GM derivatives with different degrees of modification (GM2, GM10), or similar degrees of modification but different methacryloyl contents (GM10, GM2A8). Rheological analysis showed that the low modified GM2 forms strong physical gels upon cooling while GM10 and GM2A8 form soft or no gels. Yet, compression testing revealed that all photo cross-linked GM(A) hydrogels were stronger if cooling was applied during hydrogel preparation. We suggest that the hydrophobic methacryloyl and acetyl residues disturb triple helix formation with increasing degree of modification, but additionally form hydrophobic structures, which facilitate chemical cross-linking.

Expanding the Range of Available Isoelectric Points of Highly Methacryloylated Gelatin

“…The reason for the decline in G′ of GM5A5 compared to GM5 hydrogels was interpreted before by a reduction of physical interactions between gelatin derivative macromolecules due to the higher total degree of modification, as was also observed for GM hydrogels which were cured above the gelation point, like in this study . GM5 hydrogels assumingly contain a relevant concentration of relatively strong physical cross‐links in addition to chemical cross‐links, making the hydrogel stiffer than GM5A5 hydrogels and similarly stiff like GM10 hydrogels.…”

“…However, it has to be recognized that the DM not only has an impact on the cross‐link density of resulting hydrogels. Upon methacryloylation, many other relevant physico‐chemical properties are changed too, such as hydrophilicity, isoelectric point (IEP), or the ability to form physical hydrogels . For example, previous data suggested that, in fact, the hydrophilicity of GM‐based materials had an impact on releases of vascular endothelial growth factor .…”

Differentiation of physical and chemical cross-linking in gelatin methacryloyl hydrogels

“…Several studies investigated in how far the formation of both, physical and chemical cross-links, in GM hydrogels can act synergistically to improve mechanical properties. To this end, a sequential cross-linking procedure of GM hydrogels was applied by several authors, which increased the maximum strength 6 , compressive modulus 7 , 8 , storage modulus 9 , 10 and E-modulus distinctly 11 . During this sequential cross-linking procedure, the hydrogel precursor solutions were held at rather low temperatures, e.g .…”

Advanced gelatin-based vascularization bioinks for extrusion-based bioprinting of vascularized bone equivalents

“…It can also be used to tune the properties of the crosslinked gels by reducing the number of crosslinks at preserved biopolymer concentration: GMA is covalently integrated into the biopolymer network due to the presence of methacrylic groups. However, masking of amino-and hydroxy groups by acetylation results in less effective crosslinking due to sterical hindrance and impeded physical interactions 44 .…”

“…However, it has to be noted that lower degrees of modification lead to stronger physical gel formation if the processing temperature is below the gelation temperature. This is associated with helix-formation of G and GM molecules, more effective crosslinking and thus stiffer gels 44 . Consequently, the synthesis and handling of tailored GM derivatives requires much experience.…”