Phenylalanine Based Multicomponent Self-assembled Hydrogels With Enhanced Mechanical Properties For Biological Application

Supramolecular hydrogels(SMHs)till date remains one of the top contenders with regards to materials considered for biomedical applications.This is mainly due to their desirable properties,including biocompatibility,good water content,biodegradability,high porosity,response to external stimuli,and tunable mechanical properties.As a result,SMHs have been widely applied as biomaterials for cell culture,drug delivery,antimicrobial agents,and tissue regeneration.Most of the SMHs reported so far are homotypic(i.e.,involving only one kind of molecule),hence these materials possess some intrinsic weakness such as their inability to fully match and interact with the extracellular matrix(ECM)or their low mechanical properties,which is rather very common.In contrast,the conversion of SMHs through co-assembly to multicomponent self-assembling hydrogels(MSHs)provides a facile approach to significantly improve the weakness of these SMHs whiles introducing more desirable attributes.Based on the above research background,this thesis proposes the use of the concept of co-assembly,functionalization of biomolecules,and the design of a hydrazide system to enhance the mechanical properties of a C2 phenylalanine supramolecular hydrogel system.Additionally,antimicrobial activity was also introduced in the same system,which boosted their potential for use as biomaterials.This thesis titled ’phenylalanine based multicomponent self-assembled hydrogels with enhanced mechanical properties for biological application’ is made up of two main parts as follows:1.Mechanically Stable C2-Phenylalanine Multicomponent Hydrogels for Manipulating Cell AdhesionIn the quest to enhance the stability and mechanical properties of a derived C2-phenylalanine gelator(LPF),derivatives of the polysaccharide dextran were incorporated as additives to promote hydrogen bonding and π-π stacking with the gelator.Dextran was esterified to yield carboxymethyl dextran(CMDH),which was subsequently amidated to furnish amino dextran(AD).The resulting multicomponent hydrogels were denoted as LPF-ADx and LPF-CMDHx,where x represents the amount of AD and CMDH(mg).The LPF gelator interacted with the carboxyl and amino functional groups of the CMDH and AD,respectively,through hydrogen bonding and π-π stacking,resulting in mechanically stable hydrogels.Morphological studies revealed that the multicomponent hydrogels were formed as a result of dense,highly branched thin and broad fibers for LPF-AD and LPF-CMDH,respectively.Rheological studies confirmed the superiority of the multicomponent hydrogels over the neat hydrogel,where LPFCMDH3 exhibited the best mechanical properties with an improved elastic modulus of 11 654 Pa over 1518 and 140 Pa for LPF-AD4.5 and LPF,respectively.The adhesion and spreading behavior of NIH 3T3 fibroblast cells were significantly improved on the LPFCMDH3 substrate owing to their enhanced mechanical properties.The tuning of the mechanical properties of the therein hydrogels via the facile incorporation of biodegradable and biocompatible functionalized additives opens up avenues for strengthening the supposed weak supramolecular gelators,hence increasing their potential of being mainly employed in the field of tissue engineering.2.Antimicrobial Activity with Enhanced Mechanical Properties in PhenylalanineBased Chiral Multicomponent Hydrogels: The Influence of Pyridine Hydrazide DerivativesHydrazide derivatives are known to display a wide range of biological properties,including antimicrobial activities,hence making them desirable candidates for soft biomaterials.Thus through the co-assembly of two dicarbohydrazide molecules(pyridine-2,6-dicarbohydrazide(PDH)and(2,2′-bipyridine)-5,5′-dicarbohydrazide(BDH))and two phenylalanine gelators(L/DPF and B2L/D),we obtained multicomponent hydrogels that exhibited enhanced mechanical properties,chirality modulation,and antimicrobial activity.The co-assembled hydrogels(i.e.,L/DPF-PDH,L/DPF-BDH,B2L/D-PDH,and B2L/D-BDH)were obtained through hydrogen bonding and π-π stacking with some level of an interpenetrating network,as revealed by the structural characterization analysis.Mechanical properties were significantly improved,especially in the case of multicomponent gels involving BDH,with improved average elastic modulus(G′)values of 3430 and 3167 Pa for DPF-BDH and B2D-BDH(1:3,molar concentration)over 140 and 1680 Pa for DPF and B2 D gelators,respectively.The improved mechanical property was attributed to the enhanced π-π stacking and interpenetrating network due to the bipyridine group and its ease of forming fibrous precipitates in the process of heating and cooling to room temperature.PDH,on the other hand,was able to modulate chirality in the L/DPF gelator due to its more planar and less bulky nature and showed antimicrobial activity against Pseudomonas aeruginosa(Gramnegative).Interestingly,when PDH was co-assembled with the B2L/D gelator,the multicomponent gels exhibited antimicrobial activity against Staphylococcus aureus(Gram-positive)and P.aeruginosa(Gram-negative)by virtue of a synergistic effect of the gelator and the azomethine group of PHD.Therefore,by moving from bipyridine(BDH)to pyridine(PDH)as a core structure in the hydrazide molecules,the resulting multicomponent hydrogels exhibited desirable properties of antimicrobial activity and improved mechanical attributes.