Advanced biomedical hydrogels: molecular architecture and its impact on medical applications

Abstract

Hydrogels are cross-linked polymeric networks swollen in water, physiological aqueous solutions or biological fluids. They are synthesized by a wide range of polymerization methods that allow for the introduction of linear and branched units with specific molecular characteristics. In addition, they can be tuned to exhibit desirable chemical characteristics including hydrophilicity or hydrophobicity. The synthesized hydrogels can be anionic, cationic, or amphiphilic and can contain multifunctional cross-links, junctions or tie points. Beyond these characteristics, hydrogels exhibit compatibility with biological systems, and can be synthesized to render systems that swell or collapse in response to external stimuli. This versatility and compatibility have led to better understanding of how the hydrogel's molecular architecture will affect their physicochemical, mechanical and biological properties. We present a critical summary of the main methods to synthesize hydrogels, which define their architecture, and advanced structural characteristics for macromolecular/biological applications.

Keywords: biological applications; biomedical applications; hydrogel reactions; hydrogels; mesh size; networks.

Figure 1.

Theoretical swelling predictions at comparable ionic strength conditions for an anionic network with: (1) $\stackrel{-}{M_C}$ = 2000, (2) $\stackrel{-}{M_C}$ = 4000, (3) $\stackrel{-}{M_C}$ = 6000, (4) $\stackrel{-}{M_C}$ = 8000, (5) $\stackrel{-}{M_C}$ = 10 000, (6) $\stackrel{-}{M_C}$ = 12 000 and (7) $\stackrel{-}{M_C}$ = 15 000. Reproduced with permission from Ref. [35]

Figure 2.

Theoretical swelling predictions at comparable ionic strength conditions for an anionic network with: (1) χ = 0.1, (2) χ = 0.3, (3) χ = 0.45, (4) χ = 0.6, (5) χ = 0.8 and (6) χ = 0.9. Reproduced with permission from Ref. [35]

Figure 3.

Theoretical swelling predictions at ionic strength (I) conditions for an anionic network with: (1) I =0.05, (2) I =0.1, (3) I =0.25, (4) I =0.5, (5) I =0.75, (6) I =1.0 and (7) I =2.0. Reproduced with permission from Ref. [35]

Figure 4.

Theoretical swelling predictions at comparable ionic strength conditions for an anionic network with: (1) pKa=2.0, (2) pKa=4.0, (3) pKa=5.0, (4) pKa=6.0, (5) pKa=7.0, (6) pKa=8.0 and (7) pKa=10.0. Reproduced with permission from Ref. [35]

Figure 5.

Equilibrium swelling ratio with increasing temperature of P(NIPAAm-co-Acrylamide)(left) P(NIPAAm-co-Acrylic acid)(right). Percentages are molar percentages of total monomer concentration in mol%. Equilibrium swelling ratio = (d/d₆₀)³. Acrylamide (AAm), acrylic acid (AA)

Figure 6.

Stimuli-responsive hydrogels. Chemical, physical and biological stimuli have been used to create environmentally responsive hydrogels for various biomedical applications

Figure 7.

Schematic representation of a swelling hydrogel microneedle array for transdermal drug delivery. Responsive hydrogels can be used to fabricate microneedle array systems for transdermal delivery of drugs (A). Upon the application of the stimulus, the swelling of the hydrogel microneedles allows the diffusion of drugs to epidermis and dermis, bypassing the stratum corneum and promoting absorption to blood stream (B)