Biomimetic strain hardening in interpenetrating polymer network hydrogels

In this paper, we present the systematic development of mechanically enhanced interpenetrating polymer network (IPN) hydrogels with Young's moduli rivaling those of natural load-bearing tissues. The IPNs were formed by synthesis of a crosslinked poly(acrylic acid) (PAA) network within an end-linked poly(ethylene glycol) (PEG) macromonomer network. The strain-hardening behavior of these PEG/PAA IPNs was studied through uniaxial tensile testing and swelling measurements. The interaction between the independently crosslinked networks within the IPN was varied by (1) changing the molecular weight of the PEG macromonomer, (2) controlling the degree of PAA ionization by changing pH, and (3) increasing the polymer content in the PAA network. Young's moduli and the maximum stress-at-break of the swollen hydrogels were normalized on the basis of their polymer content. Strain hardening in the IPNs exhibited a strong dependence on the molecular weight of the first network macromonomer, the pH of the swelling buffer, as well as the polymer content of the second network. The results indicate that the mechanical enhancement of these IPNs is mediated by the strain-induced intensity of physical entanglements between the two networks. The strain can be applied either by mechanical deformation or by changing the pH to modulate the swelling of the PAA network. At pHs below the pK_a of PAA (4.7), entanglements between PEG and PAA are reinforced by interpolymer hydrogen bonds, yielding IPNs with high fracture strength. At pHs above 4.7, a “pre-stressed” IPN with dramatically enhanced modulus is formed due to ionization-induced swelling of the PAA network within a static PEG network. The modulus enhancement ranged from two-fold to over 10-fold depending on the synthesis conditions used. Variation of the network parameters and swelling conditions enabled “tuning” of the hydrogels' physical properties, yielding materials with water content between 58% and 90% water, tensile strength between 2.0 MPa and 12.0 MPa, and initial Young's modulus between 1.0 MPa and 19.0 MPa. Under physiologic pH and salt concentration, these materials attain “biomimetic” values for initial Young's modulus in addition to high tensile strength and water content. As such, they are promising new candidates for artificial replacement of natural tissues such as the cornea, cartilage, and other load-bearing structures.