Block copolymer micelles (BCMs) were prepared from amphiphilic diblock copolymers of poly(n-butyl acrylate) and poly(acrylic acid) partially modified with 2-hydroxyethyl acrylate. Radical polymerization of acrylamide in the presence of micellar crosslinkers gave rise to elastomeric hydrogels (BCM-PAAm) whose mechanical properties can be tuned by varying the BCM composition. Transmission electron microscopy (TEM) imaging revealed stretch-induced, reversible micelle deformation in BCM-PAAm gels. A model hydrophobic drug, pyrene, loaded into the micelle core prior to the formation of BCM-PAAm gels, was dynamically released in response to externally applied mechanical forces. The BCM-crosslinked hydrogels with combined strength and force-modulated drug release are attractive candidates for the repair and regeneration of mechanically-active tissues.

Amphiphlic block copolymers consisting of hydrophilic, poly(acrylic acid) randomly decorated with acrylate groups and hydrophobic, rubbery poly(n-butyl acrylate) self-assembled into welldefined micelles with an average diameter of ~21 nm. Radical polymerization of acrylamide in the presence of the crosslinkable micelles gave rise to hybrid, elastomeric hydrogels whose mechancial properties can be readily tuned by varying the BCM concentration.Hydrogels are macroscopic, polymeric networks that imbibe large amount of water. Due to their biocompatibility, tissue-like viscoelasticity and structural similarity to the native extracelluar matrices (ECM), hydrogels are widely used in tissue engineering and drug delivery applications. [1][2][3] Traditional hydrogels are derived from molecularly-dispersed, soluble precursors (monomers and multifunctional crosslinkers or macromers) that are randomly interconnected, lacking the structural complexity, mechanical integrity and functional diversity seen in the natural ECM. 4 Novel hybrid hydrogels with hierarchical structures and robust mechanical properties have been synthesized using organic or inorganic particles of nano or micron dimensions as the constituent building blocks or multifunctional crosslinkers. For example, nanocomposite hydrogels with unprecedented mechanical strength have been constructed by initiating radical polymerization from the surface of clay nanoparticles. The unique mechanical properties were attributed to the reduced fluctuation in the crosslinking density and the cooperativity of the polymer chains connecting the same clays. 5,6 Soft hydrogel particles have also been exploited as the multifunctional, microscopic crosslinkers. 7-10 Our group has created hyaluronic acid (HA)-based doubly crosslinked networks with densely crosslinked, nanoporous HA hydrogel particles covalently interconnected by a loose secondary network that is also HA-based. 11-15 Such hierarchically-structured hydrogels permit the controlled release of bone morphogenetic protein 2 (BMP-2) with reduced initial bursts over prolonged periods of time. 12 Block copolymer micelles (BCMs) are yet another class of microscopic, spherical objects consisting of a segregated hydrophobic interior and a stealth, hydrophilic corona that stablizes the assembled structure and interacts with the aqueous environment. 16 Unlike inorganic nanoparticles or covalently crosslinked hydrogel particles (microgels and nanogels), BCMs exhibit distinct core-shell structure, capable of sequestering hydrophobic molecules and modulating their release kinetics, thereby, extending their pharmacokinetics. 17 Although water-dispersed BCMs have been extensively explored as drug delivery vehicles, they have not been investigated as multifunctional, microscopic crosslinkers for the formation of elastomeric hydrogels with desirable pharmacological activities. We hypothesize that strategic integration of well-defined hydrophobic microdomains within the hydrogel matrix will not only provide a local depot for therap...