Programming Stimuli-Responsive Behavior into Biomaterials

Abstract

Stimuli-responsive materials undergo triggered changes when presented with specific environmental cues. These dynamic systems can leverage biological signals found locally within the body as well as exogenous cues administered with spatiotemporal control, providing powerful opportunities in next-generation diagnostics and personalized medicine. Here, we review the synthetic and strategic advances used to impart diverse responsiveness to a wide variety of biomaterials. Categorizing systems on the basis of material type, number of inputs, and response mechanism, we examine past and ongoing efforts toward endowing biomaterials with customizable sensitivity. We draw an analogy to computer science, whereby a stimuli-responsive biomaterial transduces a set of inputs into a functional output as governed by a user-specified logical operator. We discuss Boolean and non-Boolean operations, as well as the various chemical and physical modes of signal transduction. Finally, we examine current limitations and promising directions in the ongoing development of programmable stimuli-responsive biomaterials.

Self‐healing injectable gelatin hydrogels for localized therapeutic cell delivery

“…Hydrogels are comprised of hydrophilic macromolecular polymeric networks of natural, synthetic, or mixed origin that retain a high water content while preserving their 3D structural integrity (Hoffman, ). Over the past many decades, these materials have been extensively employed in a variety of biomedical applications including for the delivery of therapeutic agents (Badeau, Comerford, Arakawa, Shadish, & DeForest, ; Badeau & DeForest, ; Hoare & Kohane, ; Youngblood, Truong, Segura, & Shea, ); to support 3D cell culture and dynamically direct cell fate (Caliari & Burdick, ; DeForest & Anseth, ; Healy, Rezania, & Stile, ; Shadish, Benuska, & DeForest, ; Tibbitt & Anseth, ); as scaffolds for tissue engineering and regenerative medicine (Drury & Mooney, ; Ifkovits & Burdick, ; Khademhosseini & Langer, ; Nicodemus & Bryant, ); and as components in biomedical devices, bioadhesives, and biosealants (Annabi, Yue, Tamayol, & Khademhosseini, ; Caló & Khutoryanskiy, ; Ghobril & Grinstaff, ). This growing list of applications stems directly from the materials' ability to be formulated in manners that are biocompatible, support nutrient diffusion, and offer tunable physiochemistry that mimics critical aspects of the native extracellular matrix (ECM; Seliktar, ).…”

Three‐dimensional cryogels for biomedical applications

“…Responsive cryogels undergo triggered changes when presented with specific environmental cues. These dynamic systems can leverage biological signals found locally within the body (known as bioresponsive systems) as well as exogenous cues (known as externally responsive systems) administered with spatiotemporal control (Badeau & DeForest, ). Bioresponsive systems react to intrinsic cues provided by the physiological environment such as temperature (Bencherif et al, ) or moisture (Shiekh et al, ), whereas externally responsive systems react to extrinsically administered cues such as electrical current (Vishnoi & Kumar, ).…”

“…Responsive cryogels are designed to degrade, swell, or dissociate from a therapeutic in response to a given stimulus to confine oxygen or drug release to specific cells, tissues, or organs within the body. Such site-specific therapeutic delivery can reduce or eliminate adverse effects arising from off-target distribution, enhancing the efficacy of conventional drugs (e.g., chemotherapies) while potentially rescuing the use of otherwise-flawed compounds with systemic toxicity, poor solubility, or untenable pharmacokinetics (Badeau & DeForest, 2019).…”

Stimuli-Responsive Materials for Tissue Engineering and Drug Delivery

“…They can be used on their own or as part of composites/hybrids in order to impart other functionality and tune their bulk properties, and their surface properties can be tailored through a variety of surface modification techniques [9][10][11]. The ability of a material to respond to different stimuli is related to their physico-chemical characteristics [12][13][14][15][16]. Taking advantage of such features with the recent developments in technology, we expect to be able to control the interaction between the biomaterial and its contents (e.g., cells, drugs) and surrounding environment in response to various stimuli (including but not limited to pH, temperature, redox potential, magnetic fields, and light) [12,13,17,18].…”