*#align(center)[#smallcaps[@thermosetting-materials-and-their-limitations[Chapter]]]* = #smallcaps[Thermosetting materials and their limitations] == Introduction The crosslinking of polymers to create thermosets was a crucial innovation in human history. The first polymer scientists, the ancient Olmec, were known to extract latex from _Castilla elastica_ trees and mix it with juice from the _Ipomoea alba_ vine to convert the latex into rubber as early as 1600 B.C.E. In fact, the name Olmec means \"rubber people\" in Nahuatl. Olmec derives from the Nahuatl Ōlmēcatl (singular) or Ōlmēcah (plural), which in turn is derived from ōlli, meaning \"natural rubber\", and mēcatl, meaning \"people.\"@coe2017 Archaeologists applied this name to the ancient culture before it was understood that the rubber people the Nahuas referred to were their contemporary neighbors in the Gulf Lowlands since the time of the Aztecs (more properly the Mēxihcah), not the ancient Olmecs of 2000 years prior. The name stuck, and it wonderfully illustrates the ingenuity of the Olmecs.@diehl2004 #figure(image("Images/RubberBall.png", width: 80.0%), placement: auto, caption: [Mesoamerican people were the first polymer scientists. An image of a rubber ball preserved in soil, from El Manatí, 1600 BC.@perez2024] ) The Olmec used this rubber to fashion elastic balls as heavy as 9 lbs for use in the mesoamerican ballgame. By varying the ratio of latex to juice, rubbers of varying elasticity could be produced suited to different needs. In addition to making game balls (@fig:rubberball), they would also make rubber soled sandals, watertight containers, and waterproof fabrics by impregnating fabric with the latex/juice mixture.@tarkanian2011@hosler1999@tarkanian2003@ricarte2024 This technology would spread to later mesoamericans, and eventually be noted by colonists. While this rubber was initially viewed as a curiosity by Europeans, some three and a half millennia later, this class of materials and its characteristic liquid to solid transition would come to underpin many developments in polymer science. Charles de la Condamine sent a sample of rubber to the Académie Royale des Sciences from Ecuador in 1736. La Condamine described rubber as originating from the milk, or as he called it \"latex,\" a term still in use today, of Hévé trees. Joseph Priestley coined the term \"indiarubber\" in 1770 after coming across a sample in an artist supply shop being sold to rub off pencil markings, eventually being shortened to just rubber.@wake1983 In 1844 Charles Goodyear rediscovered and received a patent for the process of vulcanization of natural rubber.@fisher1939@guise-richardson2010 In 1907 Leo Baekeland introduced the first commercial synthetic plastic, phenol-formaldehyde resin Bakelite, \"the material with a thousand uses.\"@baekeland1909 The molecular underpinnings of these materials was put forward by the \"father of polymer chemistry\" Hermann Staudinger in his groundbreaking paper \"On polymerization\" in 1920.@frey2020 Staundinger himself unintentionally supported his macromolecular hypothesis with cyclopentadiene crosslinked by Diels-Alder reactions, which would not be understood until 1928.@bruson1926@veldman2009@diels1928 The concept of gelation, the point at which polymers are crosslinked into a single molecule that spans a given volume element, was then first quantitatively described by Paul Flory in 1941,@flory1941 as well as a statistical mechanical treatment of crosslinked polymers in 1943.@flory1943@flory1943a The years since have seen momentous developments in the field of polymer chemistry enabling the synthesis of polymers, and by extension thermosets, by radical polymerizations with predictable molecular weights, low dispersity, and diverse functionality. Prior, free-radical polymerizations would produce \"dead\" polymers, those that cannot participate in further monomer addition, with heterogeneous degrees of polymerization. In 1956, Szwarc introduced the concept of a \"living\" polymerization,@szwarc1956 in which the propagating carbanion remains active even after all monomer is consumed. However, carbanions are easily destroyed by impurities and cannot be regenerated after their destruction. In 1993, Georges _et al._ demonstrated a \"living\" free-radical polymerization with a narrow dispersity using nitroxide-mediated polymerization (NMP).@georges1993 In 1995, Wang & Matyjaszewski and Kato _et al._ independently introduced atom transfer radical polymerization (ATRP).@kato1995@wang1995 In 1997, the third of the three major reversible deactivation radical polymerizations (RDRP), reversible addition-fragmentation chain transfer (RAFT) polymerization, was introduced by Chiefari _et al._@chiefari1998 All three methods produce polymers with stable, dormant end groups that can subsequently be reinitiated. Suddenly chemists and engineers had several techniques at their disposal for easily preparing well defined polymers with low dispersity, a variety of functional groups, and with controlled architectures, enabling the production of ever more sophisticated thermosets. Polymer thermosets have since come a long way, rising to dominate much of our world. By adjusting the crosslink density, as the ancient Olmecs discovered, and chemical structure the properties of the final material can be tuned to suit a whole host of applications. Additionally, the crosslinked nature of thermosetting polymers impart solvent resistance, thermo-mechanical resistance, and chemical, wear, and creep resistance.@alabiso2020 The combination of these properties, as well as their light weight, have made them irreplaceable in high performance environments such as aerospace@ma2023 and renewable energy.@wang2024 With applications further ranging the gamut from soft materials like touch sensors,@reynolds2020 tissue mimicking hydrogels for cell culture,@jansen2022 re-processable pressure sensitive adhesives,@arrington2018 to high-modulus materials like printed circuit boards,@lee2016 protective coatings,@kathalewar2014 structural composite materials,@li2022 and many more too numerous to list, crosslinked materials have become completely irreplaceable. == Mechanoresponsive Thermosetting Materials === Introduction Until recently, virtually all thermosetting materials have been crosslinked, a.k.a. cured, by either temperature, radiation, or simply spontaneous reactions upon mixing. These techniques generally induce the formation of covalent bonds between polymer chains or the polymerization of small multifunctional molecules to form a three-dimensional network structure. Each approach to crosslinking has distinct advantages and disadvantages. Thermal curing involves using high temperatures to drive forward crosslinking reactions that either occur very slowly at room temperature or not at all.@engels2004 Thermal curing is well suited for large samples, but is very energy intensive and requires an understanding of the thermal properties of the substrate to drive full conversion.@abliz2013 Spontaneously thermosetting materials are cured by mixing, often by step polymerization, however this relinquishes spatiotemporal control over gelation and can make applying the mixture difficult. Radiation-based curing, often achieved through free radical polymerization (FRP) with photosensitive radical initiators, can be very fast and energy efficient, but the penetration depth of light or electrons is limiting and the byproducts of radical initiators can be toxic. Reaching full cure is often not possible, and further thermal curing is required in addition to radiation exposure.@raghavan2000 Additionally, radiation curing cannot be conducted through opaque materials, limiting their application space. As such, there is a need to develop new methods of curing thermosets that can be conducted through opaque materials, with lower energy cost, and with spatiotemporal control. Nature has had eons to develop and refine exquisite molecular machinery that puts even the very best of modern chemistry and engineering to shame. Looking across the natural world, one will find it replete with stimuli responsiveness. Retinal based photosynthesis captures and stores the energy of light through cis-trans isomerization coupled to ion pumps,@ernst2014 and chlorophyll based photosynthesis stores the energy of light through electron transfer.@vishniac1958 It's worth noting that chlorophylls have been harnessed by polymer chemists to induce polymerization with light.@shanmugam2015 Methods of sensing oxygen content, temperature, and pH just to name a few more, are crucial for survival.@kumar2007@damaghi2013@tan2016 More rare in synthetic materials, but common in nature, is constructive responsive to mechanical forces.@eyckmans2011 Natural materials can respond to mechanical force constructively by polymerizing under deformation, as is the case for fibronectin.@gee2008@gee2013@klotzsch2009@mao2005 Under stain, the tertiary structure of fibronectin partially unravels, exposing cryptic binding sites that then participate in mechanically-induced polymerization and fibril formation. Mechanical force can also change gene expression. Extracellular mechanical forces can be propagated from focal adhesions through the cytoskeleton and LINC complex directly to chromatin, causing chromatin stretching and mechanosensitive gene expression.@dupont2022 Taking mechanically-induced unfolding of proteins and protein complexes as inspiration, our lab and others have developed gels that stiffen in response to applied cyclic compression by forming interchain disulfide bonds and thioethers.@lee2016a@tran2017@sonu2023 However, these gels are not currently well suited for adhesives or coatings due to the difficulties of applying solid materials to substrates. The development of liquid pre-cursor solutions that can crosslink via mechanical perturbation for easy solution spread across a chosen substrate would transform a range of industries where reliance on thermal, UV, and electron beam curing makes on-demand curing of adhesives and post-crosslinking strengthening of coatings difficult. === Sonication as a tool for applying targeted force Imparting force onto polymer chains is commonly achieved when the polymer is in a fluid state, either as a melt, a glassy liquid, or a solution. When studying polymers, shear is most often applied, and shear is applied through the oscillations of parallel plates, extrusion, or ultrasonic waves. In solution, linear polymers exist in a solvent dependent coiled state (a Gaussian coil) in which the end-to-end distance is much smaller than the contour length of the polymer (the length of the polymer at maximum extension).@rubinstein2003 When polymer solutions flow rapidly near a surface (as in the case of parallel plate rheology or extrusion through a narrow opening)@graham2011@boger1987 or are sonicated,@akbulatov2017 the shear forces cause this coiled structure to be disrupted. Commonly, and perhaps intuitively, it is thought that tension along the polymer backbone reaches a maximum at the chain center, at which point enough force is accumulated along the backbone such that mechanochemistry can occur. Models have been proposed based on this, one suggesting polymers fully stretch, with the end-to-end distance reaching the contour length (overstretched chain), or there is only partial unfolding of the polymer coil based around the chain center (overstretched segment, @fig:dynamicchain).@diesendruck2023 More recent work has suggested instead that polymer unfolding in response to shear force may instead be a dynamic process in which chain unfolding begins at the polymer ends, with the overstretched segment propagating and growing along the backbone until it is sufficiently strained to react mechanochemically.@oneill2023 #figure(image("Images/DynamicChain.png", width: 80.0%), placement: auto, caption: [ Dynamic overstretched chain model. Overstretched segments of polymer (red) propagate and grow along the backbone in response to cavitations caused by ultrasound. ] ) In the case of polymers flowing near a surface, the shear forces are driven by physically pushing a solution through an opening or moving a surface rapidly parallel to the liquid. In the case of sonication, force is generated through the application of ultrasound, which has been known to degrade polymer chains since 1939.@schmid1939 Ultrasound consists of high frequency sound waves, with the 20 kHz to 2 MHz regime being \"destructive\" ultrasound necessary for for sonochemical and mechanochemical transformations. Sound waves compress and expand liquids as they are ultrasonicated, in places causing distances that are large enough to \"break\" the liquid and form cavitation bubbles. These bubbles expand over several cycles of compression and rarefaction until they grow large enough to become unstable, at which point it collapses. The collapse generates strong pressure gradients, causing a shear force as the surrounding area is pulled towards the center of the implosion, affecting an area on a micrometer scale.@paulusse2006 These pressure gradients and resultant shear forces are commonly cited as the source of mechanochemical transformations of polymers in response to sonication. Sonication as a means to drive chemical changes offers advantages over radiation and thermal curing. For one, sonication can be focused through opaque materials.@kuang2023 Additionally, sonication consumes up to 25,000 times less energy than thermal curing processes.@biswal2023 However, sonication also generates heat, and the strong shear forces generated can cause chain scission events. === Mechanophores The field of polymer mechanochemistry has its origins in papers published by none other than Staudinger himself in the 1930s describing the reduction in molecular weight of polystyrene samples after ball milling.@staudinger1930a@staudinger1930@staudinger1934 The idea that this decrease in molecular weight was a direct result of shear forces causing homolytic C--C bond cleavage was put forward by Kauzmann and Eyring in 1940,@kauzmann1940 and then confirmed by Tabata _et al._ by studying ultrasonicated polymers with electron paramagnetic resonance in 1980.@tabata1980 That same year, Encina _et al._ demonstrated that polymers containing randomly distributed peroxide linkages preferentially undergo scission at O--O bonds over C--C bonds.@encina1980 In 2005, Berkowski _et al._ took the field a step further from random cleavages to targeted cleavages by demonstrating the preferential cleavage of chain-centered azo linkages.@berkowski2005 Around this time at an Army Research Office workshop on polymer mechanochemistry, Caster suggested the name \"mechanophore\" for functional groups that undergo chemical transformations in response to mechanical force.@li2015 The field grew after Hickenboth _et al._ published on biasing reaction pathways with mechanical force,@hickenboth2007 and while Woodward and Hoffman may have been certain there would never and could never be exceptions to their pericyclic selection rules,@woodward1969 exceptions would indeed arise. In this case, Hickenboth et al. conclusively showed that both cis and trans isomers of polymer chain centered 1,2-diacetoxybenzocyclobutene undergo a disrotary and conrotary, respectively, electrocyclic ring opening to form the E,E isomer of ortho-quinodimethide in response to mechanical force, in direct violation of the Woodward-Hoffman rules (@fig:HickenbothFig). This of course caused an explosion of interest in polymer mechanochemistry, and mechanophores have since been developed for several applications including strain sensing,@raisch2018 catalysis,@groote2013 and of course, crosslinking.@wang2015@groote2014@ramirez2013 Whereas previously mechanochemical reactions resulted in the breaking and weakening of polymer chains, now there are ways to link chains together to form crosslinked solids through mechanical force.@willis-fox2018@ghanem2021 #figure(image("Images/HickenbothFig.png", width: 100.0%), placement: auto, caption: [ Cartoon depiction of the predicted reaction pathways of 1,2-diacetoxybenzocyclobutene. Reproduced from Hickenboth et al. @hickenboth2007 ] ) === Limitations A popular route to achieve mechanochemical transformation of polymeric materials is to employ mechanophores. These motifs are specially tailored weak bonds that can be incorporated into polymer chains that transform into predictable products upon application of force.@brantley2013@kean2013@kean2015@jung2021 However, mechanophore-mediated strengthening of polymeric materials remains a challenging approach for mechanical force curing of polymers for several reasons. First, these moieties typically are restrained by limited incorporation in polymer chains resulting in low crosslinking densities upon activation. Further, conversion of mechanophores is often low, resulting in poor activation even with good incorporation.@lloyd2023 The chemistry necessary to implement mechanophores is complex in its design and execution, making the approach inaccessible. These moieties are not commercially available. Typical means of mechanochemical activation tend to introduce significant and destructive bond scission, which one must be careful to avoid by selecting appropriate force regimes.@grandbois1999@garnier2000 Chapter 2 describes my approach using off the shelf chemistries to produce materials that are constructively sensitive to mechanical force with high conversions. == Polymer architecture and bulk properties === Introduction Likely the first report of controlled polymer architecture and the first report of comb polymers arrived in the 1944 when Rehberg and Fisher prepared high $n$-alkyl polyacrylates.@rehberg1944 This was followed by Kaufman _et al_. 1948 who observed that higher $n$-alkyl polyacrylates show sidechain crystallization.@kaufman1948 These comb-like polymers were defined as polymers where each monomer bears its own polymer sidechain@plate1974, though in modern polymer science they can be defined as polymers were only some monomers bear their own polymer sidechains. Another early example of controlled polymer architecture, block polymers, arrived in 1951 when Vaughn et al. published a study of new nonionic surfactants, including block copolymers of poly(ethylene oxide) (a.k.a. poly(ethylene glycol) (PEG)) or poly(propylene oxide).@vaughn1951@mankowich1954 Known commercially as poloxamers, this particular class of polymers remains highly studied and useful examples of molecular design to this day.@surve2024 Living polymerizations would be described just a few years later in 1956,@szwarc1956 which would subsequently enable the facile preparation of whole new classes of block polymers as well as far more exotic examples of molecular architecture. Living polymerizations would enable far more exotic examples of polymer architecture compared to linear polymers.@hadjichristidis2006 In the absence of impurities, the carbanion active site remains intact even at full monomer conversion, meaning a wealth of facile chain end modifications were now within reach. In 1984, Rempp et al. published the first synthesis of macromonomers by modification of the carbanion.@rempp1984@rempp1985 This would soon be followed up by the first publications on what are now called bottlebrush polymers by Tsukahara et al. in 1989@tsukahara1989 through a combination of living anionic polymerization and FRP, and then a more detailed investigation into their physical properties in 1994.@tsukahara1994 At this point however, the preparation of bottlebrush polymers was still quite difficult. The free radical homopolymerization of $omega$-methacryloyl functionalized polymers has several limitations, chiefly among them the dilute nature of the methacrylate functional group.@muehlebach2003 It would take further progress in polymer synthesis to unlock new routes to bottlebrush polymers, with ring opening metathesis polymerization and RDRPs in particular enabling the routine synthesis of cylindrical molecular brushes with a huge array of monomers. === Comb polymers Polymer thermosets have several advantages over their small molecule counterparts, including shortened gelation time due to less reactions needing to take place to achieve a volume spanning element, tunable architecture and phase behavior inherited from the polymer architecture, and the formation of stable one-pot latexes. Properties of the final crosslinked material are often inherited from the properties of the constituent linked polymers. For example, the fibrillar structure of collagen I results in strain stiffening behavior,@motte2013 and synthetic block copolymers exhibit microphase separation affecting vitrimer processing,@lessard2020 allowing for additional handles to control the properties of these crosslinked networks. Comb polymers are no exception to this, and the vast design space of these branched polymers allows for the preparation of polymers with interesting phase behavior and conformation. For example, synthesizing reactive comb polymers with easily crystallizable sidechains allows for the preparation of crosslinked thermosets containing crystalline domains in the cured product,@claesson2004@lorenzana2024 increasing it's toughness and modulus. Their high molecular weight allows for quick gelation times,@reynolds2020 consequently requiring less energy to cure. The low viscosity of comb polymer solutions and melts further reduces the energy needed to process polymer combs,@kong2021 and can be used to modify the viscosity of polymer blends.@2009 Moreover, by adjusting the composition and stiffness of the backbone, combs can be used as next-generation compatibilizers between immiscible polymer phases@dong2015 as well as tough networks and adhesives on their own.@zhang2016a@ohnsorg2024 === Bottlebrush polymers Formally defined as a subset of comb polymers, bottlebrush polymers are a class of polymers characterized by the presence of densely grafted side chains along a main backbone. These polymers can be described using three variables: the degree of polymerization between each graft $(n_g)$, the degree of polymerization of the main backbone $(n_(b b))$, and the degree of polymerization of the side chains $(n_(s c))$. The crowding parameter $(ϕ)$ is defined by $n_g$ and $n_(s c)$, and provides a mathematical definition for the transition from loosely grafted comb to densely grafted bottlebrush polymer (@fig:BottlebrushPhases). Above a threshold $ϕ$, the intense sterics of the densely grafted side chains increase the rigidity of and creates tension along@panyukov2009 the main backbone, causing the brush to adopt a wormlike morphology, and preventing polymer chain entanglements.@reynolds2020@sheiko2019@xie2019 This lack of polymer entanglements, evidenced by the zero shear viscosity deviating from $eta_0 tilde.op N^3.4$,@dalsin2014 is most often exploited to create super soft additive free elastomers. #figure(image("Images/BottlebrushPhase.svg", width: 100.0%), placement: auto, caption: [ Phase diagram for methacrylic bottlebrush polymers. Depending on $n_(s c)$, $n_(b b)$, and $n_g$ polymers with grafted sidechains can be categorized either as combs, bottlebrushes with rigid sidechains (RSC), stretched sidechains (SSC), or stretched backbones (SBB). ] ) Perhaps owing to their recent discovery, bottlebrush polymers as a class of materials are relatively unexplored, and as a consequence poorly understood. Models of describing the conformation of individual bottlebrushes@liang2018 and their melt behavior@liang2017 have been put forward, but these almost always describe bottlebrush polymers with homopolymer side chains. Only recently has the self assembly of bottlebrush block polymers in melt@dalsin2015 and solution@pan2021 been described. Bottlebrush polymers with more complicated architecture, such as block polymer sidechains (core-shell architecture) are poorly described. Relatively well understood parameters of linear polymers such as the Flory-Huggins polymer-solvent interaction parameter, $χ$, are far less well modeled for bottlebrush architectures, and only grow more difficult to understand when secondary interactions like hydrogen bonding are taken into account.@bates2017 Predicting the Kuhn lengths and persistence lengths of bottlebrush polymers as well remains a challenge, with experimental and theoretical studies offering contradicting conclusions.@dutta2019@lecommandoux2002@feuz2005@yethiraj2006@clarke2024 Studies of bottlebrush polymers composed of reactive monomers capable of participating in crosslinking are almost completely absent, and only studied as additives to other thermosetting resins.@moon2021 Some samples of bottlebrush mechanochemistry have been published, though these have very low functionality, only bearing mechanophores at the backbone-arm junction.@noh2021@peterson2021 Given the unique morphology, lack of entanglements, large size, and potential for phase separation and microdomain formation, bottlebrush polymers present an opportunity to design high performance thermosetting materials. Already they have found applications in fields such as touch sensors,@reynolds2020 pressure sensitive adhesives,@arrington2018@maw2023 solvent free elastomers,@daniel2016 nanocapsules for drug delivery,@huang2011 and antifouling coatings,@yoshikawa2022 but highly crosslinked bottlebrushes have not been studied to date. === Highly crosslinked combs Chapter 3 details my work preparing robust, highly crosslinked comb polymers. When designing these materials, I imagined a polymer of extremely high molecular weight with a high density of crosslinkable sites. The final crosslinked material should be a high modulus, insoluble solid. To achieve this, I selected GMA as the reactive monomer, which bears a pendent epoxide ring capable of participating in nucleophilic additions to create intermolecular crosslinks. To investigate the spatial effects of crosslinks on toughness of the final thermoset, I identified BMA as an attractive copolymer for GMA to act as a small spacer and internal plasticizer. My approach to identifying a highly crosslinkable, tough combs was to first synthesize a suite of polymers of different architectures: linear and comb, homopolymer and copolymer, and random and block. Then, I investigated crosslinking these polymers with succinic acid, a small di-carboxylic acid, to create a tightly crosslinked network. Finally, we investigated the toughness of the resultant materials. Comb polymers with random sidechains produced crosslinked materials with higher modulus and toughness than polymers with block or homopolymer sidechains. == Hydrogel preparation === Introduction Whereas the previously discussed thermosets are designed to be dispersed in organic solvents or used neat, polymers can also be designed to be hydrophilic. When crosslinked, hydrophilic polymers form hydrogels that swell in the presence of water but do not dissolve. Mammalian, plant, and bacterial cells are known to synthesize, secrete, and assemble a mix of proteins, proteoglycans, and sugars to create extracellular matrices (ECM).@flemming2010@mouw2014@seifert2010 The ECM in turn provides both chemical and mechanical cues to cells,@ringer2017 directing cell fate, morphology, and phenotype.@lantoine2016@wei2022@peyton2008@yeung2005 Hydrogels have for decades attracted researchers due to their 3D network structure closely mimicking that of natural ECM, with the first cell encapsulation being demonstrated in 1980.@lim1980 Synthetic analogues in particular have been an area of intense focus as means to more precisely control the encapsulated cell environment compared to natural products, which often show large lot-to-lot variability.@kozlowski2021 The first report of synthetic hydrogels as we currently know them appeared in 1958 in a publication by Danno in which poly(vinyl alcohol) in aqueous solution was crosslinked under gamma irradiation to form an insoluble gel.@danno1958 This was soon followed up by Wichterle and Lím when they polymerized 2-hydroxyethyl methacrylate in the presence of ethylene glycol dimethacrylate to create water swollen gels for use as contact lenses,@wichterle1960 which is still the basis for many contact lens formulations to this day.@teichroeb2008@nicolson2001 In 1970 PEG hydrogels were prepared by irradiation with gamma and electron radiation,@stafford1970@king1970 and PEG gels started to attract attention due to their favorable biocompatibility and non-fouling properties.@zhu2010 The chain end alcohols of PEG have since been functionalized with methacrylates for the preparation of gels by FRP,@tanaka1977 isocyanates@graham1984 and succinimidyl esters,@sakai2008 and a variety of chemistries capable of participating in Michael-type additions.@jansen2018@buwalda2014@metters2005 === Mixing and light Cell encapsulation techniques within hydrogels must be both rapid enough to prevent cell settling and cytocompatible.@caliari2016 Free radicals and high energy UV light are well known to cause cellular damage,@chen1999 though UV photoinitiators and vinyl monomers are used to encapsulate cells. Michael-type reactions are commonly used as bio-orthoganol methods of crosslinking hydrogels, and are useful for their ability to incorporate bioactive peptides by exploiting Michael donors present in amino acids, such as the thiol in cysteine.@peyton2006@galarza2020 Additionally, the A--B type crosslinking by Michael-type reactions often produces highly homogenous gels.@sakai2008 However, the reaction kinetics vary amongst chemistries used, and tuning the kinetics within the framework of physiological conditions can be a challenge, not to mention relative difficulties of biology labs synthesizing functional PEG not commercially available.@rizzo2023@paez2020 Moreover, Michael-type reactions most often do not allow for spatiotemporal control, meaning the homogeneity of the network is dependent on the reaction kinetics.@darling2016 === Reversible deactivation radical polymerizations RDRPs, by contrast, are rarely used in biomedical applications. The reasons for this vary, though in general, RDRPs are slower than FRPs, are sensitive to trace oxygen and are traditionally thermally initiated. These aspects make them unsuitable for polymerization in the presence of living cells. ATRP most commonly requires cytotoxic metal halide salts among several other reactants, although there are efforts to replace them with powerful organic reducing agents capable of homolytically cleaving carbon-halogen bonds.@corbin2022 NMP is traditionally extremely slow@grubbs2011 and has serious challenges with monomer compatibility.@guegain2015 RAFT requires tuning of the chain transfer agent to match the desired monomers@keddie2012 and is expensive to source. Despite all of this, RDRPs offer significant benefits over FRPs. FRPs produce gels with heterogeneous networks due to unavoidable termination, slow initiation relative to propagation, and slow segmental relaxation relative to chain growth in the gel phase.@lovestead2003@gu2020 FRPs commonly overcome inhibition from oxygen by overwhelming it with excess radical species, to the detriment of cytocompatibility. In contrast, RDRPs are able to produce highly homogenous gel networks due to their high initiation relative to propagation rates and low radical concentrations which minimize irreversible termination events as well as minimizing cellular damage. Furthermore, the reversible nature of RDRPs enable living gels@peyton2023 by postpolymerization modifications of gels.@bagheri2021 Chapter 4 of this dissertation will harness RDRPs using the photoiniferter process to rapidly polymerize and crosslink biocompatible hydrophilic monomers. == Hypothesis Current methods of curing thermosets are limited in their applications and cannot be applied in all circumstances. This is particularly true of biomedical applications, where conditions must be kept within the strict confines of physiological conditions. I hypothesize that grafting pendent PEG chains along the main polymer backbone will provide a facile way to install mechanosensitivity by sterically shielding reactive sites, enabling on demand gelation. Furthermore, I hypothesize densely grafted bottlebrush polymers with reactive side chains can be prepared as high-modulus, tough thermosets by adjusting the sidechain architecture to favor intermolecular crosslinking. Finally, I hypothesize that rapid fragmentation of xanthogen disulfides in response to visible light will enable rapid preparation and crosslinking of biocompatible hydrogels. I predict that that this work will enable new methods of bottom up design of thermosetting materials. == Objectives The following were the objectives for this dissertation: + Optimize a library of sparsely grafted copolymers carrying reactive pendent groups and methoxy poly(ethylene glycol) (PEG) grafts for use as mechanically activated crosslinkable materials; + Synthesize and characterize novel mechanically responsive core-shell bottlebrush polymers furnished with a high density of crosslinkable pendant groups; + Develop a method to rapidly crosslink hydrogels in response to light in the visible range. == Significance I have identified a new path for easy installation of mechano-responsiveness into synthetic polymers using off-the-shelf chemistries and materials. Further, I have developed strategies to combat intramolecular crosslinking in densely grafted reactive polymers. Finally, I have designed a method of rapidly synthesizing and crosslinking biocompatible hydrogels. Overall, this dissertation presents easy and accessible approaches to designing strain sensitive polymers as well as preparing hydrogels by reversible deactivation radical polymerization that will enable more rapid translation of mechanosensitive polymers and tailor-made hydrogels. Additionally, this dissertation provides new strategies for preparing tough thermosets from high molecular weight resins.