PhD-Dissertation / Chapter1.typ

*#align(center)[#smallcaps[@thermosetting-materials-and-their-limitations[Chapter]]]*
= #smallcaps[Thermosetting materials and their limitations]
<thermosetting-materials-and-their-limitations>

== Introduction
<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]
)
<fig:rubberball>

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
<mechanoresponsive-thermosetting-materials>
=== Introduction
<introduction-1>
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
<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.
  ]
)
<fig:dynamicchain>

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
<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
  ]
)
<fig:HickenbothFig>

=== Limitations
<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
<polymer-architecture-and-bulk-properties>
=== Introduction
<introduction-2>
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
<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
<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).
  ]
)
<fig:BottlebrushPhases>

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
<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
<hydrogel-preparation>
=== Introduction
<introduction-3>
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
<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
<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
<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
<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
<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.