New directions in thermoresponsive polymers Roy, Debashish; Brooks, William L. A; Sumerlin, Brent S
Chemical Society reviews,
01/2013, Letnik:
42, Številka:
17
Journal Article
Recenzirano
Interest in thermoresponsive polymers has steadily grown over many decades, and a great deal of work has been dedicated to developing temperature sensitive macromolecules that can be crafted into new ...smart materials. However, the overwhelming majority of previously reported temperature-responsive polymers are based on poly(
N
-isopropylacrylamide) (PNIPAM), despite the fact that a wide range of other thermoresponsive polymers have demonstrated similar promise for the preparation of adaptive materials. Herein, we aim to highlight recent results that involve thermoresponsive systems that have not yet been as fully considered. Many of these (co)polymers represent clear opportunities for advancements in emerging biomedical and materials fields due to their increased biocompatibility and tuneable response. By highlighting recent examples of newly developed thermoresponsive polymer systems, we hope to promote the development of new generations of smart materials.
While the majority of reported thermoresponsive polymeric materials have been composed of poly(
N
-isopropylacrylamide), increasing demand for diversity has driven a rapid expansion of structural and chemical variety in the field of temperature-responsive polymers.
Mesenchymal stem or stromal cells (MSC) are under investigation as a potential immunotherapy. MSC are usually administered via intravenous infusion, after which they are trapped in the lungs and die ...and disappear within a day. The fate of MSC after their disappearance from the lungs is unknown and it is unclear how MSC realize their immunomodulatory effects in their short lifespan. We examined immunological mechanisms determining the fate of infused MSC and the immunomodulatory response associated with it. Tracking viable and dead human umbilical cord MSC (ucMSC) in mice using Qtracker beads (contained in viable cells) and Hoechst33342 (staining all cells) revealed that viable ucMSC were present in the lungs immediately after infusion. Twenty‐four hours later, the majority of ucMSC were dead and found in the lungs and liver where they were contained in monocytic cells of predominantly non‐classical Ly6Clow phenotype. Monocytes containing ucMSC were also detected systemically. In vitro experiments confirmed that human CD14++/CD16‐ classical monocytes polarized toward a non‐classical CD14++CD16+CD206+ phenotype after phagocytosis of ucMSC and expressed programmed death ligand‐1 and IL‐10, while TNF‐α was reduced. ucMSC‐primed monocytes induced Foxp3+ regulatory T cell formation in mixed lymphocyte reactions. These results demonstrate that infused MSC are rapidly phagocytosed by monocytes, which subsequently migrate from the lungs to other body sites. Phagocytosis of ucMSC induces phenotypical and functional changes in monocytes, which subsequently modulate cells of the adaptive immune system. It can be concluded that monocytes play a crucial role in mediating, distributing, and transferring the immunomodulatory effect of MSC. Stem Cells 2018;36:602–615
Overview of the interaction of monocytic cells with infused mesenchymal stem or stromal cells (MSCs). Umbilical cord MSC (ucMSC) get entrapped in the lungs after intravenous infusion and are rapidly cleared from the system through phagocytosis by neutrophils, lung resident macrophages, and circulating monocytes. Monocytes containing ucMSC migrate via the blood stream to other sites, in particular to the liver. In addition, debris of ucMSC ends up in the liver where it is phagocytosed by liver‐resident Kupffer cells. Phagocytosis of ucMSC induces an immunomodulatory phenotype in monocytes and ucMSC‐primed monocytes induces Foxp3+CD25hiCD127‐CD4+ regulatory T cells.
Well-defined boronic acid block copolymers were demonstrated to exhibit glucose-responsive disassembly at physiological pH. A boronic acid-containing acrylamide monomer with an electron-withdrawing ...substituent on the pendant phenylboronic acid moiety was polymerized by reversible addition–fragmentation chain transfer (RAFT) polymerization to yield a polymer with a boronic acid pK a = 8.2. Below this value, a block copolymer of this monomer with poly(N,N-dimethylacrylamide) self-assembled into aggregates. Addition of base to yield a pH > pK a or addition of glucose at pH = 7.4 resulted in aggregate dissociation that may prove promising for controlled delivery applications under physiological relevant conditions.
Boronic acid-containing block copolymers capable of solution self-assembly into micelles and reverse micelles in response to changes in temperature, pH, and sugar concentration were prepared by ...reversible addition-fragmentation chain transfer (RAFT) polymerization.
A single-mode microwave reactor was employed for the synthesis of well-defined homopolymers and block copolymers of acrylamido and acrylate monomers via reversible addition−fragmentation chain ...transfer (RAFT) polymerization. The rates of polymerization of N,N-dimethylacrylamide and N-isopropylacrylamide were significantly higher than those observed under conventional heating conditions, yet the resulting homopolymers retained thiocarbonylthio end group functionality, as evidenced by efficient extension during block copolymerizations. Moreover, the dramatically enhanced rates of polymerization observed under microwave conditions did not negatively affect molecular weight control during homopolymerization or block copolymerization. In all cases, low polydispersity indices were observed, and the agreement between theoretical and experimental molecular weights was excellent. Rate enhancement may ultimately be the result of thermal effects not easily duplicated under conventional heating conditions. The methods outlined herein permit the total synthesis of block copolymers in a dramatically shortened period of time.
Novel sugar-responsive block copolymers were prepared by RAFT block copolymerization of unprotected boronic acid monomers, providing a direct route to supramolecular assemblies that dissociate upon ...the addition of glucose.
Reversible addition−fragmentation chain transfer (RAFT) polymerization was used to control the grafting of styrene from a cellulose substrate. The hydroxyl groups of the cellulose fiber were ...converted into thiocarbonyl-thio chain transfer agent, and were further used to mediate the RAFT polymerization of styrene. The graft copolymers were analyzed by gravimetry, attenuated total reflectance Fourier transform infrared spectroscopy, contact angle measurements, scanning electron microscopy, differential scanning calorimetry, and thermogravimetry. The results obtained from these analytical techniques confirm that grafting occurred from the surface of the cellulose fibers. The poly(styrene) chains were also cleaved from the cellulose backbone and analyzed by size exclusion chromatography and showed narrow polydispersity.
Well-defined homopolymers and block copolymers with boronic acid-functional end groups were prepared by reversible addition−fragmentation chain transfer (RAFT) polymerization and subsequently ...investigated for the potential to undergo model supramolecular and dynamic covalent self-assembly in aqueous and organic media. By employing a boronic acid-functionalized RAFT chain transfer agent, end-functional polymers were prepared without recourse to postpolymerization functionalization. The polymerizations of styrene, N,N-dimethylacrylamide, and N-isopropylacrylamide all led to homopolymers of controlled molecular weight that were capable of subsequent chain extension to form well-defined block copolymers. The amphiphilic and stimuli-responsive block copolymers were capable of self-assembly into micellar aggregates. Quantitative retention of the boronic acid chain termini during polymerization was spectroscopically demonstrated, and two types of dynamic covalent transformations involving these moieties were investigated. The formation of boronic esters with a model 1,2-diol proved to be a highly efficient process in nonaqueous media. Additionally, Lewis base-promoted trimerization of the boronic acid end groups led to three-arm star polymers with boroxine junction points. Both of these covalent interactions were readily reversible upon the introduction of water, suggesting the potential application of these polymers to construct dynamic covalent macromolecular assemblies.
Well-defined homopolymers and block copolymers of vinyl esters were synthesized under microwave irradiation via reversible addition-fragmentation chain transfer (RAFT)/macromolecular design via ...interchange of xanthates (MADIX) polymerization without the significant inhibition or retardation often observed under conventional heating conditions. Poly(vinyl acetate) (PVAc) with molecular weights of 1000−10 000 g/mol was prepared in less than 15 min under microwave irradiation at an apparent temperature of 70 °C in the presence of the commercially available chain transfer agent ethylxanthogenacetic acid. The polymerizations were well-controlled, leading to polymers with narrow molecular weight distributions and excellent agreement between theoretical and experimental number average molecular weights. Despite the high rates of polymerization, the resulting PVAc homopolymers retained a high degree of thiocarbonylthio end group functionality that allowed the synthesis of block copolymers by chain extension with vinyl benzoate and vinyl pivalate. The rates of polymerization during the addition of the second blocks were also high, and the resulting block copolymers were obtained in good yield with excellent blocking efficiencies.
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A facile route to well-defined boronic acid (co)polymers from stable and easily manipulated boronic ester monomers is presented. The polymerization of 4-pinacolatoborylstyrene by reversible ...addition−fragmentation chain transfer (RAFT) yielded polymeric boronic acid precursors. Selection of stoichiometry allowed tuning of polymerization kinetics and targeting specific molecular weights in the range of M n = 17000−32000 g/mol. The resulting low polydispersity poly(4-pinacolatoborylstyrene) homopolymers were employed as macro-chain transfer agents for block copolymerization with N,N-dimethylacrylamide to yield amphiphilic block copolymers that formed micelles in aqueous media. The pinacol ester derivatized (co)polymers were easily deprotected by a mild and convenient strategy to yield free boronic acid polymers
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