Bacterial infections are one of the major threats to human health due to the raising crisis of antibiotic resistance. Herein, second generation antibacterial heterofunctional dendrimers based on 2,2-bis(methylol)propionic acid were synthesized. The dendrimers possessed six alkenes and 12 ammonium end-groups per molecule and were used to fabricate antibacterial hydrogels together with dithiol-functional polyethylene glycol (mol wt of 2, 6 and 10 kDa) as crosslinkers via thiol-ene chemistry. The network formation can be completed within 10 s upon UV-irradiation as determined by the stabilization of the storage modulus in a rheometer. The hydrogels swelled in aqueous media and could be functionalized with the N-hydroxysuccinimide ester of the dye disperse red 13, which allowed for visually studying the degradation of the hydrogels through the hydrolysis of the ester bonds of the dendritic component. The maximum swelling ratio of the gels was recorded within 4–8 h and the swelling ratios increased with higher molecular weight of the polyethylene glycol crosslinker. The gel formed with 10 kDa polyethylene glycol crosslinker showed the highest swelling ratio of 40 and good mechanical properties, with a storage modulus of 8 kPa. In addition, the hydrogels exhibited good biocompatibility towards both human fibroblasts and mouse monocytes, while showing strong antibacterial activity against both gram-positive and gram-negative bacteria.

Chemoselective reactions are a highly desirable approach to generate well-defined functional macromolecules. Their extraordinary efficiency and selectivity enable the development of flawless structures, such as dendrimers, with unprecedented structure-to-property capacity but with typically tedious synthetic protocols. Here we demonstrate the potency of chemoselective reactions to accomplish sequence-controlled heterolayered dendrimers. An accurate accelerated design of bis-MPA monomers with orthogonally complementary moieties and a wisely selected chemical toolbox generated highly complex monodisperse dendrimers through simplified protocols. The versatility of the strategy was proved by obtaining different dendritic families with different properties after altering the order of addition of the monomers. Moreover, we evaluated the feasibility of the one-pot approach toward these heterolayered dendrimers as proof-of-concept.

This chapter will provide a descriptive overview of the different classes that define dendritic polymers and their subcategories. These include monodisperse dendrons and dendrimers as well as polydisperse hyperbranched polymers, linear-dendritic copolymer hybrids, dendronized polymers and dendrigrafts. Its content will give the reader interested in venturing into the field of dendritic polymers, the general synthetic options with respect to choice of scaffolds. From a researcher point of view, a major drawback to exploiting this class of polymers is strongly related to their accessibility, especially synthetically challenging and flawless dendritic scaffolds. As monodisperse dendrimers are the pinnacle of dendritic polymers that are synthesized via a cascade of successful reactions steps, it is pivotal that chemists utilize reactions known for their robustness and simple purification. Consequently, a large part of this chapter describes previous and recent synthetic approaches to dendrimers that have successfully been accomplished, such as traditional and accelerated growth strategies, as well as their pros and cons. A rationale on how to synthetically approach dendrimers is provided, from choice of monomers, growth route and pitfalls that accompany their construction. More in-depth synthetic description and their related references for structurally specific architectures can be found in the later chapters in this book.

This chapter describes recent synthetic advances and cutting-edge applications of dendritic polyesters. We present the synthetic evolution from traditional approaches to new chemistries, which translate to a large library of structurally diverse dendritic materials including monodisperse dendrimers and dendrons, linear-dendritic and surface-dendritic hybrids, and larger dendritic assemblies. Within each sub-family, various elegant approaches have been detailed in which click chemistry plays a fundamental role in overcoming existing challenges in the synthesis of advanced and monodisperse dendritic polymers. This includes orthogonal and accelerated growth to dendrimers with sequence-controlled linkages, heterofunctional dendrimers with precise representation of the functional groups displayed at the exterior and interior of the skeleton and dendritic hybrids that take advantage of the intrinsic properties of both blocks. Dendritic polyesters based on 2,2-bis(hydroxymethyl)propanoic acid (bis-MPA), as the main AB2 monomer building block, are one of the most dominant families today, being biocompatible, biodegradable and commercially available, thereof represented extensively in this chapter. Additionally, a detailed overview of reported building blocks is included, aiming to address current challenges through chemical modification of the monomer or the hybridization with other synthons. Structural perfection, characterization techniques and innovative applications are thoroughly discussed to give the readers an overall picture of the landscape presented in the literature.

Heterofunctional dendrimers with internal and external representations of functionalities are considered as the ultimate dendritic frameworks. This is reflected by their unprecedented scaffolding, such as precise control over the structure, molecular weight, number, and location of different cargos across the whole dendritic skeleton. Consequently, these dendrimers with multipurpose characters are the pinnacle of precision polymers and thereof are highly attractive to the scientific community as they can find use in a great number of cutting-edge applications, especially as discrete unimolecular carriers for therapeutic exploitation. Unfortunately, most established dendrimer families display external functionalities but lack internal scaffolding ability, which leads to inherent limitations to their full potential use as precision carriers. Consequently, here, we embark on a novel synthetic strategy facilitating the introduction of internal functionalization of established dendrimers. As a proof of concept, a new class of internally and externally functionalized multipurpose dendrimers based on the established 2,2-bis(methylol)propionic acid (bis-MPA) was successfully obtained by the elegant and simple design of AB2C monomers, amalgamated from two traditional AB2 monomers. Utilizing fluoride-promoted esterification (FPE), straightforward layer-by-layer divergent growth up to the fourth generation was successful in less than one day of reaction time, with a molecular weight of 15 kDa, and displaying 93 reactive groups divided by 45 internal and 48 external functionalities. The feasibility of postfunctionalization through click reactions is demonstrated, where the fast and effective attachment of drugs, dyes, and PEG chains is achieved, as well as cross-linking into multifunctional hydrogels. The simplicity and versatility of the presented strategy can easily be transferred to generate a myriad of functional materials such as polymers, surfaces, nanoparticles, or biomolecules.

Polycarbonates from isosorbide and dihydroxyacetone (DHA) have been synthesised using organocatalytic step-growth polymerization of their corresponding diols and bis-carbonylimidazolides monomers. By choice of feed ratio and monomer activation, either isosorbide or ketal protected DHA, random and alternating poly(Iso-co-DHA) carbonates have been formed. Thermal properties by DSC and TGA were herein strongly correlated to monomer composition. Dilution studies using 1H-NMR of a model compound DHA-diethyl carbonate in acetonitrile and deuterated water highlighted the influence of α-substituents on the keto/hydrate equilibrium of DHA. Further kinetics studies of in the pH* range of 4.7 to 9.6 serve to show the hydrolytic pH-profile of DHA-carbonates. The Hydrolytic degradation of deprotected polymer pellets show an increased degradation with increasing DHA content. Pellets with a random or alternating configuration show different characteristics in terms of mass loss and molecular weight loss profile over time.

The use of adhesives for fracture fixation can revolutionize the surgical procedures toward more personalized bone repairs. However, there are still no commercially available adhesive solutions mainly due to the lack of biocompatibility, poor adhesive strength, or inadequate fixation protocols. Here, a surgically realizable adhesive system capitalizing on visible light thiol–ene coupling chemistry is presented. The adhesives are carefully designed and formulated from a novel class of chemical constituents influenced by dental resin composites and self-etch primers. Validation of the adhesive strengthis conducted on wet bone substrates and accomplished via fiber-reinforced adhesive patch (FRAP) methodology. The results unravel, for the first time, on the promise of a thiol–ene adhesive with an unprecedented shear bondstrength of 9.0 MPa and that surpasses, by 55%, the commercially available acrylate dental adhesive system Clearfil SE Bond of 5.8 MPa. Preclinical validation of FRAPs on rat femur fracture models details good adhesion to the bone throughout the healing process, and are found biocompatible not giving rise to any inflammatory response. Remarkably, the FRAPs are found to withstand loads up to 70 N for 1000 cycles on porcine metacarpal fractures outperforming clinically used K-wires and match metal plates and screw implants.