Antimicrobial resistance (AMR) is one of the major global threats to thehealth of humans, animals, plants and ecosystems. AMR arises whenbacteria, viruses, fungi, and parasites undergo changes over time; makingmedicines such as antibiotics, antivirals, antifungals and antiparasiticineffective at treating infections. In 2014, it caused approximately 700 000deaths worldwide which increased to 1.27 million deaths in 2019.Consequently, there is a need to explore novel technologies andtreatments. Within the development of alternatives to conventional smallmoleculeantibiotics, polycationic macromolecules have emerged, such asdendritic polymers and their nanomaterials.Dendrimers are high precision, branched macromolecules with a highdensity of terminal functional groups. Their unique architecture and abilityfor precise control over both shape and surface functionality make themsuitable for biomedical applications such as drug delivery, gene deliveryand antimicrobials.Cellulose nanofibrils (CNFs) are nanoscale fibrils of cellulose, an abundantpolymer typically derived from wood. The prolonged reliance on fossilbasedproducts is associated with a wide range of adverse environmentalconsequences which have prompted the exploration of raw materialsderived from renewable resources. The intriguing properties of CNFs, suchas high elastic moduli and low densities, have made them attractive asstructural materials from sustainable sources that can form 3D networks.The combination of cationic dendritic polymers and cellulose nanofibrils isexplored in this thesis and presents an exciting avenue for the developmentof innovative biomaterials with antibacterial properties andbiocompatibility. Part of the work focuses on the synthesis of cationicdendritic polymers, with varying types of cationic groups at the peripheralthrough the use of fluoride-promoted esterification chemistry and thioleneclick reactions. Another part focuses on creating crosslinked hybridhydrogels using cationic dendrimers and anionic CNFs. Finally, a part ofthe thesis presents the preparation of hydrogels consisting of dendriticlinear-dendritic (DLD) polymer solutions and anionic CNFs. Overall, thefindings showcase the versatility and promise of the developed cationicdendritic polymers and CNF-based hydrogels against Escherichia coli,Pseudomonas aeruginosa and Staphylococcus aureus bacterial strainswhilst exhibiting low cytotoxicity.

Antimikrobiell resistens (AMR) är ett av dem stora globala hoten motmänniskors, djurs, växters och ekosystemens hälsa. AMR uppstår närbakterier, virus, svampar och parasiter genomgår förändringar över tid,vilket gör läkemedel som antibiotika, antivirala, svampdödande ochantiparasitära medel ineffektiva vid behandling av infektioner. År 2014orsakade AMR ungefär 700 000 dödsfall över hela världen och siffranökade till 1,27 miljoner under 2019. Därför finns det ett behov av attutforska nya teknologier och behandlingar. Inom utvecklingen avalternativ till konventionella småmolekylära antibiotika harpolykatjoniska makromolekyler såsom dendritiska polymerer framträtt.Dendrimerer är kraftigt förgrenade makromolekyler och perfektdefinierade med en hög densitet av funktionella grupper. Deras unikaarkitektur gör dem intressanta för biomedicinska applikationer somfrisättning av läkemedel och antimikrobiella material.Cellulosa nanofibriller (CNF) är fibriller av cellulosa med en diameter inanoskala, en polymer som vanligtvis utvinns från trä. Det långvarigaberoendet av fossilbaserade produkter har resulterat i allvarligamiljökonsekvenser, vilket har drivit på utvecklingen av materialproducerade från förnyelsebara råvaror. CNF har fascinerande egenskapersom hög elasticitetsmodul och låga densiteter, vilket har gjort demattraktiva som strukturella material från hållbara källor som kan bilda 3Dnätverk.Kombinationen av katjoniska dendritiska polymerer och cellulosananofibriller utforskas i detta arbete och presenterar en spännandeutveckling av innovativa biomaterial som är antibakteriella ochbiokompatibla. En del av arbetet är fokuserad på syntesen av katjoniskadendritiska polymerer med varierande typer av katjoniska funktionalitetpå ytan genom att använda esterifieringsreaktioner som katalyseras avcesiumfluorid och därefter tiol-en-klickreaktioner. En annan del ärfokuserad på att skapa hybridhydrogeler som består av katjoniskadendritiska polymerer och anjoniska CNF. Vidare undersöktes hydrogelerbestående av dendritiska-linjära-dendritiska (DLD) polymerer ochanjoniska CNF. Sammanfattningsvis påvisade resultaten mångsidighetenoch potentialen hos dem utvecklade katjoniska dendritiska polymerernaoch CNF-baserade hydrogelerna mot bakteriestammar som Escherichiacoli, Pseudomonas aeruginosa och Staphylococcus aureus, samtidigt somde visade låg cytotoxicitet.

Structurally perfect cationic polyester dendrimers based on 2,2 dimethylolpropionic acid (bis-MPA) were exploited in combination with anionic cellulose nanofibrils (CNFs) in the fabrication of a comprehensive library of electrostatically cross-linked hybrid hydrogels. Three distinct families of cationic bis-MPA dendrimers ranging from first to third generation were used, displaying up to 24 peripheral ammonium groups. The dendrimer families covering different hydrolytic stability and peripheral ammonium groups, β-alanine, cysteamine hydrochloride, and N,N-dimethylcysteamine hydrochloride were chosen as ammonium groups. The self-assembly process occurred spontaneously without external stimuli, resulting in well-organized and self-supporting hydrogels. The water content of the hydrogels reached values up to 99.6 wt % with a storage modulus ranging from 1.2 to 3.0 kPa which is within the range of skin tissue. The antibacterial activity of the dendrimers and the formed hydrogels was evaluated against Gram-negative and Gram-positive bacteria strains, and the cytotoxicity was determined by measured cell viability prevention of diverse cell lines. The hydrogels based on TMP-G1-[Cys]6 exhibited the highest antibacterial activity without showcasing toxicity. To demonstrate its effectiveness, the hydrogel was freeze-dried, resulting in a porous aerogel that exhibited significantly greater antibacterial activity than commercially available band-aids.

Hydroxyapatite (HA) infused triazine-trione (TATO) composites have emerged as an injectable platform for customizable bone fixators due to their fast and benign curing via high-energy visible light-induced thiol-ene chemistry (HEV-TEC), promising mechanical performance, and preclinical outcomes. These composites can overcome many of the existing limitations accompanying metal implants such as poor patient customizability, soft tissue adhesions, and stress shielding. Taking into account that the promising benchmarked TATO composite (BC) is based on stable sulfur-carbon bonds, we herein investigate the impact of introducing polyester dendritic cross-linkers based on bis-MPA as chemically integrated branched additives that display labile esters in a branched configuration. The inclusion of dendrimers, G1 and G3, in concentrations of 1, 3, and 5 wt % in the composite formulations were found to (i) decrease the processing viscosity of the composite formulations, reaching Newtonic and nonshear thinning behavior at 37 degree celsius and (ii) impact the size distribution of bubble cavities in the composite cross sections. The lowest collected T-g for the dendrimer-containing composites was noted to be 73.2 degree celsius, a temperature well above physiological temperature. Additionally, all composites displayed flexural modulus above 6 GPa and flexural strength of ca. 50 MPa under dry conditions. The composites comprising 5 wt % of G1 and G3 dendrimers, with ester bond densities of 0.208 and 0.297 mmol/g, respectively, reached a mass loss up to 0.27% in phosphate buffered saline at 37 degree celsius, which is within the range of established polycaprolactone (PCL). Combined with the nontoxic properties extracted from the cell viability study, polyester dendrimers were determined as promising additives which compatibilized well with the TATO formulation and cross-linked efficiently resulting in strong composites suited for bone fracture fixations.

Singlet fission and triplet-triplet annihilation upconversion are two multiexciton processes intimately related to the dynamic interaction between one high-lying energy singlet and two low-lying energy triplet excitons. Here, we introduce a series of dendritic macromolecules that serve as platform to study the effect of interchromophore interactions on the dynamics of multiexciton generation and decay as a function of dendrimer generation. The dendrimers (generations 1–4) consist of trimethylolpropane core and 2,2-bis(methylol)propionic acid (bis-MPA) dendrons that provide exponential growth of the branches, leading to a corona decorated with pentacenes for SF or anthracenes for TTA-UC. The findings reveal a trend where a few highly ordered sites emerge as the dendrimer generation grows, dominating the multiexciton dynamics, as deduced from optical spectra, and transient absorption spectroscopy. While the dendritic structures enhance TTA-UC at low annihilator concentrations in the largest dendrimers, the paired chromophore interactions induce a broadened and red-shifted excimer emission. In SF dendrimers of higher generations, the triplet dynamics become increasingly dominated by pairwise sites exhibiting strong coupling (Type II), which can be readily distinguished from sites with weaker coupling (Type I) by their spectral dynamics and decay kinetics.

Polyester dendrimers based on 2,2 bis(hydroxymethyl)propionic acid have been reported to be degradable, non-toxic, and exhibit good antimicrobial activity when decorated with cationic charges. However, these systems exhibit rapid depolymerization, from the outer layer inwards in physiological neutral pHs, which potentially restricts their use in biomedical applications. In this study, we present a new generation of amine functional bis-MPA polyester dendrimers with increased hydrolytic stability as well as antibacterial activity for Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli) and Pseudomonas aeruginosa (P. aeruginosa) planktonic bacteria strains. These new derivatives show generally good cytocompatibility for the concentrations they are active toward bacteria, in monocyte/macrophage-like cells (Raw 264.7), and human dermal fibroblasts. Fluoride - promoted esterification chemistry, anhydride chemistry, and click reactions were utilized to produce a library from generations 1–3 and with cationic peripheral groups ranging from 6 to 24 groups, respectively. The dendrimers were successfully purified using conventional purification techniques as well as characterized by matrix-assisted laser desorption ionization time-of-flight mass spectroscopy, nuclear magnetic resonance, and size exclusion chromatography. As proof of synthetic versatility, dendritic-linear-dendritic block copolymer were successfully synthesized to display cysteamine peripheral functionalities as well as the scaffolding ability with biomedically relevant lipoic acid and methoxy polyethylene glycol.

Cationic dendrimers are intriguing materials that can be used as antibacterial materials; however, they display significant cytotoxicity towards diverse cell lines at high generations or high doses, which limits their applications in biomedical fields. In order to decrease the cytotoxicity, a series of biocompatible hybrid hydrogels based on cationic dendrimers and carboxylated cellulose nanofibrils were easily synthesized by non-covalent self-assembly under physiological conditions without external stimuli. The cationic dendrimers from generation 2 (G2) to generation 4 (G4) based on trimethylolpronane (TMP) and 2,2-bis (methylol)propionic acid (bis-MPA) were synthesized through fluoride promoted esterification chemistry (FPE chemistry). FTIR was used to show the presence of the cationic dendrimers within the hybrid hydrogels, and the distribution of the cationic dendrimers was even verified using elemental analysis of nitrogen content. The hybrid hydrogels formed from G3 and G4 showed 100% killing efficiency towards Escherichia coli (E. coli), Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa) with bacterial concentrations ranging from 10(5) CFU/mL to 10(7) CFU/mL. Remarkably, the hybrid hydrogels also showed good biocompatibility most probably due to the incorporation of the biocompatible CNFs that slowed down the release of the cationic dendrimers from the hybrid hydrogels, hence showing great promise as an antibacterial material for biomedical applications.

Understanding wood’s complex nanostructure and interactions inspires the development of bio-mimetic engineering materials with similar structural and performance characteristics. Their strength, stiffness, toughness, and resilience enable them to resist tensions more effectively and adapt to varying mechanical demands, deriving from the alignment of cellulose nanofibers (CNFs) and the cohesion between them. We have utilized a composite dispersion of CNF and a dendritic polyampholyte, Helux, to: (i) assess the simultaneous effect of alignment and interactions on mechanical properties, and (ii) spin functional tough filaments. Amidation chemistry offers the opportunity for post-functionalization of filaments through Helux-accessible amines, which also enhance mechanical properties via covalent cross-linking at elevated temperatures. Composite filaments exhibited 60% higher ultimate strength and roughly five times higher toughness despite lower fibril alignment (as evidenced by wide-angle X-ray scattering) and a corresponding lower elastic modulus in the presence of Helux. We further investigate the trade-off between CNF alignment and mechanical properties using our desktop polarized optical microscopy (POM) flow-stop technique and in-situ small-angle X-ray scattering (SAXS) in conjunction with its digital twin. A lower degree of alignment in composite dispersions is attributed to faster fibril dynamics and higher rotary diffusion in the presence of negatively charged Helux molecules, facilitating de-alignment. However, Helux can ionically interact with multiple fibrils and physically link them together, forming a tougher and stronger 3D network with a denser morphology and fewer voids, owing to its multi-valent nature. Indeed, there is an affinity between these interactions and those formed between cellulose and lignin/hemicellulose in wood.