Dendritic Hydrogels Research Articles

Fine-Tuning the Amphiphilic Properties of Carbosilane Dendritic Networks towards High-Swelling Thermogels.

Dendritic hydrogels based on carbosilane crosslinkers are promising drug delivery systems, as their amphiphilic nature improves the compatibility with poorly water-soluble drugs. In this work, we explored the impact of the complementary polymer on the amphiphilic properties of the dendritic network. Different polymers were selected as precursors, from the highly lipophilic propylene glycol (PPG) to the hydrophilic polyethylene glycol (PEG), including amphiphilic Pluronics L31, L35 and L61. The dithiol polymers reacted with carbosilane crosslinkers through UV-initiated thiol-ene coupling (TEC), and the resultant materials were classified as non-swelling networks (for PPG, PLUL31 and PLUL61) and high-swelling hydrogels (for PEG and PLUL35). The hydrogels exhibited thermo-responsive properties, shrinking at higher temperatures, and exhibited an intriguing drug release pattern due to internal nanostructuring. Furthermore, we fine-tuned the dendritic crosslinker, including hydroxyl and azide pendant groups in the focal point, generating functional networks that can be modified through degradable (ester) and non-degradable (triazol) bonds. Overall, this work highlighted the crucial role of the amphiphilic balance in the design of dendritic hydrogels with thermo-responsive behavior and confirmed their potential as functional networks for biomedical applications.

Bifunctional Carbosilane Dendrimers for the Design of Multipurpose Hydrogels with Antibacterial Action.

The emergence of antibiotic resistance is a serious global health problem. There is an incessant demand for new antimicrobial drugs and materials that can address this global issue from different angles. Dendritic hydrogels have appeared as a promising strategy. A family of bifunctional amphiphilic carbosilane dendrimers was designed and employed as nanosized cross-linking points for the synthesis of high-swelling hydrogels using the highly efficient Thiol-Ene click reaction for their preparation. Both stoichiometric and off-stoichiometric conditions were studied, generating hydrogels with pendant hydroxyl or alkene moieties. These hydrogels were found to be tunable antibacterial materials. They can easily be postmodified with relevant antibiotic moieties through covalent attachment on the hydroxyl or alkene pendant groups, generating ammonium-decorated networks with temperature and pH-responsive properties. Additionally, they can efficiently encapsulate drugs with poor solubility in water, like ciprofloxacin, and perform a sustained release over time, as demonstrated in preliminary assays against Staphylococcus aureus.

Amphiphilic Dendritic Hydrogels with Carbosilane Nanodomains: Preparation and Characterization as Drug Delivery Systems.

Carbosilane dendrimers are hyperbranched lipophilic scaffolds widely explored in biomedical applications. This work exploits, for the first time, the ability of these scaffolds to generate functional hydrogels with amphiphilic properties. The monodispersity and multivalency enable a precise synthetic control of the network, while the lipophilicity improves the compatibility with poorly soluble cargo. The first family of cleavable carbosilane dendrimers was designed for this purpose, overcoming one of the main drawbacks of these type of dendrimers. Biodegradable dendritic low-swelling hydrogels with aromatic nanodomains were easily prepared using the highly efficient click thiol-ene chemistry. Our studies through electron-paramagnetic resonance, molecular dynamics simulations, and experimental assays confirmed the impact of the carbosilane dendritic nanodomains in both the encapsulation and the release pattern of model drugs such as ibuprofen and curcumin. Curcumin-loaded hydrogels were further tested in in vitro assays against advanced prostate cancer cells. The dendritic hydrogels not only enabled drugs encapsulation; as proof of concept, ibuprofen was efficiently attached via fluoride-promoted esterification and was enzymatically cleaved, achieving a controlled release over time.

Dendrimer as a momentous tool in tissue engineering and regenerative medicine

Dendrimers have been comprehensively used for cargo delivery, nucleic acid delivery (genes, miRNA/siRNAs), delivery of macromolecules, and other various biomedical applications. Dendrimers are highly versatile in function and can be engineered as multifunctional biomacromolecules by modifying the surface for fulfilling different applications. Dendrimers are being used for crosslinking of existing synthetic and natural polymeric scaffolds to regulate their binding efficiency, stiffness, biocompatibility, transfection, and many other properties to mimic the in vivo extracellular matrix in tissue engineering and regenerative medicine (TERM). Dendritic inter-cellular linkers can enhance the linkages between cells and result in scaffold-independent tissue constructs. Effectively engineered dendrimers are the ideal molecules for delivering bioactive molecules such as cytokines, chemokines, growth factors, etc., and other metabolites for efficaciously regulating cell behavior. Dendrimeric nanostructures have shown tremendous results in various TERM fields like stem cells survival, osteogenesis, increased crosslinking for eye and corneal repair, and proliferation in cartilage. This review highlights the role and various aspects of dendritic polymers for TERM in general and with respect to specific tissues. This review also covers novel explorations and insights into the use of dendrimers in TERM, focusing on the developments in the past decade and perspective of the future.

Dendritic Hydrogels with Robust Inherent Antibacterial Properties for Promoting Bacteria-Infected Wound Healing.

Bacterial infections are a common problem associated with wound treatment that imposes a significant burden on healthcare systems and patients. As a result, healthcare providers urgently need new treatment strategies to protect people. Hydrogel biomaterials with inherent antimicrobial properties offer an attractive and viable solution to this issue. Here, for the first time, we have developed a new efficient synthetic strategy to prepare cationic hydrogels (PHCI) with intrinsically efficient antimicrobial properties by chemically cross-linking trans-1,4-cyclohexanediamine with 1,3-dibromo-2-propanol using a condensation reaction without the use of toxic cross-linking agents. As expected, the prepared PHCI hydrogel possessed an inherent antibacterial ability that can adsorb and kill Staphylococcus aureus and Escherichia coli electrostatically. Notably, in vivo experiments on normal and diabetic rat models confirmed that the PHCI hydrogel can quickly stop bleeding, efficiently kill bacteria, promote the conversion of macrophages from the proinflammatory M1 phenotype to the repaired M2 phenotype, and accelerate collagen deposition and blood vessel formation, thereby achieving rapid wound healing. Overall, this work presents an effective antibacterial dressing that might provide a facile but effective approach for clinical wound management.

Dendritic Hydrogels Induce Immune Modulation in Human Keratinocytes and Effectively Eradicate Bacterial Pathogens.

Infections caused by antibiotic-resistant bacteria are globally a major threat, leading to high mortality rates and increased economic burden. Novel treatment strategies are therefore urgently needed by healthcare providers to protect people. Biomaterials that have inherent antibacterial properties and do not require the use of antibiotics present an attractive and feasible avenue to achieve this goal. Herein, we demonstrate the effect of a new class of cationic hydrogels based on amino-functional hyperbranched dendritic–linear–dendritic copolymers (HBDLDs) exhibiting excellent antimicrobial activity toward a wide range of clinical Gram-positive and Gram-negative bacteria, including drug-resistant strains isolated from wounds. Intriguingly, the hydrogels can induce the expression of the antimicrobial peptides RNase 7 and psoriasin, promoting host-mediated bacterial killing in human keratinocytes (HaCaT). Moreover, treatment with the hydrogels decreased the proinflammatory cytokine IL-1β, reactive nitrogen species (NO), and mitochondrial reactive oxygen species (ROS) in S. aureus-infected HaCaT cells, conjunctively resulting in reduced inflammation.

Covering soy polysaccharides gel on the surface of β-cyclodextrin-based metal–organic frameworks

In this study, β-cyclodextrin-based metal–organic frameworks (β-CDMOFs) were successfully prepared using alkaline potassium ions through a hydrothermal method. Based on post-synthesis strategy, a facile protocol could enable exploitation of a green soft matter including rigid β-CDMOF through coating a natural edible soybean hull polysaccharides (SHPs). The morphology, crystal structure, thermal, infrared properties of β-CDMOF, dendricolloids and β-CDMOF complexes (β-CDMOF@SHP) were investigated. Optical and scanning electron microscopy results showed that SHP could capture scattered β-CDMOF into a formed dendritic hydrogel. Further, a weak interplay (coordination and hydrogen bonding) that occurred between SHP and β-CDMOF was confirmed by X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR) analysis. Considering this renewable, rigid and soft dendritic β-CDMOF@SHP exhibits potential advantages in food, filtration membranes and the formation of pharmaceutical products. Schematic illustration of the synthesis of cubic β-CDMOF, and soft dendritic β-CDMOF@SHP.

Dendritic Hydrogel Bioink for 3D Printing of Bacterial Microhabitat.

A glucose-modified dendritic hydrogel is used as a bioink for bacterial encapsulation. This biocompatible hydrogel is a potentially suitable alternative to conventional alginate hydrogel for bacterial encapsulation, as it readily forms gel in the presence of Na+ or K+ ions without any additional stimuli such as pH, temperature, sonication, or the presence of divalent metal ions. We created a bacterial microhabitat by adding the gelator to phosphate-buffered saline containing live bacteria at physiological pH and using an additive three-dimensional (3D) printing technique. The bacteria remained viable and metabolically active within the 3D printed bacterial microhabitat, as shown with confocal laser scanning microscopy (CLSM) and scanning electrochemical microscopy (SECM).

Antibiotic-Free Cationic Dendritic Hydrogels as Surgical-Site-Infection-Inhibiting Coatings.

A non-toxic hydrolytically fast-degradable antibacterial hydrogel is herein presented to preemptively treat surgical site infections during the first crucial 24 h period without relying on conventional antibiotics. The approach capitalizes on a two-component system that form antibacterial hydrogels within 1 min and consist of i) an amine functional linear-dendritic hybrid based on linear poly(ethylene glycol) and dendritic 2,2-bis(hydroxymethyl)propionic acid, and ii) a di-N-hydroxysuccinimide functional poly(ethylene glycol) cross-linker. Broad spectrum antibacterial effect is achieved by multivalent representation of catatonically charged β-alanine on the dendritic periphery of the linear dendritic component. The hydrogels can be applied readily in an in vivo setting using a two-component syringe delivery system and the mechanical properties can accurately be tuned in the range equivalent to fat tissue and cartilage (G' = 0.5-8 kPa). The antibacterial effect is demonstrated both in vitro toward a range of relevant bacterial strains and in an in vivo mouse model of surgical site infection.

On-Demand Dissolution of Chemically Cross-Linked Hydrogels.

The formation and subsequent on-demand dissolution of chemically cross-linked hydrogels is of keen interest to chemists, engineers, and clinicians. In this Account, we summarize our recent advances in the area of dissolvable chemically cross-linked hydrogels and provide a comparative discussion of other recent hydrogel systems. Using biocompatible macromonomers, we developed a library of cross-linked dendritic hydrogels that possess favorable properties, including biocompatibility, tissue adhesion, and swelling. Additionally, these hydrogels possess the unique ability to dissolve on-demand via application of a biocompatible aqueous solution. Each of the three hydrogel systems described employs a thiol-thioester exchange reaction as the mechanism of dissolution. These new materials successfully decrease bleeding in in vivo models of hepatic and aortic hemorrhage and dissolve on-demand, providing easy removal. In addition, we evaluated these hydrogels as dressings for second-degree burn wounds and performed proof-of-concept in vivo studies. These hydrogel wound dressings provide a means of repeatedly changing the dressing in a minimally invasive and atraumatic manner while also serving as a protective barrier against bacterial infection. Finally, we highlight the seminal work of other researchers in the field of dissolvable chemically cross-linked hydrogels using thiol-disulfide exchange, retro-Michael-type, and retro-Diels-Alder reactions. These chemistries provide a versatile synthetic toolbox to dissolve hydrogels in a controlled manner on time scales from minutes to weeks. Continued investigation of these dissolution approaches as well as the development of new chemical reactions will open doors to other avenues of on-demand dissolution and expand the application space for these materials. In summary, the management and closure of wounds after traumatic injury or surgical intervention are of significant clinical importance. Stimuli-responsive hydrogels that function as sealants, adhesives, or dressings are emerging as vital alternatives to current standards of care that rely upon conventional sutures, staples, or dressings.

Recent Advances in Dendritic Macromonomers for Hydrogel Formation and Their Medical Applications.

Hydrogels represent one of the most important classes of biomaterials and are of interest for various medical applications including wound repair, tissue engineering, and drug release. Hydrogels possess tunable mechanical properties, biocompatibility, nontoxicity, and similarity to natural soft tissues. The need for hydrogels with specific properties, based on the design requirements of the in vitro, in vivo, or clinical application, motivates researchers to develop new synthetic approaches and cross-linking methodologies to form novel hydrogels with unique properties. The use of dendritic macromonomers represents one elegant strategy for the formation of hydrogels with specific properties. Specifically, the uniformity of dendrimers combined with the control of their size, architecture, density, and surface groups make them promising cross-linkers for hydrogel formation. Over the last two decades, a large variety of dendritic-based hydrogels are reported for their potential use in the clinic. This review describes the state of the art with these different dendritic hydrogel formulations including their design requirements, the synthetic routes, the measurement and determination of their properties, the evaluation of their in vitro and in vivo performances, and future perspectives.

Novel Citric Acid Dendritic Hydrogels for the Delivery of Econazole Nitrate and its Antifungal Activity

Novel Citric Acid Dendritic Hydrogels for the Delivery of Econazole Nitrate and its Antifungal Activity

Dendritic hydrogels: From exploring various crosslinking chemistries to introducing functions and naturally abundant resources

Dendritic hydrogels from dendritic-linear-dendritic (DLD) block copolymers based on PEG and bis-MPA dendrons were constructed via UV-initiated thiol-ene, thiol-yne, CuAAC, and amine-NHS crosslinkin ...

Multipurpose heterofunctional dendritic scaffolds as crosslinkers towards functional soft hydrogels and implant adhesives in bone fracture applications.

Two sets of heterofunctional dendritic frameworks displaying an inversed and exact number of ene and azide groups have successfully been synthesized and post-functionalized with biorelevant molecules. Their facile scaffolding ability enabled the fabrication of soft and azide functional dendritic hydrogels with modulus close to muscle tissue. The dendritic scaffolds are furthermore shown to be promising primers for the development of novel bone fracture stabilization adhesives with shear strengths succeeding commercial Histroacryl®.