Biocompatible Hydrogel Research Articles

Challenges in Nasal Cartilage Tissue Engineering to Restore the Shape and Function of the Nose.

The repair of nasal septal cartilage is a key challenge in cosmetic and functional surgery of the nose, as it determines its shape and its respiratory function. Supporting the dorsum of the nose is essential for both the prevention of nasal obstruction and the restoration of the nose structure. Most surgical procedures to repair or modify the nasal septum focus on restoring the external aspect of the nose by placing a graft under the skin, without considering respiratory concerns. Tissue engineering offers a more satisfactory approach, in which both the structural and biological roles of the nose are restored. To achieve this goal, nasal cartilage engineering research has led to the development of scaffolds capable of accommodating cartilaginous extracellular matrix-producing cells, possessing mechanical properties close to those of the nasal septum, and retaining their structure after implantation in vivo. The combination of a non-resorbable core structure with suitable mechanical properties and a biocompatible hydrogel loaded with autologous chondrocytes or mesenchymal stem cells is a promising strategy. However, the stability and immunotolerance of these implants are crucial parameters to be monitored over the long term after in vivo implantation, to definitively assess the success of nasal cartilage tissue engineering. Here, we review the tissue engineering methods to repair nasal cartilage, focusing on the type and mechanical characteristics of the biomaterials; cell and implantation strategy; and the outcome with regard to cartilage repair.

Versatile tissue‐injectable hydrogels capable of the extended hydrolytic release of bioactive protein therapeutics

AbstractHydrogels are extensively employed in healthcare due to their adaptable structures, high water content, and biocompatibility, with FDA‐approved applications ranging from spinal cord regeneration to local therapeutic delivery. However, clinical hydrogels encounter challenges related to inconsistent therapeutic exposure, unmodifiable release windows, and difficulties in subsurface polymer insertion. Addressing these issues, we engineered injectable, biocompatible hydrogels as a local therapeutic depot, utilizing poly(ethylene glycol) (PEG)‐based hydrogels functionalized with bioorthogonal SPAAC handles for network polymerization and functionalization. Our hydrogel solutions polymerize in situ in a temperature‐sensitive manner, persist in tissue, and facilitate the delivery of bioactive therapeutics in subsurface locations. Demonstrating the efficacy of our approach, recombinant anti‐CD47 monoclonal antibodies, when incorporated into subsurface‐injected hydrogel solutions, exhibited cytotoxic activity against infiltrative high‐grade glioma xenografts in the rodent brain. To enhance the gel's versatility, recombinant protein cargos can undergo site‐specific modification with hydrolysable “azidoester” adapters, allowing for user‐defined release profiles from the hydrogel. Hydrogel‐generated gradients of murine CXCL10, linked to intratumorally injected hydrogel solutions via azidoester linkers, resulted in significant recruitment of CD8+ T‐cells and the attenuation of tumor growth in a “cold” syngeneic melanoma model. This study highlights a highly customizable, hydrogel‐based delivery system for local protein therapeutic administration to meet diverse clinical needs.

Multifunctional Ionic Hydrogel-Based Transdermal Delivery of 5-Fluorouracil for the Breast Cancer Treatment.

Transdermal drug delivery systems (TDDS) are a promising and innovative approach for breast cancer treatment, offering advantages such as noninvasiveness, potential for localized and prolonged drug delivery while minimizing systemic side effects through avoiding first-pass metabolism. Utilizing the distinctive characteristics of hydrogels, such as their biocompatibility, versatility, and higher drug loading capabilities, in the present work, we prepared ionic hydrogels through synergistic interaction between ionic liquids (ILs), choline alanine ([Cho][Ala]), and choline proline ([Cho][Pro]) with oleic acid (OA). ILs used in the study are biocompatible and enhance the solubility of 5-fluorouracil (5-FU), whereas OA is a known chemical penetration enhancer. The concentration-dependent (OA) change in morphological aggregates, that is, from cylindrical micelles to worm-like micelles to hydrogels was formed with both ILs and was characterized by SANS measurement, whereas the interactions involved were confirmed by FTIR spectroscopy. The hydrogels have excellent mechanical properties, which studied by rheology and their morphology through FE-SEM analysis. The in vitro skin permeation study revealed that both hydrogels penetrated 255 times ([Cho][Ala]) and 250 times ([Cho][Pro]) more as compared to PBS after 48 h. Those ionic hydrogels exhibited the capability to change the lipid and keratin arrangements within the skin layer, thereby enhancing the transdermal permeation of the 5-FU. Both ionic hydrogels exhibit excellent biocompatibility with normal cell lines (L-132 cells) as well as cancerous cell lines (MCF-7 cells), demonstrating over 92% cell viability after 48 h in both cell lines. In vitro, the cytotoxicity of the 5-FU-loaded hydrogels was evaluated on MCF-7 and HeLa cell lines. These results indicate that the investigated biocompatible and nontoxic ionic hydrogels enable the transdermal delivery of hydrophilic drugs, making them a viable option for effectively treating breast cancer.

In vitro and in vivo evaluation of periosteum-derived cells and iPSC-derived chondrocytes encapsulated in GelMA for osteochondral tissue engineering.

Osteochondral defects are deep joint surface lesions that affect the articular cartilage and the underlying subchondral bone. In the current study, a tissue engineering approach encompassing individual cells encapsulated in a biocompatible hydrogel is explored in vitro and in vivo. Cell-laden hydrogels containing either human periosteum-derived progenitor cells (PDCs) or human induced pluripotent stem cell (iPSC)-derived chondrocytes encapsulated in gelatin methacryloyl (GelMA) were evaluated for their potential to regenerate the subchondral mineralized bone and the articular cartilage on the joint surface, respectively. PDCs are easily isolated and expanded progenitor cells that are capable of generating mineralized cartilage and bone tissue in vivo via endochondral ossification. iPSC-derived chondrocytes are an unlimited source of stable and highly metabolically active chondrocytes. Cell-laden hydrogel constructs were cultured for up to 28 days in a serum-free chemically defined chondrogenic medium. On day 1 and day 21 of the differentiation period, the cell-laden constructs were implanted subcutaneously in nude mice to evaluate ectopic tissue formation 4 weeks post-implantation. Taken together, the data suggest that iPSC-derived chondrocytes encapsulated in GelMA can generate hyaline cartilage-like tissue constructs with different levels of maturity, while using periosteum-derived cells in the same construct type generates mineralized tissue and cortical bone in vivo. Therefore, the aforementioned cell-laden hydrogels can be an important part of a multi-component strategy for the manufacturing of an osteochondral implant.

Nanofibrous Material-Reinforced Printable Ink for Enhanced Cell Proliferation and Tissue Regeneration.

The three-dimensional (3D) printing of biomaterials, cells, and bioactive components, including growth factors, has gained interest among researchers in the field of tissue engineering (TE) with the aim of developing many scaffolds to sustain size, shape fidelity, and structure and retain viable cells inside a network. The biocompatible hydrogel employed in 3D printing should be soft enough to accommodate cell survival. At the same time, the gel should be mechanically strong to avoid the leakage of cells into the surrounding medium. Considering these basic criteria, researchers have developed nanocomposite-based printable inks with suitable mechanical and electroconductive properties. These nanomaterials, including carbon family nanomaterials, transition metal dichalcogenides, and polymeric nanoparticles, act as nanofillers and dissipate stress across polymeric networks through their electroactive interactions. Nanofiber-reinforced printable ink is one kind of nanocomposite-based ink that comprises dispersed nanofiber components in a hydrogel matrix. In this current review, we compile various TE applications of nanofiber-reinforced printable ink and describe the 3D-printing parameters, classification, and impact of cross-linkage. Furthermore, we discuss the challenges and future perspectives in this field.

Chitosan-PNIPAM Thermogel Associated with Hydrogel Microspheres as a Smart Formulation for MSC Injection.

Regenerative medicine based on cell therapy has emerged as a promising approach for the treatment of various medical conditions. However, the success of cell therapy heavily relies on the development of suitable injectable hydrogels that can encapsulate cells and provide a conducive environment for their survival, proliferation, and tissue regeneration. Herein, we address the medical need for cyto- and biocompatible injectable hydrogels by reporting on the synthesis of a hydrogel-forming thermosensitive copolymer. The copolymer was synthesized by grafting poly(N-isopropylacrylamide-co-carboxymethyl acrylate) (PNIPAM-COOH) onto chitosan through amide coupling. This chemical modification resulted in the formation of hydrogels that exhibit a sol-gel transition with an onset at approximately 27 °C, making them ideal for use in injectable applications. The hydrogels supported the survival and proliferation of cells for several days, which is critical for cell encapsulation. Furthermore, the study evaluates the addition of collagen/chitosan hybrid microspheres to support the adhesion of mesenchymal stem cells within the hydrogels. Altogether, these results demonstrate the potential of the PNIPAM-chitosan thermogel for cell encapsulation and its possible applications in regenerative medicine.

A Gelatin/Alginate Double Network Hydrogel Nerve Guidance Conduit Fabricated by a Chemical-Free Gamma Radiation for Peripheral Nerve Regeneration.

Nerve guidance conduits (NGCs) are widely developed using various materials for the functional repair of injured or diseased peripheral nerves. Especially, hydrogels are considered highly suitable for the fabrication of NGCs due to their beneficial tissue-mimicking characteristics (e.g., high water content, softness, and porosity). However, the practical applications of hydrogel-based NGCs are hindered due to their poor mechanical properties and complicated fabrication processes. To bridge this gap, a novel double-network (DN) hydrogel using alginate and gelatin by a two-step crosslinking process involving chemical-free gamma irradiation and ionic crosslinking, is developed. DN hydrogels (1% alginate and 15% gelatin), crosslinked with 30 kGy gamma irradiation and barium ions, exhibit substantially improved mechanical properties, including tensile strength, elastic modulus, and fracture stain, compared to single network (SN) gelatin hydrogels. Additionally, the DN hydrogel NGC exhibits excellent kink resistance, mechanical stability to successive compression, suture retention, and enzymatic degradability. In vivo studies with a sciatic defect rat model indicate substantially improved nerve function recovery with the DN hydrogel NGC compared to SN gelatin and commercial silicone NGCs, as confirm footprint analysis, electromyography, and muscle weight measurement. Histological examination reveals that, in the DN NGC group, the expression of Schwann cell and neuronal markers, myelin sheath, and exon diameter are superior to the other controls. Furthermore, the DN NGC group demonstrates increased muscle fiber formation and reduced fibrotic scarring. These findings suggest that the mechanically robust, degradable, and biocompatible DN hydrogel NGC can serve as a novel platform for peripheral nerve regeneration and other biomedical applications, such as implantable tissue constructs.

Asymmetric porous composite hydrogel patch for microenvironment-adapted repair of contaminated abdominal wall defects

Effective antibacterial property and long-term mechanical support are essential for the repair of complex abdominal wall defects associated with infection. However, clinically available repair materials often fail to meet these requirements, resulting in high surgical failure rate and complications. In this study, an asymmetric porous composite hydrogel patch (cCS/PVA@BAC) with antibacterial, anti-adhesion, pro-healing, and durable mechanical support properties is designed for the efficient repair of contaminated abdominal wall defects. By stepwise phase-conversion and soaking method, robust and stable polyvinyl alcohol hydrogel (PVAH) is integrated with the biocompatible multicomponent hydrogel made of chitosan and carboxymethyl chitosan (cCS), and benzalkonium chloride (BAC) is loaded to enhance the antibacterial property. The cCS layer of cCS/PVA@BAC has an extracellular matrix-like porous structure, which can promote fibroblasts adhesion and wound healing. In contrast, the PVAH layer on the other side with a smooth and dense structure, which can reduce fibroblasts adhesion and prevent visceral adhesion. In addition, the composite hydrogel patch has good anti-swelling and anti-deformation properties as well as stable mechanical strength, thus can withstand high intraperitoneal pressure in the wet internal microenvironment. The loaded BAC can efficiently kill bacteria and improve the local inflammatory microenvironment. With these advantages, cCS/PVA@BAC can significantly reduce inflammation, promote tissue remodeling, and accelerate the healing of contaminated abdominal wall defects in the rat model. These findings suggest a potential use of multifunctional hydrogel patch as an ideal material for effective repair of contaminated soft tissue defects.

Versatile Mechanically Tunable Hydrogels for Therapeutic Delivery Applications.

Hydrogels provide a versatile platform for biomedical material fabrication that can be structurally and mechanically fine-tuned to various tissues and applications. Applications of hydrogels in biomedicine range from highly dynamic injectable hydrogels that can flow through syringe needles and maintain or recover their structure after extrusion to solid-like wound-healing patches that need to be stretchable while providing a selective physical barrier. In this study, a toolbox is designed using thermo-responsive poly(N-isopropylacrylamide) (PNIPAM) polymeric matrices and nanocelluloses as reinforcing agent to obtain biocompatible hydrogels with altering mechanical properties, from a liquid injectable to a solid-like elastic hydrogel. The liquid hydrogels possess low viscosity and shear-thinning properties at 25 °C, which allows facile injection at room temperature, while they become viscoelastic gels at body temperature. In contrast, the covalently cross-linked solid-like hydrogels exhibit enhanced viscoelasticity. The liquid hydrogels are biocompatible and are able to delay the in vitro release and maintain the bioactivity of model drugs. The antimicrobial agent loaded solid-like hydrogels are effective against typical wound-associated pathogens. This work presents a simple method of tuning hydrogel mechanical strength to easily adapt to applications in different soft tissues and broaden the potential of renewable bio-nanoparticles in hybrid biomaterials with controlled drug releasecapabilities.

Surface modification of titanium foams for modulated and targeted release of drug-loaded biocompatible hydrogel. Proof of concept

Bone-tissue replacement surgeries usually need medication to mitigate implant rejections or prevent local infections. In this study, a modulated and targeted tetracycline (TC) loaded gelatine type A hydrogel is release from Ti foams as a proof of concept for an innovative and intelligent drug release system. The drugs are released in a localized and controlled manner. The Ti foams fabricated by the space holder technique were surface modified by two different techniques of surface modification, i.e., thermal oxidation and acid etching, to assess their influence on TC release. The characterization carried out after the surface modification indicated that samples modified with acid etching have produced a rougher surface, increasing the diameter of pores (from 500 μm to 700 μm, approximately) due to coalescence of pores. The increase of pore roughness has demonstrated the delaying of the TC release due to the greater adhesion between the surface roughness and the hydrogel. In addition, the increase of pore size improves the possibility to infiltrate high amount of drug-loaded biocompatible hydrogel. Opposite, oxidized surface samples have generated a rutile type TiO2 layer that, because of its hydrophilic nature facilitate the degradation of the hydrogel, and consequently, the TC release from the Ti foams. Therefore, both methods show opposite behaviour, available to increase (acid etching) or decrease (thermal oxidation) the TC release thanks to the different kinetic degradation of hydrogel, as a potential way for drug-release from metallic implants. Thus, while acid-etched samples showed maximum TC release value of 35 wt%, after 120 min, the oxidized samples surpassed the 40 % of TC release after same 120 min of release time treatment.

Functionalized Gelatin/Polysaccharide Hydrogels for Encapsulation of Hepatocytes.

Liver diseases represent a considerable burden to patients and healthcare systems. Hydrogels play an important role in the engineering of soft tissues and may be useful for embedding hepatocytes for different therapeutic interventions or the development of in vitro models to study the pathogenesis of liver diseases or testing of drugs. Here, we developed two types of hydrogels by crosslinking hydrazide-functionalized gelatin with either oxidized dialdehyde hyaluronan or alginate through the formation of hydrazone bonds. Gel formulations were studied through texture analysis and rheometry, showing mechanical properties comparable to those of liver tissue while also demonstrating long-term stability. The biocompatibility of hydrogels and their ability to host hepatocytes was studied in vitro in comparison to pure gelatin hydrogels crosslinked by transglutaminase using the hepatocellular line HepG2. It was found that HepG2 cells could be successfully embedded in the hydrogels, showing no signs of gel toxicity and proliferating in a 3D environment comparable to pure transglutaminase cross-linked gelatin hydrogels used as control. Altogether, hydrazide gelatin in combination with oxidized polysaccharides makes stable in situ gelling systems for the incorporation of hepatocytes, which may pave the way for use in liver tissue engineering and drug testing.

Application of hydrogel scaffolds as a cell substrate for cartilage tissue regeneration

Cell therapy or tissue engineering is currently one of the potentially effective strategies for repairing cartilage defects. Mesenchymal stromal cells and autologous and allogeneic chondrocytes obtained from cartilage biopsies from patients undergoing arthroscopic surgery are the most commonly used cells for tissue engineering. Matrices (scaffolds) often used during cell implantation can facilitate successful cell implantation. These can be static supporting or plastic hydrogel substances obtained by various methods from natural or synthetic materials, allowing cells to be delivered to the site damaged by injection. Significant advantages of biocompatible hydrogels in cartilage injury therapy are determined based on the properties of the natural extracellular matrix and the high plasticity required for adapting to irregular surfaces of the tissue defect and allowing injectable cell delivery. These characteristics make injectable hydrogels a promising tool for cartilage bioengineering.
 This study highlights the progress in injectable hydrogels as carriers of different cells in the repair of cartilage tissue defects, as well as the current requirements and unresolved issues related to the use of such therapeutic approaches.

Naturally Derived Injectable Dual-Cross-Linked Adhesive Hydrogel for Acute Hemorrhage Control and Wound Healing.

Developing biocompatible injectable hydrogels with high mechanical strength and rapid strong tissue adhesion for hemostatic sealing of uncontrolled bleeding remains a prevailing challenge. Herein, we engineer an injectable and photo-cross-linkable hydrogel based on naturally derived gelatin methacrylate (GelMA) and N-hydroxysuccinimide-modified poly(γ-glutamic acid) (γPGA-NHS). The chemically dual-cross-linked hydrogel rapidly forms after UV light irradiation and covalently bonds to the underlying tissue to provide robust adhesion. We demonstrate a significantly improved hemostatic efficacy of the hydrogel using various injury models in rats compared to the commercially available fibrin glue. Notably, the hydrogel can achieve hemostasis in porcine liver and spleen incision, and femoral artery puncture models. Moreover, the hydrogel is used for sutureless repair of the liver defect in a rat model with a significantly suppressed inflammatory response, enhanced angiogenesis, and superior healing efficacy compared to fibrin glue. Together, this study offers a promising bioadhesive for treating severe bleeding and facilitating wound repair.

Abstract 3188: Chitosan-glycerol injectable gel for intratumoral retention of immunotherapeutics

Abstract A novel, injectable chitosan-glycerol hydrogel was developed and characterized. Upon injection with co-formulated therapeutics, the gel vastly improved molecule retention at the injection site, as compared to molecule delivery in less viscous media. Methods. The hydrogel was formed through a centrifugation process. 70% deacetylated, medium viscosity chitosan was dissolved in 0.1M HCl. Glycerol was then added, followed by vortexing. Next, 1x PBS and 1M NaOH were added to neutralize the mixture, which induced gelation. After hydrogel centrifugation at 10,000 rpm for 5 minutes, a hydrogel was separated from precipitate. Several formulation parameters were tested, including chitosan:glycerol volume ratio, chitosan concentration, chitosan degree of deacetylation, and chitosan molecular weight. The retention of model therapeutics, formulated in hydrogel or saline vehicles, following injection in agar-based tumor phantoms was quantified via absorbance and fluorescence readings. To assess biocompatibility, a non-contact cell viability assay was performed utilizing 3T3 fibroblasts seeded in the bottom of transmembrane wells with hydrogels added to the upper chamber. After 48 hours, cells were collected and counted utilizing trypan blue. New Data. A hydrogel for intratumoral therapeutic delivery was constructed with several desirable qualities, including biocompatibility and injectability through a 25-gauge needle. Different relative glycerol to chitosan volumes, from 5 to 95 w/v % glycerol, were tested to determine a range of gelation conditions. Glycerol volume most significantly impacted gelation conditions independent of chitosan concentration, with gelation occurring between 70-85% relative volume glycerol. Increasing chitosan solution concentration and chitosan molecular weight increased the range of chitosan:glycerol ratios resulting in gelation. The hydrogel improved load retention at the agar tumor phantom injection site for various sizes of model therapeutics compared to less viscous solutions. Cytotoxicity testing of the hydrogel showed a statistically insignificant difference between the live:dead cell ratios of the experimental and negative control groups. Conclusion. An injectable, biocompatible hydrogel was created through the neutralization and centrifugation of a chitosan-glycerol solution. The hydrogel displays physiological pH, injectability through a 25-gauge needle, biocompatibility, and vastly improved therapeutic load retention at the injection site compared to less-viscous delivery media. Chitosan-glycerol hydrogels may be useful for intratumoral delivery and retention of immunomodulators within the tumor microenvironment. Citation Format: Robert L. Kobrin, Siena M. Mantooth, David A. Zaharoff. Chitosan-glycerol injectable gel for intratumoral retention of immunotherapeutics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3188.

Liposome-integrated hydrogel hybrids: Promising platforms for cancer therapy and tissue regeneration

Drug delivery platforms have gracefully emerged as an indispensable component of novel cancer chemotherapy, bestowing targeted drug distribution, elevating therapeutic effects, and reducing the burden of unwanted side effects. In this context, hybrid delivery systems artfully harnessing the virtues of liposomes and hydrogels bring remarkable benefits, especially for localized cancer therapy, including intensified stability, excellent amenability to hydrophobic and hydrophilic medications, controlled liberation behavior, and appropriate mucoadhesion to mucopenetration shift. Moreover, three-dimensional biocompatible liposome-integrated hydrogel networks have attracted unprecedented interest in tissue regeneration, given their tunable architecture and physicochemical properties, as well as enhanced mechanical support. This review elucidates and presents cutting-edge developments in recruiting liposome-integrated hydrogel systems for cancer treatment and tissue regeneration.

Preparation of stable polyvinyl alcohol/polyurea hydrogel using oligomeric compounds containing urea-bonded

The aim of this research is the production of a biocompatible hydrogel film with high stability; the polymer should absorb enough water, and its structure should be preserved in water for a long time and not disintegrate. Polyvinyl alcohol (PVA) was chosen as the main polymeric base of the desired hydrogel. Oligomeric compounds with urea bonded containing active groups at two chain ends can react with the hydroxyl groups of the polymer and play the role of a cross-linker. Urea linkage oligomers (ULO) were prepared by reacting 2 mol of sulfamic acid, 3 mol of phosphorus, and 8 mol of urea in a molten state. The amount of PVA was kept constant, while the amount of ULO was different, the prepolymer solution was mold-dried at ambient temperature and subjected to a heat press. The gel behavior and characterization of the polymer films were investigated by FT-IR, NMR, SEM, ion chromatography, and XRD analyses, the data on the tensile strength and antibacterial properties of the samples are also reported. The production of a hybrid composite consisting of PVA and polyurea under the heat press has been confirmed; the ammonium phosphate, sulfate, nitrate, and melamine powder were produced in the layer of polymer structure. This innovative hybrid polymer with a network of urea bonds can be a favorable option for skin treatment applications due to the specific characteristic of urea known as keratolytic.

3D Bioprinting Highly Elastic PEG-PCL-DA Hydrogel for Soft Tissue Fabrication and Biomechanical Stimulation.

3-D bioprinting is a promising technology to fabricate custom geometries for tissue engineering. However, most bioprintable hydrogels are weak and fragile, difficult to handle and cannot mimetic the mechanical behaviors of the native soft elastic tissues. We have developed a visible light crosslinked, single-network, elastic and biocompatible hydrogel system based on an acrylated triblock copolymer of poly(ethylene glycol) PEG and polycaprolactone (PCL) (PEG-PCL-DA). To enable its application in bioprinting of soft tissues, we have modified the hydrogel system on its printability and biodegradability. Furthermore, we hypothesize that this elastic material can better transmit pulsatile forces to cells, leading to enhanced cellular response under mechanical stimulation. This central hypothesis was tested using vascular conduits with smooth muscle cells (SMCs) cultured under pulsatile forces in a custom-made bioreactor. The results showed that vascular conduits made of PEG-PCL-DA hydrogel faithfully recapitulate the rapid stretch and recoil under the pulsatile pressure from 1 to 3 Hz frequency, which induced a contractile SMC phenotype, consistently upregulated the core contractile transcription factors. In summary, our work demonstrates the potential of elastic hydrogel for 3D bioprinting of soft tissues by fine tuning the printability, biodegradability, while possess robust elastic property suitable for manual handling and biomechanical stimulation.

Biocompatible Hydrogel Nanoparticles with Lysosomal Escape Properties for the Delivery of siRNA for the Gene Therapy of Colorectal Carcinoma

Biocompatible Hydrogel Nanoparticles with Lysosomal Escape Properties for the Delivery of siRNA for the Gene Therapy of Colorectal Carcinoma

Antibacterial Micelles-Loaded Carboxymethyl Chitosan/Oxidized Konjac Glucomannan Composite Hydrogels for Enhanced Wound Repairing.

Antibacterial hydrogels have emerged as a promising approach for effective wound treatment. However, despite extensive research on the fabrication of antibacterial hydrogels, it remains challenging to develop injectable, biocompatible, transparent, and mass-producible hydrogels with antibacterial properties. In this study, we successfully fabricated an antibacterial drug-loaded composite hydrogel, named CC45/OKG40/HS, through a Schiff base reaction between carboxymethyl chitosan (CC) and oxidized konjac glucomannan (OKG), followed by the encapsulation of stevioside-stabilized honokiol (HS) micelles. The CC45/OKG40/HS hydrogel exhibited several favorable properties, including a short gel time (<10 min), high water content (>92%), injectability, good adhesiveness, self-healing ability, and high transparency. In vitro experiments confirmed its excellent antibacterial properties, antioxidant activities, and high biocompatibility (no cytotoxicity, hemolysis ratio <5%). Furthermore, in vivo evaluation demonstrated that the CC45/OKG40/HS0.5 hydrogel accelerated wound healing by relieving inflammatory responses and enhancing re-epithelization. Given its feasibility for mass production, the findings showed that the CC45/OKG40/HS hydrogel has the potential as an advanced antibacterial wound dressing for commercial use.

Telodendrimer functionalized hydrogel platform for sustained antibiotics release in infection control

Wound infection commonly causes delayed healing, especially in the setting of chronic wounds. Local release of antibiotics is considered a viable approach to treat chronic wounds. We have developed a versatile telodendrimer (TD) platform for efficient loading of charged antibiotic molecules via a combination of multivalent and synergistic charge and hydrophobic interactions. The conjugation of TD in biocompatible hydrogel allows for topical application to provide sustained antibiotic release. Notably, a drug loading capacity as high as 20 % of the drug-to-resin dry weight ratio can be achieved. The payload content (PC) and release profile of the various antibiotics can be optimized by fine-tuning TD density and valency in hydrogel based on the charge and hydrophobic features of the drug, e.g., polymyxin B (PMB), gentamycin (GM), and daptomycin (Dap), for effective infection control. We have shown that hydrogel with moderately reduced TD density demonstrates a more favorable release profile than hydrogel with higher TD density. Antibiotics loaded in TD hydrogel have comparable antimicrobial potency and reduced cytotoxicity compared to the free antibiotics due to a prolonged, controlled drug release profile. In a mouse model of skin and soft tissue infection, the subcutaneous administration of PMB-loaded TD hydrogel effectively eliminated the bacterial burden. Overall, these results suggest that engineerable TD hydrogels have great potential as a topical treatment to control infection for wound healing. Statement of significanceWound infection causes a significant delay in the wound healing process, which results in a significant financial and resource burden to the healthcare system. PEGA-telodendrimer (TD) resin hydrogel is an innovative and versatile platform that can be fine-tuned to efficiently encapsulate different antibiotics by altering charged and hydrophobic structural moieties. Additionally, this platform is advantageous as the TD density in the resin can also be fine-tuned to provide the desired antibiotic payload release profile. Sustained antibiotics release through optimization of TD density provides a prolonged therapeutic window and reduces burst release-induced cytotoxicity compared to conventional antibiotics application. Studies in a preclinical mouse model of bacteria-induced skin and soft tissue infection demonstrated promising therapeutic efficacy as evidenced by effective infection control and prolonged antibacterial efficacy of antibiotics-loaded PEGA-TD resin. In conclusion, the PEGA-TD resin platform provides a highly customizable approach for effective antibiotics release with significant potential for topical application to treat various bacterial wound infections to promote wound healing.