Advances in Biomedical Hydrogels

Diabetic wound healing poses a significant clinical dilemma. Bacterial infection and immune dysregulation are the predominant reasons. However, conventional wound dressings with a single treatment approach often limit therapeutic efficacy and continue working with difficulty. These limitations cause high treatment failure for diabetic wounds. In this study, we developed a multiple drug-loaded carbomer hydrogel containing Que/Van/Rif (QVR-CBMG) for the simultaneous treatment of infection and immune dysregulation. Honeycomb-like QVR-CBMG hydrogel exhibits excellent abilities to eliminate bacterial infection and biofilms in vitro. Moreover, QVR-CBMG hydrogel possesses an immunomodulatory capacity via affecting the Sirt3/SOD2 signaling pathway to promote M2 macrophages. Furthermore, QVR-CBMG hydrogel effectively promotes wound healing in diabetic rats through several mechanisms. The multidrug-loaded wound dressing not only eliminates bacterial infection and facilitated angiogenesis but also promotes collagen deposition and remodulates the local immune microenvironment in the areas of wounds. In summary, this synthetic strategy to eliminate infection and regulate immune disorders has potential translational value for the prevention and management of diabetic wounds. Full article

Protein engineering allows for the programming of specific building blocks to form functional and novel materials with customisable physical properties suitable for tailored engineering applications. We have successfully designed and programmed engineered proteins to form covalent molecular networks with defined physical characteristics. Our hydrogel design incorporates the SpyTag (ST) peptide and SpyCatcher (SC) protein that spontaneously form covalent crosslinks upon mixing. This genetically encodable chemistry allowed us to easily incorporate two stiff and rod-like recombinant proteins in the hydrogels and modulate the resulting viscoelastic properties. We demonstrated how differences in the composition of the microscopic building blocks change the macroscopic viscoelastic properties of the hydrogels. We specifically investigated how the identity of the protein pairs, the molar ratio of ST:SC, and the concentration of the proteins influence the viscoelastic response of the hydrogels. By showing tuneable changes in protein hydrogel rheology, we increased the capabilities of synthetic biology to create novel materials, allowing engineering biology to interface with soft matter, tissue engineering, and material science. Full article

Conventional eye drops are most commonly employed topically in the eye for the management of bacterial conjunctivitis. Eye drops have a low corneal residence time and 90–95% of the administered dose is eliminated from the eye by blinking and the nasolacrimal drainage system. This problem can be minimized by formulating a mucoadhesive ocular in-situ gel system that undergoes sol-gel transition upon stimulation by temperature, pH, and ions. The goal of this study was to develop ciprofloxacin (CIP) loaded bilosomes (BLO) in-situ gel for the improvement of therapeutic efficacy. The BLO was prepared by the thin-film hydration method and optimized by the Box–Behnken design. Cholesterol (CHO), surfactant (Span 60), and bile salt (sodium deoxycholate/SDC) were used as formulation factors. The vesicle size (nm) and entrapment efficiency (%) were selected as responses (dependent factors). The optimized CIP-BLO (CIP-BLO-opt) formulation displayed a vesicle size of 182.4 ± 9.2 nm, a polydispersity index of 0.274, a zeta potential of −34,461.51 mV, and an entrapment efficiency of 90.14 ± 1.24%. Both x-ray diffraction and differential scanning calorimetry spectra did not exhibit extensive peaks of CIP in CIP-BLO-opt, revealing that CIP is encapsulated in the BLO matrix. The CIP-BLO-opt formulation was successfully incorporated into an in-situ gel system using a gelling agent, i.e., Carbopol 934P and hydroxyl propyl methyl cellulose (HPMC K100 M). CIP-BLO-opt in-situ gel formulation (CIP-BLO-opt-IG3) was evaluated for gelling capacity, clarity, pH, viscosity, in-vitro CIP release, bio-adhesive, ex-vivo permeation, toxicity, and antimicrobial study. The CIP-BLO-opt-IG3 exhibited satisfactory gelling properties with a viscosity of 145.85 ± 9.48 cP in the gelling state. CIP-BLO-opt-IG3 displayed sustained CIP release (83.87 ± 5.24%) with Korsmeyer–Peppas kinetic as a best-fitted model (R2 = 0.9667). CIP-BLO-opt-IG3 exhibited a 1.16-fold than CIP-IG and a 2.08-fold higher permeability than pure CIP. CIP-BLO-opt-IG3 displayed a significantly greater bio-adhesion property (924.52 ± 12.37 dyne/cm²) than tear film. Further, CIP-BLO-opt-IG3 does not display any toxicity as confirmed by corneal hydration (76.15%), histology, and the HET-CAM test (zero scores). CIP-BLO-opt-IG3 shows significantly higher (p < 0.05) antimicrobial activity against P. aeruginosa and S. aureus than pure CIP. From all these findings, it could be concluded that CIP-BLO-opt-IG3 might be an effective strategy for the increment of corneal residence time and therapeutic activity of CIP. Full article

Major causes of the radiation-induced disease include nuclear accidents, war-related nuclear explosions, and clinical radiotherapy. While certain radioprotective drug or bioactive compounds have been utilized to protect against radiation-induced damage in preclinical and clinical settings, these strategies are hampered by poor efficacy and limited utilization. Hydrogel-based materials are effective carriers capable of enhancing the bioavailability of compounds loaded therein. As they exhibit tunable performance and excellent biocompatibility, hydrogels represent promising tools for the design of novel radioprotective therapeutic strategies. This review provides an overview of common approaches to radioprotective hydrogel preparation, followed by a discussion of the pathogenesis of radiation-induced disease and the current states of research focused on using hydrogels to protect against these diseases. These findings ultimately provide a foundation for discussions of the challenges and future prospects associated with the use of radioprotective hydrogels. Full article

The incidence of skin cancer has increased dramatically in recent years, particularly in Caucasian populations. Specifically, the metastatic melanoma is one of the most aggressive cancers and is responsible for more than 80% of skin cancer deaths around the globe. Though there are many treatment techniques, and drugs have been used to cure this belligerent skin cancer, the side effects and reduced bioavailability of drug in the targeted area makes it difficult to eradicate. In addition, cellular metabolic pathways are controlled by the skin cancer driver genes, and mutations in these genes promote tumor progression. Consequently, the MAPK (RAS–RAF–MEK–ERK pathway), WNT and PI3K signaling pathways are found to be important molecular regulators in melanoma development. Even though hydrogels have turned out to be a promising drug delivery system in skin cancer treatment, the regulations at the molecular level have not been reported. Thus, we aimed to decipher the molecular pathways of hydrogel drug delivery systems for skin cancer in this review. Special attention has been paid to the hydrogel systems that deliver drugs to regulate MAPK, PI3K–AKT–mTOR, JAK–STAT and cGAS-STING pathways. These signaling pathways can be molecular drivers of skin cancers and possible potential targets for the further research on treatment of skin cancers. Full article

Poloxamer is a triblock copolymer with amphiphilicity and reversible thermal responsiveness and has wide application prospects in biomedical applications owing to its multifunctional properties. Poloxamer hydrogels play a crucial role in the field of tissue engineering and have been regarded as injectable scaffolds for loading cells or growth factors (GFs) in the last few years. Hydrogel micelles can maintain the integrity and stability of cells and GFs and form an appropriate vascular network at the application site, thus creating an appropriate microenvironment for cell growth, nerve growth, or bone integration. The injectability and low toxicity of poloxamer hydrogels make them a noninvasive method. In addition, they can also be good candidates for bio-inks, the raw material for three-dimensional (3D) printing. However, the potential of poloxamer hydrogels has not been fully explored owing to the complex biological challenges. In this review, the latest progress and cutting-edge research of poloxamer-based scaffolds in different fields of application such as the bone, vascular, cartilage, skin, nervous system, and organs in tissue engineering and 3D printing are reviewed, and the important roles of poloxamers in tissue engineering scaffolds are discussed in depth. Full article