Hydrogels as a Potential Biomaterial for Multimodal Therapeutic Applications

Abstract

Hydrogels, composed of hydrophilic polymer networks, have emerged as versatile materials in biomedical applications due to their high water content, biocompatibility, and tunable properties. They mimic natural tissue environments, enhancing cell viability and function. Hydrogels' tunable physical properties allow for tailored antibacterial biomaterial, wound dressings, cancer treatment, and tissue engineering scaffolds. Their ability to respond to physiological stimuli enables the controlled release of therapeutics, while their porous structure supports nutrient diffusion and waste removal, fostering tissue regeneration and repair. In wound healing, hydrogels provide a moist environment, promote cell migration, and deliver bioactive agents and antibiotics, enhancing the healing process. For cancer therapy, they offer localized drug delivery systems that target tumors, minimizing systemic toxicity and improving therapeutic efficacy. Ocular therapy benefits from hydrogels' capacity to form contact lenses and drug delivery systems that maintain prolonged contact with the eye surface, improving treatment outcomes for various eye diseases. In mucosal delivery, hydrogels facilitate the administration of therapeutics across mucosal barriers, ensuring sustained release and the improved bioavailability of drugs. Tissue regeneration sees hydrogels as scaffolds that mimic the extracellular matrix, supporting cell growth and differentiation for repairing damaged tissues. Similarly, in bone regeneration, hydrogels loaded with growth factors and stem cells promote osteogenesis and accelerate bone healing. This article highlights some of the recent advances in the use of hydrogels for various biomedical applications, driven by their ability to be engineered for specific therapeutic needs and their interactive properties with biological tissues.

Keywords: Cancer immunotherapy; Injectable hydrogels; Periodontitis; Smart hydrogels; Tissue regeneration; Wound healing.

Figure 1

Types of natural polymers used from hydrogel preparation, and its application as an antibacterial agent for wound healing. Parts of the figure were drawn by using pictures from Servier Medical Art. Servier Medical Art is licensed under CC BY 4.0.

Figure 2

(A) Inhibition zones on three strains of bacteria, 1, 2, and 3, representing blank, chitosan hydrogel, and chitosan hydrogel loaded with doxycycline, respectively, showing the effective antibacterial activity of chitosan hydrogel loaded with doxycycline. (B) Hemolytic activity assay of the hydrogels where 0.1% triton is a positive control. (C) Histocompatibility with HE staining of skin tissue after hydrogel incubation at different weight ratios. (D) In vivo wound healing outcome on the 3rd, 7th, and 14th days for different groups showing doxycycline loading having effective would closure. Adapted with permission from ref (67). Copyright 2020 American Chemical Society.

Figure 3

(A) Cell migration assay using the Transwell chamber showing gingipain-responsive hydrogel having efficient cell migration. (B) Three-dimensional reconstructed images of micro-CT and measurement of alveolar bone absorption 4 weeks after hydrogel injection showing PEGPD@SDF-1 with the most potent activity. Data are presented as mean ± SD, N = 6. *, p < 0.05; **, p < 0.01; ***, p < 0.001; ****, p < 0.0001. (C) H&E staining images of periodontal tissue between the maxillary first molar and the second molar, 4 weeks after hydrogel injection. Adapted with permission from ref (31). Copyright 2021 American Chemical Society

Figure 4

(A) Confocal real-time fluorescence images of B16-GFP cells treated with the melittin-RADA32-Dox (MR-Dox) hydrogel. For estimating cell death, propidium iodide (red) was used. Untreated cells showed green fluorescence, while with increasing MR hydrogel treatment duration, cells showed yellow fluorescence (red + green), indicating increased cell death. (B) In vivo NIR fluorescence imaging of the distribution of MR-Cy7 hydrogel and Cy7 dye after subcutaneous injection at various time points (C) along with its quantitative data showing more cy7 accumulation in the case of hydrogel-mediated delivery for a prolonged period. (D) Tumor growth curves for mice intratumorally injected with PBS, DOX, RD, MR, or MRD hydrogel. (E) Quantification of the second tumor growth showing long-term immune-memory effects of MRD hydrogel. Adapted with permission from ref (144). Copyright 2018 American Chemical Society.

Figure 5

(A) Dilution of star-PEG-A (20 wt/vol %) with a nonreactive PEG-based diluent (here, 0.2 kDa PEG-OH) led to a visually white, heterogeneous hydrogel (left) consisting of water-filled micrometer-scale voids and nanoporous polymer regions, whereas by diluting with water, a homogeneous hydrogel (right) was formed with a transparent appearance and pores in the nanometer scale (scale bar is 2 mm in macroscopic hydrogel and 5 μm for FESEM). (B) Ability of the Anisogel to align fibroblasts when mixed with different concentrations (1.0, 2.0, and 3.0 vol %) of soft microgels, which aligned in a magnetic field of 130 mT. Premixed fibroblasts extended along the longitudinal microgel axis (green, fluorescein), visible by the stretched F-actin filaments (red, Alexa Fluor 594 phalloidin), depending on the microgel concentration (scale bar is 50 μm). (C) DRGs were positioned in hydrogels with 3 vol % microgels (green, fluorescein) containing random or magnetically aligned microgels. β-Tubulin staining (red, Alexa Fluor 633) revealed neurite outgrowth parallel to the aligned microgels (outside full white circle; scale bar is 200 μm). Adapted with permission from ref (201). Copyright 2017 American Chemical Society.

Figure 6

(A) Scanning electron microscopy image of chitosan and hyaluronic acid hydrogel at 100× and 200× magnification. (B) Biocompatibility of the hydrogel as observed from a L929 cell growth study in (a) the control group and (b) hydrogel treated. (C) In vivo biocompatibility of hydrogel on skin tissue at week 1, 2, 3, 4, 6, and 8 (a1, a2, a3, a4, a5, and a6, respectively) after hydrogel treatment. H&E stained images of subcutaneous tissue at the injection sites at the same time duration (b1–b6). Adapted with permission from ref (214). Copyright 2020 Elsevier Ltd.