Evolution of Hybrid Hydrogels: Next-Generation Biomaterials for Drug Delivery and Tissue Engineering

Abstract

Hydrogels, being hydrophilic polymer networks capable of absorbing and retaining aqueous fluids, hold significant promise in biomedical applications owing to their high water content, permeability, and structural similarity to the extracellular matrix. Recent chemical advancements have bolstered their versatility, facilitating the integration of the molecules guiding cellular activities and enabling their controlled activation under time constraints. However, conventional synthetic hydrogels suffer from inherent weaknesses such as heterogeneity and network imperfections, which adversely affect their mechanical properties, diffusion rates, and biological activity. In response to these challenges, hybrid hydrogels have emerged, aiming to enhance their strength, drug release efficiency, and therapeutic effectiveness. These hybrid hydrogels, featuring improved formulations, are tailored for controlled drug release and tissue regeneration across both soft and hard tissues. The scientific community has increasingly recognized the versatile characteristics of hybrid hydrogels, particularly in the biomedical sector. This comprehensive review delves into recent advancements in hybrid hydrogel systems, covering the diverse types, modification strategies, and the integration of nano/microstructures. The discussion includes innovative fabrication techniques such as click reactions, 3D printing, and photopatterning alongside the elucidation of the release mechanisms of bioactive molecules. By addressing challenges, the review underscores diverse biomedical applications and envisages a promising future for hybrid hydrogels across various domains in the biomedical field.

Advances in Hydrogel-Based Drug Delivery Systems

“…These networks, capable of absorbing and retaining substantial volumes of water, are distinguished by their remarkable ability to swell without dissolution, maintaining structural integrity through chemical or physical cross-linking mechanisms [9,10]. This intrinsic property allows hydrogels to mimic the physicochemical aspects of the natural extracellular matrix, making them particularly suited for applications in drug delivery systems [7,9,[11][12][13][14][15][16][17][18][19], tissue engineering [20][21][22][23][24], wound healing [25][26][27][28], and beyond, as illustrated in Figure 1. The initiation of hydrogel research and its expansion into biomedical sciences exemplify a trajectory of innovation, highlighting the versatility of these materials in solving complex biological challenges and their role in advancing biomedical solutions.…”

Synthesis of Thermoresponsive Chitosan-graft-Poly(N-isopropylacrylamide) Hybrid Copolymer and Its Complexation with DNA

“…PNIPAM is an acrylamide synthetic polymer for grafting of Chit backbones [20,23,34,35,37]. Chit-g-PNIPAM copolymers have been identified as potentially thermoresponsive and pHresponsive materials for drug delivery [38][39][40] and tissue engineering [41,42]. Additionally, it has been shown that they improve the oral delivery of hydrophobic medications, such as naproxen, caffeine, and paclitaxel, and favors the mucosal delivery of hydrophobic pharmaceuticals [40].…”

Keratin–PNIPAM Hybrid Microgels: Preparation, Morphology and Swelling Properties

“…Among these materials, hybrid systems combining synthetic polymers with natural biomolecules have emerged as promising candidates in the biomedical field, offering tailored properties and enhanced functionalities [5][6][7][8][9][10]. One of the most relevant examples is the combination of proteins with synthetic polymers [11,12], which has been demonstrated to affect cell adhesion, differentiation and proliferation and is thus appealing for applications such as drug delivery, tissue engineering and wound healing [5,[13][14][15][16]. In this context, the integration of poly(N-isopropylacrylamide) (PNIPAM) microgels with keratin, a fibrous protein, offers a promising approach for the development of novel biomaterials with a wide range of applications.…”