This review critically analyzes the structure–function engineering principles governing hydrogel–MOF hybrid systems and examines how established regenerative functions may be integrated with emerging antiviral biointerface concepts.
Abstract
Chronic wounds constitute a major clinical and socioeconomic burden owing to prolonged inflammation, persistent bacterial infection, impaired angiogenesis, and defective extracellular matrix remodeling. Advanced wound dressings have traditionally been developed to promote tissue regeneration, control bacterial infection, and restore the wound microenvironment. Recent advances have focused on multifunctional biomaterials integrating regenerative, antibacterial, anti-inflammatory, antioxidant, and controlled drug-delivery properties. Within this context, antiviral biointerface engineering has emerged as a promising, although still exploratory, materials-engineering perspective rather than an established function of wound dressings. Hydrogel–metal–organic framework (MOF) hybrid polymer composites have emerged as versatile platforms for multifunctional wound dressings. Hydrogels provide hydrated three-dimensional matrices with tunable porosity, swelling behavior, mechanical compliance, and biocompatibility, whereas MOFs contribute high surface area, adjustable pore architectures, chemically tailorable active sites, and controlled ion release. Their integration generates synergistic systems whose performance is governed by structure–function relationships involving polymer crosslinking density, MOF dispersion, pore hierarchy, interfacial adhesion, swelling dynamics, and surface functionalization. Collectively, these parameters regulate mass transport, mechanical stability, therapeutic delivery, and cytocompatibility while potentially influencing virus–material interactions through engineered biointerfaces. Current evidence indicates that direct experimental demonstrations of antiviral performance in hydrogel–MOF wound dressing systems remain limited. Accordingly, antiviral biointerface functions should be regarded as emerging engineering opportunities requiring further experimental validation before clinical translation. This review critically analyzes the structure–function engineering principles governing hydrogel–MOF hybrid systems and examines how established regenerative functions may be integrated with emerging antiviral biointerface concepts. Unlike previous reviews focused primarily on drug delivery, antibacterial activity, or tissue engineering, this review emphasizes the relationships between polymer architecture, MOF chemistry, interfacial design, and transport phenomena while explicitly distinguishing experimentally supported evidence from prospective mechanistic concepts. Particular attention is given to current limitations, translational challenges, and future directions for the rational design of next-generation multifunctional hydrogel–MOF wound dressings.
The skin serves as the primary barrier against external physical damage and microbial invasion. When the skin is compromised, effective wound management becomes essential for maintaining tissue integrity and preventing complications. Although conventional wound dressings provide basic protection, they often fail to meet the complex and dynamic requirements of different stages of wound healing. Owing to their highly hydrated three-dimensional networks, tunable physicochemical properties, and excellent biocompatibility, hydrogels have emerged as promising platforms for advanced wound care. Recent advances in material engineering have enabled hydrogels to integrate multiple therapeutic functions, including hemostasis, antibacterial activity, immunomodulation, antioxidant regulation, angiogenesis promotion, scar reduction, and controlled drug delivery, thereby facilitating coordinated tissue regeneration. This review summarizes recent advances in hydrogel-based wound dressings, including the biological process of skin wound healing, hydrogel material classification, fabrication and crosslinking strategies, and multifunctional hydrogel design. Particular attention is given to the relationship between hydrogel functions and different stages of wound healing, as well as the advantages and limitations of various hydrogel systems. Finally, current challenges related to mechanical properties, clinical translation, large-animal evaluation, and manufacturing standardization are discussed, together with emerging strategies such as stimulus-responsive hydrogels and programmable therapeutic systems for future wound management.
Healing a wound is a complex biological process involving hemostasis, inflammation, cell proliferation, and tissue remodeling. Ad interim, polysaccharide based biomaterials have also attracted significant attention in wound healing due to their intrinsic biocompatibility, biodegradability and structural versatility, and ability to actively modulate the wound microenvironment. This review focuses on key polysaccharides, including alginate, chitosan and hyaluronic acid and discusses their roles across different stages of wound healing by correlating material structure with biological performance. The relationship between material structure and biological performance is discussed to understand their therapeutic effects. Recent advances in hybrid biomaterials, ion-coordination strategies, and stimuli-responsive dressings are highlighted for their roles in enhancing antimicrobial activity, promoting angiogenesis, and enabling controlled therapeutic delivery. Special emphasis is also placed on the emerging role of polysaccharide-based biomaterials in combating chronic wound-associated biofilms through disruption of the extracellular polymeric substance matrix, modulation of quorum-sensing pathways, and localized antimicrobial delivery. These multifunctional approaches improve infection control while simultaneously supporting tissue regeneration, thereby addressing one of the principal challenges associated with chronic wound management. The purpose of this review is to look at the impact of the use of these materials on the environment, specifically by looking at both their biodegradability and lessening of our dependency on synthetic polymers, as well as presenting an integrated design framework that links the composition, physicochemical characteristics, and biological demands of biomaterials within a time-based context to provide a rational approach for developing future wound dressings. Despite promising progress, challenges related to reproducibility, scalability, and clinical translation remain significant, underscoring the need for standardized evaluation and interdisciplinary approaches.
Pritiman Pothal, Sunny Chugh, Guramrit Kaur et al.· Frontiers in Cellular and In...· 0 citations
Chronic wounds are complex environments marked by persistent inflammation, oxidative stress, hypoxia, and conditions that favor antimicrobial resistance (AMR). Conventional antibiotics often fail due to bacterial persistence and the physicochemical barriers of the wound milieu. Biofilm-associated extracellular polymeric substances (EPS), efflux pump activity, quorum sensing (QS), and horizontal gene transfer (HGT) collectively drive antimicrobial tolerance and resistance dissemination, turning chronic wounds into reservoirs of multidrug-resistant pathogens. Consequently, emerging wound therapies demand multifunctional strategies that modulate the wound microenvironment while interfering with resistance-associated phenotypes. Hydrogel–metal–organic framework (MOF) composites have been explored as multifunctional interfaces that combine extracellular matrix-mimetic properties, tunable porosity, stimuli-responsiveness, and controlled therapeutic delivery with the bioactive functions of MOFs. Depending on their composition and architecture, these systems may exert antimicrobial and antibiofilm effects through ionic, electrostatic, osmotic, catalytic, and oxidative mechanisms, while also influencing ROS levels, inflammation, angiogenesis, and local drug transport. However, antimicrobial activity alone does not equate to resistance modulation. Evidence for direct effects on efflux systems, resistance phenotypes, or HGT remains inconsistent across reported platforms. This review critically examines representative hydrogel–MOF systems for chronic wound applications, comparing their composition, physicochemical properties, biological functions, proposed resistance-related mechanisms, advantages, limitations, and current level of evidence. We emphasize distinguishing experimentally demonstrated resistance-modulating effects from mechanistically proposed functions, and identifying design trade-offs and evidence gaps that must be addressed to develop wound interfaces capable of both supporting tissue regeneration and improving infection control.
Nallely G. Hernández-Hernández, Irving A. González-Lara, L. K. Usme-Duque et al.· Gels· 0 citations
Acute and chronic wounds remain a major clinical burden, motivating the design of multilayer biomedical composite systems capable of combining structural support, antimicrobial protection, and controlled release of therapeutic agents within a single device. These architectures integrate natural and synthetic biomaterials, hydrogels, electrospun membranes, bioactive nanoparticles, and 3D-printed scaffolds to reproduce the multifunctionality of the native extracellular matrix. This review examines how layer-by-layer design and biomaterial selection govern mechanical strength, as well as bioactivity, and how these parameters can be tuned to the distinct phases of wound repair. Particular emphasis is placed on strategies for incorporating growth factors, antimicrobial agents, metal/metal-oxide nanoparticles to enhance re-epithelialization, angiogenesis, and infection control; emerging gene-based delivery strategies are also discussed. The main technologies and biomaterial combinations reported to date are compared, alongside a critical overview of their in vitro and in vivo performance. Reproducibility, scalability, and regulatory standardization remain the main barriers to clinical translation. We conclude by outlining priority research directions to advance multilayer composites from bench-scale prototypes toward approved wound-care products.
Jocelyn Marcela Alcalá-Zacarías, J. M. Cornejo-Bravo, A. Serrano-Medina et al.· Journal of Composites Scienc...· 0 citations
A green, sustainable strategy for fabricating antibacterial, immunomodulatory bioactive granular hydrogels (GHs) for infected wound regeneration and provides a biomaterial-based strategy for remodeling the immune microenvironment.
Refractory diabetic wounds are chronic healing disorders characterized by a complex pathological microenvironment involving excessive oxidative stress, persistent inflammation, bacterial infection, and impaired angiogenesis. Existing functional nanobiomaterials often exhibit rapid release and limited therapeutic functionality, resulting in insufficient retention at wound sites and inadequate regulation of the different stages of wound healing. To address these limitations, we developed a composite hydrogel incorporating organic-inorganic peptide-zinc nanoflowers for sustained local delivery. The nanoflowers were formed through the co-assembly of Zn²⁺ with azide-functionalized FP2 (N₃-ERGVVSIKGV) and subsequently covalently immobilized within a click-crosslinked hyaluronic acid network via strain-promoted azide-alkyne cycloaddition. The hierarchical nanoflower architecture, covalent immobilization, and hydrogel network confinement collectively prolonged local retention and enabled sustained release of the bioactive components. The resulting hydrogel regulated the diabetic wound microenvironment through antibacterial, antioxidant, anti-inflammatory, and pro-angiogenic activities, thereby promoting tissue regeneration and accelerating wound closure. These findings demonstrate a multifunctional sustained-delivery strategy for the treatment of complex diabetic wounds.
Xin Dan, Han Chen, Song-Jie Li et al.· Regenerative Biomaterials· 0 citations
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