Aug 2026· Frontiers in Cell and Developmental Biology· Vol 14· 0 citations· 105 references
Medicine
TL;DR
A hydrogel-enabled perspective supports indication-driven design and more rigorous evaluation of local biomaterial strategies for PJI and indicates that hydrogels are not universally superior when mechanical support, established surgical familiarity, or long-term structural stability is required.
Abstract
Periprosthetic joint infection (PJI) is sustained by implant-associated biofilms, ineffective immune activation, oxidative stress, and impaired osseointegration, and therefore requires more than local bacterial killing alone. Hydrogel-based therapies have attracted growing attention, but their biological effects are often attributed indiscriminately to the hydrogel even when they are primarily produced by incorporated antibiotics, antimicrobial peptides, enzymes, nanoparticles, growth factors, or cells. This narrative review develops a material-centered framework that distinguishes three sources of therapeutic activity: matrix-intrinsic functions, payload-derived biological effects, and hydrogel-enabled effects. We summarize the interface-specific pathophysiology of PJI and analyze the hydrogel properties most relevant to peri-implant treatment, including local retention, injectability, conformability to irregular dead space, wet-surface and implant-interface adaptation, tunable degradation, controlled or stimuli-responsive release, and extracellular matrix-like support. Representative antibacterial, antibiofilm, redox-regulating, immunomodulatory, angiogenic, and osteogenic systems are assessed according to their material composition, payload, release mechanism, experimental model, and direct relevance to true PJI. Hydrogels are also compared with polymethylmethacrylate cement, calcium sulfate carriers, nanoparticles or microspheres, electrospun scaffolds, and conventional implant coatings to clarify their scenario-specific advantages and limitations. The available evidence indicates that hydrogels are most valuable when they improve spatial retention, temporal sequencing, interface contact, or compatibility with labile therapeutics; they are not universally superior when mechanical support, established surgical familiarity, or long-term structural stability is required. Translation will depend on clinically representative implant-associated models, standardized reporting, sterilization and storage compatibility, reproducible manufacturing, surgical usability, and proportionate regulatory complexity. This hydrogel-enabled perspective supports indication-driven design and more rigorous evaluation of local biomaterial strategies for PJI.
Periprosthetic joint infection (PJI) remains one of the most serious complications of arthroplasty, largely due to the formation of microbial biofilms on implant surfaces. Biofilm-associated infections exhibit increased tolerance to antimicrobial therapy and host immune responses, making eradication difficult and often requiring repeated surgical interventions. Consequently, there is a growing need for effective local therapeutic strategies capable of delivering high concentrations of antimicrobial agents directly to the site of infection while minimizing systemic toxicity. Hydrogels have emerged as promising drug delivery platforms for the management of biofilm-associated PJI. Their biocompatibility, injectability, high water content, and tunable physicochemical properties enable controlled and localized release of therapeutic agents within the infected peri-implant environment. This narrative review summarizes recent advances in hydrogel-based approaches, including antibiotic-loaded hydrogels, systems incorporating anti-biofilm enzymes, bacteriophage-loaded formulations, and nanoparticle-enhanced platforms. It also highlights future research directions, with particular emphasis on the need for expanded clinical studies to facilitate the translation of emerging hydrogel-based therapies into clinical practice. Further development of these systems should focus on the incorporation of novel therapeutic agents into hydrogel platforms, aiming to enhance biofilm eradication and improve treatment outcomes in patients with PJI. Particular attention is given to stimuli-responsive (“smart”) hydrogels that release therapeutic payloads in response to infection-related triggers such as pH changes, with emphasis on the need for expanded clinical studies to facilitate the translation of emerging hydrogel-based therapies into clinical practice. Further development of these systems should focus on the incorporation of novel therapeutic agents into hydrogel platforms, aiming to enhance biofilm eradication and improve treatment outcomes in patients with PJI.
Karolina Kraus, Paweł Mikziński, Bindu Subhadra et al.· Microorganisms· 0 citations
Bacterial infection, biofilm formation, and the associated oxidative stress and persistent inflammation represent major obstacles to wound healing, tissue engineering, and implantable medical devices. Owing to their highly hydrated three-dimensional networks, favorable tissue compatibility, and versatile capacity for functional loading, hydrogels have been widely investigated for the treatment of infected wounds. This review systematically summarizes the major antibacterial mechanisms of hydrogels, including cationic contact-killing, chemical antibacterial activity mediated by metal ions and reactive halogen species, nanozyme-catalyzed reactions and bidirectional regulation of reactive oxygen species, as well as photothermal synergistic antibacterial therapy. Key design strategies are also discussed, including natural polymer-based matrices, multiple dynamic crosslinking, stimuli-responsive controlled release, three-dimensional printing, and spatial compartmentalization. In addition, recent advances in infection-microenvironment regulation, wet-interface adaptation, temporally coordinated tissue repair, and integrated diagnosis and therapy are highlighted. The field is currently shifting from single-mode bacterial eradication toward multistage tissue repair and intelligent theranostics. However, major challenges remain, including balancing antibacterial efficacy with biosafety, achieving reproducible manufacturing and sterilization-compatible formulations, maintaining functional stability during storage, and improving the clinical relevance and standardization of preclinical evaluation. In addition, most smart systems still lack quantitative coupling among pathological signals, therapeutic dosage, and treatment outcomes. Future studies should therefore integrate mechanistic design with manufacturing reproducibility, clinically relevant validation, and quantitative feedback regulation, thereby advancing antibacterial hydrogels from multifunctional proof-of-concept systems toward precise, controllable, and clinically translatable therapeutic platforms.
Implant-associated infections (IAIs) persist as a critical complication in biomaterial transplantation, driven by rapid microbial colonization, biofilm encapsulation, and escalating antibiotic resistance. Conventional antibiotic-based treatments and passive antimicrobial coatings often fail to achieve long-term infection control due to limited biofilm penetration, localized cytotoxicity, and active agent depletion. To overcome these limitations, piezoelectric nanocomposite coatings utilize a dynamic, stimulus-responsive framework that converts physiological mechanical forces or external ultrasound into localized electrical signals. These surface-bound electric fields systematically mitigate bacterial adhesion, eradicate mature biofilms via targeted reactive oxygen species (ROS) generation, disrupt microbial metabolic pathways, and favorably modulate the peri-implant immune microenvironment while supporting host tissue repair. This review evaluates the material design principles and classifications of inorganic, organic, and hybrid piezoelectric nanocoatings. We detail their multifaceted antibacterial mechanisms and trace their therapeutic potential in orthopedic and dental implants, as well as wound management. Lastly, we analyze current engineering bottlenecks to chart a clear trajectory for their clinical translation.
Antibiotic resistance and biofilm-associated infections represent persistent barriers to effective tissue healing, particularly in chronic and implant-associated wounds. Despite substantial advances in material design, most antibacterial wound dressings remain passive, empirically developed, and poorly adapted to the dynamic biological microenvironment of infection. Nanocellulose (NC), offers exceptional mechanical strength, high surface area, and excellent biocompatibility, positioning it as a versatile matrix for advanced therapeutic applications. Recent innovations focus on engineering NC composites through functionalization with bioactive moieties that enable the activation or localized release of antimicrobial agents selectively within pathological microenvironments. These advanced NC systems are specifically designed to overcome biofilm penetration barriers while minimizing systemic toxicity through site-specific intervention. This review delineates the evolution from fundamental material design principles, such as NC morphology control and surface chemistry modulation, to the development of NC-based platforms capable of disrupting mature biofilms and eliminating pathogenic bacteria. We highlight the breadth, versatility, and long-term potential of NC derivatives and composites as adaptable platforms for antibacterial and antibiofilm applications across multiple infected tissues, including skin, bone, diabetic foot ulcers, and dental infections. Furthermore, we emphasize the translational significance of NC-based hydrogels and scaffolds in future healthcare, positioning them as next-generation, clinically relevant platforms.
Tejal V. Patil, Rumi Acharya, Ki‐Taek Lim· Small· 0 citations
Periodontal diseases are highly prevalent conditions characterized by chronic inflammation, which leads to progressive destruction of tooth-supporting tissues. Conventional therapies, including scaling and root planing, grafting, and surgical procedures, are effective in controlling infection but show limited regenerative capacity. In this context, hydrogels—three-dimensional, highly hydrated polymeric biomaterials that mimic the extracellular matrix—have emerged as promising tools in periodontal regeneration. These materials can be engineered to modulate mechanical properties, porosity, and the delivery of bioactive molecules. Hydrogels can function as barrier membranes for guided tissue regeneration, scaffolds for stem cell support, and carriers for antimicrobial, anti-inflammatory, and osteogenic agents, enabling sustained and localized drug release. Recent studies have demonstrated their potential to inhibit bacterial biofilms, enhance osteogenic differentiation, and reduce inflammation in preclinical models. However, challenges remain regarding mechanical stability in the oral environment, controlled and sequential release of therapeutic agents, biocompatibility, and cost-effectiveness. Overall, hydrogels represent a promising adjunct in regenerative periodontal therapy, although further research is required to support their translation into routine clinical practice.
Francisco Jean Pierre Romero Febres, Mateus Teles Artioli Godoi, Fernando Afonso de Oliveira et al.· Applied Sciences· 0 citations
Osteoarthritis (OA) is a chronic, progressive degenerative joint disease defined by the degradation of articular cartilage, with pathological involvement of periarticular tissues including the synovium and subchondral bone. Existing conservative interventions for OA are limited to symptomatic relief and cannot reverse established cartilage degeneration, underscoring the critical unmet need to address prevailing clinical treatment bottlenecks. Hydrogel microspheres, as an emerging delivery platform integrating drug delivery capabilities with tissue engineering scaffold functions, hold substantial promise for targeted OA therapy and cartilage repair. Their core beneficial properties include minimally invasive injectability, favorable biocompatibility, sustained drug release capacity, and intelligent responsiveness. This review systematically explores the application of hydrogel microspheres in the treatment of OA and provides a detailed summary of material systems and preparation techniques—covering natural materials, synthetic polymers, and composite/hybrid materials, as well as processes such as emulsion cross-linking, microfluidics, electrospray, photolithography, and 3D printing. This paper places particular emphasis on the modulation of mechanical properties, smart responsive release mechanisms, and strategies to enhance bioactivity. Furthermore, it summarizes various therapeutic strategies supported by hydrogel microspheres, including the precise controlled release of small-molecule drugs, the regulation of endogenous stem cell recruitment and directed differentiation, the targeted delivery of gene therapy drugs, and synergistic treatment modalities. By synthesizing core research advances in this field in recent years and elucidating key technological development directions, this review provides a comprehensive reference for advancing the translation of hydrogel microspheres from basic research to clinical applications in the management of OA.
Zhuoxuan Song, Xin-Yue Song, Rui Zhao et al.· Journal of Tissue Engineerin...· 0 citations
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