Conductive biomaterials based on conductive polymers, carbon nanomaterials, or conductive inorganic nanomaterials demonstrate great potential in wound healing and skin tissue engineering, owing to the similar conductivity to human skin, good antioxidant and antibacterial activities, electrically controlled drug delivery, and photothermal effect. However, a review highlights the design and application of conductive biomaterials for wound healing and skin tissue engineering is lacking. In this review, the design and fabrication methods of conductive biomaterials with various structural forms including film, nanofiber, membrane, hydrogel, sponge, foam, and acellular dermal matrix for applications in wound healing and skin tissue engineering and the corresponding mechanism in promoting the healing process were summarized. The approaches that conductive biomaterials realize their great value in healing wounds via three main strategies (electrotherapy, wound dressing, and wound assessment) were reviewed. The application of conductive biomaterials as wound dressing when facing different wounds including acute wound and chronic wound (infected wound and diabetic wound) and for wound monitoring is discussed in detail. The challenges and perspectives in designing and developing multifunctional conductive biomaterials are proposed as well.
Highlights:
1 The design and application of conductive biomaterials for wound healing are comprehensively reviewed, including versatile conductive agents, the various forms of conductive wound dressings, and different in vivo applications.2 Three main strategies of which conductive biomaterials realizing their applications in wound healing and skin tissue engineering are discussed.3 The challenges and perspectives in designing multifunctional conductive biomaterials and further clinical translation are proposed.

Conductive Biomaterials as Bioactive Wound Dressing for Wound Healing and Skin Tissue Engineering.

Due to the emerging bacterial resistance and the protection of tenacious biofilms, it is hard for the single antibacterial modality to achieve satisfactory therapeutic effects nowadays. In recent years, photothermal therapy (PTT)-derived multimodal synergistic treatments have received wide attention and exhibited cooperatively enhanced bactericidal activity. PTT features spatiotemporally controllable generation of hyperthermia that could eradicate bacteria without inducing resistance. The synergy of it with other treatments, such as chemotherapy, photo-dynamic/catalytic therapy (PDT/PCT), immunotherapy, and sonodynamic therapy (SDT), could lower the introduced laser density in PTT and avoid undesired overheating injury of normal tissues. Simultaneously, by heat-induced improvement of the bacterial membrane permeability, PTT is conducive for accelerated intracellular permeation of chemotherapeutic drugs as well as reactive oxygen species (ROS) generated by photosensitizers/sonosensitizers, and could promote infiltration of immune cells. Thereby, it could solve the currently existing sterilization deficiencies of other combined therapeutic modes, for example, bacterial resistance for chemotherapy, low drug permeability for PDT/PCT/SDT, adverse immunoreactions for immunotherapy, etc. Admittedly, PTT-derived synergistic treatments are becoming essential in fighting bacterial infection, especially those caused by antibiotic-resistant strains. This review firstly presents the classical and newly reported photothermal agents (PTAs) in brief. Profoundly, through the introduction of delicately designed nanocomposite platforms, we systematically discuss the versatile photothermal-derived multimodal synergistic therapy with the purpose of sterilization application. At the end, challenges to PTT-derived combinational therapy are presented and promising synergistic bactericidal prospects are anticipated.

Emerging photothermal-derived multimodal synergistic therapy in combating bacterial infections.

Application of conducting polymers to wound care and skin tissue engineering: A review.

An upsurge in the multidrug-resistant (MDR) bacterial pestilence is a global cause for concern in terms of human health. Lately, nanomaterials with photothermal effects have assisted in the efficient killing of MDR bacteria, attributable to their uncommon plasmonic, photocatalytic, and structural properties. Examinations of substantial amounts of photothermally enabled nanomaterials have shown bactericidal effects in an optimized time under near-infrared (NIR) light irradiation. In this review, we have compiled recent advances in photothermally enabled nanomaterials for antibacterial activities and their mechanisms. Photothermally enabled nanomaterials are classified into three groups, including metal-, carbon-, and polymer-based nanomaterials. Based on substantial accomplishments with photothermally enabled nanomaterials, we have inferred current trends and their prospective clinical applications.

Nanomaterials for the photothermal killing of bacteria

Bacterial infectious diseases and bacterial-infected environments have been threatening the health of human beings all over the world. In view of the increased bacteria resistance caused by overuse or improper use of antibiotics, antibacterial biomaterials are developed as the substitutes for antibiotics in some cases. Among them, antibacterial hydrogels are attracting more and more attention due to easy preparation process and diversity of structures by changing their chemical cross-linkers via covalent bonds or noncovalent physical interactions, which can endow them with various specific functions such as high toughness and stretchability, injectability, self-healing, tissue adhesiveness and rapid hemostasis, easy loading and controlled drug release, superior biocompatibility and antioxidation as well as good conductivity. In this review, the recent progress of antibacterial hydrogel including the fabrication methodologies, interior structures, performances, antibacterial mechanisms, and applications of various antibacterial hydrogels is summarized. According to the bacteria-killing modes of hydrogels, several representative hydrogels such as silver nanoparticles-based hydrogel, photoresponsive hydrogel including photothermal and photocatalytic, self-bacteria-killing hydrogel such as inherent antibacterial peptides and cationic polymers, and antibiotics-loading hydrogel are focused on. Furthermore, current challenges of antibacterial hydrogels are discussed and future perspectives in this field are also proposed.

Antibacterial Hybrid Hydrogels.

The introduction and designing of functional thermoresponsive hydrogels have been recommended as recent potential therapeutic approaches for biomedical applications. The development of bioactive materials such as thermosensitive gelatin-incorporated nano-organic materials with a porous structure and photothermally triggerable and cell adhesion properties may potentially achieve this goal. This novel class of photothermal hydrogels can provide an advantage of hyperthermia together with a reversibly transformable hydrogel for tissue engineering. Polypyrrole (Ppy) is a bioorganic conducting polymeric substance and has long been used in biomedical applications owing to its brilliant stability, electrically conductive features, and excellent absorbance around the near-infrared (NIR) region. In this study, a cationic photothermal triggerable/guidable gelatin hydrogel containing a polyethylenimine (PEI)–Ppy nanocomplex with a porous microstructure was established, and its physicochemical characteristics were studied through dynamic light scattering, scanning electronic microscopy, transmission electron microscopy, an FTIR; and cellular interaction behaviors towards fibroblasts incubated with a test sample were examined via MTT assay and fluorescence microscopy. Photothermal performance was evaluated. Furthermore, the in vivo study was performed on male Wistar rat full thickness excisions model for checking the safety and efficacy of the designed gelatin–PEI–Ppy nanohydrogel system in wound healing and for other biomedical uses in future. This photothermally sensitive hydrogel system has an NIR-triggerable property that provides local hyperthermic temperature by PEI–Ppy nanoparticles for tissue engineering applications. Features of the designed hydrogel may fill other niches, such as being an antibacterial agent, generation of free radicals to further improve wound healing, and remodeling of the promising photothermal therapy for future tissue engineering applications.

https://www.mdpi.com/1420-3049/23/6/1256/pdf

Po Hsien Ho

Papers

A Gelatin Hydrogel-Containing Nano-Organic PEI⁻Ppy with a Photothermal Responsive Effect for Tissue Engineering Applications.