Stimuli-Mediated Macrophage Switching, Unraveling the Dynamics at the Nanoplatforms-Macrophage Interface.

Macrophages play an essential role in immunotherapy and tissue regeneration owing to their remarkable plasticity and diverse functions. Recent bioengineering developments have focused on using external physical stimuli such as electric and magnetic fields, temperature, and compressive stress, among others, on micro/nanostructures to induce macrophage polarization, thereby increasing their therapeutic potential. However, it is difficult to find a concise review of the interaction between physical stimuli, advanced micro/nanostructures, and macrophage polarization. This review examines the present research on physical stimuli-induced macrophage polarization on micro/nanoplatforms, emphasizing the synergistic role of fabricated structure and stimulation for advanced immunotherapy and tissue regeneration. We provide a concise overview of the research advancements investigating the impact of physical stimuli-including electric fields, magnetic fields, compressive forces, fluid shear stress, photothermal stimuli, and multiple stimulations on the polarization of macrophages within complex engineered structures. The prospective implications of these strategies in regenerative medicine and immunotherapeutic approaches have been highlighted. This review will aid in creating stimuli-responsive platforms for immunomodulation and tissue regeneration. This article is protected by copyright. All rights reserved.

Recent advances and biomedical application of 3D printed nanocellulose-based adhesive hydrogels: A review.

Nanocellulose-based tissue adhesives show promise for achieving rapid hemostasis and effective wound healing. Conventional methods, such as sutures and staples, have limitations, prompting the exploration of bioadhesives for direct wound adhesion and minimal tissue damage. Nanocellulose, a hydrolysis product of cellulose, exhibits superior biocompatibility and multifunctional properties, gaining interest as a base material for bioadhesive development. This study explores the potential of nanocellulose-based adhesives for hemostasis and wound healing using 3D printing techniques. Nanocellulose enables the creation of biodegradable adhesives with minimal adverse effects and opens avenues for advanced wound healing and complex tissue regeneration, such as skin, blood vessels, lungs, cartilage, and muscle. This study reviews recent trends in various nanocellulose-based 3D printed hydrogel patches for tissue engineering applications. The review also introduces various types of nanocellulose and their synthesis, surface modification, and bioadhesive fabrication techniques via 3D printing for smart wound healing.

Stimuli-Responsive 3D Printable Conductive Hydrogel: A Step toward Regulating Macrophage Polarization and Wound Healing.

Conductive hydrogels (CHs) are promising alternatives for electrical stimulation of cells and tissues in biomedical engineering. Wound healing and immunomodulation are complex processes that involve multiple cell types and signaling pathways. 3D printable conductive hydrogels have emerged as an innovative approach to promote wound healing and modulate immune responses. CHs can facilitate electrical and mechanical stimuli, which can be beneficial for altering cellular metabolism and enhancing the efficiency of the delivery of therapeutic molecules. This review summarizes the recent advances in 3D printable conductive hydrogels for wound healing and their effect on macrophage polarization. This report also discusses the properties of various conductive materials that can be used to fabricate hydrogels to stimulate immune responses. Furthermore, this review highlights the challenges and limitations of using 3D printable CHs for future material discovery. Overall, 3D printable conductive hydrogels hold excellent potential for accelerating wound healing and immune responses, which can lead to the development of new therapeutic strategies for skin and immune-related diseases.

Polyphenolic Carbon Quantum Dots with Intrinsic Reactive Oxygen Species Amplification for Two-Photon Bioimaging and In Vivo Tumor Therapy.

Recent studies indicate that mitochondrial dysfunctions and DNA damage have a critical influence on cell survival, which is considered one of the therapeutic targets for cancer therapy. In this study, we demonstrated a comparative study of the effect of polyphenolic carbon quantum dots (CQDs) on in vitro and in vivo antitumor efficacy. Dual emissive (green and yellow) shape specific polyphenolic CQDs (G-CQDs and Y-CQDs) were synthesized from easily available nontoxic precursors (phloroglucinol), and the antitumor property of the as-synthesized probe was investigated as compared to round-shaped blue emissive CQDs (B-CQDs) derived from well-reported precursor citric acid and urea. The B-CQDs had a nuclei-targeting property, and G-CQDs and Y-CQDs had mitochondria-targeting properties. We have found that the polyphenol containing CQDs (at a dose of 100 µg mL-1) specifically attack mitochondria by excess accumulation, altering the metabolism, inhibiting branching pattern, imbalanced Bax/Bcl-2 homeostasis, and ultimately generating oxidative stress levels, leading to oxidative stress-induced cell death in cancer cells in vitro. We show that G-CQDs are the main cause of oxidative stress in cancer cells because of their ability to produce sufficient •OH- and 1O2 radicals, evidenced by electron paramagnetic resonance spectroscopy and a terephthalic acid test. Moreover, the near-infrared absorption properties of the CQDs were exhibited in two-photon (TP) emission, which was utilized for TP cellular imaging of cancer cells without photobleaching. The in vivo antitumor test further discloses that intratumoral injection of G-CQDs can significantly augment the treatment efficacy of subcutaneous tumors without any adverse effects on BalB/c nude mice. We believe that shape-specific polyphenolic CQD-based nanotheranostic agents have a potential role in tumor therapy, thus proving an insight on treatment of malignant cancers.

A Review on Electroactive Polymer-Metal Composites: Development and Applications for Tissue Regeneration.

Electroactive polymer-metal composites (EAPMCs) have gained significant attention in tissue engineering owing to their exceptional mechanical and electrical properties. EAPMCs develop by combining an electroactive polymer matrix and a conductive metal. The design considerations include choosing an appropriate metal that provides mechanical strength and electrical conductivity and selecting an electroactive polymer that displays biocompatibility and electrical responsiveness. Interface engineering and surface modification techniques are also crucial for enhancing the adhesion and biocompatibility of composites. The potential of EAPMC-based tissue engineering revolves around its ability to promote cellular responses, such as cell adhesion, proliferation, and differentiation, through electrical stimulation. The electrical properties of these composites can be used to mimic natural electrical signals within tissues and organs, thereby aiding tissue regeneration. Furthermore, the mechanical characteristics of the metallic components provide structural reinforcement and can be modified to align with the distinct demands of various tissues. EAPMCs have extraordinary potential as regenerative biomaterials owing to their ability to promote beneficial effects in numerous electrically responsive cells. This study emphasizes the characteristics and applications of EAPMCs in tissue engineering.

Trackable and highly fluorescent nanocellulose-based printable bio-resins for image-guided tissue regeneration.

Dynamic tracking of cell migration during tissue regeneration remains challenging owing to imaging techniques that require sophisticated devices, are often lethal to healthy tissues. Herein, we developed a 3D printable non-invasive polymeric hydrogel based on 2,2,6,6-(tetramethylpiperidin-1-yl) oxyl (TEMPO)-oxidized nanocellulose (T-CNCs) and carbon dots (CDs) for the dynamic tracking of cells. The as-prepared T-CNC@CDs were used to fabricate a liquid bio-resin containing gelatin methacryloyl (GelMA) and polyethylene glycol diacrylate (GPCD) for digital light processing (DLP) bioprinting. The shear-thinning properties of the GPCD bio-resin were further improved by the addition of T-CNC@CDs, allowing high-resolution 3D printing and bioprinting of human cells with higher cytocompatibility (viability ∼95 %). The elastic modulus of the printed GPCD hydrogel was found to be ∼13 ± 4.2 kPa, which is ideal for soft tissue engineering. The as-fabricated hydrogel scaffold exhibited tunable structural color property owing to the addition of T-CNC@CDs. Owing to the unique fluorescent property of T-CNC@CDs, the human skin cells could be tracked within the GPCD hydrogel up to 30 days post-printing. Therefore, we anticipate that GPCD bio-resin can be used for 3D bioprinting with high structural stability, dynamic tractability, and tunable mechanical stiffness for image-guided tissue regeneration.