Front Cover: For fabricating organs, it is essential to form specific structures. In article 2300069, Kosuke Ino, Hitoshi Shiku and co-workers present a simple, rapid, and large-scale fabrication method for multi-branched hydrogels like vasculature. Vascular cells can be cultured in the multi-branched biomaterials, which will be useful to fabricate vascularized organs.

Back Cover: Pure Positive electrostatic charges (PPECs) are used for the delivery of drug-loaded (Paclitaxel) polymeric nanoparticles (DLNs) capped with negatively charged poly(lactide-coglycolide) (PLGA) and Poly (vinyl alcohol) PVA into the tumor site. In article 2300181, Mohammad Abdolahad and co-workers find that DLNs synthesized by PLGA show great attraction to PPECs due to their stable negative charges. Regarding deposition of the PVA on the surface of drug-loaded nanoparticles, opsonization will be decreased. PPECs have many potential clinical applications for advanced-targeted chemotherapy with the lowest discernible side effects.

This review describes the classification and advantages of intelligent stimuli-responsive microneedles and emphasizes their application in the biomedical field.

Wound infections slow down the healing process and lead to complications such as septicemia, osteomyelitis, and even death. Chitosan-based hydrogels possess outstanding advantages for infected wound healing. In this review, the recent research progress of chitosan-based hydrogels for infected wound treatment is summarized. A concise assessment of current limitations and future trends is presented.

This review summarizes four leading strategies used to promote the therapeutic effects of immunogenic cell death (ICD) via nanotechnology, including increasing the localized concentration of an ICD inducer in tumor, inducing various intracellular reactions, catalyzing the activity of antigen-presenting cells, and protecting the function of cytotoxic T cells, together with an overview of the state-of-the-art clinical applications of ICD via nanotechnology.

The general properties of Polyetheretherketone (PEEK) are discussed, which can be potentially used for bone repair due to its elastic modulus and good biocompatibility and chemical stability. The study also demonstrates about the modification methods of PEEK materials, and reviewed the biological applications in bone repair and optimization strategy, inspired by structure and compositions.

Polymers are employed in gene delivery as an alternative to lipid nanoparticles. Among polymeric materials, of particular interest there are those based on repetitive units of sugars, such as oligosaccharides-based polymers and polysaccharides. Carbohydrates-based polyplexes are widely investigated in preclinical studies and can be further translated into clinically-relevant nanomedicines for the delivery of therapeutic nucleic acids for cancer therapy.

A simple, rapid, and large-scale fabrication process based on viscous fingering for forming multi-branched hydrogels for cell culture applications is proposed. In this study, only one solution and two substrates are used to form multi-branched structures within 1 min. In addition, the scaffolds are used for cell culture of vascular endothelial cells.

An external positive electrostatic charge applied to the drug-loaded polymeric (PLGA+PVA) nanoparticles introduce a new targeted approach to drug delivery. With an electrostatic patch applied on top of the skin, drug-loaded polymeric nanoparticles are guided to the tumor region, the aim is decreasing required doses of PTX in mice with similar tumor destruction.

Colloidal Gels

In article 2300122, Lin and co-workers show that polyurethane based colloidal gels provide synchronized mechanomorphological guidance for the aggregation and organization of the cells to control their functional state in 3D microenvironment. Chondrogenesis of mesenchymal stem cells and network formation of endothelial cells are promoted on these gel matrices.

Colloidal gels are developed from the aggregation of ionic polyurethane colloids. The spatial organization of interconnected particles in the gel defines the microstructural morphology, which is engineered in a bidirectional manner with respect to gel mechanics. The mechanomorphology of the gels provides spatial guidance for cell organization through balanced cell–cell and cell–matrix interactions during endothelial morphogenesis and mesenchymal chondrogenesis.

PP/PE surgical sutures are functionalized with a conducting polymer using an approach that combines low-pressure plasma treatment with both chemical and electrochemical polymerizations. The obtained smart sutures allow real-time monitoring of bacteria growth through the detection of oxidation of specific metabolites, demonstrating that this is a promising approach to preventing bacterial infections.

The possibility of blending carbon dots (CDs) with silk fibres (SF) is explored by directly feeding silkworms with a CD-modified diet. The major highlights of this study involve i) synthesis of CDs from the Morus rubra variant of mulberry leaves (MB-CDs) for the first time, ii) utilizing MB-CDs as fluorescent probes for Dopamine (DA) detection, iii) Feeding MB-CD-sprayed mulberry leaf diets to Bombyx mori variant of silkworms from their third instar to synthesize augmented SF, and iv) development of a novel, cost-effective method for the detection of DA by utilizing augmented SF.

An epsin-mimetic UPI peptide can block internalization of vascular endothelial growth factor receptor 2, which has promise for improving vascular graft endothelialization. This study shows that incorporation of UPI peptides into vascular grafts via a fibrin coating can promote endothelial cell attachment and migration in vitro and endothelialization in vivo. A low dose of the peptide also improves graft viability.

This work demonstrates using polyphenolic carbon quantum dots embedded in 3D bioprinted hydrogels with multi-faceted applications. The dynamic M2 macrophage polarization and light-controlled drug delivery synergistically promote bone regeneration via controlled osteosarcoma eradication and osteoblast differentiation.

Biocompatible porous scaffolds that mimic the properties of extracellular matrices have great potential for cell proliferation and differentiation. The application of a composite system (Alg-SF-LM) can lead to the differentiation of SSCs and the progression of meiosis to elongated spermatid stage, paving the way for a novel infertility treatment landscape and various tissue engineering in the future.

An insoluble thermosensitive microneedle (ITMN) is designed to control the release of insulin by adjusting the temperature in response to the glucose concentration, enabling effective regulates blood glucose and precise treatment of diabetes. It has the potential to form an integrated and precise closed-loop treatment for diabetes, which is of great importance in diabetes management.

The sustainable bioactive composite knitted silk meshes carrying phytochemicals are mechanically strong, hydrophilic, biocompatible, and nontoxic. The meshes are antibacterial , activate cell migration and express wound healing genes . These coated meshes can be suitable candidates for hernia repair as well as regeneration in other load bearing applications.

An improved method to produce hydrogels with tunable elastic moduli for cell culture studies is presented. This method avoids the costly and labor-intensive need for chemically treating glass coverslips and produces much larger surfaces, suitable for preparing cells in sufficient numbers for protein analyses. Examples of mechanosensing by multiple cell types illustrate the improvised utility of these gels.

The development of an effective vaccine can prevent urinary tract infections caused by Pseudomonas aeruginosa (P. aeruginosa). A novel multi-epitope candidate is designed and encapsulated in silk fibroin nanoparticles (SFNPs). Immunization of mice with the multi-epitope-SFNPs induces significant immune responses. The multi-epitope-SFNPs protect mice against experimental infection with P. aeruginosa, demonstrating the therapeutic potential of the vaccine candidate.

In this study, folate functionalized and evodiamine (Evo) loaded pluronic nano micelles (ENM) is synthesized and characterized, aiming to enhance delivery and anticancer activity of Evo. ENM enhances cellular uptake, induces cytotoxicity and apoptosis, inhibits migration, reduces colony formation, and alters the expression of apoptotic genes. Therefore, designed ENM could be potential targeted delivery system for Evo.

The efficiency and antibacterial activity of thiol-mediated immobilization strategies for the coupling of antimicrobial peptides (AMPs) is assessed through a one-step thiol–maleimide, or a two-step thiol–ene “photo-click” approach. It is demonstrated that both methods offer versatile platforms to tether AMPs while preserving their activity; however, the thiol–ene “photo-click” minimizes competitive interactions, allowing for higher AMP loading and prolonged antibacterial activity.

An ultrasound-controlled monodisperse lipid vesicles' (U-CMLVs') hydrogel dressing is described. The U-CMLVs formed by microfluidic have the characteristics of high drug encapsulation efficiency, quantitative encapsulation of ultrasonic response materials, controllable size, and uniform distribution. It combines different frequencies and powers ultrasound to compose a transdermal drug delivery system to achieve deep, controllable, efficient, and safe drug delivery.

Here exo-polysaccharide (EPS)-incorporated marine-derived collagen scaffolds are fabricated for burn wound healing applications. Instrumental characterizations do not indicate a significant difference in physical properties. However, in vitro and in vivo biological studies show higher cell biocompatibility and accelerated wound healing rate in EPS-incorporated collagen scaffolds.

A small-diameter vascular graft is fabricated by integrating an electrospun silk fibroin membrane with decellularized small intestinal submucosa. The graft sequentially releases VEGF and TGF-β1 inhibitors to promote rapid endothelialization and limit collagen deposition and provides a mechanical structure for stabilizing the integration process with degradation. This bioengineered graft aims to prevent intimal hyperplasia and facilitate vascular regeneration.

Reducing pro-inflammatory macrophage activation is conducive to inhibiting inflamed chronic wounds. Suppressors of cytokine signaling (SOCS) proteins can be utilized to target the JAK/STAT pathway, which in turn reduces inflammatory signaling. This study introduces a PEGDA hydrogel platform to investigate a peptide mimicking the kinase inhibitory region of SOCS (SOCS1-KIR) as an effective therapeutic for macrophage manipulation.