A scaffold vaccine to promote tumor antigen cross-presentation via sustained toll-like receptor-2 (TLR2) activation.

Cancer vaccination holds great promise for cancer treatment, but its effectiveness is hindered by suboptimal activation of CD8+ cytotoxic T lymphocytes, which are potent effectors to mediate anti-tumor immune responses. A possible solution is to switch antigen-presenting cells to present tumor antigens via the major histocompatibility complex class I (MHC-I) to CD8+ T cells - a process known as cross-presentation. To achieve this goal, we develop a three-dimensional (3D) scaffold vaccine to promote antigen cross-presentation by persisted toll-like receptor-2 (TLR2) activation after one injection. This vaccine comprises polysaccharide frameworks that "hook" TLR2 agonist (acGM) via tunable hydrophobic interactions and forms a 3D macroporous scaffold via click chemistry upon subcutaneous injection. Its retention-and-release of acGM enables sustained TLR2 activation in abundantly recruited dendritic cells in situ, inducing intracellular production of reactive oxygen species (ROS) in optimal kinetics that crucially promotes efficient antigen cross-presentation. The scaffold loaded with model antigen ovalbumin (OVA) or tumor specific antigen can generate potent immune responses against lung metastasis in B16-OVA-innoculated wild-type mice or spontaneous colorectal cancer in transgenic ApcMin/+ mice, respectively. Notably, it requires neither additional adjuvants nor external stimulation to function and can be adjusted to accommodate different antigens. The developed scaffold vaccine may represent a new, competent tool for next-generation personalized cancer vaccination.

Research progress in clinical trials of stem cell therapy for stroke and neurodegenerative diseases.

The incidence of stroke and neurodegenerative diseases is gradually increasing in modern society, but there is still no treatment that is effective enough. Stem cells are cells that can reproduce (self-renew) and differentiate into the body, which have shown significance in basic research, while doctors have also taken them into clinical trials to determine their efficacy and safety. Existing clinical trials mainly include middle-aged and elderly patients with stroke or Parkinson's disease (mostly 40-80 years old), mainly involving injection of mesenchymal stem cells and bone marrow mesenchymal stem cells through the veins and the putamen, with a dosage of mostly 106-108 cells. The neural and motor functions of the patients were restored after stem cell therapy, and the safety was found to be good during the follow-up period of 3 months to 5 years. Here, we review all clinical trials and the latest advances in stroke, Alzheimer's disease, and Parkinson's disease, with the hope that stem cell therapy will be used in the clinic in the future to achieve effective treatment rates and benefit patients.

Differential Foreign Body Reactions between Branched and Linear Glucomannan Scaffolds.

The extent and patterns of foreign body reaction (FBR) influence the function and feasibility of biomaterials. Polysaccharides, as an important biomaterial category, have received increasing attention in diverse biomaterials design and biomedical applications due to their excellent polymeric and biocompatible characteristics. Their biological effects are usually associated with their monosaccharide composition or functional groups, yet the contribution of their glycan structure is still unknown. Herein, two glucomannans, similar in composition and molecular weight with differences in glycan structure, linear-chain (Konjac glucomannan, KGM), and branched-chain (Bletilla striata polysaccharide, BSP), were adopted to explore the host-biomaterials interaction. After acetyl modification, these polysaccharides were fabricated into electrospun scaffolds to reduce the impacts derived from the physical properties and surface morphology. According to a systematic study of their biological effects on immune cells and host response in a subcutaneous implantation model in vivo, it was revealed that acetyl KGM (acKGM) scaffolds caused a stronger FBR than acetyl BSP materials. Additionally, acKGM could stimulate macrophages to release pro-inflammatory cytokines, suggesting the influence of sugar chain arrangement on FBR and providing clues for the fine regulation of immune response and novel biomaterials design.

A Toll-like Receptor-Activating, Self-Adjuvant Glycan Nanocarrier.

The global pandemic of COVID-19 highlights the importance of vaccination, which remains the most efficient measure against many diseases. Despite the progress in vaccine design, concerns with suboptimal antigen immunogenicity and delivery efficiency prevail. Self-adjuvant carriers-vehicles that can simultaneously deliver antigens and act as adjuvants-may improve efficacies in these aspects. Here, we developed a self-adjuvant carrier based on an acetyl glucomannan (acGM), which can activate toll-like receptor 2 (TLR2) and encapsulate the model antigen ovalbumin (OVA) via a double-emulsion process. In vitro tests showed that these OVA@acGM-8k nanoparticles (NPs) enhanced cellular uptake and activated TLR2 on the surface of dendritic cells (DCs), with increased expression of co-stimulatory molecules (e.g. CD80 and CD86) and pro-inflammatory cytokines (e.g. TNF-α and IL12p70). In vivo experiments in mice demonstrated that OVA@acGM-8k NPs accumulated in the lymph nodes and promoted DCs' maturation. The immunization also boosted the humoral and cellular immune responses. Our findings suggest that this self-adjuvant polysaccharide carrier could be a promising approach for vaccine development.

Reprograming the immune niche for skin tissue regeneration - From cellular mechanisms to biomaterials applications.

Despite the rapid development of therapeutic approaches for skin repair, chronic wounds such as diabetic foot ulcers remain an unaddressed problem that affects millions of people worldwide. Increasing evidence has revealed the crucial and diverse roles of the immune cells in the development and repair of the skin tissue, prompting new research to focus on further understanding and modulating the local immune niche for comprehensive, 'perfect' regeneration. In this review, we first introduce how different immunocytes and certain stromal cells involved in innate and adaptive immunity coordinate to maintain the immune niche and tissue homeostasis, with emphasis on their specific roles in normal and pathological wound healing. We then discuss novel engineering approaches - particularly biomaterials systems and cellular therapies - to target different players of the immune niche, with three major aims to i) overcome 'under-healing', ii) avoid 'over-healing', and iii) promote functional restoration, including appendage development. Finally, we highlight how these strategies strive to manage chronic wounds and achieve full structural and functional skin recovery by creating desirable 'soil' through modulating the immune microenvironment.

Live cell mitochondrial 3-dimensional dynamic ultrastructures under oxidative phosphorylation revealed by a Pyridine-BODIPY probe.

Recent advancements in super-resolution nanoscopy allowed the study of mitochondrial biology at nanoscale and boosted the understanding its correlated cellular processes those were previously poorly understood. Nevertheless, studying mitochondrial ultrastructure remains a challenge due to the lack of probes that could target specific mitochondrial substances (e.g. cristae or mtDNA) and survive under harsh super-resolution optical conditions. Herein, in this work, we have rationally constructed a pyridine-BODIPY (Py-BODIPY) derivative that could target mitochondrial membrane in living cells without interfering its physiological microenvironments. Furthermore, we found Py-BODIPY is a membrane potential independent probe, hence it is not limit to live-cell staining but also showed a strong internalization into pre-fixed and stimulus disrupted sample. Importantly, its cristae specificity and superb photostability allow the observation of mitochondrial dynamic nano-structures with an unprecedented resolution, allow demonstrating how mitochondrial 3D ultrastructure evolved under oxidative phosphorylation condition.