Silk Fibroin Microneedles Loaded with Lipopolysaccharide-Pretreated Bone Marrow Mesenchymal Stem Cell-Derived Exosomes for Oral Ulcer Treatment.

Oral ulcers, superficial lesions on the surface of the oral mucosa, have a high incidence rate, and their main symptoms include local pain and erosion. Lipopolysaccharide (LPS)-preconditioned bone marrow mesenchymal stem cells and their secreted exosomes (LPS-pre-Exos) have been shown to promote recovery in various inflammatory conditions and wounds. However, studies documenting LPS-pre-Exos as a therapeutic intervention for oral mucosal-like diseases are lacking. In this study, we prepared a silk fibroin microneedle (MN) patch consisting of LPS-pre-Exos and zeolitic imidazolate framework-8 (ZIF-8) that localized at the tip and base, respectively, and used this MN patch for oral ulcer treatment. Upon insertion into the oral mucosa, continuous LPS-pre-Exos release was observed, which promoted macrophage polarization and tissue healing. Additionally, the ZIF-8 framework in the MN patch facilitated the controlled release of Zn2+, which demonstrated potent antimicrobial properties via synergistic effects. The in vitro experimental results showed that the silk fibroin MN patch can continuously release LPS-pre-Exos and Zn2+ for more than 7 days. Thus, the LPS-pre-Exos and ZIF-8-loaded silk fibroin MN patch exhibited good anti-inflammatory and antibacterial properties, promoting oral ulcer healing, and showed good histocompatibility. Hence, it may represent a potentially valuable strategy for facilitating oral ulcer healing.

Multifunctional hyaluronic acid/gelatin methacryloyl core-shell microneedle for comprehensively treating oral mucosal ulcers.

Oral ulceration is the most common oral mucosal disease. Oral mucosal ulcers are extremely painful, may interfere with eating and speaking, and potentially complicate systemic symptoms in severe cases. The humid and highly dynamic environment of the oral cavity makes local drug administration for treating oral mucosal ulcers challenging. To overcome these challenges, we designed and prepared a novel dissolving microneedle (MN) patch containing multiple drugs in a core-shell to promote oral ulcer healing. The MNs contained a methacrylate gelatin shell layer of basic fibroblast growth factor (bFGF), a hyaluronic acid (HA) core loaded with dexamethasone (DXMS), and zeolite imidazoline framework-8 (ZIF-8) encapsulated in the HA-based backplane. Progressive degradation of gelatin methacryloyl (GelMA) from the tip of the MN patch in the oral mucosa resulted in sustained bFGF release at the lesion site, significantly promoting cell migration, proliferation, and angiogenesis. Moreover, the rapid release of HA and, subsequently, DXMS inhibited inflammation, and the remaining MN backing after the tip dissolved behaved as a dressing, releasing ZIF-8 for its antimicrobial effects. This novel, multifunctional, transmucosal core-shell MN patch exhibited excellent anti-inflammatory, antimicrobial, and pro-healing effects in vivo and in vitro, suggesting that it can promote oral ulcer healing.

Developing Chinese herbal-based functional biomaterials for tissue engineering.

The role of traditional Chinese medicine (TCM) in treating diseases is receiving increasing attention. Chinese herbal medicine is an important part of TCM with various applications and the active ingredients extracted from Chinese herbal medicines have physiological and pathological effects. Tissue engineering combines cell biology and materials science to construct tissues or organs in vitro or in vivo. TCM has been proposed by the World Health Organization as an effective treatment modality. In recent years, the potential use of TCM in tissue engineering has been demonstrated. In this review, the classification and efficacy of TCM active ingredients and delivery systems are discussed based on the TCM theory. We also summarized the current application status and broad prospects of Chinese herbal active ingredients in different specialized biomaterials in the field of tissue engineering. This review provides novel insights into the integration of TCM and modern Western medicine through the application of Chinese medicine in tissue engineering and regenerative medicine.

Multifunctional polysaccharide composited microneedle for oral ulcers healing.

Oral ulcers have periodicity and recurrence, and the etiology and causative mechanisms remain unclear; therefore, it is difficult to treat oral ulcers effectively. Current clinical treatment methods mainly include pain relief and administration of anti-inflammatories to prevent secondary infections and a prolonged recurrence cycle. However, these traditional treatment methods are administered independently and are susceptible to muscle movements and constant salivary secretion in the mouth, resulting in ineffective drug functioning. Therefore, development of a novel treatment to reduce wound infection and accelerate wound healing for oral ulcers is required for effective treatment. Herein, we report a multifunctional polysaccharide composite microneedle patch based on hyaluronic acid (HA) and hydroxypropyl trimethyl ammonium chloride chitosan (HACC) loaded with dexamethasone (DXMS) and basic fibroblast growth factor (bFGF) for oral ulcer healing. DXMS and bFGF encapsulated the HA tip portion of the microneedle patch, endowing the microneedle patches with anti-inflammatory and angiogenic properties. HACC was applied to the back of the microneedle patch, adding antibacterial properties. The experimental results indicated that the prepared dressings exhibited good antibacterial activity and effectively promoted cell migration growth and angiogenesis. More importantly, animal experiments have shown that multifunctional microneedle patches can effectively promote oral ulcer healing. Thus, these novel multifunctional polysaccharide composite microneedle patches have great potential for oral ulcers treatment.

Supramolecular Transistors with Quantum Interference Effect.

The charge transport through supramolecular junctions exhibits unique quantum interference (QI) effects, which provide an opportunity for the design of supramolecular transistors. Benefiting from the configuration dependence of QI, configuration control of the supramolecular assemblies to demonstrate the QI features is a key but challenging step. In this work, we fabricated the supramolecular transistors and investigated the charge transport through the conducting channel of the individual π-stacked thiophene/phenylene co-oligomers (TPCOs) using the electrochemically gated scanning tunneling microscope break junction technique. We controlled the configuration of the supramolecular channel and switched the QI features between the anti-resonance and resonance states of the supramolecular channels. We observed the supramolecular transistor with its on/off ratio above 103 (∼1300), a high gating efficiency of ∼165 mV/dec, a low off-state leakage current of ∼30 pA, and the channel length scaled down to <2.0 nm. Density functional theory calculations suggested that the QI features in π-stacked TPCOs vary depending on the supramolecular architecture and can be manipulated efficiently by fine-tuning the supramolecular configurations. This work reveals the potential of the supramolecular channels for molecular electronics and provides a fundamental understanding of intermolecular charge transport.

Combination therapy using multifunctional dissolvable hyaluronic acid microneedles for oral ulcers.

Oral ulcers are common in the oral mucosa. Frequent occurrences of oral ulcers commonly afflict patients, seriously impacting their daily life. Treatments with good anti-inflammatory and antibacterial properties are important for promoting the healing of oral ulcers. In this study, a multifunctional, soluble hyaluronic acid (HA) microneedle (MN) patch was prepared to promote oral ulcer healing. The tip layer of the MN patch was loaded with triamcinolone acetonide (TA) and epidermal growth factor (EGF) to inhibit inflammation and promote angiogenesis. Zeolitic imidazolate framework-8 (ZIF-8) was loaded onto the base layer of the MN patch, which effectively released Zn2+ to mediate antibacterial effects. In addition, HA exerts a protective effect on the mucous membrane. Owing to these properties, the multifunctional MN patches were found to have good anti-inflammatory, antibacterial, and tissue-healing abilities, indicating that the multifunctional MN patch design successfully promoted the healing of oral ulcers.

Biomaterial-based gene therapy.

Gene therapy, a medical approach that involves the correction or replacement of defective and abnormal genes, plays an essential role in the treatment of complex and refractory diseases, such as hereditary diseases, cancer, and rheumatic immune diseases. Nucleic acids alone do not easily enter the target cells due to their easy degradation in vivo and the structure of the target cell membranes. The introduction of genes into biological cells is often dependent on gene delivery vectors, such as adenoviral vectors, which are commonly used in gene therapy. However, traditional viral vectors have strong immunogenicity while also presenting a potential infection risk. Recently, biomaterials have attracted attention for use as efficient gene delivery vehicles, because they can avoid the drawbacks associated with viral vectors. Biomaterials can improve the biological stability of nucleic acids and the efficiency of intracellular gene delivery. This review is focused on biomaterial-based delivery systems in gene therapy and disease treatment. Herein, we review the recent developments and modalities of gene therapy. Additionally, we discuss nucleic acid delivery strategies, with a focus on biomaterial-based gene delivery systems. Furthermore, the current applications of biomaterial-based gene therapy are summarized.

Characterization and Application of Supramolecular Junctions.

The convergence of supramolecular chemistry and single-molecule electronics offers a new perspective on supramolecular electronics, and provides a new avenue toward understanding and application of intermolecular charge transport at the molecular level. In this review, we will provide an overview of the advances in the characterization technique for the investigation of intermolecular charge transport, and summarize the experimental investigation of several non-covalent interactions, including π-π stacking interactions, hydrogen bonding, host-guest interactions and σ-σ interactions at the single-molecule level. We will also provide a perspective on supramolecular electronics and discuss the potential applications and future challenges.

Strain of Supramolecular Interactions in Single-Stacking Junctions.

Supramolecular electronics provide opportunities to integrate molecular building blocks into electronic circuits, and investigations of the mechanical properties of the non-covalent interactions are necessary to understand the role of the assembly configuration in the electronic coupling among different assembly blocks. However, the mechanical characterization of supramolecular interactions remains experimentally challenging. We investigated the strain distribution of the supramolecular interactions through a series of single-stacking junctions. The alpha values exhibit a clear odd-even effect versus the numbers of thiophene rings. The theoretical calculations demonstrated that a larger rotational barrier of the single-stacking junctions with an even number of thiophene rings leads to limited torsional freedom and thus a smaller strain distribution. These results provide new insights into the control of supramolecular interactions by the design of the basic molecular building blocks.

Tim-3 as a diagnostic and prognostic biomarker of osteosarcoma.

Osteosarcoma is the most frequent primary bone tumor that affects adolescents and children. However, diagnostic and prognostic biomarkers for osteosarcoma remain lacking. (Tim-3) T-cell immunoglobulin domain and mucin domain-3, which negatively regulates T cell helper (Th1) cells and affects cytokine expression, has attracted increasing attention due to its critical role in regulating both adaptive and innate immune cells. In this study, we evaluated serum soluble Tim-3 level in osteosarcoma patients to explore its diagnostic and prognostic value for this particular malignancy. Serum soluble Tim-3 level was measured with enzyme-linked immunosorbent assay in 120 osteosarcoma patients, 120 benign bone tumors patients and 120 healthy controls, followed by analysis of the correlation with clinic pathological characteristics. Receiver operating curves, Kaplan-Meier curves, and log-rank analyses as well as Cox proportional hazard models were used to evaluate the diagnostic and prognostic significance. Serum solubleTim-3 level was remarkably elevated in osteosarcoma patients. Osteosarcoma patients with larger tumor size, late stages and distant metastases were accompanied with higher levels of Tim-3. ROC/AUC analysis indicated thatTim-3 served as a reliable marker to distinguish healthy participants from Tim-3 patients. Osteosarcoma patients with higher Tim-3 had relatively lower survival. Multivariate analyses for overall survival revealed that high serum soluble Tim-3 level was an independent prognostic factor for osteosarcoma. Furthermore, Tim-3 levels of CD8+ and CD4+ T cells were elevated in peripheral circulation of osteosarcoma patients. Therefore, It was indicated in our research that elevated serum soluble Tim-3 level might be a novel potential diagnostic and prognostic biomarker for osteosarcoma patients.