No abstract

Chronic wounds are difficult to heal spontaneously largely due to the corrupted extracellular matrix (ECM) where cell ingrowth is obstructed. Thus, the objective of this study was to develop a three-dimensional (3D) biodegradable scaffold mimicking native ECM to replace the missing or dysfunctional ECM, which may be an essential strategy for wound healing. The 3D fibrous scaffolds of poly(lactic acid-co-glycolic acid) (PLGA) were successfully fabricated by liquid-collecting electrospinning, with 5~20 µm interconnected pores. Surface modification with the native ECM component aims at providing biological recognition for cell growth. Human dermal fibroblasts (HDFs) successfully infiltrated into scaffolds at a depth of ~1400 µm after seven days of culturing, and showed significant progressive proliferation on scaffolds immobilized with collagen type I. In vivo models showed that chronic wounds treated with scaffolds had a faster healing rate. These results indicate that the 3D fibrous scaffolds may be a potential wound dressing for chronic wound repair.

Effective reversal of tumor immunosuppression is of critical importance in cancer therapy. A multifunctional delivery vector that can effectively deliver CRISPR‐Cas9 plasmid for β‐catenin knockout to reverse tumor immunosuppression is constructed. The multi‐functionalized delivery vector is decorated with aptamer‐conjugated hyaluronic acid and peptide‐conjugated hyaluronic acid to combine the tumor cell/nuclear targeting function of AS1411 with the cell penetrating/nuclear translocation function of TAT‐NLS. Due to the significantly enhanced plasmid enrichment in malignant cell nuclei, the genome editing system can induce effective β‐catenin knockout and suppress Wnt/β‐catenin pathway, resulting in notably downregulated proteins involved in tumor progression and immunosuppression. Programmed death‐ligand 1 (PD‐L1) downregulation in edited tumor cells not only releases the PD‐1/PD‐L1 brake to improve the cancer killing capability of CD8+ T cells, but also enhances antitumor immune responses of immune cells. This provides a facile strategy to reverse tumor immunosuppression and to restore immunosurveillance and activate anti‐tumor immunity.

No abstract

Favorable physical and chemical properties endow Au nanoparticles (Au NPs) with various biomedical applications. After appropriate surface functionalization, Au NPs could construct promising drug/gene carriers with multiple functions. There is now ample evidence that physicochemical properties, such as size, shape, and surface chemistry, can dramatically influence the behaviors of Au NPs in biological systems. Investigation of these parameters could be fundamentally important for the application of Au NPs as drug/gene carriers. In this work, we designed a series of novel gene carriers employing polycation-functionalized Au NPs with five different morphologies (including Au nanospheres, Au nano-octahedra, arrow-headed Au nanorods, and Au nanorods with different aspect ratios). The effects of the particle size and shape of these different carriers on gene transfection were investigated in detail. The morphology of Au NPs is demonstrated to play an important role in gene transfection. The most efficient gene carriers are those fabricated with arrow-headed Au nanorods. Au nanosphere-based carriers exhibit the poorest performance in gene transfection. In addition, Au nanorods with smaller aspect ratios perform better than longer ones. These results may provide new avenues to develop promising gene carriers and gain useful information on the interaction of Au NPs with biological systems.

No abstract

Sustained ocular drug delivery is difficult to achieve. Most drugs have poor penetration due to the multiple physiological barriers of the eye and are rapidly cleared if applied topically. Biodegradable subconjunctival implants with controlled drug release may circumvent these two problems. In our study, two microfilms (poly [d,l-lactide-co-glycolide] PLGA and poly[d,l-lactide-co-caprolactone] PLC were developed and evaluated for their degradation behavior in vitro and in vivo. We also evaluated the biocompatibility of both microfilms. Eighteen eyes (9 rabbits) were surgically implanted with one type of microfilm in each eye. Serial anterior-segment optical coherence tomography (AS-OCT) scans together with serial slit-lamp microscopy allowed us to measure thickness and cross-sectional area of the microfilms. In vitro studies revealed bulk degradation kinetics for both microfilms, while in vivo studies demonstrated surface erosion kinetics. Serial slit-lamp microscopy revealed no significant inflammation or vascularization in both types of implants (mean increase in vascularity grade PLGA50/50 12±0.5% vs. PLC70/30 15±0.6%; P = 0.91) over a period of 6 months. Histology, immunohistochemistry and immuno-fluorescence also revealed no significant inflammatory reaction from either of the microfilms, which confirmed that both microfilms are biocompatible. The duration of the drug delivery can be tailored by selecting the materials, which have different degradation kinetics, to suit the desired clinical therapeutic application.

No abstract