Arteriovenous malformation (AVM) refers to a vascular anomaly where arteries and veins are directly connected through a complex, tangled web of abnormal AV fistulae without a normal capillary network. Hereditary hemorrhagic telangiectasia (HHT) types 1 and 2 arise from heterozygous mutations in endoglin (ENG) and activin receptor-like kinase 1 (ALK1), respectively. HHT patients possess AVMs in various organs, and telangiectases (small AVMs) along the mucocutaneous surface. Understanding why and how AVMs develop is crucial for developing therapies to inhibit the formation, growth, or maintenance of AVMs in HHT patients. Previously, we have shown that secondary factors such as wounding are required for Alk1-deficient vessels to develop skin AVMs. Here we present evidences that AVMs establish from nascent arteries and veins rather than from remodeling of a preexistent capillary network in the wound-induced skin AVM model. We also show that VEGF can mimic the wound effect on skin AVM formation, and VEGF neutralizing antibody can prevent skin AVM formation and ameliorate internal bleeding in Alk1-deficient adult mice. With topical applications at different stages of AVM development, we demonstrate that the VEGF blockade can prevent the formation of AVM and cease the progression of AVM development. Taken together, the presented experimental model is an invaluable system for precise molecular mechanism of action of VEGF blockades as well as for preclinical screening of drug candidates for epistaxis and gastrointestinal bleedings.

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Magnesium has recently received an increased amount of interest due to its potential use in biodegradable implant applications. The rapid degradation of conventional Mg is, however, a major limitation that needs to be addressed in the design of these materials, along with consideration of toxicity in selection of alloying elements. In this study, five alloys in the Mg-xCa-ySr system (x = 0.5-7.0 wt %; y = 0.5-3.5 wt %) were prepared and characterized for their suitability as degradable orthopedic implant materials. The alloys were characterized using optical microscopy, scanning electron microscopy, energy-dispersive X-ray spectroscopy, X-ray diffraction, degradation measurements in Hanks' solution at 37°C, compression testing, and in vitro cytotoxicity testing with a mouse osteoblastic cell line. The results indicate that the Mg-1.0Ca-0.5Sr alloy is the most promising alloy for orthopedic implant applications since it showed the lowest degradation rate in Hanks' solution (0.01 mL cm(-2) h(-1)) along with no significant toxicity to MC3T3-E1 osteoblasts and a compressive strength of 274 ± 4 MPa.

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Covalent organic frameworks (COFs) are porous organic polymeric materials that are composed of organic elements and linked together by the thermodynamically stable covalent bonds. The applications of COFs in energy sector and drug delivery are afforded because of the desirable properties of COFs, such as high stability, low density, large surface area, multidimensionality, porosity, and high‐ordered crystalline structure expanded. In this review COFs are reviewed, from the perspective of different types of reported COFs, different methods for their synthesis, and their potential applications in the biomedical field. The main goal of this review is to introduce COFs as a biomaterial and to identify specific advantages of different types of COFs that can be exploited for specialized biomedical applications, such as immune engineering.