Advances in bioelectronics have great potential to address unsolvable biomedical problems in the cardiovascular system. By using poly(L-lactide-co-ε-caprolactone) (PLC) that encapsulates the liquid metal to make flexible and bio-degradable electrical circuitry, we develop an electronic blood vessel that can integrate flexible electronics with three layers of blood vessel cells, to mimic and go beyond the natural blood vessel. It can improve the endothelization process through electrical stimulation and can enable controlled gene delivery into specific part of the blood vessel via electroporation. The electronic blood vessel has excellent biocompatibility in the vascular system and shows great patency three months post-implantation in a rabbit model. The electronic blood vessel would be an ideal platform to enable diagnostics and treatments in the cardiovascular system and can greatly empower personalized medicine by creating a direct link of vascular tissue-machine interface.
Aiming to construct small diameter (ID <6 mm) off‐the‐shelf tissue‐engineered vascular grafts, the end‐group heparinizd poly(ε‐caprolactone) (PCL) is synthesized by a three‐step process and then electrospun into an inner layer of double‐layer vascular scaffolds (DLVSs) showing a hierarchical double distribution of nano‐ and microfibers. Afterward, PCL without the end‐group heparinization is electrospun into an outer layer. A steady release of grafted heparin and the existence of a glycocalyx structure give the grafts anticoagulation activity and the conjugation of heparin also improves hydrophilicity and accelerates degradation of the scaffolds. The DLVSs are evaluated in six rabbits via a carotid artery interpositional model for a period of three months. All the grafts are patent until explantation, and meanwhile smooth endothelialization and fine revascularization are observed in the grafts. The composition of the outer layer of scaffolds exhibits a significant effect on the aneurysm dilation after implantation. Only one aneurysm dilation is detected at two months and no calcification is formed in the follow‐up term. How to prevent aneurysms remains a challenging topic.
Small-diameter vascular grafts (inner diameter < 6 mm) are useful in treating cardiovascular diseases. The off-the-shelf small-diameter vascular grafts for clinical applications remain a great limitation owing to their thrombogenicity or intimal hyperplasia. Herein, bilayer anticoagulant hydrogel tubes with poly( -caprolactone) (PCL) sheaths are prepared by freeze-thawing and electrospinning, which contain nanofibrillated cellulose (NFC)/poly(vinyl alcohol) (PVA)-heparin/poly-L-lysine nanoparticles tube as an inner layer and PCL sheath as an outer layer. The structure, anticoagulant property, and biocompatibility of the inner layer are studied. The effects of thickness of the outer layer on perfusion performance and mechanical property of hydrogel tubes with PCL sheaths (PCL-NFC/PVA-NPs tubes) are investigated. The effect of compliance of PCL-NFC/PVA-NPs tubes on their blood flow is studied by numerical simulation. The tissue compatibility and the patency of PCL-NFC/PVA-NPs tubes are evaluated by implantation in subcutaneous tissue of rats and carotid artery of rabbits. PCL-NFC/PVA-NPs tubes have prominent anticoagulation, sufficient burst pressure and good compliance similar to native arteries. PCL-NFC/PVA-NPs tubes facilitate infiltration of host cells and achieve active proliferation of recruited cells, which will be a promising candidate for small-diameter vascular grafts.
Intimal hyperplasia (IH) in vein grafts (VGs) is a major issue in coronary artery bypass grafting (CABG) surgery. Although external stents can attenuate IH of VGs to some extent, none of the existing external stents have shown satisfactory clinical outcomes. Here we develop a flexible, biodegradable, and conductive external metal−polymer conductor stent (MPCS) that can electroporate the vessel wall and produce a protein that prevents IH. We designed the plasmid DNA encoding the tissue inhibitor of metalloproteinases-3 (TIMP-3) and lyophilized it on the inner surface of the MPCS to deliver into the adventitia and the middle layer of VGs for gene therapy. Coupled with its continuous mechanical support to prevent dilation after implanting, the MPCS can inhibit the IH of VGs significantly in the rabbit model. This proof-of-concept demonstration may aid the development of other implantable bioelectronics for electroporation gene therapy.
Herein biodegradable poly(e-caprolactone) was electrospun into tubular microfibrous scaffolds and modified by the surface heparinization and wrapping of Type I collagen suture for enhancing anticoagulation activity and mechanical properties. The resulting scaffolds were featured by a double distribution of microfiber diameters ranged in 2.74 AE 0.44 and 5.15 AE 0.63 mm on the outer surface with tensile strength of 1.36 AE 0.37 MPa and Young's modulus of 8.31 AE 1.87 MPa. The burst pressure after embedded with collagen suture was increased to 2419 AE 121 mmHg, remarkably higher than that of the poly(e-caprolactone)-only scaffolds (1500 AE 136 mmHg) and native vessels. The scaffolds were evaluated in six rabbits for 20 weeks via a carotid artery interpositional model demonstrating a good patency. The effective cell infiltration, and rapid endothelialization and smooth muscle cell maturation were observed. There was no calcification in 20 weeks, and only one developed the aneurysm dilation after 16 weeks. It suggested that the surface heparinization is beneficial to improve the hydrophilicity and anticoagulation property of scaffolds, and embedment of collagen suture is useful to reinforce the mechanical properties and burst pressure.
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