Remodeling of a Cell-Free Vascular Graft with Nanolamellar Intima into a Neovessel

Abstract

Advances in cardiovascular materials have brought us improved artificial vessels with larger diameters for reducing adverse responses that drive acute thrombosis and the associated complications. Nonetheless, the challenge is still considerable when applying these materials in small-diameter blood vessels. Here we report the biomimetic design of an acellular small-diameter vascular graft with specifically lamellar nanotopography on the luminal surface via a modified freeze-cast technique. The experimental findings verify that the well-designed nanolamellar structure is able to inhibit the adherence and activation of platelets, induce oriented growth of endothelial cells, and eventually remodel a neovessel to maintain long-term patency in vivo. Furthermore, the results of numerical simulations in physically mimetic conditions reveal that the regularly lamellar nanopattern can manipulate blood flow to reduce the flow disturbance compared with random topography. Our current work not only creates a freeze-cast small-diameter vascular graft that employs topographic architecture to direct the vascular cell fates for revasculature but also rekindles confidence in biophysical cues for modulating in situ tissue regeneration.

The basement membrane as a structured surface – role in vascular health and disease

“…This effect was subsequently confirmed in human patients where microgrooved stents were found to be associated with significantly lower levels of neointimal hyperplasia (abnormal proliferation and migration of SMCs leading to restenosis) and appeared to promote a more homogeneous surface healing of the stent compared to standard bare metal stents (Vesga et al, 2017). More recently, a freeze-cast technique has been used to develop a small-diameter vascular graft with luminal nano-grooves; this surface was able to induce EC alignment and reduce the number of adherent platelets (Wang et al, 2019). In addition, numerical simulations revealed that this lamellar topography reduced blood flow disturbance compared to a random topography.…”

Supramolecular Biopolymers for Tissue Engineering

“…The presence of a cross-bridging motif would favor the binding among the diverse sticky-end sequences; in addition to the degradation of the complex structures by RNases, this allows the creation of complex-shaped droplets. Although this project's scope seems to tackle a drug delivery matter, it could allow the development of regenerative medicine approaches, such as bioactive molecule encapsulation within cell-free tissue-engineered vascular drafts [14,112].…”

“…To give an example, Muller et al used biomaterials with solid fractions, such as bioceramics or nanoparticles for bone or cartilage tissue regeneration. Because of the presence of two different materials, the particles and the hydrogel produce inconsistent dispersion of 14 Advances in Polymer Technology particles; thus, the printing or the formation of the desired morphology is difficult to achieve. The group solved this issue by the use of gellan gum methacrylate, hyaluronic acid methacrylate with hydroxyapatite crystals or particles that enhanced the ink's printability.…”

“…Currently, the state-of-the-art of TE is switching from simple in vitro replicas of tissue sections to structurally and biologically complex models of whole organs [10][11][12]. Researchers are also developing dynamic and cell-free scaffolds for regeneration [13][14][15], patient-derived organ models [16], and more elegant molecular delivery systems [17,18].…”

Insights into the angiogenic effects of nanomaterials: mechanisms involved and potential applications

“…Poly (styrene) and poly (4-bromostyrene) consisting of nanohills 13 and 35 nm in height presented greater adhesion and better spreading of HUVECs and human microendothelial cells. The best endothelialized poly (styrene) and poly (4-bromostyrene) surfaces of 13 nm nanohills exhibited the lowest monocyte and granulocyte adherence [89,90], and the oriented nanotopography surface and the lower depth structure (< 40 nm) always exhibited fewer platelets adhesion [91,92]. A comparison of gradient nanopatterned plates consisting of nanopillars with different diameters ranging from 120-200, 200-280, to 280-360 nm has shown that the cytoskeletal integrity and focal adhesion of human endothelial colony-forming cells (hECFCs) on nanopatterned plates are better than PLLA nanofibrous membrane…”