Biomimetic Vascular Grafts with Circumferentially and Axially Oriented Microporous Structures for Native Blood Vessel Regeneration

Abstract

Porous grafts facilitate constructive remodeling of blood vessels. Incorporating multiple biomimetic cues to porous grafts can promote vascular regeneration. However, the fabrication of such medical devices remains challenging. Here, beta‐sheet rich silk nanofibers (BSN) are added to poly(vinyl alcohol) (PVA) solution and aggregated under a cylindric electric field to form circumferentially and axially oriented tubular structures, to simulate the endothelial and media layers of blood vessels. PVA in the aligned tubes is then crystallized through repeat freezing–thawing process to offer mechanical performances. Through tuning the ratio of BSN and PVA, the composite tubes with dual anisotropic microstructures exhibit better mechanical properties than pure PVA vascular grafts. Significantly improved cell adhesion, spreading, proliferation, and alignment are achieved. Both endothelial and smooth muscle cells show improved biological activity on the grafts due to the regulatory roles of the aligned structures. In vivo studies reveal the formation of endothelial layers within four weeks of implantation, ensuring long‐term patency. The endothelial and smooth muscle double layers are regenerated after eight months postimplantation, forming hierarchical microstructures and compositions similar to native vessels. The porous composite grafts with multiple aligned structures guide vascular remodeling to regenerate blood vessels, demonstrating potential for clinical translation.

Review of Spider Silk Applications in Biomedical and Tissue Engineering

“…Considering this, the spider silk matrix has been used to develop artificial blood vessels [ 140 ]. The biomimetic design of structures with silk nanofibers has enabled constructs of vascular grafts with porous structures for blood vessel regeneration [ 141 , 142 ] or for small vascular grafts [ 143 , 144 ].…”

“…Silk-based microspheres can be added to the cell cultures to enhance cell growth and adhesion [ 199 ]. The biomimetic approach in material design has opened up many new directions in material structures, as well as final applications [ 129 , 141 ] and including adjustments of existing fabrication technologies for silk fibers [ 30 , 200 ].…”

Biomimetic Approaches in Scaffold-Based Blood Vessel Tissue Engineering

“…COL-rich connective tissues were produced at the outermost layer of the vascular scaffold, indicating its potential for in situ vascular repair or regeneration [121]. More recently, a scaffold reproducing the endothelial and media layers of blood vessels was developed by Ding et al [122], using a combination of beta-sheet-rich silk nanofibers (BSN) and poly(vinyl alcohol) (PVA). BSN and PVA were blended in an aqueous solution and processed using a tubular electrode to form tubular scaffolds composed of circumferentially and axially oriented BSN near the positive electrode and non-crosslinked PVA.…”

Cryostructuring of Polymeric Systems: 67 Properties and Microstructure of Poly(Vinyl Alcohol) Cryogels Formed in the Presence of Phenol or Bis-Phenols Introduced into the Aqueous Polymeric Solutions Prior to Their Freeze–Thaw Processing

“…Such physical (non-covalent) PVACGs are of a high practical interest in various fields, especially as materials for biomedical applications [ 4 , 5 , 16 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ]. With regard to medical aspects, the use of cryogels based on PVA itself [ 19 , 20 , 22 , 28 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 ] and its blends with other (both synthetic and natural) polymers [ 18 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 ] and composite cryogels that contain entrapped functional disperse fillers [ …”