Inverted human umbilical arteries with tunable wall thicknesses for nerve regeneration

Abstract

Tubular nerve guides have shown a potential to bridge nerve defects, by directing neuronal elongation, localizing growth factors, and inhibiting fibrotic cellular ingrowth. These investigations describe a novel acellular scaffold derived from the human umbilical cord artery that aims to enhance nerve regeneration by presenting a unique mechanical and chemical environment to the damaged nerve ends. A rapid, semiautomated dissection technique is described that isolates the human umbilical artery (HUA) from the umbilical cord, after which the vessel is decellularized using sodium dodecyl sulfate (SDS). The artery is turned inside out to produce a 3D scaffold, that unlike previous vessels for nerve repair, is more resistant to collapse. The scaffold has the potential as either an acellular bridge-implant, or for in vitro nerve regeneration. Stress-strain relationships and suture retention were assessed to determine whether the material had similar mechanical properties to native nerves. A dual process-flow perfusion bioreactor was developed to assess glucose mass transfer, and to investigate the culture of neuronal-like PC12 cells within the scaffold. These investigations have shown the automated dissecting method yields a smooth tubular scaffold, where wall thickness can be tuned to alter the mechanical behavior of the scaffold. Inverting the scaffold prevents collapse, with the decellularized iHUA having comparable mechanical properties to native nerves. Bioreactor cultures with PC12 cells seeded within iHUA lumenal void were shown to adhere and migrate into the preexisting ECM after 11 days of culture. These investigations show the potential of the iHUA as a unique 3D scaffold that may enhance nerve regeneration.

Preimplantation processing of ex vivo‐derived vascular biomaterials: Effects on peripheral cell adhesion

“…Human umbilical veins (HUV) were isolated from the surrounding tissue using an automated dissection procedure that has been described previously 20. In brief, umbilical cords were rinsed clean and cut into 10 cm sections.…”

“…Decellularization of allo‐/xenografts is often performed to abate the immune response generated upon implantation of the scaffold by solubilizing and stripping out antigenic cellular components while preserving the native architecture of the extracellular matrix 12, 13. Decellularized donor tissues have shown great promise in applications both as acellular, implantable biomaterials as well as scaffolding material for cell‐seeded tissue engineered constructs 14–20. However, the chemical21, 22 (e.g.…”

Human Perinatal‐Derived Biomaterials

“…[3, 59] Engineered bioscaffolds derived from decellularized umbilical arteries have comparable biomechanical properties relative to native nerves, and have been shown to effectively serve as a basis for the adherence and migration of neuronal-like PC12 cells. [3]…”

“…[1] In recent years, both clinical and research applications of these biomaterials have increased in scope to include roles in tissue engineering, regenerative medicine, and cell-based therapies, especially in the field of orthobiologics. [2, 3] Perinatal tissues are an abundant source of extracellular matrix components, discrete biomolecules, and growth factors with potential use in wide ranging surgical procedures. [4] Clinical sucess with current products have driven broader applications and novel materials that span most clinical specialities, see Table A.…”

Synergistic effects of G‐CSF and bone marrow stromal cells on nerve regeneration with acellular nerve xenografts

“…The structural and functional reconstruction of peripheral nerve defects has not yet been solved in clinical practice, particularly for extensive nerve gaps. With the development of nerve tissue engineering, the regenerated microenvironment may be optimized by applying a combination of biomaterial scaffolds, seed cells and growth‐promoting factors (Ao et al, ; Ciardelli and Chiono, ; Crouzier, McClendon, Tosun, & McFetridge, ). Transplantation of seed cells is the critical strategy in neural tissue engineering, and the implanted cells are thought to have positive functions in improving the microenvironment of regenerating axons.…”