Patent ID: 8399243
Filing Date: 2013-03-19
Classification: A01N,A61F,A61K,C12M,C12N

Abstract:
1. A method of manufacturing a tissue-engineered prosthesis having at least in an open condition a flow passage, wherein the prosthesis is a heart valve, comprising the steps of: placing a seeded 3D scaffold in a bioreactor chamber, providing at least one perfusion flow of a nutrient medium in the bioreactor chamber to supply said seeded 3D scaffold and/or a thereon developing tissue with nutrients, wherein the at least one perfusion flow has substantially no pulsation and whereby a flow passage of the seeded 3D scaffold and/or the thereon developing tissue in relation to the flow passage of the finished prosthesis is restricted or zero during tissue development during the duration stay in the bioreactor chamber, and wherein the at least one perfusion flow is less than 50 ml/min, applying in addition a dynamic pressure difference with a frequency of 0.1 to 10 Hz over the 3D scaffold and/or thereon developing tissue depending on the condition and/or stage of tissue development to create strain in the 3D scaffold and/or thereon developing tissue by restricting or closing the flow passage of the developing prosthesis during the duration stay in the bioreactor chamber, wherein the dynamic pressure difference is a difference in pressure upstream and downstream of the restricted flow passage, removing the 3D scaffold from the bioreactor chamber, and subsequently opening the restricted or zero flow passage to its finished size, wherein the restricted or zero flow passage is at least 20% smaller than the flow passage of the finished prosthesis.