Peptide-Functionalized Electrospun Meshes for the Physiological Cultivation of Pulmonary Alveolar Capillary Barrier Models in a 3D-Printed Micro-Bioreactor

ACS Biomaterials Science & Engineering, vol. 9, pp. 4878–4892

Abstract

High Resolution Image Download MS PowerPoint Slide In vitro environments that realize biomimetic scaffolds, cellular composition, physiological shear, and strain are integral to developing tissue models of organ-specific functions. In this study, an in vitro pulmonary alveolar capillary barrier model is developed that closely mimics physiological functions by combining a synthetic biofunctionalized nanofibrous membrane system with a novel three-dimensional (3D)-printed bioreactor. The fiber meshes are fabricated from a mixture of polycaprolactone (PCL), 6-armed star-shaped isocyanate-terminated poly(ethylene glycol) (sPEG-NCO), and Arg-Gly-Asp (RGD) peptides by a one-step electrospinning process that offers full control over the fiber surface chemistry. The tunable meshes are mounted within the bioreactor where they support the co-cultivation of pulmonary epithelial (NCI-H441) and endothelial (HPMEC) cell monolayers at air–liquid interface under controlled stimulation by fluid shear stress and cyclic distention. This stimulation, which closely mimics blood circulation and breathing motion, is observed to impact alveolar endothelial cytoskeleton arrangement and improve epithelial tight junction formation as well as surfactant protein B production compared to static models. The results highlight the potential of PCL-sPEG-NCO:RGD nanofibrous scaffolds in combination with a 3D-printed bioreactor system as a platform to reconstruct and enhance in vitro models to bear a close resemblance to in vivo tissues.

Authors 6

1. Puja Jain Aachen DWI - Leibniz Institute for Interactive Materials

   RWTH Aachen University · DWI – Leibniz Institute for Interactive Materials

   Affiliation as printed

   DWI─Leibniz Institute for Interactive Materials, RWTH Aachen University, 52074 Aachen, Germany

2. Daniel Felder Aachen DWI - Leibniz Institute for Interactive Materials

   RWTH Aachen University · DWI – Leibniz Institute for Interactive Materials

   Affiliation as printed

   DWI─Leibniz Institute for Interactive Materials, RWTH Aachen University, 52074 Aachen, Germany

3. John Linkhorst Aachen Institute for Chemical Process Engineering

   RWTH Aachen University

   Affiliation as printed

   Institute for Chemical Process Engineering, RWTH Aachen University, 52074 Aachen, Germany

4. Martin Möller Aachen DWI - Leibniz Institute for Interactive Materials

   RWTH Aachen University · DWI – Leibniz Institute for Interactive Materials

   Affiliation as printed

   DWI─Leibniz Institute for Interactive Materials, RWTH Aachen University, 52074 Aachen, Germany

5. Matthias Weßling corresponding Aachen DWI - Leibniz Institute for Interactive Materials Institute for Chemical Process Engineering

   RWTH Aachen University · DWI – Leibniz Institute for Interactive Materials

   Affiliation as printed

   DWI─Leibniz Institute for Interactive Materials, RWTH Aachen University, 52074 Aachen, Germany

   Institute for Chemical Process Engineering, RWTH Aachen University, 52074 Aachen, Germany

6. Smriti Singh corresponding

   Max Planck Institute for Medical Research

   Affiliation as printed

   Max Planck Institute for Medical Research, Jahnstraße 29, 69120 Heidelberg, Germany