Creation of Porous, Perfusable Microtubular Networks for Improved Cell Viability in Volumetric Hydrogels

ACS Appl Mater Interfaces. 2024 Apr 17;16(15):18522-18533. doi: 10.1021/acsami.4c00716. Epub 2024 Apr 2.

Abstract

The creation of large, volumetric tissue-engineered constructs has long been hindered due to the lack of effective vascularization strategies. Recently, 3D printing has emerged as a viable approach to creating vascular structures; however, its application is limited. Here, we present a simple and controllable technique to produce porous, free-standing, perfusable tubular networks from sacrificial templates of polyelectrolyte complex and coatings of salt-containing citrate-based elastomer poly(1,8-octanediol-co-citrate) (POC). As demonstrated, fully perfusable and interconnected POC tubular networks with channel diameters ranging from 100 to 400 μm were created. Incorporating NaCl particulates into the POC coating enabled the formation of micropores (∼19 μm in diameter) in the tubular wall upon particulate leaching to increase the cross-wall fluid transport. Casting and cross-linking gelatin methacrylate (GelMA) suspended with human osteoblasts over the free-standing porous POC tubular networks led to the fabrication of 3D cell-encapsulated constructs. Compared to the constructs without POC tubular networks, those with either solid or porous wall tubular networks exhibited a significant increase in cell viability and proliferation along with healthy cell morphology, particularly those with porous networks. Taken together, the sacrificial template-assisted approach is effective to fabricate tubular networks with controllable channel diameter and patency, which can be easily incorporated into cell-encapsulated hydrogels or used as tissue-engineering scaffolds to improve cell viability.

Keywords: 3D embedded printing; GelMA cell casting; poly(1,8-octanediol-co-citrate); polyelectrolyte complex (PEC); tubular networks.

MeSH terms

  • Cell Survival
  • Gelatin / chemistry
  • Humans
  • Hydrogels* / chemistry
  • Porosity
  • Printing, Three-Dimensional
  • Tissue Engineering / methods
  • Tissue Scaffolds* / chemistry

Substances

  • Hydrogels
  • Gelatin