Micro-precise spatiotemporal delivery system embedded in 3D printing for complex tissue regeneration

Biofabrication. 2016 Apr 25;8(2):025003. doi: 10.1088/1758-5090/8/2/025003.

Abstract

Three dimensional (3D) printing has emerged as an efficient tool for tissue engineering and regenerative medicine, given its advantages for constructing custom-designed scaffolds with tunable microstructure/physical properties. Here we developed a micro-precise spatiotemporal delivery system embedded in 3D printed scaffolds. PLGA microspheres (μS) were encapsulated with growth factors (GFs) and then embedded inside PCL microfibers that constitute custom-designed 3D scaffolds. Given the substantial difference in the melting points between PLGA and PCL and their low heat conductivity, μS were able to maintain its original structure while protecting GF's bioactivities. Micro-precise spatial control of multiple GFs was achieved by interchanging dispensing cartridges during a single printing process. Spatially controlled delivery of GFs, with a prolonged release, guided formation of multi-tissue interfaces from bone marrow derived mesenchymal stem/progenitor cells (MSCs). To investigate efficacy of the micro-precise delivery system embedded in 3D printed scaffold, temporomandibular joint (TMJ) disc scaffolds were fabricated with micro-precise spatiotemporal delivery of CTGF and TGFβ3, mimicking native-like multiphase fibrocartilage. In vitro, TMJ disc scaffolds spatially embedded with CTGF/TGFβ3-μS resulted in formation of multiphase fibrocartilaginous tissues from MSCs. In vivo, TMJ disc perforation was performed in rabbits, followed by implantation of CTGF/TGFβ3-μS-embedded scaffolds. After 4 wks, CTGF/TGFβ3-μS embedded scaffolds significantly improved healing of the perforated TMJ disc as compared to the degenerated TMJ disc in the control group with scaffold embedded with empty μS. In addition, CTGF/TGFβ3-μS embedded scaffolds significantly prevented arthritic changes on TMJ condyles. In conclusion, our micro-precise spatiotemporal delivery system embedded in 3D printing may serve as an efficient tool to regenerate complex and inhomogeneous tissues.

Publication types

  • Evaluation Study

MeSH terms

  • Animals
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Connective Tissue Growth Factor / metabolism
  • Connective Tissue Growth Factor / pharmacology
  • Drug Delivery Systems / instrumentation
  • Drug Delivery Systems / methods*
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / metabolism
  • Printing, Three-Dimensional / statistics & numerical data*
  • Rabbits
  • Regeneration
  • Temporomandibular Joint / injuries
  • Temporomandibular Joint / metabolism
  • Temporomandibular Joint / physiopathology*
  • Tissue Engineering / instrumentation
  • Tissue Scaffolds / chemistry
  • Transforming Growth Factor beta3 / metabolism
  • Transforming Growth Factor beta3 / pharmacology

Substances

  • Transforming Growth Factor beta3
  • Connective Tissue Growth Factor