Investigation of multiphasic 3D-bioplotted scaffolds for site-specific chondrogenic and osteogenic differentiation of human adipose-derived stem cells for osteochondral tissue engineering applications

J Biomed Mater Res B Appl Biomater. 2020 Jul;108(5):2017-2030. doi: 10.1002/jbm.b.34542. Epub 2019 Dec 27.

Abstract

Osteoarthritis is a degenerative joint disease that limits mobility of the affected joint due to the degradation of articular cartilage and subchondral bone. The limited regenerative capacity of cartilage presents significant challenges when attempting to repair or reverse the effects of cartilage degradation. Tissue engineered medical products are a promising alternative to treat osteochondral degeneration due to their potential to integrate into the patient's existing tissue. The goal of this study was to create a scaffold that would induce site-specific osteogenic and chondrogenic differentiation of human adipose-derived stem cells (hASC) to generate a full osteochondral implant. Scaffolds were fabricated using 3D-bioplotting of biodegradable polycraprolactone (PCL) with either β-tricalcium phosphate (TCP) or decellularized bovine cartilage extracellular matrix (dECM) to drive site-specific hASC osteogenesis and chondrogenesis, respectively. PCL-dECM scaffolds demonstrated elevated matrix deposition and organization in scaffolds seeded with hASC as well as a reduction in collagen I gene expression. 3D-bioplotted PCL scaffolds with 20% TCP demonstrated elevated calcium deposition, endogenous alkaline phosphatase activity, and osteopontin gene expression. Osteochondral scaffolds comprised of hASC-seeded 3D-bioplotted PCL-TCP, electrospun PCL, and 3D-bioplotted PCL-dECM phases were evaluated and demonstrated site-specific osteochondral tissue characteristics. This technique holds great promise as cartilage morbidity is minimized since autologous cartilage harvest is not required, tissue rejection is minimized via use of an abundant and accessible source of autologous stem cells, and biofabrication techniques allow for a precise, customizable methodology to rapidly produce the scaffold.

Keywords: 3D-printing; chondrogenic differentiation; human adipose derived stem cells; osteochondral; osteogenic differentiation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adipose Tissue / metabolism
  • Biocompatible Materials / chemistry*
  • Bone and Bones
  • Calcium Phosphates / chemistry
  • Calcium Phosphates / metabolism
  • Cartilage, Articular / metabolism
  • Cell Differentiation
  • Cells, Cultured
  • Chondrogenesis / physiology*
  • Collagen Type I / genetics
  • Collagen Type I / metabolism
  • Extracellular Matrix / chemistry
  • Extracellular Matrix / metabolism
  • Humans
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / metabolism
  • Osteogenesis / physiology*
  • Polyesters / chemistry*
  • Polyesters / metabolism
  • Printing, Three-Dimensional
  • Tissue Engineering
  • Tissue Scaffolds / chemistry*

Substances

  • Biocompatible Materials
  • Calcium Phosphates
  • Collagen Type I
  • Polyesters
  • beta-tricalcium phosphate
  • polycaprolactone