Preparation of Decellularized Triphasic Hierarchical Bone-Fibrocartilage-Tendon Composite Extracellular Matrix for Enthesis Regeneration

Adv Healthc Mater. 2019 Oct;8(19):e1900831. doi: 10.1002/adhm.201900831. Epub 2019 Aug 28.

Abstract

Tendon to bone (enthesis) rupture, which may cause disability and persistent pain, shows high rate of re-rupture after surgical repair. Tendon or enthesis scaffolds have been widely studied, but few of these materials can recapitulate the tissue continuity. Thus, this study is conducted to prepare a triphasic decellularized bone-fibrocartilage-tendon (D-BFT) composite scaffold. The D-BFT scaffold is developed using a combination of physical, chemical, and enzymatic treatments using liquid nitrogen, Triton-X 100, sodium-dodecyl sulfate, and DNase I, which effectively removes the cell components while preserving the biological composite and microstructure. Moreover, the mechanical properties of D-BFT are highly preserved and similar to those of the human Achilles tendon. Additionally, in vitro, mesenchymal stem cells (MSCs) adhered, proliferated, and infiltrated into the D-BFT scaffold, and MSC differentiation is confirmed by up-regulation of osteogenic-related and tenogenic-related genes. The repair outcomes are explored by applying the D-BFT scaffold in the model of femur-tibia defects in vivo, which shows good repair results. Thus, the D-BFT scaffold developed in this study is a promising graft for enthesis regeneration.

Keywords: biomechanics; decellularization; enthesis regeneration; fibrocartilage; tendon-to-bone junctions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Achilles Tendon / physiology*
  • Animals
  • Bone and Bones / physiology*
  • Cell Adhesion
  • Cell Differentiation
  • Cell Proliferation
  • Collagen / chemistry
  • Extracellular Matrix / chemistry*
  • Fibrocartilage / physiology*
  • Humans
  • Mesenchymal Stem Cells / cytology
  • Mice
  • Mice, Inbred C57BL
  • Nitrogen / chemistry
  • Osteogenesis
  • Regeneration*
  • Regenerative Medicine / instrumentation
  • Regenerative Medicine / methods
  • Stress, Mechanical
  • Tissue Engineering / methods
  • Tissue Scaffolds / chemistry*
  • X-Ray Microtomography

Substances

  • Collagen
  • Nitrogen