Cell-Free HA-MA/PLGA Scaffolds with Radially Oriented Pores for In Situ Inductive Regeneration of Full Thickness Cartilage Defects

Macromol Biosci. 2016 Nov;16(11):1632-1642. doi: 10.1002/mabi.201600218. Epub 2016 Jul 26.

Abstract

A bioactive scaffold with desired microstructure is of great importance to induce infiltration of somatic and stem cells, and thereby to achieve the in situ inductive tissue regeneration. In this study, a scaffold with oriented pores in the radial direction is prepared by using methacrylated hyaluronic acid (HA-MA) via controlled directional cooling of a HA-MA solution, and followed with photo-crosslinking to stabilize the structure. Poly(lactide-co-glycolide) (PLGA) is further infiltrated to enhance the mechanical strength, resulting in a compressive modulus of 120 kPa. In vitro culture of bone marrow stem cells (BMSCs) reveals spontaneous cell aggregation inside this type of scaffold with a spherical morphology. In vivo transplantation of the cell-free scaffold in rabbit knees for 12 w regenerates simultaneously both cartilage and subchondral bone with a Wakitani score of 2.8. Moreover, the expression of inflammatory factor interleukin-1β (IL-1β) is down regulated, although tumor necrosis factor-α (TNF-α) is remarkably up regulated. With the anti-inflammatory, bioactive properties and good restoration of full thickness cartilage defect in vivo, the oriented macroporous HA-MA/PLGA hybrid scaffold has a great potential for the practical application in the in situ cartilage regeneration.

Keywords: cartilage regeneration; hyaluronic acid; in situ inductivity; microstructure; scaffolds.

MeSH terms

  • Animals
  • Cartilage / injuries
  • Cartilage / physiology*
  • Hyaluronic Acid* / chemistry
  • Hyaluronic Acid* / pharmacology
  • Interleukin-1beta / metabolism
  • Knee Injuries / metabolism
  • Knee Injuries / pathology
  • Knee Injuries / therapy*
  • Lactic Acid* / chemistry
  • Lactic Acid* / pharmacology
  • Methacrylates* / chemistry
  • Methacrylates* / pharmacology
  • Polyglycolic Acid* / chemistry
  • Polyglycolic Acid* / pharmacology
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Rabbits
  • Regeneration / drug effects*
  • Tissue Scaffolds / chemistry*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Interleukin-1beta
  • Methacrylates
  • Tumor Necrosis Factor-alpha
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Hyaluronic Acid