Biofunctionalized chondrogenic shape-memory ternary scaffolds for efficient cell-free cartilage regeneration

Acta Biomater. 2020 Mar 15:105:97-110. doi: 10.1016/j.actbio.2020.01.015. Epub 2020 Jan 15.

Abstract

Cartilage defect repair remains a great clinical challenge due to the limited self-regeneration capacity of cartilage tissue. Surgical treatment of injured cartilage is rather difficult due to the narrow space in the articular cavity and irregular defect area. Herein, we designed and fabricated chondrogenic and physiological-temperature-triggered shape-memory ternary scaffolds for cell-free cartilage repair, where the poly (glycerol sebacate) (PGS) networks ensured elasticity and shape recovery, crystallized poly (1,3-propylene sebacate) (PPS) acted as switchable phase, and immobilized bioactive kartogenin (KGN) endowed the scaffolds with chondrogenic capacity. The resultant scaffolds exhibited shape-memory properties with shape-memory fixed ratio of 98% and recovered ratio of 97% at 37°C for PPS/PGS/KGN-100, indicating a good potential for minimally invasive implantation. The scaffolds gradually degraded in Dulbecco's phosphate-buffered saline and released KGN up to 12 weeks in vitro. In addition, the scaffolds promoted chondrogenic differentiation while inhibiting osteogenic differentiation of bone marrow-derived mesenchymal stem cells in a concentration-dependent manner and cartilage regeneration in full-thickness defects of rat femoropatellar groove for 12 weeks. Consequently, the PPS/PGS/KGN-100 scaffolds stimulated the formation of an overlying layer of neocartilage mimicking the characteristic architecture of native articular cartilage even in the absence of exogenous growth factors and seeded cells. This study provides much inspiration for future research on cartilage tissue engineering. STATEMENT OF SIGNIFICANCE: There are two crucial challenges for cartilage defect repair: the lack of self-regeneration capacity of cartilage tissue and difficult scaffold implantation via traditional open surgery due to space-limited joints. Herein, bioactive body-temperature-responsive shape memory scaffolds are designed to simultaneously address the challenges. The scaffolds can be readily implanted by minimally invasive approach and recover by body-temperature of patient. The integration of kartogenin endows scaffolds the bioactivity, leading to the first example of bulk shape-memory scaffolds for cell-free cartilage repair. These characteristics make the scaffolds advantageous for clinical translation. Moreover, our developed material is easy to be functionalized due to the presence of extensive free hydroxyl groups and provides a versatile platform to design diverse functional shape memory biomaterials.

Keywords: Cell-free cartilage regeneration; Chondrogenic; Kartogenin; Minimally invasive implantation; Shape-memory scaffold.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anilides / chemistry
  • Anilides / pharmacology
  • Animals
  • Cartilage, Articular / physiology*
  • Cell Survival / drug effects
  • Cells, Cultured
  • Chondrogenesis* / drug effects
  • Decanoates / chemistry
  • Decanoates / pharmacology
  • Delayed-Action Preparations / pharmacology
  • Gene Expression Regulation / drug effects
  • Glycerol / analogs & derivatives
  • Glycerol / chemistry
  • Glycerol / pharmacology
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / drug effects
  • Phthalic Acids / chemistry
  • Phthalic Acids / pharmacology
  • Polymers / chemistry
  • Polymers / pharmacology
  • Rats, Sprague-Dawley
  • Regeneration / drug effects*
  • Smart Materials / pharmacology*
  • Temperature
  • Tissue Scaffolds / chemistry*

Substances

  • Anilides
  • Decanoates
  • Delayed-Action Preparations
  • Phthalic Acids
  • Polymers
  • Smart Materials
  • poly(glycerol-sebacate)
  • Glycerol
  • kartogenin