Creation of Bony Microenvironment with Extracellular Matrix Doped-Bioactive Ceramics to Enhance Osteoblast Behavior and Delivery of Aspartic Acid-Modified BMP-2 Peptides

Int J Nanomedicine. 2020 Oct 29:15:8465-8478. doi: 10.2147/IJN.S272571. eCollection 2020.

Abstract

Introduction: Decellularized matrix from porcine small intestinal submucosa (SIS) endows scaffolds with an ECM-like surface, which enhances stem cell self-renewal, proliferation, and differentiation. Mesoporous bioactive glass (MBG) is extensively recognized as an excellent bio-ceramic for fabricating bone grafts.

Materials and methods: In the current study, SIS was doped on an MBG scaffold (MBG/SIS) using polyurethane foam templating and polydopamine chemistry method. To mimic the bony environment of a natural bone matrix, an ECM-inspired delivery system was constructed by coupling the BMP2-related peptide P28 to a heparinized MBG/SIS scaffold (MBG/SIS-H-P28). The release of P28 from MBG/SIS-H-P28 and its effects on the proliferation, viability, and osteogenic differentiation of bone marrow stromal stem cells were investigated in vitro and in vivo.

Results: Our research indicated that the novel tissue-derived ECM scaffold MBG/SIS has a hierarchical and interconnected porous architecture, and superior biomechanical properties. MBG/SIS-H-P28 released P28 in a controlled manner, with the long-term release time of 40 d. The results of in vitro experiments showed improvements in cell proliferation, cell viability, alkaline phosphatase activity, and mRNA expression levels of osteogenesis-related genes (Runx-2, OCN, OPN, and ALP) compared to those of MBG/SIS or MBG/SIS-P28 and MBG/SIS-H-P28. The in vivo results demonstrated that MBG/SIS-H-P28 scaffolds evidently increased bone formation in rat calvarial critical-sized defect compared to that in controls.

Conclusion: MBG/SIS-H-P28 scaffolds show potential as ideal platforms for delivery of P28 and for providing a bony environment for bone regeneration.

Keywords: BMP2-related peptide; mesoporous bioactive glass; microenvironment; osteogenesis; small intestinal submucosa.

MeSH terms

  • Animals
  • Aspartic Acid / chemistry*
  • Biocompatible Materials / pharmacology*
  • Bone Morphogenetic Protein 2 / pharmacology*
  • Bone Regeneration / drug effects
  • Bone and Bones / drug effects*
  • Cell Differentiation / drug effects
  • Cell Line
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Ceramics / pharmacology*
  • Extracellular Matrix / metabolism*
  • Gene Expression Regulation / drug effects
  • Kinetics
  • Male
  • Mice
  • Osteoblasts / drug effects*
  • Osteogenesis / drug effects
  • Osteogenesis / genetics
  • Peptides / pharmacology*
  • Porosity
  • Rats, Sprague-Dawley
  • Recombinant Proteins / pharmacology
  • Swine
  • Tissue Scaffolds / chemistry
  • Transforming Growth Factor beta / pharmacology*

Substances

  • Biocompatible Materials
  • Bone Morphogenetic Protein 2
  • Peptides
  • Recombinant Proteins
  • Transforming Growth Factor beta
  • recombinant human bone morphogenetic protein-2
  • Aspartic Acid

Grants and funding

This research was financially supported by the National Natural Science Foundation of China (grant numbers 81902219, 81672158 and 81873999) and the National Key R&D Program of China (2016YFC1100100).