2. Academic Validation
  3. Improving the Intercellular Uptake and Osteogenic Potency of Calcium Phosphate via Nanocomplexation with the RALA Peptide

Improving the Intercellular Uptake and Osteogenic Potency of Calcium Phosphate via Nanocomplexation with the RALA Peptide

  • Nanomaterials (Basel). 2020 Dec 7;10(12):2442. doi: 10.3390/nano10122442.
Michelle O'Doherty 1,  Eoghan J Mulholland 1,  Philip Chambers 1,  Sreekanth Pentlavalli 1,  Monika Ziminska 1,  Marine J Chalanqui 1,  Hannah M Pauly 2,  Binulal N Sathy 3,  Tammy H Donahue 2 4,  Daniel J Kelly 3 5 6 7,  Nicholas Dunne 1 3 5 7 8 9 10 11,  Helen O McCarthy 1 12
Affiliations

Affiliations

  • 1 School of Pharmacy, Queen's University Belfast, Belfast BT9 7BL, UK.
  • 2 Department of Biomedical Engineering, University Colorado State University, 1374 Campus Delivery, Fort Collins, CO 80523, USA.
  • 3 Trinity Centre for Bioengineering, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland.
  • 4 School of Biomedical Engineering, University of Massachusetts Amherst, 130 Natural Resources Road, Amherst, MA 01003, USA.
  • 5 Department of Mechanical and Manufacturing Engineering, School of Engineering, Trinity College Dublin, Dublin 2, Ireland.
  • 6 Department of Anatomy, Royal College of Surgeons in Ireland, Dublin 2, Ireland.
  • 7 Advanced Materials and Bioengineering Research Centre (AMBER), Royal College of Surgeons in Ireland and Trinity College Dublin, Dublin 2, Ireland.
  • 8 School of Mechanical and Manufacturing Engineering, Dublin City University, Dublin 9, Ireland.
  • 9 Centre for Medical Engineering Research, School of Mechanical and Manufacturing Engineering, Dublin City University, Dublin 9, Ireland.
  • 10 Advanced Manufacturing Research Centre (I-Form), School of Mechanical and Manufacturing Engineering, Dublin City University, Glasnevin, Dublin 9, Ireland.
  • 11 Advanced Processing Technology Research Centre, Dublin City University, Dublin 9, Ireland.
  • 12 School of Chemical Sciences, Dublin City University, Dublin 9, Ireland.
PMID: 33297306 DOI: 10.3390/nano10122442
Abstract

Calcium phosphate-base Materials (e.g., alpha tri-calcium phosphate (α-TCP)) have been shown to promote osteogenic differentiation of stem/progenitor cells, enhance osteoblast osteogenic activity and mediate in vivo bone tissue formation. However, variable particle size and hydrophilicity of the calcium phosphate result in an extremely low bioavailability. Therefore, an effective delivery system is required that can encapsulate the calcium phosphate, improve cellular entry and, consequently, elicit a potent osteogenic response in osteoblasts. In this study, collagenous matrix deposition and extracellular matrix mineralization of osteoblast lineage cells were assessed to investigate osteogenesis following intracellular delivery of α-TCP nanoparticles. The nanoparticles were formed via condensation with a novel, cationic 30 Mer amphipathic peptide (RALA). Nanoparticles prepared at a mass ratio of 5:1 demonstrated an average particle size of 43 nm with a zeta potential of +26 mV. The average particle size and zeta potential remained stable for up to 28 days at room temperature and across a range of temperatures (4-37 °C). Cell viability decreased 24 h post-transfection following RALA/α-TCP nanoparticle treatment; however, recovery ensued by Day 7. Immunocytochemistry staining for Type I Collagen up to Day 21 post-transfection with RALA/α-TCP nanoparticles (NPs) in MG-63 cells exhibited a significant enhancement in Collagen expression and deposition compared to an untreated control. Furthermore, in porcine mesenchymal stem cells (pMSCs), there was enhanced mineralization compared to α-TCP alone. Taken together these data demonstrate that internalization of RALA/α-TCP NPs elicits a potent osteogenic response in both MG-63 and pMSCs.

Keywords

RALA; bone engineering; calcium phosphate; intercellular; osteogenic; peptide.

Figures
Products
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  • HY-P5284
    99.16%, Amphiphilic Delivery Agent