The effect of aging on the bone healing properties of blood plasma

Faez Saleh Al-Hamed; Rania Rodan; Jose Luis Ramirez-Garcialuna; Osama Elkashty; Nasser Al-Shahrani; Simon D Tran; Marie Lordkipanidzé; Mari Kaartinen; Zahi Badran; Faleh Tamimi

doi:10.1016/j.injury.2021.05.001

The effect of aging on the bone healing properties of blood plasma

Injury. 2021 Jul;52(7):1697-1708. doi: 10.1016/j.injury.2021.05.001. Epub 2021 May 9.

Affiliations

¹ Faculty of Dentistry, McGill University, Montreal, QC, Canada.
² Faculty of Dentistry, McGill University, Montreal, QC, Canada; Senior specialist in periodontology, Royal Medical Services, Amman, Jordan.
³ Faculty of Medicine, McGill University, Montreal, QC, Canada; The Bone Engineering Labs, Research Institute McGill University Health Center, Montreal, QC, Canada.
⁴ Faculty of Dentistry, McGill University, Montreal, QC, Canada; Faculty of Dentistry, Mansoura University, Mansoura, Egypt.
⁵ Faculté de pharmacie, Université de Montréal, Montréal, QC, Canada; Research Center, Montreal Heart Institute, Montreal, QC, Canada.
⁶ Faculty of Dentistry, McGill University, Montreal, QC, Canada; Department of Periodontology (CHU/Rmes Inserm U1229/UIC11), Faculty of Dental Surgery, University of Nantes, Nantes, France; College of Dental Medicine, University of Sharjah, Sharjah, United Arab Emirates.
⁷ College of Dental Medicine, Qatar University, Doha, Qatar. Electronic address: fmarino@qu.edu.qa.

PMID: 34049703
DOI: 10.1016/j.injury.2021.05.001

Abstract

Objectives: Age-related changes in blood composition have been found to affect overall health. Thus, this study aimed to understand the effect of these changes on bone healing by assessing how plasma derived from young and old rats affect bone healing using a rat model.

Methods: . Blood plasma was collected from 6-month and 24-month old rats. Differences in elemental composition and metabolome were assessed using optical emission spectrometry and liquid mass spectrometry, respectively. Bilateral tibial bone defects were created in eight rats. Young plasma was randomly applied to one defect, while aged plasma was applied to the contralateral one. Rats were euthanized after two weeks, and their tibiae were analyzed using micro-CT and histology. The proteome of bone marrow was analyzed in an additional group of three rats.

Results: Bone-defects treated with aged-plasma were significantly bigger in size and presented lower bone volume/tissue volume compared to defects treated with young-plasma. Histomorphometric analysis showed fewer mast cells, macrophages, and lymphocytes in defects treated with old versus young plasma. The proteome analysis showed that young plasma upregulated pathways required for bone healing (e.g. RUNX2, platelet signaling, and crosslinking of collagen fibrils) whereas old plasma upregulated pathways, involved in disease and inflammation (e.g. IL-7, IL-15, IL-20, and GM-CSF signaling). Plasma derived from old rats presented higher concentrations of iron, phosphorous, and nucleotide metabolites as well as lower concentrations of platelets, citric acid cycle, and pentose phosphate pathway metabolites compared to plasma derived from young rats.

Conclusion: bone defects treated with plasma-derived from young rats showed better healing compared to defects treated with plasma-derived from old rats. The application of young and old plasmas has different effects on the proteome of bone defects.

Keywords: Aging; Biomaterials; Bone healing; Immune response; Plasma concentrates.

MeSH terms

Aging
Animals
Bone Regeneration*
Plasma
Rats
Tibia
Wound Healing*