Exosome-Functionalized Ceramic Bone Substitute Promotes Critical-Sized Bone Defect Repair in Rats

Research output: Contribution to journalArticle

Abstract

Ceramic biomaterials are promising alternatives to bone autografts. However, limited bioactivity affects their performance. Therefore, bioactive molecules and cells are often added to enhance their performance. Exosomes have emerged as cell-secreted vesicles, delivering proteins, lipids, and nucleic acids in a paracrine/endocrine fashion. We studied two complementary aspects required for exosome activity/therapy using purified exosomes: first, the intracellular uptake of labeled exosomes and second, the influence of delivered exosomes on cell behavior. Origin-specific differences in the characteristics of purified exosomes, quantification of time-dependent intracellular uptake of PKH-26-labeled exosomes by mesenchymal stem cells (MSCs) and preosteoblasts, and influence on cell behavior were evaluated. Furthermore, exosomes from osteoblasts and MSCs cultured under normal and osteogenic environments were isolated. There is little data available on the concentration and dose of exosomes required for bone regeneration. Therefore, equal amounts of quantified exosomes were implanted in vivo in rat tibia critical defects using a calcium sulfate-nano-hydroxyapatite nanocement (NC) bone filler as the carrier. Bone regeneration was quantified using micro-computed tomography and histology. Along with inducing early maturation and mineral deposition by primary preosteoblasts in vitro, exosome treatment also demonstrated a positive effect on bone mineralization in vivo. Our study concludes that providing a local delivery of exosomes loaded onto a slowly resorbing NC bone filler can provide a potential alternate to autografts as a bone substitute.

Details

Authors
  • Arun K. Teotia
  • Irfan Qayoom
  • Prerna Singh
  • Ankita Mishra
  • Deepika Jaiman
  • Jukka Seppälä
  • Lars Lidgren
  • Ashok Kumar
Organisations
External organisations
  • Indian Institute of Technology Kanpur
  • Aalto University
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Biomaterials Science

Keywords

  • bone cement, carrier, exosomes, nano-hydroxyapatite, osteogenic, osteopromotive
Original languageEnglish
Pages (from-to)3716-3726
Number of pages11
JournalACS Applied Bio Materials
Volume4
Issue number4
Publication statusPublished - 2021
Publication categoryResearch
Peer-reviewedYes

Bibliographic note

Funding Information: The authors acknowledge the Department of Biotechnology (DBT) (DBT-VINNOVA, Indo-Swedish project BT/IN/Sweden/08/AK/2017–18); the Science and Engineering Research Board (SERB), Govt of India (Project# IPA/2020/000026) and the Department of Science and Technology (DST), (DST-VR, Indo-Swedish project), Ministry of Science and Technology, Govt. of India, for financial support. The authors also acknowledge the partial funding from the Ministry of Human Resource Development (MHRD)- and Indian Council of Medical Research (ICMR)-funded Uchhatar Avishkar Yojana (UAY) scheme (Project# MHRD_IITK_006), MHRD-IMPRINT (MHRD_6714/Healthcare), MHRD-SPARC (SPARC/2018–2019/P612/SL), Govt. of India. A.K.T., D.J., and I.Q. acknowledge the Ministry of Human Resource and Development, Govt. of India, and IIT Kanpur for PhD fellowships and AK acknowledges Rajeeva and Sangeeta Lahri Chair, IITK. PS would like to acknowledge Council of Scientific and Industrial Research (CSIR), India for providing fellowship as research associate. A.M would like to acknowledge IIT Kanpur for Institute post-doctoral fellowship.