Strontium substituted hydroxyapatite with β-lactam integrin agonists to enhance mesenchymal cells adhesion and to promote bone regeneration

Martina Cirillo, Giulia Martelli, Elisa Boanini, Katia Rubini, Mara Di Filippo, Paola Torricelli, Stefania Pagani, Milena Fini, Adriana Bigi, Daria Giacomini

Research output: Contribution to journalArticlepeer-review

Abstract

Multi-functionalization of calcium phosphates to get delivery systems of therapeutic agents is gaining increasing relevance for the development of functional biomaterials aimed to solve problems related to disorders of the muscolo-skeletal system. In this regard, we functionalized Strontium substituted hydroxyapatite (SrHA) with some β-lactam integrin agonists to develop materials with enhanced properties in promoting cell adhesion and activation of intracellular signaling as well as in counteracting abnormal bone resorption. For this purpose, we selected two monocyclic β-lactams on the basis of their activities towards specific integrins on promoting cell adhesion and signalling. The amount of β-lactams loaded on SrHA could be modulated on changing the polarity of the loading solution, from 3.5-24 wt% for compound 1 and from 3.2-8.4 wt% for compound 2. Studies on the release of the β-lactams from the functionalized SrHA in aqueous medium showed an initial burst followed by a steady-release that ensures a small but constant amount of the compounds over time. The new composites were fully characterized. Co-culture of human primary mesenchymal stem cells (hMSC) and human primary osteoclast (OC) demonstrated that the presence of β-lactams on SrHA favors hMSC adhesion and viability, as well as differentiation towards osteoblastic lineage. Moreover, the β-lactams were found to enhance the inhibitory role of Strontium on osteoclast viability and differentiation.

Original languageEnglish
Pages (from-to)1-9
Number of pages9
JournalColloids and Surfaces B: Biointerfaces
Volume200
Early online dateJan 16 2021
DOIs
Publication statusPublished - Apr 2021

Keywords

  • Apatite nanoparticles
  • Biomedical applications
  • Cell adhesion
  • Delivery vehicle
  • Osteoinduction
  • β-lactams

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