Droplet microfluidics as a tool for production of bioactive calcium phosphate microparticles with controllable physicochemical properties

Affordable and therapeutically effective biomaterials are required for successful treatment of orthopaedic critical-size bone defects. Calcium phosphate (CaP) ceramics are widely used for bone repair and regen-eration, however, further optimization of their properties and biological performance is still required. To improve the existing CaP bone graft substitutes, novel synthesis and production approaches are needed that provide a fine control over the chemical and physical properties and versatility in the delivery for-mat. In this study, a microfluidic strategy for production of CaP microparticles with different sizes derived from highly monodisperse droplets is proposed for the controlled synthesis of bioactive CaP ceramics. Mi-crofluidic droplets, that served as microreactors for CaP precipitation, allowed the production of different CaP phases, as well as strontium-substituted CaP. By varying the concentration of the precursor solution, microparticles with different porosity were obtained. The droplet microfluidic system allowed direct vi-sualization and quantification of the reaction kinetics. Upon production and purification of the micropar-ticles, the biocompatibility and bioactivity were tested in vitro using human mesenchymal stromal cells (hMSCs). Cell attachment was analysed by imaging of the cytoskeleton and focal adhesions Moreover, cell proliferation, metabolic activity, alkaline phosphatase activity and mRNA expression of a set of os-teogenic markers were quantified. We demonstrated that droplet microfluidics is a functional technique for the synthesis of a range of bioactive CaP-based ceramics with controlled properties. Statement of significance Calcium phosphate (CaP) ceramics are widely applied synthetic biomaterials for repair and regeneration of damaged bone; yet, CaP bone graft substitutes require further improvement to fully replace natural bone grafts in challenging clinical situations. To this end, novel synthesis and production approaches are needed that provide a fine control over the chemical and physical properties. Here, we developed a mi-crofluidic platform for production of CaP microparticles with different size, composition and porosity, derived from monodisperse droplets. We demonstrated that CaP microparticles produced using this plat-form supported growth and differentiation of human mesenchymal stromal cells. This platform is a useful tool for developing a variety of CaPs in a controlled manner to study their physicochemical properties in relation to their bioactivity. (c) 2021 The Authors. Published by Elsevier Ltd on behalf of Acta Materialia Inc. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ )

Automated summary

Affordable and effective biomaterials are needed for successful treatment of orthopaedic bone defects. Calcium phosphate ceramics are commonly used for bone repair, but further optimization is necessary. A microfluidic strategy for producing CaP microparticles with controlled properties was developed in this study, showing potential for bioactive ceramics synthesis.