Achieving tunable and interconnected porosity of biomimetic apatite scaffolds through Pickering emulsion templates

Introduction

Synthetic apatitic calcium phosphates (CaP) are widely used as precursors to develop biomaterial devices due to their excellent biological properties, including biocompatibility, bioactivity and bioresorbability. These properties can be significantly enhanced by improving their biomimetism, that is, using fabrication processes to generate biomaterials with similar chemical compositions, structures and surface properties as biological compounds. Nanocrystalline apatitic calcium phosphates (NCA), named biomimetic apatites, constitute the mineral part of calcified tissue such as bone mineral [1,2]. Moreover, bioactive materials have been shown to form a nanocrystalline apatite layer with bone tissue, which is essential in the biointegration of implants [1,2]. Compared with stoichiometric hydroxyapatite (HA, Ca10(PO4)6(OH)2), which is the most stable and least soluble apatitic CaP at ambient conditions, NCA are more soluble and have greater surface reactivity due to the existence around an apatitic core of a structured but non-apatitic hydrated surface layer rich in labile ions (Ca2+, HPO42−, CO32−) [3]. Thus, synthetic nanocrystalline apatites are used in several bio-inspired apatite-based implants due to their unique physicochemical and surface properties. Although NCA are proposed as coatings on metallic implants, composites biomaterials or bone cements [4], they are rarely used as bioceramics because the processing of such unstable phases by conventional techniques, at a high temperature (more than 1000°C) [5], strongly alters their physico-chemical properties, surface reactivity and biological activity.

Another key parameter influencing bone reconstruction is the porous architecture of bone substitutes, including bone cells colonisation [6,7]. The pore size distribution is of great importance. Three pore size ranges have been established by International Union of Pure and Applied Chemistry (IUPAC): micropores (< 2 nm), mesopores (2–50 nm) and macropores (> 50 nm) [6]. In the biomaterials field, the description of the commonly used pore size varies based on the IUPAC values, due to the large size of pores and the fact that two pore size ranges support bone formation: macroporosity refers to pores with a diameter greater than 50 µm, while microporosity refers to pores with a diameter of < 50 µm [6]. From a biological point of view, the presence of macropores ensures the invasion of the cavities by the cells, along with the introduction of vascularisation, which supplies biological fluids necessary for survival and cell differentiation. Macroporosity plays a key role in osteoblast infiltration within the scaffold, as well as cell attachment, proliferation and differentiation, which may then promote integration with the host tissue [6]. Thus, according to the scaffold types, the optimum range of pore size for bone regeneration appears to be between 100 and 500 μm [[8], [9], [10]], but interconnection is also essential to allow the circulation of biological fluids and complete cellular colonisation of pores [11]. Other properties of pore architecture, such as morphology and pore distribution, have an effect on cellular activity [6]. Several techniques have been proposed to produce macroporous CaP-based biomaterials, including freeze casting [12,13], sol-gel process [14], 3D printing [15,16] and self-setting cement [17,18]. Moreover, microporosity is known to influence bone regeneration: it has a positive effect on cellular activity and increases protein adsorption, which improves the osteoconductive capacity of the implant [6]. Finally, controlling the macro- and microporosity of scaffolds also controls their mechanical function, which is important for successful bone regeneration [19].

The development of a material that can fill bone defects in maxillofacial or orthopaedic surgery involves a complex and optimised balance between the different physical (mechanical), chemical (reactivity and solubility) and biological (osteoconductivity) properties. The manufacturing process used in this study to produce CaP scaffolds is based on the use of Pickering emulsion as a pore-forming agent. Very few studies have reported the use of Pickering emulsions as templates to produce biomaterials such as CaP composite scaffolds [20] or hybrid microspheres [21,22]. The aim of this study was to develop NCA-based apatitic bioceramics with interconnecting and adjustable size pores, manufactured by using an original and previously published low-temperature method of elaboration using biocompatible Pickering emulsions [23], without organic part and sintering to preserve surface reactivity and to improve bioactivity.

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Pickering emulsion

Direct type (oil-in-water) homogeneous Pickering emulsions stabilised by hydroxyapatite particles were obtained using a published emulsification process [23]. Stoichiometric HA powder was synthesised by double decomposition technique [24]. The aqueous phase containing HA was prepared using 0.5 M NaCl, Miglyol 812 (pharmaceutical grade, medium-chain triglyceride biocompatible oil, INRESA, France) used as an organic phase was added to the aqueous phase .

Karline Pascaud, Christophe Tenailleau, Benjamin Duployer, Romain Sescousse, Fabien Brouillet, Cristiano C. Jayme, Daniela S. Fernandes, Antonio C. Tedesco, Stéphanie Sarda, Maria Ines Ré, Achieving tunable and interconnected porosity of biomimetic apatite scaffolds through Pickering emulsion templates, Materialia, 2024, 102308, ISSN 2589-1529, https://doi.org/10.1016/j.mtla.2024.102308.

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