Abstract
A biomaterial that is both bioactive and capable of controlled drug release is highly attractive for bone regeneration. In previous works, we demonstrated the possibility of combining activated carbon fiber cloth (ACC) and biomimetic apatite (such as calcium-deficient hydroxyapatite (CDA)) to develop an efficient material for bone regeneration. The aim to use the adsorption properties of an activated carbon/biomimetic apatite composite to synthetize a biomaterial to be used as a controlled drug release system after implantation. The adsorption and desorption of tetracycline and aspirin were first investigated in the ACC and CDA components and then on ACC/CDA composite. The results showed that drug adsorption and release are dependent on the adsorbent material and the drug polarity/hydrophilicity, leading to two distinct modes of drug adsorption and release. Consequently, a double adsorption approach was successfully performed, leading to a multifunctional and innovative ACC-aspirin/CDA-tetracycline implantable biomaterial. In a second step, in vitro tests emphasized a better affinity of the drug (tetracycline or aspirin)-loaded ACC/CDA materials towards human primary osteoblast viability and proliferation. Then, in vivo experiments on a large cortical bone defect in rats was carried out to test biocompatibility and bone regeneration ability. Data clearly highlighted a significant acceleration of bone reconstruction in the presence of the ACC/CDA patch. The ability of the aspirin-loaded ACC/CDA material to release the drug in situ for improving bone healing was also underlined, as a proof of concept. This work highlights the possibility of bone patches with controlled (multi)drug release features being used for bone tissue repair.
Highlights
Calcium phosphates (CaPs) have been used in dental and bone surgery since the 1980s, mainly in the form of hydroxyapatite, which has become an essential bone substitute in orthopedic, maxillofacial and implant surgery [1,2,3,4,5]
The experimental conditions were optimized in a previous work [46]. This led to the formation of a biomimetic apatite consisting of a carbonated calcium-deficient hydroxyapatite (CDA) phase deposited on a activated carbon fiber cloth (ACC) substrate, as we reported previously [47]
The adsorption and desorption of both drugs were studied, highlighting drug release specificities between CDA and ACC loaded materials and the propensity to apply this approach to actual ACC/CDA composites
Summary
Calcium phosphates (CaPs) have been used in dental and bone surgery since the 1980s, mainly in the form of hydroxyapatite, which has become an essential bone substitute in orthopedic, maxillofacial and implant surgery [1,2,3,4,5]. The occurrence of a hydrated ionic layer on their surface of bone(-like) apatite nanocrystals allows rapid ion exchanges with body fluids [9,10] and a significantly increased reactivity for the adsorption of active (bio)molecules and drugs [11,12] This is why the synthesis of nanocrystalline biomimetic apatites has been a focus of research, as bone cements [13,14] and coatings [15,16], and in other domains such as medical imaging [17,18,19] and nanomedicine [20]. Synthetic nanocrystalline and non-stoichiometric apatites, referred to as “biomimetic”, seem excellent candidates for biomaterial support for in situ delivery systems These biomimetic apatites have a high surface reactivity, directly related to the presence of the above-mentioned non-apatitic hydrated layer containing labile ions on the nanocrystal surface [11,15,23]. The possibility of providing additional and new functionalities is a means of adapting the biomaterials used for bone regeneration to support clinical needs and patient well-being [11,15], e.g., to accelerate bone regeneration and limit complications such as infections or bone necrosis
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