Full length articleCellulose acetate membranes functionalized with resveratrol by covalent immobilization for improved osseointegration
Introduction
Polymeric membranes possess an unique own place in the current materials usage because of their core property − selectivity [1], which allows their use in a large field of applications, such as water purification [2], [3], proteins separation [4], fuel cells [5], or sensors [6], [7], [8]. One of the most studied domain is the biomedical applications field, such as haemodialysis and drug controlled release [9] or antimicrobial membranes [10]. Among the different polymers used in membranes applications, cellulose derivatives are among the utmost used polymers because of their wide spread nature (the most abundant material- 5 × 1011 tones generated in the biosphere in a year [11]), pronounced mechanical properties [12], [13], thermal resistance [14], [15] and the versatility of processing methods [16], [17]. A new and diminutive studied field is that of membranes for osteointegration − polymeric membranes favouring the welding of metal or graft implants, defective bones, membranes used especially in dentistry [18]. Membranes for such applications favour the proliferation of osteoblasts from the bone to the metallic implant [19], [20], [21], and must also be obtained from biodegradable and bioresorbable polymers [22], [23], [24]. The possibility to obtain these materials from biocompatible and bioresorbable polymers such as chitosan [25], collagen [26], [27] cellulose derivatives [28], or caprolactone [29] has been studied in detail. Other studies have been performed on biocompatible, non-biodegradable polymers, but with high capacity for osteointegration such as polytetrafluoroethylene (PTFE) [30]. Different synthetic methods such as precipitation or sol-gel synthesis [31] have also been studied, as well as the possibility of combining membrane osteointegration with controlled release [32], [33].
The present study comes as a continuation of previous research performed by the same team on the synthesis of functionalized membranes with potential for osteointegration, the molecule initially studied being sericin [28]. Thus, in this case, cellulose acetate (CA) membrane was functionalized with resveratrol (Res), a natural polyphenolic compound that has been shown to have a stimulatory effect on bone formation both in vitro [34], [35] and in vivo [36].
In vitro studies are often performed in order to assess the bioactvity of a material used as potential candidate for bone tissue engineering [34], [37]. Bone formation involves active and differentiated osteoblaststs which induce the synthesis of extracellular matrix that will support the mineralization process [35], [38]. This natural function of osteoblasts might be influenced by the presence of a degradable implant [36], [39]. Recent investigations have shown that magnesium (Mg) itself has the capacity to stimulate the osteoblasts and to induce osteoinductive properties [37], [38], [39], [40] [40], [41], [42], [43]. However, the rapid degradation rate of Mg remains a critical challenge. To prevent the fast dissolution of a Mg alloy, namely Mg-1Ca-0.2Mn-0.6Zr alloy, in the present work cellulose acetate (CA) coatings or CA coatings functionalized with resveratrol (CA-Res) are proposed. In vitro tests of cellular proliferation and differentiation are performed in order to evaluate these novel biomaterials for their bone forming potential using MC3T3-E1 cell line. The obtained results could provide additional information for the development of novel materials for application in bone tissue engineering that enhance bone repair and regeneration.
The aim of this paper was to develop a facile method for immobilizing resveratrol (Res) on the surface of a cellulose acetate CA membrane using aminopropyl triethoxysilane (APTS) and glutaraldehyde as linker molecules. The obtained membraness were morphologically and structurally characterized, and cell culture-based tests were also performed to verify the character of osteointegration.
In order to cover the implants made by Mg alloy, the membrane for coating can be synthesized by dipping the alloy in any shape in polymer solution, followed by solvent evaporation. By solvent evaporation, very compact polymeric films are synthesized with small-diameter pores, conferring a smooth character to the surface. The strength of the coating and also the adhesion is indicated by its block uniformity [44].
Section snippets
Membranes synthesis
For the immobilization of resveratrol, the cellulose derivative −cellulose acetate was used. The membranes were prepared using a 12% cellulose acetate solution (CA, Sigma Aldrich, 67% acetylation degree) in N, N'-dimethylformamide (DMF, Sigma Aldrich analytical purity 99.96%). Membranes synthesis was done using inversion of the phase by precipitation in water. For this, a polymer film of 300 μm thickness is deposited on the glass and immersed in the clotting bath until the formed membranes
Cellulose acetate-based membrane characteristics
Recently, magnesium and its alloys have been considered ideal candidates as temporary implants due to their excellent particularities such as strength and ductility and the capability to degrade. However, the main drawback of Mg-based materials is its corrosion resistance which often led to local alkalization and a high amount of hydrogen and other ions accumulation in the cavity around the implant resulting in a rapid loss of the mechanical integrity. In order to overcome these side effects,
Conclusions
Covalent immobilization of resveratrol Res onto cellulose acetate CA polymeric membranes was presented for potential application in the improvement of osseointegration processes. Resveratrol was immobilized onto membranes using glutaraldehyde as linker after initial reaction between hydrolysed cellulose acetate and amino propyl triethoxy silane. Scanning electron microscopy revealed morphological changes (due to the crosslinking effect of APTS and glutaraldehyde reactions), correlated with
Acknowledgement
The authors gratefully acknowledge the financial support through project PN II-PT-PCCA-195/2014, acronym BioCoatMag, financed by the Romanian Ministry of National Education, CNCS − UEFISCDI Romania.
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