Sustainable Bio-Based Membranes As Coatings For Metallic Implants Can Improve Osseointegration

During the last few decades, polymeric materials have reigned as the cornerstone of different developments across the globe, especially in the economic and social sectors. Recently in today’s multifaceted ecosphere, there has been a great universal initiative toward the development of new, high-value sustainable polymers and composite materials procured from bio-renewable resources. These bio-based materials are highly desired in a number of applications, especially in the biomedical industry such as Osseointegration.

Particularly in case of major bone defects, metallic implants for bone substitution represents a common therapeutic solution. In many cases, the need for specific dimensions or shapes require some heavy manufacturing steps, such as for classical titanium implants. One of the solutions to these problems could be the use of magnesium-calcium alloys with mechanical properties closer to the natural bone.

However, one of the major drawbacks for these alloys is that on coming in contact with water, hydrogen is released. This issue could be overcome via the use of sustainable polymeric materials such as cellulose, according to a research team that included researchers from the University Politehnica from Bucharest; Carol Davila University of Medicine and Pharmacy, and Cranfield University. Professors Voicu, Miculescu, and Thakur contributed their extensive expertise in materials and polymers chemistry to the study.

In this work, researchers studied a new application of bio-based sustainable polymeric membranes as novel coatings for such state-of-the-art alloys. These coatings play a double role — to protect the alloy from releasing hydrogen into the organism and to improve the Osseointegration by functionalizing the membrane surface with resveratrol (an antioxidant found in red wine with high potential for proliferation of osteoblasts – the cells that form the bone). So all the materials used are obtained from the natural resources, which is amazing from an environmental and health point of view.

Basically, a membrane is a selective barrier for some particles, molecules, and ions. These materials are well-known for their selective properties and are used as filters in a wide range of applications from water filtration to biomedical applications like hemodialysis or artificial lungs. But due to their porosity, they have the potential to also be used to “induce” a way for bone cells to proliferate from bone to metallic implant and to integrate the implant in the bone. But, the cells must be stimulated to proliferate, and this was the main reason for resveratrol immobilization in this research. If the metallic implant can be covered with resveratrol functionalized polymeric membrane, it will offer marvelous advantages over the currently used ones. This was successfully accomplished in this work.

In the first step, the osteoblasts (cells that form the bone) are stimulated to multiply due to the presence of resveratrol. A higher number of cells that appear will need a place “to go,” and this is the porosity of the membrane. The cells occupy the pores and proliferate to the metallic implant, but at the same time, due to the presence of biological fluids, the membrane will be degraded. Synthesized membrane for this study was made from cellulose acetate – a natural polymer formed from glucose units. On this way, by the degradation of the membrane inside the organism, only acetic acid and glucose will be released, providing a friendly and healthy material. At the end of this process, when all the membrane will be degraded (after 6-12 months), we will have only bone with the integrated metallic implant.

During the synthesis of such materials, analytical methods are very important to prove the obtaining of the right material. But also, cytotoxicity tests must be performed to prove the non-cytotoxic behavior of the material. In this case, we incubated the resveratrol functionalized membrane with MC3T3-E1 cells, which are the precursors for osteoblasts. The tests showed the cells multiplied at the surface of the materials without stress and with a shape very close to the natural bone. Initial tests performed on mice at 3, 6, and 9 months proved the success for use of cellulose acetate membrane for osseointegration applications.

Polymeric membranes are very well known for their uses in biomedical field with different applications like hemodialysis, controlled drug delivery, antimicrobial activity, or as a medium for cell culture. One of the most emerging field, i.e. membranes, for osteointegration include their high potential in a number of applications such as polymeric membranes favoring the welding of metal or graft implants.

The research team has developed a new unique method for synthesis of functionalized cellulose acetate membranes with resveratrol for improving the osseointegration. Cellulose is the most abundant reservoir of renewable materials in the world. The prime advantage of using cellulose acetate include its nifty solubility in different aprotic polar organic solvents, the most important being that inside an organism, it releases acetic acid and glucose, both of which are inoffensive to the human body. Resveratrol is a very well-known antioxidant, present in red wine, with proven activity for osteoblasts and pre-osteoblast proliferation.

In this study, the research group engineered cellulose acetate to produce a functionalized version that is highly sustainable and friendly to health. Indeed, there is a vital need for new sustainable and health friendly materials for implants that both promote rapid osseointegration and prevent bacterial colonization.

This study has successfully developed a new unique coating to enhance osseointegration and has opened the ways for further applications as it is envisioned to reduce the incidence of implant failure (it will save health care a huge amount of money by diminishing the requirement for subsequent surgical procedures). It will also reduce the pain and suffering of patients that arise because of currently-used materials.

These findings are described in the article entitled, Cellulose acetate membranes functionalized with resveratrol by covalent immobilization for improved osseointegration, recently published in the journal Applied Surface Science.

This work was conducted by A. M. Pandele, F. Miculescu, A. Iordache, and S. I. Voicu from the University Politehnica from Bucharest, P.Neacsu, A.Cimpean, and A.I.Staras from the University of Bucharest, V.K. Thakur from the University of Cranfield, and O.D. Toader from the Carol Davila University of Medicine and Pharmacy.

Reference:

1. A.M. Pandele, P. Neacsu, A. Cimpean, A.I. Staras, F. Miculescu, A. Iordache, S.I. Voicu, V.K. Thakur, O.D. Toader, Cellulose acetate membranes functionalized with resveratrol by covalent immobilization for improved Osseointegration, Applied Surface Science, 438, 2-13, 2018, DOI: 10.1016/j.apsusc.2017.11.102.