Therapeutic strategies for enhancing bone healing response by using bioactive coatings for bioresorbable magnesium-based implants
Assoc. Prof. Anisoara Cimpean
Phone number: 021.318.15.75/int 106
Fax : 021.318.15.75/int 102
University of Bucharest
Faculty of Biology, Department of Biochemistry and Molecular Biology
Partners involved in the project:
P1 – Polytechnic University of Bucharest
P2 – University of Agronomic Sciences and Veterinary Medicine of Bucharest
P3 – R&D Consulting and Services S.R.L.
P4 – Tehnomed Impex Co S.A.
Project type and number:
During last decade, orthopedic implants have attracted an increasing interest for research and clinical applications but still can be said that they are far from being optimal. Current metallic implanted biomaterials remain permanent in the body and the long-term exposure of these non-degradable implants significantly increases the risk of complications such as chronic inflammation and associated foreign body reaction. The implant encapsulation represents one of the major drawbacks of these implants. Besides, several implantable devices are used to achieve a temporary function and a second procedure to remove them is often difficult. The current research is focused on investigating the application of bioresorbable metals, which are expected to support the healing process of the damaged tissue and to degrade further as the functional regenerated tissue is formed. Magnesium (Mg)- based alloys represents o novel class of biodegradable biomaterials with high specific strength and biocompatibility able to achieve a temporary function making possible the avoidance of the costly second replacement. However, the side effects such as hydrogen gas bubbles formed around the implant and a localized pH change, generated by extremely high degradation rate of magnesium in body fluids, can negatively impact on its host-tissue integration.
In this context, the aim of this project is to develop a new biotechnological strategy to overcome the issues previously mentioned and improve the osseointegration capacity of magnesium-based implants. Therefore, a novel coated alloy based on MgCaMnZr system will be developed and investigated by innovative technologies and techniques to obtain a controlled dissolution rate and to reduce the hydrogen gas production.
This material will be thermomechanically processed to allow its structural adjustment and to meet the expected properties. Moreover, the coatings based on cellulose will be functionalized with resveratrol or sericin, two biomolecules recently characterized for their beneficial effects on bone regeneration. We are expecting that the selected novel Mg-based alloy along with the developed coatings will protect the alloy slowing down its rate of degradation, providing the implant with the desired strength in the initial period of healing process and avoiding side effects associated to its rapid degradation. Furthermore, the functionalization of these coatings is expected to accelerate the healing process and the osseointegration of the implant. The project approaches an experimental multidisciplinary research seeking significant advancement in more than one field of science (i.e., biotechnology, material science, medicine etc), involving a qualified research team with specific skills and expertise. Thus, complex in vitro biological investigations consisting of interface studies will be performed in order to select the most suitable alloy formula for the targeted application and further to establish its in vivo biological performance on experimental animal models. The selected samples will be implanted as prototypes in Wistar rats and small domestic animals for in vivo monitoring of host tissue response and defect repair. The developed material and the demonstrator product will be also investigated to evaluate the physico-chemical properties. All the data obtained will be integrated in order to identify the best material’s features for targeted application. The original and innovative biotechnological approach of this project is expected to have an important impact on health related life standard and contribute to increasing life expectancy. We also hope into a positive impact of the project on the health care-associated costs, educational system and human resources.
The overall objective of the project is to develop a new Mg-based bioresorbable implant by designing new coating strategies for enhancing the osseointegration.
The specific objectives of this project are:
i) To approach novel technological strategies in order to improve the biological performance of temporary bone implants;
ii) To establish an original composition for the novel Mg-based alloys with high biocompatibility and low degradation rate in physiological fluids and to develop laboratory technologies for its synthesis;
iii) To establish the procedure and parameters for biomaterial thermo-mechanical processing of a novel Mg-based alloy with high biocompatibility and low degradation rate in physiological fluids and to define its characteristics;
iv) To obtain novel cellulose-coatings for Mg-based biomaterials and functionalize them with sericin or resveratrol;
v) To obtain the demonstrator product – coated and functionalized temporary implant based on the new Mg alloy;
vi) To establish and define the final coated Mg-based alloys, non-functionalized and functionalized with biomolecules displaying the best biological performance based on in vitro studies;
vii) To demonstrate the developed technologies and to obtain the demonstrator novel Mg-based temporary implant;
viii) To develop an experimental in vivo model for Mg-based implants manufactured by newly-developed biotechnological strategies;
Expected results of the project are:
The expected results of the project are:
i) Execution of the demonstrator product – bioresobable implant with high biocompatibility, enhanced bone healing and anti-inflammatory response, and controlled degradation rate, features that are demonstrated by in vitro and in vivo testing.
ii) Development of a new technology for the new Mg-based alloy synthesis, thermo-mechanical processing, implant manufacturing, surface coating and functionalization, in order to be industrially implemented.
iii) Dissemination of the results through the project web page, by which we will inform the public, surgeons and companies about our products and models.
v) Dissemination of the results through 2 ISI scientific papers, 4 national and international communication for informing the scientific community to increase the Romanian research visibility.
vi) Elaboration of PhD (1) and Master (1) theses
Neacsu P, Staras AI, Voicu SI, Ionascu I, Soare T, Uzun S, Cojocaru VD, Pandele AM, Croitoru SM, Miculescu F, Cotrut CM, Dan I, Cimpean A. Characterization and In vitro and In vivo Assessment of a Novel Cellulose Acetate-coated Mg-based Alloy for Orthopaedic Applications, Materials, 2017, 10 (7), 686 (2017) http://www.mdpi.com/1996-1944/10/7/686/htm
Voicu SI, Condruz RM, Mitran V, Cimpean A, Miculescu F, Andronescu C, Miculescu M, Thakur VK. Sericin Covalent Immobilization onto Cellulose Acetate Membrane for Potential Osseointegration Applications. ACS Sustainable Chem Eng, 4, 1765-1774 (2016).http://pubs.acs.org/doi/abs/10.1021/acssuschemeng.5b01756
Voicu SI, Muhulet A, Antoniac IV, Corobea MS. Cellulose derivatives based membranes for biomedical applications. Key Engineering Materials, 638, 27-30 (2015).
Neacsu P, Ion RN, Mitran V, Staras AI, Cimpean A. State of the art and recent patents on Mg-based biodegradable bone implants. Rec. Pat. Regen. Med., Vol. 4, Nr. 3, 168-188, DOI: 10.2174/2210296505666150205155811 (2015).
Communications to scientific reunions
Voicu SI, Pandele MA, Staras AI, Neacsu P, Cimpean A, Miculescu F, Iordache A, Thakur VK. Resveratrol covalent immobilization onto cellulose acetate membranes for improved osseointegration, 10th International Conference on Materials Science & Engineering Bramat 2017, 8-10 martie 2017, Brasov, Romania (oral presentation)
Voicu SI. Bioactive compounds covalent immobilization onto cellulose acetate membranes for biomedical applications, 7th International Conference “Biomaterials, Tissue Engineering & Medical Devices Biommedd 2016, 15-17 Septembrie 2016, Constanta, Romania (invited lecture)
Voicu SI, Muhulet A, Antoniac I. Cellulose derivatives based membranes for biomedical applications, 6th International Conference “Biomaterials, Tissue Engineering and Medical Devices” (BiomMedD 2014), 17-20 Septembrie 2014, Constanta, Romania, ISSN 2069-0193, pp.107 (oral presentation).
PhD thesis on project’s topic
Staras Adela: In vitro biological performance assessment of surface-modified biomaterials (2014-2017).