Additive Manufacturing of Mg-based Porous Tissue Scaffolds

Regeneration of the bone tissue is very limited when it is severely affected by traumatic injuries or age-related diseases. Today, synthetic grafting is the widely employed method to aid the healing of the affected tissues. Presently employed materials in synthetic grafting such as stainless steels, titanium, and cobalt–chromium-based alloys possess mechanical properties dissimilar to human bone, do not degrade in body fluid, and induce toxicity to the human body. The so-called stress shielding phenomenon associated with the mismatch of the mechanical properties between the bone and implant material can cause loosening of the implant and premature failure. In the usual practice, these implants are removed by secondary surgical operations after the healing is complete, which increases morbidity to the patient and cost on the healthcare institutions. Even in the case that the implant is permanently fixed in the body and no additional surgery is required, bone regeneration may not be complete. Thus, biodegradability of the implant materials has been considered a key function to mitigate the abovementioned shortcomings associated with synthetic grafting. Biodegradable implants are expected to withstand the anatomic loads during the healing period and then degrade completely without leaving any debris in the affected tissue. Among the available biodegradable materials, magnesium (Mg) possesses favorable mechanical and biological properties, and its degradation rate can be adjusted with the healing rate of the tissue in several ways such as by alloying with other metals, porous implant design, and surface modification techniques. The attachment, proliferation, and differentiation of new cells, as well as the vascularization on the grafted Mg can be promoted by careful design of the implants that possess a porous structure with a high surface area. A large implant surface lands itself for cell attachment and high porosity allows diffusion of nutrition and oxygen to the cells, excretion of the metabolic wastes from the cells, and the formation of blood vessels. Porous implants, so-called scaffolds, can be designed according to the patient-specific anatomic data in the form of three-dimensional (3D) architecture through Computer-Aided Design (CAD) models, and then materialized by advanced manufacturing technologies with high dimensional accuracy. Despite the recent research efforts to develop biodegradable scaffolds using a number of manufacturing methods, there are no clinical applications reported for such scaffolds thus far. This project proposes to develop a facile process for manufacturing Mg-based porous biodegradable scaffolds with favorable mechanical and biological properties through careful material preparation, model design, and materialization. It is targeted to produce favorable scaffolds with high dimensional accuracy and high-reproducibility to aid the healing of injured/diseased tissues that will promote the clinical applications of biodegradable Mg. Upon the successful completion of the project, the developed process will allow on-site manufacturing of customized biodegradable scaffolds using time- and cost-effective manufacturing methods. The project proposes a comprehensive research that includes feedstock material preparation & characterization, advanced manufacturing of scaffolds by additive manufacturing (AM) or 3D printing (3DP), post-processing according to the clinical needs, in vitro biodegradation analysis, cell culture tests for biocompatibility, implanting the fabricated scaffolds in sawbones and cadavers, and mechanical testing. Intensive interdisciplinary efforts are needed for the successful completion of such comprehensive work. Therefore, the project will be carried out in collaboration amongst Hamad Bin Khalifa University (HBKU), Sidra Medicine, and Hamad Medical Corporation (HMC) in Qatar, and Middle East Technical University (METU), Turkey. Material preparation, characterization, and manufacturing tasks will be carried out in HBKU. HMC will apply post-processing to the printed scaffolds. Clinical needs will be defined by HMC and Sidra Medicine doctors for the manufacturing of ideal tissue scaffolds for adult patients and pediatric patients, respectively. Microstructural investigations, in vitro studies in simulated body fluid (SBF) for biodegradation, and cell culture tests for biocompatibility of the scaffolds will be carried out at METU. Mechanical tests on the developed scaffolds will be carried out at HBKU labs. Further, the scaffolds will be implanted in sawbones and cadavers by HMC and Sidra Medicine doctors and mechanically tested in HBKU labs. Finally, protocols will be developed for the whole preparation process of the scaffolds by HBKU, Sidra Medicine, and HMC. This collaborative work is anticipated to promote the clinical applications of Mg scaffolds through the successful development of a facile process that will enable the manufacturing of Mg scaffolds according to the patient-specific anatomic data at high dimensional accuracy and reproducibility.

Hamad Bin Khalifa University (HBKU)