Abstract
Additive manufacturing has facilitated fabrication of complex and patient-specific metallic meta-biomaterials that offer an unprecedented collection of mechanical, mass transport, and biological properties as well as a fully interconnected porous structure. However, applying meta-biomaterials for addressing unmet clinical needs in orthopedic surgery requires additional surface functionalities that should be induced through tailor-made coatings. Here, we developed multi-functional layer-by-layer coatings to simultaneously prevent implant-associated infections and stimulate bone tissue regeneration. We applied multiple layers of gelatin- and chitosan-based coatings containing either bone morphogenetic protein (BMP)-2 or vancomycin on the surface of selective laser melted porous structures made from commercial pure Titanium (CP Ti) and designed using a triply periodic minimal surface (i.e., sheet gyroid). The additive manufacturing process resulted in a porous structure and met the the design values comparatively. X-ray photoelectron spectroscopy spectra confirmed the presence and composition of the coating layers. The release profiles showed a continued release of both vancomycin and BMP-2 for 2–3 weeks. Furthermore, the developed meta-biomaterials exhibited a very strong antibacterial behavior with up to 8 orders of magnitude reduction in both planktonic and implant-adherent bacteria and no signs of biofilm formation. The osteogenic differentiation of mesenchymal stem cells was enhanced, as shown by two-fold increase in the alkaline phosphatase activity and up to four-fold increase in the mineralization of all experimental groups containing BMP-2. Eight-week subcutaneous implantation in vivo showed no signs of a foreign body response, while connective tissue ingrowth was promoted by the layer-by-layer coating. These results unequivocally confirm the superior multi-functional performance of the developed biomaterials.
Highlights
Meta-biomaterials are rationally designed and topologically complex porous structures with rare or unprecedented combinations of mechanical, physical, and biological properties [1,2,3]
The AM process resulted in porous structures whose morphological characteristics closely matched those of the CAD design
The results of the current study show how layer-by-layer coating can offer such a paradigm to complete the landscape of performance-adjustability in the design of AM porous metallic biomaterials
Summary
Meta-biomaterials are rationally designed and topologically complex porous structures with rare or unprecedented combinations of mechanical, physical, and biological properties [1,2,3]. The rate of biodegradation of metabiomaterials is known to be adjustable by topological design [30], because the exposed surface area and the transport of fluid and biodegradation products are highly topology-dependent. All these favorable properties, in conjunction with a fully-interconnected porous structure, are highly beneficial for enhancing the regenerative performance of bone substitutes and for improving the osseointegration of orthopedic implants, as clearly demonstrated in multiple in vivo experiments [31,32,33]
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