Additively Manufactured Macroporous Titanium with Silver-Releasing Micro-/Nanoporous Surface for Multipurpose Infection Control and Bone Repair – A Proof of Concept

Abstract

Restoring large-scale bone defects, where osteogenesis is slow while infections lurk, with biomaterials represents a formidable challenge in orthopedic clinics. Here, we propose a scaffold-based multipurpose anti-infection and bone repairing strategy to meet such restorative needs. To do this, personalized multifunctional titanium meshes were produced through an advanced additive manufacturing process and dual "TiO-poly(dopamine)/Ag (nano)" post modifications, yielding macroporous constructs with micro-/nanoporous walls and nanosilver bullets immobilized/embedded therein. Ultrahigh loading capacity and durable release of Ag were accomplished. The scaffolds were active against planktonic/adherent bacteria (Gram-negative and positive) for up to 12 weeks. Additionally, they not only defended themselves from biofilm colonization but also helped destroy existing biofilms, especially in combination with antibiotics. Further, the osteoblasts/bacteria coculture study displayed that the engineered surfaces aided MG-63 cells to combat bacterial invasion. Meanwhile, the scaffolds elicited generally acceptable biocompatibility (cell adhesion, proliferation, and viability) and hastened osteoblast differentiation and maturation (alkaline phosphatase production, matrix secretion, and calcification), by synergy of micro-/nanoscale topological cues and bioactive catecholamine chemistry. Although done ex vivo, these studies reveal that our three-in-one strategy (infection prophylaxis, infection fighting, and bone repair) has great potential to simultaneously prevent/combat infections and bridge defected bone. This work provides new thoughts to the use of enabling technologies to design biomaterials that resolve unmet clinical needs.

Polydopamine-assisted functionalization of heparin and vancomycin onto microarc-oxidized 3D printed porous Ti6Al4V for improved hemocompatibility, osteogenic and anti-infection potencies

“…Both micro-/nanoporous topography of MAO and the functional groups of PDA and heparin are previously shown to direct protein adsorption and cell adhesion and further promote osteoblast spreading, migration and proliferation [5]. Further, the release of Ca 2+ from the scaffold into the extracellular environment is beneficial to promoting the osteogenic differentiation of hMSCs on the scaffold [47].…”

“…Generally, these coatings can be sorted into two types: inorganic and organic antimicrobial coatings. As a most widely used inorganic antimicrobial agent, nanosilver has been loaded into TiO 2 micronanopores [5] and nanotubes [4] and dispersed into graphene oxide coatings [50], which endows bioceramic or biometallic scaffolds with strong bacteria elimination potencies. Nanosilver-based implant coatings possess advantages such as excellent antibacterial efficiency, good stability, and low occurrence of drug resistance.…”

“…The scaffold-bacterium constructs were rinsed thrice and fixed in 95% ethyl alcohol and the biomass of adhered biofilms was quantified by the crystal violet staining, as described previously [5]. In short, each scaffold was added with 1% (w/v) crystal violet at room temperature and kept for 15 min.…”

“…2a presents the XPS survey spectra of surface elements for scaffold samples at respective modification stages. On the TS, the major surface composition was identified as Ti, O and C, wherein the latter two were likely a result of oxidization and environmental contamination [5]. For TS-M, weakened substrate signals were witnessed while new peaks of Ca, P, and Na emerged, as thick TiO 2 /apatite layers (4-5 μm) were readily produced via MAO treatment on scaffold surface [10].…”

“…With respect to porous titanium, enhancement of bone ingrowth efficiency and biointegration performances and the prevention/fighting of biomedical device-associated infections (BAI) are two major keys to overcome implant looseness and ultimately establish stable functional implant/bone interfaces [4]. BAI is a prominent cause of clinical implant failure whose occurrences range averagely between 2% and 5% and can reach up to 30% in the cases of open fractures [5]. The handle of an infected implant is notoriously excruciating, expensive, and time consuming [6].…”