Biomaterials against Bone Infection

Abstract

Chronic bone infection is considered as one of the most problematic biofilm-related infections. Its recurrent and resistant nature, high morbidity, prolonged hospitalization, and costly medical care expenses have driven the efforts of the scientific community to develop new therapies to improve the standards used today. There is great debate on the management of this kind of infection in order to establish consistent and agreed guidelines in national health systems. The scientific research is oriented toward the design of anti-infective biomaterials both for prevention and cure. The properties of these materials must be adapted to achieve better anti-infective performance and good compatibility, which allow a good integration of the implant with the surrounding tissue. The objective of this review is to study in-depth the antibacterial biomaterials and the strategies underlying them. In this sense, this manuscript focuses on antimicrobial coatings, including the new technological advances on surface modification; scaffolding design including multifunctional scaffolds with both antimicrobial and bone regeneration properties; and nanocarriers based on mesoporous silica nanoparticles with advanced properties (targeting and stimuli-response capabilities).

Keywords: bone infections; mesoporous silica nanoparticles; nanocarriers; scaffolds.

Figure 1

Main strategies to combat bone infection, object of study in this review manuscript. In this sense, this manuscript addresses antimicrobial coating including the new technological advances on surface modification; scaffolding design including multifunctional scaffolds with both antimicrobial and bone regeneration properties; and nanocarriers with advanced properties (targeting and stimuli-response capabilities).

Figure 2

Results derived from the antimicrobial properties of Ti6Al4V implants by means of a nanopatterning coating enhanced by MDGLAD.^[68] Top: SEM micrographs showed the full coating onto Ti-based implant by well-defined nanocolumns. Down: Confocal microscopy studies compared the surface of naked titanium, before and after coating, upon incubation with S. aureus bacteria. The reusable samples show that when the titanium implant is bare the biofilm is formed, while the nanocolumns coating inhibits the formation of the biofilm.

Figure 3

Schematic representation of 3D multifunctional scaffolds development by Rapid Prototyping technique.^[111,114] A photography of a 3D-bioplotter envisiontec device is shown in the upper image. On the right, SEM micrographs display the hierarchical macro-mesoporosity of 3D scaffolds derived of this technique. Confocal microscope study showing de antimicrobial effect of 3D scaffolds containing three different antibiotics (levofloxacin, vancomycin, and rifampicin) distributed in different compartments of the 3D scaffold is shown on the bottom.

Figure 4

Schematic representation of the MSNs versatility and their functionalization properties. Left: TEM micrographs showed different MSN-based NPs with different size, mesoporous arrangement, and core@shell type. Right: Depiction of the high MSNs versatility with different capabilities (targeting, drug delivery, stimuli-response, gene therapy, and diagnostic imaging).

Figure 5

Schematic representation of MSNs with targeting capability to both bacteria and biofilm. Because of the negative charges in the surface of the bacteria wall, one of the strategies to target bacteria is to functionalize the surface with positive charges. In this sense, several small molecules and biomacromolecules have been used: amines, polycationic dendrimers, and cationic polyaminoacid (among others). On the other hand, the biofilm is formed by a protective external layer of mucopolysaccharide, which has high affinity properties. In this case, this glycoconjugate has been used successfully as targeting agent.

Figure 6

Confocal microscopy images of (left) bacteria-targeting capability of MSN-G3 materials and (right) biofilm-targeting capability of MSN-ConA, respectively. The external functionalization with a polycationic dendrimer (G3) favors the internalization ofthese modified nanosystems (MSN-G3) within the E. coli bacteria. The left image shows the bacterial wall in red and MSN-G3 nanosystem in green.^[177] In the case of the external functionalization with the lectin (ConA), such modification enhances the internalization of the MSN-ConA nanosystem into the biofilm, even penetrating its innermost parts. The right image shows the biofilm composed by living bacteria in green and the biofilm matrix in blue, in this case the NPs are stained in red.^[174]

Figure 7

Schematic representation of the antimicrobial efficacy of (top) levofloxacin-loaded MSN-G3 and (down) levofloxacin-containing MSN-ConA. Both cases reveal that the targeting effect enhances significantly the antimicrobial effect of loaded antibiotic. These results are derived from refs. [177] and [174], respectively.