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Treating bone infections with common antibiotics is challenging, since pathogens like Staphylococcus aureus can reside inside macrophages. To target these intracellular bacteria, we have proposed nanoparticles (NPs) as drug carriers. This study aims to investigate the efficacy of hydroxyapatite and gelatin NPs, selected in view of their bone mimicry and potential for targeted delivery, as carriers for the antibacterial agents zinc and vancomycin. Therefore, two distinct NPs are fabricated: zinc-doped hydroxyapatite (ZnHA) and vancomycin-loaded gelatin (VGel) NPs. The NPs are characterized based on morphology, size, chemical composition, cellular internalization, and intracellular bactericidal efficacy. Specifically, the intracellular bactericidal efficacy is tested using a validated coculture model of human THP-1 derived macrophages and phagocytosed S. aureus bacteria. Scanning electron microscopy (SEM) and Fourier transform-infrared spectroscopy (FTIR) results show that the spherical NPs are synthesized successfully. These NPs are internalized by THP-1 cells and show >75% colocalization with lysosomes without compromising the viability of the THP-1 cells. Both ZnHA and VGel NPs substantially reduce the intracellular survival of S. aureus compared to the direct addition of dissolved zinc and vancomycin. Concluding, our NPs are highly effective drug delivery vehicles to kill intracellular S. aureus , which stress the potential of these NPs for future clinical translation. [ABSTRACT FROM AUTHOR]

Osteons, the main organizational components of human compact bone, are cylindrical structures composed of layers of mineralized collagen fibrils, called lamellae. These lamellae have different orientations, different degrees of organization, and different degrees of mineralization where the intrafibrillar and extrafibrillar minerals are intergrown into one continuous network of oriented crystals. While cellular activity is clearly the source of the organic matrix, recent in vitro studies call into question whether the cells are also involved in matrix mineralization and suggest that this process could be simply driven by the interactions of the mineral with extracellular matrix. Through the remineralization of demineralized bone matrix, the complete multiscale reconstruction of the 3D structure and composition of the osteon without cellular involvement are demonstrated. Then, this cell‐free in vitro system is explored as a realistic, functional model for the in situ investigation of matrix‐controlled mineralization processes. Combined Raman and electron microscopy indicate that glycosaminoglycans (GAGs) play a more prominent role than generally assumed in the matrix–mineral interactions. The experiments also show that the organization of the collagen is in part a result of its interaction with the developing mineral. [ABSTRACT FROM AUTHOR]

Polyisocyanopeptide (PIC) hydrogels are proposed as promising wound dressings. These gels are thermo-sensitive, allow application as a cold liquid, and rely on gelation through body heat. It is supposed that the gel can be easily removed by reversing the gelation and washing it away with a cold irrigation solution. The impact on wound healing of the regular application and removal of PIC dressings is compared to a single application of PIC and the clinically used Tegaderm™ in murine splinted full-thickness wounds for up to 14 days. SPECT/CT analysis of 111In-labelled PIC gels showed that, on average, 58% of the PIC gel could be washed out of the wounds with the employed method, which is, however, heavily influenced by personal technique. Evaluation with photography and (immuno-)histology showed that wounds in which PIC dressings were regularly removed and replaced were smaller at 14 days post-injury but performed on par with the control treatment. Moreover, the encapsulation of PIC in wound tissue was less severe and occurred less often when PIC was regularly refreshed. In addition, no morphological damage related to the removal procedure was observed. Thus, PIC gels are atraumatic and perform similarly to currently employed wound dressing materials, offering possible future benefits for both clinicians and patients. [ABSTRACT FROM AUTHOR]

Graphene-based materials (GBMs) hold strong promise to restore the spinal cord microenvironment and promote functional recovery after spinal cord injury (SCI). Nanocomposites consisting of reduced graphene oxide (rGO) and adipose tissue-derived extracellular matrix (adECM) are known to promote neuronal growth in vitro and to evoke a biocompatible response in vivo when implanted on top of the intact spinal cord. In this study, pristine adECM and adECM-rGO nanocomposites are implanted directly after hemisection SCI in rats. Scaffolds composed of collagen type I (COL) are applied as negative control, based on evidence that COL triggers integrin-mediated astrogliosis. However, COL scaffolds induce orthotopic bone formation in the lesion site and are therefore excluded from further analyses. Compared to pristine adECM, adECM-rGO nanocomposites completely restore spinal cord integrity. Macrophage-mediated uptake and clearance of rGO remnants is observed as early as 3 weeks post-implantation. Nanocomposites show an elevated presence of βIII-tubulin-positive axons in the host-material interface after 8 weeks, yet scaffold penetration by axons is only occasionally observed. This is partially due to an increased expression of chondroitin sulfate proteoglycans (CSPGs) within the nanocomposites, even though reactive astrogliosis is unaltered. Despite the complete restoration of tissue architecture, adECM-rGO treatment does not significantly improve functional recovery., (© 2024 The Author(s). Advanced Healthcare Materials published by Wiley‐VCH GmbH.)

Objectives: This study was aimed to comparatively evaluate new bone formation into the pores of a flexible titanium fiber mesh (TFM) applied on the surface of implant., Methods: Twenty-eight custom made cylindrical titanium implants (4 ×10 mm) with and without a layer of two different types of TFM (fiber diameter of 22 µm and 50 µm, volumetric porosity ~70%) were manufactured and installed bilaterally in the femoral condyles of 14 rabbits. The elastic modulus for these two TFM types was ~20 GPa and ~5 GPa respectively, whereas the solid titanium was ~110 GPa. The implants (Control, TFM-22, TFM-50) were retrieved after 14 weeks of healing and prepared for histological assessment. The percentage of the bone area (BA%), the bone-to-implant contact (BIC%) and amount were determined., Results: Newly formed bone into mesh porosity was observed for all three types of implants. Histomorphometric analyses revealed significantly higher (~2.5 fold) BA% values for TFM-22 implants (30.9 ± 9.5%) compared to Control implants (12.7 ± 6.0%), whereas BA% for TMF-50 did not significantly differ compared with Control implants. Furthermore, both TFM-22 and TFM-50 implants showed significantly higher BIC% values (64.9 ± 14.0%, ~2.5 fold; 47.1 ± 14.1%, ~2 fold) compared to Control (23.6 ± 17.4%). Finally, TFM-22 implants showed more and thicker trabeculae in the peri-implant region., Significance: This in vivo study demonstrated that implants with a flexible coating of TFM improve bone formation within the inter-fiber space and the peri-implant region., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)