Anne Eriksson Agger

Poloxamer 407, also known as Pluronic® F127, is gaining interest in the cosmetic, biomedical and pharmaceutical fields for its biocompatibility, safety and thermo-sensitive properties. Ensuring sterility is critical in clinical applications, and sterilization is often preferred over aseptic processing. However, sterilization can impact the functional properties of the hydrogel. In this study, we investigate the effects of steam heat (121°C, 20 min), dry heat (160°C, 1 h), gamma irradiation (25 kGy) and electron beam (e-beam) irradiation (15 and 25 kGy) on a 30% w/v Poloxamer 407 hydrogel formulation. Our analysis encompasses gelling properties, pH, Fourier-transform infrared spectroscopy, gel permeation chromatography, small-angle X-ray scattering, rheology, swelling, degradation by-products and lactate dehydrogenase release of the sterilized hydrogels, comparing them to a non-sterile counterpart. We demonstrated that heat sterilization alters the hydrogel’s gelling and structural properties due to water evaporation and oxidation under harsh temperature conditions, especially when applying the dry heat method. Gamma irradiation proved unsuitable, resulting in an acidic and cytotoxic hydrogel due to oxidative degradation. In contrast, e-beam irradiation preserves the hydrogel’s elasticity, gelling and structural properties while enhancing mechanical resilience and moderating swelling. Therefore, e-beam irradiation within the 15–25 kGy range appears to be the most suitable method for sterilizing a 30% w/v Poloxamer 407 hydrogel.

To combat the ever-growing increase of multidrug-resistant (MDR) bacteria, action must be taken in the development of antibiotic formulations. Colistin, an effective antibiotic, was found to be nephrotoxic and neurotoxic, consequently leading to a ban on its use in the 1980s. A decade later, colistin use was revived and nowadays used as a last-resort treatment against Gram-negative bacterial infections, although highly regulated. If cytotoxicity issues can be resolved, colistin could be an effective option to combat MDR bacteria. Herein, we investigate the complexation of colistin with poly(ethylene oxide)-b-poly(methacrylic acid) (PEO-b-PMAA) block copolymers to form complex coacervate core micelles (C3Ms) to ultimately improve colistin use in therapeutics while maintaining its effectiveness. We show that well-defined and stable micelles can be formed in which the cationic colistin and anionic PMAA form the core while PEO forms a protecting shell. The resulting C3Ms are in a kinetically arrested and stable state, yet they can be made reproducibly using an appropriate experimental protocol. By characterization through dynamic light scattering (DLS) and small-angle X-ray scattering (SAXS), we found that the best C3M formulation, based on long-term stability and complexation efficiency, is at charge-matching conditions. This nanoparticle formulation was compared to noncomplexed colistin on its antimicrobial properties, enzymatic degradation, serum protein binding, and cytotoxicity. The studies indicate that the antimicrobial properties and cytotoxicity of the colistin-C3Ms were maintained while protein binding was limited, and enzymatic degradation decreased after complexation. Since colistin-C3Ms were found to have an equal effectivity but with increased cargo protection, such nanoparticles are promising components for the antibiotic formulation toolbox.

Surface chemistry evaluation is crucial in assessing the efficacy of chemical decontamination products for titanium implants. This study aimed to investigate the effectiveness of chemical decontamination solutions in cleaning a contaminated dental implant surface and to evaluate the potential of combining Pluronic gel with hydrogen peroxide (NuBone^®Clean) by evaluating pellicle disruption and re-formation on implant surfaces. In addition, ensuring safety with in vitro and human testing protocols. X-ray Photoelectron Spectroscopy (XPS) was utilised for surface analysis. All the tested gels had some effect on the surface cleanness except for PrefGel^®. Among the tested chemical decontamination candidates, NuBone^®Clean demonstrated effectiveness in providing a cleaner titanium surface. Furthermore, none of the tested chemical agents exhibited cytotoxic effects, and the safety assessment showed no adverse events. The results of this study highlight the significance of conducting comprehensive evaluations, encompassing safety and efficacy, before introducing new chemical agents for dental treatments. The findings suggest that NuBone^®Clean shows potential as a chemical decontamination solution for implant surfaces. However, further investigation through randomised clinical trials is necessary. By adhering to rigorous testing protocols, the development of safe and efficient chemical decontamination strategies can be advanced, benefiting patients and promoting progress in implant dentistry.

Surface chemistry evaluation plays a crucial role in assessing the efficacy of chemical decontamination products for titanium implants. This study aimed to investigate the effectiveness of chemical decontamination solutions in cleaning a contaminated dental implant surface and to evaluate the potential of combining Pluronic gel with hydrogen peroxide (NuBone®Clean) by evaluating pellicle disruption and re-formation on implant surfaces. In addition, ensuring safety with in- vitro and human testing protocols. X-ray Photoelectron Spectroscopy (XPS) was utilized for surface analysis. All the tested gels had some effect on the surface cleanness except for PrefGel®. Among the tested chemical decontamination candidates, NuBone®Clean demonstrated effectiveness in providing a cleaner titanium surface. Furthermore, none of the tested chemical agents exhibited any cytotoxic effects, and the safety assessment showed no adverse events. The results of this study highlight the significance of conducting comprehensive evaluations, encompassing safety and efficacy, before introducing new chemical agents for dental treatments. The findings suggest that NuBone®Clean shows potential as a chemical decontamination solution for implant surfaces. However, further investigation through randomized clinical trials is necessary. By adhering to rigorous testing protocols, the development of safe and efficient chemical decontamination strategies can be advanced, benefiting patients and promoting progress in the field of implant dentistry.

Background: Irisin is expressed in human periodontal ligament (hPDL), and its administration enhances growth, migration and matrix deposition in hPDL cells cultured in monolayers in vitro.Objectives: To identify whether irisin affects the gene expression patterns directing the morphology, mechanical properties, extracellular matrix (ECM) formation, osteogenic activity and angiogenic potential in hPDL cell spheroids cultured in 3D.Materials and Methods: Spheroids of primary human hPDL cells were generated in a rotational 3D culture system and treated with or without irisin. The gene expression patterns were evaluated by Affymetrix microarrays. The morphology of the spheroids was characterized using histological staining. Mechanical properties were quantified by nanoindentation. The osteogenic and angiogenic potential of spheroids were assessed through immunofluorescence staining for collagen type I, periostin fibronectin and von Willebrand factor (vWF), and mRNA expression of osteogenic markers. The secretion of multiple myokines was evaluated using Luminex immunoassays.Results: Approximately 1000 genes were differentially expressed between control and irisin‐treated groups by Affymetrix. Several genes related to ECM organization were differentially expressed, and multiple deubiquitinating enzymes were upregulated in the irisin‐exposed samples analyzed. These represent cellular and molecular mechanisms indicative of a role for irisin in tissue remodeling. Irisin induced a rim‐like structure on the outer region of the hPDL spheroids, ECM‐related protein expression and the stiffness of the spheroids were enhanced by irisin. The expression of osteogenic and angiogenetic markers was increased by irisin.Conclusions: Irisin altered the morphology in primary hPDL cell‐derived spheroids, enhanced its ECM deposition, mechanical properties, differentiation and remodeling potential.