Purpose: Osteoporosis is a severe health problem with social and economic impacts on society. The standard treatment consists of the systemic administration of drugs such as bisphosphonates, with alendronate (ALN) being one of the most common. Nevertheless, complications of systemic administration occur with this drug. Therefore, it is necessary to develop new strategies, such as local administration. Methods: In this study, emulsion/dispersion scaffolds based on W/O emulsion of PCL and PF68 with ALN, containing hydroxyapatite (HA) nanoparticles as the dispersion phase were prepared using electrospinning. Scaffolds with different release kinetics were tested in vitro on the co-cultures of osteoblasts and osteoclast-like cells, isolated from adult osteoporotic and control rats. Cell viability, proliferation, ALP, TRAP and CA II activity were examined. A scaffold with a gradual release of ALN was tested in vivo in the bone defects of osteoporotic and control rats. Results: The release kinetics were dependent on the scaffold composition and the used system of the poloxamers. The ALN was released from the scaffolds for more than 22 days. The behavior of cells cultured in vitro on scaffolds with different release kinetics was comparable. The difference was evident between cell co-cultures isolated from osteoporotic and control animals. The PCL/HA scaffold show slow degradation in vivo and residual scaffold limited new bone formation inside the defects. Nevertheless, the released ALN supported bone formation in the areas surrounding the residual scaffold. Interestingly, a positive effect of systemic administration of ALN was not proved. Conclusion: The prepared scaffolds enabled tunable control release of ALN. The effect of ALN was proved in vitro and in in vivo study supported peri-implant bone formation.

Cadmium has no known physiological function in the body; however, its adverse effects are associated with cancer and many types of organ system damage. Although much has been shown about Cd toxicity, the underlying mechanisms of its responses to the organism remain unclear. In this study, the role of Tor1, a catalytic subunit of the target of rapamycin complex 2 (TORC2), in Cd-mediated effects on cell proliferation, the antioxidant system, morphology, and ionome balance was investigated in the eukaryotic model organism Schizosaccharomyces pombe. Surprisingly, spectrophotometric and biochemical analyses revealed that the growth rate conditions and antioxidant defense mechanisms are considerably better in cells lacking the Tor1 signaling. The malondialdehyde (MDA) content of Tor1-deficient cells upon Cd treatment represents approximately half of the wild-type content. The microscopic determination of the cell morphological parameters indicates the role for Tor1 in cell shape maintenance. The ion content, determined by inductively coupled plasma optical emission spectroscopy (ICP-OES), showed that the Cd uptake potency was markedly lower in Tor1-depleted compared to wild-type cells. Conclusively, we show that the cadmium-mediated cell impairments in the fission yeast significantly depend on the Tor1 signaling. Additionally, the data presented here suggest the yet-undefined role of Tor1 in the transport of ions.

Chronic wounds represent a significant socio-economic problem, and the improvement of their healing is therefore an essential issue. This paper describes the preparation and biological properties of a novel functionalized nanofiber wound dressing consisting of a polycaprolactone nanofiber carrier modified by a drug delivery system, based on the lipid particles formed by 1-tetradecanol and encapsulated gentamicin and tocopherol acetate. The cytotoxicity of extracts was tested using a metabolic activity assay, and the antibacterial properties of the extracts were tested in vitro on the bacterial strains Staphylococcus aureus and Pseudomonas aeruginosa. The effect of the wound dressing on chronic wound healing was subsequently tested using a mouse model. Fourteen days after surgery, the groups treated by the examined wound cover showed a lower granulation, reepithelization, and inflammation score compared to both the uninfected groups, a lower dermis organization compared to the control, a higher scar thickness compared to the other groups, and a higher thickness of hypodermis and bacteria score compared to both the uninfected groups. This work demonstrates the basic parameters of the safety (biocompatibility) and performance (effect on healing) of the dressing as a medical device and indicates the feasibility of the concept of its preparation in outpatient conditions using a suitable functionalization device.

This study investigates the impact of hydroxyapatite (HA) nanoparticles (NPs) on the cellular responses of poly(L-lactide-co-ε-caprolactone) (PLCL) scaffolds in bone tissue engineering applications. Three types of PLCL scaffolds were fabricated, varying in HANPs content. Saos-2 osteoblast-like cells (OBs) and THP-1-derived osteoclast-like cells (OCs) were co-cultured on the scaffolds, and cell proliferation was assessed using the MTS assay. The amount of double-stranded DNA (dsDNA) was quantified to evaluate cell proliferation. Expression levels of OBs and OCs markers were analyzed via quantitative polymerase chain reaction (qPCR) and the production of Collagen type I was visualized using confocal microscopy. Additionally, enzymatic activity of alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP or ACP5) was measured to assess OB and OC function, respectively. Interestingly, despite the scaffold’s structured character supporting the growth of the Saos-2 OBs and THP-1-derived OCs coculture, the incorporation of HANPs did not significantly enhance cellular responses compared to scaffolds without HANPs, except for collagen type I production. These findings suggest the need for further investigation into the potential benefits of HANPs in bone tissue engineering applications. Nevertheless, our study contributes valuable insights into optimizing biomaterial design for bone tissue regeneration, with implications for drug screening and material testing protocols.

Background: Axial spondyloarthritis (axSpA) is characterized by coexisting bone loss and pathological new bone formation. Although alterations in circulating markers and osteoclastogenesis from peripheral blood monocytes (PBM) are documented in radiographic axSpA (r-axSpA), their status in non-radiographic axSpA (nr-axSpA) and association with bone loss remain unresolved. In this study, we evaluated serum markers of bone metabolism and inflammation, PBM osteoclastogenic capacity, and their association with bone mineral density across both axSpA phenotypes. Methods: In 81 axSpA patients, clinical characteristics and DEXA-based BMD were recorded. Serum TSH, PTH, 25(OH)D3, bCTX, PINP, osteocalcin, bALP, RANKL, OPG, CTSK, CRP, IL-6 and IL-17 were measured. PBM from a patient subset (N=26) were used for in vitro osteoclastogenesis assays. Results: In a multivariable model, femoral neck Z-scores were strongly negatively associated with serum OPG/RANKL ratio in males (48% OPG/RANKL increase per one-unit Z-score decrease, p< 0.01). Additionally, each one-unit decrease in femoral neck Z-score was associated with increased odds of r-axSpA (OR 1.96, p< 0.05), independently of OPG/RANKL. Though patients with r-axSpA had lower femoral neck Z-scores than nr-axSpA (mean −0.50 vs. 0.03, p< 0.05), their in vitro osteoclastogenesis did not differ significantly (median 21 vs. 40, p=NS). Instead, osteoclastogenesis associated with BMD, being lower in patients with reduced femoral neck BMD compared to normal BMD (mean 22 vs. 51, p< 0.05). Conclusions: This study highlights the femoral neck as a region of interest for studying bone loss in nr-axSpA and r-axSpA and supports a link between systemic bone loss, circulating OPG/RANKL levels, and precursor osteoclastogenic potential in axSpA.