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The intricate interaction of the scaffold's architecture/geometry and with the cells is essential for tissue engineering and regenerative medicine. Cells sense their surrounding dynamic cues such as biophysical, biomechanical, and biochemical, and respond to them differently. Numerous studies have recently explored and reported the effect of contact guidance by culturing various types of cells on different types of micropatterned substrates such as microgrooves, geometric (square and triangle) micropattern, microstrips, micropatterned nanofibers. Amongst all of these micropatterned polymeric substrates; electrospun nanofibers have been regarded as a suitable substrate as it mimics the native ECM architectures. Therefore, in the present study; stencil-assisted electrospun Grid-lined micropatterned PCL-Collagen nanofibers (GLMPCnfs) were fabricated and its influence on the alignment and differentiation of pre-osteoblast cells (MC3T3-E1) was investigated. The randomly orientated Non-patterned PCL-Collagen nanofibers (NPPCnfs) were used as control. The patterns were characterized for their geometrical features such as area and thickness of deposition using surface profiler and scanning electron microscopy. A 61 % decrease in the overall area of GLMPCnfs as compared to the stencil area demonstrated the potential of electrofocusing phenomenon in the process of patterning electrospun nanofibers into various micron-scale structures. The MC3T3-E1 cells were confined and aligned in the direction of GLMPCnfs as confirmed by a high cellular aspect ratio (AR = 5.41), lower cellular shape index (CSI = 0.243), and cytoskeletal reorganization assessed through the F-actin filament immunocytochemistry (ICC) imaging. The aligned cells along the GLMPCnfs exhibited elevated alkaline phosphatase activity and enhanced mineralization. Furthermore, the gene expression profiling revealed upregulation of key osteogenic markers, such as ALP, OCN, OPN, COL1A1, and osteocyte markers DMP1, and SOST. Consequently, the research highlights the impact of GLMPCnfs on the cellular behaviour that results to the pre-osteoblast differentiation and the potential for stimulant-free early osteogenesis. These results offer an extensive understanding and mechanistic insight into how scaffold topography can be modified to influence cellular responses for effective bone regeneration strategies., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Rajesh Vasita reports financial support was provided by Nanomission, DST, and Govt. of India project grant [No. SR/NM/NB-1079/2017(G)] and Science and Engineering Research Board, Department of Science and Technology, Govt. of India [TTR/2021/00120] that includes: funding grants. Rajesh vasita has patent: Prasoon Kumar, Rajesh Vasita, Bindiya Dhimmar, Kaushik Choudhary. Process of Fabrication of Polymer-based 3D multiscale structure for micro/nanosystem. Patent No. 377541, date of filing: 14/07/2019, Date of grant: 22/09/2021. Complete Patent filed on 30/04/2022. Granting country: India. pending to Rajesh vasita. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Despite of being in different microenvironment, breast cancer cells influence the bone cells and persuade cancer metastasis from breast to bone. Multiple co-culture approaches have been explored to study paracrine signaling between these cells and to study the progression of cancer. However, lack of native tissue microenvironment remains a major bottleneck in existing co-culture technologies. Therefore, in the present study, a tumorigenic and an osteogenic microenvironment have been sutured together to create a multi-cellular environment and has been appraised to study cancer progression in bone tissue. The PCL-polystyrene and PCL-collagen fibrous scaffolds were characterized for tumorigenic and osteogenic potential induction on MDA-MB-231 and MC3T3-E1 cells respectively. Diffusion ability of crystal violet, glucose, and bovine serum albumin across the membrane were used to access the potential paracrine interaction facilitated by device. While in co-cultured condition, MDA-MB-231 cells showed EMT phenotype along with secretion of TNFα and PTHrP which lower down the expression of osteogenic markers including alkaline phosphatase, RUNX2, Osteocalcin and Osteoprotegerin. The cancer progression in bone microenvironment demonstrated the role and necessity of creating multiple tissue microenvironment and its contribution in studying multicellular disease progression and therapeutics., Competing Interests: Declaration of competing interest All the Authors show no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Scaffolds for bone tissue engineering require considerable mechanical strength to repair damaged bone defects. In this study, we designed and developed mechanically competent composite shape memory triphasic bone scaffolds using fused filament fabrication (FFF) three dimensional (3D) printing. Wollastonite particles (WP) were incorporated into the poly lactic acid (PLA)/polycaprolactone (PCL) matrix as a reinforcing agent (up to 40 wt%) to harness osteoconductive and load-bearing properties from the 3D printed scaffolds. PCL as a minor phase (20 wt%) was added to enhance the toughening effect and induce the shape memory effect in the triphasic composite scaffolds. The 3D-printed composite scaffolds were studied for morphological, thermal, and mechanical properties, in vitro degradation, biocompatibility, and shape memory behaviour. The composite scaffold had interconnected pores of 550 μm, porosity of more than 50%, and appreciable compressive strength (∼50 MPa), which was over 90% greater than that of the pristine PLA scaffolds. The flexural strength was improved by 140% for 40 wt% of WP loading. The inclusion of WP did not affect the thermal property of the scaffolds; however, the inclusion of PCL reduced the thermal stability. An accelerated in vitro degradation was observed for WP incorporated composite scaffolds compared to pristine PLA scaffolds. The inclusion of WP improved the hydrophilic property of the scaffolds, and the result was significant for 40 wt% WP incorporated composite scaffolds having a water contact angle of 49.61°. The triphasic scaffold exhibited excellent shape recovery properties with a shape recovery ratio of ∼84%. These scaffolds were studied for their protein adsorption, cell proliferation, and bone mineralization potential. The incorporation of WP reduced the protein adsorption capacity of the composite scaffolds. The scaffold did not leach any toxic substance and demonstrated good cell viability, indicating its biocompatibility and growth-promoting behavior. The osteogenic potential of the WP incorporated scaffolds was observed in MC3T3-E1 cells, revealing early mineralization in pre-osteoblast cells cultured in different WP incorporated composite scaffolds. These results suggest that 3D-printed WP reinforced PLA/PCL composite bioactive scaffolds are promising for load bearing bone defect repair.

Luliconazole is a broad-spectrum topical antifungal agent that acts by altering the synthesis of fungi cell membranes. Literature suggests that the recurrence of fungal infection can be avoided by altering the pH of the site of infection. Studies have also suggested that fungi thrive by altering skin pH to be slightly acidic, i.e., pH 3-5. The current study is aimed to design, develop, characterize, and evaluate an alkaline pH-based antifungal spray solution for antifungal effects. Luliconazole was used as an antifungal agent and an alkaline spray was formulated for topical application by using Eudragit RS 100, propylene glycol (PG), water, sodium bicarbonate, and ethanol via solubilization method. Herein, sodium bicarbonate was used as an alkalizing agent. Based on DSC, FTIR, PXRD, scanning electron microscopy (SEM), and rheological analysis outcomes, the drug (luliconazole) and polymer were found to be compatible. F-14 formulation containing 22% Eudragit RS 100 (ERS), 1.5% PG, and 0.25% sodium bicarbonate was optimized by adopting the quality by design approach by using design of experiment software. The viscosity, pH, drying time, volume of solution post spraying, and spray angle were, 14.99 ± 0.21 cp, 8 pH, 60 s, 0.25 mL ± 0.05 mL, and 80 ± 2, respectively. In vitro drug diffusion studies and in vitro antifungal trials against Candida albicans revealed 98.0 ± 0.2% drug diffusion with a zone of inhibition of 9 ± 0.12 mm. The findings of the optimized luliconazole topical film-forming solution were satisfactory, it was compatible with human skin, and depicted sustained drug release that suggests promising applicability in facilitated topical antifungal treatments.

Physiological inflammation has been shown to promote bone regeneration; however, prolonged inflammation impedes the osteogenesis and bone repair process. To overcome the latter we aimed to develop a dual drug delivering nanofibrous scaffold to promote osteogenic differentiation of mesenchymal stromal cells (MSCs) and modulate the pro-inflammatory response of macrophages. The polycaprolactone (PCL)-collagen nanofibrous delivery system incorporating dexamethasone and simvastatin was fabricated by electrospinning process. The morphological analysis and mRNA, as well as protein expression of proinflammatory and anti-inflammatory cytokines in human monocytes (U937 cells), demonstrated the immunocompatibility effect of dual drug-releasing nanofibrous scaffolds. Nitric oxide estimation also demonstrated the anti-inflammatory effect of dual drug releasing scaffolds. The scaffolds demonstrated the osteogenic differentiation of adipose-derived MSCs by enhancing the alkaline phosphatase (ALP) activity and mineral deposition after 17 days of cell culture. The increased expression of Runt-related transcription factor-2 (RUNX-2) and osteocalcin at mRNA and protein levels supported the osteogenic potential of dual drug-loaded fibrous scaffolds. Hence, the results indicate that our fabricated nanofibrous scaffolds exhibit immunomodulatory properties and could be employed for bone regeneration applications after further in-vivo validation., Competing Interests: Authors declare no conflict of interest for manuscript titled “Polycaprolactone-collagen nanofibers loaded with dexamethasone and simvastatin as osteoinductive and immunocompatible scaffold for bone regeneration applications”, (© 2022 The Authors.)