The aim of the study is to determine the effectiveness of stem cells in scaffolds in the treatment of bone deficits, in regard of bone regeneration, safety, rehabilitation and quality of life in humans. The systematic review was conducted in accordance with PRISMA 2020. A systematic search was conducted in three search engines and two registries lastly in 29-9-2022.for studies of the last 15 years. The risk of bias was assessed with RoB-2, ROBINS- I and NIH Quality of Before-After (Pre-Post) Studies with no Control group. The certainty of the results was assessed with the GRADE assessment tool. Due to heterogeneity, the results were reported in tables, graphs and narratively. The study protocol was published in PROSPERO with registration number CRD42022359049. Of the 10,091 studies retrieved, 14 were meeting the inclusion criteria, and were qualitatively analyzed. 138 patients were treated with mesenchymal stem cells in scaffolds, showing bone healing in all cases, and even with better results than the standard care. The adverse events were mild in most cases and in accordance with the surgery received. When assessed, there was a rehabilitation of the deficit and a gain in quality of life was detected. Although the heterogeneity between the studies and the small number of patients, the administration of mesenchymal stem cells in scaffolds seems safe and effective in the regeneration of bone defects. These results pave the way for the conduction of more clinical trials, with greater number of participants, with more standardized procedures. Graphical Abstract

In the present study, a customized device (Epi-ExPer) was designed and fabricated to facilitate an epithelial organ culture, allowing for controlled exposure to exogenous chemical stimuli and accommodating the evaluation of permeation of the tissue after treatment. The Epi-ExPer system was fabricated using a stereolithography (SLA)-based additive manufacturing (AM) method. Human and porcine oral epithelial mucosa tissues were inserted into the device and exposed to resinous monomers commonly released by dental restorative materials. The effect of these xenobiotics on the morphology, viability, permeability, and expression of relevant markers of the oral epithelium was evaluated. Tissue culture could be performed with the desired orientation of air-liquid interface (ALI) conditions, and exposure to xenobiotics was undertaken in a spatially guarded and reproducible manner. Among the selected monomers, HEMA and TEGDMA reduced tissue viability at high concentrations, while tissue permeability was increased by the latter. Xenobiotics affected the histological image by introducing the vacuolar degeneration of epithelial cells and increasing the expression of panCytokeratin (pCK). Epi-ExPer device offers a simple, precise, and reproducible study system to evaluate interactions of oral mucosa with external stimuli, providing a biocompatibility and permeability assessment tool aiming to an enhanced in vitro/ex vivo-to-in vivo extrapolation (IVIVE) that complies with European Union (EU) and Food and Durg Administration (FDI) policies.

Periodontitis is a chronic inflammatory disease that progressively destroys periodontal tissues and can lead to tooth loss, affecting more than one billion people worldwide. Here, we developed coaxial electrospun core-shell scaffolds designed for local periodontal therapy, comprising a polycaprolactone (PCL) core and a polyvinylpyrrolidone (PVP) shell. Nanohydroxyapatite and lignin-silver nanoparticles (Lig-Ag NPs) were incorporated in the core to support regenerative and antimicrobial functions, while ketoprofen was loaded in the shell for localized anti-inflammatory delivery. The coaxial architecture enabled spatial compartmentalization of bioactive components and produced membranes with ketoprofen encapsulation efficiencies of 79-89.5%. Drug release was burst-dominated and reached a plateau within 48 h, with the 0.75HADL formulation achieving 92% cumulative release within 24 h. This release behavior is attributed to the rapid dissolution of the hydrophilic PVP shell, enabling immediate drug availability at the target site. In vitro testing showed cytocompatibility toward human gingival fibroblasts and immunomodulatory activity in RAW 264.7 macrophages, including marked suppression of MCP-1 and MMP-9 expression. The Lig-Ag NP-functionalized membranes reduced Enterococcus faecalis counts by 2-3 log10 CFU/mL over 48 h and exerted a mycostatic effect against Candida albicans. Together, these results indicate a coordinated biological response, combining cytocompatibility, antimicrobial activity, and controlled immunomodulation. Overall, the 0.75HADL coaxial membrane provided the most favorable balance of physicochemical performance and biological activity, supporting its potential as a local multifunctional scaffold for periodontal applications.

Bone healing, remodeling, and pathology are strongly regulated by mechanical stimulation. However, conventional two-dimensional (2D) in vitro culture systems fail to reproduce the complex mechanical and biological microenvironment of human bone, limiting their translational relevance. In recent years, bone-on-chip (BoC) platforms, as part of the broader organ-on-chip (OoC) technology, have emerged as advanced microfluidic systems that enable the study of bone biology under dynamic and highly controlled conditions that more closely mimic in vivo physiology. This systematic review aimed to gather the available in vitro evidence on mechanically stimulated BoC models, with a particular focus on osteogenic differentiation outcomes and the technical characteristics underlying these platforms. Following a comprehensive literature search and structured data extraction, biological parameters (cell types, culture conditions, scaffolds), chip design and fabrication strategies, mechanical loading modalities, and assessment assays were systematically analyzed. Across the included studies, fluid shear stress was the most frequently applied mechanical stimulus and was generally associated with enhanced osteogenic differentiation compared with static cultures, although substantial heterogeneity was observed in loading protocols and outcome measures. Overall, this review provides a consolidated technical and biological overview of mechanically stimulated BoC systems and highlights key methodological considerations for future platform development. By integrating microengineering approaches with bone and stem cell biology, BoC models hold significant potential for advancing bone tissue engineering, mechanobiology research, and translational applications, including dentistry-related bone regeneration and biomaterial testing.