Smart hydrogels embedding mesenchymal stromal cells are receiving increasing attention as a potential solution for preventing articular cartilage degeneration in knee osteoarthritis (OA). In this work we demonstrate that an injectable piezoelectric hydrogel embedding autologous adipose tissue-derived mesenchymal stromal cells (ASCs), stimulated by low-intensity pulsed ultrasound (LIPUS), is effective in reducing knee OA in two preclinical surgically induced OA models. A medium-sized rabbit model was used to evaluate sex differences in treatment efficacy, while a large-sized sheep model was employed to assess the translatability of this innovative approach to a scenario with similarities to human conditions. We developed computational models to ensure reliable and precise delivery of a specific ultrasound dose to the target, modelling wave propagation through tissues and considering the anatomy of the two experimental animal models. Sex-based differences in therapy effectiveness were observed in rabbits, with better macroscopic and microscopic outcomes in counteracting OA in female animals. Furthermore, we found that the combination of ASC-laden piezoelectric hydrogel and LIPUS can be scaled in a large-sized sheep model, proving effective in counteracting OA.

Osteoarthritis (OA) is a severe musculoskeletal disease with an increasing incidence in the worldwide population. Recent research has focused on the development of innovative strategies to prevent articular cartilage damage and slow down OA progression, and nanotechnologies applied to hydrogels have gained particular interest. The aim of this systematic review is to investigate the state of the art on preclinical in vitro and in vivo efficacy studies applying nanotechnologies to hydrogels in OA models to elucidate the benefits of their applications. Three databases were consulted for eligible papers. The inclusion criteria were in vitro and in vivo preclinical studies, using OA cells or OA animal models, and testing hydrogels and nanoparticles (NPs) over the last ten years. Data extraction and quality assessment were performed. Eleven papers were included. In vitro studies evidenced that NP-gels do not impact on cell viability and do not cause inflammation in OA cell phenotypes. In vivo research on rodents showed that these treatments could increase drug retention in joints, reducing inflammation and preventing articular cartilage damage. Nanotechnologies in preclinical efficacy tests are still new and require extensive studies and technical hits to determine the efficacy, safety, fate, and localization of NPs for translation into an effective therapy for OA patients.

In the field of biomaterials for prosthetic reconstructive surgery, there is the lack of advanced innovative methods to investigate the potentialities of smart biomaterials before in vivo tests. Despite the complex osteointegration process being difficult to recreate in vitro, this study proposes an advanced in vitro tissue culture model of osteointegration using human bone. Cubic samples of trabecular bone were harvested, as waste material, from hip arthroplasty; inner cylindrical defects were created and assigned to the following groups: (1) empty defects (CTRneg); (2) defects implanted with a cytotoxic copper pin (CTRpos); (3) defects implanted with standard titanium pins (Ti). Tissues were dynamically cultured in mini rotating bioreactors and assessed weekly for viability and sterility. After 8 weeks, immunoenzymatic, microtomographic, histological, and histomorphometric analyses were performed. The model was able to simulate the effects of implantation of the materials, showing a drop in viability in CTR+, while Ti appears to have a trophic effect on bone. MicroCT and a histological analysis supported the results, with signs of matrix and bone deposition at the Ti implant site. Data suggest the reliability of the tested model in recreating the osteointegration process in vitro with the aim of reducing and refining in vivo preclinical models.

Adolescent idiopathic scoliosis (AIS) is a multifactorial spinal deformity with variable progression patterns, making early risk stratification challenging. Circulating and tissue biomarkers, including inflammatory, metabolic, endocrine, epigenetic, and bone-related markers, have recently been investigated as potential predictors of disease severity and progression. This systematic review evaluated the current evidence on circulating and tissue biomarkers associated with AIS severity and progression. PubMed, Scopus, and Web of Science were searched for studies published between April 2016 and April 2026. Studies assessing circulating or tissue-based inflammatory, metabolic, epigenetic, and bone-related biomarkers in AIS patients were included. Data on study design, biomarker type, analytical methods, and associations with curve severity or progression were extracted. Twenty-nine studies involving more than 4000 participants were included. Biomarkers identified included inflammatory cytokines, microRNAs, metabolic hormones, and bone metabolism markers. Most studies reported significant associations between biomarkers and curve severity, particularly for inflammatory mediators, epigenetic regulators, and bone-related markers. However, few studies evaluated longitudinal progression, and only a limited number of studies identified predictive biomarkers, including circulating miRNA panels and spermidine levels. ROBINS-I assessment showed substantial risk of bias, mainly related to confounding and selective reporting. Heterogeneity was observed across study designs and outcome definitions. Current evidence supports associations between biomarkers and AIS severity, but predictive value for progression remains limited.