An Advanced Human Bone Tissue Culture Model for the Assessment of Implant Osteointegration In Vitro.

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.

Decellularized biological matrices for the repair of rotator cuff lesions: a systematic review of preclinical in vivo studies.

Background: Rotator cuff tears (RCTs), resulting from degeneration or trauma of the shoulder tendons, are one of the main causes of shoulder pain. In particular, massive RCTs represent 40% of all injuries, require surgical treatment, and are characterized by poor clinical outcomes and a high rate of failure. In recent years, the use of biological decellularized patches for augmentation procedures has received great interest owing to their excellent self-integration properties, improving healing and, thus, presenting an innovative therapeutic option. However, the findings from clinical studies have emerged with conflicting viewpoints regarding the benefits of this procedure, as an excessive tension load might compromise the integrity of the tendon-to-bone connection when the patch exhibits low elasticity or insufficient strength. This could prevent the healing process, leading to unpredictable results in clinical practice. Methods: This systematic review was conducted following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines across three databases (PubMed, Scopus, and Web of Knowledge) to underline the results obtained in preclinical studies involving animal models of RCT surgeries that utilized the biological decellularized matrix augmentation technique in the last 5 years. Results: Thirteen articles were included after the screening, and the SYRCLE tools were applied to assess the risk of bias in in vivo studies. Open-surgery techniques were conducted to create tendon defects or detachment in different animal models: rat (31%), rabbit (46%), dog (15%), and sheep (8%). Patches decellularized with non-standardized protocols were used in 77% of studies, while commercially available matrices were used in 15%. Of the studies, 31% used allogenic patches, 61% used xenogenic patches, and 8% utilized both xenogenic and autologous patches. Conclusion: Overall, this review provides a comprehensive overview of the use of acellular patches and their effective therapeutic potential in rotator cuff (RC) repair at the preclinical level with the aim of expanding the strategies and matrices available for surgeons. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023468716.

Ultrasound Stimulation of Piezoelectric Nanocomposite Hydrogels Boosts Chondrogenic Differentiation in Vitro, in Both a Normal and Inflammatory Milieu.

The use of piezoelectric nanomaterials combined with ultrasound stimulation is emerging as a promising approach for wirelessly triggering the regeneration of different tissue types. However, it has never been explored for boosting chondrogenesis. Furthermore, the ultrasound stimulation parameters used are often not adequately controlled. In this study, we show that adipose-tissue-derived mesenchymal stromal cells embedded in a nanocomposite hydrogel containing piezoelectric barium titanate nanoparticles and graphene oxide nanoflakes and stimulated with ultrasound waves with precisely controlled parameters (1 MHz and 250 mW/cm2, for 5 min once every 2 days for 10 days) dramatically boost chondrogenic cell commitment in vitro. Moreover, fibrotic and catabolic factors are strongly down-modulated: proteomic analyses reveal that such stimulation influences biological processes involved in cytoskeleton and extracellular matrix organization, collagen fibril organization, and metabolic processes. The optimal stimulation regimen also has a considerable anti-inflammatory effect and keeps its ability to boost chondrogenesis in vitro, even in an inflammatory milieu. An analytical model to predict the voltage generated by piezoelectric nanoparticles invested by ultrasound waves is proposed, together with a computational tool that takes into consideration nanoparticle clustering within the cell vacuoles and predicts the electric field streamline distribution in the cell cytoplasm. The proposed nanocomposite hydrogel shows good injectability and adhesion to the cartilage tissue ex vivo, as well as excellent biocompatibility in vivo, according to ISO 10993. Future perspectives will involve preclinical testing of this paradigm for cartilage regeneration.

Benefits of Applying Nanotechnologies to Hydrogels in Efficacy Tests in Osteoarthritis Models-A Systematic Review of Preclinical Studies.

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.