We propose a culture-free approach to osteochondral repair with minced autologous cartilage fragments loaded onto a scaffold composed of a hyaluronic acid (HA)-derived membrane, platelet-rich fibrin matrix (PRFM) and fibrin glue. The aim of the study was to demonstrate in vitro
In bone tissue engineering research, bioreactors designed for replicating the main features of the complex native environment represent powerful investigation tools. Moreover, when equipped with automation, their use allows reducing user intervention and dependence, increasing reproducibility and the overall quality of the culture process. In this study, an automated uni-/bi-directional perfusion bioreactor combinable with pulsed electromagnetic field (PEMF) stimulation for culturing 3D bone tissue models is proposed. A user-friendly control unit automates the perfusion, minimizing the user dependency. Computational fluid dynamics simulations supported the culture chamber design and allowed the estimation of the shear stress values within the construct. Electromagnetic field simulations demonstrated that, in case of combination with a PEMF stimulator, the construct can be exposed to uniform magnetic fields. Preliminary biological tests on 3D bone tissue models showed that perfusion promotes the release of the early differentiation marker alkaline phosphatase. The histological analysis confirmed that perfusion favors cells to deposit more extracellular matrix (ECM) with respect to the static culture and revealed that bi-directional perfusion better promotes ECM deposition across the construct with respect to uni-directional perfusion. Lastly, the Real-time PCR results of 3D bone tissue models cultured under bi-directional perfusion without and with PEMF stimulation revealed that the only perfusion induced a ~ 40-fold up-regulation of the expression of the osteogenic gene collagen type I with respect to the static control, while a ~ 80-fold up-regulation was measured when perfusion was combined with PEMF stimulation, indicating a positive synergic pro-osteogenic effect of combined physical stimulations.
The elbow ligamentous and bony structures play essential roles in the joint stability. Nevertheless, the contribution of different structures to joint stability is not yet clear and a comprehensive experimental investigation into the ligament and osseous constraints changes in relation to joint motions would be uphill and somehow unattainable, due to the impossibility of obtaining all the possible configurations on the same specimen. Therefore, a predictive tool of the joint behavior after the loss of retentive structures would be helpful in designing reconstructive surgeries and in pre-operative planning. In this work, a multibody model consisting of bones and non-linear ligamentous structures is presented and validated through comparison with experimental data. An accurate geometrical model was equipped with non-linear ligaments bundles between optimized origin and insertion points. The joint function was simulated according to maneuvers accomplished in published experimental studies which explored the posteromedial rotatory in-stability (PMRI) in coronoid and posterior medial collateral ligament (PB) deficient elbows. Moreover, a complete design of experiments (DOE) was explored, investigating the influence of the elbow flexion degree, of the coronoid process and of the medial collateral ligaments (MCL) structures (anterior and posterior bundles) in the elbow joint opening. The implemented computational model accurately predicted the joint behavior with intact and deficient stabilizing structures at each flexion degree, and highlighted the statistically significant influence of the MCL structures (P<0.05) on the elbow stability. The predictive ability of this multibody elbow joint model let foresee that future investigations under different loading scenarios and injured or surgically reconstructed states could be effectively simulated, helping the ligaments reconstruction optimization in terms of bone tunnel localizations and grafts pre-loading. Level of evidence: V.
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