Rodriguez-Florez, N. (Naiara)
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- Analytical model for the prediction of permeability of triply periodic minimal surfaces(Elsevier, 2021) Asbai-Ghoudan, R. (Reduan); Rodriguez-Florez, N. (Naiara); Ruiz-de-Galarreta-Moriones, S.(Sergio)Triply periodic minimal surfaces (TPMS) are mathematically defined cellular structures whose geometry can be quickly adapted to target desired mechanical response (structural and fluid). This has made them desirable for a wide range of bioengineering applications; especially as bioinspired materials for bone replacement. The main objective of this study was to develop a novel analytical framework which would enable calculating permeability of TPMS structures based on the desired architecture, pore size and porosity. To achieve this, computer-aided designs of three TPMS structures (Fisher-Koch S, Gyroid and Schwarz P) were generated with varying cell size and porosity levels. Computational Fluid Dynamics (CFD) was used to calculate permeability for all models under laminar flow conditions. Permeability values were then used to fit an analytical model dependent on geometry parameters only. Results showed that permeability of the three architectures increased with porosity at different rates, highlighting the importance of pore distribution and architecture. The computed values of permeability fitted well with the suggested analytical model (R2>0.99, p<0.001). In conclusion, the novel analytical framework presented in the current study enables predicting permeability values of TPMS structures based on geometrical parameters within a difference <5%. This model, which could be combined with existing structural analytical models, could open new possibilities for the smart optimisation of TPMS structures for biomedical applications where structural and fluid flow properties need to be optimised.
- Three-dimensionalenvironment and vascularization induce osteogenic maturation of human adipose-derived stem cells comparable to that of bone-derived progenitors(Wiley, 2020) Rodriguez-Florez, N. (Naiara); Ferretti, P. (Patrizia); New, S.E.P. (Sophie E. P.); Gardner, O.F.W. (Oliver F.W.); Dunaway, D.J. (David J.); Bulstrode, N.W. (Neil W.); Ibrahim, A. (Amel); Borghi, A. (Alessandro); Zucchelli, E. (Eleonora)While human adipose-derived stem cells (hADSCs) are known to possess osteogenic differentiation potential, the bone tissues formed are generally considered rudimentary and immature compared with those made by bone-derived precursor cells such as human bone marrow-derived mesenchymal stem cells (hBMSCs) and less commonly studied human calvarium osteoprogenitor cells (hOPs). Traditional differentiation protocols have tended to focus on osteoinduction of hADSCs through the addition of osteogenic differentiation media or use of stimulatory bioactive scaffolds which have not resulted in mature bone formation. Here, we tested the hypothesis that by reproducing the physical as well as biochemical bone microenvironment through the use of three-dimensional (3D) culture and vascularization we could enhance osteogenic maturation in hADSCs. In addition to biomolecular characterization, we performed structural analysis through extracellular collagen alignment and mineral density in our bone tissue engineered samples to evaluate osteogenic maturation. We further compared bone formed by hADSCs, hBMSCs, and hOPs against mature human pediatric calvarial bone, yet not extensively investigated. Although bone generated by all three cell types was still less mature than native pediatric bone, a fibrin-based 3D microenvironment together with vascularization boosted osteogenic maturation of hADSC making it similar to that of bone-derived osteoprogenitors. This demonstrates the important role of vascularization and 3D culture in driving osteogenic maturation of cells easily available but constitutively less committed to this lineage and suggests a crucial avenue for recreating the bone microenvironment for tissue engineering of mature craniofacial bone tissues from pediatric hADSCs, as well as hBMSCs and hOPs.
- The esthetic perception of morphological severity in scaphocephalic patients is correlated with specific head geometrical features(2023) Rodriguez-Florez, N. (Naiara); Koudstaal, M. (M.); Schievano, S. (Silvia); Ruggiero, F. (Federica); Dunaway, D.J. (David J.); Heutinck, P. (Pam); Jeelani, O. (Owase); Borghi, A. (Alessandro); Ajami, S. (Sima)Objective To investigate the relationship between perception of craniofacial deformity, geometric head features, and 3D head shape analyzed by statistical shape modeling (SSM). Patients A total of 18 unoperated patients with scaphocephaly (age = 5.2 +/- 1.1m)-6 were followed-up after spring-assisted cranioplasty (SAC) (age = 9.6 +/- 1.5m)-and 6 controls (age = 6.7 +/- 2.5m). Main Outcome Measures 3D head shapes were retrieved from 3D scans or computed tomography (CTs). Various geometrical features were measured: anterior and posterior prominence, take-off angle, average anterior and posterior lateral and horizontal curvatures, cranial index (CI) (cranial width over length), and turricephaly index (TI) (cranial height over length). SSM and principal component analysis (PCA) described shape variability. All models were 3D printed; the perception of deformity was blindly scored by 9 surgeons and 1 radiologist in terms of frontal bossing (FB), occipital bulleting (OB), biparietal narrowing (BN), low posterior vertex (LPV), and overall head shape (OHS). Results A moderate correlation was found between FB and anterior prominence (r = 0.56, P < .01) and take-off angle (r = - 0.57, P < .01). OB correlated with average posterior lateral curvature (r = 0.43, P < 0.01) similarly to BPN (r = 0.55, P < .01) and LPV (r = 0.43, P < .01). OHS showed strong correlation with CI (r = - 0.68, P < .01) and TI (r = 0.63, P< .01). SSM Mode 1 correlated with OHS (r = 0.66, p < .01) while Mode 3 correlated with FB (r = - 0.58, P < .01). Conclusions Esthetic cranial appearance in craniofacial patients is correlated to specific geometric parameters and could be estimated using automated methods such as SSM.
- An engineered periosteum for efficient delivery of rhBMP-2 and mesenchymal progenitor cells during bone regeneration(2023) Granero-Moltó, F. (Froilán); López-Martínez, T. (Tania); Riera-Alvarez, L. (Luis); Rodriguez-Florez, N. (Naiara); Elizalde, R. (Reyes); Ripalda-Cemboráin, P. (Purificación); Ruiz-de-Galarreta-Moriones, S.(Sergio); Juan-Pardo, E.M. (Elena M.) de; Childs, P. (Peter); Echanove-González De Anleo, M. (Miguel); Lamo-de-Espinosa-Vázquez-de-Sola, J.M. (José María); Valdés-Fernández, J. (José); Salmeron-Sanchez, M. (Manuel); Muiños-López, E. (Emma); Romero-Torrecilla, J.A. (Juan Antonio); Prosper-Cardoso, F. (Felipe); López-Barberena, A. (Asier); Abizanda-Sarasa, G. (Gloria); Jayawarna, V. (Vineetha)During bone regeneration, the periosteum acts as a carrier for key regenerative cues, delivering osteochondroprogenitor cells and crucial growth factors to the injured bone. We developed a biocompatible, 3D polycaprolactone (PCL) melt electro-written membrane to act as a mimetic periosteum. Poly (ethyl acrylate) coating of the PCL membrane allowed functionalization, mediated by fibronectin and low dose recombinant human BMP-2 (rhBMP-2) (10-25 mu g/ml), resulting in efficient, sustained osteoinduction in vitro. In vivo, rhBMP-2 functionalized mimetic periosteum demonstrated regenerative potential in the treatment of rat critical-size femoral defects with highly efficient healing and functional recovery (80%-93%). Mimetic periosteum has also proven to be efficient for cell delivery, as observed through the migration of transplanted periosteum-derived mesenchymal cells to the bone defect and their survival. Ultimately, mimetic periosteum demonstrated its ability to deliver key stem cells and morphogens to an injured site, exposing a therapeutic and translational potential in vivo when combined with unprecedentedly low rhBMP-2 doses.
- Additively manufactured lattice structures with controlled transverse isotropy for orthopedic porous implants(Elsevier, 2022) Rodriguez-Florez, N. (Naiara); Ruiz-de-Galarreta-Moriones, S.(Sergio); Alaña-Olivares, M. (Markel); Lopez-Arancibia, A. (Aitziber); Ghouse, S. (Shaaz)Additively manufactured lattice structures enable the design of tissue scaffolds with tailored mechanical properties, which can be implemented in porous biomaterials. The adaptation of bone to physiological loads results in anisotropic bone tissue properties which are optimized for site-specific loads; therefore, some bone sites are stiffer and stronger along the principal load direction compared to other orientations. In this work, a semi-analytical model was developed for the design of transversely isotropic lattice structures that can mimic the anisotropy characteristics of different types of bone tissue. Several design possibilities were explored, and a particular unit cell, which was best suited for additive manufacturing was further analyzed. The design of the unit cell was parameterized and in-silico analysis was performed via Finite Element Analysis. The structures were manufactured additively in metal and tested under compressive loads in different orientations. Finite element analysis showed good correlation with the semi-analytical model, especially for elastic constants with low relative densities. The anisotropy measured experimentally showed a variable accuracy, highlighting the deviations from designs to additively manufactured parts. Overall, the proposed model enables to exploit the anisotropy of lattice structures to design lighter scaffolds with higher porosity and increased permeability by aligning the scaffold with the principal direction of the load.
- In silico assessment of the bone regeneration potential of complex porous scaffolds(Elsevier, 2023) Asbai-Ghoudan, R. (Reduan); Rodriguez-Florez, N. (Naiara); Pérez, M.A. (María Ángeles); Nasello, G. (Gabriele); Ruiz-de-Galarreta-Moriones, S.(Sergio); Verbruggen, S.W. (Stefaan W.)Mechanical environment plays a crucial role in regulating bone regeneration in bone defects. Assessing the mechanobiological behavior of patient-specific orthopedic scaffolds in-silico could help guide optimal scaffold designs, as well as intra- and post-operative strategies to enhance bone regeneration and improve implant longevity. Additively manufactured porous scaffolds, and specifically triply periodic minimal surfaces (TPMS), have shown promising structural properties to act as bone substitutes, yet their ability to induce mechanobiologially-driven bone regeneration has not been elucidated. The aim of this study is to i) explore the bone regeneration potential of TPMS scaffolds made of different stiffness biocompatible materials, to ii) analyze the influence of pre-seeding the scaffolds and increasing the post-operative resting period, and to iii) assess the influence of patient-specific parameters, such as age and mechanosensitivity, on outcomes. To perform this study, an in silico model of a goat tibia is used. The bone ingrowth within the scaffold pores was simulated with a mechano-driven model of bone regeneration. Results showed that the scaffold's architectural properties affect cellular diffusion and strain distribution, resulting in variations in the regenerated bone volume and distribution. The softer material improved the bone ingrowth. An initial resting period improved the bone ingrowth but not enough to reach the scaffold's core. However, this was achieved with the implantation of a pre-seeded scaffold. Physiological parameters like age and health of the patient also influence the bone regeneration outcome, though to a lesser extent than the scaffold design. This analysis demonstrates the importance of the scaffold's geometry and its material, and highlights the potential of using mechanobiological patient-specific models in the design process for bone substitutes.
- Critical analysis of the suitability of crack propagation direction criteria for 2D cylindrical plain fretting contact.(Pergamon-Elsevier Science LTD., 2019-06) Gómez-Mitxelena, X. (Xabier); Rodriguez-Florez, N. (Naiara); Llavori, I. (Iñigo); Zabala, A. (Alaitz); Giner, E. (Eugenio); Infante-Garcia, D. (Diego); Aginagalde, A. (Andrea)In this work the suitability of the criterion of maximum effective amplitude of the normal stress (Delta sigma(n,eff))(max) and the criterion of minimum shear stress range (Delta tau)(min) for 2D cylindrical plain fretting contact condition has been analysed. The numerical analysis has been performed by means of the extended finite element method, which takes into account the contact between crack faces during the closing part, and the results have been compared with experiments reported in the literature. Results show that overall the (Delta tau)(min) criterion predominates in intermediate stage, while the (Delta sigma(n,eff))(max) shows less deviation in the final stage. However, the predicted crack path by the latter criterion shifts toward the outer side, which do not correlate with the experimental results reported in the literature. Additional studies should investigate the variables that are affecting this change in the behaviour along the crack in order to set a criteria that is able to predict the plain fretting condition crack paths accurately.
- Meeting high precision requirements of additively manufactured components through hybrid manufacturing(Elsevier, 2023) Rodriguez-Florez, N. (Naiara); Arizmendi-Jaca, M. (Mikel); Jiménez-Zabaleta, A. (Amaia); Ruiz-de-Galarreta-Moriones, S.(Sergio); Loyda-Quiroz, A. (Alejandro)A hybrid approach combining the laser powder bed fusion (LPBF) process and post-processing operations through 5-axis milling was employed to manufacture a Ti6Al4V aerospace component. From the design step, the requirements and needs in all the stages of the Hybrid Additive Manufacturing process were taken into account. A numerical simulation of distortions promoted by residual stresses during the additive process was employed to consider material allowance. The status of the as-built and post-processed component was analysed through scanning and CMM inspection and roughness measurements. The 3D scanned model of the as-built LPBF-ed component was used to understand the distortion behaviour of the component and compared to the numerical simulation. Finally, 5-axis milling operations were conducted in some critical surfaces in order to improve surface quality and dimensional accuracy of the as-built com- ponent. The inspection of the as-built and post-processed component showed the improvement achieved through the proposed hybrid approach. The work aims to provide the baselines needed to enable the metal Hybrid Additive Manufacturing of components with complex geometries where mandatory precision is required by integrating high accuracy machining operations as post-processing technique.
- Intracranial volume and head circumference in children with unoperated syndromic craniosynostosis.(LIPPINCOTT WILLIAMS & WILKINS, 2018-11) Rodriguez-Florez, N. (Naiara); Schievano, S. (Silvia); O'Hara, J. (Justine); James, G. (Gregory); Dunaway, D.J. (David J.); Jeelani, O. (Owase); Borghi, A. (Alessandro); Knoops, P.G.M. (Paul G. M.); Breakey, R.W.F. (Richard W. F.)Background: When analyzing intracranial volume gain resulting from operative intervention in craniosynostosis, it is necessary to understand the underlying growth. The authors sought to create comprehensive intracranial volume and occipitofrontal circumference growth charts, as measured on unoperated craniosynostotic children, and aimed to investigate whether intracranial volume and occipitofrontal circumference could act as proxy measures for each other. Methods: All preoperative Great Ormond Street Hospital patients with a diagnosis of Apert, Crouzon-Pfeiffer, or Saethre-Chotzen syndrome from the year 2004 onward were considered for this study. A control group of unaffected Great Ormond Street Hospital patients were also measured. Intracranial volume and occipitofrontal circumference were measured on the same scans. To study correlation between intracranial volume and occipitofrontal circumference, logarithmic fits were assessed. Results: One hundred forty-seven craniosynostotic children with 221 preoperative scans were included (81 Apert, 81 Crouzon, 31 Pfeiffer, and 28 Saethre-Chotzen). The control group comprised 56 patients with 58 scans. Apert intracranial volume curves were significantly larger than those of other syndromes from 206 days onward; occipitofrontal circumference curves were not significantly different. The correlation coefficient between intracranial volume and occipitofrontal circumference was R-2 = 0.87 for all syndromes combined and R-2 = 0.91 for the control group. Conclusions: Apert syndrome children have a larger intracranial volume than children with other syndromic craniosynostotic conditions and unaffected children but maintain a similar occipitofrontal circumference. This study demonstrates high correlation between intracranial volume and occipitofrontal circumference with clinical care implications. The authors' reference growth curves can be used to monitor intracranial volume change over time and correct operative change for underlying growth.
- A novel soft tissue prediction methodology for orthognathic surgery based on probabilistic finite element modelling(Public Library of Science, 2018) Rodriguez-Florez, N. (Naiara); Badiali, G. (Giovanni); Schievano, S. (Silvia); Ruggiero, F. (Federica); Dunaway, D.J. (David J.); Marchetti, C. (Claudio); Jeelani, O. (Owase); Bianchi, A. (Alberto); Borghi, A. (Alessandro); Knoops, P.G.M. (Paul G. M.); Breakey, R.W.F. (Richard W. F.)Repositioning of the maxilla in orthognathic surgery is carried out for functional and aesthetic purposes. Pre-surgical planning tools can predict 3D facial appearance by computing the response of the soft tissue to the changes to the underlying skeleton. The clinical use of commercial prediction software remains controversial, likely due to the deterministic nature of these computational predictions. A novel probabilistic finite element model (FEM) for the prediction of postoperative facial soft tissues is proposed in this paper. A probabilistic FEM was developed and validated on a cohort of eight patients who underwent maxillary repositioning and had pre- and postoperative cone beam computed tomography (CBCT) scans taken. Firstly, a variables correlation assessed various modelling parameters. Secondly, a design of experiments (DOE) provided a range of potential outcomes based on uniformly distributed input parameters, followed by an optimisation. Lastly, the second DOE iteration provided optimised predictions with a probability range. A range of 3D predictions was obtained using the probabilistic FEM and validated using reconstructed soft tissue surfaces from the postoperative CBCT data. The predictions in the nose and upper lip areas accurately include the true postoperative position, whereas the prediction under-estimates the position of the cheeks and lower lip. A probabilistic FEM has been developed and validated for the prediction of the facial appearance following orthognathic surgery. This method shows how inaccuracies in the modelling and uncertainties in executing surgical planning influence the soft tissue prediction and it provides a range of predictions including a minimum and maximum, which may be helpful for patients in understanding the impact of surgery on the face.