Elizalde, R. (Reyes)
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- 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.
- Anisotropic cryostructured collagen scaffolds for efficient delivery of RhBMP–2 and enhanced bone regeneration(MDPI AG, 2019) Ewald, A. (Andrea); Andreu-Arzuaga, I. (Ion); Granero-Moltó, F. (Froilán); Groll, J. (Jürgen); Flandes-Iparraguirre, M. (María); Elizalde, R. (Reyes); Ripalda-Cemboráin, P. (Purificación); Stuckensen, K. (Kai); Lopez, T. (Tania); Pons-de-Villanueva, J. (Juan); Muiños-López, E. (Emma); Nickel, J. (Joachim); Iglesias, E. (Elena); Prosper-Cardoso, F. (Felipe); Lamo-Espinosa, J.M. (J. M.); Abizanda-Sarasa, G. (Gloria); Gbureck, U. (Uwe)In the treatment of bone non-unions, an alternative to bone autografts is the use of bone morphogenetic proteins (BMPs), e.g., BMP–2, BMP–7, with powerful osteoinductive and osteogenic properties. In clinical settings, these osteogenic factors are applied using absorbable collagen sponges for local controlled delivery. Major side effects of this strategy are derived from the supraphysiological doses of BMPs needed, which may induce ectopic bone formation, chronic inflammation, and excessive bone resorption. In order to increase the efficiency of the delivered BMPs, we designed cryostructured collagen scaffolds functionalized with hydroxyapatite, mimicking the structure of cortical bone (aligned porosity, anisotropic) or trabecular bone (random distributed porosity, isotropic). We hypothesize that an anisotropic structure would enhance the osteoconductive properties of the scaffolds by increasing the regenerative performance of the provided rhBMP–2. In vitro, both scaffolds presented similar mechanical properties, rhBMP–2 retention and delivery capacity, as well as scaffold degradation time. In vivo, anisotropic scaffolds demonstrated better bone regeneration capabilities in a rat femoral critical-size defect model by increasing the defect bridging. In conclusion, anisotropic cryostructured collagen scaffolds improve bone regeneration by increasing the efficiency of rhBMP–2 mediated bone healing.
- Changes in mechanical properties of adipose tissue after bariatric surgery driven by extracellular matrix remodelling and neovascularization are associated with metabolic improvements(Elsevier, 2022) Unamuno, X. (Xabier); Valenti, V. (Víctor); Ezquerro-Ezquerro, S. (Silvia); Elizalde, R. (Reyes); Ramirez, B. (Beatriz); Catalan, V. (Victoria); Álvarez-Cienfuegos, J. (Javier); Mentxaka, A. (Amaia); Becerril, S. (Sara); Frühbeck, G. (Gema); Moncada, R. (Rafael); Silva, C. (Camilo); Llorente-Ortega, M. (Marcos); Gomez-Ambrosi, J. (Javier); Rodriguez, A. (Amaia)Biomechanical properties of adipose tissue (AT) are closely involved in the development of obesity- associated comorbidities. Bariatric surgery (BS) constitutes the most effective option for a sustained weight loss in addition to improving obesity-associated metabolic diseases including type 2 diabetes (T2D). We aimed to determine the impact of weight loss achieved by BS and caloric restriction (CR) on the biomechanical properties of AT. BS but not CR changed the biomechanical properties of epididymal white AT (EWAT) from a diet-induced obesity rat model, which were associated with metabolic improve- ments. We found decreased gene expression levels of collagens and Lox together with increased elastin and Mmps mRNA levels in EWAT after BS, which were also associated with the biomechanical properties. Moreover, an increased blood vessel density was observed in EWAT after surgery, confirmed by an up- regulation of Acta2 and Antxr1 gene expression levels, which was also correlated with the biomechanical properties. Visceral AT from patients with obesity showed increased stiffness after tensile tests compared to the EWAT from the animal model. This study uncovers new insights into EWAT adaptation after BS with decreased collagen crosslink and synthesis as well as an increased degradation together with en- hanced blood vessel density providing, simultaneously, higher stiffness and more ductility. Statement of Significance Biomechanical properties of the adipose tissue (AT) are closely involved in the development of obesity- associated comorbidities. In this study, we show for the first time that biomechanical properties of AT determined by E, UTS and strain at UTS are decreased in obesity, being increased after bariatric surgery by the promotion of ECM remodelling and neovascularization. Moreover, these changes in biomechanical properties are associated with improvements in metabolic homeostasis. Consistently, a better character- ization of the plasticity and biomechanical properties of the AT after bariatric surgery opens up a new field for the development of innovative strategies for the reduction of fibrosis and inflammation in AT as well as to better understand obesity and its associated comorbidities.