Person:
Lozano Borregón, Daniel

First Name

Daniel

Last Name

Lozano Borregón

URI

https://hdl.handle.net/20.500.14352/77556

Affiliation

Universidad Complutense de Madrid

Faculty / Institute

Farmacia

Department

Química en Ciencias Farmacéuticas

Area

Química Inorgánica

Identifiers

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Now showing 1 - 8 of 8

In vivo behavior in rabbit radius bone defect of scaffolds based on nanocarbonate hydroxyapatite
(Journal of Biomedical Materials Research Part B: Applied Biomaterials, 2024) García Lamas, Lorena; Peña López, Juan; Román Zaragoza, Jesús; Cabañas Criado, María Victoria; Bravo Giménez, Beatriz; Jiménez Díaz, Verónica; Sánchez Salcedo, Sandra; Jiménez Holguín, Javier; Abella, Mónica; Desco, Manuel; Lozano Borregón, Daniel; Cecilia López, David; Salinas Sánchez, Antonio Jesús
Bone defects treatment may require the use of biomaterials that behave as a support and promote bone regeneration. Limitations associated with the use of autografts and allografts make it necessary to design new synthetic bone substitutes. Some of the most promising biomaterials currently under investigation are based on nanocarbonate hydroxyapatite (nCHA). In this study, we studied the bone-inducing capacity of nCHA-based scaffolds alone (SAG) and enriched with osteostatin (SAGO) or with bone marrow aspirate(SAGB) after implantation for 12 weeks in a 15-mm long critical defect performed in the radius of New Zealand rabbits. Bone formation obtained was compared with a group with the unfilled defect (CE), as control group, and other with the defect filed with iliac crest autograft (GS), as gold standard. X-ray follow-up was performed at 2, 4, 6 and 12 weeks and μCT and histological studies at 12 weeks. The radiological results showed a greater increment in bone formation in the GS group (75%–100%), followed by the SAG and SAGB groups (50%–75%). μCT results showed an increase of bone volume/tissue volume values in GS group followed by SAG and SAGB groups (0.53, 0.40, and 0.31 respectively) compared with CE group (0.26). Histological results showed limited resorption of the nCHA scaffolds and partial osseointegration in the SAG and SAGB groups. However, in the SAGO group, the presence of connective tissue encapsulating the scaffold was detected. In SAG, SAGB, and increase of bone formation were observed compared with CE group, but less than the GS group. Thus, the investigated materials represent a significant advance in the design of synthetic materials for bone grafting, but further studies are needed to bring their in vivo behavior closer to autograft, the gold standard.
Local delivery of parathyroid hormone-related protein-derived peptides coated onto a hydroxyapatite-based implant enhances bone regeneration in old and diabetic rats
(Journal of Biomedical Materials Research Part A, 2016) Ardura, Juan A.; Portal Núñez, Sergio; Lozano Borregón, Daniel; Gutiérrez Rojas, Irene; Sánchez Salcedo, Sandra; López Herradón, Ana; Mulero, Francisca; Villanueva Penacarrillo, Maria L.; Vallet Regí, María Dulce Nombre; Esbrit, Pedro
Diabetes mellitus (DM) and aging are associated with bone fragility and increased fracture risk. Both (1-37) N- and (107-111) C-terminal parathyroid hormone-related protein (PTHrP) exhibit osteogenic properties. We here aimed to evaluate and compare the efficacy of either PTHrP (1-37) or PTHrP (107-111) loaded into gelatin-glutaraldehyde-coated hydroxyapatite (HA-Gel) foams to improve bone repair of a transcortical tibial defect in aging rats with or without DM, induced by streptozotocin injection at birth. Diabetic old rats showed bone structural deterioration compared to their age-matched controls. Histological and -computerized tomography studies showed incomplete bone repair at 4 weeks after implantation of unloaded Ha-Gel foams in the transcortical tibial defects, mainly in old rats with DM. However, enhanced defect healing, as shown by an increase of bone volume/tissue volume and trabecular and cortical thickness and decreased trabecular separation, occurred in the presence of either PTHrP peptide in the implants in old rats with or without DM. This was accompanied by newly formed bone tissue around the osteointegrated HA-Gel implant and increased gene expression of osteocalcin and vascular endothelial growth factor (bone formation and angiogenic markers, respectively), and decreased expression of Sost gene, a negative regulator of bone formation, in the healing bone area. Our findings suggest that local delivery of PTHrP (1-37) or PTHrP (107-111) from a degradable implant is an attractive strategy to improve bone regeneration in aged and diabetic subjects. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2060-2070, 2016.
Enriched mesoporous bioactive glass scaffolds as bone substitutes in critical diaphyseal bone defects in rabbits
(Acta Biomaterialia, 2024) García Lamas, Lorena; Lozano Borregón, Daniel; Jiménez Díaz, Verónica; Bravo Giménez, Beatriz; Sánchez Salcedo, Sandra; Abella, Mónica; Desco, Manuel; Jiménez Holguín, Javier; Vallet Regí, María Dulce Nombre; Cecilia López, David; Salinas Sánchez, Antonio Jesús
In the field of orthopedic surgery, there is an increasing need for the development of bone replacement materials for the treatment of bone defects. One of the main focuses of biomaterials engineering are ad- vanced bioceramics like mesoporous bioactive glasses (MBG´s). The present study compared the new bone formation after 12 weeks of implantation of MBG scaffolds with composition 82,5SiO2 –10CaO–5P2 O5 - x 2.5SrO alone (MBGA), enriched with osteostatin, an osteoinductive peptide, (MBGO) or enriched with bone marrow aspirate (MBGB) in a long bone critical defect in radius bone of adult New Zealand rab- bits. New bone formation from the MBG scaffold groups was compared to the gold standard defect filled with iliac crest autograft and to the unfilled defect. Radiographic follow-up was performed at 2, 6, and 12 weeks, and microCT and histologic examination were performed at 12 weeks. X-Ray study showed the highest bone formation scores in the group with the defect filled with autograft, followed by the MBGB group, in addition, the microCT study showed that bone within defect scores (BV/TV) were higher in the MBGO group. This difference could be explained by the higher density of newly formed bone in the os- teostatin enriched MBG scaffold group. Therefore, MBG scaffold alone and enriched with osteostatin or bone marrow aspirate increase bone formation compared to defect unfilled, being higher in the osteo- statin group. The present results showed the potential to treat critical bone defects by combining MBGs with osteogenic peptides such as osteostatin, with good prospects for translation into clinical practice.
Osteostatin potentiates the bioactivity of mesoporous glass scaffolds containing Zn2+ ions in human mesenchymal stem cell cultures
(Acta Biomaterialia, 2019) Heras, Clara; Sánchez Salcedo, Sandra; Lozano Borregón, Daniel; Peña, Juan; Esbrit, Pablo; Vallet Regí, María Dulce Nombre; Salinas Sánchez, Antonio J.
There is an urgent need of biosynthetic bone grafts with enhanced osteogenic capacity. In this study, we describe the design of hierarchical meso-macroporous 3D-scaffolds based on mesoporous bioactive glasses (MBGs), enriched with the peptide osteostatin and Zn2+ ions, and their osteogenic effect on human mesenchymal stem cells (hMSCs) as a preclinical strategy in bone regeneration. The MBG compositions investigated were 80%SiO2– 15%CaO–5%P2O5 (in mol-%) Blank (BL), and two analogous glasses containing 4% ZnO (4ZN) and 5% ZnO (5ZN). By using additive fabrication techniques, scaffolds exhibiting hierarchical porosity: mesopores (around 4 nm), macropores (1-600 m) and big channels ( 1000 m), were prepared. These MBG scaffolds with or without osteostatin were evaluated in cell cultures of hMSCs. Zinc promoted hMSCs colonization (both the surface and inside) of MBG scaffolds. Moreover, Zn2+ ions and osteostatin together, but not independently, in the scaffolds were found to induce the osteoblast differentiation genes runt related transcription factor-2 (RUNX2) and alkaline phosphatase (ALP) in hMSCs after 7 d of culture in the absence of an osteogenic differentiation-promoting medium. These results add credence to the combined use of zinc and osteostatin as an effective strategy for bone regeneration applications.
Diseño y comparativa de biomateriales para el tratamiento de defectos óseos. Estudio de su comportamiento in vivo en modelo animal de conejo
(Revista Española de Cirugía Ortopédica y Traumatología, 2023) García Lamas, L.; Sánchez Salcedo, Sandra; Jiménez Díaz, V.; Bravo Giménez, B.; Cabañas Criado, María Victoria; Peña López, Juan; Román, J.; Jiménez Holguín, Javier; Abella, M.; Desco, M.; Lozano Borregón, Daniel; Cecilia López, D.; Salinas Sánchez, Antonio Jesús
Objetivo: Comparar in vivo la capacidad de formación ósea de dos tipos de biomateriales diseñados como sustitutivos óseos respecto a autoinjerto de cresta iliaca, uno basado en carbonatohidroxiapatita y otro en vidrio mesoporoso bioactivo. Material y método: Estudio experimental compuesto por 14 conejos de Nueva Zelanda hembras adultas donde se realizó un defecto crítico en hueso radio. La muestra fue dividida en cuatro grupos: defecto sin material, con autoinjerto de cresta iliaca, con soporte de carbonatohidroxiapatita y con soporte de vidrio mesoporoso bioactivo. Se realizaron estudios seriados de radiología simple a las 2, 4, 6 y 12 semanas y estudio de micro-TC a eutanasia a las 6 y 12 semanas. Resultados: En el estudio de radiología simple, el grupo de autoinjerto mostró las mayores puntuaciones de formación ósea (7,5 puntos). Ambos grupos de biomateriales presentaron formación ósea similar (5,3 y 6 puntos, respectivamente) y mayor al defecto sin material (4 puntos), pero siempre menor que el grupo de autoinjerto. Los resultados del estudio de micro-TC mostraron el mayor volumen de hueso en el área de estudio en el grupo de autoinjerto. Los grupos con sustitutivos óseos presentaron mayor volumen de hueso que el grupo sin material, pero siempre menor que en el grupo de autoinjerto.
ZnO-mesoporous glass scaffolds loaded with osteostatin and mesenchymal cells improve bone healing in a rabbit bone defect.
(Journal of Materials Science: Materials in Medicine, 2020) Lozano Borregón, Daniel; Gil Alvaroba, J; Heras Rubio, Clara; Sánchez Salcedo, Sandra; Gómez Palacio, V. E.; Gómez Blasco, A; Doadrio Villarejo, Juan Carlos; Vallet Regí, María Dulce Nombre; Salinas Sánchez, Antonio J.
The use of 3D scaffolds based on mesoporous bioactive glasses (MBG) enhanced with therapeutic ions, biomolecules and cells is emerging as a strategy to improve bone healing. In this paper, the osteogenic capability of ZnO-enriched MBG scaffolds loaded or not with osteostatin (OST) and human mesenchymal stem cells (MSC) was evaluated after implantation in New Zealand rabbits. Cylindrical meso-macroporous scaffolds with composition (mol %) 82.2SiO2–10.3CaO–3.3P2O5–4.2ZnO (4ZN) were obtained by rapid prototyping and then, coated with gelatin for easy handling and potentiating the release of inorganic ions and OST. Bone defects (7.5 mm diameter, 12 mm depth) were drilled in the distal femoral epiphysis and filled with 4ZN, 4ZN+MSC, 4ZN+OST or 4ZN+MSC+OST materials to evaluate and compare their osteogenic features. Rabbits were sacrificed at 3 months extracting the distal third of bone specimens for necropsy, histological and microtomography (µCT) evaluations. Systems investigated exhibited bone regeneration capability. Thus, trabecular bone volume density (BV/TV) values obtained from µCT showed that the good bone healing capability of 4ZN was significantly improved by the scaffolds coated with OST and MSC. Our findings in vivo suggest the interest of these MBG complete systems to improve bone repair in the clinical practice.
Parathyroid hormone-related protein (107-111) improves the bone regeneration potential of gelatin-glutaraldehyde biopolymer-coated hydroxyapatite
(Acta Biomaterialia, 2014) Lozano Borregón, Daniel; Sánchez Salcedo, Sandra; Portal Núñez, Sergio; Vila, Mercedes; López Herradón, Ana; Ardura, Juan A.; Mulero, Francisca; Gómez Barrena, Enrique; Vallet Regí, María Dulce Nombre; Esbrit, Pedro
Biopolymer-coated nanocrystalline hydroxyapatite (HA) made as macroporous foams which are degradable and flexible are promising candidates as orthopaedic implants. The C-terminal (107-111) epitope of parathyroid hormone-related protein (PTHrP) exhibits osteogenic properties. The main aim of this study was to evaluate whether PTHrP (107-111) loading into gelatin-glutaraldehyde biopolymer-coated HA (HA(GIu)) scaffolds would produce an optimal biomaterial for tissue engineering applications. HA(GIu) scaffolds with and without PTHrP (107-111) were implanted into a cavitary defect performed in both distal tibial metaphysis of adult rats. Animals were sacrificed after 4 weeks for histological, microcomputerized tomography and gene expression analysis of the callus. At this time, bone healing occurred only in the presence of PTHrP (107-111)-containing HA(Giu) implant, related to an increase in bone volume/tissue volume and trabecular thickness, cortical thickness and gene expression of osteocalcin and vascular cell adhesion molecule I, but a decreased gene expression of Wnt inhibitors, SOST and dickkopf homolog 1. The autonomous osteogenic effect of the PTHrP (107-111)-loaded HA(Giu) scaffolds was confirmed in mouse and human osteoblastic cell cultures. Our findings demonstrate the advantage of loading PTHrP (107-111) into degradable HA(GIu) scaffolds for achieving an optimal biomaterial that is promising for low load bearing clinical applications. (C) 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
Osteogenic potential of a biomaterial enriched with osteostatin and mesenchymal stem cells in osteoporotic rabbits
(Biomolecules, 2024) Luengo Alonso, Gonzalo; Bravo Giménez, Beatriz; Lozano Borregón, Daniel; Heras, Clara; Sánchez Salcedo, Sandra; Benito Garzón, Lorena; Abella, Mónica; Vallet Regí, María Dulce Nombre; Cecilia Lopez, David; Salinas Sánchez, Antonio Jesús
Mesoporous bioactive glasses (MBGs) of the SiO2–CaO–P2O5 system are biocompatible materials with a quick and effective in vitro and in vivo bioactive response. MBGs can be enhanced by including therapeutically active ions in their composition, by hosting osteogenic molecules within their mesopores, or by decorating their surfaces with mesenchymal stem cells (MSCs). In previous studies, our group showed that MBGs, ZnO-enriched and loaded with the osteogenic peptide osteostatin (OST), and MSCs exhibited osteogenic features under in vitro conditions. The aim of the present study was to evaluate bone repair capability after large bone defect treatment in distal femur osteoporotic rabbits using MBGs (76%SiO2–15%CaO–5%P2O5–4%ZnO (mol-%)) before and after loading with OST and MSCs from a donor rabbit. MSCs presence and/or OST in scaffolds significantly improved bone repair capacity at 6 and 12 weeks, as confirmed by variations observed in trabecular and cortical bone parameters obtained by micro-CT as well as histological analysis results. A greater effect was observed when OST and MSCs were combined. These findings may indicate the great potential for treating critical bone defects by combining MBGs with MSCs and osteogenic peptides such as OST, with good prospects for translation to clinical practice.