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Acta Biomater. 2019 Apr 6. pii: S1742-7061(19)30253-3. doi: 10.1016/j.actbio.2019.04.019. [Epub ahead of print]

Mesoporous bioactive glass/ɛ-polycaprolactone scaffolds promote bone regeneration in osteoporotic sheep.

Author information

1
Departamento de Química en Ciencias Farmacéuticas, Facultad de Farmacia, Universidad Complutense de Madrid, Instituto de Investigación Sanitaria Hospital, 12 de Octubre i+12, Plaza Ramón y Cajal s/n, 28040 Madrid, Spain; CIBER de Bioingeniería Biomateriales y Nanomedicina (CIBER-BBN), Spain.
2
Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Químicas, Universidad Complutense de Madrid, Instituto de Investigación Sanitaria Hospital Clínico San Carlos (IdISSC), 28040 Madrid, Spain.
3
Servicio de Anatomía Patológica. Hospital Clínico San Carlos, Facultad de Medicina Universidad Complutense de Madrid, Instituto de Investigación Sanitaria Hospital Clínico San Carlos (IdISSC), 28040 Madrid, Spain.
4
Centro de Cirugía de Mínima Invasión Jesús Usón, Cáceres, Spain.
5
Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Químicas, Universidad Complutense de Madrid, Instituto de Investigación Sanitaria Hospital Clínico San Carlos (IdISSC), 28040 Madrid, Spain. Electronic address: portoles@quim.ucm.es.
6
Departamento de Química en Ciencias Farmacéuticas, Facultad de Farmacia, Universidad Complutense de Madrid, Instituto de Investigación Sanitaria Hospital, 12 de Octubre i+12, Plaza Ramón y Cajal s/n, 28040 Madrid, Spain; CIBER de Bioingeniería Biomateriales y Nanomedicina (CIBER-BBN), Spain. Electronic address: arcosd@ucm.es.
7
Departamento de Química en Ciencias Farmacéuticas, Facultad de Farmacia, Universidad Complutense de Madrid, Instituto de Investigación Sanitaria Hospital, 12 de Octubre i+12, Plaza Ramón y Cajal s/n, 28040 Madrid, Spain; CIBER de Bioingeniería Biomateriales y Nanomedicina (CIBER-BBN), Spain. Electronic address: vallet@ucm.es.

Abstract

Macroporous scaffolds made of a SiO2-CaO-P2O5 mesoporous bioactive glass (MBG) and ɛ-polycaprolactone (PCL) have been prepared by robocasting. These scaffolds showed an excellent in vitro biocompatibility in contact with osteoblast like cells (Saos 2) and osteoclasts derived from RAW 264.7 macrophages. In vivo studies were carried out by implantation into cavitary defects drilled in osteoporotic sheep. The scaffolds evidenced excellent bone regeneration properties, promoting new bone formation at both the peripheral and the inner parts of the scaffolds, thick trabeculae, high vascularization and high presence of osteoblasts and osteoclasts. In order to evaluate the effects of the local release of an antiosteoporotic drug, 1% (%wt) of zoledronic acid was incorporated to the scaffolds. The scaffolds loaded with zoledronic acid induced apoptosis in Saos 2 cells, impeded osteoclast differentiation in a time dependent manner and inhibited bone healing, promoting an intense inflammatory response in osteoporotic sheep. STATEMENT OF SIGNIFICANCE: In addition to an increase in bone fragility and susceptibility to fracture, osteoporosis also hinders the clinical success of endosseous implants and grafting materials for the treatment of bone defects. For the first time, macroporous scaffolds made of mesoporous bioactive glass and ε-caprolactone have been evaluated in a sheep model that mimics the osteoporosis conditions in humans. These implants fostered bone regeneration, promoting new bone formation at both the peripheral and the inner parts of the scaffolds, showing thick trabeculae and a high vascularization degree. Our results indicate that macroporous structures containing highly bioactive mesoporous glasses could be excellent candidates for the regenerative treatment of bone defects in osteoporotic patients.

KEYWORDS:

Bone regeneration; Mesoporous bioactive glass; Osteoporosis; Scaffolds; Zoledronic acid

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