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Novel nanocomposite biomaterials with controlled copper/calcium release capability for bone tissue engineering multifunctional scaffolds.

ABSTRACT: This work aimed to develop novel composite biomaterials for bone tissue engineering (BTE) made of bioactive glass nanoparticles (Nbg) and alginate cross-linked with Cu(2+) or Ca(2+) (AlgNbgCu, AlgNbgCa, respectively). Two-dimensional scaffolds were prepared and the nanocomposite biomaterials were characterized in terms of morphology, mechanical strength, bioactivity, biodegradability, swelling capacity, release profile of the cross-linking cations and angiogenic properties. It was found that both Cu(2+) and Ca(2+) are released in a controlled and sustained manner with no burst release observed. Finally, in vitro results indicated that the bioactive ions released from both nanocomposite biomaterials were able to stimulate the differentiation of rat bone marrow-derived mesenchymal stem cells towards the osteogenic lineage. In addition, the typical endothelial cell property of forming tubes in Matrigel was observed for human umbilical vein endothelial cells when in contact with the novel biomaterials, particularly AlgNbgCu, which indicates their angiogenic properties. Hence, novel nanocomposite biomaterials made of Nbg and alginate cross-linked with Cu(2+) or Ca(2+) were developed with potential applications for preparation of multifunctional scaffolds for BTE.

SUBMITTER: Cattalini JP

PROVIDER: S-EPMC4614462 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Novel nanocomposite biomaterials with controlled copper/calcium release capability for bone tissue engineering multifunctional scaffolds.

Cattalini J P JP Hoppe A A Pishbin F F Roether J J Boccaccini A R AR Lucangioli S S Mouriño V V

Journal of the Royal Society, Interface 20150901 110

This work aimed to develop novel composite biomaterials for bone tissue engineering (BTE) made of bioactive glass nanoparticles (Nbg) and alginate cross-linked with Cu(2+) or Ca(2+) (AlgNbgCu, AlgNbgCa, respectively). Two-dimensional scaffolds were prepared and the nanocomposite biomaterials were characterized in terms of morphology, mechanical strength, bioactivity, biodegradability, swelling capacity, release profile of the cross-linking cations and angiogenic properties. It was found that bot ...[more]

PMID: 26269233

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Project description:Recent challenges in post-surgical bone tumor management have elucidated the need for a multifunctional scaffold, which can be used for residual tumor-cell suppression, defect repair, and simultaneous bone regeneration. In this perspective, 3D printing allows to create a wide variety of patient-specific implant with complex porous architecture and compatible mechanical strength to that of cancellous bone. Here, a multifunctional bone graft substitute is designed by incorporating the three primary soy isoflavones: genistein, daidzein, and glycitein onto a 3D printed (3DP) tricalcium phosphate (TCP) scaffolds with designed pores, endowing them with in vitro chemopreventive, bone-cell proliferating and immune-modulatory potential. The interconnected porosity and biodegradability of 3DP TCP ceramics have allowed controlled release kinetics of genistein, daidzein and glycitein in acidic and physiological buffer medium for 16 days, which is fitted with Korsmeyer-Peppas model. Presence of genistein, a well-known natural biomolecule shows a 90% reduction in vitro osteosarcoma (MG-63) cell viability and proliferation after 11 days. Meanwhile, daidzein, the other primary isoflavone, promotes in vitro cellular attachment and enhances viability and proliferation of human fetal osteoblast cell (hFOB). Furthermore, controlled release of genistein, daidzein, and glycitein from 3DP TCP scaffold demonstrates improved hFOB cell proliferation, viability, and differentiation in a dynamic flow-perfusion bioreactor, which is utilized to better simulate the clinical microenvironment. Finally, in vivo H&E staining confirms controlled co-delivery of genistein-daidzein-glycitein from 3DP scaffold carefully modulated neutrophil recruitment to the surgery site after 24 h of implantation in a rat distal femur model. These results advance our understanding towards multipronged therapeutic approaches utilizing synthetic bone graft substitutes as a drug delivery vehicle, and more importantly, demonstrate the feasibility of localized tumor cell suppression and bone cell proliferation for post-surgical defect repair application. STATEMENT OF SIGNIFICANCE: Designed multimodal porosity of 3D printed TCP scaffold allows a controlled and sustained release of soy isoflavones, genistein, daidzein and glycitein in both physiological and acidic pH. Presence of genistein shows 90% reduction in vitro bone cancer cell viability and proliferation. Meanwhile, controlled release of genistein, daidzein, and glycitein from 3DP TCP scaffolds demonstrate improved osteoblast cell proliferation, viability, and differentiation in static and dynamic flow-perfusion bioreactor. Furthermore, H&E staining at 24 h post-surgical specimens from rat distal femur model shows neutrophil recruitment at the surgery site is significantly decreased, suggesting the anti-inflammatory property of soy isoflavones. This work provides deeper understanding on the design of a multifunctional 3D printed patient-specific scaffold with enhanced in vitro chemopreventive, osteogenic and in vivo anti-inflammatory ability.

Dataset Information

Novel nanocomposite biomaterials with controlled copper/calcium release capability for bone tissue engineering multifunctional scaffolds.

Publications

Novel nanocomposite biomaterials with controlled copper/calcium release capability for bone tissue engineering multifunctional scaffolds.

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