Bacterial cellulose membrane functionalized with hydroxiapatite and anti-bone morphogenetic protein 2: A promising material for bone regeneration.

Fernanda Coelho,Alexandra Ivo De Medeiros,Ticiana Sidorenko De Oliveira Capote,Letícia De Aquino Penteado,Maurício Cavicchioli,Sybele Saska Specian,Raquel Mantuaneli Scarel-Caminaga,Sidney José De Lima Ribeiro,Masaya Yamamoto

doi:10.1371/journal.pone.0221286

Fernanda Coelho, Alexandra Ivo De Medeiros + Show 7 more

Open Access

https://doi.org/10.1371/journal.pone.0221286

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Journal: PloS one	Publication Date: Aug 19, 2019
Citations: 36	License type: CC BY 4.0

Affiliation: Universidade Estadual Paulista (Unesp)

Abstract

Bone tissue engineering seeks to adequately restore functions related to physical and biological properties, aiming at a repair process similar to natural bone. The use of compatible biopolymers, such as bacterial cellulose (BC), as well as having interesting mechanical characteristics, presents a slow in vivo degradation rate, and the ability to be chemically modified. To promote better bioactivity towards BC, we synthesized an innovative BC membrane associated to hydroxyapatite (HA) and anti-bone morphogenetic protein antibody (anti-BMP-2) (BC-HA-anti-BMP-2). We present the physical-chemical, biological and toxicological characterization of BC-HA-anti-BMP-2. Presence of BC and HA components in the membranes was confirmed by SEM-EDS and FTIR assays. No toxic potential was found in MC3T3-E1 cells by cytotoxicity assays (XTT Assay and Clonogenic Survival), genotoxicity (Comet Assay) and mutagenicity (Cytokinesis-blocked micronucleus Test). The in vitro release kinetics of anti-BMP-2 antibodies detected gradually reducing antibody levels, reducing approximately 70% in 7 days and 90% in 14 days. BC-HA-anti-BMP-2 increased SPP1, BGLAP, VEGF, ALPL, RUNX2 and TNFRSF11B expression, genes involved in bone repair and also increased mineralization nodules and phosphatase alcalin (ALP) activity levels. In conclusion, we developed BC-HA-anti-BMP-2 as an innovative and promising biomaterial with interesting physical-chemical and biological properties which may be a good alternative to treatment with commercial BMP-2 protein.

Highlights

Bone regeneration is a complex multiple event process that includes necrotic bone tissue and clot reabsorption subsequent to trauma
We found that bacterial cellulose (BC)-HA-anti-Bone morphogenetic proteins (BMPs)-2 enhanced the expression of several genes involved in bone repair, and increased both mineralization nodules and alkaline phosphatase (ALP) activity suggesting that bacterial celulose/hydroxyapatite membranes (BC-HA)-anti-BMP-2 is an innovative and promising biomaterial when combined with BMP-2 protein in bone regeneration therapy
energy dispersive X-ray spectroscopy (EDS) data showed that qualitatively measured Ca/P molar ratios are in agreement with observed HA crystal morphology for BC-HA

Summary

Introduction

Bone regeneration is a complex multiple event process that includes necrotic bone tissue and clot reabsorption subsequent to trauma. A promising material for bone regeneration inflammatory process that facilitates the release of growth factors that assist in cell differentiation, and in the formation of bone tissue [1]. The bone regeneration process runs without complications (90 to 95%) [2]. Prolonged bone defects following trauma or resection of cancer or unbound fractures may require more sophisticated treatment. In these cases, a combination of bone substitutes, such as biomaterials, with living cells/tissues or the use of these biomaterials alone may be appropriate [3]

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