Silane-modified hydroxyapatite nanoparticles incorporated into polydioxanone/poly(lactide- co-caprolactone) creates a novel toughened nanocomposite with improved material properties and in vivo inflammatory responses

将硅烷改性的羟基磷灰石纳米粒子掺入聚二氧化酮/聚(丙交酯-共-己内酯)中,可形成一种新型增韧纳米复合材料,具有改善的材料性能和体内炎症反应

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作者:Behzad Shiroud Heidari, Emma Muinos Lopez, Peilin Chen, Rui Ruan, Ebrahim Vahabli, Seyed Mohammad Davachi, Froilán Granero-Moltó, Elena M De-Juan-Pardo, Minghao Zheng, Barry Doyle

Abstract

The interface tissue between bone and soft tissues, such as tendon and ligament (TL), is highly prone to injury. Although different biomaterials have been developed for TL regeneration, few address the challenges of the TL-bone interface. Here, we aim to develop novel hybrid nanocomposites based on poly(p-dioxanone) (PDO), poly(lactide-co-caprolactone) (LCL), and hydroxyapatite (HA) nanoparticles suitable for TL-bone interface repair. Nanocomposites, containing 3-10% of both unmodified and chemically modified hydroxyapatite (mHA) with a silane coupling agent. We then explored biocompatibility through in vitro and in vivo studies using a subcutaneous mouse model. Through different characterisation tests, we found that mHA increases tensile properties, creates rougher surfaces, and reduces crystallinity and hydrophilicity. Morphological observations indicate that mHA nanoparticles are attracted by PDO rather than LCL phase, resulting in a higher degradation rate for mHA group. We found that adding the 5% of nanoparticles gives a balance between the properties. In vitro experiments show that osteoblasts' activities are more affected by increasing the nanoparticle content compared with fibroblasts. Animal studies indicate that both HA and mHA nanoparticles (10%) can reduce the expression of pro-inflammatory cytokines after six weeks of implantation. In summary, this work highlights the potential of PDO/LCL/HA nanocomposites as an excellent biomaterial for TL-bone interface tissue engineering applications.

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