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迈向一种颠覆性的、微创的小指关节植入物概念:体内细胞与材料的相互作用。

Toward a disruptive, minimally invasive small finger joint implant concept: Cellular and molecular interactions with materials in vivo.

作者信息

Ben Amara Heithem, Farjam Pardis, Lutz Theresa M, Omar Omar, Palmquist Anders, Lieleg Oliver, Browne Martin, Taylor Andy, Verkerke Gijsbertus J, Rouwkema Jeroen, Thomsen Peter

机构信息

Department of Biomaterials, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sweden.

Department of Biomechanical Engineering, Faculty of Engineering Technology, University of Twente, Enschede, the Netherlands.

出版信息

Acta Biomater. 2024 Jul 15;183:130-145. doi: 10.1016/j.actbio.2024.05.042. Epub 2024 May 28.

Abstract

Osteoarthritis (OA) poses significant therapeutic challenges, particularly OA that affects the hand. Currently available treatment strategies are often limited in terms of their efficacy in managing pain, regulating invasiveness, and restoring joint function. The APRICOT implant system developed by Aurora Medical Ltd (Chichester, UK) introduces a minimally invasive, bone-conserving approach for treating hand OA (https://apricot-project.eu/). By utilizing polycarbonate urethane (PCU), this implant incorporates a caterpillar track-inspired design to promote the restoration of natural movement to the joint. Surface modifications of PCU have been proposed for the biological fixation of the implant. This study investigated the biocompatibility of PCU alone or in combination with two surface modifications, namely dopamine-carboxymethylcellulose (dCMC) and calcium-phosphate (CaP) coatings. In a rat soft tissue model, native and CaP-coated PCU foils did not increase cellular migration or cytotoxicity at the implant-soft tissue interface after 3 d, showing gene expression of proinflammatory cytokines similar to that in non-implanted sham sites. However, dCMC induced an amplified initial inflammatory response that was characterized by increased chemotaxis and cytotoxicity, as well as pronounced gene activation of proinflammatory macrophages and neoangiogenesis. By 21 d, inflammation subsided in all the groups, allowing for implant encapsulation. In a rat bone model, 6 d and 28 d after release of the periosteum, all implant types were adapted to the bone surface with a surrounding fibrous capsule and no protracted inflammatory response was observed. These findings demonstrated the biocompatibility of native and CaP-coated PCU foils as components of APRICOT implants. STATEMENT OF SIGNIFICANCE: Hand osteoarthritis treatments require materials that minimize irritation of the delicate finger joints. Differing from existing treatments, the APRICOT implant leverages polycarbonate urethane (PCU) for minimally invasive joint replacement. This interdisciplinary, preclinical study investigated the biocompatibility of thin polycarbonate urethane (PCU) foils and their surface modifications with calcium-phosphate (CaP) or dopamine-carboxymethylcellulose (dCMC). Cellular and morphological analyses revealed that both native and Ca-P coated PCU elicit transient inflammation, similar to sham sites, and a thin fibrous encapsulation in soft tissues and on bone surfaces. However, dCMC surface modification amplified initial chemotaxis and cytotoxicity, with pronounced activation of proinflammatory and neoangiogenesis genes. Therefore, native and CaP-coated PCU possess sought-for biocompatible properties, crucial for patient safety and performance of APRICOT implant.

摘要

骨关节炎(OA)带来了重大的治疗挑战,尤其是影响手部的OA。目前可用的治疗策略在控制疼痛、调节侵入性和恢复关节功能方面的疗效往往有限。奥罗拉医疗有限公司(英国奇切斯特)开发的APRICOT植入系统引入了一种微创、保留骨组织的方法来治疗手部OA(https://apricot-project.eu/)。通过使用聚碳酸酯聚氨酯(PCU),这种植入物采用了受履带启发的设计,以促进关节自然运动的恢复。已有人提出对PCU进行表面改性以实现植入物的生物固定。本研究调查了单独的PCU或与两种表面改性(即多巴胺-羧甲基纤维素(dCMC)和磷酸钙(CaP)涂层)组合后的生物相容性。在大鼠软组织模型中,天然PCU箔和CaP涂层PCU箔在3天后并未增加植入物-软组织界面处的细胞迁移或细胞毒性,其促炎细胞因子的基因表达与未植入的假手术部位相似。然而,dCMC引发了放大的初始炎症反应,其特征为趋化性增加和细胞毒性增强,以及促炎巨噬细胞和新生血管生成的明显基因激活。到21天时,所有组的炎症均消退,植入物被包裹。在大鼠骨模型中,骨膜松解后6天和28天,所有类型的植入物均与骨表面适应,周围有纤维囊,未观察到持久的炎症反应。这些发现证明了天然PCU箔和CaP涂层PCU箔作为APRICOT植入物组件的生物相容性。重要性声明:手部骨关节炎治疗需要能将对手指关节的刺激降至最低的材料。与现有治疗方法不同,APRICOT植入物利用聚碳酸酯聚氨酯(PCU)进行微创关节置换。这项跨学科的临床前研究调查了薄聚碳酸酯聚氨酯(PCU)箔及其用磷酸钙(CaP)或多巴胺-羧甲基纤维素(dCMC)进行表面改性后的生物相容性。细胞和形态学分析表明,天然PCU和Ca-P涂层PCU均引发短暂炎症,与假手术部位相似,并在软组织和骨表面形成薄纤维包裹。然而,dCMC表面改性放大了初始趋化性和细胞毒性,促炎和新生血管生成基因明显激活。因此,天然PCU和CaP涂层PCU具有理想的生物相容性特性,这对患者安全和APRICOT植入物的性能至关重要。

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