Nalesso Paulo Roberto Lopes, Vedovatto Matheus, Gregório Julia Eduarda Schneider, Huang Boyang, Vyas Cian, Santamaria-Jr Milton, Bártolo Paulo, Caetano Guilherme Ferreira
Graduate Program in Biomedical Sciences, University Centre of Hermínio Ometto Foundation, Araras 13607-339, SP, Brazil.
Singapore Centre for 3D Printing, School of Mechanical and Aerospace Engineering, Nanyang Technological University, Jurong West, Singapore 639798, Singapore.
Polymers (Basel). 2023 Jul 5;15(13):2952. doi: 10.3390/polym15132952.
The development of advanced biomaterials and manufacturing processes to fabricate biologically and mechanically appropriate scaffolds for bone tissue is a significant challenge. Polycaprolactone (PCL) is a biocompatible and degradable polymer used in bone tissue engineering, but it lacks biofunctionalization. Bioceramics, such as hydroxyapatite (HA) and β tricalcium phosphate (β-TCP), which are similar chemically to native bone, can facilitate both osteointegration and osteoinduction whilst improving the biomechanics of a scaffold. Carbon nanotubes (CNTs) display exceptional electrical conductivity and mechanical properties. A major limitation is the understanding of how PCL-based scaffolds containing HA, TCP, and CNTs behave in vivo in a bone regeneration model. The objective of this study was to evaluate the use of three-dimensional (3D) printed PCL-based composite scaffolds containing CNTs, HA, and β-TCP during the initial osteogenic and inflammatory response phase in a critical bone defect rat model. Gene expression related to early osteogenesis, the inflammatory phase, and tissue formation was evaluated using quantitative real-time PCR (RT-qPCR). Tissue formation and mineralization were assessed by histomorphometry. The CNT+HA/TCP group presented higher expression of osteogenic genes after seven days. The CNT+HA and CNT+TCP groups stimulated higher gene expression for tissue formation and mineralization, and pro- and anti-inflammatory genes after 14 and 30 days. Moreover, the CNT+TCP and CNT+HA/TCP groups showed higher gene expressions related to M1 macrophages. The association of CNTs with ceramics at 10wt% (CNT+HA/TCP) showed lower expressions of inflammatory genes and higher osteogenic, presenting a positive impact and balanced cell signaling for early bone formation. The association of CNTs with both ceramics promoted a minor inflammatory response and faster bone tissue formation.
开发先进的生物材料和制造工艺以制造适合骨组织的生物和机械性能的支架是一项重大挑战。聚己内酯（PCL）是一种用于骨组织工程的生物相容性和可降解聚合物，但它缺乏生物功能化。生物陶瓷，如羟基磷灰石（HA）和β-磷酸三钙（β-TCP），其化学性质与天然骨相似，可以促进骨整合和骨诱导，同时改善支架的生物力学性能。碳纳米管（CNT）具有卓越的导电性和机械性能。一个主要的限制是了解含有HA、TCP和CNT的基于PCL的支架在骨再生模型中的体内行为。本研究的目的是在严重骨缺损大鼠模型的初始成骨和炎症反应阶段，评估包含CNT、HA和β-TCP的三维（3D）打印基于PCL的复合支架的应用。使用定量实时PCR（RT-qPCR）评估与早期成骨、炎症阶段和组织形成相关的基因表达。通过组织形态计量学评估组织形成和矿化。CNT+HA/TCP组在7天后呈现出更高的成骨基因表达。CNT+HA和CNT+TCP组在14天和30天后刺激了更高的组织形成和矿化相关基因表达以及促炎和抗炎基因表达。此外，CNT+TCP和CNT+HA/TCP组显示出与M1巨噬细胞相关的更高基因表达。10wt%的CNT与陶瓷的组合（CNT+HA/TCP）显示出更低的炎症基因表达和更高的成骨作用，对早期骨形成具有积极影响并平衡细胞信号传导。CNT与两种陶瓷的组合促进了轻微的炎症反应和更快的骨组织形成。
