Development of 3D printed scaffolds for bone reconstruction and evaluation of interaction through cellular study

• Grant number: 19/23027-8
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: March 01, 2020
• End date: February 28, 2021
• Field of knowledge: Engineering - Materials and Metallurgical Engineering - Nonmetallic Materials
• Principal Investigator: Luiz Henrique Capparelli Mattoso
• Grantee: Marcela Piassi Bernardo
• Supervisor: Martin Zenke
• Host Institution: Embrapa Instrumentação Agropecuária. Empresa Brasileira de Pesquisa Agropecuária (EMBRAPA). Ministério da Agricultura, Pecuária e Abastecimento (Brasil). São Carlos , SP, Brazil
• Institution abroad: Uniklinik RWTH Aachen, Germany
• Associated to the scholarship: 18/07860-9 - Development of nanocomposite polymer filaments with anti-inflammatory properties for 3D printing as bone substituent, BP.PD

Abstract

There is a growing number of bone injury cases worldwide requiring effective surgical procedures. Biomaterial nanocomposites are promising materials for bone tissue engineering due to the possibility to combine both the appropriate polymer matrix and inorganic filler to obtain material with biocompatibility, bio absorption and mechanical resistance properties to be used as bone substituents. Rapid prototyping techniques (3D printing) have become popular, making possible to fabricate bone implant structures with complex shapes at a suitable scale. One of the main techniques with equipment already available in the market is based on polymer filaments melting, specifically, the fusion deposition modelling (FDM) 3D printing. However, pure polymer filaments are limited due to the lack of functional and biological properties. Nanocomposites filaments (poly-(lactic acid)-PLA and hydroxyapatite) have been developed for FDM 3D printer. Physico-chemical, morphological and mechanical properties have been already studied for the scaffolds developed for this project. Still for the complete success of this work, it is necessary a complete study of the interactions between the scaffolds and the cells: reactions from the immune system cells; induction of differentiation of mesenchymal stem cells (MSC) into osteoblast, besides the biocompatibility and cytotoxicity assays. The scaffold material composition may significantly influence on both cellular behaviors and the efficacy of the bone graft. In order to understand the cell interaction with 3D printed scaffolds, this project will be centered (i) on the derivation of functionally homogenous mesenchymal stem cells (MSC) from human pluripotent stem cells (iPS cells) and the analysis of their osteogenic differentiation potential and (ii) the immune response of dendritic cells to 3D printed scaffold. The use of iPS cells will establish the basis for a personalized treatment of bone defects for example after accidents or other injuries, trauma, infections and tumor resection. This study will be based on flow cytometry, confocal laser scanning microscopy (CLSM), live cell imaging, total internal reflection fluorescence (TIRF) microscopy and RT-PCR. It will take full advantage of the expertise of the group of Prof. M. Zenke and Dr. A. Sechi, of Institute of Biomedical Engineering, RWTH Aachen University, Germany, which is a reference group for studies on biomaterial-cell interactions. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

BLANCO, GUILHERME E. DE O.; DE SOUZA, CLOVIS W. O.; BERNARDO, MARCELA P.; ZENKE, MARTIN; MATTOSO, LUIZ H. C.; MOREIRA, FRANCYS K. V.. Antimicrobially active gelatin/[Mg-Al-CO3 ]-LDH composite films based on clove essential oil for skin wound healing. MATERIALS TODAY COMMUNICATIONS, v. 27, JUN 2021. (19/23027-8, 18/07860-9)

BERNARDO, MARCELA P.; DA SILVA, BRUNA C. R.; HAMOUDA, I, AHMED E.; DE TOLEDO, MARCELO A. S.; SCHALLA, CARMEN; RUTTEN, STEPHAN; GOETZKE, ROMAN; MATTOSO, LUIZ H. C.; ZENKE, MARTIN; SECHI, ANTONIO. LA/Hydroxyapatite scaffolds exhibit in vitro immunological inertness and promote robust osteogenic differentiation of human mesenchymal stem cells without osteogenic stimul. SCIENTIFIC REPORTS, v. 12, n. 1, FEB 11 2022. (18/07860-9, 19/23027-8)