resumo
Replacement orthopedic surgeries are among the most common surgeries worldwide, but clinically used passive implants cannot prevent failure rates and inherent revision arthroplasties. Optimized non-instrumented implants, resorting to preclinically tested bioactive coatings, improve initial osseointegration but lack long-term personalized actuation on the bone-implant interface. Novel bioelectronic devices comprising biophysical stimulators and sensing systems are thus emerging, aiming for long-term control of peri-implant bone growth through biointerface monitoring. These acting-sensing dual systems require high frequency (HF) operations able to stimulate osteoinduction/osteoconduction, including matrix maturation and mineralization. A sensing-compatible capacitive stimulator of thin interdigitated electrodes and delivering an electrical 60 kHz HF stimulation, 30 min/day, is here shown to promote osteoconduction in pre-osteoblasts and osteoinduction in human adipose-derived mesenchymal stem cells (hASCs). HF stimulation through this capacitive interdigitated system had significant effects on osteoblasts' collagen-I synthesis, matrix, and mineral deposition. A proteomic analysis of microvesicles released from electrically-stimulated osteoblasts revealed regulation of osteodifferentiation and mineralization-related proteins (e.g. Tgfb3, Ttyh3, Itih1, Aldh1a1). Proteomics data are available via ProteomeXchange with the identifier PXD028551. Further, under HF stimulation, hASCs exhibited higher osteogenic commitment and enhanced hydroxyapatite deposition. These promising osteoinductive/conductive capacitive stimulators will integrate novel bioelectronic implants able to monitor the bone-implant interface and deliver personalized stimulation to peri-implant tissues.
palavras-chave
TOTAL HIP-ARTHROPLASTY; ELECTRICAL-STIMULATION; EXTRACELLULAR VESICLES; ORTHOPEDIC IMPLANTS; KNEE REPLACEMENT; MATRIX VESICLES; GENE-EXPRESSION; BONE-FORMATION; UP-REGULATION; STEM-CELLS
categoria
Cell & Tissue Engineering; Engineering, Biomedical
autores
de Sousa, BM; Correia, CR; Ferreira, JAF; Mano, JF; Furlani, EP; dos Santos, MPS; Vieira, SI
nossos autores
Clara R. Correia
Investigador
João Mano
Vice-Diretoragradecimentos
This work was funded by the Fundacao para a Ciencia e a Tecnologia (FCT) through the fellowship SFRH/BPD/117475/2016, support to the Centre for Mechanical Technology & Automation (TEMA; UID/EMS/00481/2019) and to the Institute of Biomedicine (iBiMED; UID/BIM/04501/2019). B. M. de Sousa acknowledges the financial support from FCT through the PhD research scholarship 2020.06525.BD. The authors also acknowledge the support of: the European Research Council (ERC) for project ATLAS (grant agreement ERC-H20202014-ADG-669858); FCT and CENTRO2020 to TEMA via research project POCI-01-0145-FEDER-031132 and CEN-TRO01-0145-FEDER-022083, respectively; the Aveiro Institute of Materials-CICECO (UIDB/50011/2020 & UIDP/50011/2020 financed by national funds through the FCT/MCTES) and the LiM Bioimaging Facility-a PPBI node (POCI-01-0145-FEDER022122). The mass spectrometry technique was performed at the Proteomics i3S Scientific Platform with the assistance of Dr. Hugo Oso ' rio. This work had support from the Portuguese Mass Spectrometry Network, integrated in the National Roadmap of Research Infrastructures of Strategic Relevance (ROTEIRO/0028/2013; LISBOA-01-0145-FEDER-022125).