Capacitive interdigitated system of high osteoinductive/conductive performance for personalized acting-sensing implants

Abstract

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.

Multiscale Sensing of Bone-Implant Loosening for Multifunctional Smart Bone Implants: Using Capacitive Technologies for Precision Controllability

“…Furthermore, many research efforts have been conducted to develop more sophisticated bioactive biomaterials for coating uncemented implants [ 14 , 15 ]. Even so, these methodologies will not conduct optimal bone–implant fixation states, mainly due to their inability to consider the bone–implant fixation state to personalize bioactivity [ 16 , 17 , 18 ]. So, an effective monitoring of the bone–implant fixation is required to minimize revision surgeries.…”

“…These methods have low accuracy in detecting early loosening stages and cannot be performed throughout the daily life of patients. By consequence, they cannot establish high-performance osteoinduction and osteoconduction processes according to personalized requirements [ 18 , 19 ]. Instrumented multifunctional implants hold the potential to monitor the bone–implant interface and deliver personalized stimulation to peri-implant tissues [ 7 , 20 , 21 ].…”

“…Indeed, the following problems still need to be addressed [ 19 ]: (i) provide flexible integration to sensing systems inside the instrumented implants; (ii) provide an easy way to redesign the detection technologies for different geometries of implant surfaces; (iii) provide target-oriented monitoring of peri-implant regions; (iv) provide continuous monitoring of patients during their quotidian life. Soares dos Santos et al [ 7 , 18 , 20 ] recently proposed cosurface capacitive technologies both to deliver electrical stimuli to bone structures and to monitor bone–implant fixation states. They found promising in vitro results to enhance osteoconduction and to detect both macro-scale and micro-scale biointerface bone loss.…”

“…They found promising in vitro results to enhance osteoconduction and to detect both macro-scale and micro-scale biointerface bone loss. Furthermore, these capacitive systems are low cost and non-complex architectures, well-suited for multiple implant surfaces and with the ability to perform stimulating-sensing operations in target bone regions [ 18 , 20 ]. Therefore, they demonstrated the ability to overcome the limitations of the previously proposed sensing methodologies.…”

Current Development in Interdigital Transducer (IDT) Surface Acoustic Wave Devices for Live Cell In Vitro Studies: A Review

“…Therefore, it has recently stimulated interest as a tool for manipulating, coordinating, organising, and characterising cell properties. For instance, mechanical stimuli such as cyclic stretching [3], fluid shear stress [4], electrical [5] and magnetic fields [6], substrate stimulation [7], and acoustic waves technique [8] have been used to address a variety of challenges in biomedical research, especially in the fields of clinical diagnostics and therapy.…”