Study and development of a novel radio frequency electromedical device for the treatment of peri-implantitis: experimental performance analysis, modelling of the electromagnetic interaction with tissues and in vitro and in vivo evaluation

La peri-implantite (PI) è una grave patologia che interessa tessuti peri-implantari molli e duri. Ad oggi, la prevenzione è l’unico mezzo per contrastarla. Recentemente, è stata sperimentata una terapia basata sulla somministrazione di corrente elettrica a radio frequenza (successo: 81%). Il trattamento è stato simulato numericamente, fornendo le distribuzioni di corrente (EC) e campo elettrico (EF) nei tessuti: l’effetto anti-infiammatorio è attribuibile alla EC, quello di rigenerazione ossea al EF. Sono state considerate le misure di bioimpedenza (BM) per individuare le infiammazioni; numericamente si sono osservati cambiamenti nel modulo di impedenza del 4-20% (secondo diversi parametri), anche più alti sperimentalmente (35% infiammazione, 56% PI). Le BM permettono quindi di identificare il tessuto da trattare. Per la ripetibilità, sono state considerate radici di denti naturali, numericamente e sperimentalmente; l’ordine di grandezza è lo stesso (qualche kΩ), anche se ci sono differenze legate alle condizioni di misura. La variabilità intra-soggetto è il 10% in uno stesso giorno, fino al 26% in giorni diversi; quella inter-soggetto è più alta. La sicurezza elettrica è stata attentamente esaminata e si sono individuate le direttive applicabili (IEC 60601-1, 60601-1-2 and 60601-2-2). Sono stati fatti test in vitro per valutare l’effetto della terapia sulla vitalità cellulare: non c’è un significativo aumento della necrosi (vitalità: 85% test, 94% controlli), l’effetto negativo principale è l’apoptosi. Sono stati numericamente indagati possibili effetti termici: non sono stati individuati riscaldamenti nocivi dei tessuti. Si è progettato un nuovo dispositivo (PeriCare®) per trattare la PI, con parti diagnostica (BM) e terapeutica. Si stanno progettando elettrodi specifici e realizzando il prototipo. Si sta compilando il fascicolo tecnico e pianificando i test di conformità, in vista della certificazione. Il dispositivo medico dovrebbe entrare nel mercato entro l’anno.Peri-implantitis is a severe disease affecting hard and soft peri-implant tissues. At present, prevention is the only means to contrast it. Recently, a therapy based on the administration of radio frequency electric current was experimented (success rate: 81%). The treatment was numerically simulated, providing the electric current (EC) and field (EF) distributions in peri-implant tissues: the anti-inflammatory effect can be associated to EC, the bone regeneration to the EF. Bioimpedance measurements (BM) were investigated to detect inflammation; changes in the measured impedance modulus are equal to 4-20% (depending on different parameters) from numerical results, also more evident experimentally (35% inflammation, 56% peri-implantitis). So, BM could allow to detect the tissue to be treated. To evaluate the repeatability, natural tooth roots were numerically and experimentally measured; the order of magnitude is the same (some kΩ), even if there are differences probably due to the measurement conditions. Intra-subject variability was of 10% in the same day, but up to 26% in different days; inter-subject variability was higher. The electrical safety was accurately taken into account. The applicable directives were individuated (IEC 60601-1, 60601-1-2 and 60601-2-2). In vitro tests were carried out to evaluate the effect of the therapy on cell vitality: there is not a significant increase in necrosis (vitality: 85% tests, 94% controls), the main negative effect is apoptosis. Possible thermal effects were numerically investigated: no dangerous tissue heating was observed. A new device for the peri-implantitis treatment, PeriCare®, was designed, with diagnostic (BM) and therapeutic parts. Proper electrodes are being designed and the prototype is being realized. The technical file is being compiled and the conformity verification tests are being planned towards the certification process. Hopefully, the medical device will be placed into the market within this year

Southwest Research Institute assistance to NASA in biomedical areas of the technology utilization program Final report, 1 Feb. 1969 - 24 Aug. 1970

Research progress in technology transfer by NASA Biomedical Application Tea

Doctor of Philosophy

dissertationDiabetes mellitus affects 5% of the world's population and requires constant monitoring to avoid fatality. Tight control of blood glucose levels has shown to reduce the long-term effects of diabetes. Finger-stick blood glucose measurements are the gold standard for glucose monitoring that are painful and only provide intermittent glucose values. Continuous glucose monitoring (CGM) is an improvement in this technology but is severely limited in its performance abilities beyond the currently approved implantation time lasting up to a week. CGM is still performed as an adjunct to finger-stick measurements since they are unreliable even during the approved usage durations. Implantation of a biomaterial induces a wound (catheter, hernia meshes, etc.) or disturbance in local tissue (contact lens, etc.). Wound healing response in the host mediates the formation of scar tissue and healing of the injury site. Host foreign body response (FBR) deviates from its healing response in the presence of a foreign body i.e, an implant, and tries to isolate it from the host via fibrous encapsulation. FBR is considered as one of the primary reasons for CGM sensor failure. FBR encapsulates the sensor implant, creating a barrier between the sensing electrode and essential analytes (glucose, oxygen, etc.) required for measuring glucose levels. This phenomenon results in painful and expensive CGM sensor replacements. Work described in this dissertation focuses on improving the clinical performance of CGM sensors by extending their functional lifetimes. Combination device strategies involving the use of a drug (dexamethasone, etc.), or a biologic (VEGF, siRNA, etc.), or a combination of these have been studied to reduce implant-associated FBR. In this dissertation, we targeted mast cells that are believed to orchestrate the FBR by secreting several key granules containing inflammatory cytokines, vasodilators, chemokines, etc. that result in an increased influx of inflammatory cells to the wound site. A novel tyrosine kinase inhibitor- masitinib was used to target the c-KIT receptor on the cell surface of mast cells. Stem cell factor and its ligand c-KIT are considered critical for mast cell survival, proliferation, and degranulation and the hypothesis driving this research is that targeting mast cell degranulation via the c-KIT pathway results in a reduced foreign body response. To test our hypothesis, we developed a local drug delivery formulation comprised of PLGA microsphere drug carriers embedded in a PEG matrix around implants. The effect of the drug was initially evaluated in wild-type (mast cell competent) and sash (mast cell-deficient) mice for up to 28 days. The results from these studies confirmed previous claims that mast cells play an important role in mediating FBR-associated fibrosis around implanted biomaterials and that the use of a mast cell stabilizing tyrosine kinase inhibitor reduced fibrous capsule thickness around implants in wild-type mice but had no effect in sash mice. The drug-releasing coating was then tested in CGM sensors in a wild-type murine percutaneous model for 21 days. Results from the CGM study indicate that drug-releasing coated sensors exhibit relatively stable response compared to control implants, suggesting that reduced fibrosis resulting from stabilizing mast cells results in improving CGM performance. The translation of these results to human subjects would enable better control of diabetes and provide the ability to better diagnose long-term effects of diabetes through long-term continuous glucose monitoring

Biomedical Engineering

Biomedical engineering is currently relatively wide scientific area which has been constantly bringing innovations with an objective to support and improve all areas of medicine such as therapy, diagnostics and rehabilitation. It holds a strong position also in natural and biological sciences. In the terms of application, biomedical engineering is present at almost all technical universities where some of them are targeted for the research and development in this area. The presented book brings chosen outputs and results of research and development tasks, often supported by important world or European framework programs or grant agencies. The knowledge and findings from the area of biomaterials, bioelectronics, bioinformatics, biomedical devices and tools or computer support in the processes of diagnostics and therapy are defined in a way that they bring both basic information to a reader and also specific outputs with a possible further use in research and development

Blood protein and platelet interactions on surface engineered biomaterials

Modification of surfaces to improve the thrombo-resistance of a synthetic biomaterial is a vital aspect in the design of haemocompatible surfaces. Recent work suggests a non-haemocompatible surface may ubiquitously adsorb specific plasma proteins that form a proteinacious layer which mediates the adhesion and activation of platelets and rejection of the material and subsequently, the implanted medical device. Currently, apart from surface chemistry and wetability of the surface, preferential adsorption of specific proteins, their exact interaction and the effect of physical and spatial cues from the nano-environment prevents us from acknowledging a general interplay between biomaterials, proteins and platelets. Thus this study aims to investigate the effect of plasma protein adsorption and subsequent platelet interactions on the smooth and nano-patterned commercially used surface coatings such as hydrogenated amorphous carbon (a-C:H), tetrahedral amorphous carbon (ta-C) and titania (TiO2) surfaces. Results have shown a-C:H and ta-C surfaces exhibited increased affinity to fibrinogen than TiO2, while facilitating similar levels of platelet attachment. A-C:H resulted in decreased cellular spreading when compared with ta-C and TiO2, while same level of platelet activation was detected indicating that platelets could exist in their activated state without spreading. When platelet interactions on nano-patterned surfaces (RMS 5-8nm) were compared against flat surfaces, nano-rough surfaces presented with increased levels of platelet attachment as well as its spreading, while similar levels of platelet activation was detected amongst the smooth and rough substrates. Increased levels of platelet adhesion and spreading were positively correlated with increased fibrinogen adsorption, reinforcing the crucial role of fibrinogen in platelet binding but also its possible role in platelet spreading

Biomaterials for Bone Tissue Engineering 2020

This book presents recent advances in the field of bone tissue engineering, including molecular insights, innovative biomaterials with regenerative properties (e.g., osteoinduction and osteoconduction), and physical stimuli to enhance bone regeneration

Southwest Research Institute assistance to NASA in biomedical areas of the technology

Significant applications of aerospace technology were achieved. These applications include: a miniaturized, noninvasive system to telemeter electrocardiographic signals of heart transplant patients during their recuperative period as graded situations are introduced; and economical vital signs monitor for use in nursing homes and rehabilitation hospitals to indicate the onset of respiratory arrest; an implantable telemetry system to indicate the onset of the rejection phenomenon in animals undergoing cardiac transplants; an exceptionally accurate current proportional temperature controller for pollution studies; an automatic, atraumatic blood pressure measurement device; materials for protecting burned areas in contact with joint bender splints; a detector to signal the passage of animals by a given point during ecology studies; and special cushioning for use with below-knee amputees to protect the integrity of the skin at the stump/prosthesis interface