356 research outputs found
Buckypaper (BP) as absorbable adhesive for surgical application in abdominal wall issues
No full textBy: Sun, P.; Hu, S. B.; Cheng, X.; Li, M.; Guo, B.; Song, Z. F.; Zhang, Y.; Zheng, Q. C.; Hoyuela, C.; Vega, L.; Carvajal, F.; Blay, L.; Juvany, M.; Camps, J.; Veres, A.; Besora, P.; Trias, M.; Feliu, X.; Bellanova, G.; Viel, G.; et al. In: Hernia. April 2015 19(1):S157-S165; Springer Paris Language: English, Database: Springer Nature Journals
PROTPCOLLO DI RICERCA PUBBLICATO SU: ClinicalTrials.gov Identifier: NCT02137018 https://register.clinicaltrials.gov FINANZIAMENTO RICERCA DI ATENEO INTERDIPARTIMENTALE prot. C26A10HCNR, founding of 35000€ DIPARTIMENTO DI CHIMICA: Prof Lucio D'Ilario, Prof. Andrea Martinelli, DIPARTIMENTO DI CHIRURGIA "PARIDE STEFANINI": Dott. Massimo Chiaretti , prot letter 0003306 project n° 304P25, interfaculty Chemistry Dep, General Surgery Paride Stefanini Dep. http://www.uniroma1.it Location National Health Institute (ISS Istituto Superiore di Sanità), Viale Regina Elena 299 Rome, Roma, Italy, 00161 "BP as a New Device for Surgery and Solid Cancer and Hematopoietic System Tumors Treatment. Effects of BP Implantation" (DM159) ClinicalTrials.gov Protocol and Results Registration System (PRS) Receipt Release Date: 12/30/2014 The objective of this project is to obtain results that can direct the search for the ultimate realization of a prosthetic device for use in abdominal surgery. Will be conducted systematic experiments in 30 New Zealand female rabbits (R1-R30), weighting about 3000 g (Harlan Laboratories).Campanelli, Giampiero. Hernia Volume: 19 Issue S1 (2015) ISSN: 1265-4906 Online ISSN: 1248-9204
Buckypaper (BP) as absorbable adhesive for surgical application in abdominal wall issues
Chiaretti M(1), Martinelli A(2), Carru GA(3), Alunni Fegatelli D(4), Chiaretti AM(5), Consentino P(6), Chiaretti AI(1), Procacciante F(1)
(1) Department of General Surgery “Paride Stefanini”, Sapienza University, Viale del Policlinico 155, Rome, 00161 (Italy)
(2) Department of Chemistry, Sapienza University, P.le Aldo Moro 5, Rome, 00185 (Italy)
(3) Policlinico Umberto I Hospital, Sapienza University, Viale del Policlinico 155, 00161 - Rome (Italy)
(4) Public Health and Infective Illness, Sapienza University, P.le Aldo Moro 5, Rome, 00185 (Italy)
(5) Istitute of Genetic Risearch G. Salvatore, Scienze e Tecnologie Genetiche Biogem;
(6) Appialab Srl V. Latina, 286 00179 Rome (+39) 067825111www.appialab.it
E-mail: [email protected]
Introduction: One of the key issues relating to abdominal prosthetic surgery is the fixation of the abdominal mesh. Mesh displacement, improper or blind application of metal tacks and staples in laparoscopic surgery are the main causes of complications such as seroma[1], postoperative pain[2] and recurrence of hernia[3]. The well-established use of fibrin glue[4], or self-gripping commercial meshes, or suture meshes to fix prosthesis to damaged tissue may represent a risk associated to the transmission of unknown diseases related to the use of blood-derived materials[4] or pain caused by nerve entrapment or displacement. Moreover, it has been observed[1,5] that the use of fibrin glue for mesh fixation may be associated with incidence of postoperative seroma. An effective alternative to the conventional prosthesis fixation methods may be represented by devices able to adhere strongly and quickly[1,5] on wet[6] biological tissue. In view of a possible application of BP as adhesive absorbable tape in surgery, preliminary in vivo experiments were carried out on large-size pigs. Methods: We investigated the potential applicability of BP, a self-standing felt composed of multi-walled carbon nanotubes, as an adhesive tape on biological tissue compared with traditional methods of fixation of prosthetic meshes. Based on biological materials from experimentation on rabbits (in progress[7]) we carried out a comparative study on two sets of meshes: one of the sets was fixed with BP and the other set was fixed with traditional methods. We did this by carrying out bench surgery and performing mechanical peeling and shear adhesiveness tests on each set[5,8,9,10]. The in vivo experimentation was carried out on 30 Landrace female pigs weighing about 15 kg initially and 60 kg when they were sacrificed. The subjects were divided into two sets i.e., 15 for laparoscopic procedure and 15 for laparotomic procedure. Each group was further subdivided into an experimental set of 11 subjects for mesh fixation with BP and a control set of 4 subjects for traditional mesh fixation. Results: Experimental and control subsets did not show mortality or morbidity. Even after 90 days from the operation no significant neurovegetative or behavioral differences were observed. The BP fixing method shows stronger adhesiveness on wet tissues[6] than the mentioned traditional fixing methods. Checks on body weight monitoring curves show no significant differences between BP and control groups. Necroscopical and histological investigations show that BP elicits minimal adverse tissue response. Nanometric carbon nanotube aggregates were phagocytized by macrophages. Further, BP fragments were also observed in Bowman's urinary space. Finally, around the BP, a capsule of loose fibrous tissue is formed by collagen fibers deposited by fibroblasts which indicate a moderate cicatrisation reaction. Conclusion: Findings from our experiment are compatible with a stronger adhesiveness on wet biological tissue for the BP fixing method compared to traditional methods. Further studies are required to fully assess the nature of the BP debris, their toxicity potential and their metabolization.
References
1. B. P. Jacob, N. J. Hogle, E. Durak, T. Kim, D. L. Fowler, Surg. Endosc. 2007, 21, 629
2. J. R. Eriksen, J. I. Bech, D. Linnemann, J. Rosemberg, Hernia 2008, 12, 483
3. W. B. Gaertner, M. E. Bonsack, J. P. Delaney, Hernia 2010, 14, 375
4. S. Olmi, A. Addis, C. Domeneghini, A. Scaini, E. Croce, Hernia. 2007, 11, 211
5. S. Bellucci, M. Chiaretti, P. Onorato, F. Rossella, M. S. Grandi, P. Galinetto, I. Sacco, F. Micciulla, Nanomedicine 2010, 5, 209
6. A. Martinelli, GA. Carru, L. D'Ilario, F. Caprioli, M. Chiaretti, F. Crisante, I. Francolini, and A. Piozzi. ACS Appl. Mater. Interfaces, DOI:10.1021/am400543s Publication Date (Web): 18 Apr 2013, http://pubs.acs.org on April 19, 2013
7. M. Chiaretti, G. A. Carru, Danilo Alunni Fegatelli, A. M. Chiaretti, A. Martinelli, (in progress)
8. M. Chiaretti, G. Mazzanti, S. Bosco, S. Bellucci, A. Cucina, F. Le Foche, G. A. Carru, S. Mastrangelo, A. Di Sotto, R. Masciangelo, A. M. Chiaretti, C. Balasubramanian, G. De Bellis, F. Micciulla, N. Porta, G. Deriu, A. Tiberia, J. Phys.: Condens. Matter 2008,20, 474203
9. A. Di Sotto, M. Chiaretti, G. A. Carru, S. Bellucci, G. Mazzanti, Toxicol. Lett. 2009, 184, 192
10. S. Bellucci, M. Chiaretti, A. Cucina, G.A. Carru,A.I. Chiaretti, Nanomedicine 2009, 4, 53
Buckypaper (bp) as absorbable adhesive for surgical application in abdominal wall defects
No full textTOPICS: Biotecnologia ed innovazioni tecnologiche. Le proposte italiane nella ricerca.
BUCKYPAPER (BP) AS ABSORBABLE ADHESIVE FOR SURGICAL APPLICATION IN ABDOMINAL WALL DEFECTS
Massimo Chiaretti(1), Andrea Martinelli(2), Giovanna Angela Carru(3), Emanuela D’Amore(4), Alessandra Maria Chiaretti(5), Fabio Faiola(6), Paola Consentino(7), Eleonora Valente(8), Annalisa Italia Chiaretti(1)
(1)Department of General Surgery “Paride Stefanini”, Sapienza University of Rome, Viale del Policlinico 155, Rome, 00161 (Italy)
(2)Department of Chemistry, Sapienza University of Rome, P.le Aldo Moro 5, Rome, 00185 (Italy)
(3)Policlinico Umberto I Hospital, Sapienza University of Rome, Viale del Policlinico 155, 00161 - Rome (Italy)
(4)National Health Institute, Viale Regina Elena 299, 00161 - Rome (Italy)
(5) Istitute of Genetic Risearch G. Salvatore, “Consorzio Interuniversitario di Scienze e Tecnologie Genetiche Biogem”;
(6)Department of Molecular Medicine, Sapienza University of Rome, Viale Regina Elena 324, Rome, 00161 (Italy)
(7)Appialab Srl V. Latina, 286 00179 Rome (+39) 067825111www.appialab.it
(8)Policlinico Agostino Gemelli, Università Cattolica del Sacro Cuore, Roma
E-mail: [email protected]
Keywords: buckypaper, BP, MWCNTs, medical application, abdominal wall defects surgery, wet adhesion, absorbable adhesive device.
Introduction: One of the main problems related to the abdominal prosthetic surgery is the mesh fixation. Mesh displacement, improper and blind application of metal tacks and staples in laparoscopy surgery are the main causes of complications such as seroma, postoperative pain and recurrence[6-9]. The use of fibrin glue between the prosthesis and the damaged tissue, although it has become a well-established surgical procedure, represents a possible risk associated to the transmission of unknown diseases related to the use of human blood-derived materials [9]. Moreover, it was observed that an increased incidence of postoperative seroma is associated to the use of fibrin glue for mesh fixation[10]. Surfaces able to adhere promptly and strongly on wet biological tissue may represent an effective alternative to the conventional prosthesis fixation methods. This study realized on animal model proposes the application of the nature inspired micro- or nano-patterned adhesive surfaces, by exploiting the scaling effect, according to which the adhesion strength can be enhanced through the reduction of interface adhesive contact size[12]. We experimented evidences on the potential applicability on biological tissue of the BP as an adhesive tape, a self-standing felt composed of entangled multi-walled carbon nanotubes. In vitro bench surgery, mechanical peeling, and shear adhesion tests, and In vivo tests were tested with prosthetic meshes[2,3,4,10]. BP shows a stronger adhesion, but only on wet tissues[12] much better than both self-gripping commercial mesh and fibrin-glue non-gripping meshes and fabrics. Prompted by these results, we implanted BP in pigs, to assess BP effectiveness as adhesive absorbable prosthetic device and its biocompatibility. After 90 days from the operation we observed no pig behavioral alteration. BP samples preserved their position in the implantation site and mechanical adhesion was enhanced, both in laparoscopy and laparotomic procedure. Materials and Methods. Operated 30 Lantrace female 40-50 Kg pigs, 15 in laparoscopic procedure and 15 in laparotomic procedure. Operated and control subjects did not show mortality or morbidity, no significant neurovegetative or behavioral differences. Results and Discussion. Body weight monitoring graph do not showed any significant difference between BP and control group. The Hematoxilin and Eeosin stained implant section reported BP surface fragmentation that shows the formation of a capsule of loose fibrous tissue, consisting of fibroblasts and collagen fibers, indicative of a weak inflammation reaction. The necroscopy examination showed that the implanted BP favors a cicatrisation process, the mesh appearing wrapped in the inflammatory reaction. Conclusions: a strong BP adhesion on wet biological tissue was measured. In view of a possible application as adhesive absorbable tape in surgery, preliminary in vivo experiments were carried out on big pig model. Necroscopical and histological investigations enlighten that as 90 days after the implantation the BP elicits minimal adverse tissue response. Nanometric carbon nanotube aggregates were phagocytised by macrophages and observed in Bowman's urinary space. The assessment of the BP debris, possible toxicity or confinement or metabolism and accumulation or excretion mechanism needs further studies.
References
1. L. Liu, W. Ma, Z. Zhang,Small 2011, 7, 1504
2. M. Chiaretti, G. Mazzanti, S. Bosco, S. Bellucci, A. Cucina, F. Le Foche, G. A. Carru, S. Mastrangelo, A. Di Sotto, R. Masciangelo, A. M. Chiaretti, C. Balasubramanian, G. De Bellis, F. Micciulla, N. Porta, G. Deriu, A. Tiberia, J. Phys.: Condens. Matter 2008,20, 474203
3. A. Di Sotto, M. Chiaretti, G. A. Carru, S. Bellucci, G. Mazzanti, Toxicol. Lett. 2009, 184, 192
4. S. Bellucci, M. Chiaretti, A. Cucina, G.A. Carru,A.I. Chiaretti, Nanomedicine 2009, 4, 531
5. a) The mean equivalent radius was evaluated by wicking tests carried out in water, assuming a water contact angle of about 80°; b) G. Callegari, I. Tyomkin, K. G. Kornev, A.V. Neimark, Y-L. Hsieh, J. Colloid Interface Sci.2011, 353, 290
6. B. P. Jacob, N. J. Hogle, E. Durak, T. Kim, D. L. Fowler, Surg. Endosc. 2007, 21, 629
7. J. R. Eriksen, J. I. Bech, D. Linnemann, J. Rosemberg, Hernia 2008, 12, 483
8. W. B. Gaertner, M. E. Bonsack, J. P. Delaney, Hernia 2010, 14, 375
9. S. Olmi, A. Addis, C. Domeneghini, A. Scaini, E. Croce, Hernia. 2007, 11, 211
10. S. Bellucci, M. Chiaretti, P. Onorato,F. Rossella, M. S. Grandi, P. Galinetto, I. Sacco,F. Micciulla, Nanomedicine 2010, 5, 209
11. massimochiaretti.wordpress.com
12. A. Martinelli, GA. Carru, L.D'Ilario, F. Caprioli, M. Chiaretti, F. Crisante, I. Francolini, and A. Piozzi. ACS Appl. Mater. Interfaces, DOI:10.1021/am400543s • Publication Date (Web): 18 Apr 2013, http://pubs.acs.org on April 19, 201
PRP (Plasma Ricco di Piastrine): trattamento delle piaghe da piede diabetico, dell'osteomielite fistolizzata postraumatica, nostre esperianze in 63 casi clinici, revisione della letteratura.
No full textPRP (PLASMA RICCO DI PIASTRINE): TRATTAMENTO DELLE PIAGHE DA PIEDE DIABETICO, DELL’OSTEOMIELITE FISTOLIZZATA POSTRAUMATICA, NOSTRE ESPERIENZE IN 63 CASI CLINICI, REVISIONE DELLA LETTERATURA.
Massimo Chiaretti*, Giovanna Angela Carru^, Annalisa Italia Chiaretti°, Giancarlo Ceccarelli^, Eleonora Valente§, Alessandra Maria Chiaretti#,
(*)Dipartimento di Chirurgia Generale, Specialità Chirurgiche e Trapianti d’Organo “Paride Stefanini” Azienda Policlinico Umberto I, Università degli Studi di Roma “La Sapienza”;
(^)Azienda Policlinico Umberto I, Università degli Studi di Roma “La Sapienza”;
(°)Azienda Ospedaliera S. Andrea, II Facoltà di Medicina e Psicologia, Università degli Studi di Roma “La Sapienza”;
(#)Istituto Ricerche Genetiche G. Salvatore, Consorzio Interuniversitario di Scienze e Tecnologie Genetiche “Biogem”;
(§)Policlinico Agostino Gemelli, Università Cattolica del Sacro Cuore, Roma
Introduzione: la nostra esperienza evidenzia l’utilità del PRP (Plasma Ricco di Piastrine) nel trattamento ambulatoriale delle piaghe torpide della pianta del piede, del malleolo e della gamba, in pazienti vasculopatici con ulcere torpide e/o diabetici. Tali lesioni richiedono, solitamente, periodi lunghissimi di medicazioni complesse, spesso senza raggiungere il risultato atteso. Materiali e Metodi: la metodica personale prevede il debridement dopo disinfezione della piaga, l’inoculazione di 1-4 UI di insulina pronta nel cratere ulcerativo, l’applicazione di circa 5 ml di PRP su spugna di acido ialuronico (Hyalofill-F Fidia® Italia che serve ad impedirne la dispersione della parte liquida o non completamente gelificata), attivata con Plateltex®. L’applicazione si esegue facendo gocciolare il PRP sulla spugna di acido ialuronico, sulla quale si fa poi gocciolare l’attivatore (bicomponente: calcio gluconato e batroxobina, 5 BU, Batroxobin Units). Gli ioni calcio (Ca++) del calcio gluconato saturano l’anticoagulante presente nel PRP, preparato dal nostro Centro Trasfusionale (CT) da sangue autologo, suddiviso in aliquote congelate. La batroxobina serve, invece, a trasformare il fibrinogeno in fibrina, in combinazione con gli ioni Ca++ del calcio gluconato, formando il reticolo gelificato. La gelatina neoformata si presenta come un panno morbido elastico-gelatinoso, applicabile nella piaga per riempire la cavità da trattare. Il PRP è ricco dei fattori di crescita (PDGF, TGF, EGF) che servono a stimolare la moltiplicazione dei fibroblasti che aumentando di numero, promuovono la fioritura dei bottoni di granulazione, depositano una quantità consistente di matrice connettivale, trasformando la piaga torpida in una ferita in cicatrizzazione per seconda intenzione. Nel caso di piaga infetta o paziente con fistola osteomielitica è indispensabile sterilizzare la lesione infetta, prima di procedere al trattamento con PRP. Tale procedura prevede esami colturali seriati con antibioticoterapia parenterale mirata. Discussione: Il metodo prevede l’esecuzione in camera operatoria sterile ambulatoriale. L’approccio multidisciplinare è indispensabile e prevede la costituzione di un PAC (Pacchetto Assistenziale Complesso) che coinvolga Chirurgo Generale e Vascolare, Diabetologo, Infettivologo, Immunotrasfusionista, Dermatologo, Ortopedico, Cardiologo e Specialista per l’esecuzione di Ecocolordoppler arterioso e venoso. Conclusioni: l’approccio multidisciplinare e lo stretto coordinamento tra ambulatorio chirurgico e CT evitano inutili attese al Paziente, accorciano i tempi di esecuzione della medicazione, abbattono i costi per l’impiego di materiali, rendendo il trattamento con PRP conveniente rispetto a quello tradizionale. Per aumentare la casistica ed ottenere i numeri necessari ad una validazione statistica è in corso la realizzazione di un protocollo multicentrico.
Bibliografia-Sitografia
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31) Gel Piastrinico: Trattamento del Piede Diabetico e dell’osteomielite fistolizzata. Revisione della letteratura e Nostra Esperienza in 61 Casi Clinici. Massimo Chiaretti*, Giancarlo Ferrazza+, Giovanna Angela Carru^, Gianna Barrella+ , Giancarlo Ceccarelli^, Pietro Bondani*, Giulia Diamantini *, Annalisa Italia Chiaretti°, Fabio Procacciante* SIC 2012 Roma, Parco della Musica
32) Gel Piastrinico: Trattamento del Piede Diabetico e dell’osteomielite fistolizzata. Revisione della letteratura e Nostra Esperienza in 61 Casi Clinici. Massimo Chiaretti*, Giovanna Angela Carru^, Giancarlo Ceccarelli^, Giulia Diamantini*, Annalisa Italia Chiaretti°, Fabio Procacciante* XXXV Congresso Nazionale Società Italiana Medicina Estetica SIME 2014 Roma, Centro Congressi Cavalieri Waldorf Astoria.compact disc ISSN 2038-331
Nuovo metodo di fissaggio per i materiali protesici sperimentato su modello animale.
No full textNuovo metodo di fissaggio per materiali protesici sperimentato su modello animale M. Chiaretti, J. Andreuccetti, A. I. Chiarettia, G.A.Carrub, D. Tuscano, Paolo Negro Chirurgia Generale e Day Surgery, Dipartimento Chirurgia Generale, “Paride Stefanini”, Università degli Studi di Roma “La Sapienza”. a Ospedale S. Andrea, II Facoltà di Medicina e Chirurgia, Università degli Studi di Roma b Ospedale Policlinico Umberto I, Università degli Studi di Roma La chirurgia dei difetti della parete addominale utilizza materiali protesici leggeri, resistenti, biocompatibili, economici, per ridurre il rischio di recidiva, migliorare il confort postoperatorio, abbreviare la degenza. La “Protesi Ideale” dovrebbe anche essere applicabile rapidamente, bioadesiva, e utilizzabile sia nella chirurgia open sia in laparoscopia. Dovrebbe poter prevenire il rischio di neuropatia dolorosa cronica, [5,6] e proteggere dalle teoriche ma possibili infezioni, non ancora conosciute e quindi non diagnosticabili, trasmissibili con i materiali biologici usati per confezionare le colle di fibrina [6]. Abbiamo studiato un nuovo materiale, il Buckypaper di nanotubi di carbonio (BP), nato per altri impieghi ma lavorabile con forbice, sterilizzabile in autoclave [1,3], superleggero, flessibile, bioadesivo e biocompatibile. Il BP risulta utile per il fissaggio di tutti i materiali protesici attualmente esistenti in commercio, compresi cateteri ed elettrodi, ai tessuti biologici viventi; è d’uso semplice, versatile, efficace, economico, affidabile e sicuro sul modello animale, permettendo di velocizzare la procedura chirurgica. Abbiamo eseguito la sperimentazione in vivo su ratti Sprague_Dawley e la sperimentazione di banco su conigli New Zeeland. Stiamo valutando l’ipotesi di utilizzare il BP in sostituzione dei mezzi di sintesi e collanti biologici attuali. [5, 6], proteggendo il paziente da teoriche ma possibili infezioni trasmissibili e neuralgia cronica legata ad eventuale “entrapment”. Il BP sembra essere un materiale protesico bioadesivo migliore di tutti quelli attualmente in commercio e pone una seria ipoteca sui sistemi di fissaggio protesico, che potrebbero cambiare radicalmente, qualora il BP confermasse la sua perfetta biocompatibilità . 1.Chiaretti, M.; Mazzanti, G.; Bosco, S.; Bellucci, S.; Cucina, A.; Le Foche, F; Carru, G A; Mastrangelo, S; Di Sotto, A ; Masciangelo, R; Chiaretti, A M; doi:10.1088/0953- 8984/20/47/474203. J. Phys.: Condened Matters 2008, 20, 47-57. 2.Chiaretti, M.; Cucina, A.; Bellucci, S.; Di Sotto A; Mazzanti G.; www.icact.com Abstract book of 20th International Congress on Anti-Cancer Treatment 2009, 438-439. 3.Bellucci S, Chiaretti M., Onorato P. Rossella F., Simone M. 2009, september 21-22 Micro-Raman study of effect of sterilization on carbon nanotubes for biomedical applications. Poster Session 2nd. National Nanomedicine Conference Padova. 4.Multi Walled Carbon Nanotube buckypaper: toxicology and biological effects in vitro and in vivo.; Bellucci, S.; Chiaretti, M..Cucina, A.; Carru, G A; Chiaretti, A I. Nanomedicine (2009) 4(5); 531-540 ISSN 1743-5889 5.Sunderland S.: Nerves and nerve jniury. Livingstone, Edinburg.1968. 6.Olmi S.Addis A: Experimental comparison of type of Tissucol dilution and composite mesh (Parietex) for laparoscopic repair of groin and abdominal hernia: observational study conducted in a university laboratory. Hernia. 11:211-215 (2007)
Buckypaper as absorbable adhesive for surgical applications
No full textFONANZIAMENTO pROGETTO DI RICERCA INTERFACOLTA' dIP pARIDE sTEFANINI Chirurgia Generale e Dip di Chimica Anno 2010 prot C26A10HCNR per 5333€ di 35000€TOPICS: Biotecnologia ed innovazioni tecnologiche. Le proposte italiane nella ricerca.
BUCKYPAPER AS ABSORBABLE ADHESIVE FOR SURGICAL APPLICATIONS
Massimo Chiaretti(1), Andrea Martinelli(2), Giovanna Angela Carru(3), Fabio Procacciante(1), Lucio D’Ilario(2), Emanuela D’Amore(4), Alessandra Maria Chiaretti(5), Fabio Faiola(6) and Paola Consentino(7).
(1)Department of General Surgery “Paride Stefanini”, Sapienza University of Rome, Viale del Policlinico 155, Rome, 00161 (Italy)
(2)Department of Chemistry, Sapienza University of Rome, P.le Aldo Moro 5, Rome, 00185 (Italy)
(3)Policlinico Umberto I Hospital, Sapienza University of Rome, Viale del Policlinico 155, 00161 - Rome (Italy)
(4)National Health Institute, Viale Regina Elena 299, 00161 - Rome (Italy)
(5)Biologic Sciences Faculty, University of Rome, P.le Aldo Moro 5, Rome, 00185 (Italy)
(6)Department of Molecular Medicine, Sapienza University of Rome, Viale Regina Elena 324, Rome, 00161 (Italy)
(7)Appialab Srl V. Latina, 286 00179 Rome (+39) 067825111www.appialab.it
E-mail: [email protected]
Keywords: buckypaper, carbon nanotubes, medical application, abdominal surgery, wet adhesion absorbable adhesive device.
Introduction: The adhesion of a surface on a biological tissue represents an important scientific and technological issue which excites the interest of many researchers. One of the main problems related to the abdominal prosthetic surgery is the mesh fixation. On the one hand suture line tension, mesh separation or displacement, improper and blind application of metal tacks and staples in laparoscopy surgery are the main causes of complications, including seroma, postoperative pain and recurrence[6-9]. On the other hand, the use of human fibrin as glue between the prosthesis and the damaged tissue, although it has become a well-established surgical procedure, presents possible risks associated to the transmission of unknown diseases related to the use of human blood-derived materials [9]. Moreover, it was observed that an increased incidence of postoperative seroma is associated to the use of fibrin glue for mesh fixation[10]. Surfaces able to adhere promptly and strongly on wet biological tissue may represent an effective alternative to the conventional prosthesis fixation methods. This study proposes the application of the nature inspired micro- or nano-patterned adhesive surfaces, by exploiting the scaling effect, according to which the adhesion strength can be enhanced through the reduction of interface adhesive contact size. We experimented evidences on the potential applicability on wet biological tissue of the Buckypaper (BP) as an adhesive tape: BP is a self-standing felt composed of entangled multi-walled carbon nanotubes. In vitro bench surgery mechanical peeling and shear adhesion tests and In vivo tests If compared to other commercial tested prosthesis meshes, BP shows a stronger adhesion, only on wet tissues. much better than both self-gripping commercial mesh and fibrin-glue non-gripping meshes and fabrics. Prompted by these results, we implanted BP in rabbits, to assess its effectiveness as adhesive absorbable prosthetic device and its biocompatibility. After 35 days from the operation we observed that no rabbit behavioral alteration occurred; the BP samples preserved their position in the implantation site and mechanical adhesion was enhanced. This is indicative of no toxicity, good integration and slow reabsorption of the synthetic material into the surrounding tissue without eliciting adverse reactions. Materials and Methods. Operated New Zeeland 3000g female rabbits (R1-R4) did not show mortality or morbidity, no significant neurovegetative or behavioral differences in comparison with the no operated control R5. Results and Discussion. Body weight monitoring graph do not showed any significant difference. The Hematoxilin and Eeosin (H&E) stained implant section reported BP surface fragmentation, shows the formation of a capsule of loose fibrous tissue, consisting of fibroblasts and collagen fibers, indicative of a weak inflammation reaction., the necroscopy examination of R2 showed that the implanted PP favors a cicatrisation process, the mesh appearing wrapped in the inflammatory reaction. In R4, the no sutured incision, tighten by the BP strep, was normally closed and healed. On the smooth BP surface facing the abdominal cavity, explanted from R3, a scarcely adherent neo-formed protein fibrous carpet, about 5 mm thick, may be observed in scansion electronic microscope (SEM). Conclusions: by peeling and shear mechanical tests, a strong BP adhesion on wet biological tissue was measured. In view of a possible application as adhesive absorbable tape in surgery, preliminary in vivo experiments were carried out on rabbit model. Necroscopical and histological investigations enlighten that 35 days after the implantation, the BP elicits minimal adverse tissue response, and when exposed to the peritoneal cavity, no adhesion of omentum or intestinal loops was observed. Nanometric carbon nanotube aggregates, deriving from the surface BP fragmentation, were phagocytised by macrophages and observed in Bowman's urinary space. The assessment of the BP debris, possible toxicity or confinement or metabolism and accumulation or excretion mechanism needs further studies. However, we believe that the results here reported can be used to propose the BP as a new wet absorbable adhesive tape to fix prosthetic materials.
References
1. L. Liu, W. Ma, Z. Zhang,Small 2011, 7, 1504
2. M. Chiaretti, G. Mazzanti, S. Bosco, S. Bellucci, A. Cucina, F. Le Foche, G. A. Carru, S. Mastrangelo, A. Di Sotto, R. Masciangelo, A. M. Chiaretti, C. Balasubramanian, G. De Bellis, F. Micciulla, N. Porta, G. Deriu, A. Tiberia, J. Phys.: Condens. Matter 2008,20, 474203
3. A. Di Sotto, M. Chiaretti, G. A. Carru, S. Bellucci, G. Mazzanti, Toxicol. Lett. 2009, 184, 192
4. S. Bellucci, M. Chiaretti, A. Cucina, G.A. Carru,A.I. Chiaretti, Nanomedicine 2009, 4, 531
5. a) The mean equivalent radius was evaluated by wicking tests carried out in water, assuming a water contact angle of about 80°; b) G. Callegari, I. Tyomkin, K. G. Kornev, A.V. Neimark, Y-L. Hsieh, J. Colloid Interface Sci.2011, 353, 290
6. B. P. Jacob, N. J. Hogle, E. Durak, T. Kim, D. L. Fowler, Surg. Endosc. 2007, 21, 629
7. J. R. Eriksen, J. I. Bech, D. Linnemann, J. Rosemberg, Hernia 2008, 12, 483
8. W. B. Gaertner, M. E. Bonsack, J. P. Delaney, Hernia 2010, 14, 375
9. S. Olmi, A. Addis, C. Domeneghini, A. Scaini, E. Croce, Hernia. 2007, 11, 211
10. S. Bellucci, M. Chiaretti, P. Onorato,F. Rossella, M. S. Grandi, P. Galinetto, I. Sacco,F. Micciulla, Nanomedicine 2010, 5, 209
11. massimochiaretti.wordpress.co
Is Less More? Intensive Versus Non-Intensive Approach to Adults with Ph+ ALL
No full textNot available
Chemotherapy-free and reduced intensity approaches in elderly patients with B-lineage acute lymphoblastic leukemia
No full textManagement of older patients - defined by convention above the age of 60 years, but varying widely within study groups - with acute lymphoblastic leukemia (ALL) is still a challenge. The complete remission (CR) rate in these patients is lower than in other age groups and the percentage of deaths in induction or in CR remains high, ranging from 7 to 40%. Overall survival rates do not exceed 30%, depending on the age group included in the different trials group and on the follow-up duration. These unsatisfactory results are sustained by the fact that pre-existing comorbidities often hamper treatment delivery and if treatment intensification improves the CR rates it also increases toxicity and the percentage of deaths. Overall, the median life expectancy is rising world-wide, being in the western world around/over 80 years (and increasing); in addition, the proportion of elderly individuals is growing progressively. This means that the management of these frail patients represents a true clinical unmet need. While in Ph+ ALL the introduction of tyrosine kinase inhibitors (TKI) has markedly impacted on the outcome of patients of all ages, in Ph− ALL prognosis in the elderly still remains largely unsatisfactory. Novel strategies - mostly based on the use of monoclonal antibodies or of targeted strategies if druggable mutations can be identified - are largely needed. In the present review, we will discuss the past and current scenario, and provide an overview on the developing approaches for both Ph− and Ph+ elderly ALL, represented in particular by immunotherapy
Supporto nutrizionale enterale capitolo 4 volume 1
No full textnutrizionale enterale totale, nutrizionale enterale domiciliare,nutrizionale enterale postoperatoria precoce,immunonutrizionale enterale
Role of Liprins in the Regulation of Tumor Cell Motility and Invasion.
No full textInvasion leading to the formation of metastasis is one of the hallmarks of cancer. Analysis of different human cancers has led to the identification of the PPFIA1 gene encoding the protein liprin-α1, a possible player in cancer. The PPFIA1 gene is amplified in malignant tumors, including about 20% of breast cancers. Also the liprin-α1 protein is found overexpressed in tumors. Liprin-α1 belongs to the liprin family of cytosolic scaffold proteins that includes four liprin-α, two liprin-β members, and liprin-γ/kazrinE. In this review we will discuss the available evidence on the role of different members of the liprin family in distinct aspects of tumor cell migration and invasion. Evidence from in vitro studies indicates that the widely expressed liprin-α1 protein regulates the migration and invasion of human breast cancer cells. Liprin-α1 affects cell migration and invasion by regulating the organization of lamellipodia and invadopodia, two structures relevant to cell invasion. In the cell liprin-α1 forms a complex with liprin-β1, ERC1/ELKS and LL5 proteins, which localizes at the front of migrating cells and positively regulates lamellipodia stability, and integrin-mediated focal adhesions. On the other hand, liprin-β2 appears to play a role as tumor suppressor by inhibiting breast cancer cell motility and invasion. The available data indicate that liprins are central players in the regulation of tumor cell invasion, therefore representing interesting targets for anti-metastatic therapy
BIOCOMPATIBLE ADHESIVE MATERIAL, ADHESIVE SURGICAL PROSTHESIS, AND RELATIVE KIT
No full text“L’effetto Geco” dei nanotubi di carbonio era già noto così come le applicazioni in ambito aerospaziale. La nostra ricerca ha documentato che l’adesività dei nanotubi di carbonio è presente anche in ambito biologico (bioadesività dei nanotubi di carbonio sia nel formato granulare che nel formato buckypaper). Tale bioadesività è importante perché potrebbe essere utile nel fissaggio dei tessuti protesici attualmente in uso (polipropilene, polietilene e PTFE nelle varie e possibili combinazioni) ai tessuti biologici viventi sia animali che umani. E’ stata dimostrata dalle nostre ricerche una innocuità sostanziale dei nanomateriali in particolare del buckypaper che applicato sulle reti protesiche, ne permette il tenace fissaggio ai tessuti senza l’impiego di altri materiali, come ad esempio le colle biologiche oppure i fili di sutura. Nel primo caso per i possibili teorici rischi connessi all’impiego di tutti i materiali biologici che potrebbero trasmettere malattie infettive non ancora conosciute e gli elevati costi delle colle biologiche. Per i fili, le suture possono determinare l’intrappolamento di terminazioni nervose che potrebbero rimanere strozzate dal nodo di sutura e provocare neuralgie durevoli di difficile trattamento e disconfort per i pazienti.
VANTAGGI TECNICI: la bioadesività è importante perché è utile nel fissaggio dei tessuti protesici attualmente in uso (polipropilene, polietilene e PTFE nelle varie e possibili combinazioni) ai tessuti biologici umani perché:
1. permette di velocizzare la procedura chirurgica ad esempio di plastica di ernia inguinale, plastica di laparocele, ancoraggio della vescica ptosica, prolassi del pavimento pelvico, rotture traumatiche del diaframma, ernia ombelicale;
2. il tenace fissaggio da buckypaper ai tessuti escludendo l’impiego di fili di sutura previene il possibile intrappolamento di terminazioni nervose che potrebbero rimanere strozzate dallo stesso nodo di sutura e provocare nel paziente neuralgie durevoli, di difficile trattamento;
3. la riduzione della durata dell’intervento chirurgico permette l’estensione di tale chirurgia, anche a pazienti cardiologicamente e/o pneumologicamente compromessi che altrimenti non possono essere operati;
VANTAGGI ECONOMICI:
1. abbreviando i tempi di sala operatoria si abbattono i relativi costi gestionali ed a parità di orario lavorativo si possono realizzare un maggior numero di interventi;
2. il tenace fissaggio ai tessuti senza l’impiego di colle biologiche mette al riparo il paziente, dai possibili rischi teorici connessi all’impiego di tutti i materiali biologici che potrebbero trasmettere malattie infettive non ancora conosciute e agevola il risparmio economico delle amministrazioni sanitarie abbattendo l’esborso dovuto agli elevati costi delle colle biologiche a volte impiegate;
AREE DI APPLICAZIONE PRINCIPALI
Chirurgia Generale, Chirurgia Vascolare, Chirurgia Colonproctologica, Chirurgia Ginecologica, Chirurgia Urologica
IMPEGNO ALLA RISERVATEZZA:
"I sottoscritti si impegnano a garantire assoluta riservatezza in merito all'oggetto dell'invenzione per la quale chiede tutela brevettuale, fatta salva la possibilità di pubblicare/divulgare i relativi dati in un momento successivo alla data di deposito della domanda di brevetto".
Roma, 07/05/2009
FIRMA DEI RICHIEDENTI/PROPONENTIrICHIESTA EL BREVETTO PTC sulla base delle evidenze scientifiche documentate con i lavori scientifici pubblicati e di seguito sotto elencati:
1: Carbon nanotubes toxicology and effects on metabolism and immunological modification in vitro and in vivo
M Chiaretti1, G Mazzanti2, S Bosco3, S Bellucci4, A Cucina5, F Le Foche6, G A Carru7, S Mastrangelo2, A Di Sotto2, R Masciangelo8, A M Chiaretti9, C Balasubramanian4, G De Bellis4, F Micciulla4, N Porta3, G Deriu3 and A Tiberia4
1 General Surgery Department ‘Paride Stefanini’, Rome University ‘La Sapienza’, Italy
2 Human Physiology and Pharmacology Department ‘V. Ersparmer’, Rome University ‘La Sapienza’, Italy
3 Cattedra di Anatomia ed Istologia Patologica IV, Universit`a degli Studi di Roma ‘La Sapienza’, Italy
4 INFN-Laboratori Nazionali di Frascati, Via E Fermi 40, 00044 Frascati, Italy
5 General Surgery Department ‘Pietro Valdoni’, Rome University ‘La Sapienza’, Italy
6 Divisione Malattie Infettive e Tropicali II, Universit`a degli Studi di Roma ‘La Sapienza’, Italy
7 Policlinico ‘Umberto I’, Roma ‘La Sapienza’ University Hospital, Italy
8 Medical Statistic Service, Dipartimento di Medicina Sperimentale, Rome University ‘La Sapienza’, Italy
9 Biology Sciences Faculty, Rome ‘La Sapienza’ University, Italy
Journal of Physics Condensed Matter, 2008, vol. 20, 474203 (10pp)
ISSN: 0953-8984, doi: 10.1088/0953-8984/20/47/474203
Abstract
The aim of this research is focused on the biological effects of multi wall carbon nano tubes
(MWCNTs) on three different human cell types, laboratory animals in vivo, and immunological effects. Large numbers of researchers are directly involved in the handling of nanostructured materials such as MWCNTs and nanoparticles. It is important to assess the potential health risks related to their daily exposure to carbon nanotubes. The administration of sterilized nanosamples has been performed on laboratory animals, in both acute and chronic administration, and the pathological effects on the parenchymal tissues have been investigated. We also studied the effects of MWCNTs on the proliferation of three different cell types. MCF-7 showed a significant inhibition of proliferation for all conditions studied, whereas hSMCs demonstrated a reduction of cell growth only for the highest MWCNTs concentrations after 72 h. Also, no growth modification was observed in the Caco-2 cell line. We observed that a low quantity of MWCNTs does not provoke any inflammatory reaction. However, for future medical applications, it is important to realize prosthesis based on MWCNTs, through studying the corresponding implantation effects. Moreover, it has to be emphasized that this investigation does not address, at the moment, the carcinogenicity of MWCNTs, which requires a detailed follow-up investigation on the specific topic. In view of the subsequent and more extensive use of MWCNTs, especially in applications where carbon nanotubes are injected into the human body for drug delivery, as a contrast agent carrying entities for MRI, or as the basic material of a new prosthesis generation, more extended tests and experiments are necessary.
2: Multi-Walled Carbon Nanotubes: lack of mutagenic activity in the bacterial reverse mutation assay
Antonella Di Sotto§, Massimo Chiaretti†, Angela Carru†, Stefano Bellucci‡, Gabriela Mazzanti§*
§ Department of Human Physiology and Pharmacology, “Sapienza” University, P.le Aldo Moro 5, 00185 Rome, Italy
† General Surgery Department “Paride Stefanini, “Sapienza” University, P.le Aldo Moro 5, 00185 Rome, Italy
‡ INFN Frascati National Laboratories, Via Enrico Fermi 40, 00044 Frascati (Rome), Italy
Toxicology Letters, 2009, vol. 184; p. 192-197, ISSN: 0378-4274, doi:10.1016/j.toxlet.2008.11.007
Abstract
The mutagenic effect of multi-walled carbon nanotubes(MWCNTs) characterised by small surface/volume ratio, high diameter and less than 0.1% of metal contaminants was evaluated by the bacterial reverse mutation assay (Ames test) on Salmonella typhimurium TA 98 and TA 100 strains, and on Escherichia coli WP2uvrA strain, in presence and in absence of the metabolic activation system S9. A preliminary cytotoxicity assay was carried out to ensure that cytotoxicity did not interfere with response.
MWCNTs resulted devoid of mutagenic effect in the bacterial cellular systems tested in that they did not significantly increase the number of revertant colonies. The mutagenic activity did not even appear in presence of the metabolic activator, so we can exclude that MWCNTs metabolites, produced via cytochrome-based P450 metabolic oxidation system, may act as mutagens.
Carbon nanomaterials seem to exhibit different biological activities and different toxicities in relation to their physico-chemical characteristics, size, shape, crystallinity and presence of metal traces, so it is difficult to establish their health risk. Due to the limited background of genotoxicity studies and the increased occupational and public exposure to nanomaterials, present results appear useful to extend the knowledge on the safety of carbon nanotubes in view of their possible applications.
3: Preliminary results on toxicology and mutagenic effects of buckypaper (BP) and multiwalled carbon nanotubes (MWCNTs) on metabolism and immunological modification in vitro and in vivo.
M. Chiaretti1, A. Cucina2, S. Bellucci3, A. Di Sotto4, G. Mazzanti4
(1) General Surgery Department “Paride Stefanini”, Rome University “La Sapienza”, Italy
(2) General Surgery Department “Pietro Valdoni”, Rome University “La Sapienza”, Italy
(3) INFN-Laboratori Nazionali di Frascati, Via E. Fermi 40, 00044 Frascati, Italy
(4) Human Physiology and Pharmacology Department "Vittorio Ersparmer", Rome University “La Sapienza”, Italy
Abstract Book of the 20th International Congress on Anti-Cancer Treatment (ICACT), Paris 3-6 February 2009, p. 438-439
Abstract
The aim of our research is focused on the biological effects of BP and functionalized MWCNTs in laboratory animals in vivo, on the immunological buckypaper effects on mice and the effects of functionalized MWCNTs on five different cell types and finally, lack of mutagenic activity in the bacterial reverse mutation assay of MWCNTs. Nanomaterials possible applications in surgery, cancer therapy and new imaging techniques involve large numbers of researchers and potential patients. It is important to assess the potential health risks related to their exposure to nanoparticles [1, 2, 3]. The implantation of sterilized BP followed the study of serum immunological modifications after MWCNTs intraperitoneal administration without antigenic humoral reactions and humoral immunity [5]. We also studied the effects of MWCNTs not functionalized on the proliferation of three different cell types. [5, 6, 7] and the effects of BP on the proliferation of five different cell types (CaCo-2 Colorectal Carcinoma cell line; MCF-7 human breast carcinoma cell line, HL-60 human promyelocytic leukaemia cell line; HASMC normal human artery smooth muscle cells and finally HF normal human fibroblasts). It seems, at a preliminary observation, that proliferation of the cancer cell lines CaCo-2, MCF-7 and HL-60 are inhibited by BP as compared to controls, whereas there is no significant modification in proliferation of the two normal primary culture cells HASMC and HF. Pathological effects on the parenchymal tissues of laboratory animals have been studied. We also studied the effects of functionalized MWCNTs on the proliferation of three different cell types: MCF-7, HASMCs, Caco-2 cell lines. We observed also that MWCNTs, evaluated in the Ames test on Salmonella typhimurium TA 98 and TA 100 and on Escherichia coli WP2uvrA, in presence and in absence of the metabolic activation system S9, resulted devoid of mutagenic effect and reduced significantly the number of spontaneous revertants in TA 98 (up to a 35.8% reduction) [4]. In view of their subsequent and more extensive use, as to say in applications where carbon nanotubes are injected into the human body for drug delivery [9] as contrast agent carrying entities for MRI [10], or as the material of a new prosthesis generation [5], further extended tests and experiments are necessary. [5] M Chiaretti, G Mazzanti, S Bosco, S Bellucci, et Al. Carbon nanotubes toxicology and effects on metabolism and immunological modification in vitro and in vivo J. Phys.: Condens. Matter 20 (2008) 10pp.
4: Buckypaper of Multi-Walled Carbon Nanotubes (MWCNTs) toxicology and effects on metabolism, in vitro and in vivo.
Stefano Bellucci3, Massimo Chiaretti1, Alessandra Cucina2, Angela Carru1
1 General Surgery Department “Paride Stefanini” “La Sapienza” University, Viale del Policlinico, 155, 00161 Rome, Italy
2 General Surgery Department “Pietro Valdoni“ “La Sapienza” University, Viale del Policlinico, 155, 00161 Rome, Italy
3 INFN Frascati National Laboratories, Via Enrico Fermi 40, 00044 Frascati (Rome), Italy
Massimo Chiaretti General Surgery Department “Paride Stefanini, “Sapienza” University, Viale del Policlinico, 155, 00161 Rome, Italy tel: +39 06 4997214; fax: +39 06 4441255; e-mail: [email protected]
Submitted to Nanomedicine, Future Science Group, London
Abstract
The aim of this research is focused on the biological effects of buckypaper (BP) of MWCnts. These materials were tested on five different human cell types in vitro, and implanted in laboratory mice. We studied the biological effects and toxicology in vitro and in vivo. Large numbers of researchers are directly involved in the handling of nanostructured materials such as MWCnts and nanoparticles. It is important to assess the potential health risks related to their daily exposure to carbon nanotubes. The administration of sterilized nanosamples and BP were been prepared and performed on cells and mice. Pathological effects on mouse tissues cicatrisation have been investigated in optical microscopy. We studied tissues modifications after buckypaper implantation along five weeks after the operation. No mutagenic effects were observed. We studied BP effects on cell proliferation of five different types of human cell cultures: two solid cancer cell lines, Caco2 and MCF-7, a leukemic cell line HL-60 and two normal primary cells, HA-SMCs (human arterial smooth muscle cells) and HFs (human dermal fibroblasts). This study showed that BP induced a significant reduction of cell proliferation in Caco2 and MCF-7 cell lines, and a complete inhibition of cell growth in HL-60 cell line. This effect of BP seems to be specific in transformed cells, because BP did not produce any reduction of the proliferation and viability of two normal primary cell cultures. Present results are useful to extend the knowledge on safety of BP in view of its possible applications. However, for future medical applications, it could be useful to realize MWCnts based prosthesis to study the implantation effects. Moreover, it has to be emphasized that our research group it is going on investigation about apoptosis and carcinogenicity of MWCnts, which requires a detailed follow-up investigation on the specific topic. In view of the subsequent and more extensive use of MWCnts, especially in medical and biological applications where MWCnts are injected into the human body for drug delivery, as a contrast agent carrying entities for MRI, or as the basic material of a new prosthesis generation, more extended tests and experiments are necessary.
5: Carbon nanotubes buckypaper toxicity: in vitro and in vivo effects on the metabolism and
immunological modifications
Stefano Bellucci1, Massimo Chiaretti2
1 INFN Frascati National Laboratories, Via Enrico Fermi 40, 00044 Frascati (Rome), Italy
2 General Surgery Department “Paride Stefanini” “La Sapienza” University, Viale del Policlinico, 155, 00161 Rome, Italy
Talk presented at the National Nanomedicine Conference NNC, 28, 29 november
2008, Centro Biotecnologie Avanzate (CBA), Genova
Abstract
We studied biological effects of Multi-Walled Carbon Nanotubes (shortly MWCnts) buckypaper on laboratory animals in vivo, as well as its immunological effects on mice. We also reported on the effects of functionalized Cnts on three different cell types and the lack of mutagenic activity in the bacterial reverse mutation assay of MWCnts. New uses of nanomaterials in surgery involve large numbers of researchers and potential patient. The implantation of sterilized buckypaper followed the study of serum immunological modifications after Cnts intraperitoneal administration without antigenic humoral reactions nor humoral immunity. We also studied the effects of functionalized Cnts on the proliferation of three different cell types: MCF-7, hSMCs, Caco-2 cell lines. We observed also that (MWCnts), evaluated in the Ames test on Salmonella typhimurium TA 98 and TA 100 and on Escherichia coli WP2uvrA, in presence and in absence of the metabolic activation system S9, resulted devoid of mutagenic effect and reduced significantly the number of spontaneous revertants in TA 98 (up to 35.8% of reduction).
[1] M Chiaretti, G Mazzanti, S Bosco, S Bellucci, et Al. J. Phys.: Condens. Matter 20 (2008) (10pp)
[2] S. Bellucci, M. Chiaretti, et al. (2008) Nanotoxicology,submitted, Preliminary study on IR active modes in sterilized carbon nanotubes: a sterilization procedure for in vivo nanotoxicity tests
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