Salih TOPÇU, Hüseyin Fatih SEZER, Göksu ÖZÇELİKAY, Betül ARICA, Aykut ELİÇORA, Kürşat YILDIZ, Şerife Tuba LİMAN

Transforme edici büyüme faktörü-beta-1 nötralizan antikoru ve transforme edici büyüme faktörü-beta-3’ün trakeal darlık gelişimi üzerine etkileri

Amaç: Bu çalışmada transforme edici büyüme faktörü-3 ve transforme edici büyüme faktörü-1 nötralizan antikoru içeren polimerik polikaprolakton film formülasyonlarının trakea cerrahisinde darlığın önlenmesi üzerine etkileri değerlendirildi.Çalışma planı: Çalışmaya 24 erkek Wistar albino sıçan (ağırlık 200 g-250 g) dahil edildi. Gruplar A) kontrol (n=6); B) boş polimerik polikaprolakton film (n=6); C) transforme edici büyüme faktörü-3 içeren polimerik polikaprolakton film formülasyonu (n=6); D) transforme edici büyüme faktörü-1 nötralizan antikoru içeren polimerik polikaprolakton film formülasyonu (n=6) olarak tanımlandı. Tüm sıçanlara ikinci ve beşinci trakeal halkalar arasında yaklaşık 0.5 cm’lik vertikal insizyon yapıldı. Grup A’da trakeal insizyon sadece sütüre edildi. Grup B, C ve D’de trakeal insizyon sütüre edildikten sonra trakeal insizyonun üzerine sırası ile boş polimerik polikaprolakton film, transforme edici büyüme faktörü-3 içeren polimerik polikaprolakton film formülasyonu, transforme edici büyüme faktörü-1 nötralizan antikoru içeren polimerik polikaprolakton film formülasyonu yerleştirildi. Cerrahiden 30 gün sonra sıçanlar sakrifiye edildi. Sonrasında sıçanların trakeaları mikroskobik olarak incelendi. Epitelizasyon, fibrozis, anjiogenezis ve inflamasyon durumları histopatolojik olarak değerlendirildi.Bulgular: Otuz gün boyunca solunum sıkıntısı, stridor ve beslenme bozukluğu açısından izlenen sıçanlarda anormal bir durum görülmedi. Gruplar enflamasyon, fibrozis, anjiyogenezis ve epitelizasyon açısından değerlendirildiğinde istatistiksel olarak anlamlı farklılık bulunmadı (p>0.05).Sonuç: Transforme edici büyüme faktörünün aktif formları dokuda oldukça kısa yarılanma ömrüne sahiptir ve hızla uzaklaştırılmaktadır. Yeni geliştirilecek preperatlar ile bioaktivite korunabilir ve kontrollü salınım sağlanabilir. Transforme edici büyüme faktörü-3’ün ve transforme edici büyüme faktörü-1 nötralizan antikorlarının trakea cerrahisi sonrasında granülasyon dokusunu önleme etkisini değerlendirmek için daha ileri detaylı araştırmalara gerek vardır.

Effects of transforming growth factor-beta-1 neutralizing antibody and transforming growth factor-beta-3 on the development of tracheal stenosis

Background: This study aims to evaluate the effects of transforming growth factor-3 and neutralizing antibody of transforming growth factor-1 containing polymeric polycaprolactone film formulations on prevention of stenosis in tracheal surgery.Methods: The study included 24 male Wistar albino rats (weight 200 g to 250 g). Groups were defined as A) control (n=6); B) blank polymeric polycaprolactone film (n=6); C) transforming growth factor-3 containing polymeric polycaprolactone film formulation (n=6); and D) transforming growth factor-1 neutralizing antibody containing polymeric polycaprolactone film formulation (n=6). Approximately a 0.5 cm vertical incision was performed on all rats between the second and fifth tracheal circles. In group A, tracheal incision was only sutured. In groups B, C and D, tracheal incision was sutured and then blank polymeric polycaprolactone film, transforming growth factor-3 containing polymeric polycaprolactone film formulation and transforming growth factor-1 neutralizing antibody containing polymeric polycaprolactone film formulation was placed on the tracheal incision, respectively. The rats were sacrificed 30 days after the surgery. Subsequently, tracheas of rats were examined microscopically. Epithelialization, fibrosis, angiogenesis and inflammation statuses were evaluated histopathologically.Results: The rats that were observed in terms of respiratory distress, stridor, and malnutrition for 30 days did not show any abnormal events. When the groups were evaluated in terms of inflammation, fibrosis, angiogenesis and epithelization, no statistically significant difference was found (p>0.05).Conclusion: The active forms of transforming growth factor have a considerably short half-life in the tissue and extracted rapidly. Bioactivity may be maintained and controlled release may be provided with preparations to be developed. Further detailed researches are required to evaluate the effect of transforming growth factor-3 and transforming growth factor-1 neutralizing antibody on prevention of granulation tissue after tracheal surgery.

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16. Woodruff, Maria A. & Hutmacher, Dietmar W. The return of a forgotten polymer: Polycaprolactone in the 21st century. Progress in Polymer Science 2010;35:1217-56.
15. Sarasam A, Madihally SV. Characterization of chitosan-polycaprolactone blends for tissue engineering applications. Biomaterials 2005;26:5500-8.
14. Ashton JH, Mertz JA, Harper JL, Slepian MJ, Mills JL, McGrath DV, et al. Polymeric endoaortic paving: Mechanical, thermoforming, and degradation properties of polycaprolactone/ polyurethane blends for cardiovascular applications. Acta Biomater 2011;7:287-94.
13. Astete CE, Sabliov CM. Synthesis and characterization of PLGA nanoparticles. J Biomater Sci Polym Ed 2006;17:247-89.
12. Eliçora A, Liman ST, Yegin BA, Akgül AG, Eroglu H, Yildiz K, et al. Effect of locally applied transforming growth factor Beta3 on wound healing and stenosis development in tracheal surgery. Respir Care 2014;59:1281-6.
11. Günay Ş, Koçarslan A, Eser İ, Yılmaz R, Özbey M. Efficiency of platelet rich plasma in tracheotomy. Turk Gogus Kalp Dama 2016;24:532-8.
10. Shah M, Foreman DM, Ferguson MW. Neutralisation of TGF-beta 1 and TGF-beta 2 or exogenous addition of TGF-beta 3 to cutaneous rat wounds reduces scarring. J Cell Sci 1995;108:985-1002.
9. Loewen MS, Walner DL, Caldarelli DD. Improved airway healing using transforming growth factor beta-3 in a rabbit model. Wound Repair Regen 2001;9:44-9.
8. Lee YC, Hung MH, Liu LY, Chang KT, Chou TY, Wang YC, et al. The roles of transforming growth factor-1 and vascular endothelial growth factor in the tracheal granulation formation. Pulm Pharmacol Ther 2011;24:23-31.
7. Reinke JM, Sorg H. Wound repair and regeneration. Eur Surg Res 2012;49:35-43.
6. Fathke C, Wilson L, Hutter J, Kapoor V, Smith A, Hocking A, et al. Contribution of bone marrow-derived cells to skin: collagen deposition and wound repair. Stem Cells 2004;22:812-22.
5. Song G, Nguyen DT, Pietramaggiori G, Scherer S, Chen B, Zhan Q, et al. Use of the parabiotic model in studies of cutaneous wound healing to define the participation of circulating cells. Wound Repair Regen 2010;18:426-32.
4. Hsu M, Peled ZM, Chin GS, Liu W, Longaker MT. Ontogeny of expression of transforming growth factor-beta 1 (TGF-beta 1), TGF-beta 3, and TGF-beta receptors I and II in fetal rat fibroblasts and skin. Plast Reconstr Surg 2001;107:1787-94.
3. Ferguson MW, O’Kane S. Scar-free healing: from embryonic mechanisms to adult therapeutic intervention. Philos Trans R Soc Lond B Biol Sci 2004;359:839-50.
2. Iro H, Zenk J, Glab WV, Weidenbecher M. Segmental resection in the treatment of tracheal stenosis. Operative Techniques in Otolaryngology-Head and Neck Surgery 1997;8:130-5.
1. Rea F, Callegaro D, Loy M, Zuin A, Narne S, Gobbi T, et al. Benign tracheal and laryngotracheal stenosis: surgical treatment and results. Eur J Cardiothorac Surg 2002;22:352-6.