Publication: Üç boyutlu biyobaskılama yöntemi ile kronik yaraların tedavisi için hidrojel yara örtülerin geliştirilmesi
Abstract
Amaç: Günümüzde kronik ve akut yaraların tedavisi, enfeksiyona yatkınlık, gecikmiş iyileşme profili ve mevcut yara örtülerinin yetersizliğinden dolayı zorlu bir iştir. Bu tez kapsamında kronik yaraların kişiselleştirilmiş tedavisi için ekstrüzyon temelli üç boyutlu (3B) biyobaskılama yöntemi ile UV çapraz bağlanabilir, hemostatik ve biyoadezif özellikli, çok fonksiyonlu hidrojel yara örtülerinin geliştirilmesi amaçlanmıştır. Bu kapsamda iç tabakada metformin yüklü ipek fibroin (İF)/ hyalüronik asit metakriloil (HaMA)/ jelatin metakriloil (JelMA); dış tabaka ise antimikrobiyal peptid Tet213 yüklü kitosan metakriloil (KitMA)/ JelMA/ HaMA hidrojeli içeren iki tabakalı yara örtüsü tasarlanmıştır. Gereç ve Yöntem: Hidrojellerde kullanılan biyopolimerlerin sentezi sonrası, 3B baskılama için hidrojel biyomürekkepler optimize edilmiştir. Hidrojellerin, mekanik özellikleri, şişme, hidrolitik degredasyon, porozite, su buharı geçirgenliği, in vitro etken madde salım özellikleri, antibakteriyel etkinliği, ex vivo doku adezyonu, in vitro kan alım, hemostatik özellikleri ve hemoliz özellikleri karakterize edilmiştir. Bulgular: KitMA (%1)/ HaMA(%0,25)/ JelMA(%12,5) a/ h oranlarında ve İF(%3)/ HaMA(%0,5)/ JelMA(%10) a/ h oranlarında 3B baskılama için optimal olarak belirlenmiş ve sırasıyla %56,056 ± 5,328 ve %43,810 ± 3,598 porozite; %424,510 ± 16,338 ve %332,050 ± 3,407 şişme oranı göstermişlerdir. KitMA/ HaMA/ JelMA ve İF/ HaMA/ JelMA yara örtüleri için sırasıyla 359,098 ± 21,286 kPa ve 312,086 ± 30,241 kPa sıkıştırma modülü; 1,618 ± 0,237 N ve 1,532 ± 0,738 N biyoadezyon kuvveti bulunmuştur. 4 Haftalık degredasyon sonunda kalan kütle %18,747 ve %27,517 olarak belirlenmiş ve bu süre sonunda yüklenen Tet213’ün %98,373 ± 5,902’u ile yüklenen metforminin %81,289 ± 4,289’u yara örtülerinden salınmıştır. Her iki yara örtüsü de hemostatik özellik, iyi kan uyumluluğu ve yüksek biyouyumluluk göstermektedir. Sonuç: Geliştirilen yara örtüleri, kronik yaraların kişiye özgü tedavisi için yara iyileşmesini sağlayan, enfeksiyon gelişimini engelleyebilen, hemostatik ve adezif özellikte çok fonksiyonlu bir platform sunmaktadır. Tasarlanan sistemin kronik yaraların kişiye özel tedavisi için önemli bir yaklaşım oluşturacağı öngörülmektedir.
Objective: The treatment of chronic, and acute wounds has been challenging issue due to the wounds' susceptibility to infection, delayed healing profile, and inadequacy of existing wound dressings, recently. Within the scope of this study, it is aimed to develop multifunctional bi-layered hydrogel wound dressings, with UV cross-linkable, hemostatic, and bioadhesive properties via extrusion-based three-dimensional (3D) bioprinting method for the personalized treatment of chronic wounds. Silk fibroin (SF)/ hyaluronic acid methacryloil (HaMA)/ gelatin methacryloil (JelMA) hydrogel loaded with metformin as an inner layer; chitosan methacryloil (ChitMA)/ GelMA/ HaMA/ hydrogel loaded with antimicrobial peptide Tet213 as an outer layer were designed to obtain the bi-layer structure. Materials and Methods: Hydrogel bioinks were optimized for 3D bioprinting after the synthesis and extraction of biopolymers. Mechanical properties, swelling and hydrolytic degradation, porosity, and water vapor permeability, in vitro release, antibacterial activity, ex vivo tissue adhesion, hemocompatibility properties of hydrogels were characterized. Results: ChitMA (%1)/ HaMA(0.25%)/ GelMA(12.5%) w/ v ratios and SF(%3)/ HaMA(0.5%)/ GelMA(10%) w/ v ratios determined as optimal for 3D bioprinting. Porosity of 56.056 ± 5,328% and 43.810 ± 3,598%, swelling rate of 424,510 ± 16,338% and 332,050 ± 3,407% were found, respectively for ChitMA/ HaMA/ GelMA and SF/ HaMA/ GelMA dressings. Compression modulus of 359,098 ± 21.286 kPa and 312,086 ± 30,241 kPa ; bioadhesion strength of 1.618 ± 0.237 N and 1.532 ± 0.738 N were found respectively, as well. After 4 weeks of degradation, 18.747% and 27.517% of the residual mass left and 98.373 ± 5.902% of loaded Tet213 and 81.289 ± 4.289% of loaded metformin were released. Both wound dressings were showed good hemostatic properties and excellent hemocompatibility. Conclusion: The developed wound dressings offer a multifunctional platform with that can prevent the development of infection, and provide wound healing for the personalized treatment of chronic wounds. The designed system possesses the potential to be a constitute with supporting approach for the personalized treatment of chronic wounds.
Objective: The treatment of chronic, and acute wounds has been challenging issue due to the wounds' susceptibility to infection, delayed healing profile, and inadequacy of existing wound dressings, recently. Within the scope of this study, it is aimed to develop multifunctional bi-layered hydrogel wound dressings, with UV cross-linkable, hemostatic, and bioadhesive properties via extrusion-based three-dimensional (3D) bioprinting method for the personalized treatment of chronic wounds. Silk fibroin (SF)/ hyaluronic acid methacryloil (HaMA)/ gelatin methacryloil (JelMA) hydrogel loaded with metformin as an inner layer; chitosan methacryloil (ChitMA)/ GelMA/ HaMA/ hydrogel loaded with antimicrobial peptide Tet213 as an outer layer were designed to obtain the bi-layer structure. Materials and Methods: Hydrogel bioinks were optimized for 3D bioprinting after the synthesis and extraction of biopolymers. Mechanical properties, swelling and hydrolytic degradation, porosity, and water vapor permeability, in vitro release, antibacterial activity, ex vivo tissue adhesion, hemocompatibility properties of hydrogels were characterized. Results: ChitMA (%1)/ HaMA(0.25%)/ GelMA(12.5%) w/ v ratios and SF(%3)/ HaMA(0.5%)/ GelMA(10%) w/ v ratios determined as optimal for 3D bioprinting. Porosity of 56.056 ± 5,328% and 43.810 ± 3,598%, swelling rate of 424,510 ± 16,338% and 332,050 ± 3,407% were found, respectively for ChitMA/ HaMA/ GelMA and SF/ HaMA/ GelMA dressings. Compression modulus of 359,098 ± 21.286 kPa and 312,086 ± 30,241 kPa ; bioadhesion strength of 1.618 ± 0.237 N and 1.532 ± 0.738 N were found respectively, as well. After 4 weeks of degradation, 18.747% and 27.517% of the residual mass left and 98.373 ± 5.902% of loaded Tet213 and 81.289 ± 4.289% of loaded metformin were released. Both wound dressings were showed good hemostatic properties and excellent hemocompatibility. Conclusion: The developed wound dressings offer a multifunctional platform with that can prevent the development of infection, and provide wound healing for the personalized treatment of chronic wounds. The designed system possesses the potential to be a constitute with supporting approach for the personalized treatment of chronic wounds.