Heparin Mimetik Peptid ile Modifiye Edilmiş Kendiliğinden Yapılanan Peptid Hidrojel ile İnsan Mezenkimal Kök Hücrelerinin Çoğalma Kinetiğinin Arttırılması

Öz

Doğal hücre dışı matris (HDM) bileşenlerinin rolünü taklit eden üç boyutlu (3B) mikro ortamların geliştirilmesi çok önemlidir. Kendiliğinden yapılanan peptit (KYP) hidrojeller, hücrelerin enkapsülasyonu, 3B kültürü, çoğalması ve farklılaşması için ve ayrıca kıkırdak dokusundaki kusurları onarmak için yapı iskeleleri olarak kullanılmıştır. KYP'ler, biyomimetik yapı iskeleleri oluşturmak için kısa peptit epitopları ile biyofonksiyonelleştirilebilir. Burada, KLD (KLDLKLDLKLDL) KYP, KLD-HM (KLDLKLDLKLDL-EGDK) KYP hidrojeli üretmek için kısa bir biyoaktif motif olan EGDK ile işlevselleştirildi ve kendiliğinden yapılandırıldı. Bu çalışmada, geliştirilen KLD-HM KYP hidrojellerinin insan mezenkimal kök hücrelerinin (iMKH'ler) canlılığı ve proliferasyonu üzerindeki etkisinin araştırılması amaçlanmıştır. KYP'lerin stabilitesini sağlamak için, üretilen KYP hidrojellerin reolojik özellikleri ve bozunma profili değerlendirildi. iMKH'lerin KYP hidrojelleri içerisine enkapsüle edilmesinden sonra, MTT tahlili ve Canlı ve Ölü boyama tahlili yapıldı. Bu biyomimetik peptit hidrojel iskelelerinin, enkapsüle edilmiş iMKH'ler için uygun bir mikro ortam sağladığını ve geliştirilen KYP hidrojellerinin iMKH'lerin yapışmasını, canlılığını ve çoğalmasını desteklediğini gösterdik. Sonuçlarımız, tasarlanmış olan biyoaktif SAP hidrojel iskelelerinin kıkırdak dokusunun yenilenmesini teşvik etmek için yararlı olabileceğini düşündürmektedir.

Anahtar Kelimeler

• Kıkırdak doku mühendisliği
• Heparin-mimetik
• Mezenkimal kök hücreler
• Peptit
• Kendiliğinden yapılanan peptid hidrojel

Enhanced Proliferation of Human Mesenchymal Stem Cells by Self-Assembled Peptide Hydrogel Modified with Heparin Mimetic Peptide

Abstract

The development of three-dimensional (3D) microenvironments that mimic the role of native extracellular matrix (ECM) components is very crucial. Self-assembling peptide (SAP) hydrogels have been utilized as scaffolds for encapsulation, 3D culture, proliferation, and differentiation of cells and also for repairing defects in cartilage tissue. SAPs can be biofunctionalized with short peptide epitopes to form biomimetic scaffolds. Herein, KLD (KLDLKLDLKLDL) SAP was functionalized with a short bioactive motif, EGDK, to fabricate KLD-HM (KLDLKLDLKLDL-EGDK) SAP hydrogel and self-assembled. In this study, it was aimed to investigate the effect of developed KLD-HM SAP hydrogels on the viability and proliferation of human mesenchymal stem cells (hMSCs). For ensuring the stability of SAPs, the rheological properties and degradation profile of produced SAP hydrogels were assessed. After the encapsulation of hMSCs in SAP hydrogels, MTT assay and Live and Dead staining assay were conducted. We showed that these biomimetic peptide hydrogel scaffolds provided a proper microenvironment for encapsulated hMSCs and the developed SAP hydrogels promoted the adhesion, viability, and proliferation of hMSCs. Our results suggest that designed bioactive SAP hydrogel scaffolds might be useful for promoting the regeneration of cartilage tissue.

Keywords

• Cartilage tissue engineering
• Heparin-mimetic
• Mesenchymal stem cells
• Peptide
• Self-assembled peptide hydrogel

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