A tissue-mimetic nano-fibrillar hybrid injectable hydrogel for potential soft tissue engineering applications

Neda Latifi,Luc Mongeau,Hojatollah Vali,Meisam Asgari

doi:10.1038/s41598-017-18523-3

Abstract

While collagen type I (Col-I) is commonly used as a structural component of biomaterials, collagen type III (Col-III), another fibril forming collagen ubiquitous in many soft tissues, has not previously been used. In the present study, the novel concept of an injectable hydrogel with semi-interpenetrating polymeric networks of heterotypic collagen fibrils, with tissue-specific Col-III to Col-I ratios, in a glycol-chitosan matrix was investigated. Col-III was introduced as a component of the novel hydrogel, inspired by its co-presence with Col-I in many soft tissues, its influence on the Col-I fibrillogenesis in terms of diameter and mechanics, and its established role in regulating scar formation. The hydrogel has a nano-fibrillar porous structure, and is mechanically stable under continuous dynamic stimulation. It was found to provide a longer half-life of about 35 days than similar hyaluronic acid-based hydrogels, and to support cell implantation in terms of viability, metabolic activity, adhesion and migration. The specific case of pure Col-III fibrils in a glycol-chitosan matrix was investigated. The proposed hydrogels meet many essential requirements for soft tissue engineering applications, particularly for mechanically challenged tissues such as vocal folds and heart valves.

Highlights

Considerable efforts have been made over the past few decades to develop scaffolding materials which mimic the extracellular matrix (ECM) for Soft Tissue Engineering (STE), the process of synthesizing natural tissue for the repair or replacement of diseased or lost tissues[1,2,3,4,5,6]
We have recently demonstrated that the incorporation of tropocollagen type III in tropocollagen type I yields the formation of heterotypic fibrils of both types I and III with smaller diameter, periodicity (Fig. 1a) and elastic moduli than those of single Collagen type I (Col-I) counterparts[23]
It was previously reported that mature scar tissue has 50% less Collagen type III (Col-III) than normal tissue, and its fibers form thick bundles arranged in parallel arrays[24]

Summary

Introduction

Considerable efforts have been made over the past few decades to develop scaffolding materials which mimic the extracellular matrix (ECM) for Soft Tissue Engineering (STE), the process of synthesizing natural tissue for the repair or replacement of diseased or lost tissues[1,2,3,4,5,6] These scaffolding materials are used in vivo, for in-situ tissue regeneration, or in vitro for the fabrication of tissue substitutes in tissue culture bioreactors[7,8], or as controlled tissue-mimetic microenvironments to investigate the effects of biomechanical and biochemical stimuli on cell behavior[2]. A low ratio of Col-III to Col-I in bladder tissue was shown to alter fibril size distribution, and to yield

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