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

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.

SUBMITTER: Latifi N

PROVIDER: S-EPMC5773686 | biostudies-other | 2018 Jan

REPOSITORIES: biostudies-other

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

Latifi Neda N Asgari Meisam M Vali Hojatollah H Mongeau Luc L

Scientific reports 20180118 1

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 nove ...[more]

PMID: 29348423

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Project description:Biodegradable injectable hydrogels have been extensively studied and evaluated in various medical applications such as for bulking agents, drug delivery reservoirs, temporary barriers, adhesives, and cell delivery matrices. Where injectable hydrogels are intended to facilitate a healing response, it may be desirable to encourage rapid cellular infiltration into the hydrogel volume from the tissue surrounding the injection site. In this study, we developed a platform technique to rapidly form pores in a thermally responsive injectable hydrogel, poly(NIPAAm-co-VP-co-MAPLA) by using mannitol particles as porogens. In a rat hindlimb muscle injection model, hydrogels incorporating porosity had significantly accelerated cellular infiltration. To influence the inflammatory response to the injected hydrogel, enzymatically digested urinary bladder matrix (UBM) was mixed with the solubilized hydrogel. The presence of UBM was associated with greater polarization of the recruited macrophage population to the M2 phenotype, indicating a more constructive foreign body response. The hybrid hydrogel positively affected the wound healing outcomes of defects in rabbit adipose tissue with negligible inflammation and fibrosis, whereas scar formation and chronic inflammation were observed with autotransplantation and in saline injected groups. These results demonstrate the value of combining the effects of promoting cell infiltration and mediating the foreign body response for improved biomaterials options soft tissue defect filling applications. STATEMENT OF SIGNIFICANCE:Our objective was to develop a fabrication process to create porous injectable hydrogels incorporating decellularized tissue digest material. This new hydrogel material was expected to exhibit faster cellular infiltration and a greater extent of pro-M2 macrophage polarization compared to control groups not incorporating each of the functional components. Poly(NIPAAm-co-VP-co-MAPLA) was chosen as the representative thermoresponsive hydrogel, and mannitol particles and digested urinary bladder matrix (UBM) were selected as the porogen and the bioactive decellularized material components respectively. In rat hindlimb intramuscular injection models, this new hydrogel material induced more rapid cellular infiltration and a greater extent of M2 macrophage polarization compared to control groups not incorporating all of the functional components. The hybrid hydrogel positively affected the wound healing outcomes of defects in rabbit adipose tissue with negligible inflammation and fibrosis, whereas scar formation and chronic inflammation were observed with autotransplantation and in saline injected groups. The methodology of this report provides a straightforward and convenient mechanism to promote cell infiltration and mediate foreign body response in injectable hydrogels for soft tissue applications. We believe that the readership of Acta Biomaterialia will find the work of interest both for its specific results and general translatability of the findings.

Dataset Information

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

Publications

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

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