In Vitro Generation of Novel Functionalized Biomaterials for Use in Oral and Dental Regenerative Medicine Applications. Running Title: Fibrin-Agarose Functionalized Scaffolds.

Cristina Blanco-Elices,Óscar García-García,Ricardo Fernández-Valadés,Miguel Alaminos,Enrique España-Guerrero,María Sánchez-Quevedo,Miguel Martín-Piedra,David Sánchez-Porras,Ingrid Garzón,Miguel Mateu-Sanz

doi:10.3390/ma13071692

Cristina Blanco-Elices, Óscar García-García + Show 8 more

Open Access

https://doi.org/10.3390/ma13071692

Copy DOI

Abstract

Recent advances in tissue engineering offer innovative clinical alternatives in dentistry and regenerative medicine. Tissue engineering combines human cells with compatible biomaterials to induce tissue regeneration. Shortening the fabrication time of biomaterials used in tissue engineering will contribute to treatment improvement, and biomaterial functionalization can be exploited to enhance scaffold properties. In this work, we have tested an alternative biofabrication method by directly including human oral mucosa tissue explants within the biomaterial for the generation of human bioengineered mouth and dental tissues for use in tissue engineering. To achieve this, acellular fibrin–agarose scaffolds (AFAS), non-functionalized fibrin-agarose oral mucosa stroma substitutes (n-FAOM), and novel functionalized fibrin-agarose oral mucosa stroma substitutes (F-FAOM) were developed and analyzed after 1, 2, and 3 weeks of in vitro development to determine extracellular matrix components as compared to native oral mucosa controls by using histochemistry and immunohistochemistry. Results demonstrate that functionalization speeds up the biofabrication method and contributes to improve the biomimetic characteristics of the scaffold in terms of extracellular matrix components and reduce the time required for in vitro tissue development.

Highlights

Regenerative medicine applies multidisciplinary biology and engineering science to therapeutic approaches to regenerate, replace, or repair tissues and organs [1]
Gross inspection of the bioartificial tissues generated by using the functionalization method described in the present work showed a compact biomaterial in which the tissue explants were immersed (Figure 1A,B), whereas acellular fibrin–agarose scaffolds (AFAS) and non-functionalized fibrin-agarose oral mucosa stroma substitutes (n-FAOM) samples were apparently more regular and homogeneous due to the lack of explants immersed within
The histological analysis using hematoxylin and eosin (H&E) revealed that the oral mucosa explants were completely surrounded by the fibrin–agarose scaffold and properly integrated in the biomaterial (Figure 1C), whereas the other tissue types (AFAS and n-FAOM) consisted of a fibrillar biomaterial with a regular structure that only contained cells in the case of n-FAOM tissues

Summary

Introduction

Regenerative medicine applies multidisciplinary biology and engineering science to therapeutic approaches to regenerate, replace, or repair tissues and organs [1]. Some of the ECM proteins employed in functionalization process are collagen and glycosaminoglycans [8], fibronectin [9], laminin [10], or short peptide sequences derived from them that have major stability and interplay with cells [11]. These molecules can be added to scaffolds by different techniques, that includes physical absorption of a solution and covalent binding [12]. All these reported techniques are intended to separately introduce functional molecules in the biomaterial, so that these molecules can later interact with cells

Methods

Results

Conclusion