Abstract

The use of porous three-dimensional (3D) composite scaffolds has attracted great attention in bone tissue engineering applications because they closely simulate the major features of the natural extracellular matrix (ECM) of bone. This study aimed to prepare biomimetic composite scaffolds via a simple 3D printing of gelatin/hyaluronic acid (HA)/hydroxyapatite (HAp) and subsequent biomineralization for improved bone tissue regeneration. The resulting scaffolds exhibited uniform structure and homogeneous pore distribution. In addition, the microstructures of the composite scaffolds showed an ECM-mimetic structure with a wrinkled internal surface and a porous hierarchical architecture. The results of bioactivity assays proved that the morphological characteristics and biomineralization of the composite scaffolds influenced cell proliferation and osteogenic differentiation. In particular, the biomineralized gelatin/HA/HAp composite scaffolds with double-layer staggered orthogonal (GEHA20-ZZS) and double-layer alternative structure (GEHA20-45S) showed higher bioactivity than other scaffolds. According to these results, biomineralization has a great influence on the biological activity of cells. Hence, the biomineralized composite scaffolds can be used as new bone scaffolds in bone regeneration.

Highlights

  • The reconstruction of damaged bone defects originating from tumors, trauma, infections, and congenital malformations is a complex biological process that requires osteoconductive scaffolds, osteogenic precursor cells, and osteoinductive growth factors, which needs precise control of bleeding disorders by congenital afibrinogenemia at the defect site [1,2]

  • The solution viscosity was found to be most critical to the 3D printing [18]

  • It was reported that the aqueous gelatin solution showed thermo-responsive behavior without chemical crosslinking [19]

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Summary

Introduction

The reconstruction of damaged bone defects originating from tumors, trauma, infections, and congenital malformations is a complex biological process that requires osteoconductive scaffolds, osteogenic precursor cells, and osteoinductive growth factors, which needs precise control of bleeding disorders by congenital afibrinogenemia at the defect site [1,2]. Tissue-engineered three-dimensional (3D) scaffolds are currently recognized as ideal substitutes for autologous bone grafts because of their biocompatibility and osteoconductivity These scaffolds should mimic the physical and chemical properties of the extracellular matrix (ECM) to promote bone regeneration, implying that they should provide a conducive microenvironment for the selected cells [5,6]. Several fabrication methods, such as freeze drying, electrospinning, and double emulsion methods, have been explored for preparing porous scaffolds for bone tissue engineering [7,8,9]. As an advanced fabrication technology, 3D printing has recently attracted great attention in the biomedical field because of its versatility, ease of use, and precise control of a customized shape with unique architecture [4,6,10]

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