Abstract

With the increased incidence of bone defects following trauma or diseases in recent years, three-dimensional porous scaffolds fabricated using bioprinting technologies have been widely explored as effective alternatives to conventional bone grafts, which provide cell-friendly microenvironments promoting bone repair and regeneration. However, the limited use of biomaterials poses a significant challenge to the robust and accurate fabrication of bioprinted bone scaffolds that enable effective regeneration of the target tissues. Although bioceramic/polymer composites can provide tunable biomimetic conditions, their effects on the bioprinting process are unclear. Thus, in this study, we fabricated hydroxyapatite (HA)/gelatin composite scaffolds containing large weight fractions of HA using extrusion-based bioprinting, with the aim to provide an adequate biomimetic environment for bone tissue regeneration with compositional and mechanical similarity to the natural bone matrix. The overall features of the bioprinted HA/gelatin composite scaffolds, including rheological, morphological, physicochemical, mechanical, and biological properties, were quantitatively assessed to determine the optimal conditions for both fabrication and therapeutic efficiency. The present results show that the bioprinted bioceramic/hydrogel scaffolds possess excellent shape fidelity; mechanical strength comparable to that of native bone; and enhanced bioactivity in terms of cell proliferation, attachment, and osteogenic differentiation. This study provides a suitable alternative direction for the fabrication of bioceramic/hydrogel-based scaffolds for bone repair based on bioprinting.

Highlights

  • The aging global population has resulted in an increased incidence of bone defects following trauma or diseases in recent years [1,2,3]

  • Among the various techniques used to fabricate tissue-engineered bone constructs, three-dimensional (3D) bioprinting has been widely explored as an effective alternative, which provides cell-friendly microenvironments with a designed shape and porosity that promote bone repair and regeneration [11,12]

  • RheologicalaCnhdar1a%ctesrtirzaaitnio. nIn the frequency sweep tests, the angular frequency was increased from 0.1 Rheologictaol 1m0e0arsaudr/ems aetn2t0s ◦oCf HwAit/hgael1a%tinstcroaminp. osites were performed with a HR-2 (TA instruments) rheometer operating in oscillatory mode, using a 20 mm parallel plate with a 500 μm gap

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Summary

Introduction

The aging global population has resulted in an increased incidence of bone defects following trauma or diseases in recent years [1,2,3]. The addition of HA to a polymer improves the osteogenic properties of the fabricated composite scaffold and its rheological properties, enhancing both mechanical strength and shape fidelity [19] Both biocompatible synthetic polymers, such as polylactic acid (PLA), polylactic-coglycolic acid (PLGA), and PCL, and natural hydrogels, such as collagen, alginate, and gelatin, have been widely used as the organic component of bioceramic/polymer composites for bone tissue engineering applications [21]. The scaffolds with 60–80% HA had higher ARS absorbance values than the 0% HA scaffold at day 21 (Figure 7b) These results imply that the HA particles incorporated in the scaffolds can promote the osteogenic differentiation of ADMSCs, likely by enhancing the ALP activity of mesenchymal stem cells and stimulating the endogenous expression of osteogenic growth factors, such as bone morphogenetic proteins [16]

Conclusions
Rheological Characterization
Fabrication of Composite Scaffolds
Physicochemical and Structural Characterization
Mechanical Characterization
Cell Viability and Attachment
Osteogenic Differentiation

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