Improved Osteogenesis by Mineralization Combined With Double-Crosslinked Hydrogel Coating for Proliferation and Differentiation of Mesenchymal Stem Cells.

Yiqun Ma,Hong Lin,Lu Cao,Bo Tian,Yuwang You,Bing Liang,Jian Dong

doi:10.3389/fbioe.2021.706423

Abstract

In consideration of improving the interface problems of poly-L-lactic acid (PLLA) that hindered biomedical use, surface coatings have been explored as an appealing strategy in establishing a multi-functional coating for osteogenesis. Though the layer-by-layer (LBL) coating developed, a few studies have applied double-crosslinked hydrogels in this technique. In this research, we established a bilayer coating with double-crosslinked hydrogels [alginate–gelatin methacrylate (GelMA)] containing bone morphogenic protein (BMP)-2 [alginate-GelMA/hydroxyapatite (HA)/BMP-2], which displayed great biocompatibility and osteogenesis. The characterization of the coating showed improved properties and enhanced wettability of the native PLLA. To evaluate the biosafety and inductive ability of osteogenesis, the behavior (viability, adherence, and proliferation) and morphology of human bone mesenchymal stem cells (hBMSCs) on the bilayer coatings were tested by multiple exams. The satisfactory function of osteogenesis was verified in bilayer coatings. We found the best ratios between GelMA and alginate for biological applications. The Alg70-Gel30 and Alg50-Gel50 groups facilitated the osteogenic transformation of hBMSCs. In brief, alginate-GelMA/HA/BMP-2 could increase the hBMSCs’ early transformation of osteoblast lineage and promote the osteogenesis of bone defect, especially the outer hydrogel layer such as Alg70-Gel30 and Alg50-Gel50.

Highlights

The treatment of bone defects still needs further exploration because of the unsatisfactory clinical outcome
Polydopamine coating is firstly formed on poly-L-lactic acid (PLLA) films in alkaline and weak oxidation environment, which has an affinity for hydroxyapatite (Wu, Zhang, Zhang, & Chen, 2021)
As sodium alginate is more viscous than Gelatin methacrylate (GelMA) at the same concentration, the protuberance on substrate surface becomes more obvious as the proportion of sodium alginate in the outer coating decreases

Summary

Introduction

The treatment of bone defects still needs further exploration because of the unsatisfactory clinical outcome. Kandziora et al (2004) used a fusion cage made of PLLA to treat cervical and lumbar spine diseases. Based on the potential application in bone engineering, PLLA is usually combined with apatite ceramics, such as hydroxyapatite or tricalcium phosphate, to improve this polymer’s property. In vitro experiments showed that the hydrophilicity of the PLLA increased and the cell attachment and proliferation enhanced as well (Szustakiewicz et al, 2021; Tan et al, 2021). All this is possible thanks to the component and microstructural similarity between the apatite ceramics and native bone

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