Abstract

Multi-layered hydrogels with organization of various functional layers have been the materials of choice for biomedical applications. This review summarized the recent progress of multi-layered hydrogels according to their preparation methods: layer-by-layer self-assembly technology, step-wise technique, photo-polymerization technique and sequential electrospinning technique. In addition, their morphology and biomedical applications were also introduced. At the end of this review, we discussed the current challenges to the development of multi-layered hydrogels and pointed out that 3D printing may provide a new platform for the design of multi-layered hydrogels and expand their applications in the biomedical field.

Highlights

  • Hydrogels are three-dimensional polymeric networks cross-linked by physical, chemical interactions or a combination of both

  • Multi-layered hydrogels with organization of various functional layers have been attracting extensive attentions, due to their ability to meet the diverse needs of biomedical applications

  • LBL self-assembly technology, the most commonly used methods for the preparation of multi-layered hydrogel, faces the following problems: (i) The construction process is carried out in a layer-by-layer fashion and the operation is cumbersome, which is not conducive to the construction of hydrogels with numerous layers and the engineering preparation of multi-layer hydrogels. (ii) The thickness of each layer within multi-layered hydrogels cannot be adjusted flexibly. (iii) The range of drugs suited to such operation is narrow and the efficiency of drug loading is low

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Summary

Introduction

Hydrogels are three-dimensional polymeric networks cross-linked by physical, chemical interactions or a combination of both. A key property of hydrogel matrices is that they have viscoelastic properties like many soft tissues and permeability to different types of molecules, such as proteins, bioactive agents and growth factors (Pan et al, 2011; Gupta et al, 2014; Lau and Kiick, 2015). To better mimic anisotropic and complex structure of body tissues, hierarchical hydrogels containing multiple layers with different biochemical cues and various mechanical properties play crucial role for biomedical applications (O’Leary et al, 2011; Hu and Chen, 2014; Martínezsanz et al, 2016). Multi-layered hydrogels, formulated by the combination of multiple cell types, drugs or some other exogenous factors, could realize the controlled release behavior or cell interactions. With the emergence of biomaterials and fabricated technologies, the multi-layered hydrogels have been widely design for achieving adequate perfusion in biomedical applications (Christensen et al, 2018; Wang et al, 2018)

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