Biohybrid materials: Structure design and biomedical applications

Abstract

Biohybrid materials are proceeded by integrating living cells and non-living materials to endow materials with biomimetic properties and functionalities by supporting cell proliferation and even enhancing cell functions. Due to the outstanding biocompatibility and programmability, biohybrid materials provide some promising strategies to overcome current problems in the biomedical field. Here, we review the concept and unique features of biohybrid materials by comparing them with conventional materials. We emphasize the structure design of biohybrid materials and discuss the structure-function relationships. We also enumerate the application aspects of biohybrid materials in biomedical frontiers. We believe this review will bring various opportunities to promote the communication between cell biology, material sciences, and medical engineering.

Keywords: Biohybrid fiber; Biohybrid microcapsule; Biohybrid microgel; Biohybrid scaffold; Biohybrid sheet.

Graphical abstract

Fig. 1

Overview of biohybrid materials for biomedical applications.

Fig. 2

Engineered cell modification. (a) Schematic showing the formation procedure of the “SupraCells” [32]. Copyright 2019, Wiley VCH. (b) Confocal image of the “SupraCell” [32]. Copyright 2019, Wiley VCH. (c) Representative confocal image showing a layer of partial silica coating on the surface of living cells [36]. Copyright 2021, Wiley VCH.

Fig. 3

Biohybrid microparticles. (a) Enrichment of single-cell-laden microgels by FACS. The live cells were stained with green fluorescence [39]. Copyright 2012, Wiley VCH. (b) Fluorescent (left) and bright-field (right) microscopic images of biohybrid microgels [42]. Red and green fluorescence represents live and dead cells, respectively. Scale bars are 50 ​μm in (a). Copyright 2015, American Chemical Society. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)

Fig. 4

Construction and fabrication of biohybrid fibers. (a) Confocal images of longitudinal (i) and axial (ii) sections of the fascicle-like biohybrid constructs [50]. Copyright 2014, Royal Society of Chemistry. (b) Schematic diagram showing the fabrication procedures of the biohybrid meter-long fibers [51]. Scales bar are 50 ​μm in (a). Copyright 2013, Springer Nature.

Fig. 5

Cell-laden biohybrid sheets. (a) Confocal images showing a stack of four cell-laden hepatic lobule-like sheets [55]. Copyright 2016, Wiley VCH. (b) Cell-laden mosaic hydrogel sheets. (i) Schematic illustration of the production of mosaic sheets; (ii) Confocal fluorescence image showing the location of cardiomyocytes in the biohybrid sheet. (iii,iv) Confocal fluorescence images showing the biohybrid sheet incorporated with fibroblasts [52]. Copyright 2012, Wiley VCH. Scale bars are 500 ​μm (a), 200 ​μm ​(b.ii), 50 ​μm ​(b.iii), and 10 ​μm ​(b.iv).

Fig. 6

Cell-laden 3D scaffolds. (a) In-situ 3D-bioprinted biohybrid scaffold. Fluorescence images indicating cell viability in a (i) 3D-bioprinted lattice scaffold and a (ii) nose-like scaffold [60]. Copyright 2017, Wiley VCH. (b) Cell enrichment in the responsive scaffold during the irradiation of NIR. (i) Schematic of the enrichment capability of the responsive scaffolds. (ii) Fluorescent images of living cells in the 3D biohybrid scaffolds after periodic irradiation of NIR [35]. Copyright 2021, Wiley VCH. (c) Pictures of 3D printed biofilms under normal (top) and UV light (bottom). The number from 1 to 3 refers to the biofilms with blue quantum dots (QDs), green QDs, and red QDs, respectively [17]. Copyright 2019, Springer Nature. Scale bars are 500 ​μm (a), 300 ​μm ​(b.ii), and 5 ​mm (c). (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)

Fig. 7

Biohybrid soft robotics. (a) Biohybrid ray: (i) schematic showing the four layers structure of the biohybrid ray; (ii) the picture of the biohybrid ray [65]. Copyright 2016, The American Association for the Advancement of Science. (b) Biohybrid fish constructed using human cardiomyocytes: (i) schematic showing the five-layer structure of the biohybrid fish; (ii) image of the biohybrid fish [66]. Copyright 2022, The American Association for the Advancement of Science.

Fig. 8

Biohybrid sensors. (a) Schematic showing the bending of the biohybrid hypomorph actuator caused by relative humidity (RH) changes [68]. Copyright 2014, Springer Nature. (b) Schematic of the biohybrid nanogenerator driven by humidity variations [69]. Copyright 2015, Springer Nature. (c) Schematic illustrating the biohybrid matrix with capabilities of substance exchange, cell/cell and cell/environment communication, and chemical sensing [73]. Copyright 2017, National Academy of Sciences.

Fig. 9

Biohybrid therapeutic agents. (a) Schematic of the therapeutic strategy using single-cell encapsulated biohybrid microgel [31]. Copyright 2017, Springer Nature. (b) Schematic of the single cell-loaded microgel (1) receiving soluble factors, (2) producing paracrine factors, and (3) correcting extracellular matrix remodeling [19]. Copyright 2022, Springer Nature. (c) Modification of probiotics with co-deposition of dopamine and chitosan [75]. Copyright 2021, Wiley VCH.

Fig. 10

Biohybrid materials promoting tissue regeneration. (a) Histological image of the chick chorioallantoic membrane (CAM) assay of the angiogenic biohybrid patch. Cell nucleus staining (blue) and alpha-smooth actin staining (brown) was applied. Two red arrows highlight the vessel areas [77]. Copyright 2016, Wiley VCH. (b) Masson's trichrome staining indicating the bone regeneration capacity of the biohybrid scaffold under NIR stimulation [35]. Copyright 2021, Wiley VCH. Scale bar is 200 ​μm. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)