Conductive single-wall carbon nanotubes/extracellular matrix hybrid hydrogels promote the lineage-specific development of seeding cells for tissue repair through reconstructing an integrin-dependent niche

Zengqiang Yuan,Zhigeng Jin,Bingshui Xiu,Chao Yuan,Yi Li,Jiao Zhang,Rui Bai,Jianfeng Liu,Zhiqiang Liu,Xiaoming Zhu,Xiaoyu Ding,Huiliang Liu,Jinmiao Shi

doi:10.1186/s12951-021-00993-3

Abstract

BackgroundThe niche of tissue development in vivo involves the growth matrix, biophysical cues and cell-cell interactions. Although natural extracellular matrixes may provide good supporting for seeding cells in vitro, it is evitable to destroy biophysical cues during decellularization. Reconstructing the bioactivities of extracellular matrix-based scaffolds is essential for their usage in tissue repair.ResultsIn the study, a hybrid hydrogel was developed by incorporating single-wall carbon nanotubes (SWCNTs) into heart-derived extracellular matrixes. Interestingly, insoluble SWCNTs were well dispersed in hybrid hydrogel solution via the interaction with extracellular matrix proteins. Importantly, an augmented integrin-dependent niche was reconstructed in the hybrid hydrogel, which could work like biophysical cues to activate integrin-related pathway of seeding cells. As supporting scaffolds in vitro, the hybrid hydrogels were observed to significantly promote seeding cell adhesion, differentiation, as well as structural and functional development towards mature cardiac tissues. As injectable carrier scaffolds in vivo, the hybrid hydrogels were then used to delivery stem cells for myocardial repair in rats. Similarly, significantly enhanced cardiac differentiation and maturation(12.5 ± 2.3% VS 32.8 ± 5%) of stem cells were detected in vivo, resulting in improved myocardial regeneration and repair.ConclusionsThe study represented a simple and powerful approach for exploring bioactive scaffold to promote stem cell-based tissue repair.Graphic abstract

Highlights

Regenerative medicine employed biomaterials, seeding cells and cytokines to repair injured tissues, or construct artificial tissues for tissue even organ replacement [1,2,3]
single-wall carbon nanotubes (SWCNTs)-extracellular matrix (ECM) hybrid hydrogel (HH) were prepared by incorporating SWCNT of different doses into ECM hydrogels (HH0: pure ECM hydrogel; HH0.5: HH containing 0.5 mg/mL SWCNT; HH1: HH containing 1 mg/mL SWCNT; HH2: HH containing 2 mg/mL SWCNT)
Based on the potent regulation of HH1 on the cardiac differentiation and maturation of Brown adiposederived stroma cells (BADSCs), we explored the construction of a functional myocardium with adult BADSCs as seeding cells and HH1 as scaffolds. 2D myocardial sheet and 3D myocardial tissue were constructed respectively. 2D myocardial sheet was constructed by seeding a monolayer BADSCs onto HH1 membrane (Additional file 1: Figure S12a)

Summary

Introduction

Regenerative medicine employed biomaterials, seeding cells and cytokines to repair injured tissues, or construct artificial tissues for tissue even organ replacement [1,2,3]. Scaffold is one of the key factors in regenerative medicine They may play multiple roles in tissue repair, such as providing temporary matrix for cell growth, promoting seeding cell survival and engraftment, regulating cell fate, and so on [8,9,10,11]. Well-decellularized tissues may preserve complete vascular structures, allowing for the ingrowth of new vessel during tissue construction Because of their natural organ source, ECM materials should be the optimal ones among various scaffolds to provide the closest conditions to in vivo microenvironments for seeding cells [20]. Despite the outstanding performance of ECM-based materials, the decellularization process is evitable to impair niches in natural tissues, leading to the loss of some bioactivities. Reconstructing the bioactivities of extracellular matrix-based scaffolds is essential for their usage in tissue repair

Methods

Results

Conclusion