Currently, cardiovascular diseases are the predominant cause of human mortality worldwide [[1], [2], [3], [4]]. Vascular implantation is considered to be the mainstream therapeutic strategy for cardiovascular diseases; consequently, there is an urgent demand for vascular grafts (e.g., vascular patches and tubular grafts) [[5], [6], [7], [8]]. Although autologous vascular grafts are the preferred choice, their availability is greatly restricted by donor source and secondary injury [[8], [9], [10], [11]]. Accordingly, a series of artificial vascular grafts have been proposed as potential substitutes; unfortunately, these vascular grafts tend to induce thrombosis and intimal hyperplasia, resulting in unsatisfactory outcomes, especially for small-diameter vascular grafts [3,6,11,12]. Developing vascular grafts with rapid endothelialization is highly desirable but remains challenging.

Bacterial cellulose (BC), a natural polysaccharide polymer mainly produced by Komagataeibacter xylinus (formerly Acetobacter xylinus), possesses 3D fibrous network similar to natural extracellular matrix, favorable biocompatibility, excellent in situ mouldability, high water-holding capacity, and non-immunogenicity [13,14]. These unique properties endow BC with great potential for biomedical applications, such as wound dressing [15,16], bone/cartilage tissue engineering [17,18], artificial corneal stroma [19], and vascular implantation [9,20,21]. As early as 2001, Klemm et al. [20] reported that BC tube maintained a patency rate of ∼100 % as an artificial blood vessel for microsurgery, thus manifesting the considerable feasibility of BC for vascular applications. To date, remarkable progress on BC vascular grafts has been achieved through various of strategies including structural design, composite construction, and biomolecule immobilization [3,9,[21], [22], [23], [24], [25]].

Among these strategies, constructing dense fibrous structure is an effective approach for enhancing the performance of BC vascular grafts. For example, Hong's group [21,25] reported an ex situ densification strategy for BC vascular grafts, in which BC tubes were mercerized in high-concentration NaOH solution to reduce wall thickness and improve fiber diameter and density. The improved burst strength and compliance were achieved after the densification treatment. Meanwhile, the dense fibrous structure suppressed platelet adhesion and promoted the spreading and proliferation of human umbilical vein endothelial cells (HUVECs). More importantly, the mercerized BC vascular graft maintained satisfactory patency and accelerated the formation of complete endothelial layer after 5 months of implantation in a rat abdominal aorta model. Besides, regulating initial bacterial number [26] or using chitosan-containing culture medium [27] also tends to form dense fibrous structure, namely, in situ densification strategy; however, these in situ strategies have limited densification effect. Considering the convenience and time saving of in situ strategy, great attention should be paid to exploiting new in situ strategy to obtain dense BC for vascular applications.

In addition, biomolecule immobilization on vascular grafts is a common and effective approach for achieving remarkable hemocompatibility and rapid endothelialization, thus ensuring the clinical applicability of vascular grafts [6,[28], [29], [30]]. Among various of biomolecules, heparin (Hep) with a structure of linear polysaccharide containing sulfonic, carboxylic and sulfanilamide groups is extensively immobilized on vascular grafts to attain excellent hemocompatibility [8,29,30]. Meanwhile, it has been also confirmed that Hep can bind and stabilize vascular endothelial growth factor secreted by HUVECs to promote the proliferation and adhesion of HUVECs, contributing to the endothelialization process of vascular grafts [3,29,31]. There have been some reports that Hep immobilization can improve the hemocompatibility and cytocompatibility of BC-based vascular grafts [24,32].

Recently, Rühs et al. [33] claimed that BC coating was created on objects of any shape and composition with the aid of polydopamine (PDA) modification and the formed BC coating displayed high water content and low stiffness compared with routine BC. Inspired by this pioneering work, dense BC fibrous structure is in situ synthesized by employing dopamine (DA, the precursor of PDA)-containing culture medium, in which DA can significantly increase BC fiber diameter and density. Meanwhile, BC fibers can be modified by DA during in situ synthesis process. Then DA on BC fibers self-polymerizes into PDA accompanied with the removal of bacteria in NaOH solution, forming PDA-modified dense BC (PDBC) vascular patch. This is essentially different from that BC fibers are modified by PDA coatings or particles by treating the harvested BC with DA, which usually doesn't lead to the formation of dense fibrous structure [[34], [35], [36], [37]]. Hep is subsequently covalently immobilized on PDBC vascular patch via esterification reactions between Hep and BC and Michael-type addition reactions between Hep and PDA to obtain Hep-immobilized PDBC (Hep@PDBC) vascular patch. PDBC and Hep@PDBC vascular patches display superior tensile and burst strength to BC vascular patch due to their dense fibrous structure compared with that of BC vascular patch. The simultaneous presence of dense fibrous structure and PDA modification effectively improves the cytocompatibility, but is not beneficial for hemocompatibility may due to the negative effect of PDA modification outweighing the positive effect of dense fibrous structure on hemocompatibility. Hep immobilization only not completely reverses the negative effect on hemocompatibility, but also further endows Hep@PDBC vascular patch with improved cytocompatibility compared with PDBC vascular patch. Hep@PDBC vascular patch constructed by this combined strategy of in situ densification and Hep immobilization exhibits multifunctional advantages of tensile and burst strength, hemocompatibility, and cytocompatibility, demonstrating considerable feasibility for potential vascular applications.