Bacterial cellulose-based hydrogel with regulated rehydration and enhanced antibacterial activity for wound healing.

Bacterial cellulose (BC) hydrogels are promising medical biomaterials that have been widely used for tissue repair, wound healing and cartilage engineering. However, the high water content of BC hydrogels increases the difficulty of storage and transportation. Moreover, they will lose their original hydrogel structure after dehydration, which severely limits their practical applications. Introducing the bio-based polyelectrolytes is expected to solve this problem. Here, we modified BC and combined it with quaternized chitosan (QCS) via a chemical reaction to obtain a dehydrated dialdehyde bacterial cellulose/quaternized chitosan (DBC/QCS) hydrogel with repeated swelling behavior and good antibacterial properties. The hydrogel can recover the initial state on the macro scale with a swelling ratio over 1000 % and possesses excellent antimicrobial properties against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) with a killing rate of 80.8 % and 81.3 %, respectively. In addition, the hydrogel has excellent biocompatibility, which is conducive to the stretching of L929 cells. After 14 d of in vivo wound modeling in rats, it was found that the hydrogel loaded with pirfenidone (PFD) could promote collagen deposition and accelerate wound healing with scar prevention. This rehydratable hydrogel can be stored and transported under dry conditions, which is promising for practical applications.

Urethra-inspired biomimetic scaffold: A therapeutic strategy to promote angiogenesis for urethral regeneration in a rabbit model.

Limited angiogenesis and epithelialization make urethral regeneration using conventional tissue-engineered grafts a great challenge. Consequently, inspired from the native urethra, bacterial cellulose (BC) and bladder acellular matrix (BAM) were combined to design a three dimensional (3D) biomimetic scaffold. The developed BC/BAM scaffold was engineered for accelerating urethral regeneration by enhancing angiogenesis and epithelialization. The BC/BAM scaffold reveals the closest mimic of native urethra in terms of the 3D porous nanofibrous structure and component including collagen, glycosaminoglycans, and intrinsic vascular endothelial growth factor (VEGF). In vitro studies showed that the bioinspired BC/BAM scaffold promoted in vitro angiogenesis by facilitating human umbilical vein endothelial cells (HUVECs) growth, expression of endothelial function related proteins and capillary-like tube formation. Effect of the BC/BAM scaffold on angiogenesis and epithelialization was studied by its implantation in a rabbit urethral defect model for 1 and 3 months. Results demonstrated that the improved blood vessels formation in the urethra-inspired BC/BAM scaffold significantly promoted epithelialization and accelerated urethral regeneration. The urethra-inspired BC/BAM scaffold provides us a new design approach to construct grafts for urethral regeneration. STATEMENT OF SIGNIFICANCE: Findings in urethral regeneration demonstrate that an ideal tissue-engineered urethra should have adequate angiogenesis to support epithelialization for urethral regeneration in vivo. In this study, inspired from the native urethra, a bioinspired bacterial cellulose/bladder acellular matrix (BC/BAM) scaffold was developed to promote angiogenesis and epithelialization. The designed scaffold showed the closest physical structure and component to natural urethra, which is beneficial to angiogenesis and regeneration of urethral epithelium. This is the first time to utilize BC and dissolved BAM to develop biomimetic scaffold in urethral tissue engineering. Our biomimetic strategy on urethra graft design provided enhanced angiogenesis and epithelialization to achieve an accelerated and successful rabbit urethral repair. We believe that our urethra-inspired biomimetic scaffold would provide new insights into the design of urethral tissue engineering grafts.

Use of heparinized bacterial cellulose based scaffold for improving angiogenesis in tissue regeneration.

Vascularization is a prerequisite to achieve tissue regeneration especially for long-term survival of a scaffold. During the regeneration process, the delivery of angiogenic factors is very important for developing a vascular network. In this paper, vascular endothelial growth factor (VEGF)-loaded 3D porous bacterial cellulose/gelatin (B/G) scaffolds modified with heparin were firstly prepared. The pro-angiogenic effects of scaffolds towards proliferation and migration of endothelial cells (PIECs) were evaluated as well as in vivo implantation. Results showed that the B/G scaffold modified with heparin could provide a prolonged release of VEGF for two weeks. In vitro cellular assays showed that proliferation and migration were promoted in the presence of VEGF. Subcutaneous implantation demonstrated that angiogenesis was significantly improved for the heparinized scaffolds loaded with VEGF (V-B/G/H), compared to B/G scaffold. The resulting scaffold with sustained delivery of VEGF could be potential and effective tissue engineered candidates in tissue regeneration for future clinical applications.

Urethral reconstruction with a 3D porous bacterial cellulose scaffold seeded with lingual keratinocytes in a rabbit model.

The goal of this study was to evaluate the effects of urethral reconstruction with a three-dimensional (3D) porous bacterial cellulose (BC) scaffold seeded with lingual keratinocytes in a rabbit model. A novel 3D porous BC scaffold was prepared by gelatin sponge interfering in the BC fermentation process. Rabbit lingual keratinocytes were isolated, expanded, and seeded onto 3D porous BC. BC alone (group 1, N = 10), 3D porous BC alone (group 2, N = 10), and 3D porous BC seeded with lingual keratinocytes (group 3, N = 10) were used to repair rabbit ventral urethral defects (2.0 × 0.8 cm). Scanning electron microscopy revealed that BC consisted of a compact laminate while 3D porous BC was composed of a porous sheet buttressed by a dense outer layer. The average pore diameter and porosity of the 3D porous BC were 4.23 ± 1.14 µm and 67.00 ± 6.80%, respectively. At 3 months postoperatively, macroscopic examinations and retrograde urethrograms of urethras revealed that all urethras maintained wide calibers in group 3. Strictures were found in all rabbits in groups 1 and 2. Histologically, at 1 month postoperatively, intact epithelium occurred in group 3, and discontinued epithelium was found in groups 1 and 2. However, groups 2 and 3 exhibited similar epithelial regeneration, which was superior to that of group 1 at 3 months (p < 0.05). Comparisons of smooth muscle content and endothelia density among the three groups revealed a significant increase at each time point (p < 0.05). Our results demonstrated that 3D porous BC seeded with lingual keratinocytes enhanced urethral tissue regeneration. 3D porous BC could potentially be used as an optimized scaffold for urethral reconstruction.