Bacterial Cellulose Scaffolds Research Articles

Hierarchical porous bacterial cellulose scaffolds with natural biomimetic nanofibrous structure and a cartilage tissue-specific microenvironment for cartilage regeneration and repair

The limited three-dimensional (3D) nano-scale pore structure and lack of biological function hamper the application of bacterial cellulose (BC) in cartilage tissue engineering. To address this challenge, 3D hierarchical porous BC/decellularized cartilage extracellular matrix (DCECM) scaffolds with structurally and biochemically biomimetic cartilage regeneration microenvironment were fabricated by freeze-drying technique after EDC/NHS chemical crosslinking. The BC/DCECM scaffolds exhibited excellent mechanical properties, water superabsorbency and shape-memory properties. Compared with the BC control, the BC/DCECM scaffolds exhibited enhanced cell adhesion and proliferation. Cartilage regeneration in vitro and in vivo indicated that the BC/DCECM scaffolds achieved satisfactory neocartilage tissue regeneration with superior original shape fidelity, exterior natural cartilage-like appearance and histologically cartilage-specific lacuna formation and ECM deposition. Furthermore, the BC/DCECM scaffolds achieved superior repair outcomes, as hyaline cartilage-like tissue formed within the defect sites. The present study constitutes a strong step toward the further application of BC in cartilage tissue engineering.

Bacterial Cellulose as a Potential Bio-Scaffold for Effective Re-Epithelialization Therapy.

Currently, there are several therapeutic approaches available for wound injury management. However, a better understanding of the underlying mechanisms of how biomaterials affect cell behavior is needed to develop potential repair strategies. Bacterial cellulose (BC) is a bacteria-produced biopolymer with several advantageous qualities for skin tissue engineering. The aim here was to investigate BC-based scaffold on epithelial regeneration and wound healing by examining its effects on the expression of scavenger receptor-A (SR-A) and underlying macrophage behavior. Full-thickness skin wounds were generated on Sprague-Dawley rats and the healing of these wounds, with and without BC scaffolds, was examined over 14 days using Masson’s trichome staining. BC scaffolds displayed excellent in vitro biocompatibility, maintained the stemness function of cells and promoted keratinocyte differentiation of cells, which are vital in maintaining and restoring the injured epidermis. BC scaffolds also exhibited positive in vivo effects on the wound microenvironment, including improved skin extracellular matrix deposition and controlled excessive inflammation by reduction of SR-A expression. Furthermore, BC scaffold significantly enhanced epithelialization by stimulating the balance of M1/M2 macrophage re-programming for beneficial tissue repair relative to that of collagen material. These findings suggest that BC-based materials are promising products for skin injury repair.

Fabrication of Robust, Shape Recoverable, Macroporous Bacterial Cellulose Scaffolds for Cartilage Tissue Engineering.

Recently, the fabricating of three-dimensional (3D) macroporous bacterial cellulose (MP-BC) scaffolds with mechanically disintegrated BC fragments has attracted considerable attention. However, the successful implementation of these materials depends mainly on their mechanical stability and robustness. Here, a non-toxic crosslinker, 1-ethyl-3-(-3-dimethylaminopropyl) carbodiimide hydrochloride/N-hydroxysuccinimide (EDC/NHS), is employed to induce crosslinking reactions between BC fragments. In addition to their large pore sizes, the EDC/NHS-crosslinked MP-BC scaffolds exhibit excellent compression properties and shape recovery ability, owing to the EDC/NHS-induced crosslinking on the BC nanofibers. The results of in vitro studies reveal that the biocompatibility of MP-BC scaffolds is better than that of pristine BC scaffolds because the former provided more space for cell proliferation. The results of in vivo studies show that the neocartilage tissue with native cartilage appearance and abundant cartilage-specific extracellular matrix deposition is successfully regenerated in nude mice. The findings reveal the immense application potential of mechanically robust BC scaffolds with controllable pore sizes and shape-recoverable properties in tissue engineering.

Preparation and characterization of a 3-dimensional macroporous bacterial cellulose scaffold for in vitro tissue engineering applications

The increasing need for a new tissue engineering scaffold has revived interest in bacterial cellulose (BC) and its water holding capacity (WHC), porosity, and biocompatibility. Bacterial cellulose was produced using Gluconacetobacter xylinus, and bacterial cellulose film (BCF) was prepared by lyophilization. To obtain macroporous bacterial cellulose (MBCS), BCF was rinsed with poly(ethylene glycol) (PEG-400), adjusted to 0.25% BC concentration, and freeze-dried. The objective of this study to compare BCF and MBCS in terms of porosity, in vitro degradation, WHC, and the cell viability of mouse fibroblast cell line (NIH-3T3). The results showed that the MBCS has great potential for tissue engineering.

In vitro adipogenesis and long-term adipocyte culture in adipose tissue-derived cell banks

There is a critical need to develop in vitro culture systems appropriate for the expansion of adipose tissue, in order to gain new insights into metabolic diseases and to assist in the restoration of tissue defects. Conventional two- or three-dimensional (2D or 3D) in vitro models of adipocytes require a combination of supplements to induce adipocyte maturation that greatly increases the cost of large-scale industrial production. In the present study, a microporous, perforated bacterial cellulose (BC)-assisted culture system was developed that promoted the adhesion, proliferation, and adipogenic differentiation of preadipocytes. Additionally, the system maintained the cells as mature unilocular adipocytes ex vivo in normal cell culture medium in long-term culture. All cells were derived from isolated adipose tissue without the use of expensive enzymes for tissue digestion. In contrast to culture in hard tissue culture plates, preadipocytes in the soft 3D environments formed multidimensional interlaced cell contacts, undergoing significant spontaneous lipid accumulation and could be cultured for up to threemonths in maintenance medium. More importantly, the cultured adipose tissue-derived cell bank created here was able to produce injury repair activators that promoted the proliferation of fibroblasts with little fibrosis and the functional differentiation of myoblasts, displaying the potential for use in adipose reconstruction. Thus, the present study demonstrates the potential of a mechanically flexible BC scaffold to generate volume tunable adipose constructs and provides a low-cost and user-friendly strategy for large-scale industrial production of adipose tissue.

Cellulose-Based Fibrous Materials From Bacteria to Repair Tympanic Membrane Perforations.

Perforation is the most common illness of the tympanic membrane (TM), which is commonly treated with surgical procedures. The success rate of the treatment could be improved by novel bioengineering approaches. In fact, a successful restoration of a damaged TM needs a supporting biomaterial or scaffold able to meet mechano-acoustic properties similar to those of the native TM, along with optimal biocompatibility. Traditionally, a large number of biological-based materials, including paper, silk, Gelfoam®, hyaluronic acid, collagen, and chitosan, have been used for TM repair. A novel biopolymer with promising features for tissue engineering applications is cellulose. It is a highly biocompatible, mechanically and chemically strong polysaccharide, abundant in the environment, with the ability to promote cellular growth and differentiation. Bacterial cellulose (BC), in particular, is produced by microorganisms as a nanofibrous three-dimensional structure of highly pure cellulose, which has thus become a popular graft material for wound healing due to a number of remarkable properties, such as water retention, elasticity, mechanical strength, thermal stability, and transparency. This review paper provides a comprehensive overview of the current experimental studies of BC, focusing on the application of BC patches in the treatment of TM perforations. In addition, computational approaches to model cellulose and TM are summarized, with the aim to synergize the available tools toward the best design and exploitation of BC patches and scaffolds for TM repair and regeneration.

Permeation of Silver Sulfadiazine Into TEMPO-Oxidized Bacterial Cellulose as an Antibacterial Agent.

Surface oxidation of bacterial cellulose (BC) was done with the TEMPO-mediated oxidation mechanism system. After that, TEMPO-oxidized bacterial cellulose (TOBC) was impregnated with silver sulfadiazine (AgSD) to prepare nanocomposite membranes. Fourier transform infrared spectroscopy (FTIR) was carried out to determine the existence of aldehyde groups on BC nanofibers and X-ray diffraction (XRD) demonstrated the degree of crystallinity. FESEM analysis revealed the impregnation of AgSD nanoparticles at TOBC nanocomposites with the average diameter size ranging from 11 nm to 17.5 nm. The sample OBCS3 showed higher antibacterial activity against Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli by the disc diffusion method. The results showed AgSD content, dependent antibacterial activity against all tested bacteria, and degree of crystallinity increases with TOBC and AgSD. The main advantage of the applications of TEMPO-mediated oxidation to BC nanofibers is that the crystallinity of BC nanofibers is unchanged and increased after the oxidation. Also enhanced the reactivity of BC as it is one of the most promising method for cellulose fabrication and functionalization. We believe that the novel composite membrane could be a potential candidate for biomedical applications like wound dressing, BC scaffold, and tissue engineering.

Developing “Off the Shelf” Pancreases for Diabetic Patients Using Bacterial and Kombucha Tea Waste

The advent of tissue and organ engineering provides long-term treatment for conditions previously considered chronic and untreatable. Through advances in the field of tissue engineering, patients have the potential to receive synthetic replacements of damaged tissues and cellular grafts. Scaffolds, based in either synthetic or natural polymers, are fundamental to tissue engineering approaches because they provide a structure that mimics the native environment which facilitates cellular differentiation, organization, and functionality. However, current protocols for creating scaffolds remain complex and difficult to translate to the clinic. Our investigation aimed to provide potential solutions to fundamental issues associated with islet cell transplantation, a possible cure for type 1 diabetes. In this study, we used bacterial cellulose as the polymer to create scaffolds. We modulated the structural characteristics of the bacterial cellulose to aid cellular infiltration. After processing, scanning electron micrographs of the scaffolds showed that a favorable blood vessel morphology was maintained and an open pore geometry was obtained. We effectively manipulated the porosity of the scaffold by altering agarose concentrations. The 0.5% agarose-cellulose composite group had an average pore area of 20,000 µm2, which permitted the establishment of regionalized cells islands. Notably, the popular fermented tea drink, kombucha, produces bacterial cellulose as a waste product. Kombucha is made using a symbiotic culture of bacteria and yeast (SCOBY). Normally, SCOBYs are simply discarded after the fermentation process is complete, but could have untapped potential as a platform for tissue engineering and transplantation procedures. To verify that bacterial cellulose can be used as a biomimetic platform, INS-1 cells (an insulin-secreting beta cell-derived line) were seeded in the bacterial cellulose scaffold. We observed morphological changes, such as cytoplasmic extensions and clustering, suggesting reestablishment of functional cell islands. Hence, the results of our experiments suggested that bacterial cellulose is a cost-effective scaffolding platform that can be used to house islet cells as a promising tool in islet cell transplantation, a possible cure for diabetes.

3-D macro/microporous-nanofibrous bacterial cellulose scaffolds seeded with BMP-2 preconditioned mesenchymal stem cells exhibit remarkable potential for bone tissue engineering

Bone repair using BMP-2 is a promising therapeutic approach in clinical practices, however, high dosages required to be effective pose issues of cost and safety. The present study explores the potential of low dose BMP-2 treatment via tissue engineering approach, which amalgamates 3-D macro/microporous-nanofibrous bacterial cellulose (mNBC) scaffolds and low dose BMP-2 primed murine mesenchymal stem cells (C3H10T1/2 cells). Initial studies on cell-scaffold interaction using unprimed C3H10T1/2 cells confirmed that scaffolds provided a propitious environment for cell adhesion, growth, and infiltration, owing to its ECM-mimicking nano-micro-macro architecture. Osteogenic studies were conducted by preconditioning the cells with 50 ng/mL BMP-2 for 15 min, followed by culturing on mNBC scaffolds for up to three weeks. The results showed an early onset and significantly enhanced bone matrix secretion and maturation in the scaffolds seeded with BMP-2 primed cells compared to the unprimed ones. Moreover, mNBC scaffolds alone were able to facilitate the mineralization of cells to some extent. These findings suggest that, with the aid of ‘osteoinduction’ from low dose BMP-2 priming of stem cells and ‘osteoconduction’ from nano-macro/micro topography of mNBC scaffolds, a cost-effective bone tissue engineering strategy can be designed for quick and excellent in vivo osseointegration.

Production and characterization of bacterial cellulose scaffold and its modification with hyaluronic acid and gelatin for glioblastoma cell culture

Three-dimensional (3D) in vitro cell culture models have recently gained increasing interest in predicting the response of anticancer drugs. In this study first, we tried to obtain a novel hyaluronic acid (HA)/gelatin (Gel) modified bacterial cellulose (BC) composite scaffolds by in situ fermentation method. Morphological and chemical structures, wettability, and thermal stability of scaffolds were evaluated. In particular, the human glioblastoma (GBM) cancer cell line (U251) was seeded into BC/HA/Gel scaffolds to evaluate their potential as in vitro 3D cancer cell culture. MTT proliferation assay, scanning electron microscopy, and confocal microscopy were utilised to determine cell proliferation, morphology and adhesion. The results suggest that our hyaluronic acid and gelatin modified bacterial cellulose scaffold is promising to be used as in vitro 3D culture of GBM cells and may be used to predict treatment response or reactions of new therapeutics.

Proton-conductive membranes with percolated transport paths for aqueous redox flow batteries

Tremendous efforts have been dedicated to developing sustainable and affordable ion exchange membranes for flow batteries. Challenges remain in terms of high cost, low coulombic efficiency caused by the crossover of active species, and stability. Inspired by the highly hydrophilic and interconnected 3D networks of nanofibers of bacterial cellulose (BC), an unprecedented ion exchange membrane possessing high ionic selectivity is created by impregnating a hydrophobic copolymer poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) into BC aerogel scaffolds. The high proton conductivity of the membrane stems from the intrinsically high hydrophilic network of the BC fibrils, which offers a percolated pathway for the proton conduction. At the same time, the selectivity arises from the hydrophobic lamination on the BC scaffold that acts as a barrier for the migration of vanadium ions and reduces its crossover. Therefore, the hydrophilic ion transport paths of BC inside of a stable PVDF-HFP matrix result in a high proton conductivity of 0.0095 S cm−1 at 25 °C and a significantly less vanadium permeation rate. Besides, the membrane yields a high tensile strength of 114 MPa and excellent thermal stability. Moreover, vanadium redox flow battery assembled using the BC/PVDF-HFP membrane demonstrated cyclings for 300 continuous cycles at a constant current density of 100 mA cm−2 and achieved an average coulombic efficiency of 97.56%, voltage efficiency of 81.56%, and energy efficiency of 79.49%. The higher CE, and, therefore, energy efficiency of the BC/PVDF-HFP membrane than those of the Nafion 115 can be attributed to the natural percolated 3D networks of BC.

Crystalline CdS/MoS2 shape-controlled by a bacterial cellulose scaffold for enhanced photocatalytic hydrogen evolution

The conversion of sunlight into H2 by noble-metal-free photocatalysts is a promising approach for the production of easy-to-store chemical energy. For this purpose, higher efficiency is achieved by photocatalysts with heterojunctions preventing fast charge recombination. Most processes for the synthesis of high-performance heterojunction photocatalysts require solvents harmful to living organisms. Here, berry-shaped (b)-CdS/MoS2 particles were fabricated instead by a hydrothermal process where non-toxic bacterial cellulose was used to mold b-CdS into nanostructures with enhanced spatial arrangement. Subsequently, MoS2 was combined with b-CdS resulting in a composite with suitable shape and intimate semiconductor contacts beneficial for charge transfer. The photocatalytic H2 evolution (PHE) of b-CdS/1%MoS2 was 63.59 mmol g−1 h−1. It was 61.1 times, 397 times, and 10.2 times higher than PHE with b-CdS, CdS fabricated without BC scaffold, and b-CdS doped with Pt, respectively. These results show the high potential of b-CdS/MoS2 and the associated synthesis method for PHE.

Anti-aggregation and morphology-controlled effects of bacterial cellulose encapsulated BiOBr for enhanced photodegradation efficiency

A series of morphology-controlled BiOBr nano/macrostructures was successfully synthesized via a novel biomass-route derived from bacterial cellulose (BC). In the BiOBr/BC system compared with pure BiOBr, the three-dimensional BC scaffolds not only effectively prevented the aggregation of BiOBr units by pore confinement, but also strengthened the controllability of BiOBr size with the help of abundant anchoring sites provided by cross-linked BC fibers. By associating the results of characterizations and the photodegradation of RhB dye, the relationship between morphology and photocatalytic activity of BiOBr/BC was investigated. In addition, a possible mechanism for the enhanced photocatalytic activity of the optimized BiOBr/BC has been discussed. This biomass-derived route provides a platform for further design of bismuth-based composite photocatalysts with potential advantages of being anti-aggregation, highly-dispersed, easily recovered and having enhanced catalytic performance.

Incorporating graphene oxide into biomimetic nano-microfibrous cellulose scaffolds for enhanced breast cancer cell behavior

The impact of graphene oxide (GO) on normal cells has been widely investigated. However, much less is known on its effect on cancer cells. Herein, GO nanosheets were incorporated into electrospun cellulose acetate (CA) microfibers. The GO-incorporated CA (GO/CA) microfibers were combined with bacterial cellulose (BC) nanofibers via in situ biosynthesis to obtain the nano-microfibrous scaffolds. The GO/CA–BC scaffolds were characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), Raman spectroscopy, and X-ray photoelectron spectroscopy (XPS). The GO/CA–BC scaffolds were used for breast cancer cell culture to evaluate the effect of GO on cancer cell behavior. Fluorescence images revealed large multicellular clusters on the surface of GO/CA–BC scaffolds. Compared to the bare CA–BC scaffold, the GO/CA–BC scaffolds not only showed enhanced mechanical properties but also improved cell proliferation. It is expected that the GO/CA–BC scaffolds would provide a suitable microenvironment for the culture of cancer cells which is necessary for drug screening and cell biology study.

Biocompatibility evaluation of bacterial cellulose as a scaffold material for tissue-engineered corneal stroma

In this work, biocompatibility of bacterial cellulose (BC) was assessed as the scaffold for corneal stroma replacement. Biocompatibility was evaluated by examining rabbit corneal epithelial and stromal cells cultured on the BC scaffold. The growth of primary cells was assessed by optical microscope, scanning electron microscope (SEM), and transmission electron microscope (TEM). Live/dead viability/cytotoxicity assay and CCK-8 assay were used to evaluate cell survival. BC was surgically implanted in vivo into a stromal pocket. During a 3-month follow-up, the biocompatibility of BC was assessed. We found that epithelial and stromal cells grew well on BC and showed a survival rate of nearly 100%. The SEM examination for both kinds of cell showed abundant leafy protrusions, spherical projections, filopodia, cytoskeletons, and cellular interconnections. The stromal cells cultured on BC arranged regularly. TEM observation revealed normal cellular microstructure and a tight adhesion to the BC membrane. In vivo observation confirmed the optical transparency of BC during 3-month follow-up. The results demonstrated that BC had good biocompatibility for the tissue engineering of corneal stroma.

Interpenetrated nano- and submicro-fibrous biomimetic scaffolds towards enhanced mechanical and biological performances.

Developing fibrous scaffolds with hierarchical structures that closely mimic natural extracellular matrix (ECM) is highly desirable. However, fabricating scaffolds with true nanofibers (<100 nm) and submicrofibers (<1 μm) remains a big challenge. In this work, to mimic the fibrillar structure of natural ECM, bacterial cellulose (BC) nanofibers were hybridized with cellulose acetate (CA) submicrofibers for the first time. The interpenetrated nano-submicron fibrous BC/CA scaffold was fabricated using the combined electrospinning and modified in situ biosynthesis method. The BC/CA scaffold has an integrated symmetrical nanostructure in which BC nanofibers (42 nm in diameter) penetrate into the submicrofibrous CA (820 nm in diameter) scaffold. The BC/CA scaffold shows an interconnected porous structure with a high porosity of >90%. Additionally, the combination of CA submicrofibers with BC nanofibers leads to significantly improved mechanical properties over nanofibrous BC and submicrofibrous CA scaffolds and enlarged pores over nanofibrous BC scaffold. In addition, the biological behaviors of prepared BC/CA on MC3T3-E1 cells were investigated. Results suggested that BC/CA scaffold is beneficial for cell migration and proliferation. Moreover, the BC/CA scaffold shows higher alkaline phosphatase (ALP) activity, and calcium depositions. In addition, the hierarchical structures can effectively improve the expression of osteogenic gene (ALP mRNA and Runx2 mRNA) and protein (ALP). We believe that the methodology might provide biomimetic morphological microenvironments for enhanced tissue regeneration.

Bone-Inspired Mineralization with Highly Aligned Cellulose Nanofibers as Template.

Bioinspired by the aligned structure and building blocks of bone, this work mineralized the aligned bacterial cellulose (BC) through in situ mineralization using CaCl2 and K2HPO4 solutions. The cellulose nanofibers were aligned by a scalable stretching process. The aligned and mineralized bacterial cellulose (AMBC) homogeneously incorporated hydroxyapatite (HAP) with a high mineral content and exhibited excellent mechanical strength. The ordered 3D structure allowed the AMBC composite to achieve a high elastic modulus and hardness and the development of a nanostructure inspired by natural bone. The AMBC composite exhibited an elastic modulus of 10.91 ± 3.26 GPa and hardness of 0.37 ± 0.18 GPa. Compared with the nonaligned mineralized bacterial cellulose (NMBC) composite with mineralized crystals of HAP randomly distributed into the BC scaffolds, the AMBC composite possessed a 210% higher elastic modulus and 95% higher hardness. The obtained AMBC composite had excellent mechanical properties by mimicking the natural structure of bone, which indicated that the organic BC aerogel with aligned nanofibers was a promising template for biomimetic mineralization.

A facile green approach for fabricating bacterial cellulose scaffold with macroporous structure and cell affinity

Bacterial cellulose holds great promise for tissue engineering, but its application is greatly limited due to the lack of large pores and poor cell affinity. In this study, macroporous bacterial cellulose was fabricated through the dissolution of gelatin microspheres, which were incorporated with bacterial cellulose during bacterial cellulose fabrication. Then, gelatin was immobilized onto bacterial cellulose surface via procyanidins crosslinking. The results confirmed that the scaffolds possessed interconnected macroporous structure, high porosity, good water uptake ability, and good mechanical properties. The results of evaluation of cells showed that cells migrated to the inner of macroporous affinitive bacterial cellulose and displayed better spreading as well as proliferation than that on pure bacterial cellulose surfaces. The macroporous affinitive bacterial cellulose show potential as a scaffold for tissue engineering.

Production of hydroxyapatite–bacterial cellulose composite scaffolds with enhanced pore diameters for bone tissue engineering applications

Bone tissue engineering scaffolds used for the treatment of bone defects are required to be osteoconductive, osteoinductive, osteogenic, biocompatible, and have enough porosity to allow osteointegration, as well as vascularization. It is known that addition of the hydroxyapatite (HAp) to bone tissue scaffolds promotes bone formation by increasing osteoconductivity. Bacterial cellulose (BC) is a highly biocompatible material, and its mechanical properties and fibrous structure allow that it can be used as a bone tissue scaffold; yet, the nano-porous structure of BC (50–200 nm) prevents or limits cell migration and vascularization. In this study, it is intended to take advantage of the porous structure and mechanical strength of BC and osteoconductive properties of HAp for the production of tissue engineering scaffolds. Pore sizes of BC were enhanced to 275 μm by a novel shredded agar technique, and SaOs-2 cells were shown to migrate between the fibers of the modified BC. It was observed that mineralization of SaOs-2 cells was enhanced on in situ produced HAp-BC nano-composites compared to BC scaffolds.

Fabrication of a novel hierarchical fibrous scaffold for breast cancer cell culture

Scaffolds combining nano- and submicro-fibers closely mimicking extracellular matrix (ECM) have been poorly exploited for in vitro cancer cell culture. Herein, a combined electrospinning and modified in situ biosynthesis method has been developed to fabricate a novel scaffold consisting of bacterial cellulose (BC) nanofibers and electrospun cellulose acetate (CA) submicrofibers to mimic the fibrillar structure of natural ECM. The CA/BC nano/submicrofibrous scaffold was characterized by scanning electron microscopy (SEM), mechanical strength tests, porosity measurements, and cell studies using the MCF-7 breast cancer cells. In addition, the sensitivity of the cancer cells seeded in the CA/BC nano/submicrofibrous scaffold to an anticancer drug was assessed. It was found that the CA/BC scaffold exhibited an interconnected porous structure in which BC nanofibers penetrated into the submicrofibrous CA scaffold. Such sophisticated structure was responsible for the improved mechanical properties of CA/BC scaffold over the ones obtained using a single kind of fibers. More importantly, the CA/BC scaffold showed improved cell adhesion, migration, and proliferation over single BC or CA scaffold. Finally, cells grown on CA/BC scaffold exhibited a greater doxorubicin resistance than those on single CA or BC scaffold. The results suggest that the CA/BC nano/submicrofibrous scaffold has potential for application in in vitro tumor model for the study of cancer progression and drug screening.