Highly Aligned Bacterial Nanocellulose Films Obtained During Static Biosynthesis in a Reproducible and Straightforward Approach.

Bacterial nanocellulose (BNC) is usually produced as randomly-organized highly pure cellulose nanofibers films. Its high water-holding capacity, porosity, mechanical strength, and biocompatibility make it unique. Ordered structures are found in nature and the properties appearing upon aligning polymers fibers inspire everyone to achieve highly aligned BNC (A-BNC) films. This work takes advantage of natural bacteria biosynthesis in a reproducible and straightforward approach. Bacteria confined and statically incubated biosynthesized BNC nanofibers in a single direction without entanglement. The obtained film is highly oriented within the total volume confirmed by polarization-resolved second-harmonic generation signal and Small Angle X-ray Scattering. The biosynthesis approach is improved by reusing the bacterial substrates to obtain A-BNC reproducibly and repeatedly. The suitability of A-BNC as cell carriers is confirmed by adhering to and growing fibroblasts in the substrate. Finally, the thermal conductivity is evaluated by two independent approaches, i.e., using the well-known 3ω-method and a recently developed contactless thermoreflectance approach, confirming a thermal conductivity of 1.63 W mK-1 in the direction of the aligned fibers versus 0.3 W mK-1 perpendicularly. The fivefold increase in thermal conductivity of BNC in the alignment direction forecasts the potential of BNC-based devices outperforming some other natural polymer and synthetic materials.

In vivo soft tissue reinforcement with bacterial nanocellulose.

The use of surgical meshes to reinforce damaged internal soft tissues has been instrumental for successful hernia surgery; a highly prevalent condition affecting yearly more than 20 million patients worldwide. Intraperitoneal adhesions between meshes and viscera are one of the most threatening complications, often implying reoperation or side effects such as chronic pain and bowel perforation. Despite recent advances in the optimization of mesh porous structure, incorporation of anti-adherent coatings or new approaches in the mesh fixation systems, clinicians and manufacturers are still pursuing an optimal material to improve the clinical outcomes at a cost-effective ratio. Here, bacterial nanocellulose (BNC), a bio-based polymer, is evaluated as a soft tissue reinforcement material regarding mechanical properties and in vivo anti-adhesive performance. A double-layer BNC laminate proved sufficient to meet the standards of mechanical resistance for abdominal hernia reinforcement meshes. BNC-polypropylene (BNC-PP) composites incorporating a commercial mesh have also been prepared. The in vivo study of implanted BNC patches in a rabbit model demonstrated excellent anti-adherent characteristics of this natural nanofibrous polymer 21-days after implantation and the animals were asymptomatic after the surgery. BNC emerges as a novel and versatile hernioplasty biomaterial with outstanding mechanical and anti-adherent characteristics.

Limbal Stem Cells on Bacterial Nanocellulose Carriers for Ocular Surface Regeneration.

Limbal stem cells (LSCs) are already used in cell-based treatments for ocular surface disorders. Clinical translation of LSCs-based therapies critically depends on the successful delivery, survival, and retention of these therapeutic cells to the desired region. Such a major bottleneck could be overcome by using an appropriate carrier to provide anchoring sites and structural support to LSC culture and transplantation. Bacterial nanocellulose (BNC) is an appealing, yet unexplored, candidate for this application because of its biocompatibility, animal-free origin and mechanical stability. Here, BNC as a vehicle for human embryonic stem cells-derived LSC (hESC-LSC) are investigated. To enhance cell-biomaterial interactions, a plasma activation followed by a Collagen IV and Laminin coating of the BNC substrates is implemented. This surface functionalization with human extracellular matrix proteins greatly improved the attachment and survival of hESC-LSC without compromising the flexible, robust and semi-transparent nature of the BNC. The surface characteristics of the BNC substrates are described and a preliminary ex vivo test in simulated transplantation scenarios is provided. Importantly, it is shown that hESC-LSC retain their self-renewal and stemness characteristics up to 21 days on BNC substrates. These results open the door for future research on hESC-LSC/BNC constructs to treat severe ocular surface pathologies.

Correction: PLGA protein nanocarriers with tailor-made fluorescence/MRI/PET imaging modalities.

Correction for 'PLGA protein nanocarriers with tailor-made fluorescence/MRI/PET imaging modalities' by Yajie Zhang et al., Nanoscale, 2020, 12, 4988-5002, DOI: .

Correction: Bacterial nanocellulose as a corneal bandage material: a comparison with amniotic membrane.

Correction for 'Bacterial nanocellulose as a corneal bandage material: a comparison with amniotic membrane' by Irene Anton-Sales et al., Biomater. Sci., 2020, 8, 2921-2930, DOI: .

Bacterial nanocellulose as a corneal bandage material: a comparison with amniotic membrane.

Corneal trauma and ulcerations are leading causes of corneal blindness around the world. These lesions require attentive medical monitoring since improper healing or infection has serious consequences in vision and quality of life. Amniotic membrane grafts represent the common solution to treat severe corneal wounds. However, amniotic membrane's availability remains limited by the dependency on donor tissues, its high price and short shelf life. Consequently, there is an active quest for biomaterials to treat injured corneal tissues. Nanocellulose synthetized by bacteria (BNC) is an emergent biopolymer with vast clinical potential for skin tissue regeneration. BNC also exhibits appealing characteristics to act as an alternative corneal bandage such as; high liquid holding capacity, biocompatibility, flexibility, natural - but animal free-origin and a myriad of functionalization opportunities. Here, we present an initial study aiming at testing the suitability of BNC as corneal bandage regarding preclinical requirements and using amniotic membrane as a benchmark. Bacterial nanocellulose exhibits higher mechanical resistance to sutures and slightly longer stability under in vitro and ex vivo simulated physiological conditions than amniotic membrane. Additionally, bacterial nanocellulose offers good conformability to the shape of the eye globe and easy manipulation in medical settings. These excellent attributes accompanied by the facts that bacterial nanocellulose is stable at room temperature for long periods, can be heat-sterilized and is easy to produce, reinforce the potential of bacterial nanocellulose as a more accessible ocular surface bandage.

PLGA protein nanocarriers with tailor-made fluorescence/MRI/PET imaging modalities.

Designing theranostic nanocarriers with high protein payload and multimodality tracking without cross interferences between the different imaging probes and the delicate protein cargo is challenging. Here, chemical modifications of poly(lactic-co-glycolic acid) (PLGA) to produce nanocapsules (NCs) that incorporate several imaging moieties are reported. The biocompatible and biodegradable PLGA-NCs can be endowed with a magnetic resonance imaging (MRI) reporter, two fluorescence imaging probes (blue/NIR) and a positron emission tomography (PET) reporter. The modular integration of these imaging moieties into the shell of the NCs is successfully achieved without affecting the morphochemical properties of the nanocarrier or the protein loading capacity. In vivo biodistribution of the NCs is monitored by MRI, PET and NIRF and the results from different techniques are analyzed comparatively. The viabilities of two different human endothelial cells in vitro show no toxicity for NC concentration up to 100 µg mL-1. The morbidity of mice for 2 weeks after systemic administration and the hepatic/pancreatic enzymes at the plasma level indicate their in vivo biosafety. In summary, the new theranostic PLGA nanoplatform presented here shows versatile in vitro/in vivo multimodal imaging capabilities, excellent biosafety and over 1 wt% protein loading.

Bacterial Nanocellulose and Titania Hybrids: Cytocompatible and Cryopreservable Cell Carriers.

Carrier-assisted cell transplantation offers new strategies to improve the clinical outcomes of cellular therapies. Bacterial nanocellulose (BC) is an emerging biopolymer that might be of great value in the development of animal-free, customizable, and temperature-stable novel cell carriers. Moreover, BC exhibits a myriad of modification possibilities to incorporate additional functionalities. Here, we have synthesized BC-titanium dioxide (TiO2) nanocomposites (BC/TiO2) to evaluate and compare the suitability of not only BC but also a model hybrid nanobiomaterial as cell transplantation supports. This work provides thorough information on the interactions between BC-based substrates and model human cells in terms of cell attachment, morphology, proliferation rate, and metabolic activity. Two methods to partially retrieve the adhered cells are also reported. Both BC and BC/TiO2 substrates are positively evaluated in terms of cytocompatibility and endotoxin content without detecting major differences between BC and BC nanocomposites. Lastly, the effective cryopreservation of cells-BC and cells-BC/TiO2 constructs, yielding high cell viability and intact cell carrier's characteristics after thawing, is demonstrated. Taken together, our results show that both BC and BC/TiO2 enable to integrate the processes of expansion and long-term storage of human cells in transportable, robust and easy to manipulate supports.

Opportunities of Bacterial Cellulose to Treat Epithelial Tissues.

In this mini-review, we highlight the potential of the biopolymer bacterial cellulose to treat damaged epithelial tissues. Epithelial tissues are cell sheets that delimitate both the external body surfaces and the internal cavities and organs. Epithelia serve as physical protection to underlying organs, regulate the diffusion of molecules and ions, secrete substances and filtrate body fluids, among other vital functions. Because of their continuous exposure to environmental stressors, damage to epithelial tissues is highly prevalent. Here, we first compare the properties of bacterial cellulose to the current gold standard, collagen, and then we examine the use of bacterial cellulose patches to heal specific epithelial tissues; the outer skin, the ocular surface, the oral mucosa and other epithelial surfaces. Special emphasis is made on the dermis since, to date, this is the most widespread medical use of bacterial cellulose. It is important to note that some epithelial tissues represent only the outermost layer of more complex structures such as the skin or the cornea. In these situations, depending on the penetration of the lesion, bacterial cellulose might also be involved in the regeneration of, for instance, inner connective tissue.