The role of microbiota in tissue repair and regeneration.

A comprehensive understanding of the human body endogenous microbiota is essential for acquiring an insight into the involvement of microbiota in tissue healing and regeneration process in order to enable development of biomaterials with a better integration with human body environment. Biomaterials used for biomedical applications are normally germ-free, and the human body as the host of the biomaterials is not germ-free. The complexity and role of the body microbiota in tissue healing/regeneration have been underestimated historically. Traditionally, studies aiming at the development of novel biomaterials had focused on the effects of environment within the target tissue, neglecting the signals generated from the microbiota and their impact on tissue regeneration. The significance of the human body microbiota in relation to metabolism, immune system, and consequently tissue regeneration has been recently realised and is a growing research field. This review summarises recent findings on the role of microbiota and mechanisms involved in tissue healing and regeneration, in particular skin, liver, bone, and nervous system regrowth and regeneration highlighting the potential new roles of microbiota for development of a new generation of biomaterials.

Biofabrication of Bacterial Constructs: New Three-Dimensional Biomaterials.

An enormous number of bacteria live in almost every environment; from deep oceans to below the surface of the earth or in our gastrointestinal tract. Although biofabrication is growing and maturing very quickly, the involvement of bacteria in this process has not been developed at a similar pace. From the development of a new generation of biomaterials to green bioremediation for the removal of hazardous environmental pollutants or to develop innovative food products in a recent trend, researchers have used cutting-edge biofabrication techniques to reveal the great potential of 3D structured bacterial constructs. These 3D bacterial workhouses may fundamentally change our approach toward biomaterials.

Physico-mechanical Characterization of Liquid versus Solid Applications of Visible Light Cross-Linked Tissue Sealants.

The limitations of commercially available tissue sealants have resulted in the need for a new tissue adhesives with adequate adhesion, improved mechanical properties, and innocuous degradation products. To address current limitations, a visible light cross-linking method for the preparation of hydrogel tissue sealants, based on natural polymers (chitosan or alginate), is presented. Water-soluble chitosan was generated via modification with vinyl groups. To form hydrogels, alginate and chitosan were cross-linked by green light illumination, with or without the use of a bifunctional cross-linker. Evaluation of the mechanical properties through rheological characterization demonstrated an increased viscosity of polymer blends, and differences in shear moduli despite similar gelation points upon photo-cross-linking. A comparative study on the burst pressure properties of liquid versus solid material applications was performed to determine if the tissue sealants can perform under physiological lung pressures and beyond using different application methods. Higher burst pressure values were obtained for the sealants applied as a liquid compared to the solid application. The hydrogel tissue sealants revealed no cytotoxic effects toward primary human mesenchymal stem cells. This is the first report of a direct comparison between hydrogel tissue sealants of the same formulation applied in liquid versus solid form.

Shear thinning/self-healing hydrogel based on natural polymers with secondary photocrosslinking for biomedical applications.

Injectable hydrogel systems are useful in many biomedical applications, including drug or cell delivery carriers and scaffolds. Here, we describe the design and characterization of a shear thinning hydrogel that undergoes a disassembly when shear forces are applied during injection and is self-healing once the shear forces are removed. This hydrogel is based on a cyclodextrin modified alginate, and a methacrylated gelatin which initially forms through a weak guest-host interaction between hydrophobic cyclodextrin cavities and the aromatic residue of gelatin. Methacrylated gelatin possesses photocrosslinkable functionalities which can go through a light-initiated polymerization to create secondary crosslinking sites and further crosslink the matrix. The shear thinning and self-healing behavior of these gels monitored in low and high strain range, viscosity of the hydrogels components and gelation kinetic were studied. The rheological analyses showed the formation of shear thinning gels which were further stabilized by visible light exposure. The cytotoxicity of the hydrogels towards human mesenchymal stem cells were assessed and the rate of mass loss over a week period was studied.

In situ-forming and pH-responsive hydrogel based on chitosan for vaginal delivery of therapeutic agents.

One of the important routes of drug administration for localized delivery of contraceptives and cervical cancer treatment agents is vaginal canal. Due to the low pH of vagina, a pH-responsive drug delivery system was developed. This hydrogel was synthesized based on a mucoadhesive biopolymer, chitosan (CS), that promotes the interaction between the hydrogel and mucosal surface of the vagina, potentially increasing the residence time of the system. This injectable hydrogel was formed via acid-labile Schiff-base linkages between free amine groups and aldehyde functionalities on modified chitosan. A novel approach was taken to add aldehyde functionalities to chitosan using a two-step reaction. Two types of slow and fast degrading hydrogels were prepared and loaded with iron (II) gluconate dihydrate, a non-hormonal spermicide, and doxorubicin hydrochloride, an anti-cancer drug. The release profiles of these drugs at different pH environments were assessed to determine the pH-dependent release mechanism. Mechanical properties, swell-ability and degradation rate of these matrices were studied. The cross-linking density of the hydrogel as well as pH changes played an important role in the characteristic of these hydrogels. The hydrogels degraded faster in lower pH, while the hydrogel with lower cross-linking density showed longer gelation time and faster degradation rate compared to the gel with higher cross-linking density. In vitro cytotoxicity assessment of these hydrogels in 48 h indicated the non-toxic effect of these hydrogels toward mesenchymal stem cells (MSCs) in the test period.

Cyclodextrin-polyhydrazine degradable gels for hydrophobic drug delivery.

An injectable and biocompatible hydrogel system was designed for hydrophobic drug delivery. This hydrogel consisted of degradable polymers with cyclodextrin (CD) moieties. CD groups were used to increase the solubility of a hydrophobic molecule (nicardipine) in an aqueous solution through the formation of the inclusion complex. Two sets of gels were prepared by mixing oxidized dextran (DA) and CD functionalized polyhydrazine (PH) at physiological conditions and different level of crosslinking via hydrazone bonds. Cytotoxicity studies on the gels and their components confirmed the biocompatibility of these materials. Gel-30 with higher crosslinking density showed a two week degradation period whereas this period was 10days for gel-10, with lower crosslinking density, to complete degradation. The results from swelling tests and rheological measurements were also found to be dependent on crosslinking density of the hydrogels. Release profile of the hydrogel displayed a sustained release of nicardipin up to 6days for gel-30 and a 4day release with initial burst release for gel-10.