Thermogelling amphiphilic block copolymers have been widely investigated in the development of pharmaceutical drug carriers. In particular, thermosensitive gels based on poloxamer 407 (P407) have great potential for periodontal disease treatment, thanks to their ability to be liquid at room temperature and become viscous gels at body temperature. However, some problems, related to short in situ residence time, reduce their feasible clinical use. Thus, in order to improve the effective applicability of these materials, we studied how P407 thermogels are affected by the pH and by the inclusion of different hydrophilic polymers, used as excipients for increasing the gel stiffness. For this scope, a complete chemical-physical characterization of the synthesized gels is provided, in terms of determination of sol-gel transition temperature, viscosity and erosion degree. The data are correlated according to a statistical multivariate approach based on Principal Component Analysis and their mucoadhesion properties are also tested by Tapping mode-Atomic Force Microscopy (TM-AFM) imaging. Finally, we studied how the different P407 formulations are able to influence the release pathway of two antibacterial drugs (i.e., chlorhexidine digluconate and doxycycline hyclate) largely used in oral diseases.
Mandibular tissue engineering aims to develop synthetic substitutes for the regeneration of critical size defects (CSD) caused by a variety of events, including tumor surgery and post‐traumatic resections. Currently, the gold standard clinical treatment of mandibular resections (i.e., autologous fibular flap) has many drawbacks, driving research efforts toward scaffold design and fabrication by additive manufacturing (AM) techniques. Once implanted, the scaffold acts as a support for native tissue and facilitates processes that contribute to its regeneration, such as cells infiltration, matrix deposition and angiogenesis. However, to fulfil these functions, scaffolds must provide bioactivity by mimicking natural properties of the mandible in terms of structure, composition and mechanical behavior. This review aims to present the state of the art of scaffolds made with AM techniques that are specifically employed in mandibular tissue engineering applications. Biomaterials chemical composition and scaffold structural properties are deeply discussed, along with strategies to promote osteogenesis (i.e., delivery of biomolecules, incorporation of stem cells, and approaches to induce vascularization in the constructs). Finally, a comparison of in vivo studies is made by taking into consideration the amount of new bone formation (NB), the CSD dimensions, and the animal model.
In recent decades, hydrogels have emerged as innovative soft materials with widespread applications in the medical and biomedical fields, including drug delivery, tissue engineering, and gel dosimetry. In this work, a comprehensive study of the macroscopic and microscopic properties of hydrogel matrices based on Poly(vinyl-alcohol) (PVA) chemically crosslinked with Glutaraldehyde (GTA) was reported. Five different kinds of PVAs differing in molecular weight and degree of hydrolysis were considered. The local microscopic organization of the hydrogels was studied through the use of the 1H nuclear magnetic resonance relaxometry technique. Various macroscopic properties (gel fraction, water loss, contact angle, swelling degree, viscosity, and Young’s Modulus) were investigated with the aim of finding a correlation between them and the features of the hydrogel matrix. Additionally, an optical characterization was performed on all the hydrogels loaded with Fricke solution to assess their dosimetric behavior. The results obtained indicate that the degree of PVA hydrolysis is a crucial parameter influencing the structure of the hydrogel matrix. This factor should be considered for ensuring stability over time, a vital property in the context of potential biomedical applications where hydrogels act as radiological tissue-equivalent materials.
Bioinspired soft robotics aims at reproducing the complex hierarchy and architecture of biological tissues within artificial systems to achieve the typical motility and adaptability of living organisms. The development of suitable fabrication approaches to produce monolithic bodies provided with embedded variable morphological and mechanical properties, typically encountered in nature, is still a technological challenge. Here we report on a novel manufacturing approach to produce three-dimensional functionally graded hydrogels (3D-FGHs) provided with a controlled porosity gradient conferring them variable stiffness. 3D-FGHs are fabricated by means of a custom-designed liquid foam templating (LFT) technique, which relies on the inclusion of air bubbles generated by a blowing agent into the monomer-based template solution during ultraviolet-induced photopolymerization. The 3D-FGHs' apparent Young's modulus ranges from 0.37 MPa (bulky hydrogel region) to 0.09 MPa (highest porosity region). A fish-shaped soft swimmer is fabricated to demonstrate the feasibility of the LFT technique to produce bioinspired robots. Mobility tests show a significant improvement in terms of swimming speed when the robot is provided with a graded body. The proposed manufacturing approach constitutes an enabling solution for the development of macroscopic functionally graded hydrogel-based structures usable in biomimetic underwater soft robotics applications.
Biological methods for mosquito larvae control are completely biodegradable and have null or limited effects on nontarget organisms. However, commercially available products have a low residual activity, with the consequent need for multiple applications that inevitably increase costs and the risk of resistance phenomena insurgence. Smart delivery systems made of hydrogels proved their efficacy in increasing the action duration of biolarvicides up to several months, but the lack of an efficient baiting mechanism to strongly attract the target pest remains a problem in practical applications. In this work, we investigated two novel hydrogel-based formulations of completely natural composition for baiting and killing larvae of Aedes albopictus mosquitos. The proposed materials consist of charged crosslinked polysaccharides (chitosan and cellulose) and are specifically manufactured to float in water, simulating organic matter usually present at breeding sites. Within the hydrogels’ matrix, yeast colonies of Saccharomyces cerevisiae were embedded as phagostimulants alongside a biolarvicide (Bacillus thuringiensis var. israelensis (Bti)). Despite the similar chemical nature and structure, chitosan-based hydrogels exhibited a markedly superior baiting potential compared to those made of cellulose and also succeeded in efficiently killing mosquito larvae just after a few hours from administration. We are confident that the proposed smart delivery hydrogel made of chitosan can be an enabling tool to attract mosquito larvae towards biopesticides of different nature without delocalizing active ingredients away from the breeding site and to simultaneously increase their residual activity, thus holding the potential of minimizing environmental pollution related to pest control and vector-borne disease prevention.
7 November 2019 in Annals of Biomedical Engineering