Multifunctional Hydrogels Based on Cellulose and Modified Lignin for Advanced Wounds Management.

Considering the complex process of wound healing, it is expected that an optimal wound dressing should be able to overcome the multiple obstacles that can be encountered in the wound healing process. An ideal dressing should be biocompatible, biodegradable and able to maintain moisture, as well as allow the removal of exudate, have antibacterial properties, protect the wound from pathogens and promote wound healing. Starting from this desideratum, we intended to design a multifunctional hydrogel that would present good biocompatibility, the ability to provide a favorable environment for wound healing, antibacterial properties, and also, the capacity to release drugs in a controlled manner. In the preparation of hydrogels, two natural polymers were used, cellulose (C) and chemically modified lignin (LE), which were chemically cross-linked in the presence of epichlorohydrin. The structural and morphological characterization of CLE hydrogels was performed by ATR-FTIR spectroscopy and scanning electron microscopy (SEM), respectively. In addition, the degree of swelling of CLE hydrogels, the incorporation/release kinetics of procaine hydrochloride (PrHy), and their cytotoxicity and antibacterial properties were investigated. The rheological characterization, mechanical properties and mucoadhesion assessment completed the study of CLE hydrogels. The obtained results show that CLE hydrogels have an increased degree of swelling compared to cellulose-based hydrogel, a better capacity to encapsulate PrHy and to control the release of the drug, as well as antibacterial properties and improved mucoadhesion. All these characteristics highlight that the addition of LE to the cellulose matrix has a positive impact on the properties of CLE hydrogels, confirming that these hydrogels can be considered as potential candidates for applications as oral wound dressings.

Insight into the Latest Medical Applications of Nanocellulose.

Nanocelluloses (NCs) are appealing nanomaterials that have experienced rapid development in recent years, with great potential in the biomedical field. This trend aligns with the increasing demand for sustainable materials, which will contribute both to an improvement in wellbeing and an extension of human life, and with the demand to keep up with advances in medical technology. In recent years, due to the diversity of their physical and biological properties and the possibility of tuning them according to the desired goal, these nanomaterials represent a point of maximum interest in the medical field. Applications such as tissue engineering, drug delivery, wound dressing, medical implants or those in cardiovascular health are some of the applications in which NCs have been successfully used. This review presents insight into the latest medical applications of NCs, in the forms of cellulose nanocrystals (CNCs), cellulose nanofibers (CNFs) and bacterial nanocellulose (BNC), with an emphasis on the domains that have recently experienced remarkable growth, namely wound dressing, tissue engineering and drug delivery. In order to highlight only the most recent achievements, the presented information is focused on studies from the last 3 years. Approaches to the preparation of NCs are discussed either by top-down (chemical or mechanical degradation) or by bottom-up (biosynthesis) techniques, along with their morphological characterization and unique properties, such as mechanical and biological properties. Finally, the main challenges, limitations and future research directions of NCs are identified in a sustained effort to identify their effective use in biomedical fields.

3D Matrices for Enhanced Encapsulation and Controlled Release of Anti-Inflammatory Bioactive Compounds in Wound Healing.

Current trends in the development of wound dressings are oriented towards the use of biopolymer-based materials, due to their unique properties such as non-toxicity, hydrophilicity, biocompatibility and biodegradability, properties that have advantageous therapeutic characteristics. In this regard, the present study aims to develop hydrogels based on cellulose and dextran (CD) and to reveal their anti-inflammatory performance. This purpose is achieved by incorporating plant bioactive polyphenols (PFs) in CD hydrogels. The assessments include establishing the structural characteristics using attenuated total reflection Fourier transformed infrared (ATR-FTIR) spectroscopy, the morphology by scanning electron microscopy (SEM), the swelling degree of hydrogels, the PFs incorporation/release kinetics and the hydrogels' cytotoxicity, together with evaluation of the anti-inflammatory properties of PFs-loaded hydrogels. The results show that the presence of dextran has a positive impact on the hydrogel's structure by decreasing the pore size at the same time as increasing the uniformity and interconnectivity of the pores. In addition, there is an increased degree of swelling and of the encapsulation capacity of PFs, with the increase of the dextran content in hydrogels. The kinetics of PFs released by hydrogels was studied according to the Korsmeyer-Peppas model, and it was observed that the transport mechanisms depend on hydrogels' composition and morphology. Furthermore, CD hydrogels have been shown to promote cell proliferation without cytotoxicity, by successfully culturing fibroblasts and endothelial cells on CD hydrogels (over 80% viability). The anti-inflammatory tests performed in the presence of lipopolysaccharides demonstrate the anti-inflammatory properties of the PFs-loaded hydrogels. All these results provide conclusive evidence on the acceleration of wound healing by inhibiting the inflammation process and support the use of these hydrogels encapsulated with PFs in wound healing applications.

Natural Polymers in Heart Valve Tissue Engineering: Strategies, Advances and Challenges.

In the history of biomedicine and biomedical devices, heart valve manufacturing techniques have undergone a spectacular evolution. However, important limitations in the development and use of these devices are known and heart valve tissue engineering has proven to be the solution to the problems faced by mechanical and prosthetic valves. The new generation of heart valves developed by tissue engineering has the ability to repair, reshape and regenerate cardiac tissue. Achieving a sustainable and functional tissue-engineered heart valve (TEHV) requires deep understanding of the complex interactions that occur among valve cells, the extracellular matrix (ECM) and the mechanical environment. Starting from this idea, the review presents a comprehensive overview related not only to the structural components of the heart valve, such as cells sources, potential materials and scaffolds fabrication, but also to the advances in the development of heart valve replacements. The focus of the review is on the recent achievements concerning the utilization of natural polymers (polysaccharides and proteins) in TEHV; thus, their extensive presentation is provided. In addition, the technological progresses in heart valve tissue engineering (HVTE) are shown, with several inherent challenges and limitations. The available strategies to design, validate and remodel heart valves are discussed in depth by a comparative analysis of in vitro, in vivo (pre-clinical models) and in situ (clinical translation) tissue engineering studies.

Advanced Functional Materials Based on Nanocellulose for Pharmaceutical/Medical Applications.

Nanocelluloses (NCs), with their remarkable characteristics, have proven to be one of the most promising "green" materials of our times and have received special attention from researchers in nanomaterials. A diversity of new functional materials with a wide range of biomedical applications has been designed based on the most desirable properties of NCs, such as biocompatibility, biodegradability, and their special physicochemical properties. In this context and under the pressure of rapid development of this field, it is imperative to synthesize the successes and the new requirements in a comprehensive review. The first part of this work provides a brief review of the characteristics of the NCs (cellulose nanocrystals-CNC, cellulose nanofibrils-CNF, and bacterial nanocellulose-BNC), as well as of the main functional materials based on NCs (hydrogels, nanogels, and nanocomposites). The second part presents an extensive review of research over the past five years on promising pharmaceutical and medical applications of nanocellulose-based materials, which have been discussed in three important areas: drug-delivery systems, materials for wound-healing applications, as well as tissue engineering. Finally, an in-depth assessment of the in vitro and in vivo cytotoxicity of NCs-based materials, as well as the challenges related to their biodegradability, is performed.

Cellulose-Based Hydrogels as Sustained Drug-Delivery Systems.

Hydrogels, three-dimensional (3D) polymer networks, present unique properties, like biocompatibility, biodegradability, tunable mechanical properties, sensitivity to various stimuli, the capacity to encapsulate different therapeutic agents, and the ability of controlled release of the drugs. All these characteristics make hydrogels important candidates for diverse biomedical applications, one of them being drug delivery. The recent achievements of hydrogels as safe transport systems, with desired therapeutic effects and with minimum side effects, brought outstanding improvements in this area. Moreover, results from the utilization of hydrogels as target therapy strategies obtained in clinical trials are very encouraging for future applications. In this regard, the review summarizes the general concepts related to the types of hydrogel delivery systems, their properties, the main release mechanisms, and the administration pathways at different levels (oral, dermal, ocular, nasal, gastrointestinal tract, vaginal, and cancer therapy). After a general presentation, the review is focused on recent advances in the design, preparation and applications of innovative cellulose-based hydrogels in controlled drug delivery.