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.

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.

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.

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.

Hydrogel features can be designed and optimized using different crosslinking agents to meet specific requirements. In this regard, the present work investigates the physico-chemical features of cellulose-based hydrogels, designed by using different epoxy crosslinkers from the same glycidyl family, namely epichlorohydrin (ECH), 1,4-butanediol diglycidyl ether (BDDE), and trimethylolpropane triglycidyl ether (TMPTGE). The effect of the crosslinker’s structure (from simple to branched) and functionality (mono-, bi- and tri-epoxy groups) on the hydrogels’ features was studied. The performances of the hydrogels were investigated through the gel fraction, as well as by ATR-FTIR, DVS, SEM, DSC, and TG analyses. Also, the swelling and rheological behaviors of the hydrogels were examined. The advantages and limitations of each approach were discussed and a strong correlation between the crosslinker structure and the hydrogel properties was established. The formation of new ether bonds was evidenced by ATR-FTIR spectroscopy. It was emphasized that the pore size is directly influenced by the crosslinker type, namely, it decreases with the increasing number of epoxy groups from the crosslinker molecule, i.e., from 46 ± 11.1 µm (hydrogel CE, with ECH) to 12.3 ± 2.5 µm (hydrogel CB, with BDDE) and 6.7 ± 1.5 µm (hydrogel CT, with TMPTGE). The rheological behavior is consistent with the swelling data and hydrogel morphology, such as CE with the highest Qmax and the largest pore size being relatively more elastic than CB and CT. Instead, the denser matrices obtained by using crosslinkers with more complex structures have better thermal stability. The experimental results highlight the possibility of using a specific crosslinking agent, with a defined structure and functionality, in order to establish the main characteristics of hydrogels and, implicitly, to design them for a certain field of application.