Significance: The regeneration of healthy and functional skin remains a huge challenge due to its multilayer structure and the presence of different cell types within the extracellular matrix in an organized way. Despite recent advances in wound care products, traditional therapies based on natural origin compounds, such as plant extracts, honey, and larvae, are interesting alternatives. These therapies offer new possibilities for the treatment of skin diseases, enhancing the access to the healthcare, and allowing overcoming some limitations associated to the modern products and therapies, such as the high costs, the long manufacturing times, and the increase in the bacterial resistance. This article gives a general overview about the recent advances in traditional therapies for skin wound healing, focusing on the therapeutic activity, action mechanisms, and clinical trials of the most commonly used natural compounds. New insights in the combination of traditional products with modern treatments and future challenges in the field are also highlighted. Recent Advances: Natural compounds have been used in skin wound care for many years due to their therapeutic activities, including anti-inflammatory, antimicrobial, and cell-stimulating properties. The clinical efficacy of these compounds has been investigated through in vitro and in vivo trials using both animal models and humans. Besides the important progress regarding the development of novel extraction methods, purification procedures, quality control assessment, and treatment protocols, the exact mechanisms of action, side effects, and safety of these compounds need further research. Critical Issues: The repair of skin lesions is one of the most complex biological processes in humans, occurring throughout an orchestrated cascade of overlapping biochemical and cellular events. To stimulate the regeneration process and prevent the wound to fail the healing, traditional therapies and natural products have been used with promising results. Although these products are in general less expensive than the modern treatments, they can be sensitive to the geographic location and season, and exhibit batch-to-batch variation, which can lead to unexpected allergic reactions, side effects, and contradictory clinical results. Future Directions: The scientific evidence for the use of traditional therapies in wound healing indicates beneficial effects in the treatment of different lesions. However, specific challenges remain unsolved. To extend the efficacy and the usage of natural substances in wound care, multidisciplinary efforts are necessary to prove the safety of these products, investigate their side effects, and develop standard controlled trials. The development of good manufacturing practices and regulatory legislation also assume a pivotal role in order to improve the use of traditional therapies by the clinicians and to promote their integration into the national health system. Current trends move to the development of innovative wound care treatments, combining the use of traditional healing agents and modern products/practices, such as nanofibers containing silver nanoparticles, Aloe vera loaded into alginate hydrogels, propolis into dressing films, and hydrogel sheets containing honey.

Sodium alginate films with aloe vera extract were prepared by the casting/solvent evaporation technique. The resulting films were characterized by differential scanning calorimetry, Fourier transform-infrared spectroscopy, scanning electron microscopy, and mechanical and water absorption tests. The in vitro degradation of the films was also investigated over 14 days. Results show that aloe vera contributes to both enhancing the thermal and mechanical properties of the films and decreasing the weight loss during in vitro degradation.

Skin is the largest organ of human body, acting as a barrier with protective, immunologic and sensorial functions. Its permanent exposure to the external environment can result in different kinds of damage with loss of variable volumes of extracellular matrix. For the treatment of skin lesions, several strategies are currently available, such as the application of autografts, allografts, wound dressings and tissue-engineered substitutes. Although proven clinically effective, these strategies are still characterized by key limitations such as patient morbidity, inadequate vascularization, low adherence to the wound bed, the inability to reproduce skin appendages and high manufacturing costs. Advanced strategies based on both bottom-up and top-down approaches offer an effective, permanent and viable alternative to solve the abovementioned drawbacks by combining biomaterials, cells, growth factors and advanced biomanufacturing techniques. This review details recent advances in skin regeneration and repair strategies, and describes their major advantages and limitations. Future prospects for skin regeneration are also outlined.

Today, innovative three-dimensional (3D) cell culture models have been proposed as viable and biomimetic alternatives for initial drug screening, allowing the improvement of the efficiency of drug development. These models are gaining popularity, given their ability to reproduce key aspects of the tumor microenvironment, concerning the 3D tumor architecture as well as the interactions of tumor cells with the extracellular matrix and surrounding non-tumor cells. The development of accurate 3D models may become beneficial to decrease the use of laboratory animals in scientific research, in accordance with the European Union’s regulation on the 3R rule (Replacement, Reduction, Refinement). This review focuses on the impact of 3D cell culture models on cancer research, discussing their advantages, limitations, and compatibility with high-throughput screenings and automated systems. An insight is also given on the adequacy of the available readouts for the interpretation of the data obtained from the 3D cell culture models. Importantly, we also emphasize the need for the incorporation of additional and complementary microenvironment elements on the design of 3D cell culture models, towards improved predictive value of drug efficacy.

Three‐dimensional (3D) bioprinting comprises a group of biofabrication technologies for the additive manufacturing of 3D constructs by precisely printing biocompatible materials, cells and biochemicals in predesigned spatial positions. These technologies have been successfully applied to fabricate biodegradable 3D constructs with intricate architectures and heterogeneous composition, assuming a pivotal role in the field of tissue engineering. However, the full implementation of bioprinting strongly depends on the development of novel biomaterials exhibiting fast crosslinking schemes and appropriate printability, cell‐compatibility and biomechanical properties. Photocrosslinkable hydrogels are attractive materials for bioprinting as they provide fast polymerization under cell‐compatible conditions and exceptional spatiotemporal control over the gelation process. Photopolymerization can also be performed during the bioprinting to promote the instantaneous formation of hydrogel with high well‐defined architecture and structural stability. In this review paper, we summarize the most recent developments on bioprinting of photocrosslinkable biodegradable hydrogels for tissue engineering, focusing on the chemical modification strategies and the combination of photocrosslinking reactions with other gelation modalities. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42458.