Sustainable Silk-Based Particulate Systems for the Controlled Release of Pharmaceuticals and Bioactive Agents in Wound Healing and Skin Regeneration.

The increasing demand for innovative approaches in wound healing and skin regeneration has prompted extensive research into advanced biomaterials. This review focuses on showcasing the unique properties of sustainable silk-based particulate systems in promoting the controlled release of pharmaceuticals and bioactive agents in the context of wound healing and skin regeneration. Silk fibroin and sericin are derived from well-established silkworm production and constitute a unique biocompatible and biodegradable protein platform for the development of drug delivery systems. The controlled release of therapeutic compounds from silk-based particulate systems not only ensures optimal bioavailability but also addresses the challenges associated with conventional delivery methods. The multifaceted benefits of silk proteins, including their inherent biocompatibility, versatility, and sustainability, are explored in this review. Furthermore, the intricate mechanisms by which controlled drug release takes place from silk-based carriers are discussed.

End-of-life management strategies of pharmaceuticals in Portuguese households.

The end of life of pharmaceutical products through environmentally unsafe routes is a growing concern in our society. However, the studies reported so far, apart from being limited in number, do not reflect the current management practices for the end-of-life management of pharmaceuticals. Published work lacks an in-depth analysis in focusing on the pharmaceutical waste in households. The present work focused on (1) performing a state-of-the art overview to compare worldwide studies and the results and (2) implementing a comprehensive survey in Portugal (n = 454 respondents). The results showed that the delivery to pharmacies was used by the majority of the respondents (72%), indicating a good awareness of pharmaceutical waste management issues, when compared to the reviewed studies. Statistically significant variables for the destination of end-of-use pharmaceuticals include gender, age and distance from the residence to the pharmacy (p < 0.05). Most participants believe that educating the population on existing structures of medication and packaging management is of the utmost importance to improve the national managing system. This is the first study conducted in Portugal; it includes statistical analysis of the data and reflects on the practices that should be adopted to reduce incorrect pharmaceutical waste disposal. These findings call upon the strategies to strengthen the pharmaceutical waste management programme.

Continuous Production of Highly Tuned Silk/Calcium-Based Composites: Exploring New Pathways for Skin Regeneration.

Calcium plays an important role in barrier function repair and skin homeostasis. In particular, calcium phosphates (CaPs) are well established materials for biomedical engineering due to their biocompatibility. To generate biomaterials with a more complete set of biological properties, previously discarded silk sericin (SS) has been recovered and used as a template to grow CaPs. Crucial characteristics for skin applications, such as antibacterial activity, can be further enhanced by doping CaPs with cerium (Ce) ions. The effectiveness of cell attachment and growth on the materials highly depends on their morphology, particle size distribution, and chemical composition. These characteristics can be tailored through the application of oscillatory flow technology, which provides precise mixing control of the reaction medium. Thus, in the present work, CaP/SS and CaP/SS/Ce particles were fabricated for the first time using a modular oscillatory flow plate reactor (MOFPR) in a continuous mode. Furthermore, the biological behavior of both these composites and of previously produced pure CaPs was assessed using human dermal fibroblasts (HDFs). It was demonstrated that both CaP based with plate-shaped nanoparticles and CaP-SS-based composites significantly improved cell viability and proliferation over time. The results obtained represent a first step towards the reinvention of CaPs for skin engineering.

Expanding the boundaries of silk sericin biomaterials in biomedical applications.

Silk sericin (SS) has a long history as a by-product of the textile industry. SS has emerged as a sustainable material for biomedical engineering due to its material properties including water solubility, diverse impact on biological activities including antibacterial and antioxidant properties, and ability to promote cell adhesion and proliferation. This review addresses the origin, structure, properties, extraction, and underlying functions of this protein. An overview of the growing research studies and market evolution is presented, along with highlights of the most common fabrication matrices (hydrogels, bioinks, porous and fibrous scaffolds) and tissue engineering applications. Finally, the future trends with this protein as a multifaceted toolbox for bioengineering are explored, along with the challenges with SS. Overall, the present review can serve as a foundation for the creation of innovative biomaterials utilizing SS as a fundamental building block that hold market potential.

An update on hydroxyapatite/collagen composites: What is there left to say about these bioinspired materials?

Hydroxyapatite (HAp)/collagen-based composite materials have been a constant in the development of bioinspired materials for bone tissue engineering. The most fundamental research works focus on combining HAp, due to its chemical similarity with the mineral component of bones, and collagen, which is the most abundant protein in the body. Modern studies have explored different two-dimensional (2D) and 3D structures, in order to obtain biomaterials with specific physicochemical, mechanical, and biological characteristics that can be applied in distinct biomedical applications. However, as there is already so much work developed with these materials, it is crucial to question: what can still be done? What is the importance of current know-how for the future of bioinspired materials? In this paper we intend to review and update the available methodologies to synthesize HAp/collagen composites, along with their characteristics. In addition, the future of these materials in terms of applications and their potential as a cutting-edge technology is discussed.

Current Trends on Protein Driven Bioinks for 3D Printing.

In the last decade, three-dimensional (3D) extrusion bioprinting has been on the top trend for innovative technologies in the field of biomedical engineering. In particular, protein-based bioinks such as collagen, gelatin, silk fibroin, elastic, fibrin and protein complexes based on decellularized extracellular matrix (dECM) are receiving increasing attention. This current interest is the result of protein's tunable properties, biocompatibility, environmentally friendly nature and possibility to provide cells with the adequate cues, mimicking the extracellular matrix's function. In this review we describe the most relevant stages of the development of a protein-driven bioink. The most popular formulations, molecular weights and extraction methods are covered. The different crosslinking methods used in protein bioinks, the formulation with other polymeric systems or molecules of interest as well as the bioprinting settings are herein highlighted. The cell embedding procedures, the in vitro, in vivo, in situ studies and final applications are also discussed. Finally, we approach the development and optimization of bioinks from a sequential perspective, discussing the relevance of each parameter during the pre-processing, processing, and post-processing stages of technological development. Through this approach the present review expects to provide, in a sequential manner, helpful methodological guidelines for the development of novel bioinks.

Silk-based microcarriers: current developments and future perspectives.

Cell-seeded microcarriers (MCs) are currently one of the most promising topics in biotechnology. These systems are supportive structures for cell growth and expansion that allow efficient nutrient and gas transfer between the media and the attached cells. Silk proteins have been increasingly used for this purpose in the past few years due to their biocompatibility, biodegradability and non-toxicity. To date, several silk fibroin spherical MCs in combination with alginate, gelatin and calcium phosphates have been reported with very interesting outcomes. In addition, other silk-based three-dimensional structures such as microparticles with chitosan and collagen, as well as organoids, have been increasingly studied. In this study, the physicochemical and biological properties of these biomaterials, as well as the recent methodologies for their processing and for cell culture, are discussed. The potential biomedical applications are also addressed. In addition, an analysis of the future perspectives is presented, where the potential of innovative silk-based MCs processing technologies is highlighted.

Protein-Based Hydroxyapatite Materials: Tuning Composition toward Biomedical Applications.

Synthetic hydroxyapatite (HAp) has been successfully produced with the aim of obtaining biomaterials that meet the biomechanical requirements for bone tissue engineering, while being compatible with the surrounding biochemical and cellular environment. Combining proteins with HAp can generate improved composite biomaterials, which are environmentally friendly, renewable, and biocompatible. In this context, HAp/protein-based composite materials have been widely exploited since the late 20th century to the present day. In this review, we explore the biomedical relevance of the association of HAp with several proteins of interest such as fibroin, sericin, fibrin, and keratin. The processing strategies for their synthesis and effect on the obtained shape and physicochemical, mechanical, and biological performance are herein discussed. This work can provide useful information for the design of HAp-based biomaterials with specific emphasis on bone tissue regeneration characteristics for biomedical applications.

Hydroxyapatite/sericin composites: A simple synthesis route under near-physiological conditions of temperature and pH and preliminary study of the effect of sericin on the biomineralization process.

Synthesis of hydroxyapatite (HAp) and sericin (SS) nanocomposites was carried out by a simple precipitation method performed in batch in a stirred tank reactor (ST). The reaction was achieved by mixing a solution of calcium chloride dihydrate, in which SS was dissolved, with a solution of disodium hydrogen phosphate at 37 °C. Three experimental conditions were studied by varying the concentration of SS: HAp, HAp/SS1 (0.01 g/L of SS) and HAp/SS2 (1 g/L of SS). The chemical and physical properties of the resulting HAp/SS nanocomposites were studied using several techniques (Atomic Absorption Spectrometry, Ultraviolet-Visible Spectrophotometry, Fourier Transform Infrared Spectroscopy (FTIR), X-ray diffraction (XRD), Scanning electron microscopy (SEM), Transmission electron microscopy (TEM), Selected area diffraction (SAED) and Thermogravimetric analysis (TGA)). pH profile was also monitored over time for each experimental condition. The results revealed that nano single-phased HAp was formed with both rod and plate-like shape. Additionally, the particles have low crystallinity, characteristic similar to biological HAp. Regarding the influence of SS, one observed that with increasing SS concentration there is an increase in the mean particle size and the number of plate-like particles, as well as an increase in the aggregation degree and a decrease of the crystallinity. Further, the composites obtained have an inorganic/organic composition comparable to bone. Finally, in vitro cytotoxicity showed that the synthetized nanoparticles are non-toxic and cell viability is higher for HAp and HAp/SS samples when compared to a commercially available HAp. The produced materials can thus be considered suitable candidates for bone related applications.