Feasibility of lignin-based platforms for the development of healthcare applications.

Lignin, a naturally occurring aromatic biomacromolecule, which is available in large amounts as a byproduct from pulping industries and lignocellulosic biorefineries, has attracted growing interest in recent years. The rise of these modern biorefineries is dedicated to converting lignocellulosic biomass into biofuels or advanced bioproducts. This, coupled with a growing emphasis on environmental sustainability, has sparked great interest in the valorization of lignin in various fields, including chemicals or materials. Natural polymers obtained from biological systems have been widely employed for the development of biomedical applications in recent decades. The most used materials for this purpose include alginate, chitosan, collagen, gelatin, and cellulose, among others. Unfortunately, lignin remains relatively underexplored in the biomedical field. The heterogeneity of natural and technical lignin samples, arising from the various lignocellulosic resources and extraction methods used to obtain this biomacromolecule, may hinder its applicability in healthcare applications. Additionally, the lack of in vivo biocompatibility and biodegradability studies to fully understand how this biomacromolecule can be degraded by the human body remains the biggest limitation to the use of lignin in the biomedical field. Despite these drawbacks mentioned earlier, lignin possesses several distinctive properties, such as antioxidant and antimicrobial capabilities, UV-absorbing capabilities, and low cytotoxicity, which are not found in other natural polymers. Antioxidant materials have potential for biomedical applications as they contribute to reduce the concentration of reactive oxygen species and free radicals, which can preclude wound healing (Barapatre et al., 2015). Furthermore, the incorporation of materials with antimicrobial properties in the development of healthcare applications, such as wound dressings, may help prevent infections and enhance wound healing (Domínguez-Robles et al., 2020). Therefore, this biomacromolecule can be a promising good candidate to be incorporated in the development of healthcare applications (Domínguez-Robles et al., 2020; Sugiarto et al., 2022). This work discusses some recent advances in the valorization of lignin through the development of drug delivery platforms

Different Solvents for Organosolv Pulping

Organosolv pulping is a two-stage process involving hydrolysis (decomposition of wood by use of a catalyst) and removal of lignin with an organic solvent (usually a mixture of alcohol and water). The main disadvantage of using an alcohol is its low boiling point, which requires operating at a high pressure and hence using special equipment that is expensive to purchase and operate. One solution to this problem is using alternative organic solvents that afford operation at pressure levels similar to those of classic pulping processes (e.g., the Kraft process). This chapter provides a comprehensive literature review on the organosolv-based production of cellulose pulp by using alternative solvents such as glycols, phenols, esters, organic acids, acetone and amines

Phenotypic diploidization in plant functional traits uncovered by synthetic neopolyploids in Dianthus broteri

Whole-genome duplication and post-polyploidization genome downsizing play key roles in the evolution of land plants; however, the impact of genomic diploidization on functional traits still remains poorly understood. Using Dianthus broteri as a model, we compared the ecophysiological behaviour of colchicine-induced neotetraploids (4xNeo) to diploids (2x) and naturally occurring tetraploids (4xNat). Leaf gas-exchange and chlorophyll fluorescence analyses were performed in order to asses to what extent post-polyploidization evolutionary processes have affected 4xNat. Genomic diploidization and phenotypic novelty were evident. Distinct patterns of variation revealed that post-polyploidization processes altered the phenotypic shifts directly mediated by genome doubling. The photosynthetic phenotype was affected in several ways but the main effect was phenotypic diploidization (i.e. 2x and 4xNat were closer to each other than to 4xNeo). Overall, our results show the potential benefits of considering experimentally synthetized versus naturally established polyploids when exploring the role of polyploidization in promoting functional divergence.España Ministerio de Ciencia e Innovación project POLYTRANSECO (PGC2018-098358-B-I00)Spanish Ministerio de Universidades (FPU19/02936

Challenges for the Adoption of Model-Driven Web Engineering Approaches in Industry

Model-driven web engineering approaches have become an attractive research and technology solution for Web application development. However, after 20 years of development, they have attracted little attention from the Industry due to the mismatch between technical versus research requirements. In this joint work between academia and industry, the authors present the current problems of using these approaches in scale and provide guidelines to convert them into viable industry solutions.Ministerio de ciencia e Innovación TIN2016-76956-C3-2-RMinisterio de Economía y Competitividad TIN2015-71938-RED

Development of a Biodegradable Subcutaneous Implant for Prolonged Drug Delivery Using 3D Printing

Implantable drug delivery devices offer many advantages over other routes of drug delivery. Most significantly, the delivery of lower doses of drug, thus, potentially reducing side-effects and improving patient compliance. Three dimensional (3D) printing is a flexible technique, which has been subject to increasing interest in the past few years, especially in the area of medical devices. The present work focussed on the use of 3D printing as a tool to manufacture implantable drug delivery devices to deliver a range of model compounds (methylene blue, ibuprofen sodium and ibuprofen acid) in two in vitro models. Five implant designs were produced, and the release rate varied, depending on the implant design and the drug properties. Additionally, a rate controlling membrane was produced, which further prolonged the release from the produced implants, signalling the potential use of these devices for chronic conditions

Implantable Polymeric Drug Delivery Devices: Classification, Manufacture, Materials, and Clinical Applications

The oral route is a popular and convenient means of drug delivery. However, despite its advantages, it also has challenges. Many drugs are not suitable for oral delivery due to: first pass metabolism; less than ideal properties; and side-effects of treatment. Additionally, oral delivery relies heavily on patient compliance. Implantable drug delivery devices are an alternative system that can achieve effective delivery with lower drug concentrations, and as a result, minimise side-effects whilst increasing patient compliance. This article gives an overview of classification of these drug delivery devices; the mechanism of drug release; the materials used for manufacture; the various methods of manufacture; and examples of clinical applications of implantable drug delivery devices

3D-printed implantable devices with biodegradable rate-controlling membrane for sustained delivery of hydrophobic drugs

Implantable drug delivery systems offer an alternative for the treatments of long-term conditions (i.e. schizophrenia, HIV, or Parkinson's disease among many others). The objective of the present work was to formulate implantable devices loaded with the model hydrophobic drug olanzapine (OLZ) using robocasting 3D-printing combined with a pre-formed rate controlling membrane. OLZ was selected as a model molecule due to its hydrophobic nature and because is a good example of a molecule used to treat a chronic condition schizophrenia. The resulting implants consisted of a poly(ethylene oxide) (PEO) implant coated with a poly(caprolactone) (PCL)-based membrane. The implants were loaded with 50 and 80% (w/w) of OLZ. They were prepared using an extrusion-based 3D-printer from aqueous pastes containing 36-38% (w/w) of water. The printing process was carried out at room temperature. The resulting implants were characterized by using infrared spectroscopy, scanning electron microscopy, thermal analysis, and X-ray diffraction. Crystals of OLZ were present in the implant after the printing process. release studies showed that implants containing 50% and 80% (w/w) of OLZ were capable of providing drug release for up to 190 days. On the other hand, implants containing 80% (w/w) of OLZ presented a slower release kinetics. After 190 days, total drug release was ca. 77% and ca. 64% for implants containing 50% and 80% (w/w) of OLZ, respectively. The higher PEO content within implants containing 50% (w/w) of OLZ allows a faster release as this polymer acts as a co-solvent of the drug

Development of drug loaded cardiovascular prosthesis for thrombosis prevention using 3D printing

Cardiovascular disease (CVD) is a general term for conditions which are the leading cause of death in the world. Quick restoration of tissue perfusion is a key factor to combat these diseases and improve the quality and duration of patients' life. Revascularization techniques include angioplasty, placement of a stent, or surgical bypass grafting. For the latter technique, autologous vessels remain the best clinical option; however, many patients lack suitable autogenous due to previous operations and they are often unsuitable. Therefore, synthetic vascular grafts providing antithrombosis, neointimal hyperplasia inhibition and fast endothelialization are still needed. To address these limitations, 3D printed dipyridamole (DIP) loaded biodegradable vascular grafts were developed. Polycaprolactone (PCL) and DIP were successfully mixed without solvents and then vascular grafts were 3D printed. A mixture of high and low molecular weight PCL was used to better ensure the integration of DIP, which would offer the biological functions required above. Moreover, 3D printing technology provides the ability to fabricate structures of precise geometries from a 3D model, enabling to customize the vascular grafts' shape or size. The produced vascular grafts were fully characterized through multiple techniques and the last step was to evaluate their drug release, antiplatelet effect and cytocompatibility. The results suggested that DIP was properly mixed and integrated within the PCL matrix. Moreover, these materials can provide a sustained and linear drug release without any obvious burst release, or any faster initial release rates for 30 days. Compared to PCL alone, a clear reduced platelet deposition in all the DIP-loaded vascular grafts was evidenced. The hemolysis percentage of both materials PCL alone and PCL containing 20% DIP were lower than 4%. Moreover, PCL and 20% DIP loaded grafts were able to provide a supportive environment for cellular attachment, viability, and growth