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New Nanomedicines for the topical treatment of complex wounds

Acute and chronic wounds are a growing global health problem. The incidence of non-healing chronic wounds has exponentially increased with the aging of the population and chronic diseases. It has been estimated that there is a 2% prevalence of chronic wounds in the general population, which is associated with an annual estimated cost of more than US$50 billion. Biomaterial-based treatments are helpful in improving small-sized and uncomplicated ulcers. Biologic molecules, named epidermal growth factors (EGFs) have demonstrated potent therapeutic efficacy along with limited side effects, however, exogenous EGF is rapidly cleared from the topical application site.

Jaume Veciana, Nora Ventosa and co-workers have reported a soft, reliable, and scalable method based on compressed CO2 for obtaining nanoconjugates of recombinant human epidermal growth factors and nanovesicles. These nanoconjugates exhibit appropriate physicochemical properties together with an antimicrobial activity preventing infections that promote complete closure of complex wounds. Therefore, such nanoconjugates are a potential nanomedicine for the topical treatment of complex wounds, particularly diabetic foot ulcers. The article published by the medical journal Advances in Therapy was chosen to be the cover of number 6 in June.

“The use of NANBIOSIS Unit 6 of Biomaterial Processing and Nanostructuring Unit (from CIBER-BBN and ICMAB-CSIC) has allowed the obtaining of various versions of the nanoconjugates as well as their physical-chemical characteristics” – explained prof. Jaume Veciana

Article of reference: Nanoconjugates: Lidia Ferrer-Tasies, Hector Santana, Ingrid Cabrera-Puig, Elisabet González-Mira, Lídia Ballell-Hosa, Carla Castellar-Álvarez, Alba Córdoba, Josep Merlo-Mas, Haydee Gerónimo, Glay Chinea, Viviana Falcón, Evelyn Moreno-Calvo, Jan Skov Pedersen, Jessica Romero, Claudia Navarro-Requena, Calixto Valdés, Miladys Limonta, Jorge Berlanga, Santiago Sala, Eduardo Martínez, Jaume Veciana and Nora Ventosa, Recombinant Human Epidermal Growth Factor/Quatsome Nanoconjugates: A Robust Topical Delivery System for Complex Wound Healing.  Adv. Therap. 2021 14 June, 2000260 [DOI]

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Purchase, installation and implementation of a treatment, distribution and management system for the environmental control and registration of animal housing rooms

There is a growing demand, coming from the scientific community, to carry out studies with animal models in the best conditions for them. For this reason, the need of implementing a new control and recording system of environmental conditions within the stabling rooms of the CCMIJU Animal Housing arises.

The whole process and the awarded company, General de Instalaciones y Conservación S.L., have been published in the following link of the Public Sector Contracting Platform, within the framework of the project “Updating of the Infrastructures and implementation of a document control and LIMS management system to enhance the capacities of the NANBIOSIS Distributed ICTS Units managed by the CCMIJU (AILIMS-NANBIOSIS)”

Link

AILIMS has been co-funded by the European Regional Development Fund (FEDER) within the framework of the Pluriregional Operational Program of Spain (POPE) of Singular Scientific and Technical Infrastructures (ICTS) 2014-2020.

The following actions are considered in the framework of the project:

-Within Unit 22 or Animal Facility, the Installation and development of an environmental treatment-control system of the housing rooms, an Improvement and adaptation of the spaces for experimental models, the Acquisition, installation and development of a two-door ultra- filtered air shower and the Acquisition, installation and development of a post-procedural recovery chamber.

– For the rest of the NANBIOSIS Units managed by the CCMIJU: Acquisition, installation and development of a LIMS Software.

The actions and their budget are detailed below, together with the FEDER co-funded rate and the national contribution.

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U8-S05. Deposition of thin films (Polyimide, Parylene) for the fabrication of flexible devices or encapsulation purposes (On-site&Remote) OUTSTANDING.

Deposition of thin films (Polyimide, Parylene) for the fabrication of flexible devices or encapsulation purposes (On-site&Remote) OUTSTANDING.

Deposition of Polyimide (PI-2611) via spin-coating for the fabrication of flexible free-standing structures.
Conformal deposition of Parylene (different types available)

Customer benefits

  • Possibility to access to the PI deposition system in self-service mode to adapt the process to the customer needs.
  • Different Parylene types available for deposition to match customer needs

Target customer

Research groups and SMEs

References

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U8-S06. Encapsulation or fabrication of 3D strcutures via 3D printing.

Encapsulation or fabrication of 3D strcutures via 3D printing.

Fabrication of 3D structures using a dual extrusion 3D printer that delivers high-quality, composite-ready performance – in a smaller footprint

Customer benefits

Possibility to access to the 3D printing equipment in self-service mode to adapt the process to the customer needs.

Target customer

Research groups and SMEs

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U8-E15. Dual extrusion 3D printer (Ultimaker S3, Ultimaker BV)

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U8-E14. Oven for Polyimide curing in inert conditions (Ovenvan N67, Ovan).

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U8-E13 Spin coater for Polyimide depositon (W6-650-23B, Laurell Technologies Corp.)

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Awarded works for improvement and adaptation of the spaces for the maintenance of the experimental models in the CCMIJU’s Animal Housing

The Public Sector Contracting Platform has published the awarding to the company “Depur GM Deseño e Obra S.L” to carry out the improvement works in the CCMIJU’s Animal Housing within the framework of the project “Updating the Infrastructures and implementation of a LIMS document control and management system to enhance the capacities of the Distributed ICTS NANBIOSIS Units managed by the CCMIJU (AILIMS-NANBIOSIS).

For further details, please click here

The mentioned project has been co-funded by the European Regional Development Fund (FEDER) through the Ministry of Science and Innovation within the framework of the Programa Operativo Plurirregional de España (POPE) for Singular Scientific and Technical Infrastructures (ICTS) 2014-2020 and by the Consejería de Economía, Ciencia y Agenda Digital of Junta de Extremadura.

The following actions are considered in the framework of the project:

-Within Unit 22 or Animal Facility, the Installation and development of an environmental treatment-control system of the housing rooms, an Improvement and adaptation of the spaces for experimental models, the Acquisition, installation and development of a two-door ultra- filtered air shower and the Acquisition, installation and development of a post-procedural recovery chamber.

– For the rest of the NANBIOSIS Units managed by the CCMIJU: Acquisition, installation and development of a LIMS Software.

The actions and their budget are detailed below, together with the FEDER co-funded rate and the national contribution.

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A project by NANBIOSIS researchers, focused on COVID-19 detection and therapy, selected in ‘La Marató’ research program

The Scientific Commission of ‘La Marató TV3’ has seleced the project entitled “Diagnosis and treatment of Sars-Cov-2 by triplex formation”, led by Ramon Eritja, Scientific Director of NANBIOSIS Unit 29 Oligonucleotide Synthesis Platform (OSP) from CIBER-BBN and IQAC_CSIC to be financed with € 398,750.00. Verónica Noé from the Fundació Bosch i Gimpera Universitat de Barcelona, ​​the CIBERESP researcher Enrique Calderón Sandubete, from the Virgen del Rocío University Hospital and María Valeria Grazú Bonavía, from the Institute of Nanoscience and Materials of Aragón, INMA (CSIC- UNIZE) also participate in this project.

The edition of this solidarity initiative promoted by the Corporació Catalana de Mitjans Audiovisuals, raised more than twelve million euros to finance research against COVID-19. The project was selected, among the 229 submitted, to receive funding for its development.
“Our project wants to solve two important problems in the fight against the COVID-19 pandemic: the first is how to quickly and specifically detect people infected by this virus; and the second is that right now we do not have a effective therapy specifically designed to be used against the virus that causes COVID-19 “explains Dr. Eritja.

The project will try to solve both problems using synthetic oligonucleotides with high and specific affinity for viral RNA. “In recent years, a dozen oligonucleotides have been approved by Health agencies (EMA and FDA) for the treatment of genetic diseases such as Duchene muscular dystrophy as well as metabolic diseases such as familial hypercholesterolemia. In the project we will use specific oligonucleotides, procuced at NANBIOSIS U29, to bind viral RNA that could be used in vitro for the selective capture and diagnosis of the SARS-.COV-2 virus, but also in vivo to inhibit the replication of viral RNA “adds Ramón Eritja.

The call for grants from ‘La Marató’ was carried out, exceptionally, between the months of December and January. Until May, the 229 candidate projects have been reviewed electronically, following a process of proven rigor and transparency, coordinated by the Catalan Agency for Quality and Health Evaluation, in which 95 international evaluators have participated. The assessment, among other aspects, of the quality, the methodology, the scientific, health and social relevance, the innovative value and the viability of the candidate works has determined which projects have been financed with the resources of La Marató 2020.

With this new edition from La Marató, the solidarity project of the Catalan Audiovisual Media Corporation and the Foundation since 1992 an amount of € 216 million have been awarded and a total of 949 research projects hve been promoted, with participation of 9,350 researchers have participated.

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New drug delivery system for prolonged pain relief

The management of musculoskeletal pain is a key challenge due to the short duration of anesthetic effect produced by existing clinical treatments, in addition to their potential side effects. Researchers from the CIBER-BBN, the Institute of Nanoscience and Materials of Aragón (INMA), CSIC-University of Zaragoza and the Institute of Health Research of Aragón (IIS Aragón), in collaboration with researchers from the Faculty of Veterinary Medicine of the University of Zaragoza and with participation of NANBIOSIS Unit 9 Synthesis of Nanoparticles Unit, have developed nanogels loaded with nanocrystals of bupivacaine (an anesthetic commonly used in epidural anesthesia and in the control of postoperative pain) obtaining a high drug content for a prolonged duration of local anesthesia.

These nanogels are an alternative to the most prescribed analgesics (antipyretics, steroids and opioids), which frequently present adverse effects such as nausea, vomiting, dizziness and physical dependence, among others. They consist of a biocompatible polymer derived from polyethylene glycol (PEG) that has heat-sensitive properties, so that they would be injected at room temperature and upon reaching body temperature after administration they undergo a change in their structure, resulting in a reduction in their volume. and transforming into a hydrophobic structure, thus controlling the release of the drug encapsulated within.

According to Manuel Arruebo, INMA-CIBER-BBN researcher, “we have validated this new way of dispensing the local anesthetic both in cell cultures and in animal experiments, showing that it increases the duration of sciatic nerve block twice compared to the same dose of free anesthetic. The synthesis of the drug nanocrystals has been carried out in NANBIOSIS U9 (from CIBER-BBN and University of Zaragoza) thanks to the wet chemical synthesis systems of the platform“.

The prolonged duration of anesthetic action can be explained by the regional immobilization of the nanogels at the injection site around the sciatic nerve due to their hydrophobic nature, preventing the diffusion of drug particles and their rapid elimination while interacting efficiently with the tissues thanks to to its temperature-induced conformational change. Studies have shown that this delivery system has low toxicity and does not give rise to an inflammatory response due to the slow release of the drug and the high biocompatibility of the polymer used.

The encapsulation of drug nanocrystals is a promising strategy, which allows reducing the total amount of drug necessary to produce pain relief with the consequent benefits obtained from the reduction of toxicity.

For their part, the researchers Teresa Alejo (INMA) and Víctor Sebastián (CIBER-BBN-INMA) affirm that “through these systems we seek to obtain an effective vehicle capable of prolonging the anesthetic effect in its place of action, avoiding as far as possible the side effects. In this way, they could be used to avoid systemic administration, reduce high concentrations in the blood and reduce the unwanted side effects of some conventional treatments, since they allow to control the release of the drug within the desired therapeutic range, avoiding the consequences of an excess of drug and the negative effects that this implies ”.

Likewise, with this technique the satisfaction and comfort of the patient is considered, since with a single dosage a prolonged therapeutic effect would be achieved. In Europe, with more than 500 million days of sick leave per year, musculoskeletal pain causes almost 50% of all absences from work lasting at least three days and 60% of permanent absences from work. Consequently, pain has a huge impact on work productivity. Some data indicate that the annual cost of pain is greater than the cost of heart disease, cancer and diabetes.

Therefore, the development of an effective injectable local anesthetic with a prolonged duration of action can improve the quality of life of patients affected by these diseases.

Article of refernce:

Teresa Alejo, Laura Usón, Guillermo Landa, Martin Prieto, Cristina Yus Argón, Sara García-Salinas, Ricardo de Miguel, Ana Rodríguez-Largo, Silvia Irusta, Victor Sebastián, Gracia Mendoza and Manuel Arruebo. Nanogels with High Loading of Anesthetic Nanocrystals for Extended Duration of Sciatic Nerve Block, ACS Appl. Mater. Interfaces, 13, 15, 17220–17235. 2021 April 6. [DOI]

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