Neural Repair and Biomaterials

Grupo Reparación Neural y Biomateriales

Neural Repair and Biomaterials

 

Principal investigator: Jorge E. Collazos Castro, MD. PhD.

E-mail: jcollazos@sescam.org

 

 

Our objective is to contribute to the development of an effective treatment for human spinal cord injury (SCI). We have two complementary research lines to accomplish this goal. A part of our effort is devoted to investigate models of SCI and techniques for neurological assessment in rodents and pigs, in order to provide insight into the nature of the functional deficits and document the effects of experimental therapies. In addition, we investigate neural growth and its control by electroactive materials, with the final aim of designing implantable bio-electronic systems that may help to promote the recovery of sensory and motor functions ensuing SCI.

 

We characterized the deficits and adaptive mechanisms for locomotion in rats with cervical spinal cord hemisection (López-Dolado et al., J Neurotrauma 2013), cervical contusion (Collazos-Castro et al., J Neurotrauma 2005), thoracic contusion (Collazos-Castro et al., J Neurotrauma 2006), and thoracic transection. The biomechanics of locomotion is studied at high temporal resolution, whereas the remaining neural connectivity is investigated by neural tracing and other neuroanatomical methods (Collazos-Castro et al., J Neurotrauma 2005; Lucas-Osma y Collazos-Castro, J Comp Neurol 2009; López-Dolado et al., J Neurotrauma 2013). By combining those techniques we achieve a good correlation between anatomy, physiology and behavior. In 2016 we started to study the recovery of motor function in pigs with cervical SCI. This preclinical model is critical to inform the design of human clinical trials, as it allows a better assessment of the proposed implants, as well as investigation of the pharmacological doses and routes of administration that may have positive effects on the human condition.

 

Initially we searched substrates made of inorganic oxides for neural cell growth (Collazos-Castro et al., Thin Solid Films 2009; Carballo-Vila et al., J Biomed Mater Res A 2009; Cruz et al., J Phys Chem C 2012), but later we focused on conducting polymers (PEDOT) because they offer advantages for interfacing neural cells and designing electroactive implants for the central nervous system (CNS). We developed different surface biofunctionalization schemes that allowed selective growth of neurons or glial cells as well as a dynamic control of cell responses on PEDOT (Collazos-Castro et al., Biomaterials 2010). These results led us to propose the use of PEDOT-coated, electroconducting microfibers to stimulate CNS repair. The microfibers can be used as an ultrasmall electrode for recording or driving neuronal activity, and also as support, stimulus and guidance for regenerative cells (Collazos-Castro et al., Biomaterials 2013, patent PCT/ES2013/070879; Vara et al., ACS Appl Mater Interfaces 2015; Alves-Sampaio et al., Biomaterials 2016). Depending on the biomolecules attached to the surface, the microfibers can either support axonal growth directly (Collazos-Castro et al., Biomaterials 2013) or can induce the proliferation and migration of glial precursors, which then stimulate axonal elongation (Collazos-Castro et al., Acta Biomater 2016).

 

More recently, we demonstrated that the microfibers also promote spinal cord repair in rats (Alves-Sampaio et al., Biomaterials 2016). Currently we search for efficient methods to electrically interconnect the microfibers and for protocols of electrical stimulation through the microfibers in order to increase axonal regeneration and synaptic reconnection. The beginning of this research line received support from the European Commission through the NERBIOS project, which was coordinated by J. Collazos in the period 2006-2009. There, we investigated the interaction between neural cells and electroactive materials in collaboration with research centers from Spain (CSIC y UCLM), United Kingdom, Greece and Portugal. After developing the biofunctionalized microfibers, we have received a new grant from the European Commission to coordinate the NEUROFIBRES project, to be executed between 2017 and 2020. The objective of Neurofibres is to refine the electrical, mechanical and biochemical properties of the microfibers, and also to develop an advanced system for electronic interconnection. We will evaluate the effectiveness of microfiber implantation and microstimulation for the treatment of SCI in rats and pigs, paving the pathway for the development of an electroactive implant for human use. Neurofibres joins the efforts of our laboratory in collaboration with researchers from France, United Kingdom, Italy, Germany and Sweden.

 

 

Selected publications

 

Alves-Sampaio A, García-Rama C, and Collazos-Castro JE (2016) Biofunctionalized PEDOT-coated microfibers for the treatment of spinal cord injury. Biomaterials 89:98–113. DOI: 10.1016/j.biomaterials.2016.02.037.  I.F. 8.557

 

Collazos-Castro JE, García-Rama C, Alves-Sampaio A (2016) Glial progenitor cell migration promotes CNS axon growth on functionalized electroconducting microfibers. Acta Biomater. 35:42-56. DOI: 10.1016/j.actbio.2016.02.023. I.F. 6.025

 

Vara H, and Collazos-Castro JE (2015) Biofunctionalized conducting polymer / carbon microfiber electrodes for ultrasensitive neural recordings. ACS Appl Mater Interfaces. 7:27016-27026. DOI: 10.1021/acsami.5b09594. I.F. 6.723

 

Collazos-Castro JE, Hernández-Labrado G, Polo JL, García-Rama C (2013) N-Cadherin and L1-functionalised conducting polymers for synergistic stimulation and guidance of neural cell growth. Biomaterials 34: 3603 - 3617I.F: 8.312

 

López-Dolado E, Lucas-Osma A and Collazos-Castro JE (2013) Dynamic motor compensations with permanent, focal loss of forelimb force after cervical spinal cord injury. J Neurotrauma 30: 191-210. I.F: 3.968

 

Hernandez-Labrado GR, Polo JL, López-Dolado E and Collazos-Castro JE (2011) Spinal cord direct current stimulation: finite element analysis of the electric field and current density. Med. Biol. Eng. Comput. 49: 417 – 429. I.F: 1.878

 

Collazos-Castro JE, Polo JL, Hernández-Labrado G, Padial-Cañete V, García-Rama C (2010) Bioelectrochemical Control of Neural Cell Development on Conducting Polymers. Biomaterials 31: 9244 – 9255. I.F: 7.882

 

 

Patents

 

PATENT TITLE: Materials, methods and devices to stimulate and direct the proliferation and migration of neural progenitors and axonal and dendritic growth

INVENTORS: Jorge Eduardo Collazos Castro, José Luis Polo Sanz, Gabriel Raúl Hernández Labrado, Concepción García Pacheco

APPLICATION No: P201231969. Priority country: Spain. PCT/ES2013/070879

PRIORITY DATE: December 19, 2012.

INTELECTUAL PROPERTY HOLDER: Research Foundation of the National Hospital for Paraplegics; University of Castilla La Mancha

 

 

Personnel

 

Jorge E. Collazos Castro: Laboratory chief; MD., PhD. in Neurosciences.

 

Hugo Vara Rivera: Postdoctoral researcher; PhD. in Neurosciences.

 

Alexandra Manuela Alves Sampaio: Postdoctoral researcher; PhD. in Molecular Biology .

 

Gemma Riquelme Alacid: Predoctoral researcher; Master in Neurosciences.

 

Patricia del Cerro de Pablo: Predoctoral researcher; Master in Neurosciences.

 

Esteban González Valdizán: Laboratory assistant, Master in Medicine.

 

Concepción García Rama Pacheco: Laboratory technician.

 

Paloma Ania Benito: Laboratory technician.

 

 

 

Ongoing projects

 

NEUROFIBRES: Biofunctionalised Electroconducting Microfibres for the Treatment of Spinal Cord Injury.

Sponsor: European Commission, FET-Proactive, Contract Nº 732344.

European Coordinator: Jorge E. Collazos Castro, Hospital Nacional de Parapléjicos.

Partners: SESCAM (Spain), University of Cambridge (UK), AXON'Cable SAS (France), University of Trento (Italy), Aix-Marseille University (France), Royal Institute of Technology (Sweden), University of Saarland (Germany).

Period: 01/2017 - 12/2020.

www.neurofibres.eu

 

 

Electroconducting microfibers as a multifunctional tool for repairing the spinal cord.

Sponsor: Ministerio de Economía y Competitividad, Spain. SAF2015-65236R

Principal Investigator: Jorge E. Collazos Castro, Hospital Nacional de Parapléjicos.

Period: 2016-2018.

 

 

Effects of rehabilitation on synaptic plasticity and functional recovery after cervical spinal cord injury. A preclinical study on minipigs.

Sponsor: Fundación Mutua Madrileña, Spain

Principal Investigator: Jorge E. Collazos Castro, Hospital Nacional de Parapléjicos.

Period: 2015-2017.