Investigation of cell adhesion in chitosan membranes for peripheral nerve regeneration

Peripheral nerve injuries have produced major concerns in regenerative medicine for several years, as the recovery of normal nerve function continues to be a significant clinical challenge. Chitosan (CHT), because of its good biocompatibility, biodegradability and physicochemical properties, has been widely used as a biomaterial in tissue engineering scaffolding. In this study, CHT membranes were produced with three different Degrees of Acetylation (DA), envisioning its application in peripheral nerve regeneration. The three CHT membranes (DA I: 1%, DA II: 2%, DA III: 5%) were extensively characterized and were found to have a smooth and flat surface, with DA III membrane having slightly higher roughness and surface energy. All the membranes presented suitable mechanical properties and did not show any signs of calcification after SBF test. Biodegradability was similar for all samples, and adequate to physically support neurite outgrowth. The in vitro cell culture results indicate selective cell adhesion. The CHT membranes favoured Schwann cells invasion and proliferation, with a display of appropriate cytoskeletal morphology. At the same time they presented low fibroblast infiltration. This fact may be greatly beneficial for the prevention of fibrotic tissue formation, a common phenomenon impairing peripheral nerve regeneration. The great deal of results obtained during this work permitted to select the formulation with the greatest potential for further biological tests.This work has received funding from the European Community's Seventh Framework Programme (FP7-HEALTH-2011) under grant agreement no 278612 (BIOHYBRID). This study was also funded by European Union's FP7 Programme under grant agreement no REGPOT-CT2012-316331-POLARIS.The authors thank the chitosan raw material provided by Altakitin S.A., (Lisboa, Portugal). We are further thankful to Silke Fischer, Natascha Heidrich, Kerstin Kuhlemann, Jennifer Metzen, Hildegard Streich and Maike Wesemann (all from the Institute of Neuroanatomy, Hannover Medical School) for their technical support

Nanotechnology in peripheral nerve repair and reconstruction

The recent progress in biomaterials science and development of tubular conduits (TCs) still fails in solving the current challenges in the treatment of peripheral nerve injuries (PNIs), in particular when disease-related and long-gap defects need to be addressed. Nanotechnology-based therapies that seemed unreachable in the past are now being considered for the repair and reconstruction of PNIs, having the power to deliver bioactive molecules in a controlled manner, to tune cellular behavior, and ultimately guide tissue regeneration in an effective manner. It also offers opportunities in the imaging field, with a degree of precision never achieved before, which is useful for diagnosis, surgery and in the patientâ s follow-up. Nanotechnology approaches applied in PNI regeneration and theranostics, emphasizing the ones that are moving from the lab bench to the clinics, are herein overviewed.The authors acknowledge the Portuguese Foundation for Science and Technology (FCT) for the financial support provided to Joaquim M. Oliveira (IF/01285/2015) and Joana Silva-Correia (IF/00115/2015) under the program “Investigador FCT”.info:eu-repo/semantics/publishedVersio

Peripheral nerve injury: current challenges, conventional treatment approaches, and new trends in biomaterials-based regenerative strategies

Damage to peripheral nerves is a widely extended health problem, causing important socio-economic costs worldwide. Indeed, peripheral nerve injuries (PNI) have been concerning the medical community for many decades. Nevertheless, despite the increase in knowledge in the injury physiopathology and the great research efforts being undertaken, the current standard grafting strategies used to repair PNI are not as efficient as desired. Although alternative engineered nerve grafts are already commercialized, their clinical performance is suboptimal. In this review, a general description of the circumstances and repercussions surrounding the PNI pathological state are presented, together with the treatment limitations and current challenges when addressing both short- and long-gap defects. In addition, potential therapeutic molecules are considered, while innovative regenerative strategies have been identified. Finally, the most relevant advances on the use of a wide range of biomaterials for the development of novel medical devices are also overviewed in depth, either considering strategies making use of empty or filled nerve conduits for guided tissue regeneration.This work has received funding from the European Community’s Seventh Framework Programme (FP7- HEALTH-2011) under grant agreement 278612 (BIOHYBRID), from ERDF/POCTEP 2007-2013 under project 0687_NOVOMAR_1_P, from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement number REGPOT-CT2012-316331-POLARIS, and from the ComplexiTE − An integrated multidisciplinary tissue engineering approach combining novel high-throughput screening and advanced methodologies to create complex biomaterials-stem cells constructs (ERC-2012-ADG_20120216- 321266). Portuguese Foundation for Science and Technology (FCT) is also acknowledged for the funds provided under the program Investigador FCT to J.S.C. (IF/00115/2015) and J.M.O. (IF/00423/2012 and IF/01285/2015).info:eu-repo/semantics/publishedVersio

Dual delivery of hydrophilic and hydrophobic drugs from chitosan/diatomaceous earth composite membranes

Oral administration of drugs presents important limitations, which are frequently not granted the importance that they really have. For instance, hepatic metabolism means an important drug loss, while some patients have their ability to swell highly compromised (i.e. unconsciousness, cancer...). Sublingual placement of an accurate Pharmaceutical Dosage Form is an attractive alternative. This work explores the use of the beta-chitosan membranes, from marine industry residues, composed with marine sediments for dual sublingual drug delivery. As proof of concept, the membranes were loaded with a hydrophilic (gentamicin) and a hydrophobic (dexamethasone) drug. The physico-chemical and morphological characterization indicated the successful incorporated of diatomaceous earth within the chitosan membranes. Drug delivery studies showed the potential of all formulations for the immediate release of hydrophilic drugs, while diatomaceous earth improved the loading and release of the hydrophobic drug. These results highlight the interest of the herein developed membranes for dual drug delivery.The research leading to these results has received funding from Erasmus Mundus Joint Programmes, ERDF / POCTEP 2007-2013 under project 0687_NOVOMAR_1_P, from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement number REGPOT-CT2012-316331-POLARIS, and from the North Portugal Regional Operational Programme (ON.2 - O Novo Norte), within the National Strategic Reference Framework (QREN 2007-2013) under the project NORTE-01-0124-FEDER-000018. Portuguese Foundation for Science and Technology is also acknowledged for the post-doctoral fellowship SFRH/BPD/112140/2015, for the doctoral fellowship SFRH/BD/112139/2015 and for the funds provided under the program Investigador FCT 2012 (IF/00423/2012). Dr. Helder Santos (University of Helsinki) is also acknowledged for valuable discussions on the concept.The research leading to these results has received funding from Erasmus Mundus Joint Programmes, ERDF / POCTEP 2007–2013 under project 0687_NOVOMAR_1_P, from the European Union Seventh Framework Programme (FP7/2007–2013) under grant agreement number REGPOT-CT2012-316331-POLARIS, and from the North Portugal Regional Operational Programme (ON.2 – O Novo Norte), within the National Strategic Reference Framework (QREN 2007-2013) under the project NORTE-01-0124-FEDER-000018. Portuguese Foundation for Science and Technology is also acknowledged for the post-doctoral fellowship SFRH/BPD/112140/2015, for the doctoral fellowship SFRH/BD/112139/2015 and for the funds provided under the program Investigador FCT 2012 (IF/00423/2012). Dr. Hélder Santos (University of Helsinki) is also acknowledged for valuable discussions on the concept.info:eu-repo/semantics/publishedVersio