Fundamentals and current strategies for Peripheral Nerve Repair and Regeneration

A body of evidence indicates that peripheral nerves have an extraordinary yet limited capacity to regenerate after an injury. Peripheral nerve injuries have confounded professionals in this field, from neuroscientists to neurologists, plastic surgeons, and the scientific community. Despite all the efforts, full functional recovery is still seldom. The inadequate results attained with the â gold standardâ autograft procedure still encourage a dynamic and energetic research around the world for establishing good performing tissue engineered alternative grafts. Resourcing to nerve guidance conduits, a variety of methods have been experimentally used to bridge peripheral nerve gaps of limited size, up to 30-40 mm in length, in humans. Herein, we aim to summarize the fundamentals related to peripheral nerve anatomy and overview the challenges and scientific evidences related to peripheral nerve injury and repair mechanisms. The most relevant reports dealing with the use of both synthetic and natural-based biomaterials used in tissue engineering strategies when treatment of nerve injuries is envisioned are also discussed in depth, along with the state-of-the-art approaches in this field.This work was supported by Cristiana Carvalho PhD scholarship (Norte-08-5369-FSE-000037). J. M. Oliveira also thanks the FCT for the funds provided under the program Investigador FCT 2015 (IF/01285/2015).The authors are also thankful to the FCT funded project NanoOptoNerv(ref. PTDC/NAN-MAT/29936/2017).The authors would also like to acknowledge the project: “Nano-accelerated nerve regeneration and optogenetic empowering of neuromuscular functionality” (ref.PTDC/NAN-MAT/29936/2017)

Finding the perfect match between nanoparticles and microfluidics to respond to cancer challenges

The clinical translation of new cancer theranostic has been delayed by inherent cancerâ s heterogeneity. Additionally, this delay has been enhanced by the lack of an appropriate in vitro model, capable to produce accurate data. Nanoparticles and microfluidic devices have been used to obtain new and more efficient strategies to tackle cancer challenges. On one hand, nanoparticles-based therapeutics can be modified to target specific cells, and/or molecules, and/or modified with drugs, releasing them over time. On the other hand, microfluidic devices allow the exhibition of physiologically complex systems, incorporation of controlled flow, and control of the chemical environment. Herein, we review the use of nanoparticles and microfluidic devices to address different cancer challenges, such as detection of CTCs and biomarkers, point-of-care devices for early diagnosis and improvement of therapies. The future perspectives of cancer challenges are also addressed herein.F.R. Maia acknowledges Portuguese Foundation for Scienceand Technology (FCT) for her work contract under theTransitional Rule DL 57/2016 (CTTI-57/18-I3BS5). J. M.Oliveira thanks FCT for his distinction attributed under theFCT Investigator program (IF/01285/2015)

Advances on gradient scaffolds for osteochondral tissue engineering

The osteochondral (OC) tissue is one of the most hierarchical and complex structures known and it is composed by two main compartments of hyaline articular cartilage and subchondral bone. It exhibits unique cellular and molecular transitions from the cartilage to the bone layers. OC diseases such as osteoarthritis and traumatic lesions may affect the articular cartilage, calcified cartilage (interface region) and subchondral bone, thus posing great regenerative challenges. Tissue engineering (TE) principles can offer novel technologies and combinatorial approaches that can better recapitulate the biological OC challenges and complexity in terms of biochemical, mechanical, structural and metabolic gradients, and ultimately can provide biofunctional 3D scaffolds with high reproducibility, versatility and adaptability to each patientâ s needs, as it occurs in OC tissue defects. The recent reports and future directions dealing with gradient scaffolds for OCTE strategies are overviewed herein. A special focus on clinical translation/regulatory approval is given.The authors thank the financial support provided by the EU-EC through the BAMOS project (H2020-MSCA-RISE-2016-734156). Viviana P Ribeiro acknowledge for the Junior Researcher contract (POCI-01-0145-FEDER-031367) attributed by the Portuguese Foundation for Science and Technology to Fun4TE project (PTDC/EMD-EMD/31367/2017)

Dendrimer nanoparticles for colorectal cancer applications

Accepted ManuscriptCancer nanotechnology is a prolific field of research, where nanotools are employed to diagnose and treat cancer with unprecedented precision. Targeted drug delivery is fundamental for more efficient cancer treatments. For this, nanoparticles have been extensively used during the last years in order to improve the specificity, selectivity and controlled release of drug delivery. It holds potential in minimizing systemic toxicity through the development of functionalized particles for targeted treatment. Among all the type of nanoparticles, dendrimers display several advantages, which make them ideal candidates for improved and targeted drug delivery in cancer research. Dendrimers can transport large amount of drug into specific areas. In addition, they can be employed for monitoring the progress of the treatment process, with an  unprecedented theranostic capability. Special emphasis is given in colorectal cancer, as well as the preferred employed strategies for producing drug-loaded/functionalized NPâ s for cancer therapy in the last years

Preparation of bioactive coatings on the surface of bioinert polymers through an innovative auto-catalytic electroless route

The aim of this research was to develop a new methodology to obtain bioactive coatings on bioinert and biodegradable polymers that are not intrinsically bioactive. In this study, three types of materials were used as substrates: (i) high molecular weight polyethylene (HMWPE) and two different types of starch based blends (ii) starch/ethylene vinyl alcohol blends, SEVA-C, and (iii) starch/cellulose acetate blends, SCA. These materials were obtained by injection moulding and by extrusion with blowing agents in order to obtain compact/porous 3D architectures. Three types of baths were developed in order to produce the newly proposed auto-catalytic Ca-P coatings: (i) alkaline, (ii) acid, and (iii) oxidant bath. The obtained results indicated that it was possible to coat the materials surfaces with calcium phosphate (Ca-P) layer with only 60 min of immersion in the different types of auto-catalytic solutions. These innovative auto-catalytic electroless route allows for the production of an adherent bioactive film on the polymeric surfaces. Furthermore, it was possible observe by SEM/EDS the clear bioactive nature of the Ca-P coatings after different immersion periods, in a simulated body fluid (SBF)

Development of a bilayered scaffold based on silk fibroin and silk fibroin/nano-calcium phosphate for osteochondral regeneration

Objectives: Osteochondral defect is a common condtion in clinic. Satisfactory outcomes are rarely achieved by traditional methods. Tissue engineering might be a promising strategy for this hinder. The aim of this study is to mimick the stratified structure of osteochondral tissue, by developing a bilayered scaffold for osteochondral regeneration. The developed bilayered scaffold is composed of a porous silk fibroin scaffold as the cartilage-like layer and a porous silk fibroin/nano-calcium phosphate (CaP) scaffold as the bone-like layer

Silk Fibroin/Nano-CaP Bilayered scaffolds for osteochondral tissue engineering

In this study, bilayered silk and silk/nano-CaP scaffolds were developed for osteochondral (OC) tissue engineering. Aqueous silk solution (16 wt.%) was used for preparation of the cartilage-like layer and, for generation of the silk/nano-CaP suspension and the bottom layer (CaP/Silk: 16 wt.%). The scaffolds were formed by using salt-leaching/lyophilization approach. The scanning electron microscopy revealed that the both layers presented porous structure and integrated well. Micro-computed tomography images confirmed that the CaP phase was only retained in the silk/nano-CaP layer. The hydration degree and mechanical properties of the bilayered scaffold were comparable to the ones of each single layer. The apatite crystal formation was limited to the silk/nano-CaP layer, when soaking the scaffold in a simulated body fluid solution, which is a must for the application of the developed scaffolds in OC tissue engineerin

Methacrylated gellan gum hydrogels for application in nucleus pulposus regeneration: in vitro and in vivo studies

Natural-based hydrogels have been attracting great deal of attention for tissue engineering of nucleus pulposus (NP). Gellan gum is an extracellular microbial polysaccharide from Sphingomonas elodea that forms a firm and transparent gel with interesting features for use as an in vitro 3D cell support, or as an in vivo injectable system. Recently, gellan gum-based hydrogels (ionic- and photocrosslinked methacrylated gellan gum) have been proposed as potential candidates for NP regeneration1. An important feature of these hydrogels will be their capacity to control blood vessel growth, since the NP is naturally avascular. Our aim was to investigate the biological performance of the developed hydrogels, in vitro. The angiogenic/anti-angiogenic potential of the GG-based hydrogels was also carried out in vivo, using an optimized adaptation of the chorioallantoic membrane (CAM) assay.(undefined

Current concepts and challenges in osteochondral tissue engineering and regenerative medicine

"Publication Date (Web): February 20, 2015"In the last few years, great progress has been made to validate tissue engineering strategies in preclinical studies and clinical trials on the regeneration of osteochondral defects. In the preclinical studies, one of the dominant strategies comprises the development of biomimetic/bioactive scaffolds, which are used alone or incorporated with growth factors and/or stem cells. Many new trends are emerging for modulation of stem cell fate towards osteogenic and chondrogenic differentiations, but bone/cartilage interface regeneration and physical stimulus have been showing great promise. Besides the matrix-associated autologous chondrocyte implantation (MACI) procedure, the matrix-associated stem cells implantation (MASI) and layered scaffolds in acellular or cellular strategy are also applied in clinic. This review outlines the progresses at preclinical and clinical levels, and identifies the new challenges in osteochondral tissue engineering. Future perspectives are provided, e.g., the applications of extracellular matrix-like biomaterials, computer-aided design/manufacture of osteochondral implant and reprogrammed cells for osteochondral regeneration.The authors thank the Portuguese Foundation for Science and Technology (FCT) through the projects TISSUE2TISSUE (PTDC/CTM/105703/2008) and OsteoCart (PTDC/CTM-BPC/115977/2009). We also acknowledge European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreement REGPOT-CT2012-316331-POLARIS. L-P.Y. acknowledges the PhD scholarship from FCT (SFRH/BD/64717/2009). The FCT distinction attributed to J.M.O. and A.L.O. under the Investigator FCT program (IF/00423/2012) and (IF/00411/2013) are also greatly acknowledged

Hydrogels in acellular and cellular strategies for intervertebral disc regeneration

Article first published online: 9 nov. 2011Low back pain is an extremely common illness syndrome causing patient’s suffering and disability which demands for urgent solutions in order to improve life quality of the patients. Treatment options aimed to regenerate the intervertebral disc (IVD) are still under development. The huge cellular complexity of IVD, and consequently its fine regulatory system, makes it a challenge to the scientific community. Biomaterials-based therapies are the most interesting solutions nowadays, wherein tissue engineering and regenerative medicine (TE&RM) strategies are included. By using such strategies, i.e., combining biomaterials, cells and biomolecules, the ultimate goal of reaching a complete integration between native and neo-tissue can be achieved. Hydrogels are promising materials to restore IVD, mainly nucleus pulposus (NP). Herein, an overview of the use of hydrogels in acellular and cellular strategies for intervertebral disc regeneration is presented. To better understand the IVD and its functioning, several topics will be focused, i.e., anatomy, pathophysiology, cellular and biomolecular performance, intrinsic healing processes and current therapies. In this review, the application of hydrogels as NP substitutes will be addressed, due to the similarity to NP mechanical properties and extracellular matrix. These hydrogels can be used in cellular strategies, when combined with cells from different sources,, or in acellular strategies, by performing the functionalization of the hydrogels with biomolecules. In addition, a brief summary of therapies based on simple injection envisaging primarily the biological repair will be tackled. At last, a special emphasis has been given to original works reporting the use of autologous cells and biomolecules (e.g.,Platelet-rich plasma) and envisioning the clinical application.Fundação para a Ciência e tecnologia (FCT) through POCTI and FEDER including Project Proteolight. European Union-funded Collaborative Project Disc Regeneratio