Stimuli-responsive local drug molecule delivery to adhered cells in a 3D nanocomposite scaffold

Drug delivery systems capable of providing controlled and localized drug release are a highly important tool in the biomedical field because they can provide site-specific, sustained, and controlled drug release at the place where the drug is most needed, and they allow for significantly lower doses of the drug at other parts of the body, reducing the drug\u2019s potential side effects. In this respect, we describe pH-responsive PMO/alginate nanocomposite (NC) scaffolds with different pH-responsive strengths for controlled local drug delivery applications. To prepare the PMO/alginate NC scaffolds, PMOs were first loaded with anti-cancer molecules and then coated with a non-biopolymer or a biopolymer, after which the PMOs were embedded into an alginate network. We found that drug release from the PMOs was regulated by the pH of the environment and the surface coating of the PMOs due to the different pHdependent levels of electrostatic interactions between all the charged components of the NC scaffolds. The non-biopolymer-coated formulation of the NC scaffold can be utilized to deliver higher dosages of drug molecules directly to cells, while the biopolymer-coated system is useful for slow and prolonged release of drugs and for enhanced cell adhesion. Nonetheless, both systems can be utilized, in particular, to deliver higher dosages of drug molecules directly to cancer cells while delivering less of the drug to healthy cells

Human-based fibrillar nanocomposite hydrogels as bioinstructive matrices to tune stem cell behavior

The extracellular matrix (ECM)-biomimetic fibrillar structure of platelet lysate (PL) gels along with its enriched milieu of biomolecules has drawn significant interest in regenerative medicine applications. However, PL-based gels have poor structural stability which severely limits its performance as a bioinstructive biomaterial. Here, rod-shaped cellulose nanocrystals (CNC) are used as a novel approach to modulate the physical and biochemical microenvironment of PL gels enabling their effective use as injectable human-based cell scaffolds with a level of biomimicry that is difficult to recreate with synthetic biomaterials. The incorporation of CNC (0 to 0.61 wt.%) into the PL fibrillar network during the coagulation cascade leads to decreased fiber branching, increased interfiber porosity (from 66 to 83%) and modulate fiber (from 1.4 ± 0.7 to 27 ± 12 kPa) and bulk hydrogel (from 18 ± 4 to 1256 ± 82 Pa) mechanical properties. As result of these physicochemical alterations, nanocomposite PL hydrogels resist to the typical extensive clot retraction (from 76 ± 1 to 24 ± 3 at Day 7) and show favored retention of PL bioactive molecules. The feedback of these cues on the fate of human adipose-derived stem cells is evaluated, showing how it can be explored to modulate the commitment of encapsulated stem cells toward different genetic phenotypes without the need for additional external biological stimuli. These fibrillar nanocomposite hydrogels allow therefore to explore the outstanding biological properties of human-based PL as an efficient engineered ECM which can be tailored to trigger specific regenerative pathways in minimal invasive strategies.The authors thank the Hospital da Prelada (Porto, Portugal) for providing adipose tissue samples. The authors acknowledge the financial support from project Recognize (UTAP-ICDT/CTM-BIO/0023/2014), project NORTE-01-0145FEDER-000021 supported by the Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF), the European Union Framework Programme for Research and Innovation HORIZON 2020, under the TEAMING Grant agreement No. 739572 – The Discoveries CTR EU, Forecast 668983, Marie Skłodowska-Curie grant agreement No. 706996 (PrinTendon) and CHEM2NATURE 692333; FCT/MCTES (Fundação para a Ciência e a Tecnologia/ Ministério da Ciência, Tecnologia, e Ensino Superior) and the Fundo Social Europeu através do Programa Operacional do Capital Humano (FSE/POCH) in the framework of PhD grant PD/59/2013 – PD/BD/113807/2015 for BBM, Post-Doc grant SFRH/BPD/112459/2015 for R.D.info:eu-repo/semantics/publishedVersio

Does High Frequency Transcutaneous Electrical Nerve Stimulation (TENS) Affect EEG Gamma Band Activity?

Background: Transcutaneous electrical nerve stimulation (TENS) is a noninvasive, inexpensive and safe analgesic technique used for relieving acute and chronic pain. However, despite all these advantages, there has been very little research into the therapeutic effects of TENS on brain activity. To the best of our knowledge, there is no evidence on the effect of high frequency TENS on the gamma band activity. Objective: Investigation of the effect of high frequency TENS on the electroencephalographic (EEG) gamma band activity after inducing ischemic pain in healthy volunteers is considered. Methods: The modified version of Submaximal effort tourniquet test was carried out for inducing tonic pain in 15 right-handed healthy volunteers. The high frequency TENS (150µs in duration, frequency of 100 Hz) was applied for 20 minutes. Pain intensity was assessed using Visual Analog Scale (VAS) in two conditions (after-pain, after-TENS). EEG gamma band activity was recorded by a 19-channel EEG in three conditions (baseline, after-pain and after- TENS). The repeated measure ANOVA and paired-sample T- tests were used for data analysis. Results: EEG analysis showed an increase in gamma total power after inducing pain as compared to baseline and a decrease after the application of TENS (mean±SD: .043±.029 to .088±.042 to .038±.022 μV2 ).The analysis of VAS values demonstrated that the intensity of induced pain (mean±SD: 51.53±9.86) decreased after the application of TENS (mean±SD: 18.66±10.28). All these differences were statistically significant (p<.001). Conclusion: The results of this study revealed that the high frequency TENS can reduced the enhanced gamma band activity after the induction of tonic pain in healthy volunteers. This finding might help as a functional brain biomarker which could be useful for pain treatment, specifically for EEG-based neurofeedback approaches

Committee:

b