Natural melanin nanoparticles (MNPs) extracted from Sepia officinalis: A cost-effective, chemo-photothermal, synergistic nanoplatform for osteosarcoma treatment.

Osteosarcoma conventional chemotherapeutics are known for their side effects, limited options, and induction of drug resistance. This creates the need to develop new therapeutics capable of effectively destroying cancer cells with low toxicity, improving patient survival rate and their life quality. This work reports a novel drug delivery nanoplataform made of Natural Melanin Nanoparticles (MNPs), obtained from Sepia officinalis ink, with 99% incorporation efficiency of doxorubicin (Dox) without the use of non-toxic solvents. A significant photothermal effect was shown by a 36ºC increment after 10 min of laser irradiation, surpassing reported values for synthetic melanin. A sustained drug release of ca. 23% with photothermal stimuli was observed, compared to 15% without stimuli, after 48 h. This nanoplatform is obtained as a food industry side product, which makes it a natural cost-effective biomedical material. Natural MPs were applied in an osteosarcoma cell line (SaOs-2), and internalized by the cells in less than 2 h, showing cytocompatibility up to 1000 µg/mL after 72 h of contact with cells. On the contrary, when natural MNPs loaded with Dox (Dox-MNPs) were placed in contact with the SaOs-2 cells and were simultaneously receiving NIR light it was observed a 93% reduction in cancer cells in 48 h, revealing a synergistic effect between chemotherapy and phototherapy. To our knowledge this is the first time that natural MNPs extracted from Sepia officinalis were tested on an osteosarcoma cell line as chemo-photothermal agent, showing these NPs are an effective, cost-effective, reproducible, non-toxic nanoplatform for osteosarcoma treatment using combined effects.

The efficient role of sodium alginate-based biodegradable dressings for skin wound healing application: a systematic review.

Injuries and damage to the skin can be caused by different reasons throughout human life. The use of sodium alginate in tissue dressing has been highly studied due to its intrinsic properties, including its degradation rate and biocompatibility, and the capacity of supporting tissue proliferation. The aim of this paper is to demonstrate evidences, through a systematic review method, to support the application of sodium alginate as a curative and as a potential accelerator in the healing of skin wounds. Four databases were used to develop this systematic review: Science Direct, PubMed, Scielo and Scopus. The time interval established for the search was from January 2016 to October 2023. After applying the exclusion and inclusion criteria, each selected article was evaluated and it was observed that the improvement of the mechanical properties of sodium alginate when correctly processed and crosslinked were evident. However, the increase of crosslinking affects as the wettability and the swelling of the biomaterials can cause limitations in mechanical properties and hidrophilic behavior. To achieve the ideal dressing, it is necessary to apply the optimal concentration of crosslinking and other substances, which can damage its hidrophilic characteristic. Thus, it was concluded that sodium alginate has every caracteristic desirable to develop an effective and safe dressing.

Human adipose-derived mesenchymal stem cells laden in gellan gum spongy-like hydrogels for volumetric muscle loss treatment.

BACKGROUND: volumetric muscle loss (VML) is a traumatic massive loss of muscular tissue which frequently leads to amputation, limb loss, or lifetime disability. The current medical intervention is limited to autologous tissue transfer, which usually leads to non-functional tissue recovery. Tissue engineering holds a huge promise for functional recovery. METHODS: in this work, we evaluated the potential of human adipose-derived mesenchymal stem cells (hASCs) pre-cultured in gellan gum based spongy-like hydrogels (SLHs). RESULTS: in vitro, hASCs were spreading, proliferating, and releasing growth factors and cytokines (i.e. fibroblast growth factor, hepatocyte growth factor, insulin-like growth factor 1, interleukin-6 (IL-6), IL-8, IL-10, vascular endothelial growth factor) important for muscular regeneration. After implantation into a volumetric muscle loss (VML) mouse model, implants were degrading overtime, entirely integrating into the host between 4 and 8 weeks. In both SLH and SLH + hASCs defects, infiltrated cells were observed inside constructs associated with matrix deposition. Also, minimal collagen deposition was marginally observed around the constructs along both time-points. Neovascularization (CD31+vessels) and neoinnervation (ß-III tubulin+bundles) were significantly detected in the SLH + hASCs group, in relation to the SHAM (empty lesion). A higher density ofα-SA+and MYH7+cells were found in the injury site among all different experimental groups, at both time-points, in relation to the SHAM. The levels ofα-SA, MyoD1, and myosin heavy chain proteins were moderately increased in the SLH + hASCs group after 4 weeks, and in the hASCs group after 8 weeks, in relation to the SHAM. CONCLUSIONS: taken together, defects treated with hASCs-laden SLH promoted angiogenesis, neoinnervation, and the expression of myogenic proteins.

Inconsistency in Shoulder Arthrometers for Measuring Glenohumeral Joint Laxity: A Systematic Review.

There is no consensus on how to measure shoulder joint laxity and results reported in the literature are not well systematized for the available shoulder arthrometer devices. This systematic review aims to summarize the results of currently available shoulder arthrometers for measuring glenohumeral laxity in individuals with healthy or injured shoulders. Searches were conducted on the PubMed, EMBASE, and Web of Science databases to identify studies that measure glenohumeral laxity with arthrometer-assisted assessment. The mean and standard deviations of the laxity measurement from each study were compared based on the type of population and arthrometer used. Data were organized according to the testing characteristics. A total of 23 studies were included and comprised 1162 shoulders. Populations were divided into 401 healthy individuals, 278 athletes with asymptomatic shoulder, and 134 individuals with symptomatic shoulder. Sensors were the most used method for measuring glenohumeral laxity and stiffness. Most arthrometers applied an external force to the humeral head or superior humerus by a manual-assisted mechanism. Glenohumeral laxity and stiffness were mostly assessed in the sagittal plane. There is substantial heterogeneity in glenohumeral laxity values that is mostly related to the arthrometer used and the testing conditions. This variability can lead to inconsistent results and influence the diagnosis and treatment decision-making.

Recent advances in nanomaterial-based optical biosensors for food safety applications: Ochratoxin-A detection, as case study.

Global population growth tremendously impacts the global food industry, endangering food safety and quality. Mycotoxins, particularly Ochratoxin-A (OTA), emerge as a food chain production threat, since it is produced by fungus that contaminates different food species and products. Beyond this, OTA exhibits a possible human toxicological risk that can lead to carcinogenic and neurological diseases. A selective, sensitive, and reliable OTA biodetection approach is essential to ensure food safety. Current detection approaches rely on accurate and time-consuming laboratory techniques performed at the end of the food production process, or lateral-flow technologies that are rapid and on-site, but do not provide quantitative and precise OTA concentration measurements. Nanoengineered optical biosensors arise as an avant-garde solution, providing high sensing performance, and a fast and accurate OTA biodetection screening, which is attractive for the industrial market. This review core presents and discusses the recent advancements in optical OTA biosensing, considering engineered nanomaterials, optical transduction principle and biorecognition methodologies. Finally, the major challenges and future trends are discussed, and current patented OTA optical biosensors are emphasized for a particular promising detection method.

Collagen membrane from bovine pericardium for treatment of long bone defect.

The treatment of bone regeneration failures has been constantly improved with the study of new biomaterials. Techgraft® is a collagen membrane derived from bovine pericardium, which has been shown to have biocompatibility and effectiveness in tissue repair. However, its use in orthopedics has not yet been evaluated. Therefore, the purpose of this study was to characterize a bovine pericardium collagen membrane and evaluate the effects of its use in the regeneration of a bone defect in rat tibia. Scanning electron microscopy, atomic force microscopy, weight lost and water uptake tests, and mechanical test were performed. Afterwards, the membrane was tested in an experimental study, using 12 male Sprague Dawley rats. A bone defect was surgically made in tibiae of animals, which were assigned to two groups (n = 6): bone defect treated with collagen membrane (TG) and bone defect without treatment (CONT). Then, tibiae were submitted to micro-CT. The membranes preserved their natural collagen characteristics, presenting great strength, high water absorption, hydrophilicity, and almost complete dissolution in 30 days. In the experimental study, the membrane enhanced the growth of bone tissue in contact with its surface. A higher bone volume and trabeculae number and less trabecular space was observed in bone defects of the membrane group compared to the control group at 21 days. In conclusion, the Techgraft membrane seems to have favorable characteristics for treatment of long bone repair.

Preclinical research studies for treating severe muscular injuries: focus on tissue-engineered strategies.

Severe skeletal muscle injuries are a lifelong trauma with limited medical solutions. Significant progress has been made in developing in vitro surrogates for treating such trauma. However, more attention is needed when translating these approaches to the clinic. In this review, we survey the potential of tissue-engineered surrogates in promoting muscle healing, by critically analyzing data from recent preclinical models. The therapeutic advantages provided by a combination of different biomaterials, cell types, and biochemical mediators are discussed. Current therapies on muscle healing are also summarized, emphasizing their main advantages and drawbacks. We also discuss previous and ongoing clinical trials as well as highlighting future directions for the field.

Chitosan Micro-Membranes with Integrated Gold Nanoparticles as an LSPR-Based Sensing Platform.

Currently, there is an increasing need to develop highly sensitive plasmonic sensors able to provide good biocompatibility, flexibility, and optical stability to detect low levels of analytes in biological media. In this study, gold nanoparticles (Au NPs) were dispersed into chitosan membranes by spin coating. It has been demonstrated that these membranes are particularly stable and can be successfully employed as versatile plasmonic platforms for molecular sensing. The optical response of the chitosan/Au NPs interfaces and their capability to sense the medium's refractive index (RI) changes, either in a liquid or gas media, were investigated by high-resolution localized surface plasmon resonance (HR-LSPR) spectroscopy, as a proof of concept for biosensing applications. The results revealed that the lowest polymer concentration (chitosan (0.5%)/Au-NPs membrane) presented the most suitable plasmonic response. An LSPR band redshift was observed as the RI of the surrounding media was incremented, resulting in a sensitivity value of 28 ± 1 nm/RIU. Furthermore, the plasmonic membrane showed an outstanding performance when tested in gaseous atmospheres, being capable of distinguishing inert gases with only a 10-5 RI unit difference. The potential of chitosan/Au-NPs membranes was confirmed for application in LSPR-based sensing applications, despite the fact that further materials optimization should be performed to enhance sensitivity.

Pharmacological and Non-Pharmacological Agents versus Bovine Colostrum Supplementation for the Management of Bone Health Using an Osteoporosis-Induced Rat Model.

Osteoporosis is defined by loss of bone mass and deteriorated bone microarchitecture. The present study compared the effects of available pharmacological and non-pharmacological agents for osteoporosis [alendronate (ALE) and concomitant supplementation of vitamin D (VD) and calcium (Ca)] with the effects of bovine colostrum (BC) supplementation in ovariectomized (OVX) and orchidectomized (ORX) rats. Seven-month-old rats were randomly allocated to: (1) placebo-control, (2) ALE group (7.5 µg/kg of body weight/day/5 times per week), (3) VD/Ca group (VD: 35 µg/kg of body weight/day/5 times per week; Ca: 13 mg/kg of body weight/day/3 times per week), and (4) BC supplementation (OVX: 1.5 g/day/5 times per week; ORX: 2 g/day/5 times per week). Following four months of supplementation, bone microarchitecture, strength and bone markers were evaluated. ALE group demonstrated significantly higher Ct.OV, Ct.BMC, Tb.Th, Tb.OV and Tb.BMC and significantly lower Ct.Pr, Tb.Pr, Tb.Sp, Ct.BMD and Tb.BMD, compared to placebo (p < 0.05). BC presented significantly higher Ct.Pr, Ct.BMD, Tb.Pr, Tb.Sp, and Tb.BMD and significantly lower Ct.OV, Ct.BMC, Tb.Th, Tb.OV and Tb.BMC compared to ALE in OVX rats (p < 0.05). OVX rats receiving BC experienced a significant increase in serum ALP and OC levels post-supplementation (p < 0.05). BC supplementation may induce positive effects on bone metabolism by stimulating bone formation, but appear not to be as effective as ALE.

3D bioprinting of gellan gum-based hydrogels tethered with laminin-derived peptides for improved cellular behavior.

The treatment of skeletal muscle defects is still a topic of noteworthy concern since surgical intervention is not capable of recovering muscle function. Herein, we propose myoblasts laden in laminin-inspired biofunctionalized gellan gum hydrogels as promising tissue-engineered skeletal muscle surrogates. Gellan gum-based hydrogels were developed by combining native gellan gum (GG) and GG tethered with laminin-derived peptides (CIKVAVS (V), KNRLTIELEVRTC (T) or RKRLQVQLSIRTC (Q)), using different polymer content (0.75%-1.875%). Hydrogels were characterized in terms of compressive modulus, molecules trafficking, and C2C12 adhesion. Hydrogels with higher polymeric content (1.125%-1.875%) showed higher stiffness whereas hydrogels with lower polymer content (0.75%-1.125%) showed higher fluorescein isothiocyanate-dextran molecules diffusion. Cell spreading was achieved regardless of the laminin-derived peptide but preferred in hydrogels with higher polymer content (1.125%-1.875%). Taken together, hydrogels with 1.125% of polymer content were selected for printability analysis. GG-based inks showed a non-newtonian, shear-thinning, and thixotropic behavior suitable for printing. Accordingly, all inks were printable, but inks tethered with T and Q peptides presented some signs of clogging. Cell viability was affected after printing but increased after 7 days of culture. After 7 days, cells were spreading but not showing significant signs of cell-cell communications. Therefore, cell density was increased, thus, myocytes loaded in V-tethered GG-based inks showed higher cell-cell communication, spreading morphology, and alignment 7, 14 days post-printing. Overall, myoblasts laden in laminin-inspired biofunctionalized GG-based hydrogels are a promising skeletal muscle surrogate with the potential to be used as in vitro model or explored for further in vivo applications.

Development of an antibiotics delivery system for topical treatment of the neglected tropical disease Buruli ulcer.

Skin infection by Mycobacterium ulcerans causes Buruli ulcer (BU) disease, a serious condition that significantly impact patient' health and quality of life and can be very difficult to treat. Treatment of BU is based on daily systemic administration of antibiotics for at least 8 weeks and presents drawbacks associated with the mode and duration of drug administration and potential side effects. Thus, new therapeutic strategies are needed to improve the efficacy and modality of BU therapeutics, resulting in a more convenient and safer antibiotic regimen. Hence, we developed a dual delivery system based on poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) microparticles and a gellan gum (GG) hydrogel for delivery of rifampicin (RIF) and streptomycin (STR), two antibiotics used for BU treatment. RIF was successfully loaded into PHBV microparticles, with an encapsulation efficiency of 43%, that also revealed a mean size of 10 µm, spherical form and rough topography. These microparticles were further embedded in a GG hydrogel containing STR. The resultant hydrogel showed a porous microstructure that conferred a high water retention capability (superior to 2000%) and a controlled release of both antibiotics. Also, biological studies revealed antibacterial activity against M. ulcerans, and a good cytocompatibility in a fibroblast cell line. Thus, the proposed drug delivery system can constitute a potential topical approach for treatment of skin ulcers caused by BU disease.

Biosensors Advances: Contributions to Cancer Diagnostics and Treatment.

Cancer is the second leading cause of death worldwide, and its survival rate is significantly affected by early detection and treatment. However, most current diagnostic methods are symptoms oriented, and detecting cancer only in advanced phases. The few existent screening methods, such as mammograms and papanicolaou tests are invasive and not continuous, resulting in a high percentage of non-detected cancers in the early phases. Thus, there is an urgent need to create technologies that make cancer diagnostics more accessible to populations, enabling continuous or semi-continuous, noninvasive, "long-term" screening of cancer in high-risk patients and the whole population. Biosensors are being developed to create technologies that can be applied to point-of-care, wearable, and implantable diagnostics, aiming to fill this important gap in cancer early detection, and, therefore, increase the cancer rate of survival and reduce its morbidity. The versatility of these technologies, due to their miniaturization and diverse detection modes, will enable great advances in cancer early detection, since they can be adapted to the patient and its context, allowing personalized medicine to become a reality.

Injectable laminin-biofunctionalized gellan gum hydrogels loaded with myoblasts for skeletal muscle regeneration.

Moderate muscular injuries that exceed muscular tissue's auto-healing capacity are still a topic of noteworthy concern. Tissue engineering appeared as a promising therapeutic strategy capable of overcoming this unmet clinical need. To attain such goal, herein we propose an in situ-crosslinking gellan gum (GG)-based hydrogel tethered with a skeletal muscle-inspired laminin-derived peptide RKRLQVQLSIRTC(Q) and encapsulated with skeletal muscle cells (SMCs). Pre-hydrogel solutions presented decreasing shear viscosity with increasing shear rate and shear stress, and required low forces for extrusion, validating their injectability. The GGDVS hydrogel was functionalized with Q-peptide with 30% of efficiency. C2C12 were able to adhere to the developed hydrogel, remained living and spreading 7 days post-encapsulation. Q-peptide release studies indicated that 25% of the unbound peptide can be released from the hydrogels up to 7 days, dependent on the hydrogel formulation. Treatment of a chemically-induced muscular lesion in mice with an injection of C2C12-laden hydrogels improved myogenesis, primarily promoted by the C2C12. In accordance, a high density of myoblasts (α-SA+ and MYH7+) were localized in tissues treated with the C2C12 (alone or encapsulated in the hydrogel). α-SA protein levels were significantly increased 8 weeks post-treatment with C2C12-laden hydrogels and MHC protein levels were increased in all experimental groups 4 weeks post-treatment, in relation to the SHAM. Neovascularization and neoinnervation was also detected in the defects. Altogether, this study indicates that C2C12-laden hydrogels hold great potential for skeletal muscle regeneration. STATEMENT OF SIGNIFICANCE: We developed an injectable gellan gum-based hydrogel for delivering C2C12 into localized myopathic model. The gellan gum was biofunctinalized with laminin-derived peptide to mimic the native muscular ECM. In addition, hydrogel was physically tuned to mimic the mechanical properties of native tissue. To the best of our knowledge, this formula was used for the first time under the context of skeletal muscle tissue regeneration. The injectability of the developed hydrogel provided non-invasive administration method, combined with a reliable microenvironment that can host C2C12 with nominal inflammation, indicated by the survival and adhesion of encapsulated cells post-injection. The treatment of skeletal muscle defect with the cell-laden hydrogel approach significantly enhanced the regeneration of localized muscular trauma.

Recent approaches towards bone tissue engineering.

Bone tissue engineering approaches have evolved towards addressing the challenges of tissue mimetic requirements over the years. Different strategies have been combining scaffolds, cells, and biologically active cues using a wide range of fabrication techniques, envisioning the mimicry of bone tissue. On the one hand, biomimetic scaffold-based strategies have been pursuing different biomaterials to produce scaffolds, combining with diverse and innovative fabrication strategies to mimic bone tissue better, surpassing bone grafts. On the other hand, biomimetic scaffold-free approaches mainly foresee replicating endochondral ossification, replacing hyaline cartilage with new bone. Finally, since bone tissue is highly vascularized, new strategies focused on developing pre-vascularized scaffolds or pre-vascularized cellular aggregates have been a motif of study. The recent biomimetic scaffold-based and scaffold-free approaches in bone tissue engineering, focusing on materials and fabrication methods used, are overviewed herein. The biomimetic vascularized approaches are also discussed, namely the development of pre-vascularized scaffolds and pre-vascularized cellular aggregates.

Micropatterned gellan gum-based hydrogels tailored with laminin-derived peptides for skeletal muscle tissue engineering.

The efficacy of current therapies for skeletal muscle disorders/injuries are limited urging the need for new treatments. Skeletal muscle tissue engineered platforms represent a promising tool to shed light on the pathophysiology of skeletal muscle disorders/injuries and to investigate the efficacy of new therapies. Herein, we developed a skeletal muscle platform composed of aligned and differentiated myoblasts on micropatterned gellan gum (GG)-based hydrogels tailored with a laminin-derived peptide. To this aim, the binding of murine skeletal muscle cells (C2C12) to different laminin-derived peptides (CIKVAVS (V), KNRLTIELEVRTC (T), and RKRLQVQLSIRTC (Q)) and the binding of laminin-derived peptides to chemically functionalized GG was studied. C2C12-binding to peptide V, T and Q was 10%, 48% and 25%, whereas the peptide tethering to GG was 60%, 40% and 31%, respectively. Peptide-biofunctionalized hydrogels prepared with different polymer content showed different mechanics and peptide exposure at hydrogel surface. Cellular adhesion was detected in all hydrogel formulations, but spreading and differentiation was only promoted in peptide Q-biofunctionalized hydrogels and preferably in stiffer hydrogels. Myoblast alignment was promoted in micropatterned hydrogel surfaces. Overall, the engineered skeletal muscle herein proposed can be further explored as a platform to better understand skeletal muscle disorders/injuries and to screen new therapies.

Bovine Colostrum Supplementation Improves Bone Metabolism in an Osteoporosis-Induced Animal Model.

Osteoporosis is characterized by bone loss. The present study aims to investigate the effects of bovine colostrum (BC) on bone metabolism using ovariectomized (OVX) and orchidectomized (ORX) rat models. Twenty-seven-week-old Wistar Han rats were randomly assigned as: (1) placebo control, (2) BC supplementation dose 1 (BC1: 0.5 g/day/OVX, 1 g/day/ORX), (3) BC supplementation dose 2 (BC2: 1 g/day/OVX, 1.5 g/day/ORX) and (4) BC supplementation dose 3 (BC3: 1.5 g/day/OVX, 2 g/day/ORX). Bone microarchitecture, strength, gene expression of VEGFA, FGF2, RANKL, RANK and OPG, and bone resorption/formation markers were assessed after four months of BC supplementation. Compared to the placebo, OVX rats in the BC1 group exhibited significantly higher cortical bone mineral content and trabecular bone mineral content (p < 0.01), while OVX rats in the BC3 group showed significantly higher trabecular bone mineral content (p < 0.05). ORX rats receiving BC dose 2 demonstrated significantly higher levels of trabecular bone mineral content (p < 0.05). Serum osteocalcin in the ORX was pointedly higher in all BC supplementation groups than the placebo (BC1: p < 0.05; BC2, BC3: p < 0.001). Higher doses of BC induced significantly higher relative mRNA expression of OPG, VEGFA, FGF2 and RANKL (p < 0.05). BC supplementation improves bone metabolism of OVX and ORX rats, which might be associated with the activation of the VEGFA, FGF2 and RANKL/RANK/OPG pathways.

adipoSIGHT in Therapeutic Response: Consequences in Osteosarcoma Treatment.

Chemotherapeutic resistance is a major problem in effective cancer treatment. Cancer cells engage various cells or mechanisms to resist anti-cancer therapeutics, which results in metastasis and the recurrence of disease. Considering the cellular heterogeneity of cancer stroma, the involvement of stem cells is reported to affect the proliferation and metastasis of osteosarcoma. Hence, the duo (osteosarcoma: Saos 2 and human adipose-derived stem cells: ASCs) is co-cultured in present study to investigate the therapeutic response using a nonadherent, concave surface. Staining with a cell tracker allows real-time microscopic monitoring of the cell arrangement within the sphere. Cell-cell interaction is investigated by means of E-cadherin expression. Comparatively high expression of E-cadherin and compact organization is observed in heterotypic tumorspheres (Saos 2-ASCs) compared to homotypic ones (ASCs), limiting the infiltration of chemotherapeutic compound doxorubicin into the heterotypic tumorsphere, which in turn protects cells from the toxic effect of the chemotherapeutic. In addition, genes known to be associated with drug resistance, such as SOX2, OCT4, and CD44 are overexpressed in heterotypic tumorspheres post-chemotherapy, indicating that the duo collectively repels the effect of doxorubicin. The interaction between ASCs and Saos 2 in the present study points toward the growing oncological risk of using ASC-based regenerative therapy in cancer patients and warrants further investigation.

Tumor-Associated Protrusion Fluctuations as a Signature of Cancer Invasiveness.

The generation of invasive fluctuating protrusions is a distinctive feature of tumor dissemination. During the invasion, individual cancer cells modulate the morphodynamics of protrusions to optimize their migration efficiency. However, it remains unclear how protrusion fluctuations govern the invasion of more complex multi-cellular structures, such as tumors, and their correlation with the tumor metastatic potential. Herein, a reductionist approach based on 3D tumor cell micro-spheroids with different invasion capabilities is used as a model to decipher the role of tumor-associated fluctuating protrusions in cancer progression. To quantify fluctuations, a set of key biophysical parameters that precisely correlate with the invasive potential of tumors is defined. It is shown that different pharmacological drugs and cytokines are capable of modulating protrusion activity, significantly altering protrusion fluctuations, and tumor invasiveness. This correlation is used to define a novel quantitative invasion index encoding the key biophysical parameters of fluctuations and the relative levels of cell-cell/matrix interactions, which is capable of assessing the tumor's metastatic capability solely based on its magnitude. Overall, this study provides new insights into how protrusion fluctuations regulate tumor cell invasion, suggesting that they may be employed as a novel early indicator, or biophysical signature, of the metastatic potential of tumors.

Micropatterned Silk-Fibroin/Eumelanin Composite Films for Bioelectronic Applications.

There has been growing interest in the use of natural bionanomaterials and nanostructured systems for diverse biomedical applications. Such materials can confer unique functional properties as well as address concerns pertaining to sustainability in production. In this work, we propose the biofabrication of micropatterned silk fibroin/eumelanin composite thin films to be used in electroactive and bioactive applications in bioelectronics and biomedical engineering. Eumelanin is the most common form of melanin, naturally derived from the ink of cuttlefish, having antioxidant and electroactive properties. Another natural biomaterial, the protein silk fibroin, is modified with photoreactive chemical groups, which allows the formation of electroactive eumelanin thin films with different microstructures. The silk fibroin/eumelanin composites are fabricated to obtain thin films as well as electroactive microstructures using UV curing. Here, we report for the first time the preparation, characterization, and physical, electrochemical, and biological properties of these natural silk fibroin/eumelanin composite films. Higher concentrations of eumelanin incorporated into the films exhibit a higher charge storage capacity and good electroactivity even after 100 redox cycles. In addition, the microscale structure and the cellular activity of the fibroin/eumelanin films are assessed for understanding of the biological properties of the composite. The developed micropatterned fibroin/eumelanin films can be applied as natural electroactive substrates for bioapplications (e.g., bioelectronics, sensing, and theranostics) because of their biocompatible properties.

Electro-responsive controlled drug delivery from melanin nanoparticles.

Electro-responsive controlled drug delivery has been receiving an increasing interest as one of the on-demand drug delivery systems, aiming the improvement of the therapeutics efficacy by controlling the amount of drug release at a specific time and target site. Herein, we report a simple method to develop an electro-responsive controlled drug delivery system using functionalized melanin nanoparticles (FMNPs) with polydopamine and polypyrrole to precisely control the release of dexamethasone (Dex). Optimized FMNPs showed 376.77 ± 62.05 nm of particle size, a polydispersity index of 0.26 ± 0.09 and a zeta-potential (ZP) of -32.59 ± 3.61 mV. FMNPs evidenced a spherical shape, which was confirmed by scanning electron microscopy. Fourier-transform infrared spectrometry analysis confirmed the deposition of the polymers on the FMNPs' surface. The incorporation efficiency of the optimized Dex-loaded FMNPs was 94.45 ± 0.63% and the increase of ZP to -40.34 ± 4.65 mV was attributed to the anionic nature of Dex. In vitro Dex release studies without stimuli revealed a maximum Dex release below 10%. Applying electrical stimulation, Dex release was augmented, with a maximum of ca. 32% after 24 h. The designed FMNPs provide a powerful biomaterial-based technological tool for electro-responsive controlled drug delivery, capable of surpassing the associated lack of efficiency and stability of current carriers.