scholarly journals Mechanically Activated Extracellular Vesicle Functionalised Melt Electrowritten Materials for Bone Regeneration: A Mechano-Biomimetic Scaffold

2021 ◽  
Author(s):  
Kian Eichholz ◽  
Angelica Federici ◽  
Mathieu Riffault ◽  
Ian Woods ◽  
Olwyn Mahon ◽  
...  
Keyword(s):  
Bone Repair ◽  
Extracellular Vesicle ◽  
Great Promise ◽  
Cell Behaviour ◽  
Tissue Scaffold ◽  
Biomimetic Scaffold ◽  
Indirect Cues ◽  
Mediate Cell ◽  
Alkaline Phosphatase Expression ◽  
Biophysical Cues

Mechanobiological cues arising directly via tissue/scaffold mechanics or indirectly via mechanically activated cell secretomes represent potent stimuli that mediate cell behaviour and tissue adaptation. Exploiting these cues in regeneration strategies holds great promise for tissue repair. In this study, we harness indirect biophysical cues originating from osteocytes in a combination with direct biophysical cues from Melt ElectroWritten (MEW) scaffolds to form a single engineered construct with the aim of synergistically enhancing osteogenesis. The secretome of mechanically activated osteocytes was collected within conditioned media (CM) and extracellular vesicles (EV) were subsequently isolated. Building on MEW micro-fibrous scaffolds with controlled microarchitecture and mineral nanotopography optimised for bone repair, a protocol was developed to functionalise these materials with CM or EVs. Human MSC proliferation was enhanced in both CM and EV functionalised scaffolds. EV functionalised scaffolds were further found to significantly enhance MSC osteogenesis, with enhanced alkaline phosphatase expression, collagen production, and mineralisation compared to control scaffolds. Furthermore, enhanced formation of mineralised nodules was identified in EV functionalised materials. Combining direct biophysical cues provided by the fibrous architecture/mineral nanotopography with the indirect cues provided by EVs, these constructs hold great promise to enhance the repair of damaged bone in a physiologically relevant manner.

scholarly journals Molecular Imprinting Strategies for Tissue Engineering Applications: A Review

Polymers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 548
Author(s):  
Amedeo Franco Bonatti ◽  
Carmelo De Maria ◽  
Giovanni Vozzi
Keyword(s):  
Tissue Engineering ◽  
Molecularly Imprinted Polymers ◽  
Cell Interaction ◽  
Great Promise ◽  
Molecularly Imprinted ◽  
Proliferation And Differentiation ◽  
Promising Solution ◽  
Natural Tissue ◽  
A Current ◽  
Biophysical Cues

Tissue Engineering (TE) represents a promising solution to fabricate engineered constructs able to restore tissue damage after implantation. In the classic TE approach, biomaterials are used alongside growth factors to create a scaffolding structure that supports cells during the construct maturation. A current challenge in TE is the creation of engineered constructs able to mimic the complex microenvironment found in the natural tissue, so as to promote and guide cell migration, proliferation, and differentiation. In this context, the introduction inside the scaffold of molecularly imprinted polymers (MIPs)—synthetic receptors able to reversibly bind to biomolecules—holds great promise to enhance the scaffold-cell interaction. In this review, we analyze the main strategies that have been used for MIP design and fabrication with a particular focus on biomedical research. Furthermore, to highlight the potential of MIPs for scaffold-based TE, we present recent examples on how MIPs have been used in TE to introduce biophysical cues as well as for drug delivery and sequestering.

scholarly journals Extracellular Vesicles, A Possible Theranostic Platform Strategy for Hepatocellular Carcinoma—An Overview

Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 261 ◽  
Author(s):  
Igea D’Agnano ◽  
Anna Concetta Berardi
Keyword(s):  
Hepatocellular Carcinoma ◽  
Targeted Drug Delivery ◽  
Kinase Inhibitors ◽  
Standard Treatment ◽  
Extracellular Vesicle ◽  
Great Promise ◽  
The Third ◽  
Common Cancer ◽  
Targeted Drug ◽  
Delays In Diagnosis

Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third highest cause of mortality from cancer, largely because of delays in diagnosis. There is currently no effective therapy for advanced stage HCC, although sorafenib, the standard treatment for HCC, systemic therapy (including tyrosine kinase inhibitors and anti-angiogenesis agents), and more recently, immunotherapy, have demonstrated some survival benefit. The measurement and modification of extracellular vesicle (EVs) cargoes—composed of nucleic acids, including miRNAs, proteins, and lipids—holds great promise for future HCC diagnosis, prognosis, and treatment. This review will provide an overview of the most recent findings regarding EVs in HCC, and the possible future use of EVs as “liquid biopsy”-based biomarkers for early diagnosis and as a vehicle for targeted drug-delivery.

Modelling and Tissue Engineering of Three Layers of Calvarial Bone as a Biomimetic Scaffold

2012 ◽  
Vol 15 ◽  
pp. 37-53 ◽  
Author(s):  
Fatemeh Hosseinnejad ◽  
Abbas Ali Imani Fooladi ◽  
Forough Hafezi ◽  
Soroush Mohit Mafi ◽  
Afsaneh Amiri ◽  
...  
Keyword(s):  
Bone Repair ◽  
Parietal Bone ◽  
Calvarial Bone ◽  
Spongy Layer ◽  
Composition And Structure ◽  
Excellent Candidate ◽  
Biomimetic Scaffold ◽  
Biological Tests ◽  
Main Components ◽  
Imagej Software

In this Study, a New Zealand Rabbit Parietal Bone Was Cross-Sectioned, and Parameters such as Entire Thickness and the Thicknesses of the Compact and Spongy Tables Were Morphometrically Measured by Imagej Software. the Pore Size of the Cancellous Table Was Also Analysed, and a Calvarial Bone Model Was Created. Based upon a Natural Model for Bone Repair, a Nano-Structured Scaffold Was Designed Using Bioglass and Gelatin (BG) as its Main Components. the Scaffold Was Prepared Using Layer Solvent Casting Combined with Freeze-Drying, Layering Techniques, and other Commonly Used Techniques. the Fabricated BG Scaffolds Were Made with Different Percentages of Nanoparticles, and the 10% and 30% Constructions Were Found to Be Respectively Similar to Compact and Spongy Bone. we Fabricated Three Lamellar Scaffolds with Two Compact Layers on the outside and One Spongy Layer in the Middle to Mimic the Composition and Structure of Natural Bone. the Chemical, Physical, and Biological Tests (including Cell Seeding on Scaffold and MTT Assay) that Evaluated this Scaffold Examined its Capacity to Promote Bone Repair. Fabricated Scaffolds Implanted in Rabbit Calvaria and Evaluated the Bone Repair by X-Ray. this Mimetic BG Scaffold Could Be an Excellent Candidate for a Synthetic Calvarial Bone Graft.

scholarly journals Enhanced BMP-2-Mediated Bone Repair Using an Anisotropic Silk Fibroin Scaffold Coated with Bone-like Apatite

2021 ◽  
Vol 23 (1) ◽  
pp. 283
Author(s):  
Christian Deininger ◽  
Andrea Wagner ◽  
Patrick Heimel ◽  
Elias Salzer ◽  
Xavier Monforte Vila ◽  
...  
Keyword(s):  
Bone Repair ◽  
Bone Morphogenetic Protein 2 ◽  
Great Promise ◽  
Calcium Phosphate Coating ◽  
Graft Material ◽  
Morphogenetic Protein ◽  
Silk Scaffolds ◽  
Cost Efficient

The repair of large bone defects remains challenging and often requires graft material due to limited availability of autologous bone. In clinical settings, collagen sponges loaded with excessive amounts of bone morphogenetic protein 2 (rhBMP-2) are occasionally used for the treatment of bone non-unions, increasing the risk of adverse events. Therefore, strategies to reduce rhBMP-2 dosage are desirable. Silk scaffolds show great promise due to their favorable biocompatibility and their utility for various biofabrication methods. For this study, we generated silk scaffolds with axially aligned pores, which were subsequently treated with 10× simulated body fluid (SBF) to generate an apatitic calcium phosphate coating. Using a rat femoral critical sized defect model (CSD) we evaluated if the resulting scaffold allows the reduction of BMP-2 dosage to promote efficient bone repair by providing appropriate guidance cues. Highly porous, anisotropic silk scaffolds were produced, demonstrating good cytocompatibility in vitro and treatment with 10× SBF resulted in efficient surface coating. In vivo, the coated silk scaffolds loaded with a low dose of rhBMP-2 demonstrated significantly improved bone regeneration when compared to the unmineralized scaffold. Overall, our findings show that this simple and cost-efficient technique yields scaffolds that enhance rhBMP-2 mediated bone healing.

Extracellular vesicle research in reproductive science— Paving the way for clinical achievements

2022 ◽  
Author(s):  
Elina Aleksejeva ◽  
Natasa Zarovni ◽  
Keerthie Dissanayake ◽  
Kasun Godakumara ◽  
Paola Vigano ◽  
...  
Keyword(s):  
Embryo Implantation ◽  
Cell Communication ◽  
Extracellular Vesicle ◽  
Early Embryo ◽  
Clinical Settings ◽  
Menstrual Phase ◽  
Standardized Measurement ◽  
Reproductive Science ◽  
Mediate Cell ◽  
Therapeutic Art

Abstract Mammalian conception involves a multitude of reciprocal interactions via a molecular dialogue between mother and conceptus. Extracellular vesicles (EVs) are secreted membrane-encapsulated particles that mediate cell-to-cell communication in various contexts. EVs, which are present in seminal, follicular, oviductal, and endometrial fluids, as well as in embryo secretions, carry molecular constituents that impact gamete maturation, fertilization, early embryo development, and embryo-maternal communication. The distribution, concentration, and molecular cargo of EVs are regulated by steroid hormones and the health status of the tissue of origin, and thus are influenced by menstrual phase, stage of conception, and the presence of infertility-associated diseases. EVs have been recognized as a novel source of biomarkers and potential reproductive medicine therapeutics, particularly for assisted reproductive technology (ART). There are still many technological and scientific hindrances to be overcome before EVs can be used in clinical diagnostic and therapeutic ART applications. Issues to be resolved include the lack of standardized measurement protocols and an absence of absolute EV quantification technologies. Additionally, clinically suitable and robust EV isolation methods have yet to be developed. In this review, we provide an overview of EV-mediated interactions during the early stages of reproduction from gamete maturation to embryo implantation and then outline the technological progress that must be made for EV applications to be translated to clinical settings.

A Critical Assessment of the Clinical Efficacy and Cellular Response to Low Intensity Pulsed Ultrasound for Fracture Repair

2010 ◽  
Vol 76 ◽  
pp. 195-206
Author(s):  
Cato T. Laurencin ◽  
Yusuf Khan
Keyword(s):  
Cellular Response ◽  
Large Scale ◽  
Bone Repair ◽  
Fracture Repair ◽  
Great Promise ◽  
Pulsed Ultrasound ◽  
Invasive Treatment ◽  
In Vivo Evaluation ◽  
Low Intensity Pulsed Ultrasound ◽  
Low Intensity

Fracture repair continues to be widely investigated, both within the clinical realm and at the fundamental research level. Clinical application of low intensity pulsed ultrasound (LIPUS) has shown great promise as an effective, minimally invasive treatment for accelerating fracture repair and has warranted further investigation into the cellular manifestation of applied ultrasound. Toward this end much has been learned about the response of osteoblasts to LIPUS stimulation. In vitro and in vivo evaluation of cellular response to LIPUS have revealed an increase in proliferation, protein synthesis, collagen synthesis, membrane permeability, integrin expression, and increased cytosolic calcium, to name a few, further clarifying its utility and overall impact on cellular behavior. Considerable effects of LIPUS on the cells of musculoskeletal soft tissue have been reported as well. The growing body of research in this area suggests that LIPUS may be a powerful tool in the development of novel approaches to musculoskeletal repair and regeneration. Regenerative engineering-based approaches to musculoskeletal healing and regeneration that incorporate polymeric scaffolds and stem cells may be combined with LIPUS to move beyond bone repair to large scale multicomponent tissue repair.

scholarly journals Framework for rapid comparison of extracellular vesicle isolation methods

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Dmitry Ter-Ovanesyan ◽  
Maia Norman ◽  
Roey Lazarovits ◽  
Wendy Trieu ◽  
Ju-Hyun Lee ◽  
...  
Keyword(s):  
Single Molecule ◽  
Relative Efficiency ◽  
Transmembrane Proteins ◽  
Extracellular Vesicle ◽  
Size Exclusion ◽  
Great Promise ◽  
Disease Biomarkers ◽  
Isolation Methods ◽  
Exclusion Chromatography ◽  
Protein Contamination

Extracellular vesicles (EVs) are released by all cells into biofluids and hold great promise as reservoirs of disease biomarkers. One of the main challenges in studying EVs is a lack of methods to quantify EVs that are sensitive enough and can differentiate EVs from similarly sized lipoproteins and protein aggregates. We demonstrate the use of ultrasensitive, single molecule array (Simoa) assays for the quantification of EVs using three widely expressed transmembrane proteins: the tetraspanins CD9, CD63, and CD81. Using Simoa to measure these three EV markers, as well as albumin to measure protein contamination, we were able to compare the relative efficiency and purity of several commonly used EV isolation methods in plasma and cerebrospinal fluid (CSF): ultracentrifugation, precipitation, and size exclusion chromatography (SEC). We further used these assays, all on one platform, to improve SEC isolation from plasma and CSF. Our results highlight the utility of quantifying EV proteins using Simoa and provide a rapid framework for comparing and improving EV isolation methods from biofluids.

scholarly journals Design, Manufacture, and In vivo Testing of a Tissue Scaffold for Permanent Female Sterilization by Tubal Occlusion

MRS Advances ◽  
2018 ◽  
Vol 3 (30) ◽  
pp. 1685-1690 ◽  
Author(s):  
Prajan Divakar ◽  
Isabella Caruso ◽  
Karen L. Moodie ◽  
Regan N. Theiler ◽  
P. Jack Hoopes ◽  
...  
Keyword(s):  
Processing Parameters ◽  
Great Promise ◽  
Fallopian Tubes ◽  
Female Sterilization ◽  
Tissue Scaffold ◽  
Tubal Occlusion ◽  
Non Invasive ◽  
Custom Design ◽  
In Vivo Testing

ABSTRACTCurrent FDA-approved permanent female sterilization procedures are invasive and/or require the implantation of non-biodegradable materials. These techniques pose risks and complications, such as device migration, fracture, and tubal perforation. We propose a safe, non-invasive biodegradable tissue scaffold to effectively occlude the Fallopian tubes within 30 days of implantation. Specifically, the Fallopian tubes are mechanically de-epithelialized, and a tissue scaffold is placed into each tube. It is anticipated that this procedure can be performed in less than 30 minutes by an experienced obstetrics and gynaecology practitioner. Advantages of this method include the use of a fully bio-resorbable polymer, low costs, lower risks, and the lack of general anaesthesia. The scaffold devices are freeze-cast allowing for the custom-design of structural, mechanical, and chemical cues through material composition, processing parameters, and functionalization. The performance of the biomaterial and de-epithelialization procedure was tested in an in vivo rat uterine horn model. The scaffold response and tissue-biomaterial interactions were characterized microscopically post-implantation. Overall, the study resulted in the successful fabrication of resilient, easy-to-handle devices with an anisotropic scaffold architecture that encouraged rapid bio-integration through notable angiogenesis, cell infiltration, and native collagen deposition. Successful tubal occlusion was demonstrated at 30 days, revealing the great promise of a sterilization biomaterial.

scholarly journals Mechanotransduction in Neuronal Cell Development and Functioning

2019 ◽  
Author(s):  
Matteo Chighizola ◽  
Tania Dini ◽  
Cristina Lenardi ◽  
Paolo Milani ◽  
Alessandro Podestà ◽  
...  
Keyword(s):  
Neuronal Migration ◽  
Neuronal Cell ◽  
Cell Development ◽  
Spatial Organisation ◽  
Cell Behaviour ◽  
Cell Microenvironment ◽  
Adhesion Sites ◽  
It Impacts ◽  
Adhesion Complex ◽  
Biophysical Cues

Although many details remain still elusive, it became increasingly evident in recent years that mechanosensing of microenvironmental biophysical cues and subsequent mechanotransduction are strongly involved in the regulation of neuronal cell development and functioning. This review gives an overview about the current understanding of brain and neuronal cell mechanobiology and how it impacts on neurogenesis, neuronal migration, differentiation, and maturation. Therein; we are focussing particularly on the events in the cell/microenvironment interface and the decisive extracellular matrix (ECM) parameters (i.e. rigidity and nanometric spatial organisation of adhesion sites) that modulate integrin adhesion complex-based mechanosensing and mechanotransductive signalling. It will also be outlined how biomaterial approaches mimicking essential ECM features help to understand these processes and how they can be used to control and guide neuronal cell behaviour by providing appropriate biophysical cues. In addition, principal biophysical methods will be highlighted that have been crucial for the study of neuronal mechanobiology.

Sign in / Sign up

Export Citation Format

Share Document