Unveiling the mechanical role of radial fibers in meniscal tissue: Toward structural biomimetics.

The meniscus tissue is crucial for knee joint biomechanics and is frequently susceptible to injuries resulting in early-onset osteoarthritis. Consequently, the need for meniscal substitutes spurs ongoing development. The meniscus is a composite tissue reinforced with circumferential and radial collagenous fibers; the mechanical role of the latter has yet to be fully unveiled.

Distinct HAND2/HAND2-AS1 Expression Levels May Fine-Tune Mesenchymal and Epithelial Cell Plasticity of Human Mesenchymal Stem Cells.

We previously developed several successful decellularization strategies that yielded porcine cardiac extracellular matrices (pcECMs) exhibiting tissue-specific bioactivity and bioinductive capacity when cultured with various pluripotent and multipotent stem cells. Here, we study the tissue-specific effects of the pcECM on seeded human mesenchymal stem cell (hMSC) phenotypes using reverse transcribed quantitative polymerase chain reaction (RT-qPCR) arrays for cardiovascular related gene expression. We further corroborated interesting findings at the protein level (flow cytometry and immunological stains) as well as bioinformatically using several mRNA sequencing and protein databases of normal and pathologic adult and embryonic (organogenesis stage) tissue expression.

Surface Wettability of a Natural Rubber Composite under Stretching: A Model to Predict Cell Survival.

We report the stress-strain effect of a stretchable natural rubber (NR)-calcium phosphate composite on the surface wettability (SW) using an innovative approach coupling a uniaxial tensile micromachine, goniometer, and microscope. In situ contact angle measurements in real time were performed during mechanical tension. Our results show that SW is guided by the stress-strain relationship with two different characteristics, depending on the static or dynamic experiments.

Robust Fabrication of Composite 3D Scaffolds with Tissue-Specific Bioactivity: A Proof-of-Concept Study.

The basic requirement of any engineered scaffold is to mimic the native tissue extracellular matrix (ECM). Despite substantial strides in understanding the ECM, scaffold fabrication processes of sufficient product robustness and bioactivity require further investigation, owing to the complexity of the natural ECM. A promising bioacive platform for cardiac tissue engineering is that of decellularized porcine cardiac ECM (pcECM, used here as a soft tissue representative model).

Biological and mechanical interplay at the Macro- and Microscales Modulates the Cell-Niche Fate.

Tissue development, regeneration, or de-novo tissue engineering in-vitro, are based on reciprocal cell-niche interactions. Early tissue formation mechanisms, however, remain largely unknown given complex in-vivo multifactoriality, and limited tools to effectively characterize and correlate specific micro-scaled bio-mechanical interplay. We developed a unique model system, based on decellularized porcine cardiac extracellular matrices (pcECMs)-as representative natural soft-tissue biomaterial-to study a spectrum of common cell-niche interactions.

Contact guidance for cardiac tissue engineering using 3D bioprinted gelatin patterned hydrogel.

Here, we have developed a 3D bioprinted microchanneled gelatin hydrogel that promotes human mesenchymal stem cell (hMSC) myocardial commitment and supports native cardiomyocytes (CMs) contractile functionality. Firstly, we studied the effect of bioprinted microchanneled hydrogel on the alignment, elongation, and differentiation of hMSC. Notably, the cells displayed well defined F-actin anisotropy and elongated morphology on the microchanneled hydrogel, hence showing the effects of topographical control over cell behavior.

Restoring the biophysical properties of decellularized patches through recellularization.

Various extracellular matrix (ECM) scaffolds, isolated through decellularization, were suggested as ideal biomimetic materials for 'Functional tissue engineering' (FTE). The decellularization process comprises a compromise between damaging and preserving the ultrastructure and composition of ECM-previously shown to affect cell survival, proliferation, migration, organization, differentiation and maturation. Inversely, the effects of cells on the ECM constructs' biophysical properties, under physiological-like conditions, remain still largely unknown.

Biohybrid cardiac ECM-based hydrogels improve long term cardiac function post myocardial infarction.

Unlabelled: Injectable scaffolds for cardiac tissue regeneration are a promising therapeutic approach for progressive heart failure following myocardial infarction (MI). Their major advantage lies in their delivery modality that is considered minimally invasive due to their direct injection into the myocardium. Biomaterials comprising such scaffolds should mimic the cardiac tissue in terms of composition, structure, mechanical support, and most importantly, bioactivity.

Dynamic Autologous Reendothelialization of Small-Caliber Arterial Extracellular Matrix: A Preclinical Large Animal Study.

Effective cellularization is a key approach to prevent small-caliber (<4 mm) tissue-engineered vascular graft (TEVG) failure and maintain patency and contractility following implantation. To achieve this goal, however, improved biomimicking designs and/or relatively long production times (typically several months) are required. We previously reported on porcine carotid artery decellularization yielding biomechanically stable and cell supportive small-caliber (3-4 mm diameter, 5 cm long) arterial extracellular matrix (scaECM) vascular grafts.

Natural myocardial ECM patch drives cardiac progenitor based restoration even after scarring.

Objective: To evaluate the regenerative capacity of non-supplemented and bioactive patches made of decellularized porcine cardiac extracellular matrix (pcECM) and characterize the biological key factors involved in possible cardiac function (CF) restoration following acute and 8weeks chronic MI.

Background: pcECM is a key natural biomaterial that can affect cardiac regeneration following myocardial infarction (MI), through mechanisms, which are still not clearly understood.

Methods: Wistar rats underwent MI and received pcECM patch (pcECM-P) treatment in either acute or chronic inflammatory phases.

Pushing the envelope in tissue engineering: ex vivo production of thick vascularized cardiac extracellular matrix constructs.

Functional vascularization is a prerequisite for cardiac tissue engineering of constructs with physiological thicknesses. We previously reported the successful preservation of main vascular conduits in isolated thick acellular porcine cardiac ventricular ECM (pcECM). We now unveil this scaffold's potential in supporting human cardiomyocytes and promoting new blood vessel development ex vivo, providing long-term cell support in the construct bulk.

Characterization of a bioactive fiber scaffold with entrapped HUVECs in coaxial electrospun core-shell fiber.

Human umbilical vein endothelial cells (HUVECs) were successfully entrapped in polyethylene oxide (PEO) core /polycaprolactone (PCL) shell electrospun fibers thus creating a "bioactive fiber." The viability and release of biomolecules from the entrapped cells in the bioactive fibers were characterized. A key modification to the core solution was the inclusion of 50% fetal bovine serum (FBS), which improved cell viability substantially.

Collagen-cellulose composite thin films that mimic soft-tissue and allow stem-cell orientation.

Mechanical properties of collagen films are less than ideal for biomaterial development towards musculoskeletal repair or cardiovascular applications. Herein, we present a collagen-cellulose composite film (CCCF) compared against swine small intestine submucosa in regards to mechanical properties, cell growth, and histological analysis. CCCF was additionally characterized by FE-SEM, NMR, mass spectrometry, and Raman Microscopy to elucidate its physical structure, collagen-cellulose composition, and structure activity relationships.

A mathematical model for analyzing the elasticity, viscosity, and failure of soft tissue: comparison of native and decellularized porcine cardiac extracellular matrix for tissue engineering.

The clinical success of tissue-engineered constructs commonly requires mechanical properties that closely mimic those of the human tissue. Determining the viscoelastic properties of such biomaterials and the factors governing their failure profiles, however, has proven challenging, although collecting extensive data regarding their tensile behavior is straightforward. The easily calculated Young's modulus remains the most reported mechanical measure, regardless of its limitations, even though single-relaxation-time (SRT) models can provide much more information, which remain scarce due to a lack of manageable tools for implementing these models.

A mathematical model predicting the coculture dynamics of endothelial and mesenchymal stem cells for tissue regeneration.

In most tissue engineering applications, understanding the factors affecting the growth dynamics of coculture systems is crucial for directing the population toward a desirable regenerative process. Yet, no comprehensive analysis method exists to quantify coculture population dynamics, let alone, a unifying model addressing the "environmental" factors influencing cell growth, all together. Here we suggest a modification of the Lotka-Volterra model to analyze the population dynamics of cocultured cells and predict their growth profiles for tissue engineering applications.

Thick acellular heart extracellular matrix with inherent vasculature: a potential platform for myocardial tissue regeneration.

The decellularization of porcine heart tissue offers many opportunities for the production of physiologically relevant myocardial mimetic scaffolds. Earlier, we reported the successful isolation of a thin porcine cardiac extracellular matrix (pcECM) exhibiting relevant bio-mechanical properties for myocardial tissue engineering. Nevertheless, since native cardiac tissue is much thicker, such thin scaffolds may offer limited regeneration capacity.

Porcine small diameter arterial extracellular matrix supports endothelium formation and media remodeling forming a promising vascular engineered biograft.

Patients with small caliber artery disorders, often lack the suitable autologous tissue needed for bypassing diseased vessels or for other vascular reconstructive procedures. We propose to decellularize small caliber porcine carotid artery, then recellularize it with vascular cells and function as scaffold for tissue engineering vascular graft replacements. Based on a modified decellularization method developed in our laboratory, the cellular contents of small caliber (<4 mm) arteries were carefully removed using an enzymatic and detergent decellularization procedure.

Engineering cell platforms for myocardial regeneration.

Introduction: Various engineered 'cell-platforms' have been reported in recent years for the possible treatment of myocardial infarction (MI) and end-stage heart failure. These engineered platforms rely on two key factors: cells and/or biomaterial scaffolds for the regeneration of the infarcted heart tissue.

Areas Covered: Two major cell-platform approaches are described and broadly categorized as 'injectable cell platforms' and 'patch-based cell platforms'.

Acellular cardiac extracellular matrix as a scaffold for tissue engineering: in vitro cell support, remodeling, and biocompatibility.

We have developed an efficient decellularization process for the isolation of extracellular matrix (ECM) from native cardiac tissue. The isolated ECM exhibited desirable mechanical properties in terms of elasticity, strength and durability-properties required from scaffolds used for cardiac tissue repair. This study further investigates the potential use of this scaffold for cardiac tissue engineering in terms of interactions with seeded cells and biocompatibility.