Engineering Stem Cell Fate Controlling Biomaterials to Develop Muscle Connective Tissue Layered Myofibers.

Skeletal muscle connective tissue (MCT) surrounds myofiber bundles to provide structural support, produce force transduction from tendons, and regulate satellite cell differentiation during muscle regeneration. Engineered muscle tissue composed of myofibers layered within MCT has not yet been developed. Herein, a bioengineering strategy to create MCT-layered myofibers through the development of stem cell fate-controlling biomaterials that achieve both myogenesis and fibroblast differentiation in a locally controlled manner at the single construct is introduced.

ATP/ADP biosensor organoids for drug nephrotoxicity assessment.

Drug nephrotoxicity is a common healthcare problem in hospitalized patients and a major limitation during drug development. Multi-segmented kidney organoids derived from human pluripotent stem cells may complement traditional cell culture and animal experiments for nephrotoxicity assessment. Here we evaluate the capability of kidney organoids to investigate drug toxicity .

Aerobic exercise and scaffolds with hierarchical porosity synergistically promote functional recovery post volumetric muscle loss.

Volumetric muscle loss (VML), which refers to a composite skeletal muscle defect, most commonly heals by scarring and minimal muscle regeneration but substantial fibrosis. Current surgical interventions and physical therapy techniques are limited in restoring muscle function following VML. Novel tissue engineering strategies may offer an option to promote functional muscle recovery.

Platelet-rich plasma enhances mechanical strength of strattice in rat model of ventral hernia repair.

Incisional hernia is a common complication of hernia repair despite the development of various synthetic and bio-synthetic repair materials. Poor long-term mechanical strength, leading to high recurrence rates, has limited the use of acellular dermal matrices (ADMs) in ventral hernia repair (VHR). Biologically derived meshes have been an area of increasing interest.

Customizable Composite Fibers for Engineering Skeletal Muscle Models.

Engineering tissue-like scaffolds that can mimic the microstructure, architecture, topology, and mechanical properties of native tissues while offering an excellent environment for cellular growth has remained an unmet need. To address these challenges, multicompartment composite fibers are fabricated. These fibers can be assembled through textile processes to tailor tissue-level mechanical and electrical properties independent of cellular level components.

Addition of platelet-rich plasma supports immune modulation and improved mechanical integrity in Alloderm mesh for ventral hernia repair in a rat model.

The recurrence of ventral hernias continues to be a problem faced by surgeons, in spite of efforts toward implementing novel repair techniques and utilizing different materials to promote healing. Cadaveric acellular dermal matrices (Alloderm) have shown some promise in numerous surgical subspecialties, but these meshes still suffer from subsequent failure and necessitation of re-intervention. Here, it is demonstrated that the addition of platelet rich plasma to Alloderm meshes temporally modulates both the innate and cytotoxic inflammatory responses to the implanted material.

Perforated and Endothelialized Elastomeric Tubes for Vascular Modeling.

We report the fabrication of a tubular polydimethylsiloxane (PDMS) platform containing arrays of small pores on the wall for modeling blood vessels . The thin PDMS tubes are produced following our previously reported templating approach, while the pores are subsequently generated using focused laser ablation. As such, when these perforated PDMS tube are populated with a monolayer of endothelial cells on the interior surfaces and embedded within an extracellular matrix (ECM)-like environment, the endothelial cells can sprout out from the tubes into the surrounding matrix through the open pores.

Endosomal Escape of Polymer-Coated Silica Nanoparticles in Endothelial Cells.

Current investigations into hazardous nanoparticles (i.e., nanotoxicology) aim to understand the working mechanisms that drive toxicity.

Biocompatible PLGA-Mesoporous Silicon Microspheres for the Controlled Release of BMP-2 for Bone Augmentation.

Bone morphogenetic protein-2 (BMP-2) has been demonstrated to be one of the most vital osteogenic factors for bone augmentation. However, its uncontrolled administration has been associated with catastrophic side effects, which compromised its clinical use. To overcome these limitations, we aimed at developing a safer controlled and sustained release of BMP-2, utilizing poly(lactic--glycolic acid)-multistage vector composite microspheres (PLGA-MSV).

Biomimetic cellular vectors for enhancing drug delivery to the lungs.

Despite recent advances in drug delivery, the targeted treatment of unhealthy cells or tissues continues to remain a priority. In cancer (much like other pathologies), delivery vectors are designed to exploit physical and biological features of unhealthy tissues that are not always homogenous across the disease. In some cases, shifting the target from unhealthy tissues to the whole organ can represent an advantage.

Mechanical and Biochemical Stimulation of 3D Multilayered Scaffolds for Tendon Tissue Engineering.

Tendon injuries are frequent and occur in the elderly, young, and athletic populations. The inadequate number of donors combined with many challenges associated with autografts, allografts, xenografts, and prosthetic devices have added to the value of engineering biological substitutes, which can be implanted to repair the damaged tendons. Electrospun scaffolds have the potential to mimic the native tissue structure along with desired mechanical properties and, thus, have attracted noticeable attention.

Cardiac Fibrotic Remodeling on a Chip with Dynamic Mechanical Stimulation.

Cardiac tissue is characterized by being dynamic and contractile, imparting the important role of biomechanical cues in the regulation of normal physiological activity or pathological remodeling. However, the dynamic mechanical tension ability also varies due to extracellular matrix remodeling in fibrosis, accompanied with the phenotypic transition from cardiac fibroblasts (CFs) to myofibroblasts. It is hypothesized that the dynamic mechanical tension ability regulates cardiac phenotypic transition within fibrosis in a strain-mediated manner.

Smart Bandage for Monitoring and Treatment of Chronic Wounds.

Chronic wounds are a major health concern and they affect the lives of more than 25 million people in the United States. They are susceptible to infection and are the leading cause of nontraumatic limb amputations worldwide. The wound environment is dynamic, but their healing rate can be enhanced by administration of therapies at the right time.

Patient-Specific Bioinks for 3D Bioprinting of Tissue Engineering Scaffolds.

Bioprinting has emerged as a promising tool in tissue engineering and regenerative medicine. Various 3D printing strategies have been developed to enable bioprinting of various biopolymers and hydrogels. However, the incorporation of biological factors has not been well explored.

Cell-laden composite suture threads for repairing damaged tendons.

Tendons have limited regenerative capacity due to their low cellularity and hypovascular nature, which results in poor clinical outcomes of presently used therapies. As tendon injuries are often observed in active adults, it poses an increasing socio-economic burden on healthcare systems. Currently, suture threads are used during surgical repair to anchor the tissue graft or to connect injured ends.

Engineered 3D Cardiac Fibrotic Tissue to Study Fibrotic Remodeling.

Activation of cardiac fibroblasts into myofibroblasts is considered to play an essential role in cardiac remodeling and fibrosis. A limiting factor in studying this process is the spontaneous activation of cardiac fibroblasts when cultured on two-dimensional (2D) culture plates. In this study, a simplified three-dimensional (3D) hydrogel platform of contractile cardiac tissue, stimulated by transforming growth factor-β1 (TGF-β1), is presented to recapitulate a fibrogenic microenvironment.

Ghee Butter as a Therapeutic Delivery System.

Solid lipid nanoparticles carrying a chemotherapeutic payload (i.e., temozolomide, TMZ) were synthesized using ghee, a clarified butter commonly used in traditional medicine and food products.

Localized inhibition of P2X7R at the spinal cord injury site improves neurogenic bladder dysfunction by decreasing urothelial P2X3R expression in rats.

Aims: Reestablishment of bladder function in patients with spinal cord injury (SCI) is a clinical priority. Our objectives were to determine whether SCI-localized inhibition of purinergic P2X7 receptors (P2X7R) improve bladder function by decreasing afferent signals mediated by urothelial P2X3R.

Main Methods: Systemic inhibition of P2X7R may improve locomotion in rodent SCI models; however, beneficial effects on bladder function and its physiological mechanisms have not been evaluated.

Proteomic-based biomarker discovery for development of next generation diagnostics.

In the post-genome age, proteomics is receiving significant attention because they provide an invaluable source of biological structures and functions at the protein level. The search for disease-specific biomarkers for diagnostic and/or therapeutic applications is one of the areas that proteomics is having a significant impact. Thus, the identification of a "good" biomarker enables a more accurate early diagnosis and prognosis of disease.

The design and fabrication of a three-dimensional bioengineered open ventricle.

Current treatments in hypoplastic left heart syndrome (HLHS) include multiple surgeries to refunctionalize the right ventricle and/or transplant. The development of a tissue-engineered left ventricle (LV) would provide a therapeutic option to overcome the inefficiencies and limitations associated with current treatment options. This study provides a foundation for the development and fabrication of the bioengineered open ventricle (BEOV) model.

Cell-microenvironment interactions and architectures in microvascular systems.

In the past decade, significant advances have been made in the design and optimization of novel biomaterials and microfabrication techniques to generate vascularized tissues. Novel microfluidic systems have facilitated the development and optimization of in vitro models for exploring the complex pathophysiological phenomena that occur inside a microvascular environment. To date, most of these models have focused on engineering of increasingly complex systems, rather than analyzing the molecular and cellular mechanisms that drive microvascular network morphogenesis and remodeling.

Optimizing cell seeding and retention in a three-dimensional bioengineered cardiac ventricle: The two-stage cellularization model.

Current cell seeding techniques focus on passively directing cells to a scaffold surface with the addition of dynamic culture to encourage cell permeation. In 3D tissue engineered constructs, cell retention efficiency is dependent on the cell delivery method, and biomaterial properties. Passive cell delivery relies on cell migration to the scaffold surface; biomaterial surface properties and porosity determine cell infiltration capacity.

Antibody-mediated inhibition of Nogo-A signaling promotes neurite growth in PC-12 cells.

The use of a monoclonal antibody to block the neurite outgrowth inhibitor Nogo-A has been of great interest for promoting axonal recovery as a treatment for spinal cord injury. While several cellular and non-cellular assays have been developed to quantify the bioactive effects of Nogo-A signaling, demand still exists for the development of a reliable approach to characterize the effectiveness of the anti-Nogo-A antibody. In this study, we developed and validated a novel cell-based approach to facilitate the biological quantification of a Nogo-A antibody using PC-12 cells as an in vitro neuronal cell model.

One-pot synthesis of pH-responsive hybrid nanogel particles for the intracellular delivery of small interfering RNA.

This report describes a novel, one-pot synthesis of hybrid nanoparticles formed by a nanostructured inorganic silica core and an organic pH-responsive hydrogel shell. This easy-to-perform, oil-in-water emulsion process synthesizes fluorescently-doped silica nanoparticles wrapped within a tunable coating of cationic poly(2-diethylaminoethyl methacrylate) hydrogel in one step. Transmission electron microscopy and dynamic light scattering analysis demonstrated that the hydrogel-coated nanoparticles are uniformly dispersed in the aqueous phase.

A New Class of Phantom Materials for Poroelastography Imaging Techniques.

Poroelastography is an elastographic technique used to image the temporal mechanical behavior of tissues. One of the major challenges in determining experimental potentials and limitations of this technique has been the lack of complex and realistic controlled phantoms that could be used to corroborate the limited number of theoretical and simulation studies available in the literature as well as to predict its performance in complex experimental situations and in a variety of conditions. In the study described here, we propose and analyze a new class of phantom materials for temporal elastography imaging.