Engineered extracellular vesicles from human skin cells induce pro-β-cell conversions in pancreatic ductal cells.

Direct nuclear reprogramming has the potential to enable the development of β cell replacement therapies for diabetes that do not require the use of progenitor/stem cell populations. However, despite their promise, current approaches to β cell-directed reprogramming rely heavily on the use of viral vectors. Here we explored the use of extracellular vesicles (EVs) derived from human dermal fibroblasts (HDFs) as novel non-viral carriers of endocrine cell-patterning transcription factors, to transfect and transdifferentiate pancreatic ductal epithelial cells (PDCs) into hormone-expressing cells.

Engineered Extracellular Vesicle-Based Therapies for Valvular Heart Disease.

Introduction: Valvular heart disease represents a significant burden to the healthcare system, with approximately 5 million cases diagnosed annually in the US. Among these cases, calcific aortic stenosis (CAS) stands out as the most prevalent form of valvular heart disease in the aging population.  CAS is characterized by the progressive calcification of the aortic valve leaflets, leading to valve stiffening.

Engineered Vasculogenic Extracellular Vesicles Drive Nonviral Direct Conversions of Human Dermal Fibroblasts into Induced Endothelial Cells and Improve Wound Closure.

Vasculogenic cell therapies have emerged as a powerful tool to increase vascularization and promote tissue repair/regeneration. Current approaches to cell therapies, however, rely mostly on progenitor cells, which pose significant risks (e.g.

Laser Micropatterning Promotes Rete Ridge Formation and Enhanced Engineered Skin Strength without Increased Inflammation.

Rete ridges play multiple important roles in native skin tissue function, including enhancing skin strength, but they are largely absent from engineered tissue models and skin substitutes. Laser micropatterning of fibroblast-containing dermal templates prior to seeding of keratinocytes was shown to facilitate rete ridge development in engineered skin (ES) both in vitro and in vivo. However, it is unknown whether rete ridge development results exclusively from the microarchitectural features formed by ablative processing or whether laser treatment causes an inflammatory response that contributes to rete ridge formation.

Mechanical strain induces ex vivo expansion of periosteum.

Segmental bone defects present complex clinical challenges. Nonunion, malunion, and infection are common sequalae of autogenous bone grafts, allografts, and synthetic bone implants due to poor incorporation with the patient's bone. The current project explores the osteogenic properties of periosteum to facilitate graft incorporation.

3D engineered human gingiva fabricated with electrospun collagen scaffolds provides a platform for in vitro analysis of gingival seal to abutment materials.

In order to advance models of human oral mucosa towards routine use, these models must faithfully mimic the native tissue structure while also being scalable and cost efficient. The goal of this study was to develop a low-cost, keratinized human gingival model with high fidelity to human attached gingiva and demonstrate its utility for studying the implant-tissue interface. Primary human gingival fibroblasts (HGF) and keratinocytes (HGK) were isolated from clinically healthy gingival biopsies.

Collagen-Based Electrospun Materials for Tissue Engineering: A Systematic Review.

Collagen is a key component of the extracellular matrix (ECM) in organs and tissues throughout the body and is used for many tissue engineering applications. Electrospinning of collagen can produce scaffolds in a wide variety of shapes, fiber diameters and porosities to match that of the native ECM. This systematic review aims to pool data from available manuscripts on electrospun collagen and tissue engineering to provide insight into the connection between source material, solvent, crosslinking method and functional outcomes.

In situ differentiation of human-induced pluripotent stem cells into functional cardiomyocytes on a coaxial PCL-gelatin nanofibrous scaffold.

Human-induced pluripotent stem cells (hiPSCs) derived cardiomyocytes (hiPSC-CMs) have been explored for cardiac regeneration and repair as well as for the development of in vitro 3D cardiac tissue models. Existing protocols for cardiac differentiation of hiPSCs utilize a 2D culture system. However, the efficiency of hiPSC differentiation to cardiomyocytes in 3D culture systems has not been extensively explored.

Direct comparison of reproducibility and reliability in quantitative assessments of burn scar properties.

Introduction: Determining the efficacy of anti-scar technologies can be difficult as qualitative, subjective assessments are often utilized instead of systematic, objective measures. Perceptions regarding the reliability of instruments for quantitative measurements along with their high cost and increased data collection time may discourage their use, leading to use of scar scales which are relatively quick and low-cost. To directly evaluate the reliability of instruments for quantitative measurements of scar properties, instruments and two qualitative scales were compared by assessing a variety of cutaneous scars.

Electrospun Aligned Coaxial Nanofibrous Scaffold for Cardiac Repair.

Cardiovascular diseases (CVDs) are one of the leading causes of mortality worldwide and a number one killer in the USA. Cell-based approaches to treat CVDs have only shown modest improvement due to poor survival, retention, and engraftment of the transplanted cells in the ischemic myocardium. Recently, tissue engineering and the use of 3D scaffolds for culturing and delivering stem cells for ischemic heart disease are gaining rapid potential.

Apple polyphenol-rich drinks dose-dependently decrease early-phase postprandial glucose concentrations following a high-carbohydrate meal: a randomized controlled trial in healthy adults and in vitro studies.

Background: Previous research demonstrated that a high dose of phlorizin-rich apple extract (AE) can markedly inhibit early-phase postprandial glycemia, but efficacy of lower doses of the AE is unclear.

Objective: To determine whether lower AE doses reduce early-phase postprandial glycemia in healthy adults and investigate mechanisms.

Design: In a randomized, controlled, double-blinded, cross-over acute trial, drinks containing 1.

Cultured Epithelial Autograft Combined with Micropatterned Dermal Template Forms Rete Ridges .

For patients with large, full-thickness burn wounds, sufficient donor sites for autografting are not available, and thus, alternate strategies must be used to close these wounds. Cultured epithelial autografts (CEAs) can aid in closing these wounds but are often associated with slow deposition of basement membrane proteins, leading to blistering and graft loss. Rete ridges and dermal papillae present at the dermal-epidermal junction (DEJ) play a key role in epidermal adhesion and skin homeostasis.

Improved Scar Outcomes with Increased Daily Duration of Pressure Garment Therapy.

Despite the development of a number of treatment modalities, scarring remains common postburn injury. To reduce burn scarring, pressure garment therapy has been widely utilized but is complicated by low patient adherence. To improve adherence, reduced hours of daily garment wear has been proposed.

Skin Biomechanics and miRNA Expression Following Chronic UVB Irradiation.

Exposure to ultraviolet (UV) light from the sun is known to accelerate the skin aging process and leads to significant alterations in skin biomechanics; however, the molecular mechanisms by which chronic UVB affects biomechanical properties of the skin have not been well described. A murine model for chronic UVB exposure was used to examine changes in epidermal barrier function, skin biomechanics, and miRNA expression as a result of UVB. UVB irradiation caused skin to be weaker, less elastic, stiffer, and less pliable.

Fractional CO laser micropatterning of cell-seeded electrospun collagen scaffolds enables rete ridge formation in 3D engineered skin.

Rete ridges are interdigitations of the epidermis and dermis of the skin that play multiple roles in homeostasis, including enhancing adhesion via increased contact area and acting as niches for epidermal stem cells. These structures, however, are generally absent from engineered skin (ES). To develop ES with rete ridges, human fibroblast-seeded dermal templates were treated with a fractional CO laser, creating consistently spaced wells at the surface.

Fractional CO laser ablation of porcine burn scars after grafting: Is deeper better?

Introduction: Fractional CO lasers have been used in clinical settings to improve scarring following burn injury. Though used with increasing frequency, the appropriate laser settings are not well defined and overall efficacy of this therapy has not been definitively established. As it has been proposed that for thick hypertrophic scars proportionally greater fluence and thus deeper ablation into the scar tissue would be most effective, the goal of this study was to examine the role of ablation depth on scar outcomes in a highly-controlled porcine model for burn scars-after grafting.

Role of Early Application of Pressure Garments following Burn Injury and Autografting.

Background: Pressure garment therapy, used for reduction of postburn scarring, is commonly initiated after complete healing of the wound or autograft. Although some clinicians have suggested that earlier treatment may improve outcomes, the effect of early initiation of therapy has not been studied in a controlled environment.

Methods: Full-thickness burns were created on red Duroc pigs, burn eschar was excised, and the wound bed was grafted with split-thickness autografts.

Staphylococcus aureus Biofilm Infection Compromises Wound Healing by Causing Deficiencies in Granulation Tissue Collagen.

Objective: The objective of this work was to causatively link biofilm properties of bacterial infection to specific pathogenic mechanisms in wound healing.

Background: Staphylococcus aureus is one of the four most prevalent bacterial species identified in chronic wounds. Causatively linking wound pathology to biofilm properties of bacterial infection is challenging.

Inflammatory response and biomechanical properties of coaxial scaffolds for engineered skin in vitro and post-grafting.

Engineered skin (ES) offers many advantages over split-thickness skin autografts for the treatment of burn wounds. However, ES, both in vitro and after grafting, is often significantly weaker, less elastic and more compliant than normal human skin. Biomechanical properties of ES can be tuned in vitro using electrospun co-axial (CoA) scaffolds.

Structural, Chemical, and Mechanical Properties of Pressure Garments as a Function of Simulated Use and Repeated Laundering.

Pressure garments are widely employed for management of postburn scarring. Although pressure magnitude has been linked to efficacy, maintenance of uniform pressure delivery is challenging. An understanding of garment fabric properties is needed to optimize pressure delivery for the duration of garment use.

Early cessation of pressure garment therapy results in scar contraction and thickening.

Pressure garment therapy is often prescribed to improve scar properties following full-thickness burn injuries. Pressure garment therapy is generally recommended for long periods of time following injury (1-2 years), though it is plagued by extremely low patient compliance. The goal of this study was to examine the effects of early cessation of pressure garment therapy on scar properties.

Effect of skin graft thickness on scar development in a porcine burn model.

Animal models provide a way to investigate scar therapies in a controlled environment. It is necessary to produce uniform, reproducible scars with high anatomic and biologic similarity to human scars to better evaluate the efficacy of treatment strategies and to develop new treatments. In this study, scar development and maturation were assessed in a porcine full-thickness burn model with immediate excision and split-thickness autograft coverage.

Direct conversion of injury-site myeloid cells to fibroblast-like cells of granulation tissue.

Inflammation, following injury, induces cellular plasticity as an inherent component of physiological tissue repair. The dominant fate of wound macrophages is unclear and debated. Here we show that two-thirds of all granulation tissue fibroblasts, otherwise known to be of mesenchymal origin, are derived from myeloid cells which are likely to be wound macrophages.

Effects of early combinatorial treatment of autologous split-thickness skin grafts in red duroc pig model using pulsed dye laser and fractional CO laser.

Background And Objective: The use of pulsed dye laser (PDL) and fractional CO (FX CO ) laser therapy to treat and/or prevent scarring following burn injury is becoming more widespread with a number of studies reporting reduction in scar erythema and pruritus following treatment with lasers. While the majority of studies report positive outcomes following PDL or FX CO therapy, a number of studies have reported no benefit or worsening of the scar following treatment. The objective of this study was to directly compare the efficacy of PDL, FX CO , and PDL + FX CO laser therapy in reducing scarring post burn injury and autografting in a standardized animal model.