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.

Biological attributes required for epidermal regeneration: Evaluation of the next-generation autologous cell harvesting device.

Early wound intervention and closure is critical for reducing infection and improving aesthetic and functional outcomes for patients with acute burn wounds and nonthermal full-thickness skin defects. Treatment of partial-thickness burns or full-thickness injuries with autologous skin cell suspension (ASCS) achieves robust wound closure while limiting the amount of donor skin compared with standard autografting. A Next Generation Autologous Cell Harvesting Device (NG-ACHD) was developed to standardize the preparation process for ASCS to ensure biological attributes are obtained known to correlate with well-established safety and performance data.

Safety of bempedoic acid in patients at high cardiovascular risk and with statin intolerance.

Background: Bempedoic acid is an oral adenosine triphosphate citrate lyase (ACL) inhibitor that lowers low-density lipoprotein cholesterol (LDL-C) blood levels. The Cholesterol Lowering via Bempedoic acid, an ACL-Inhibiting Regimen (CLEAR) Outcomes study demonstrated that bempedoic acid reduced cardiovascular (CV) risk in patients at high risk for CV events who were unwilling or unable to take guideline-recommended doses of statins.

Objective: To describe detailed safety information from CLEAR Outcomes, including events in the United States (US) prescribing information based on previous phase 3 hyperlipidemia studies.

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.

A role for vitamin D and the vitamin D receptor in keloid disorder.

Keloids are disfiguring fibroproliferative lesions that can occur in susceptible individuals following any skin injury. They are extremely challenging to treat, with relatively low response rates to current therapies and high rates of recurrence after treatment. Although several distinct genetic loci have been associated with keloid formation in different populations, there has been no single causative gene yet identified and the molecular mechanisms guiding keloid development are incompletely understood.

Injectable pulverized electrospun poly(lactic-co-glycolic acid) fibers improve human adipose tissue engraftment and volume retention.

Autologous adipose tissue is commonly used for tissue engraftment for the purposes of soft tissue reconstruction due to its relative abundance in the human body and ease of acquisition using liposuction methods. This has led to the adoption of autologous adipose engraftment procedures that allow for the injection of adipose tissues to be used as a "filler" for correcting cosmetic defects and deformities in soft tissues. However, the clinical use of such methods has several limitations, including high resorption rates and poor cell survivability, which lead to low graft volume retention and inconsistent outcomes.

Scar Management and Dyschromia: A Summary Report from the 2021 American Burn Association State of the Science Meeting.

Burn scars, and in particular, hypertrophic scars, are a challenging yet common outcome for survivors of burn injuries. In 2021, the American Burn Association brought together experts in burn care and research to discuss critical topics related to burns, including burn scars, at its State of the Science conference. Clinicians and researchers with burn scar expertise, as well as burn patients, industry representatives, and other interested stakeholders met to discuss issues related to burn scars and discuss priorities for future burn scar research.

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.

Myofibroblasts Are Not Characteristic Features of Keloid Lesions.

Unlabelled: Keloids are disfiguring, scar-like lesions that are challenging to treat, with low response rates to current interventions and frequent recurrence. It has been widely reported that keloids are characterized by myofibroblasts, specialized contractile fibroblasts that express alpha-smooth muscle actin (α-SMA). However, evidence supporting a role for myofibroblasts in keloid pathology is inconclusive, with conflicting reports in the literature.

Advantages and Disadvantages of Using Small and Large Animals in Burn Research: Proceedings of the 2021 Research Special Interest Group.

Multiple animal species and approaches have been used for modeling different aspects of burn care, with some strategies considered more appropriate or translatable than others. On April 15, 2021, the Research Special Interest Group of the American Burn Association held a virtual session as part of the agenda for the annual meeting. The session was set up as a pro/con debate on the use of small versus large animals for application to four important aspects of burn pathophysiology: burn healing/conversion, scarring, inhalation injury, and sepsis.

Titanium as a Possible Modifier of Inflammation Around Dental Implants.

Purpose: The exact etiopathogenesis of peri-implant diseases remains unclear. While significant information on molecular markers is available, studies on biomarkers related to possible biocorrosion are sparse. This study aimed to evaluate periimplant crevicular fluid (PICF) for possible titanium (Ti) contamination and explore associations between clinical findings, inflammatory mediators, and Ti levels.

Isolation and feeder-free primary culture of four cell types from a single human skin sample.

Four types of primary cells-dermal fibroblasts, dermal microvascular endothelial cells, epidermal keratinocytes, and epidermal melanocytes-can be isolated simultaneously from a single human skin sample, without the use of xenogeneic murine feeder cells. This protocol describes the procedures for isolation of these cells from adult full-thickness skin obtained from surgical discard tissue. The cells isolated using this protocol contain stem cell populations and are competent to form functional skin tissue in three-dimensional reconstructed skin models.

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.

Mechanomodulation of Burn Scarring Via Pressure Therapy.

The physical and psychological sequalae of burn injuries account for 10 million disability-adjusted life years lost annually. Hypertrophic scarring (HSc) after burn injury results in reduced mobility, contracture, pain, itching, and aesthetic changes for burn survivors. Despite the prevalence of scarring and the number of scar therapies available, none are highly effective at preventing HSc after burn injury.

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.

Early Intervention in Ischemic Tissue with Oxygen Nanocarriers Enables Successful Implementation of Restorative Cell Therapies.

Background: Tissue ischemia contributes to necrosis and infection. While angiogenic cell therapies have emerged as a promising strategy against ischemia, current approaches to cell therapies face multiple hurdles. Recent advances in nuclear reprogramming could potentially overcome some of these limitations.

Scalable Biomimetic Coaxial Aligned Nanofiber Cardiac Patch: A Potential Model for "Clinical Trials in a Dish".

Recent advances in cardiac tissue engineering have shown that human induced-pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) cultured in a three-dimensional (3D) micro-environment exhibit superior physiological characteristics compared with their two-dimensional (2D) counterparts. These 3D cultured hiPSC-CMs have been used for drug testing as well as cardiac repair applications. However, the fabrication of a cardiac scaffold with optimal biomechanical properties and high biocompatibility remains a challenge.