The Contractile Phenotype of Dermal Fetal Fibroblasts in Scarless Wound Healing.

Purpose Of Review: Injured skin in the mammalian fetus can heal regeneratively due to the ability of fetal fibroblasts to effectively reorganize the extracellular matrix (ECM). This process occurs without fetal fibroblasts differentiating into highly contractile myofibroblasts which cause scarring and fibrosis in adult wounds. Here, we provide a brief review of fetal wound healing and the evidence supporting a unique contractile phenotype in fetal fibroblasts.

Role of steroids in acute phonotrauma: A basic science investigation.

Objectives/hypothesis: Steroids are used for the treatment of laryngitis in vocal performers and other individuals despite the absence of evidence demonstrating their impact on vocal fold inflammation. Our objective was to examine laryngeal secretion cytokine inflammatory profile changes associated with corticosteroid treatment in a human phonotrauma model.

Study Design: Prospective, individual, randomized, double-blinded, controlled trial.

Vocal exercise may attenuate acute vocal fold inflammation.

Objectives/hypotheses: The objective was to assess the utility of selected "resonant voice" (RV) exercises for the reduction of acute vocal fold inflammation. The hypothesis was that relatively large-amplitude, low-impact vocal fold exercises associated with RV would reduce inflammation more than spontaneous speech (SS) and possibly more than voice rest.

Study Design: The study design was prospective, randomized, and double blind.

Cyclooxygenase-2 inhibition for the prevention of subglottic stenosis.

Objective: To evaluate the role of targeted cyclooxygenase-2 inhibition in reducing scarring associated with a subglottic airway mucosal injury.

Design: Thirty-four New Zealand white rabbits underwent anterior cricothyroidotomy. Subglottic stenosis (SGS) was created by carbon dioxide laser injury.

Novel rat model of tympanostomy tube otorrhea.

Objective: Tympanostomy tube otorrhea (TTO), caused by the presence of pathogenic bacteria in the middle ear, is the most common complication of TT insertion. No studies have described a reproducible animal model of TTO. We aimed to develop a rat model of TTO which, in turn, could be used to assay the levels of TNF-α and IL-1β through the course of the infection.

Biosimulation of acute phonotrauma: an extended model.

Objectives/hypothesis: Personalized, preemptive, and predictive medicine is a central goal of contemporary medical care. The central aim of the present study was to investigate the utility of mechanistic computational modeling of inflammation and healing to address personalized therapy for patients with acute phonotrauma.

Study Design: Computer simulation.

Biosimulation of inflammation and healing in surgically injured vocal folds.

Objectives: The pathogenesis of vocal fold scarring is complex and remains to be deciphered. The current study is part of research endeavors aimed at applying systems biology approaches to address the complex biological processes involved in the pathogenesis of vocal fold scarring and other lesions affecting the larynx.

Methods: We developed a computational agent-based model (ABM) to quantitatively characterize multiple cellular and molecular interactions involved in inflammation and healing in vocal fold mucosa after surgical trauma.

Subglottic stenosis examined as a fibrotic response to airway injury characterized by altered mucosal fibroblast activity.

Objective: To investigate the association between mucosal fibroblast activity and subglottic stenosis (SGS) development.

Design: Prospective study of an animal model of SGS.

Setting: Academic research laboratory.

Translational systems biology and voice pathophysiology.

Objectives/hypothesis: Personalized medicine has been called upon to tailor healthcare to an individual's needs. Evidence-based medicine (EBM) has advocated using randomized clinical trials with large populations to evaluate treatment effects. However, due to large variations across patients, the results are likely not to apply to an individual patient.

Prostaglandin E2 is activated by airway injury and regulates fibroblast cytoskeletal dynamics.

Objectives/hypothesis: To characterize the activation of cyclooxygenase (COX)-2/prostaglandin (PG) E2 signaling during airway mucosal repair and its subsequent role during the wound healing process.

Study Design: Prospective animal study.

Methods: The subglottis was approached via cricothyroidotomy.

Repair of the tympanic membrane with urinary bladder matrix.

Objectives/hypothesis: To test urinary bladder matrix (UBM) as a potential treatment for tympanic membrane (TM) healing and regeneration.

Study Design: This prospective pilot study was designed to provide both qualitative and semiquantitative assessment of temporal and spatial healing events in the chinchilla model of chronic TM perforations with and without UBM patching.

Methods: Bilateral myringotomies were performed and repeated as necessary to create subtotal perforations over an 8-week period.

Prostaglandin E2 differentially regulates contraction and structural reorganization of anchored collagen gels by human adult and fetal dermal fibroblasts.

Contraction and remodeling of granulation tissue by fibroblasts is a crucial component of dermal wound healing. Postnatal wounds heal with imperfect repair and scar formation, whereas tissue repair in fetal wounds is regenerative. Prostaglandin E2 (PGE2) modulates the behavior of fibroblasts in the wound bed.

Delayed reepithelialization and basement membrane regeneration after wounding in mice lacking CXCR3.

Wound healing is a complex, orchestrated series of biological events that is controlled by extracellular components that communicate between cell types to re-establish lost tissue. We have found that signaling by ELR-negative CXC chemokines through their common CXCR3 receptor is critical for dermal maturation during the resolving phase. In addition there needs to be complete maturation of the epidermis and regeneration of a delineating basement membrane for proper functioning.

ELR-negative CXC chemokine CXCL11 (IP-9/I-TAC) facilitates dermal and epidermal maturation during wound repair.

In skin wounds, the chemokine CXCR3 receptor appears to play a key role in coordinating the switch from regeneration of the ontogenically distinct mesenchymal and epithelial compartments toward maturation. However, because CXCR3 equivalently binds four different ELR-devoid CXC chemokines (ie, PF4/CXCL4, IP-10/CXCL10, MIG/CXCL9, and IP-9/CXCL11), we sought to identify the ligand that coordinates epidermal coverage with the maturation of the underlying superficial dermis. Because CXCL11 (IP-9 or I-TAC) is produced by redifferentiating keratinocytes late in the regenerative phase when re-epithelialization is completed and matrix maturation ensues, we generated mice in which an antisense construct (IP-9AS) eliminated IP-9 expression during the wound-healing process.

A patient-specific in silico model of inflammation and healing tested in acute vocal fold injury.

The development of personalized medicine is a primary objective of the medical community and increasingly also of funding and registration agencies. Modeling is generally perceived as a key enabling tool to target this goal. Agent-Based Models (ABMs) have previously been used to simulate inflammation at various scales up to the whole-organism level.

Acute and chronic changes in the subglottis induced by graded carbon dioxide laser injury in the rabbit airway.

Objective: To investigate the repair process following carbon dioxide laser injury to the upper airway mucosa (UAM) during the development of chronic subglottic stenosis (SGS).

Design: Animals were assigned to either sham control (cricothyroidotomy only) or injured (cricothyroidotomy and posterior subglottic laser) groups using various carbon dioxide laser exposures (8, 12, and 16 W) for 4 seconds.

Subjects: Twenty-four New Zealand white rabbits.

Age-dependent differential expression of fibronectin variants in skin and airway mucosal wounds.

Objective: To delineate age-dependent and tissue-specific molecular activities of the variant-inclusion fibronectin transcripts in fetal and postnatal skin and airway mucosal wounds during early events of the wound healing process. Fibronectin is involved in multiple steps of the wound healing process. The functional complexity of fibronectin is carried through its protein diversity, which is controlled in part by alternative RNA splicing, a coordinated transcription and RNA processing.

Fetal dermal fibroblasts retain a hyperactive migratory and contractile phenotype under 2-and 3-dimensional constraints compared to normal adult fibroblasts.

Fetal dermal fibroblasts participate in a dramatically different wound healing process compared to their adult counterparts, and it is thought that their intrinsic phenotype contributes to the unique properties of fetal repair. In particular, fibroblast migratory and contractile properties have been shown to be important in the development or lack of fibrosis/scarring. Despite extensive study to date, and multiple experimental techniques utilized by various laboratories, the precise differences between fetal and adult dermal fibroblasts remain unclear.

Delayed and deficient dermal maturation in mice lacking the CXCR3 ELR-negative CXC chemokine receptor.

Replacement of wounded skin requires the initially florid cellular response to abate and even regress as the dermal layer returns to a relatively paucicellular state. The signals that direct this "stop and return" process have yet to be deciphered. CXCR3 chemokine receptor and its ligand CXCL11/IP-9/I-TAC are expressed by basal keratinocytes and CXCL10/IP-10 by keratinocytes and endothelial cells during wound healing in mice and humans.

Differential regulation of free-floating collagen gel contraction by human fetal and adult dermal fibroblasts in response to prostaglandin E2 mediated by an EP2/cAMP-dependent mechanism.

In contrast to fetal wound healing, dermal adult wound healing results in imperfect repair and scar formation. Fibroblasts are responsible for the contraction and remodeling of the wound matrix, which is influenced by inflammatory mediators including prostaglandin E2 (PGE2). This study addresses the mechanism by which PGE2 regulates contraction of collagen gels by human fetal and adult dermal fibroblasts.

Elucidating the role of interleukin 1beta and prostaglandin E2 in upper airway mucosal wound healing.

Objectives: To determine whether (1) inflammatory mediators IL-1beta (interleukin 1beta) and prostaglandin E2 (PGE2) in mucosal secretions correlate with subglottic mucosal injury; and (2) mucosal fibroblasts contribute to PGE2 production during mucosal healing.

Design: The subglottic mucosa in rabbits was wounded by means of varied carbon dioxide laser power and duration. Subglottic fibroblasts were exposed to IL-1beta and assayed for production of PGE2.