Bending the rules: a novel approach to placement and retrospective experience with the 5 French Arndt endobronchial blocker in children <2 years.

BACKGROUND: One-lung ventilation (OLV) is frequently employed to improve surgical exposure during video-assisted thoracoscopic surgery (VATS) and thoracotomy in adults and children. Because of their small size, children under the age of 2 years are not candidates for some of the methods typically used for OLV in adults and older children, such as a double-lumen endotracheal (DLT) tube or intraluminal use of a bronchial blocker. Due to this, the clinician is left with few options. One of the most robust approaches to OLV in infants and small children has been the extraluminal placement of a 5 French (5F) Arndt endobronchial blocker (AEB). AIM: The aim of this retrospective study was to examine and describe our experience with placement and management of an extraluminal 5F AEB for thoracic surgery in children <2 years of age. METHODS: We retrospectively examined the anesthetic records for details of AEB placement, arterial blood gas (ABG) data, and intraoperative analgesic prescription in 15 children under the age of 2 years undergoing OLV with a 5F AEB for thoracic surgery at our institution from January 2010 through January 2016. RESULTS: We were able to successfully achieve lung isolation in 14 of 15 patients using a 5F AEB that was bent 35-45° 1.5 cm proximal to the inflatable cuff. In 13 of 15 patients, we were able to place the AEB into final position with the aid of video-assisted fiberoptic bronchoscopy. In two patients, fluoroscopy was required to place the 5F AEB into the left mainstem due to poor visualization of the carina and rapid desaturation during bronchoscopy. In one of these patients, even though the blocker appeared to be correctly placed by fluoroscopy, adequate lung isolation was not observed. Intraoperatively, we observed significant degrees of hypercarbia in most patients without oxygen desaturation. Analgesic regimens lacked consistency and varied among patients. Open thoracotomy procedures tended to receive more aggressive narcotic regimens than video-assisted thoracoscopic surgery (VATS) procedures. Fourteen of 15 patients were extubated in the immediate postoperative period. CONCLUSIONS: Our technique of placing a 35-45° bend in the AEB, extraluminal placement, and observed manipulation with a video-assisted flexible fiberoptic bronchoscope (FFB) within the trachea can be used to achieve consistent lung isolation in patients <2 undergoing thoracic surgery. When the use of a FFB proves unsuccessful, fluoroscopy can provide an alternative solution to successful placement. Significant respiratory derangements without long-term sequelae will occur in a majority of these patients during OLV. Several different approaches to intraoperative analgesia did not impede extubation in the early postoperative period.

Simple Technique for Microscopic Evaluation of Active Cellular Invasion into 3D Hydrogel Constructs.

Materials that are evaluated for bioengineering purposes are carefully tested to evaluate cellular interactions with respect to biocompatibility and in some cases cell differentiation. A key perspective that is often considered is the ability for decellularized synthetic or natural based matrices to facilitate cell migration or tissue ingrowth. Current methods of measuring cell migration range from simple scratch assays to Boyden chamber inserts and fluorescent imaging of seeded spheroids. Many of these methods require tissue processing for histological analysis and fixing and staining for imaging, which can be difficult and dependent on the stability of the hydrogel subject. Herein we present a simple platform that can be manufactured using 3D printing and easily applied to in vitro cell culture, allowing the researcher to image live cellular migration into a cellular materials. We found this to be an adaptable, cheap, and replicable technique to evaluate cellular interaction that has applications in the research and development of hydrogels for tissue engineering purposes.

The lubricating effect of iPS-reprogrammed fibroblasts on collagen-GAG scaffolds for cartilage repair applications.

Tissue engineering products, like collagen-glycosaminoglycan scaffolds, have been successfully applied to chondrogenic defects. Inducible Pluripotent Stem cell (iPS) technology allows reprograming of somatic cells into an embryonic-like state, allowing for redifferentiation. We postulated that a fibroblast cell line (BJ cells - 'pre-iPSF') cycled through iPS reprogramming and redifferentiated into fibroblasts (post-iPSF) could lubricate collagen-glycosaminoglycan scaffolds; fibroblasts are known to produce lubricating molecules (e.g., lubricin) in the synovium. Herein, we quantified the coefficient of friction (CoF) of collagen-glycosaminoglycan scaffolds seeded with post-iPSF; tested whether cell-free scaffolds made of post-iPSF derived extracellular matrix had reduced friction vs. pre-iPSF; and assessed lubricin quantity as a possible protein responsible for lubrication. Post-iPSF seeded CG had 6- to 10-fold lower CoF versus pre-iPSF. Scaffolds consisting of a collagen and pre-/post-iPSF extracellular matrix blend outperformed these cell-seeded scaffolds (~5-fold lower CoF), yielding excellent CoF values close to synovial fluid. Staining revealed an increased presence of lubricin within post-iPSF scaffolds (confirmed by western blotting) and on the surface of iPSF-seeded collagen-glycosaminoglycan scaffolds. Interestingly, when primary cells from patient biopsy-derived fibroblasts were used, iPS reprogramming did not further reduce the already low CoF of these cells and no lubricin expression was found. We conclude that iPS reprogramming activates lubricating properties in iPS-derived cells in a source cell-specific manner. Additionally, lubricin appears to play a lubricating role, yet other proteins also contribute to lubrication. This work constitutes an important step for understanding post-iPSF lubrication of scaffolds and its potential for cartilage tissue engineering.

Synergistic use of biomaterials and licensed therapeutics to manipulate bone remodelling and promote non-union fracture repair.

Disrupted bone metabolism can lead to delayed fracture healing or non-union, often requiring intervention to correct. Although the current clinical gold standard bone graft implants and commercial bone graft substitutes are effective, they possess inherent drawbacks and are limited in their therapeutic capacity for delayed union and non-union repair. Research into advanced biomaterials and therapeutic biomolecules has shown great potential for driving bone regeneration, although few have achieved commercial success or clinical translation. There are a number of therapeutics, which influence bone remodelling, currently licensed for clinical use. Providing an alternative local delivery context for these therapies, can enhance their efficacy and is an emerging trend in bone regenerative therapeutic strategies. This review aims to provide an overview of how biomaterial design has advanced from currently available commercial bone graft substitutes to accommodate previously licensed therapeutics that target local bone restoration and healing in a synergistic manner, and the challenges faced in progressing this research towards clinical reality.

Functionalising Collagen-Based Scaffolds With Platelet-Rich Plasma for Enhanced Skin Wound Healing Potential.

Porous collagen-glycosaminoglycan (collagen-GAG) scaffolds have shown promising clinical results for wound healing; however, these scaffolds do not replace the dermal and epidermal layer simultaneously and rely on local endogenous signaling to direct healing. Functionalizing collagen-GAG scaffolds with signaling factors, and/or additional matrix molecules, could help overcome these challenges. An ideal candidate for this is platelet-rich plasma (PRP) as it is a natural reservoir of growth factors, can be activated to form a fibrin gel, and is available intraoperatively. We tested the factors released from PRP (PRPr) and found that at specific concentrations, PRPr enhanced cell proliferation and migration and induced angiogenesis to a greater extent than fetal bovine serum (FBS) controls. This motivated us to develop a strategy to successfully incorporate PRP homogeneously within the pores of the collagen-GAG scaffolds. The composite scaffold released key growth factors for wound healing (FGF, TGFß) and vascularization (VEGF, PDGF) for up to 14 days. In addition, the composite scaffold had enhanced mechanical properties (when compared to PRP gel alone), while providing a continuous upper surface of extracellular matrix (ECM) for keratinocyte seeding. The levels of the factors released from the composite scaffold were sufficient to sustain proliferation of key cells involved in wound healing, including human endothelial cells, mesenchymal stromal cells, fibroblasts, and keratinocytes; even in the absence of FBS supplementation. In functional in vitro and in vivo vascularization assays, our composite scaffold demonstrated increased angiogenic and vascularization potential, which is known to lead to enhanced wound healing. Upon pro-inflammatory induction, macrophages released lower levels of the pro-inflammatory marker MIP-1α when treated with PRPr; and released higher levels of the anti-inflammatory marker IL1-ra upon both pro- and anti-inflammatory induction when treated with the composite scaffold. Finally, our composite scaffold supported a co-culture system of human fibroblasts and keratinocytes that resulted in an epidermal-like layer, with keratinocytes constrained to the surface of the scaffold; by contrast, keratinocytes were observed infiltrating the PRP-free scaffold. This novel composite scaffold has the potential for rapid translation to the clinic by isolating PRP from a patient intraoperatively and combining it with regulatory approved scaffolds to enhance wound repair.