Publications by authors named "Hainsworth Shin"

The specific topography of biomaterials plays an important role in their biological interactions with cells and thus the safety of medical implants. Antifouling materials can be engineered with topographic features to repel microbes. Meanwhile, undesired topographies of implants can cause complications such as breast implant-associated anaplastic large cell lymphoma (BIA-ALCL).

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Nitinol is a nickel-titanium alloy widely used in medical devices for its unique pseudoelastic and shape-memory properties. However, nitinol can release potentially hazardous amounts of nickel, depending on surface manufacturing yielding different oxide thicknesses and compositions. Furthermore, nitinol medical devices can be implanted throughout the body and exposed to extremes in pH and reactive oxygen species (ROS), but few tools exist for evaluating nickel release under such physiological conditions.

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Recent reports of adverse health effects (e.g., capsular contracture, lymphoma) linked to the absence or presence of texture on soft-tissue implants (e.

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The developers of medical devices evaluate the biocompatibility of their device prior to FDA's review and subsequent introduction to the market. Chemical characterization, described in ISO 10993-18:2020, can generate information for toxicological risk assessment and is an alternative approach for addressing some biocompatibility end points (e.g.

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Leukocytes (neutrophils, monocytes) in the active circulation exhibit multiple phenotypic indicators for a low level of cellular activity, like lack of pseudopods and minimal amounts of activated, cell-adhesive integrins on their surfaces. In contrast, before these cells enter the circulation in the bone marrow or when they recross the endothelium into extravascular tissues of peripheral organs they are fully activated. We review here a multifaceted mechanism mediated by fluid shear stress that can serve to deactivate leukocytes in the circulation.

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The skin is a barrier and part of the immune system that protects us from harmful bacteria. Because indwelling medical devices break this barrier, they greatly increase the risk of infection by microbial pathogens. To study how these infections can be prevented through improved clinical practices and medical device technology, it is important to have preclinical models that replicate the early stages of microbial contamination, ingress, and colonization leading up to infection.

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As the demand for organ transplants continues to grow faster than the supply of available donor organs, a new source of functional organs is needed. High resolution high throughput 3D bioprinting is one approach towards generating functional organs for transplantation. For high throughput printing, the need for increased print resolutions (by decreasing printing nozzle diameter) has a consequence: it increases the forces that cause cell damage during the printing process.

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Lymphatic malformations (LMs) are disfiguring congenital anomalies characterized by aberrant growth of lymphatic vessels. They are broadly categorized histopathologically as macrocystic and microcystic. Although sclerotherapy has shown some success in the treatment of macrocystic malformations, there has been less progress with developing treatment strategies for microcystic malformations.

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There is compelling evidence that circulatory hemodynamics prevent neutrophil activation, including adhesion to microvessels, in the microcirculation. However, the underlying mechanism or mechanisms by which that mechanoregulation occurs remain unresolved. Here, we report evidence that exposure to fluid shear stress (FSS) promotes neutrophils to release cathepsin B (ctsB) and that this autocrine regulatory event is antiadhesive for neutrophils on endothelial surfaces through Mac1-selective regulation.

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A flow-through electroporation system, based on a novel nanoporous membrane/electrode design, for the delivery of cell wall-impermeant molecules into model leukocytes, HL-60 promyelocytes, was demonstrated. The ability to apply low voltages to cell populations, with nm-scale concentrated electric field in a periodic array, contributes to high cell viability. With applied biases of 1-4V, delivery of target molecules was achieved with 90% viability and up to 65% transfection efficiency.

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Cell-based therapies are emerging as the next frontier of medicine, offering a plausible path forward in the treatment of many devastating diseases. Critically, current methods for antigen positive cell sorting lack a high throughput method for delivering ultrahigh purity populations, prohibiting the application of some cell-based therapies to widespread diseases. Here we show the first use of targeted, protective polymer coatings on cells for the high speed enrichment of cells.

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Activated neutrophils have been reported to affect peripheral resistance, for example, by plugging capillaries or adhering to the microvasculature. In vivo and ex vivo data indicate that activated neutrophils circulating in the blood also influence peripheral resistance. We used viscometry and microvascular mimics for in vitro corroboration.

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PEG hydrogels are routinely used in immunoprotection applications to hide foreign cells from a host immune system. Size-dependent transport is typically exploited in these systems to prevent access by macromolecular elements of the immune system while allowing the transport of low molecular weight nutrients. This work studies a nanoscale hydrogel coating for improved transport of beneficial low molecular weight materials across thicker hydrogel coatings while completely blocking transport of undesired larger molecular weight materials.

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Objective: Shear stress-induced pseudopod retraction is an anti-inflammatory measure that minimizes neutrophil activity and is regulated by membrane cholesterol. We tested the hypothesis that a hypercholesterolemic impairment of shear mechanotransduction alters the neutrophil flow behavior leading to microvascular dysfunction.

Approach And Results: We examined the shear effects on the flow behavior of human leukocytes.

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Many vasculature-related diseases affecting skeletal muscle function have been studied in mouse models. Noninvasive quantification of muscle blood flow responses during postocclusive reactive hyperemia (PORH) is often used to evaluate vascular function in human skeletal muscles. However, blood flow measurements during PORH in small skeletal muscles of mice are rare due to the lack of appropriate technologies coupled with the challenge of measurement setup resulting from the lack of large enough test sites.

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Failure of soft tissue implants has been largely attributed to the influence of biomaterial surface properties on the foreign body response, but some implant complications, e.g. macrophage accumulation and necrosis, are still not effectively addressed with surface treatments to minimize deleterious biomaterial effects.

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Previous studies showed that exposure of neutrophils to shear stress induces cysteine protease-mediated shedding of surface CD18 integrins involved in leukocyte-platelet interactions. Based on this, we hypothesized that, under noninflamed conditions, shear-induced CD18 cleavage is a control mechanism to minimize spontaneous leukocyte-platelet binding. For this purpose, we characterized the influence of shear on CD18 surface expression and platelet binding by the different leukocyte subsets.

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A significant barrier to the success of engineered tissues is the inadequate transport of nutrients and gases to, and waste away from, cells within the constructs, after implantation. Generation of microtubular networks by endothelial cells in engineered constructs to mimic the in vivo transport scheme is essential for facilitating tissue survival by promoting the in vitro formation of microvessels that integrate with host microvasculature, after implantation. Previously, we reported that select pressures stimulate endothelial proliferation involving protubulogenic molecules such as fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor-C (VEGF-C).

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Continuous exposure of polymorphonuclear leukocytes (PMNLs) to circulatory hemodynamics points to fluid flow as a biophysical regulator of their activity. Specifically, fluid flow-derived shear stresses deactivate leukocytes via actions on the conformational activities of proteins on the cell surface. Because membrane properties affect activities of membrane-bound proteins, we hypothesized that changes in the physical properties of cell membranes influence PMNL sensitivity to fluid shear stress.

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Physiological fluid shear stress evokes pseudopod retraction in normal leukocytes by a mechanism that involves the formyl peptide receptor (FPR) as mechanosensor. In hypertensives, such as the spontaneously hypertensive rat (SHR), leukocytes lack the normal fluid shear response. The increased activity of matrix metalloproteinases (MMPs, including MMP-9) in SHR plasma is associated with cleavage of several cell membrane receptors.

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We review recent evidence which suggests that leukocytes in the circulation and in the tissue may readily respond to physiological levels of fluid shear stress in the range between about 1 and 10 dyn/cm 2, a range that is below the level to achieve a significant passive, viscoelastic response. The response of activated neutrophilic leukocytes to fluid shear consists of a rapid retraction of lamellipodia with membrane detachment from integrin binding sites. In contrast, a subgroup of non-activated neutrophils may project pseudopods after exposure to fluid shear stress.

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Surface membrane expression and conformational activation of CD18 integrins into an open molecular configuration play critical roles in neutrophil ligand binding, membrane attachment, spreading on the endothelium, and cell migration to sites of inflammation. Previously, we observed pseudopod retraction and concomitant cleavage of CD18 by human neutrophils upon exposure to fluid shear stress. But the underlying cellular mechanism(s) linking these phenomena remains unknown.

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Vascular endothelial cells sense and respond to pressure by molecular mechanism(s) which, to date, remain poorly understood. The present study investigated basic fibroblast growth factor (bFGF) signaling as a putative mechanotransduction pathway involved in the proliferative responses of human umbilical vein endothelia cells (HUVECs) to 60/20 mm Hg cyclic pressure at 1 Hz for 24 h. Under these conditions, the enhanced proliferative response of these HUVECs was not associated with an increased synthesis/release of bFGF, but involved rapid (within 30 min from the onset of exposure to pressure) tyrosine phosphorylation of the bFGF receptor, FGFR-2.

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Mechanical forces modulate endothelial cell functions through several mechanisms including regulation of gene transcription. In the present study, gene transcription by human umbilical vein endothelial cells (HUVEC) either maintained under control pressure (that is, standard cell culture conditions equivalent to 0.15 mmHg sustained hydrostatic pressure) or exposed to 60/20 mmHg sinusoidal pressures at 1 Hz were compared using Affymetrix GeneChip microarrays to identify cellular/molecular mechanisms associated with endothelial cell responses to cyclic pressure.

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The present study investigated the proliferative and apoptotic responses of human umbilical vein endothelial cells (HUVECs) to well-defined, sinusoidal pressures (60/20, 100/60, and 140/100 mm Hg/mm Hg) at 1 Hz for up to 24 h under Media 199 containing either 1% FBS and 0.04% bovine brain extract (BBE) (low serum/growth factor conditions) or 10% FBS and 0.4% BBE (normal serum/growth factor conditions).

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