Modern diagnostics is pivoting towards
less invasive health monitoring in dermal interstitial
fluid, rather than blood or urine. However, the skin’s
outermost layer, the stratum corneum, makes accessing
the fluid more difficult without invasive, needle-based technology.
Simple, minimally invasive means for surpassing
this hurdle are needed. Methods: To address this problem,
a flexible, Band-Aid-like patch for sampling interstitial
fluid was developed and tested. This patch uses simple
resistive heating elements to thermally porate the stratum
corneum, allowing the fluid to exude from the deeper
skin tissue without applying external pressure. Fluid is
then transported to an on-patch reservoir through selfdriving
hydrophilic microfluidic channels. Results: Testing
with living, ex-vivo human skin models demonstrated
the device’s ability to rapidly collect sufficient interstitial
fluid for biomarker quantification. Further, finite-element
modeling showed that the patch can porate the stratum
corneum without raising the skin’s temperature to paininducing
levels in the nerve-laden dermis. Conclusion:
Relying only on simple, commercially scalable fabrication
methods, this patch outperforms the collection rate of
various microneedle-based patches, painlessly sampling a
human bodily fluid without entering the body. Significance:
The technology holds potential as a clinical device for an
array of biomedical applications, especially with the integration
of on-patch testing.
more »
« less
A Multifunctional Origami Patch for Minimally Invasive Tissue Sealing
For decades, bioadhesive materials have garnered great attention due to their potential to replace sutures and staples for sealing tissues during minimally invasive surgical procedures. However, the complexities of delivering bioadhesives through narrow spaces and achieving strong adhesion in fluid‐rich physiological environments continue to present substantial limitations to the surgical translation of existing sealants. In this work, a new strategy for minimally invasive tissue sealing based on a multilayer bioadhesive patch, which is designed to repel body fluids, to form fast, pressure‐triggered adhesion with wet tissues, and to resist biofouling and inflammation is introduced. The multifunctional patch is realized by a synergistic combination of three distinct functional layers: i) a microtextured bioadhesive layer, ii) a dynamic, blood‐repellent hydrophobic fluid layer, and iii) an antifouling zwitterionic nonadhesive layer. The patch is capable of forming robust adhesion to tissue surfaces in the presence of blood, and exhibits superior resistance to bacterial adhesion, fibrinogen adsorption, and in vivo fibrous capsule formation. By adopting origami‐based fabrication strategies, it is demonstrated that the patch can be readily integrated with a variety of minimally invasive end effectors to provide facile tissue sealing in ex vivo porcine models, offering new opportunities for minimally invasive tissue sealing in diverse clinical scenarios.
more » « less- Award ID(s):
- 1935291
- NSF-PAR ID:
- 10452205
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Advanced Materials
- Volume:
- 33
- Issue:
- 11
- ISSN:
- 0935-9648
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
more » « less
Abstract Interstitial fluid (ISF) that surrounds cells in tissues of the body is a novel source of biomarker that complements conventional sources like blood, urine, and saliva. To overcome difficulties in harvesting ISF, a minimally invasive, rapid, simple‐to‐use, cost‐effective method is developed to collect ISF from the skin involving a microneedle (MN) patch. By pressing 650 µm long MNs at an angle just below the skin surface, blood‐free ISF flows through micropores to the skin surface and is absorbed into a thin strip of paper on the MN patch backing for subsequent analysis. An optimized method in rat skin in vivo is well tolerated and able to collect >2 µL of ISF within 1 min. Brief skin pretreatment with MNs followed by a 5 min delay dramatically increases subsequent ISF collection by a mechanism believed to involve increased skin hydration. ISF collection using an MN patch has the potential to simplify access to biomarkers in ISF for research and future medical diagnostic and monitoring applications.
-
more » « less
Bioadhesives such as tissue adhesives, hemostatic agents, and tissue sealants have potential advantages over sutures and staples for wound closure, hemostasis, and integration of implantable devices onto wet tissues. However, existing bioadhesives display several limitations including slow adhesion formation, weak bonding, low biocompatibility, poor mechanical match with tissues, and/or lack of triggerable benign detachment. Here, we report a bioadhesive that can form instant tough adhesion on various wet dynamic tissues and can be benignly detached from the adhered tissues on demand with a biocompatible triggering solution. The adhesion of the bioadhesive relies on the removal of interfacial water from the tissue surface, followed by physical and covalent cross-linking with the tissue surface. The triggerable detachment of the bioadhesive results from the cleavage of bioadhesive’s cross-links with the tissue surface by the triggering solution. After it is adhered to wet tissues, the bioadhesive becomes a tough hydrogel with mechanical compliance and stretchability comparable with those of soft tissues. We validate in vivo biocompatibility of the bioadhesive and the triggering solution in a rat model and demonstrate potential applications of the bioadhesive with triggerable benign detachment in ex vivo porcine models.
-
more » « less
Combining the specificity of tumor‐targeting bacteria with the sensitivity of biomarker detection would create a screening method able to detect small tumors and metastases. To create this system, we genetically modified an attenuated strain of
Salmonella enterica to release a recombinant fluorescent biomarker (or fluoromarker).Salmonella expressing ZsGreen were intravenously administered to tumor‐bearing mice and fluoromarker production was induced after 48 hr. The quantities and locations of bacteria and ZsGreen were measured in tumors, livers and spleens by immunofluorescence, and the plasma concentration of ZsGreen was measured using single‐layer ELISA. In the plasma, the ZsGreen concentration was in the range of 0.5–1.5 ng/ml and was dependent on tumor mass (with a proportion of 0.81 ± 0.32 ng·ml−1·g−1). No adverse reaction to ZsGreen or bacteria was observed in any mice. ZsGreen was released at an average rate of 4.3 fg·CFU−1·hr−1and cleared from the plasma with a rate constant of 0.259 hr−1. ZsGreen production was highest in viable tissue (7.6 fg·CFU−1·hr−1) and lowest in necrotic tissue (0.47 fg·CFU−1·hr−1). The mass transfer rate constant from tumor to blood was 0.0125 hr−1. Based on these measurements, this system has the capability to detect tumors as small as 0.12 g. These results demonstrate four essential mechanisms of this method: (i ) preferential tumor colonization by bacteria, (ii ) fluoromarker releasein vivo , (iii ) fluoromarker transport through tumor tissue and (iv ) slow enough systemic clearance to enable measurement. This bacteria‐based blood test would be minimally invasive and has the potential to identify previously undetectable microscopic tumors. -
more » « less
Abstract Current suture‐based surgical techniques used to repair torn rotator cuff tendons do not result in mechanically competent tendon‐to‐bone attachments, leading to high postoperative failure rates. Although adhesives have been proposed to protect against sutures tearing through tendon during healing, no currently available adhesive meets the clinical needs of adhesive strength, biocompatibility, and promotion of healing. Here, a biocompatible, graded, 3,4‐dihydroxy phenyl chitosan (BGC) bioadhesive designed to meet these needs is presented. Although 3,4‐dihydroxy phenyl chitosan (DP‐chitosan) bioadhesives are biocompatible, their adhesion strength is low; soluble oxidants or cross‐linking agents can be added for higher bonding strength, but this sacrifices biocompatibility. These challenges are overcome by developing a periodate‐modified ion exchange resin‐bead filtration system that oxidizes catechol moieties to quinones and filters off the activating agent and resin. The resulting BGC bioadhesive exhibited sixfold higher strength compared to commercially available tissue adhesives, with strength in the range necessary to improve tendon‐to‐bone repair (≈1MPa, ≈20% of current suture repair strength). The bioadhesive is biocompatible and promoted tenogenesis; cells exposed to the bioadhesive demonstrated enhanced expression of collagen I and the tenogenic marker Scx. Results demonstrated that the bioadhesive has the potential to improve the strength of a tendon‐to‐bone repair and promote healing.
