Weak tissue adhesion remains a major challenge in clinical translation of microneedle patches. Mimicking the structural features of honeybee stingers, stiff polymeric microneedles with unidirectionally backward-facing barbs were fabricated and embedded into various elastomer films to produce self-interlocking microneedle patches. The spirality of the barbing pattern was adjusted to increase interlocking efficiency. In addition, the micro-bleeding caused by microneedle puncturing adhered the porous surface of the patch substrate to the target tissue via coagulation. In the demonstrative application of myocardial infarction treatment, the bioinspired microneedle patches firmly fixed on challenging beating hearts, significantly reduced cardiac wall stress and strain in the infarct, and maintained left ventricular function and morphology. In addition, the microneedle patch was minimally invasively implanted onto beating porcine heart in 10 minutes, free of sutures and adhesives. Therefore, the honeybee stinger-inspired microneedles could provide an adaptive and convenient means to implant patches for various medical applications. STATEMENT OF SIGNIFICANCE: Adhesion between tissue and microneedle patches with smooth microneedles is usually weak. We introduce a novel barbing method of fabricating unidirectionally backward facing barbs with controllable spirality on the microneedles on microneedle patches. The microneedle patches self-interlock on mechanically dynamic beating hearts, similar to honeybee stingers. The micro-bleeding and coagulation on the porous surface provide additional adhesion force. The microneedle patches attenuate left ventricular remodeling via mechanical support and are compatible with minimally invasive implantation.

Journal of Cardiovascular ElectrophysiologyVolume 13, Issue 3 p. 265-266 Pathologic Basis of Conduction Disturbances: The Challenge to Move Beyond Microscopic Anatomy JEFFREY E. SAFFITZ M.D., Ph.D., JEFFREY E. SAFFITZ M.D., Ph.D. *Department of Pathology and Immunology and the Center for Cardiovascular Research, Washington University School of Medicine, St. Louis, MissouriSearch for more papers by this authorSTARR R. KAPLAN M.D., STARR R. KAPLAN M.D. *Department of Pathology and Immunology and the Center for Cardiovascular Research, Washington University School of Medicine, St. Louis, MissouriSearch for more papers by this author JEFFREY E. SAFFITZ M.D., Ph.D., JEFFREY E. SAFFITZ M.D., Ph.D. *Department of Pathology and Immunology and the Center for Cardiovascular Research, Washington University School of Medicine, St. Louis, MissouriSearch for more papers by this authorSTARR R. KAPLAN M.D., STARR R. KAPLAN M.D. *Department of Pathology and Immunology and the Center for Cardiovascular Research, Washington University School of Medicine, St. Louis, MissouriSearch for more papers by this author First published: 12 August 2003 https://doi.org/10.1046/j.1540-8167.2002.00265.x Address for correspondence: Jeffrey E. Saffitz tz, M.D., Ph.D., Department of Pathology and Immunology, Box 8118, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110. Fax: 314-362-4096; E-mail: [email protected] J Cardiovasc Electrophysiol, Vol. 13, pp. 265–266, March 2002. AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article. Volume13, Issue3March 2002Pages 265-266 RelatedInformation

Use of fenfluramines, either alone or co-administered with phentermine (“fen-phen”) as anorexic agents in obesity, has been associated with the development of clinically significant cardiac valve disease. We present the macroscopic and histologic findings in cardiac valves explanted from three patients who presented with valvular disease after fenfluramine or fenfluramine-phentermine use and underwent single valve replacement surgery. Paraffin sections were prepared with hematoxylin and eosin, trichrome, elastic–van Gieson, and Giemsa stains, as well as immunostains using antibody to CD3 and CD20. All three patients (two females, ages 37 and 43, and a 49-year-old male) developed progressively symptomatic mitral (2 patients) or aortic (1 patient) valvular insufficiency following dexfenfluramine (2 patients) or fenfluramine-phentermine (1 patient) use. Macroscopic changes included irregular leaflet thickening, accompanied by chordal fusion in the mitral valves, but without vegetations, commissural fusion, or evidence of annular dilation. Histologically, fibromyxoid plaques and nodules just below the valve surface, superficial to a generally intact elastic fiber layer, were associated with CD3-positive lymphocytes. Valves from all three patients had central myxoid degenerative changes, which were focal/mild in one mitral valve, diffuse/moderate in one mitral valve, and diffuse/marked in one aortic valve. Focal areas of superficial fibromyxoid change or intimal thickening may also be seen in cardiac valves from patients with drug-unrelated processes leading to symptomatic or asymptomatic valvulopathy. Therefore, when valve tissue is available for histopathologic examination, valvular disease can be attributed to use of fenfluramines only if the following criteria are satisfied: (i) the macroscopic and microscopic features are consistent with fenfluramine-related valvulopathy, (ii) clinical, echocardiographic, and intraoperative findings support the diagnosis, and (iii) the history of drug exposure predates the development or exacerbation of valvular dysfunction.

Gap junction number and size vary widely in cardiac tissues with disparate conduction properties. Little is known about how tissue-specific patterns of intercellular junctions are established and regulated. To elucidate the relationship between gap junction channel protein expression and the structure of gap junctions, we analyzed Cx43 +/- mice, which have a genetic deficiency in expression of the major ventricular gap junction protein, connexin43 (Cx43). Quantitative confocal immunofluorescence microscopy revealed that diminished Cx43 signal in Cx43 +/- mice was due almost entirely to a reduction in the number of individual gap junctions (226 +/- 52 vs. 150 +/- 32 individual gap junctions/field in Cx43 +/+ and +/- ventricles, respectively; P < 0.05). The mean size of an individual gap junction was the same in both groups. Immunofluorescence results were confirmed with electron microscopic morphometry. Thus when connexin expression is diminished, ventricular myocytes become interconnected by a reduced number of large, normally sized gap junctions, rather than a normal number of smaller junctions. Maintenance of large gap junctions may be an adaptive response supporting safe ventricular conduction.