Controlled‐Potential Electromechanical Reshaping of Cartilage

Hunter, Bryan M.; Kallick, Jeremy; Kissel, Jessica; Herzig, Maya; Manuel, Cyrus; Protsenko, Dmitri; Wong, Brian J. F.; Hill, Michael G.

doi:10.1002/anie.201600856

Cited by 14 publications

(23 citation statements)

References 26 publications

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“…Previous studies in our lab have demonstrated collagen structural change in the rabbit cartilage and pig skin [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26]. This study is the first to characterize the redoxinduced alteration in the optical and mechanical behavior in the human skin.…”

Section: Introductionmentioning

confidence: 75%

“…These ions create a steep pH gradient around the electrodes, which lead to localized stress relaxation and shape change, a process we refer to as electromechanical reshaping (EMR) [27,28]. Through a series of studies, we demonstrated the safety and efficacy of this approach to reshape cartilage [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26]. During these in vivo EMR studies in rabbits, changes in skin texture were incidentally observed around the non-insulated needle-insertion sites [12,15,24].…”

Section: Discussionmentioning

confidence: 99%

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Multiphoton Microscopy of Collagen Structure in Ex Vivo Human Skin Following Electrochemical Therapy

Hong

Toubat

et al. 2019

Lasers Surg Med

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Objectives Injury to healthy dermis and the dermoepidermal junction initiates a robust healing process consisting of fibrous tissue overgrowth, collagen deposition, and scar formation. The conventional management of scars and other skin injuries has largely relied upon surgical soft tissue transfer to resurface and/or replace damaged and dysmorphic tissue with new skin. However, these strategies are invasive, expensive, and may further exacerbate integumentary injury. In this study, we examine the creation of in situ redox generated pH changes in fresh human skin. We believe this process of “electrochemical therapy” (ECT) leads to changes in collagen matrix structure. Our objective is to map local tissue pH landscapes and image changes in collagen structure of non‐injured skin following ECT. Study Design Ex vivo human study involving ECT of human skin. Methods Remnant fresh ex vivo human facial skin from facelift operations was enveloped in saline‐soaked gauze for a maximum of 2 hours prior to ECT and imaging. ECT was performed by inserting platinum‐plated needle electrodes connected to a DC power supply. Voltage (4, 5, or 6 V) and time (3, 4, or 5 minutes) were varied systematically. High frequency ultrasound (25 MHz) was performed immediately after ECT on each sample. Treated samples were also imaged using multiphoton microscopy (MPM) with second harmonic generation (SHG) to specifically visualize collagen fibers in the dermis. The pH landscapes were mapped using indicator dyes in bisected specimens and the MPM images were compared with histologic findings. Results Above 4 V and 3 minutes, a profound reduction in dermal collagen SHG signal was observed at the anode. Although there was less blunting of SHG signal seen at the cathode, a decrease in the fluorescence of the dermoepidermal junction was observed. The pH application suggests ECT spatial selectivity and a direct relationship between voltage and application time. Ultrasound demonstrated gas formation between the anode and cathode, which is consistent with ECT's mechanism of action. Importantly, these electrochemical changes occurred without disrupting dermal and epidermal histologic architecture. Conclusion ECT alters tissue pH leading to dermal collagen structural change. These results offer additional insight into the translational potential of ECT to locally remodel the soft‐tissue matrix. Future directions aim to expand into a skin injury model to determine if similar collagen effects are observed in vivo. ECT is incredibly inexpensive (~$5) and may be a means to treat soft tissue injuries using simple needle‐based devices and DC battery power supplies. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

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Section: Introductionmentioning

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Multiphoton Microscopy of Collagen Structure in Ex Vivo Human Skin Following Electrochemical Therapy

Hong

Toubat

et al. 2019

Lasers Surg Med

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“…Although the concept of ECT is derived from previous studies 1,4,5,8,19,20 on electrochemical effects in cartilage, the present study characterizes the redox-induced alteration in the optical and mechanical behavior in skin. A previous study 1 suggests that the electrochemical reactions that are triggered are related to the hydrolysis of water, which produces a localized pH perturbation that drives hydrogen and hydroxide ions into the tissue. More than half a century of detailed clinical experience has already demonstrated how topical application of acid to the skin (ie, chemical peels) alters appearance and texture for beneficial effect.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies 1,17 have specifically examined the effects that surround the electrodes, including pH mapping in cartilage. Furthermore, other studies 4,8,20,28,29 have used EMR to mimic procedures that emulate the classic cut and suture operation ex vivo and in vivo.…”

Section: Discussionmentioning

confidence: 99%

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Association of Electrochemical Therapy With Optical, Mechanical, and Acoustic Impedance Properties of Porcine Skin

Moy

Chen

et al. 2017

JAMA Facial Plast Surg

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The classic management of burn scars and other injuries to the skin has largely relied on soft-tissue transfer to resurface damaged tissue with local tissue transfer or skin graft placement. In situ generation of electrochemical reactions using needle electrodes and an application of current may be a new approach to treat scars and skin.OBJECTIVE To examine the changes in optical, mechanical, and acoustic impedance properties in porcine skin after electrochemical therapy. DESIGN, SETTING, AND PARTICIPANTSThis preclinical pilot study, performed from August 1, 2015, to November 1, 2016, investigated the effects of localized pH-driven electrochemical therapy of ex vivo porcine skin using 24 skin samples. Platinum-plated needle electrodes were inserted into fresh porcine skin samples. A DC power supply provided a voltage of 4 to 5 V with a 3-minute application time. Specimens were analyzed using optical coherence tomography, optical coherence elastography, and ultrasonography. Ultrasonography was performed under 3 conditions (n = 2 per condition), optical coherence tomography was performed under 2 conditions (n = 2 per condition), and optical coherence elastography was performed under 2 conditions (n = 2 per condition). The remaining samples were used for the positive and negative control groups (n = 10).EXPOSURES Platinum-plated needle electrodes were inserted into fresh porcine skin samples. A DC power supply provided a voltage of 4 to 5 V with a 3-minute application.MAIN OUTCOMES AND MEASURES Tissue softening was observed at the anode and cathode sites as a result of electrochemical modification. Volumetric changes were noted using each optical and acoustic technique. RESULTS A total of 24 ex vivo porcine skin samples were used for this pilot study. Optical coherence tomography measured spatial distribution of superficial tissue changes around each electrode site. At 4 V for 3 minutes, a total volumetric effect of 0.47 mm 3 was found at the anode site and 0.51 mm 3 at the cathode site. For 5 V for 3 minutes, a total volumetric effect of 0.85 mm 3 was found at the anode site and 1.05 mm 3 at the cathode site. CONCLUSIONS AND RELEVANCEElectrochemical therapy is a low-cost technique that is on par with the costs of suture and scalpel. The use of electrochemical therapy to create mechanical and physiologic changes in tissue has the potential to locally remodel the soft-tissue matrix, which ultimately may lead to an inexpensive scar treatment or skin rejuvenation therapy.LEVEL OF EVIDENCE NA.

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An Engineered Protein Adhesive with Properties of Tissue Integration and Controlled Release for Efficient Cartilage Repair

Zhang

Zuo

et al. 2021

Adv Healthcare Materials

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Cartilage damage is a prevalent health concern among humans. The inertness of cartilage, the absence of self‐healing properties, and the lack of appropriate repair materials that integrate into the tissue pose a significant challenge for cartilage repair. Thus, it is important to develop novel soft biomaterials with strong tissue adhesion and chondrogenic capabilities for cartilage repair. Herein, a new type of protein adhesive is reported that exhibits superior cartilage repair performance. The material is fabricated by the electrostatic combination of chondroitin sulfate (CS) and positively charged elastin‐like protein, which is derived from natural components of the extracellular matrix (ECM). The adhesive showed robust adhesion properties on different tissue substrates, offering a favorable environment for cartilage tissue integration. Noncovalent bonding between CS molecules in the glue allows for its controlled release, which is required for efficient chondrogenic differentiation. When implanted into a rat model of cartilage defect, this protein adhesive exhibited beneficial healing effects, as evidenced by enhanced chondrogenesis, sufficient ECM production, and lateral integration. Therefore, this engineered protein complex is a promising candidate for translational application in the field of cartilage repair.

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Controlled‐Potential Electromechanical Reshaping of Cartilage

Cited by 14 publications

References 26 publications

Multiphoton Microscopy of Collagen Structure in Ex Vivo Human Skin Following Electrochemical Therapy

Multiphoton Microscopy of Collagen Structure in Ex Vivo Human Skin Following Electrochemical Therapy

Association of Electrochemical Therapy With Optical, Mechanical, and Acoustic Impedance Properties of Porcine Skin

An Engineered Protein Adhesive with Properties of Tissue Integration and Controlled Release for Efficient Cartilage Repair

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