Safety of laser-generated shockwave treatment for bacterial biofilms in a cutaneous rodent model.

Bacterial biofilms are often found in chronically infected wounds. Biofilms protect bacteria from antibiotics and impair wound healing. Surgical debridement is often needed to remove the biofilm from an infected wound. Laser-generated shockwave (LGS) treatment is a novel tissue-sparing treatment for biofilm disruption. Previous studies have demonstrated that LGS is effective in disrupting biofilms in vitro. In this study, we aim to determine the safety threshold of the LGS technology in an in vivo rodent model. To understand the in vivo effects of LGS on healthy cutaneous tissue, the de-haired dorsal skin of Sprague-Dawley rats were treated with LGS at three different peak pressures (118, 296, 227 MPa). These pressures were generated using a 1064 nm Nd/YAG laser (pulse duration 5 ns and laser fluence of 777.9 mJ) with laser spot size diameters of 2.2, 3.0, and 4.2 mm, respectively. Following treatment, the animals were observed for 72 h, and a small subset was euthanized at 1-h, 24-h, and 72-h post-treatment and assessed for tissue injury or inflammation under histology. Each treatment group consisted of 9 rats (n = 3/time point for 1-h, 24-h, 72-h post-treatment). An additional 4 control (untreated) rats were included in the analysis, for a total of 31 animals. Gross injuries occurred in 21 (77%) animals and consisted of minor erythema, with prevalence positively correlated with peak pressure (p < 0.05). Of injuries under gross observation, 94% resolved within 24 h. Under histological analysis, the injuries and tissue inflammation were found to be localized to the epidermis and superficial dermis. LGS appears to be well tolerated by cutaneous tissue for the laser energy settings shown to be effective against bacterial biofilm in vitro. All injuries incurred, at even the highest peak pressures, were clinically mild and resolved within 1 day. This lends further support to the overall safety of LGS and serves to translate LGS towards in vivo efficacy studies.

Multi-Modal Haptic Feedback for Grip Force Reduction in Robotic Surgery.

Minimally invasive robotic surgery allows for many advantages over traditional surgical procedures, but the loss of force feedback combined with a potential for strong grasping forces can result in excessive tissue damage. Single modality haptic feedback systems have been designed and tested in an attempt to diminish grasping forces, but the results still fall short of natural performance. A multi-modal pneumatic feedback system was designed to allow for tactile, kinesthetic, and vibrotactile feedback, with the aims of more closely imitating natural touch and further improving the effectiveness of HFS in robotic surgical applications and tasks such as tissue grasping and manipulation. Testing of the multi-modal system yielded very promising results with an average force reduction of nearly 50% between the no feedback and hybrid (tactile and kinesthetic) trials (p < 1.0E-16). The multi-modal system demonstrated an increased reduction over single modality feedback solutions and indicated that the system can help users achieve average grip forces closer to those normally possible with the human hand.

Suture Breakage Warning System for Robotic Surgery.

As robotic surgery has increased in popularity, the lack of haptic feedback has become a growing issue due to the application of excessive forces that may lead to clinical problems such as intraoperative and postoperative suture breakage. Previous suture breakage warning systems have largely depended on visual and/or auditory feedback modalities, which have been shown to increase cognitive load and reduce operator performance. This work catalogues a new sensing technology and haptic feedback system (HFS) that can reduce instances of suture failure without negatively impacting performance outcomes including knot quality. Suture breakage is common in knot-tying as the pulling motion introduces prominent shear forces. A shear sensor mountable on the da Vinci robotic surgical system's Cadiere grasper detects forces that correlate to the suture's internal tension. HFS then provides vibration feedback to the operator as forces near a particular material's failure load. To validate the system, subjects tightened a total of four knots, two with the Haptic Feedback System (HFS) and two without feedback. The number of suture breakages were recorded and knot fidelity was evaluated by measuring knot slippage. Results showed that instances of suture failure were significantly reduced when HFS was enabled (p = 0.0078). Notably, knots tied with HFS also showed improved quality compared to those tied without feedback (p = 0.010). The results highlight the value of HFS in improving robotic procedure outcomes by reducing instances of suture failures, producing better knots, and reducing the need for corrective measures.

In-depth analysis of antibacterial mechanisms of laser generated shockwave treatment.

Background and Objectives Laser generated shockwave (LGS) is a novel modality for minimally invasive disruption of bacterial biofilms. The objectives of this study are to determine the mechanisms behind LGS treatment and non-biofilm effects on bacterial disruption, including (1) comparing bacterial load with and without LGS in its planktonic form and (2) estimating bacterial cell permeability following LGS. Study Design/Materials and Methods For the first study, planktonic S. epidermidis were treated with gentamicin (0, 8, 16, 32, 64 µg/ml) with and without LGS (1064 nm Nd:YAG laser, 110.14 mJ/mm2 , pulse duration 9 ns, spot size 3 mm, n = 8/group), and absorbances at 600 nm compared. For the second study, four samples of planktonic S. epidermidis were treated with LGS (same settings). Propidium iodide (PI) uptake via flow cytometry as a measure of cell permeability was measured at 0, 10, and 20 minutes following LGS. RESULTS: In comparing corresponding gentamicin concentrations within both LGS-treated samples and controls at 0 hours, there were no differences in absorbance (P = 0.923 and P = 0.814, respectively). Flow cytometry found modest PI uptake (10.4 ± 2.5%) immediately following LGS treatment, with time-dependent increase and persistence of the signal at 20 minutes (R2 = 0.449, P = 0.048). CONCLUSION: Taken together, LGS does not appear to have direct bacteriocidal properties, but rather by allowing for biofilm disruption and bacterial cell membrane permeabilization, both of which likely increase topical antibiotic delivery to pathogenic organisms. Insight into the mechanisms of LGS will allow for improved clinical applications and facilitate safe and effective translation of this technology. Lasers Surg. Med. © 2018 Wiley Periodicals, Inc.

Artificial palpation in robotic surgery using haptic feedback.

BACKGROUND: The loss of tactile feedback in minimally invasive robotic surgery remains a major challenge to the expanding field. With visual cue compensation alone, tissue characterization via palpation proves to be immensely difficult. This work evaluates a bimodal vibrotactile system as a means of conveying applied forces to simulate haptic feedback in two sets of studies simulating an artificial palpation task using the da Vinci surgical robot. METHODS: Subjects in the first study were tasked with localizing an embedded vessel in a soft tissue phantom using a single-sensor unit. In the second study, subjects localized tumor-like structures using a three-sensor array. In both sets of studies, subjects completed the task under three trial conditions: no feedback, normal force tactile feedback, and hybrid vibrotactile feedback. Recordings of correct localization, incorrect localization, and time-to-completion were used to evaluate performance outcomes. RESULTS: With the addition of vibrotactile and pneumatic feedback, significant improvements in the percentage of correct localization attempts were detected (p = 0.0001 and p = 0.0459, respectively) during the first experiment with phantom vessels. Similarly, significant improvements in correct localization were found with the addition of vibrotactile (p = 2.57E-5) and pneumatic significance (p = 8.54E-5) were observed in the second experiment involving tumor phantoms. CONCLUSIONS: This work demonstrates not only the superior benefits of a multi-modal feedback over traditional single-modality feedback, but also the effectiveness of vibration in providing haptic feedback to artificial palpation systems.

Characterization of perfused and sectioned liver tissue in a full indentation cycle using a visco-hyperelastic model.

Realistic modeling of biologic material is required for optimizing fidelity in computer-aided surgical training and assistance systems. The modeling of liver tissue has remained challenging due to its nonlinear viscoelastic properties and high hysteresis of the stress-strain relation. While prior studies have described the behavior of liver tissue during the loading status (in elongation, compression, or indentation tests) or unloading status (in stress relaxation or creep tests), a hysteresis curve with both loading and unloading processes was incompletely defined. We seek to use a single material model to characterize the mechanical properties of liver tissue in a full indentation cycle ex vivo perfused and then sectioned. Based on measurements taken from ex-vivo perfused porcine livers, we converted force-displacement curves to stress-strain curves and developed a visco-hyperelastic constitutive model to characterize the liver's mechanical behavior at different locations under various rates of indentation (1, 2, 5, 10, and 20 mm/s). The proposed model is a mixed visco-hyperelastic model with up to 6 coefficients. The normalized root mean square standard deviations of fitted curves are less than 5% and 10% in low (<0.05) and high strain (>0.3) conditions respectively.

Vibroacoustographic System for Tumor Identification.

Oral and head and neck squamous cell carcinoma (OSCC) is the sixth most common cancer worldwide. The primary management of OSCC relies on complete surgical resection of the tumor. Margin-free resection, however, is difficult given the devastating effects of aggressive surgery. Currently, surgeons determine where cuts are made by palpating edges of the tumor. Accuracy varies based on the surgeon's experience, the location and type of tumor, and the risk of damage to adjacent structures limiting resection margins. To fulfill this surgical need, we contrast tissue regions by identifying disparities in viscoelasticity by mixing two ultrasonic beams to produce a beat frequency, a technique termed vibroacoustography (VA). In our system, an extended focal length of the acoustic stress field yields surgeons' high resolution to detect focal lesions in deep tissue. VA offers 3D imaging by focusing its imaging plane at multiple axial cross-sections within tissue. Our efforts culminate in production of a mobile VA system generating image contrast between normal and abnormal tissue in minutes. We model the spatial direction of the generated acoustic field and generate images from tissue-mimicking phantoms and ex vivo specimens with squamous cell carcinoma of the tongue to qualitatively demonstrate the functionality of our system. These preliminary results warrant additional validation as we continue clinical trials of ex vivo tissue. This tool may prove especially useful for finding tumors that are deep within tissue and often missed by surgeons. The complete primary resection of tumors may reduce recurrence and ultimately improve patient outcomes.

Intraocular robotic interventional surgical system (IRISS): Semi-automated OCT-guided cataract removal.

BACKGROUND: With the development of laser-assisted platforms, the outcomes of cataract surgery have been improved by automating several procedures. The cataract-extraction step continues to be manually performed, but due to deficiencies in sensing capabilities, surgical complications such as posterior capsule rupture and incomplete cataract removal remain. METHODS: An optical coherence tomography (OCT) system is integrated into our intraocular robotic interventional surgical system (IRISS) robot. The OCT images are used for preoperative planning and intraoperative intervention in a series of automated procedures. Real-time intervention allows surgeons to evaluate the progress and override the operation. RESULTS: The developed system was validated by performing lens extraction on 30 postmortem pig eyes. Complete lens extraction was achieved on 25 eyes, and "almost complete" extraction was achieved on the remainder due to an inability to image small lens particles behind the iris. No capsule rupture was found. CONCLUSION: The IRISS successfully demonstrated semiautomated OCT-guided lens removal with real-time supervision and intervention.

Detection of surgical margins in oral cavity cancer: the role of dynamic optical contrast imaging.

PURPOSE OF REVIEW: The quantity of tissue removed during an oncologic surgical procedure is not standardized and there are numerous reports of local recurrence despite histologically adequate resection margins. The oral cavity is one of the sites in the head and neck with high chances of recurrence following negative margins. To address this need, this article reviews the recent applications of Dynamic Optical Contrast Imaging (DOCI) towards both oral screening and the intraoperative evaluation of tumor margins in head and neck surgery. RECENT FINDINGS: Human ex-vivo and in-vivo trials suggest DOCI is well tolerated, low-cost, and sensitive for differentiating cancerous from normal tissues throughout the head and neck, in addition to the oral cavity. Ex-vivo imaging of OSCC specimens generated histologically verified image contrast. Furthermore, in-vivo intraoperative results demonstrate significant potential for image-guided detection and resection of oral cavity squamous cell carcinoma (OSCC). SUMMARY: DOCI augments tissue contrast and may enable surgeons to clinically screen patients for oral cancer, make histologic evaluations in vivo with fewer unnecessary biopsies, delineate clinical margins for tumor resection, provide guidance in the choice of biopsy sites, and preserve healthy tissue to increase the postoperative functionality and quality of life of the patient.

Optical System Design for Noncontact, Normal Incidence, THz Imaging of in vivo Human Cornea.

Reflection mode Terahertz (THz) imaging of corneal tissue water content (CTWC) is a proposed method for early, accurate detection and study of corneal diseases. Despite promising results from ex vivo and in vivo cornea studies, interpretation of the reflectivity data is confounded by the contact between corneal tissue and dielectric windows used to flatten the imaging field. Herein, we present an optical design for non-contact THz imaging of cornea. A beam scanning methodology performs angular, normal incidence sweeps of a focused beam over the corneal surface while keeping the source, detector, and patient stationary. A quasioptical analysis method is developed to analyze the theoretical resolution and imaging field intensity profile. These results are compared to the electric field distribution computed with a physical optics analysis code. Imaging experiments validate the optical theories behind the design and suggest that quasioptical methods are sufficient for designing of THz corneal imaging systems. Successful imaging operations support the feasibility of non-contact in vivo imaging. We believe that this optical system design will enable the first, clinically relevant, in vivo exploration of CTWC using THz technology.

THz imaging system for in vivo human cornea.

Terahertz (THz) imaging of corneal tissue water content (CTWC) is a proposed method for early, accurate detection and study of corneal diseases. Despite promising results from ex vivo and in vivo cornea studies, interpretation of the reflectivity data is confounded by the contact between corneal tissue and rigid dielectric window used to flatten the imaging field. This work develops a novel imaging system and image reconstruction methods specifically for nearly spherical targets such as human cornea. A prototype system was constructed using a 650 GHz multiplier source and Schottky diode detector. Resolution and imaging field strength measurement from characterization targets correlate well with those predicted by the quasioptical theory and physical optics analysis. Imaging experiments with corneal phantoms and ex vivo corneas demonstrate the hydration sensitivity of the imaging system and reliable measurement of CTWC. We present successful acquisition of non-contact THz images of in vivo human cornea, and discuss strategies for optimizing the imaging system design for clinical use.

Grasper integrated tri-axial force sensor system for robotic minimally invasive surgery.

This paper describes the design, microfabrication, and characterization of a miniature force sensor for providing tactile feedback in robotic surgical systems. We demonstrate for the first time a microfabricated sensor that can provide triaxial sensing (normal, x-shear, y-shear) in a single sensor element that can be integrated with commercial robotic surgical graspers. Features of this capacitive force sensor include differential sensing in the shear directions as well as a design where all electrical connections are on one side, leaving the backside pristine as the sensing face. The sensor readout is performed by a custom-designed printed circuit board with 24-bit resolution. Experimental results of sensor performance show normal force resolution of 0.055 N, x-shear resolution of 0.25 N, and y-shear resolution of 1.45 N, all of which fall in a range of clinically relevant forces.

Laser-generated shockwaves enhance antibacterial activity against biofilms in vitro.

BACKGROUND AND OBJECTIVES: Bacterial biofilm formation within chronic wound beds, which provides an effective barrier against antibiotics, is a known cause of recalcitrant infections and a significant healthcare burden, often requiring repeated surgical debridements. Laser-generated shockwaves (LGS) is a novel, minimally invasive, and nonthermal modality for biofilm mechanical debridement which utilizes compressive stress waves, generated by photonic absorption in thin titanium films to mechanically disrupt the biofilm. Prior studies have demonstrated LGS monotherapy to be selectively efficacious for biofilm disruption and safe for host tissues. In this study, we sought to determine if LGS can enhance the antimicrobial activity and biofilm disruption capability of topical antibiotic therapy. STUDY DESIGN/MATERIALS AND METHODS: Staphylococcus epidermidis biofilms grown in vitro on glass were treated with topical gentamicin (31, 62, and 124 µg/ml) with and without LGS (n = 3-11/treatment group). Mechanical shockwaves were generated with a 1,064 nm Nd:YAG laser (laser fluence 110.14 mJ/mm2 , pulse duration 5 ns, spot size 3 mm). Following a 24-hour incubation period, bacterial viability was assessed by determining the number of colony-forming units (CFU) via the Miles and Misra method. Residual biofilm bioburden was analyzed using the crystal violet biofilm assay. RESULTS: With gentamicin monotherapy, CFU density (CFU/mm2 ) at 31, 62, and 124 µg/ml were (282 ± 84) × 104 , (185 ± 34) × 104 , and (113 ± 9) × 104 , respectively. With LGS and gentamicin therapy, CFU density decreased to (170 ± 44) × 104 , (89 ± 24) × 104 , and (43 ± 3) × 104 , respectively (P = 0.1704, 0.0302, and 0.0004 when compared with gentamicin alone). Biofilm burden as measured by the assay in the gentamicin 31, 62, and 124 µg/ml groups was reduced by 80%, 95%, and 98% when LGS was added (P = 0.0102, >0.0001, and 0.0001 for all groups when compared with gentamicin alone). Furthermore, samples treated with LGS saw an increase in susceptibility to gentamicin, in terms of reduced biofilm bioburden and CFU densities. CONCLUSION: LGS enhances the efficacy of topical antibiotics in an in vitro model. This has significant implications for clinical applications in the management of chronic soft tissue infections and recalcitrant chronic rhinosinusitis. Lasers Surg. Med. 49:539-547, 2017. © 2017 Wiley Periodicals, Inc.

Terahertz Imaging of Cutaneous Edema: Correlation With Magnetic Resonance Imaging in Burn Wounds.

OBJECTIVE: In vivo visualization and quantification of edema, or 'tissue swelling' following injury, remains a clinical challenge. Herein, we investigate the ability of reflective terahertz (THz) imaging to track changes in tissue water content (TWC)-the direct indicator of edema-by comparison to depth-resolved magnetic resonance imaging (MRI) in a burn-induced model of edema. METHODS: A partial thickness and full thickness burns were induced in an in vivo rat model to elicit unique TWC perturbations corresponding to burn severity. Concomitant THz surface maps and MRI images of both burn models were acquired with a previously reported THz imaging system and T2-weighted MRI, respectively, over 270 min. Reflectivity was analyzed for the burn contact area in THz images, while proton density (i.e., mobile TWC) was analyzed for the same region at incrementally increasing tissue depths in companion, transverse MRI images. A normalized cross correlation of THz and depth-dependent MRI measurements was performed as a function of time in histologically verified burn wounds. RESULTS: For both burn types, strong positive correlations were evident between THz reflectivity and MRI data analyzed at greater tissue depths (>258 µm). MRI and THz results also revealed biphasic trends consistent with burn edema pathogenesis. CONCLUSION: This paper offers the first in vivo correlative assessment of mobile TWC-based contrast and the sensing depth of THz imaging. SIGNIFICANCE: The ability to implement THz imaging immediately following injury, combined with TWC sensing capabilities that compare to MRI, further support THz sensing as an emerging tool to track fluid in tissue.

Non-invasive terahertz imaging of tissue water content for flap viability assessment.

Accurate and early prediction of tissue viability is the most significant determinant of tissue flap survival in reconstructive surgery. Perturbation in tissue water content (TWC) is a generic component of the tissue response to such surgeries, and, therefore, may be an important diagnostic target for assessing the extent of flap viability in vivo. We have previously shown that reflective terahertz (THz) imaging, a non-ionizing technique, can generate spatially resolved maps of TWC in superficial soft tissues, such as cornea and wounds, on the order of minutes. Herein, we report the first in vivo pilot study to investigate the utility of reflective THz TWC imaging for early assessment of skin flap viability. We obtained longitudinal visible and reflective THz imagery comparing 3 bipedicled flaps (i.e. survival model) and 3 fully excised flaps (i.e. failure model) in the dorsal skin of rats over a postoperative period of 7 days. While visual differences between both models manifested 48 hr after surgery, statistically significant (p < 0.05, independent t-test) local differences in TWC contrast were evident in THz flap image sets as early as 24 hr. Excised flaps, histologically confirmed as necrotic, demonstrated a significant, yet localized, reduction in TWC in the flap region compared to non-traumatized skin. In contrast, bipedicled flaps, histologically verified as viable, displayed mostly uniform, unperturbed TWC across the flap tissue. These results indicate the practical potential of THz TWC sensing to accurately predict flap failure 24 hours earlier than clinical examination.

Tensile strength and failure load of sutures for robotic surgery.

BACKGROUND: Robotic surgical platforms have seen increased use among minimally invasive gastrointestinal surgeons (von Fraunhofer et al. in J Biomed Mater Res 19(5):595-600, 1985. doi: 10.1002/jbm.820190511 ). However, these systems still suffer from lack of haptic feedback, which results in exertion of excessive force, often leading to suture failures (Barbash et al. in Ann Surg 259(1):1-6, 2014. doi: 10.1097/SLA.0b013e3182a5c8b8 ). This work catalogs tensile strength and failure load among commonly used sutures in an effort to prevent robotic surgical consoles from exceeding identified thresholds. Trials were thus conducted on common sutures varying in material type, gauge size, rate of pulling force, and method of applied force. METHODS: Polydioxanone, Silk, Vicryl, and Prolene, gauges 5-0 to 1-0, were pulled till failure using a commercial mechanical testing system. 2-0 and 3-0 sutures were further tested for the effect of pull rate on failure load at rates of 50, 200, and 400 mm/min. 3-0 sutures were also pulled till failure using a da Vinci robotic surgical system in unlooped, looped, and at the needle body arrangements. RESULTS: Generally, Vicryl and PDS sutures had the highest mechanical strength (47-179 kN/cm2), while Silk had the lowest (40-106 kN/cm2). Larger diameter sutures withstand higher total force, but finer gauges consistently show higher force per unit area. The difference between material types becomes increasingly significant as the diameters decrease. Comparisons of identical suture materials and gauges show 27-50% improvement in the tensile strength over data obtained in 1985 (Ballantyne in Surg Endosc Other Interv Tech 16(10):1389-1402, 2002. doi: 10.1007/s00464-001-8283-7 ). No significant differences were observed when sutures were pulled at different rates. Reduction in suture strength appeared to be strongly affected by the technique used to manipulate the suture. CONCLUSIONS: Availability of suture tensile strength and failure load data will help define software safety protocols for alerting a surgeon prior to suture failure during robotic surgery. Awareness of suture strength weakening with direct instrument manipulation may lead to the development of better techniques to further reduce intraoperative suture breakage.

Engineering A11 Minibody-Conjugated, Polypeptide-Based Gold Nanoshells for Prostate Stem Cell Antigen (PSCA)-Targeted Photothermal Therapy.

Currently, there is no curative treatment for advanced metastatic prostate cancer, and options, such as chemotherapy, are often nonspecific, harming healthy cells and resulting in severe side effects. Attaching targeting ligands to agents used in anticancer therapies has been shown to improve efficacy and reduce nonspecific toxicity. Furthermore, the use of triggered therapies can enable spatial and temporal control over the treatment. Here, we combined an engineered prostate cancer-specific targeting ligand, the A11 minibody, with a novel photothermal therapy agent, polypeptide-based gold nanoshells, which generate heat in response to near-infrared light. We show that the A11 minibody strongly binds to the prostate stem cell antigen that is overexpressed on the surface of metastatic prostate cancer cells. Compared to nonconjugated gold nanoshells, our A11 minibody-conjugated gold nanoshell exhibited significant laser-induced, localized killing of prostate cancer cells in vitro. In addition, we improved upon a comprehensive heat transfer mathematical model that was previously developed by our laboratory. By relaxing some of the assumptions of our earlier model, we were able to generate more accurate predictions for this particular study. Our experimental and theoretical results demonstrate the potential of our novel minibody-conjugated gold nanoshells for metastatic prostate cancer therapy.

Visual-perceptual mismatch in robotic surgery.

BACKGROUND: The principal objective of the experiment was to analyze the effects of the clutch operation of robotic surgical systems on the performance of the operator. The relative coordinate system introduced by the clutch operation can introduce a visual-perceptual mismatch which can potentially have negative impact on a surgeon's performance. We also assess the impact of the introduction of additional tactile sensory information on reducing the impact of visual-perceptual mismatch on the performance of the operator. METHODS: We asked 45 novice subjects to complete peg transfers using the da Vinci IS 1200 system with grasper-mounted, normal force sensors. The task involves picking up a peg with one of the robotic arms, passing it to the other arm, and then placing it on the opposite side of the view. Subjects were divided into three groups: aligned group (no mismatch), the misaligned group (10 cm z axis mismatch), and the haptics-misaligned group (haptic feedback and z axis mismatch). Each subject performed the task five times, during which the grip force, time of completion, and number of faults were recorded. RESULTS: Compared to the subjects that performed the tasks using a properly aligned controller/arm configuration, subjects with a single-axis misalignment showed significantly more peg drops (p = 0.011) and longer time to completion (p < 0.001). Additionally, it was observed that addition of tactile feedback helps reduce the negative effects of visual-perceptual mismatch in some cases. Grip force data recorded from grasper-mounted sensors showed no difference between the different groups. CONCLUSIONS: The visual-perceptual mismatch created by the misalignment of the robotic controls relative to the robotic arms has a negative impact on the operator of a robotic surgical system. Introduction of other sensory information and haptic feedback systems can help in potentially reducing this effect.

Polypeptide-Based Gold Nanoshells for Photothermal Therapy.

Targeted killing of cancer cells by engineered nanoparticles holds great promise for noninvasive photothermal therapy applications. We present the design and generation of a novel class of gold nanoshells with cores composed of self-assembled block copolypeptide vesicles with photothermal properties. Specifically, poly(L-lysine)60- block-poly(L-leucine)20 (K60L20) block copolypeptide vesicles coated with a thin layer of gold demonstrate enhanced absorption of light due to surface plasmon resonance (SPR) in the near-infrared range. We show that the polypeptide-based K60L20 gold nanoshells have low toxicity in the absence of laser exposure, significant heat generation upon exposure to near-infrared light, and, as a result, localized cytotoxicity within the region of laser irradiation in vitro. To gain a better understanding of our gold nanoshells in the context of photothermal therapy, we developed a comprehensive mathematical model for heat transfer and experimentally validated this model by predicting the temperature as a function of time and position in our experimental setup. This model can be used to predict which parameters of our gold nanoshells can be manipulated to improve heat generation for tumor destruction. To our knowledge, our results represent the first ever use of block copolypeptide vesicles as the core material of gold nanoshells.

Laser-Generated Shockwaves as a Treatment to Reduce Bacterial Load and Disrupt Biofilm.

OBJECTIVE: The goal of this paper is to demonstrate and evaluate the potential efficacy of laser-generated shockwave (LGS) therapy on biofilm infected tissue. METHODS: To demonstrate proof of concept, Staphylococcus epidermidis was allowed to proliferate on ex vivo pigskin, until mature biofilm formation was achieved, and then subjected to LGS. Bacterial load between control and treated samples was compared using the swab technique and colony counting. Scanning electron microscopy (SEM) was then used to visualize the biofilm growth and resulting reduction in biofilm coverage from treatment. Images were false colored to improve contrast of biofilm, and percent biofilm coverage was computed, along with biofilm cluster size. RESULTS: LGS reduced bacterial load by 69% (p = 0.008). Imaging showed biofilm coverage reduced by 52% and significantly reduced average cluster size (p 0.001). CONCLUSION: LGS therapy reduced the burden of bacterial biofilm on ex vivo pigskin and can be visualized using SEM imaging. SIGNIFICANCE: LGS therapy is a new treatment for infected wounds, allowing rapid disruption of biofilm to 1) remove bacteria and 2) increase susceptibility of remaining biofilm to topical antibiotics. This can lead to improved wound healing times, reduced patient morbidity, and decreased healthcare costs.