Literatura académica sobre el tema "Wound healing monitoring"

Wound healing is one of the most complex processes in the human body, supported by many cellular events that are tightly coordinated to repair the wound efficiently. Chronic wounds have potentially life-threatening consequences. Traditional wound dressings come in direct contact with wounds to help them heal and avoid further complications. However, traditional wound dressings have some limitations. These dressings do not provide real-time information on wound conditions, leading clinicians to miss the best time for adjusting treatment. Moreover, the current diagnosis of wounds is relatively subjective. Wearable electronics have become a unique platform to potentially monitor wound conditions in a continuous manner accurately and even to serve as accelerated healing vehicles. In this review, we briefly discuss the wound status with some objective parameters/biomarkers influencing wound healing, followed by the presentation of various novel wearable devices used for monitoring wounds and accelerating wound healing. We further summarize the associated device working principles. This review concludes by highlighting some major challenges in wearable devices toward wound healing that need to be addressed by the research community.

Continuous health monitoring often requires hospitalization, which can become an expensive and inconvenient choice for the patient. In this perspective, wearable sensors that allow in situ biosensing constitute a very promising technology. This work aims to develop immunosensors for continuous monitoring of the wound healing process, based on pH changes, as well as on the concentrations of inflammatory proteins such as the C-reactive protein (CRP). Sensing principles include the use of responsive hydrogels that swell in response to changes in the surroundings, and the use of functional surfaces that specifically recognize the target protein. The detection principle is based on an optical signal, using the evanescent field of light propagating along a waveguide, probing refractive index changes. An optical sensing system that can be integrated in a wound dressing patch has been designed, including a white light source (LED), and a spectrometer for detection. The sensor was successfully tested in the laboratory with biological samples (blood serum), demonstrating reversible pH measurements between pH 6-8, and detection of changes in the concentration of CRP between 1 and 100 μg/ml. The sensor will later be integrated into wound dressings or bandages, forming a sensing patch that is connected via optical fibres and electrical wires to the detection system and power supply. This novel technology will be particularly valuable in applications such as the supervision of skin grafts and ulcer treatments.

Skin wounds either minor or chronic may heal up with different time durations. But, this time duration of healing could not be easily predicted as healing is affected by different factors, e.g., age, nutrition, medication, and surroundings. Despite these factors, wound characteristic also plays a role in the healing process. Wound characteristics include wound size, wound type, internal and external wound environment, body temperature, body oxygenation, wound hydration, and infection. Therefore, monitoring of wound healing also required careful consideration of wound characteristics. Although the healthcare domain contains many applications for detection and monitoring of diseases, the wound care domain requires efficient techniques and sensing systems for the identification of wound biomarkers such as temperature, blood pressure, oxygen, and infection status of wound using biosensors. In the current research, we provide a wound care solution based on a biosensor-based sensing system to measure basic biomarkers, considered as major wound characteristics, i.e., body temperature and body oxygenation, and design a fuzzy inference system to predict their effect on wound hydration, which ultimately recommends necessary actions to boost healing.

(1) Abstract: Wound monitoring is an essential aspect in the evaluation of wound healing. This can be carried out with the multidimensional tool HELCOS, which develops a quantitative analysis and graphic representation of wound healing evolution via imaging. It compares the area and tissues present in the wound bed. This instrument is used for chronic wounds in which the healing process is altered. This article describes the potential use of this tool to improve the monitoring and follow-up of wounds and presents a case series of various chronic wounds with diverse etiology treated with an antioxidant dressing. (2) Methods: A secondary analysis of data from a case series of wounds treated with an antioxidant dressing and monitored with the HELCOS tool. (3) Results: The HELCOS tool is useful for measuring changes in the wound area and identifying wound bed tissues. In the six cases described in this article, the tool was able to monitor the healing of the wounds treated with the antioxidant dressing. (4) Conclusions: the monitoring of wound healing with this multidimensional HELCOS tool offers new possibilities to facilitate treatment decisions by healthcare professionals.

Skin wound healing is influenced by two kinds of environment i.e., exterior environment that is nearby to wound surface and interior environment that is the environment of the adjacent part under wound surface. Both types of environment play a vital role in wound healing, which may contribute to continuous or impaired wound healing. Although, different previous studies provided wound care solutions, but they focused on single environmental factors either wound moisture level, pH value or healing enzymes. Practically, it is insignificant to consider environmental effect by determination of single factors or two, as both types of environment contain a lot of other factors which must be part of investigation e.g., smoke, air pollution, air humidity, temperature, hydrogen gases etc. Also, previous studies didn’t classify overall healing either as continuous or impaired based on exterior environment effect. In current research work, we proposed an effective wound care solution based on exterior environment monitoring system integrated with Neural Network Model to consider exterior environment effect on wound healing process, either as continuous or impaired. Current research facilitates patients by providing them intelligent wound care solution to monitor and control wound healing at their home.

Early identification of infection is imperative in the management of chronic wounds in preventing limb threatening events. There is a clear requirement for the development of in situ sensors that can monitor the healing progress of chronic wounds and identify the early onset of infection, providing the clinician with a more detailed picture of the wound dynamics. A variety of carbon composite materials were employed for use in wound monitoring technologies. The mechanical flexibility of the polyethylene and polycarbonate films are ideal for incorporation within existing dressing materials and could be produced in bulk at relatively low cost, a pre-requisite given the frequency with which dressings need to be replaced. Surface modification of the films through laser ablation and electrochemical anodisation was required to enhance the sensor's electroanalytical performance and improve both the selectivity and sensitivity towards uric acid - a key wound biomarker used to assess the wound physiology through measuring both the wound pH and wound severity. A preliminary assessment of the films performance in simulated wound fluid and defibrinated horse blood was conducted. A prototype smart bandage was designed, based on interfacing the carbon film to a portable potentiostat, and the response to urate and potential interferences assessed. The sensing strategies developed were adapted in order to facilitate the monitoring of central venous catheters which are also subject to the complications of infection. Carbon fibre filaments were selected as the core substrates for the sensing electrode due to their dimensional characteristics and as such could be easily integrated within existing catheter architectures.

Leader cells are a fundamental biological process that have only been investigated since the early 2000s. These cells have often been observed emerging at the edge of an artificial wound in 2D epithelial cell collective invasion, created with either a mechanical scrape from a pipette tip or from the removal of a plastic, physical blocker. During migration, the moving cells maintain cell-cell contacts, an important quality of collective migration; the leader cells originate from either the first or the second row, they increase in size compared to other cells, and they establish ruffled lamellipodia. Recent studies in 3D have also shown that cells emerging from an invading collective group that also exhibit leader-like properties. Exactly how leader cells influence and interact with follower cells as well as other cells types during collective migration, however, is another matter, and is a subject of intense investigation between many different labs and researchers. The majority of leader cell research to date has involved epithelial cells, but as collective migration is implicated in many different pathogenic diseases, such as cancer and wound healing, a better understanding of leader cells in many cell types and environments will allow significant improvement to therapies and treatments for a wide variety of disease processes. In fact, more recent studies on collective migration and invasion have broadened the field to include other cell types, including mesenchymal cancer cells and fibroblasts. However, the proper technology for picking out dynamic, single cells within a moving and changing cell population over time has severely limited previous investigation into leader cell formation and influence over other cells. In line with these previous studies, we not only bring new technology capable of dynamically monitoring leader cell formation, but we propose that leader cell behavior is more than just an epithelial process, and that it is a critical physiological process in multiple cell types and diseases.

碩士
長庚大學
電機工程學系
101
Fractional photo-thermolysis induced by ablative fractional lasers (AFLs) or non-ablative fractional lasers (NAFLs) can remodel the skin, regenerate collagen, and remove tumor tissue. However, fractional laser treatments may result in severe side effects, and multiple treatments are required to achieve the expected outcome. Thus, the downtime and treatment outcome after fractional laser treatments are key issues to consider when developing a treatment strategy. In this study, an optical coherence tomography (OCT) system was implemented for in vivo studies of wound healing after AFL and NAFL treatments. According to the OCT scanning results, the laser-induced micro-thermal zones (MTZs) could also be morphologically identified and quantitatively evaluated. To continue monitoring the wound healing process, the treated regions were scanned using OCT at different time points, and the en-face images at various tissue depths were extracted from three-dimensional OCT images. Furthermore, to quantitatively evaluate the morphological changes at different tissue depths during wound healing, an algorithm was developed to distinguish the backscattering properties of untreated and treated tissues. The results showed that the coagulation damage induced by the NAFLs could be rapidly healed in 6 days. In contrast, the tissue volatilization induced by AFLs required a longer recovery time of 14 days. In conclusion, this study establishes the feasibility of this methodology as a means of clinically monitoring treatment outcomes and wound healing after fractional laser treatments.

碩士
國立陽明大學
醫學工程研究所
100
Abstract Previous studies evidence that transforming growth factor-beta (TGF-β) could induce breast carcinoma cells to activate down-stream signaling pathways, resulting in cellular changes on facilitating invasion and metastasis in vivo. The purpose of this study is to monitor and examine the effects of transforming growth factor-beta on cell micromotion and wound migration of two of specific lines of human breast carcinoma cells, the non-invasive cells named MCF-7 and the invasive cells called MDA-MB-231. MCF-7 and MDA-MB-231 cells were treated with fixed concentrations of TGF-β for different time periods and the effects on cell migration with time-dependent treatment would be analyzed. In this study Electric Cell-substrate Impedance Sensing (ECIS) technique was applied to examine the electrical resistance of the cells cultured on micro-electrodes. This approach offers quantification of cell migration activity in response to drugs via morphological changes of the cell layers, including junctional resistance, membrane capacitance, and cell-substrate separation. The experimental results show that the invasive breast carcinoma cells, MDA-MB-231, promotes the wound migration and micromotion in response to TGF-β, and the responses are related to the time periods of TGF-β treatment as well.

Tese de Doutoramento em Engenharia Química e Biológica
The inflammatory response is an important step in wound healing, however if there is an imbalance between the immune response and tissue regeneration, a delay on the healing process will occur, resulting in a chronic wound. Chronic wounds are a significant problem for health care system, accounting for almost 4% of its total budget, and currently increasing. Early detection of incipient wound infection and chronic inflammation reduces the severity of the disease and decreases health care expenses. Currently, it is difficult, expensive and time consuming to accurately assess a wound status, hence, there is an urgent need for a new diagnostic that would give the medical staff a fast and reliable method to determine inflammation/infection of a chronic wound at an early stage. Human neutrophil elastase (HNE) is one of the most abundant proteinases in wounds and its activity was found to be elevated in case of infection and chronic inflammation, making this enzyme a suitable marker for impaired healing. This PhD thesis intends to explore new strategies for the detection of HNE through the development of chromogenic and fluorogenic sensors that when embedded in a dressing may provide an in situ and real-time assessment of the wound status. For that, a specific cleavage sequence for HNE was designed by molecular docking studies and then confirmed in vitro. Then, this substrate was associated to chromogenic or fluorogenic detection systems. Regarding the chromogenic detection systems, two strategies were followed using ultramarine (UM), a GFP-like chromoprotein. The rationale of this approach was to use this protein’s ability to regenerate its dark blue colour (hysteresis) upon HNE cleavage, turning it into a switch-on sensor, or to lose its colour upon proteolysis, thus making a switch-off sensor. In a first attempt to convert ultramarine into a HNE substrate switch was based on a split protein strategy which would signal as a gain of colour sign. We were able to detect an absorbance increase upon HNE cleavage, but this effect was not long lasting due to an instability of the interaction between the signalling and sensing fragments. Indeed, this strategy proved it to be extremely challenging. The main motivation to pursue this work resided in its innovative aspect, as GFP-like chromogenic sensors were never reported. Then, a second strategy was investigated through sitedirected mutagenesis of ultramarine. In this latter strategy we were able to obtain sensors with an opposite signal, switch-off. To provide a better understanding regarding UM’s chromogenic environment, molecular dynamics studies coupled to protein expression were implemented to each of the seven produced UM-mutants. Our findings provided new information regarding the effect of certain mutations in UM protein conformation and allowed us to explore its application as a switch sensor. Here, we explored for the first time the development of a colour switch-on sensor based on chromogenic GFP-like proteins. Even though, we were unable to fully accomplish the regeneration of a stable chromophore environment for colour appearance, this work may serve as a starting point for advances in switch-on chromogenic sensors using non-fluorescent GFP-like proteins. For the fluorogenic detection system, the strategy studied resulted in the successful development of a FRET (Förster resonance energy transfer) peptide to monitor HNE. Upon HNE action, this peptide proved to be more effective than the traditional peptides coupled to fluorophores. Its visual detection was possible using an UV-portable light source. The embedding of this sensor in dressings would provide advantages for its application as a wearable sensor. The methods here used for the FRET-peptide immobilization onto a dressing compromised its detection. However, we envision that with the proper method of integration into a dressing, this FRET peptide could be used as a new strategy of smart materials. The strategies explored in this thesis can be further investigated and possibly implemented as point-of-care medical devices for wound control. As wound care tools, these devices would allow a prompt detection of chronic wounds, contributing to their proper and effective care and, consequently, granting a better outcome for the millions of people that suffer from non-healing wounds.
A resposta inflamatória é um importante passo no processo de cicatrização de feridas. No entanto, desequilíbrios entre a resposta do sistema imunitário e a regeneração celular podem desencadear um atraso significativo no processo de cicatrização, resultando numa ferida crónica. As feridas crónicas apresentam um problema significativo para o sistema de saúde, contabilizando 4% do orçamento total de saúde, sendo que se estima um aumento destes números nas próximas décadas. A deteção antecipada de infeção e inflamação crónica numa ferida reduz a severidade da doença, consequentemente diminuindo o seu impacto nas despesas de saúde. Atualmente, a avaliação do estado de uma ferida de forma exata e precisa é um processo difícil, dispendioso e demoroso. Por esta razão, existe uma necessidade urgente de desenvolvimento de novas ferramentas de diagnóstico que possibilitem a deteção precoce de infeção/inflamação em feridas crónicas de forma rápida e eficaz. A elastase neutrofílica humana (HNE) é uma das proteinases mais abundantes em feridas, estando os seus elevados níveis de atividade em feridas correlacionados com a ocorrência de infeção e inflamação crónica. De facto, esta enzima é considerada um excelente biomarcador para feridas cujo processo de cicatrização se encontra comprometido. O objetivo principal desta tese de doutoramento foi e exploração de novas estratégias para a deteção da HNE através do desenvolvimento de sensores cromogénicos e fluorogénicos que possam ser incorporados em pensos para feridas, possibilitando uma avaliação in situ e em temporeal do estado da ferida. Para tal, primeiramente desenharam-se sequências de clivagem específicas para HNE cuja afinidade para a enzima foi analisada através de estudos de acoplamento molecular e posteriormente foram confirmados com ensaios in vitro. Depois, o substrato foi associado a sistemas de deteção cromogénico ou fluorogénico. Relativamente aos sistemas de deteção cromogénicos, desenvolveram-se duas estratégias usando a ultramarina (UM), uma cromoproteína do tipo GFP, como substrato sinalizador. A competência desta proteína em regenerar a sua cor azul (devido à capacidade de histerese) permitiu transformá-la num sensor que se liga (switch-on) ou que se desliga (switch-off) após a sua clivagem com a HNE. A primeira tentativa para converter a proteína ultramarina num substrato comutador de sinal para a HNE consistiu na produção de uma proteína segmentada em duas partes que quando em interação resultam num sinal com ganho de cor (sensor switch-on). Após clivagem com HNE do fragmento substrato, conseguiu-se obter um aumento da absorvância, embora transiente, devido à interação com o fragmento sinalizador. De facto, esta estratégia foi muito desafiante. No entanto, a principal motivação em seguir esta linha de trabalho prendeu-se principalmente com o seu carácter inovador, visto que nunca tinham sido reportados sensores usando proteínas cromogénicas do tipo GFP. Neste seguimento, explorou-se uma segunda estratégia para o desenvolvimento de substratos sensores switch-on para a HNE através da mutagénese direcionada da proteína ultramarina. Esta abordagem permitiu também obter sensores com o sinal oposto – switch-off. Com o objetivo de melhor compreender as condições que proporcionam o ambiente cromogénico da proteína UM, foram implementados estudos de simulação de dinâmica molecular complementares à expressão das proteínas para cada um dos sete mutantes produzidos. A partir deste trabalho conseguiu-se recolher novos dados acerca do efeito de certas mutações na conformação da proteína UM e possibilitou-nos também explorar a sua aplicação como sensor comutador de sinal. Nestes trabalhos investigou-se pela primeira vez o desenvolvimento de sensores cromogénicos switch-on baseados em proteínas do tipo GFP. Embora não se tenha conseguido obter a regeneração estável do cromóforo que permite o aparecimento de cor, estes resultados poderão servir como ponto de partida para outros trabalhos em sensores cromogénicos switch-on usando proteínas não fluorescentes do tipo GFP. Em relação aos sistemas de deteção fluorogénicos, a abordagem explorada resultou no desenvolvimento bem-sucedido de um péptido FRET para monitorização de HNE. Após proteólise, este péptido provou ser mais eficaz do que os tradicionais péptidos fluorescentes (acoplados a fluoróforos). A deteção visual da fluorescência foi possível recorrendo a uma luz UV portátil. A incorporação deste sensor em pensos de feridas trará vantagens relativamente à sua aplicação como sensores wearable. Os métodos aqui descritos para a imobilização do péptido FRET em têxteis usados como material de penso comprometeram a deteção do seu sinal. No entanto, prevêse que a utilização de um método de integração mais apropriado possa permitir a sua aplicação em novas estratégias no desenvolvimento de tecidos inteligentes. A implementação da investigação aqui descrita em dispositivos médicos para a monitorização do processo de cicatrização de feridas poderá complementar o leque de ferramentas usadas no cuidado das feridas. Estes dispositivos possibilitarão a deteção atempada da cronicidade de uma ferida, contribuindo para o seu cuidado apropriado e eficaz. Consequentemente irá garantir uma melhor qualidade de vida para milhões de doentes que sofrem de feridas de difícil cicatrização.
Fundação para a Ciência e Tecnologia (FCT) e à Tecminho pelo financiamento da minha bolsa de doutoramento (SFRH/BD/113247/2015). Ao projeto da comissão europeia INFACT (FP7-NMP-2013-SME-7 - Grant agreement no. 604278)

Transcutaneous oxygen pressure measurement (TCp02) using a miniaturised Clarke electrode and a heating thermistor was developed independently by Huch et al and Eberhardt et al in 1972. After its initial use to non invasively monitor arterial partial pressure (Pa02) in neonates it was proposed as a useful test of skin blood flow and possibly amputation wound healing level selection in patients with peripheral vascular disease. Unfortunately a wide range of predictive values emerged with some authors reporting amputations healing when the TCp02 value was 0 mmHg. The investigation, while still considered useful, has not gained widespread support. This study investigates the use of TCp02, establishes a value for the use of the TCp02 Index to predict amputation wound healing potential and examines the hypothesis that the use of the TcpO Index to select amputation level can reduce patient morbidity and mortality. The literature is reviewed and a series of studies evaluating TCp02 use, undertaken in the Durban Metropolitan Vascular Service Non-Invasive Laboratories, are presented. TCp02 measurements were performed in a standardised manner with the subject supine breathing room air. Measurements were taken at fixed sites, on the mid dorsum of the foot (Foot), 10 cm distal to the tibial tuberosity and 2 cm lateral to the anterior tibial margin (BKA), 10 cm proximal to the patella in the midline (AKA) and on the chest in the mid-clavicular line. A TCp02 Index, the limb to chest ratio was defined. TCp02 data derived from control subjects asymptomatic of peripheral vascular disease were shown to be similar to age matched pooled data derived from the literature. In patients with peripheral vascular disease, absolute TCp02 and the TCp02 Index were shown to fall from proximal to distal sites and again were no different to pooled data derived from the literature. Based on presenting symptoms, the fall in TCp02 and the TCp02 Index was significant from proximal to distal sites. The reduction in absolute TCp02 and the TCp02 was also related to the most distal pulse present. TCp02 values were found to be no different in patients with peripheral vascular disease with or without diabetes. When comparing TCp02 and the TCp02 Index with Doppler pressure measurements at the Popliteal artery and at the foot, and the Doppler ankle brachial index (ABI), Doppler derived data were significantly higher in diabetic patients than in non-diabetic patients. No differences were noted in TCp02 data. TCp02 was compared with the 133Xe radio-isotope skin washout test. The best correlation was (r = 0.46) was obtained with a logarithmic curve y = 10.862Ln(x) + 38.751. TCp02 was compared with antibiotic concentrations (Cefoxitin) in muscle obtained from the site of amputation and the Cefoxitin Index, the ratio of muscle antibiotic concentration to plasma concentration, as an indication of the relationship of skin TCp02 to muscle blood flow. A significant correlation was shown between the Cefoxitin Index and TCp02 (r = 0.67, p = 0.035) and the TCp02 Index (r = 0.64, P = 0.045), suggesting that skin oxygen delivery may reflect muscle antibiotic delivery and hence blood flow. TCp02 and the TCp02 Index were compared with heated and unheated laser Doppler fluxmetry (LDF) in 35 patients undergoing amputation wound healing assessment. Significant correlations were shown between heated LDF, heated LDF Index and the TCp02 Index (r = 0.63 and r = 0.69, P < 0.0001). TCp02 Index values of 0.5 and 0.55 showed an accuracy of 96.2 % in predicting amputation outcome while LDF values of 3, 4 and 5 arbitrary units gave an accuracy of 88.5 %. Using receiver operator curves, a TCp02 Index of 0.55 was shown to be the best test. Over the years 1987 and 1988, TCp02 data were gathered on 193 patients undergoing lower limb amputation for peripheral vascular disease. Information on the outcome of the amputation was available for 152 amputations. Circumstances which might result in a reduced pre-operative TCp02 reading were identified and criteria were set for the use of TCp02 to predict amputation wound healing potential. 122 amputations which met the defined entry criteria were available for evaluation. A TCp02 Index of 0.50 gave a definitive predictive value below which no amputation healed. Similarly no amputation with an absolute TCp02 of less than 27 mmHg healed. Receiver operator characteristic curves showed the TCp02 Index to be a better test than absolute TCp02. A TCp02 Index of 0.55 was shown to have the best sensitivity of96.7 %, with a specificity of79.8 % and an accuracy of 90.2 %. When introduced to clinical practice, correct use of the TCp02 Index of 0.55 resulted in a reduction in amputation revision rate from 40.3 % in 1987, to 8.2 % in 1990. Initially some surgeons felt that the TCp02 Index predicted amputation wound failure at distal sites at which healing could be expected on clinical criteria, and chose amputate at sites with a TCp02 Index value less than 0.55. These amputations failed to heal. As surgeons gained confidence in the test, they chose to follow the TCp02 data more often and the percentage of amputations performed at sites predicted by the TCp02 Index to fail , fell from 35.5 % in 1987 to 6.6 % in 1990. Over a 15 year period at King Edward VIII Hospital, the amputation revision rate has fallen from an average of 32.7 % in the first five years when Tcp02 data were not available to the surgeon, to 21.4 % and 22.9 % in the two subsequent 5 year periods when Tcp02 data were available. The mortality rates were unchanged. The decline in revision rates was less than expected and relates to the fact that approximately only 42 % of patients requiring amputation undergo the test. This is because it is time consuming and available only during weekday office hours. These studies have confirmed the usefulness of Tcp02 measurement in the non-invasive vascular laboratory. The index is shown to be superior to absolute Tcp02 as a predictive test of amputation wound healing. The introduction of several criteria to define when Tcp02 use is appropriate has refined the investigation and made it clinically useful in our setting. A Tcp02 Index of 0.55 in the appropriate patient is a useful test to predict amputation wound healing and its use has resulted in reduced patient morbidity and mortality, confirming the hypothesis tested.
Thesis (M.D.)-University of Natal, 2001.

**English** Plasmonic particles such as gold nanorods (GNRs) are showing themselves as powerful contrast agents for important applications such as photoacoustic imaging and photothermal ablation of cancer. However, their unique photothermal conversion efficiency can turn into a practical disadvantage, and expose them to the risk of overheating and irreversible photodamage. The processes of prefusion and remodeling of GNRs under illumination with optical pulses of typical duration of the order of a few ns will be studied in depth. A retrospective classification of these approaches will be undertaken according to often implicit principles, such as: constraining the initial shape, speeding up their thermal coupling with the environment by lowering their thermal resistance at the interface, or redistributing the incoming energy among several particles. Advantages and disadvantages and contexts of practical interest in which one solution may be more appropriate than the other will be discussed. Stabilization of the optical properties of anisotropic plasmonic particles by thermal heating and laser irradiation is an important issue in many biomedical applications. The effect that small thiols have on the thermal photostability of gold nanorods will be addressed. The nanoparticles were treated with mixtures of poly-ethylene-glycol thiolate (PEG-SH) and methyl-benzene-thiol (MBT) with molar ratios ranging from 0 (for the case of pure PEG) to 20, and then incubated in an oven. under sub-boiling conditions. Small thiols have been found to greatly improve the thermal stability of GNRs. For example, after 1 hour at 90 °C the samples with pure PEG lost more than 70% of the optical absorbance in their initial peak position, while the particles covered with a dense layer of MBT remained almost unchanged. It is possible to attribute this effect to a modulation of the activation barrier for the superficial diffusion of the gold atoms. Furthermore, we addressed the translation of this effect on the photostability of irradiated gold nanorods under conditions of interest for photoacoustic imaging and it was found that small thiols delay the damage thresholds by up to a factor of 2. In this work of thesis also describes the effect of the thermal resistance at the gold-water interface (Kapitza resistance) on the photoacoustic conversion performance of gold nanorods. The results indicate possible strategies for optimizing plasmonic particles as contrast agents for imaging, or even as transducers for biosensors. An effective approach is also suggested to modulate the Kapitza resistance by including features not yet well studied such as roughness or the presence of adsorbates. Following this idea, a rough variant of gold nanorods was synthesized by galvanic deposition and replacement of a silver shell, where roughness provides photoacoustic signals approximately 70% higher and damage thresholds of 120%. Furthermore, the particles were coated with a protein crown, which brings about a decrease in photoacoustic signals as the thickness of the shell increases; this could inspire new solutions for biosensors based on a photoacoustic transduction mechanism. Both of these results are consistent with effective modulation of Kapitza resistance, which can decrease with roughening, due to an increase in specific surface area, and can increase with the introduction of a protein coating (which can act as insulation thermal). Hybrid materials consisting of core/shell Au/Ag nanorods have also been developed, included in porous biomimetic phantoms (scaffolds) of chitosan/polyvinyl alcohol (chitosan/PVA) for applications in tissue engineering and wound healing. The combination of Au and Ag in a single construct provides synergistic opportunities for optical activation of functions such as near-infrared laser tissue welding and remote interrogation for the acquisition of prognostically relevant parameters in monitoring wound healing. In particular, the bimetallic component ensures improved optical tunability, shelf life and photothermal stability, acts as a reservoir for germicidal silver cations. At the same time, the polymer blend is ideal for bonding to connective tissue following photothermal activation and for supporting manufacturing processes that provide high porosity, such as electro-spinning, thus setting all the conditions for cell repopulation and antimicrobial protection. In summary, in this work, the optimization of an important system such as GNRs for complementary applications in different biomedical fields has been addressed; their stability and photoacoustic conversion efficiency have been optimized for use as contrast agents optical, developing functional coatings with small organic molecules or with metal porous layers. Finally, the integration of Au/Ag bimetallic nanorods into hybrid scaffolds for tissue engineering was evaluated, exploiting both the photothermal conversion efficiency and the optical sensitivity to oxidative stress conditions, in order to activate processes and monitor parameters of interest in scope of wound healing. **Italiano** Le particelle plasmoniche come i nanorods d'oro (GNRs) si stanno mostrando potenti agenti di contrasto per applicazioni importanti come l'imaging fotoacustico e l'ablazione fototermica del cancro. Però, la loro efficienza unica di conversione fototermica può trasformarsi in uno svantaggio pratico, e esporli al rischio di surriscaldamento e fotodanneggiamento irreversibile. Verranno approfonditi i processi di prefusione e rimodellazione dei GNRs sotto illuminazione con impulsi ottici di durata tipica dell'ordine di pochi ns. Verrà intrapresa una classificazione retrospettiva di tali approcci secondo principi spesso impliciti, come: vincolare la forma iniziale, velocizzare il loro accoppiamento termico con l'ambiente abbassando la loro resistenza termica all'interfaccia, oppure ridistribuire l'energia in ingresso tra più particelle. Saranno discussi vantaggi e svantaggi e contesti di interesse pratico in cui una soluzione può essere più appropriata dell'altra. La stabilizzazione delle proprietà ottiche delle particelle plasmoniche anisotrope tramite riscaldamento termico e irradiazione laser è una questione importante in molte applicazioni biomediche. Verrà affrontato l'effetto che piccoli tioli hanno sulla fotostabilità termica dei nanorods d'oro. Le nanoparticelle sono state trattate con miscele di poli-etilen-glicole tiolato (PEG-SH) e metil-benzen-tiolo (MBT) con rapporti molari compresi tra 0 (per il caso del PEG puro) e 20, e poi incubati in stufa in condizioni di sub-ebollizione. È stato scoperto che i piccoli tioli migliorano notevolmente la stabilità termica dei GNRs. Ad esempio, dopo 1 ora a 90 °C i campioni con PEG puro hanno perso più del 70% dell'assorbanza ottica nella loro posizione di picco iniziale, mentre le particelle ricoperte di un denso strato di MBT sono rimaste pressoché invariate. È possibile attribuire questo effetto ad una modulazione della barriera di attivazione per la diffusione superficiale degli atomi d'oro. Inoltre, abbiamo affrontato la traduzione di questo effetto sulla fotostabilità dei nanorods d'oro irradiati in condizioni di interesse per l'imaging fotoacustico ed è stato scoperto che i piccoli tioli ritardano le soglie di danneggiamento fino a un fattore di 2. In questo lavoro di tesi viene descritto inoltre l'effetto della resistenza termica all'interfaccia oro-acqua (resistenza di Kapitza) sulle prestazioni di conversione fotoacustica dei nanorods d'oro. I risultati indicano possibili strategie per l'ottimizzazione delle particelle plasmoniche come agenti di contrasto per l'imaging, o anche come trasduttori per i biosensori. Viene inoltre suggerito un approccio efficace per modulare la resistenza di Kapitza includendo caratteristiche ancora non ben studiate come rugosità o presenza di adsorbati. Seguendo questa idea è stata sintetizzata una variante rugosa di nanorods d'oro per deposizione e sostituzione galvanica di un guscio d'argento, dove la rugosità fornisce segnali fotoacustici più elevati di circa il 70% e soglie di danneggiamento del 120%. Inoltre, le particelle sono state rivestite con una corona proteica, la quale apporta una diminuzione dei segnali fotoacustici con l'aumentare dello spessore del guscio; questo potrebbe ispirare nuove soluzioni per biosensori basate su un meccanismo di trasduzione fotoacustica. Entrambi questi risultati sono coerenti con un'efficace modulazione della resistenza di Kapitza, che può diminuire con l'irruvidimento, a causa di un aumento della superficie specifica, e può aumentare con l'introduzione di un rivestimento proteico (il quale può fungere da isolamento termico). Sono stati anche sviluppati materiali ibridi costituiti da nanorods core/shell Au/Ag, inclusi in fantocci biomimetici (scaffold) porosi di chitosano/polivinilil alcol (chitosano/PVA) per applicazioni nell'ingegneria tissutale e nella guarigione delle ferite (wound healing). La combinazione di Au e Ag in un unico costrutto fornisce opportunità sinergiche per l'attivazione ottica di funzioni come la saldatura dei tessuti con laser nel vicino infrarosso e l’interrogazione remota per l’acquisizione di parametri di rilevanza prognostica nel monitoraggio della guarigione delle ferite. In particolare, la componente bimetallica assicura sintonizzabilità ottica, durata di conservazione e stabilità fototermica migliori, funge da serbatoio di cationi d'argento germicidi. Allo stesso tempo, la miscela polimerica è ideale per essere legata al tessuto connettivo a seguito di attivazione fototermica e per supportare i processi di fabbricazione che forniscono un’elevata porosità, come l'elettrofilatura, ponendo così tutte le premesse per il ripopolamento cellulare e la protezione antimicrobica. In sintesi, in questo lavoro, è stata affrontata l'ottimizzazione di un sistema importante come i GNRs per applicazioni complementari in diversi ambiti biomedici; ne è stata ottimizzata la stabilità e l'efficienza di conversione fotoacustica per essere utilizzati come agenti di contrasto ottico, sviluppandone rivestimenti funzionali con piccole molecole organiche oppure con strati porosi metallici. Infine è stata valutata l'integrazione di nanorods bimetallici di Au/Ag in scaffold ibridi per ingegneria tissutale, sfruttandone sia l'efficienza di conversione fototermica sia la sensibilità ottica alle condizioni di stress ossidativo, allo scopo di attivare processi e monitorare parametri di interesse nell'ambito del wound healing.

The ultimate goal for all burns is to allow the wound to heal with the least amount of scarring, and this is directly related to the depth of burn injury. Superficial partial thickness burns and deeper burns of small area can be treated by suitable dressings alone and this is probably the most widely applied form of treatment for burns. Burns that are selected for treatment by dressings alone, or in combination with surgical debridement and skin grafting, require regular monitoring, both clinically and microbiologically. Modern dressings may allow a longer interval between dressing changes, but this should not be sacrificed in favour of regular review. If wound healing progresses at the expected rate, then the comfort afforded by fewer changes of dressings is advantageous, but the poorly progressing wound should be treated aggressively with a custom-designed dressing which can be tailored for the individual needs of the patient.

The healing status of chronic wounds is important for monitoring the condition of the wounds. This article designs and discusses the implementation of smartphone-enabled compression technique under a tele-wound network (TWN) system. Nowadays, there is a huge demand for memory and bandwidth savings for clinical data processing. Wound images are captured using a smartphone through a metadata application page. Then, they are compressed and sent to the telemedical hub with a set partitioning in hierarchical tree (SPIHT) compression algorithm. The transmitted image can then be reduced, followed by an improvement in the segmentation accuracy and sensitivity. Better wound healing treatment depends on segmentation and classification accuracy. The proposed framework is evaluated in terms of rates (bits per pixel), compression ratio, peak signal to noise ratio, transmission time, mean square error and diagnostic quality under telemedicine framework. A SPIHT compression technique assisted YDbDr-Fuzzy c-means clustering considerably reduces the execution time (105s), is simple to implement, saves memory (18 KB), improves segmentation accuracy (98.39%), and yields better results than the same without using SPIHT. The results favor the possibility of developing a practical smartphone-enabled telemedicine system and show the potential for being implemented in the field of clinical evaluation and the management of chronic wounds in the future.

Recently hydrogels and the treatment of skin wounds based on hydrogel dressings have become one of the research hotspots in the field of skin trauma. In this chapter, we focus on the materials and methods of hydrogel preparation, and discuss the properties that hydrogels should possess for the treatment of wounds. Moreover, we discuss the potential of non-invasive optical imaging techniques in the assessment of cutaneous wound healing. The research results of the application of non-invasive optical techniques such as diffuse reflectance spectroscopy (DRS) and optical coherence tomography (OCT) in scar identification, skin bruising, and skin and vascular structure identification are reviewed. Furthermore, we further discuss the superiority and potential of current artificial intelligence (AI) technology in dermatological diagnosis, and analyze the application status of hydrogel in skin wound treatment. Finally, we believe that the combination of AI and optical imaging technology in the development and efficacy monitoring of hydrogels will be a promising research direction in the future.