Hypertrophic scar (HS) is one of the most common challenges in the field of plastic and reconstructive surgery. HS formation is associated with the abnormal activation of fibroblasts. These fibroblasts exhibit excessive proliferative and fibrotic behavior, which can be induced by glycolysis dysregulation. Herein, self-assembled nanogels prepared by modifying IR808 with hyaluronic acid (termed HA-IR808) are introduced as selective glycolytic inhibitors to control HS formation through transdermal delivery to HS fibroblasts (HFs). HA-IR808 preferentially targets activated HFs and has a structure suitable for transdermal delivery. In vitro, HA-IR808 exhibits a glycolysis inhibition effect and regulates the fibrotic behavior and proliferation of HFs through energy depletion and macromolecule synthesis. In vivo, HA-IR808 penetrates the dermal layer, regulates glycolysis, and controls HS formation. Mechanistically, HA-IR808 regulates glycolysis by silencing the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of the rapamycin (mTOR) signaling pathway. In conclusion, this research elucidates a strategy for controlling HS formation via glycolysis regulation using self-assembled HA-IR808 nanogels to inhibit HF activation.

Surgical scar formation afflicts patients and current treatments are limited by inconsistent efficacy, long-term and painful treatment processes. In this report, a patient received 5-aminolevulinic acid-mediated photodynamic therapy (5-ALA PDT) on the first postoperative day, once a week for 5 sessions. At two-year follow-up, the intervention of 5-ALA PDT at early stage decreased the vascular density and improved extracellular matrix (ECM) deposition. The early intervention of surgical scar by 5-ALA PDT overcomes the penetration limits of photosensitizer and red light, making it a potential strategy for surgical scar prevention.

Advancements in lymphography technology are essential for comprehensive investigation of the lymphatic system and its function. Here, a shortwave infrared (SWIR) luminescence imaging of lymphatic vessels is proposed in both normal and lymphatic dysfunction in rat models with PbS quantum dots (PbS Qdots). The lymphography with PbS Qdots can clearly and rapidly demonstrate the normal lymphatic morphology in both the tail and hind limb. More importantly, compared to ICG, SWIR luminescence imaging with PbS Qdots can easily identify the dominant lymphatic vessel and node with higher luminescence signal in rats. Moreover, lymphatic pump is identified as segment contracting sections with a size of ≈1 cm in rat by in vivo SWIR lymphograhy, which propose a direct feature for precise evaluation of lymphatic function. Notably, in vivo SWIR luminescence imaging with PbS Qdots also clearly deciphers the in vivo pattern of morphological and function recovery from lymphatic system in rat model. In summary, SWIR luminescence imaging with PbS Qdots can improve the lymphography and thus deepen the understanding of the morphology and structure of the lymphatic system as well as lymphatic function such as lymphatic pump, which will facilitate the diagnosis of lymphatic dysfunction in the future.

Peripheral vessel imaging plays an important role in the assessment, treatment, and monitoring of cardiovascular diseases. Using photoacoustic imaging technology to perform peripheral vessel imaging is a potential and novel medical imaging method that visualizes the human body's peripheral blood vessels. This method can non-invasively image the vascular system in areas such as the hands and arms. To promote the clinical application of this technology, we propose an arc-shaped light-rotatable photoacoustic tomography system that can achieve multi-angle light illumination, which penetrate deeper and produce stronger photoacoustic signals. Both phantom and forearm in vivo experiments have been conducted to verify the feasibility of the proposed system. The experimental results demonstrate that the system is capable of acquiring multi-angle light illumination and more information, achieving high-quality images, and being portable.

The degradation of collagen in different body parts is a critical point for designing collagen-based biomedical products. Here, three kinds of collagens labeled by second near-infrared (NIR-II) quantum dots (QDs), including collagen with low crosslinking degree (LC), middle crosslinking degree (MC) and high crosslinking degree (HC), were injected into the subcutaneous tissue, muscle and joints of the mouse model, respectively, in order to investigate the in vivo degradation pattern of collagen by NIR-II live imaging. The results of NIR-II imaging indicated that all tested collagens could be fully degraded after 35 days in the subcutaneous tissue, muscle and joints of the mouse model. However, the average degradation rate of subcutaneous tissue (k = 0.13) and muscle (k = 0.23) was slower than that of the joints (shoulder: k = 0.42, knee: k = 0.55). Specifically, the degradation rate of HC (k = 0.13) was slower than LC (k = 0.30) in muscle, while HC showed the fastest degradation rate in the shoulder and knee joints. In summary, NIR-II imaging could precisely identify the in vivo degradation rate of collagen. Moreover, the degradation rate of collagen was more closely related to the implanted body parts rather than the crosslinking degree of collagen, which was slower in the subcutaneous tissue and muscle compared to the joints in the mouse model.

Sodium aescinate (SA) shows great potential for treating lymphedema since it can regulate the expression of cytokines in M1 macrophages, however, it is commonly administered intravenously in clinical practice and often accompanied by severe toxic side effects and short metabolic cycles. Herein, SA-loaded chiral supramolecular hydrogels are prepared to prove the curative effects of SA on lymphedema and enhance its safety and transdermal transmission efficiency. In vitro studies demonstrate that SA- loaded chiral supramolecular hydrogels can modulate local immune responses by inhibiting M1 macrophage polarization. Typically, these chiral hydrogels can significantly increase the permeability of SA with good biocompatibility due to the high enantioselectivity between chiral gelators and stratum corneum and L-type hydrogels are found to have preferable drug penetration over D-type hydrogels. In vivo studies show that topical delivery of SA via chiral hydrogels results in dramatic therapeutic effects on lymphedema. Specifically, it can downregulate the level of inflammatory cytokines, reduce the development of fibrosis, and promote the regeneration of lymphatic vessels. This study initiates the use of SA for lymphedema treatment and for the creation of an effective chiral biological platform for improved topical administration.

An increase in the levels of reactive oxygen species (ROS) and high expression levels of transforming growth factor-β (TGF-β) in wound tissue are two major problems for wound repair and scar inhibition. Modulation of the wound microenvironment is considered to be able to overcome these issues. Two possible solutions include the use of cerium oxide nanoparticles (CeO2) as an enzyme-like ROS scavenger and pirfenidone (PFD) as an anti-fibrotic drug to inhibit the expression of TGF-β. However, CeO2 is easily adsorbed by biological macromolecules and loses its enzyme-like activity. Furthermore, the intracellular delivery of PFD is difficult. Herein, the layer-by-layer method was used to prepare nanocapsules (NCs) with a sophisticated structure featuring PFD at their core and CeO2 in their shell; these NCs were referred to as PFD/CeO2 NCs. PFD/CeO2 NCs were supposed to efficiently achieve intracellular delivery of PFD and successfully scavenged ROS from the microenvironment. Cellular experiments verified that PFD/CeO2 NCs had good biocompatibility, satisfactory cellular uptake, and favorable ROS-scavenging capacity. To be applied directly to the wound, PFD/CeO2 NCs were then adhered to plasma-etched polylactic acid (PLA) fiber membranes to prepare a new wound dressing. Animal experiments further demonstrated that the dressing accelerated the epithelialization of the wound, reduced the levels of ROS and TGF-β, improved the arrangement and proportion of collagen fibers, and finally, achieved satisfactory wound-repairing and anti-scarring effects. These results provide a new concept for promoting wound repair and preventing scar formation.

目的 探讨远红外线治疗妇科癌症术后淋巴水肿患者的有效性和安全性.方法 2013年1月至2020年1月,选取74名妇科癌症术后淋巴水肿的患者,分别接受绷带治疗(n=35)和远红外线+绷带治疗(n=39).1年后评估患者淋巴水肿肢体积液量、淋巴水肿肢体周径、血清肿瘤标志物CA125;记录阴道、腹股沟-盆腔淋巴结变化情况,以及肺部有否癌症转移和其他不良反应.体外实验检测远红外线对成纤维细胞、A2780、HeLa、Ishikawa和SKOV-3细胞的细胞活力、增殖、凋亡和细胞周期的影响.结果 与绷带治疗组相比,远红外线+绷带治疗组患者1年后淋巴水肿肢体的积液量和周径显著减少(P<0.05).两组患者血清CA125均无升高,未见肿瘤复发或淋巴结肿大,无其他不良反应.经远红外线处理的成纤维细胞及A2780、HeLa、Ishikawa和SKOV-3细胞,其细胞活力、增殖、凋亡和细胞周期均无显著变化.结论 远红外线与绷带疗法相结合可以更有效地治疗妇科癌症术后淋巴水肿,并且不会促进妇科癌症的复发或转移,患者耐受性良好,未见不良反应或副作用.

Photodynamic therapy (PDT) is an emerging therapeutic strategy for hypertrophic scars (HS), which is heavily dependent on reactive oxygen species (ROS) generation. However, the unsatisfactory delivery and excitation of 5-aminolevulinic acid (ALA, a commercial photosensitizer in dermatology) result in an insufficient ROS generation, and thus limit the clinical application of PDT treating HS (HS-PDT). Consequently, sophisticated transdermal co-delivery nanoethosomes (named A/A-ES) with ALA and Au nanotriangles (AuNTs) in cores are prepared via an in-situ seed-mediated growth method, and then applied to improve HS-PDT through localized surface plasmon resonance (LSPR)-enhanced ROS generation. A/A-ES display a satisfactory performance in co-delivery in HS tissue with sufficient protoporphyrin IX production and LSPR effect in cytoplasm, which is beneficial for ALA excitation as well as ROS generation. In vitro/vivo studies reveal that A/A-ES significantly improve HS-PDT in promoting to fibroblast apoptosis and collagen remodeling through LSPR-enhanced ROS generation. Therefore, this study provides a feasible strategy that integrates transdermal delivery and LSPR to enable the beneficial effects of HS-PDT through boosting the delivery and excitation of ALA.

Background Hypertrophic scars (HS) represent one of the most common clinical challenges due to unsatisfactory therapeutic results. HS formation is associated with the abnormal activation of fibroblasts and their excessive fibrotic behavior. Glycolysis dysregulation has been shown to participate in the incidence and progression of various fibrotic diseases and shows potential as a means of controlling HS formation. This work aimed to discuss the impact of augmented glycolysis on HS and to propose a method for controlling HS formation through glycolysis regulation. Methods Here, augmented glycolysis was confirmed together with enhanced fibrotic activity in both HS fibroblasts (HFs) and HS tissues, and the suppression of glycolysis also attenuated fibroblast activation. We also introduced IR780, a heptamethine cyanine dye, to regulate glycolysis for the control of HS formation. Results In vitro, cell studies indicated that IR780 significantly down-regulated glycolysis and suppressed the fibrotic activity of HFs. In vivo, the intralesional injection of IR780 into rabbit HS models led to the downregulation of glycolysis and the control of HS formation. Furthermore, IR780 accumulated preferentially in activated fibroblasts in both in vitro and in vivo studies, and thus specifically downregulated glycolysis and efficiently controlled fibrosis by targeting activated fibroblasts. Conclusions This work identified a strategy for controlling fibrosis and HS formation from the perspective of glycolysis regulation with IR780 targeting of activated fibroblasts.

Cutaneous melanoma is one of the most common malignancies with increased incidence in the past few decades, making it a significant public health problem. The early diagnosis of melanoma is a major factor in improving patient's survival. The traditional pathway to melanoma diagnosis starts with a visual diagnosis, followed by subsequent biopsy and histopathologic evaluation. Recently, multiple innovative optical technology-based methods, including dermoscopy, reflectance confocal microscopy, optical coherence tomography, multiphoton excited fluorescence imaging and stepwise two-photon excited fluorescence (dermatofluoroscopy), have been developed to increase the diagnostic accuracy for the non-invasive melanoma diagnosis. Some of them have already been applied to real-life clinical settings, others require more research and development. These technologies show promise in facilitating the diagnosis of melanoma since they are non-invasive, sensitive, objective and easy to apply. Diagnostic accuracy, detection time, portability and the cost-effectiveness of the device are all aspects that need to be improved. This article reviews the method of these emerging optical non-invasive diagnostic technologies, their clinical application, their benefits and limitations, as well as their possible future development.

目的 探讨1470 nm裸光纤二极管激光器在病理性瘢痕治疗中的效果及安全性.方法 2020年5月至2021年5月,选取31例因各种病因引起的增生性瘢痕(n=14)及瘢痕疙瘩(n=17)患者,给予1～3次光纤治疗.使用温哥华瘢痕量表(VSS)、多普勒超声、皮肤弹性测试仪、皮肤黑色素及血红素检测仪和血流灌注成像仪进行综合评估.结果 增生性瘢痕患者的总VSS评分改善了44％,瘢痕疙瘩患者的总VSS评分改善了37.5％(P<0.001).瘢痕厚度平均减少(0.2±0.153)cm(P<0.001).其中,增生性瘢痕厚度减少21.66％(P<0.001),瘢痕疙瘩减少21.5％(P<0.001).治疗后瘢痕硬度也有所改善,R0指数增加0.89％(P<0.05),Q0指数增加0.43％(P<0.05).瘢痕疙瘩的色素沉着减少了10.04％(P<0.05).血流灌注方面,增生性瘢痕降低了28.6％(P<0.001),瘢痕疙瘩则降低了20.4％(P<0.001).未发现相关不良反应(色素沉着、皮肤感染或瘢痕复发).结论 1470 nm裸光纤二极管激光器可通过病灶内微创治疗,在增生性瘢痕和瘢痕疙瘩中实现瘢痕减容、改善瘢痕硬度、减少色沉和病灶内的血运,是一种有效的微创瘢痕治疗方法.

Photodynamic therapy (PDT) is a new therapeutic strategy for hypertrophic scars (HSs), and nanoethosomes (ES) have attracted considerable attention as an efficient transdermal delivery system for PDT of HSs (HS-PDT). However, the delivery of photosensitizers and the hypoxic microenvironment of HSs limit HS-PDT efficacy. Consequently, functional transdermal ES (A/A-ES) that are loaded with the photosensitizer, 5-aminolevulinic acid (ALA), and immobilized nanoenzyme Au nanoclusters (ANCs) within the ES surface have been developed that exhibit superior co-delivery characteristics and produce catalase that enhances HS-PDT efficacy. The unique structure of A/A-ES enables them to co-deliver ALA and ANCs into the HS tissue and to efficiently decompose the endogenous hydrogen peroxide in the HS to generate oxygen. The findings from in vitro and in vivo experiments demonstrated that A/A-ES efficiently co-delivered ALA and ANCs into the HS tissue and that they improved the hypoxic microenvironment of the HS. Systematic assessments reveal that A/A-ES enhance HS-PDT efficacy and that they are highly effective at improving the morphology and promoting HS fibroblast apoptosis and the rearrangement of collagen. These works give rise to an effective treatment option for HSs that integrates the transdermal co-delivery of ALA and nanoenzymes, thereby enabling them to exert their respective beneficial effects, and they highlight the enhancement of HS-PDT efficacy via self-generating oxygen.

Synergistic transdermal photodynamic therapy (PDT)/photothermal therapy (PTT) has emerged as a novel strategy for improving hypertrophic scar (HS) therapeutic outcomes. Herein, a near-infrared heptamethine cyanine dye, named IR-808, has been selected as the desirable photosensitizer owing to its PDT and PTT properties. Benefitting from the transdermal delivery ability of ethosomes (ESs), IR-808 loaded nanoethosomes (IR-808-ES) have been prepared as a novel nanophotosensitizer for the transdermal PDT/PTT of HSs. The special structure of IR-808 aggregate distribution in the ES lipid membrane enhances ROS generation and hyperthermia. The in vitro experiments indicate that the IR-808-ES enhances the PDT/PTT efficacy for inducing the HS fibroblast (HSF) apoptosis via the intrinsic mitochondrial pathway. Furthermore, the in vivo transdermal delivery studies reveal that the IR-808-ES efficiently delivers IR-808 into HSFs in the HS tissue. Systematic assessments in the rabbit ear HS models demonstrate that the enhanced PDT/PTT performance of the IR-808-ES has remarkable therapeutic effects on improving the HS appearance, promoting HSF apoptosis and remodeling collagen fibers. Therefore, the IR-808-ES integrates both the transdermal delivery ability and the aggregation-enhanced PDT/PTT effect, and these features endow the IR-808-ES with significant potential as a novel nanophotosensitizer for the transdermal phototherapy of HSs in the clinical field.

Transdermal drug delivery system (TDDS) is an attractive method for drug delivery with convenient application, less first-pass effect, and fewer systemic side effects. Among all generations of TDDS, transdermal nanocarriers show the greatest clinical potential because of their non-invasive properties and high drug delivery efficiency. However, it is still difficult to design optimal transdermal nanocarriers to overcome the skin barrier, control drug release, and achieve targeting. Hence, surface modification becomes a promising strategy to optimize and functionalize the transdermal nanocarriers with enhanced penetration efficiency, controlled drug release profile, and targeting drug delivery. Therefore, this review summarizes the developed transdermal nanocarriers with their transdermal mechanism, and focuses on the surface modification strategies via their different functions.