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Fibrosis is a prevalent problem that pathologically accompanies chronic inflammatory diseases. Despite the availability of various fibrosis treatments, therapeutic efficacy must be further improved to achieve better clinical outcomes. The purpose of this study is to develop a novel treatment by combining phloroglucinol (PHL) with photobiomodulation (PBM) to prevent skin fibrosis. In in vitro, 635 nm PBM at 8 J/cm2 significantly reduced TNF-alpha levels, and 100 μg/ml of PHL suppressed the expression of α-smooth muscle actin and type I collagen due to the downregulation of SMAD 2/3 and MAPK signaling pathways. The 1470 nm laser light created the initial wound (97.1 mm2), leading to scar formation after complete wound closure (21 days) on rodent skin. In comparison to other groups, the dual treatment accelerated wound closure and achieved rapid and complete healing in 17 days. Histological analysis presented the reduced fibrotic scar and collagen deposition in the dual treatment group. PHL-combined PBM treatment enhanced the anti-inflammatory effect by 36% in comparison to single treatment groups. Overall, the proposed combined treatment promoted wound healing and enhanced anti-inflammatory and anti-fibrotic effects in the overexpressed in vitro and in vivo models.

Endoscopic submucosal dissection (ESD) is clinically used to remove early gastric cancer in stomach. The aim of the current study is to examine a therapeutic capacity of pulsed Ho:YAG laser for the development of laser-assisted ESD under various surgical parameters. Ex vivo porcine stomach tissue was ablated with 1-J Ho:YAG pulses at 10 Hz at different number of treatments (NT = 1, 2, and 3) and treatment speeds (TS = 0.5, 1, and 2 mm/s) without and with saline injection. Regardless of saline injection, straight tissue ablation showed that ablation depth increased with increasing NT and decreasing TS. At NT = 3 and TS = 0.5 mm/s, no saline injection yielded the maximum ablation depth (3.4 ± 0.3 mm), partially removing muscularis propria. However, saline injection confined the tissue ablation within a submucosal layer (2.1 ± 0.3 mm). Thermal injury was found to be 0.7~1.1 mm in the adjacent tissue with superficial carbonization. Circular tissue ablation (2 cm in diameter) at NT = 3 and TS = 0.5 mm/s presented that no saline injection yielded a reduction in the lesion area, whereas saline injection maintained the ablated lesion area. Histological analysis revealed that unlike no saline injection, saline injection ablated the entire mucosal layer without perforation in the muscular propria. The pulsed Ho:YAG laser can be a potential surgical tool for clinical ESD to incise a target lesion without adverse perforation. Further investigations will validate the efficacy and safety of the Ho:YAG laser-assisted ESD in in vivo porcine stomach models for clinical translation.

Simple Summary Colorectal cancer is one of the most common cancers and the third leading cause of cancer-related deaths in the United States. As a non- or minimally invasive cancer treatment, photothermal therapy (PTT) has been widely used to generate irreversible thermal injuries in tumors. However, conventional PTT employs an end-firing flat fiber to deliver laser energy, leading to the incomplete removal of tumor tissues due to an uneven beam distribution over the tumor surface. Multi-lens arrays (MLA) generate multiple micro-beams to uniformly distribute laser energy on the tissue surface. Therefore, the application of MLA for PTT in cancer affords a spatially enhanced distribution of micro-beams and laser-induced temperature in the tumor. The purpose of the current study is to computationally and experimentally demonstrate the therapeutic benefits of MLA-assisted fractional PTT on colorectal cancer, in comparison to flat fiber-based PTT. Abstract Conventional photothermal therapy (PTT) for cancer typically employs an end-firing flat fiber (Flat) to deliver laser energy, leading to the incomplete treatment of target cells due to a Gaussian-shaped non-uniform beam profile. The purpose of the current study is to evaluate the feasibility of multi-lens arrays (MLA) for enhanced PTT by delivering laser light in a fractional micro-beam pattern. Computational and experimental evaluations compare the photothermal responses of gelatin phantoms and aqueous dye solutions to irradiations with Flat and MLA. In vivo colon cancer models have been developed to validate the therapeutic capacity of MLA-assisted irradiation. MLA yields 1.6-fold wider and 1.9-fold deeper temperature development in the gelatin phantom than Flat, and temperature monitoring identified the optimal treatment condition at an irradiance of 2 W/cm2 for 180 s. In vivo tests showed that the MLA group was accompanied by complete tumor eradication, whereas the Flat group yielded incomplete removal and significant tumor regrowth 14 days after PTT. The proposed MLA-assisted PTT spatially augments photothermal effects with the fractional micro-beams on the tumor and helps achieve complete tumor removal without recurrence. Further investigations are expected to optimize treatment conditions with various wavelengths and photosensitizers to warrant treatment efficacy and safety for clinical translation.

Thermal responses of adipose tissue to high intensity focused ultrasound (HIFU) were quantitatively evaluated for effective clinical lipolysis. A single-element HIFU transducer (4 MHz and 4.5 mm focal depth) was used in a linear motion to thermally treat the tissue at various acoustic energy densities and treatment gaps. Both interstitial temperature rise and denatured lesions increased with the energy density (up to 21.1 ± 1.9 K and 0.40 ± 0.15 mm2). No thermal overlapping was observed due to selective application of the ultrasonic beams. The optimization of noninvasive HIFU treatment parameters may ensure clinical outcomes of HIFU-assisted lipolysis in terms of efficacy and safety.