Keloids (KD) and hypertrophic scars (HTS), which are quite raised and pigmented and have increased vascularization and cellularity, are formed due to the impaired healing process of cutaneous injuries in some individuals having family history and genetic factors. These scars decrease the quality of life (QOL) of patients greatly, due to the pain, itching, contracture, cosmetic problems, and so on, depending on the location of the scars. Treatment/prevention that will satisfy patients’ QOL is still under development. In this article, we review pharmacotherapy for treating KD and HTS, including the prevention of postsurgical recurrence (especially KD). Pharmacotherapy involves monotherapy using a single drug and combination pharmacotherapy using multiple drugs, where drugs are administered orally, topically and/or through intralesional injection. In addition, pharmacotherapy for KD/HTS is sometimes combined with surgical excision and/or with physical therapy such as cryotherapy, laser therapy, radiotherapy including brachytherapy, and silicone gel/sheeting. The results regarding the clinical effectiveness of each mono-pharmacotherapy for KD/HTS are not always consistent but rather scattered among researchers. Multimodal combination pharmacotherapy that targets multiple sites simultaneously is more effective than mono-pharmacotherapy. The literature was searched using PubMed, Google Scholar, and Online search engines.

Pharmacotherapy for Keloids and Hypertrophic Scars

Corneal neovascularization can impair vision and result in a poor quality of life. The pathogenesis involves a complex interplay of angiogenic factors, notably vascular endothelial growth factor (VEGF). This review provides a comprehensive overview of potential therapies for corneal neovascularization, covering tissue inhibitors of metalloproteinases (TIMPs), transforming growth factor beta (TGF-β) inhibitors, interleukin-1L receptor antagonist (IL-1 Ra), nitric oxide synthase (NOS) isoforms, galectin-3 inhibitors, retinal pigment epithelium-derived factor (PEDF), platelet-derived growth factor (PDGF) receptor inhibitors, and surgical treatments. Conventional treatments include anti-VEGF therapy and laser interventions, while emerging therapies such as immunosuppressive drugs (cyclosporine and rapamycin) have been explored. Losartan and decorin are potential antifibrotic agents that mitigate TGF-β-induced fibrosis. Ocular nanosystems are innovative drug-delivery platforms that facilitate the targeted release of therapeutic agents. Gene therapies, such as small interfering RNA and antisense oligonucleotides, are promising approaches for selectively inhibiting angiogenesis-related gene expression. Aganirsen is efficacious in reducing the corneal neovascularization area without significant adverse effects. These multifaceted approaches underscore the corneal neovascularization management complexity and highlight ideas for enhancing therapeutic outcomes. Furthermore, the importance of combination therapies and the need for further research to develop specific inhibitors while considering their therapeutic efficacy and potential adverse effects are discussed.

Available Therapeutic Options for Corneal Neovascularization: A Review

Hypertrophic scars (HSs) develop due to excessive collagen deposition and abnormal fibroblast proliferation during wound healing, significantly impacting patient quality of life. Three dosages of GA ointments were administered to rabbit ear HS models to investigate the potential efficacy and mechanism of gallic acid (GA) on HS. Daily application of ointment was performed on the matrix group, the GA ointment groups, and the silicone gel group for 28 days. (No drug treatment was performed on the skin and model groups as a blank group and vehicle group, and silicone gel ointment was topically administered to the silicone gel group as a positive control group.) Scar specimens were collected for histopathology analysis, RNA sequencing analysis, real-time quantitative polymerase chain reaction, and Western blot analysis at the first, second, and fourth weeks after the treatment. Low-dose and medium-dose GA effectively suppressed HS formation and markedly decreased fibroblast infiltration levels and scar thickness. Moreover, decreased expression of TRPC3 mRNA and TGF-β1, p-Smad2/3, and Smad2/3 protein was observed in the low- and medium-dose GA groups and the silicone gel group. This study provides evidence for the efficacy of GA in treating HS and sheds light on its potential underlying pharmacological mechanisms.

Gallic Acid Treats Hypertrophic Scar in Rabbit Ears via the TGF-β/Smad and TRPC3 Signaling Pathways

Infection and vascular dysfunction are two major reasons for delayed wound healing, especially in the scenario of multidrug-resistant bacterial has been a challenge for antibiotics usage. Probiotics are effective in fighting pathogens, while avoiding the destruction of skin microbiome. However, the viability of probiotics is a major obstacle in clinical application. As a non-protein proangiogenic drug, deferoxamine (DFO) has significant advantages over traditional growth factors in terms of cost, storage and transportation conditions, and stability. However, there is still a problem of short half-life that requires reliable drug delivery carriers to maximize its effect. Here, we developed multiple-chambered microgels using electrospray and microfluidics. Lactobacillus fermentum (LF) and DFO, respectively, for the management of multidrug-resistant Pseudomonas aeruginosa (MPA) and promotion of wound healing. We first tested five probiotics isolated from healthy people and found LF inhibiting the growth of MPA by lowering local pH and antimicrobial substances. The multi-chambered microgels effectively inhibited MPA by delivering probiotics, they can also protect probiotics from antibiotics. DFO promoted the angiogenesis of human umbilical venous endothelial cells. The microgel system had good biocompatibility and hemocompatibility. In a MPA infected wound, the microgel system effectively alleviated wound infection by 87.44%, improved angiogenesis by 29.32% and accelerated wound healing. This work suggests that multi-compartmented microgels loaded with probiotics and deferoxamine have great potential in wounds with multidrug-resistant bacteria. 

Multi-comparted microgels delivering human derived probiotics and deferoxamine for multidrug-resistant infection and healing

The aim of this study was to study the curative effect and the relative mechanism of modified photodynamic therapy combined with Taohong Siwu Decoction in the treatment of hyperplastic scar after severe burn, in order to provide a stable, safe and satisfactory scheme for scar repair.Forty cases with hyperplastic scars after severe burns admitted to the plastic surgery department from May 2021 to May 2022 were divided into a control group and an observation group by means of the random number table method. The control group was treated with ordinary laser therapy combined with Taohong Siwu Decoction, while the observation group was treated with modified photodynamic therapy combined with Taohong Siwu Decoction. The Vancouver Scar Scale (VSS) was assessed in both groups, and the clinical effectiveness of both groups was compared. HE-staining was performed on the scar tissue of the same patient before and after treatment to observe the changes in the arrangement of fibroblasts. The Vascular Endothelial Growth Factor (VEGF), β-Transforming Growth Factor (TGF-β), and Platelet-Derived Growth Factor (PDGF) in the tissue samples of both groups were detected by quantitative real-time PCR. The patients were followed up for 6 months, and their satisfaction, side effects, and scar recurrence were observed.Compared with the control group, the VSS score in the observation group was lower (p < 0.05). The therapeutic effect of the observation group was superior to the control group after 3 months (p < 0.05). After 3-months of therapy, the arrangement of fibroblasts in the scar became looser in two groups, and the observation group was more looser. The VEGF, TGF-β and PDGF levels in tissue samples of the observation group were lower than those in the control group after 3 months of treatment (p < 0.05). The satisfaction of the observation group was higher than that of the control group (p < 0.05). The adverse reactions between the two groups showed no difference (p > 0.05), while the recurrence rate was lower in the observation group (p < 0.05).Modified photodynamic therapy combined with Taohong Siwu Decoction shows remarkable efficacy in patients with hyperplastic scars after severe burns. It can improve the color, thickness, vascular distribution, and softness of the scar, and reduce the level of cytokines related to tissue repair. At the same time, it can improve patients' satisfaction with the aesthetic appearance and reduce the recurrence rate, providing a new comprehensive therapy that is safer and more effective, simple and quick, and easy to promote in the clinic. 

Clinical study of modified photodynamic therapy combined with Taohong Siwu Decoction in treating hypertrophic scar after severe burn

Angiogenesis modulation-mediated inhibitory effects of tacrolimus on hypertrophic scar formation.

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Angiogenesis modulation-mediated inhibitory effects of tacrolimus on hypertrophic scar formation.