Pub Date : 2023-10-30eCollection Date: 2023-01-01DOI: 10.1093/burnst/tkad034
Yunwei Wang, Kuo Shen, Yulin Sun, Peng Cao, Jia Zhang, Wanfu Zhang, Yang Liu, Hao Zhang, Yang Chen, Shaohui Li, Chaolei Xu, Chao Han, Yating Qiao, Qingyi Zhang, Bin Wang, Liang Luo, Yunshu Yang, Hao Guan
Background: Non-healing wounds are an intractable problem of major clinical relevance. Evidence has shown that dermal papilla cells (DPCs) may regulate the wound-healing process by secreting extracellular vesicles (EVs). However, low isolation efficiency and restricted cell viability hinder the applications of DPC-EVs in wound healing. In this study, we aimed to develop novel 3D-DPC spheroids (tdDPCs) based on self-feeder 3D culture and to evaluate the roles of tdDPC-EVs in stimulating angiogenesis and skin wound healing.
Methods: To address the current limitations of DPC-EVs, we previously developed a self-feeder 3D culture method to construct tdDPCs. DPCs and tdDPCs were identified using immunofluorescence staining and flow cytometry. Subsequently, we extracted EVs from the cells and compared the effects of DPC-EVs and tdDPC-EVs on human umbilical vein endothelial cells (HUVECs) in vitro using immunofluorescence staining, a scratch-wound assay and a Transwell assay. We simultaneously established a murine model of full-thickness skin injury and evaluated the effects of DPC-EVs and tdDPC-EVs on wound-healing efficiency in vivo using laser Doppler, as well as hematoxylin and eosin, Masson, CD31 and α-SMA staining. To elucidate the underlying mechanism, we conducted RNA sequencing (RNA-seq) of tdDPC-EV- and phosphate-buffered saline-treated HUVECs. To validate the RNA-seq data, we constructed knockdown and overexpression vectors of Krüppel-like factor 4 (KLF4). Western blotting, a scratch-wound assay, a Transwell assay and a tubule-formation test were performed to detect the protein expression, cell migration and lumen-formation ability of KLF4 and vascular endothelial growth factor A (VEGFA) in HUVECs incubated with tdDPC-EVs after KLF4 knockdown or overexpression. Dual-luciferase reporter gene assays were conducted to verify the activation effect of KLF4 on VEGFA.
Results: We successfully cultured tdDPCs and extracted EVs from DPCs and tdDPCs. The tdDPC-EVs significantly promoted the proliferation, lumen formation and migration of HUVECs. Unlike DPC-EVs, tdDPC-EVs exhibited significant advantages in terms of promoting angiogenesis, accelerating wound healing and enhancing wound-healing efficiency both in vitro and in vivo. Bioinformatics analysis and further functional experiments verified that the tdDPC-EV-regulated KLF4/VEGFA axis is pivotal in accelerating wound healing.
Conclusions: 3D cultivation can be utilized as an innovative optimization strategy to effectively develop DPC-derived EVs for the treatment of skin wounds. tdDPC-EVs significantly enhance wound healing via KLF4/VEGFA-driven angiogenesis.
{"title":"Extracellular vesicles from 3D cultured dermal papilla cells improve wound healing via Krüppel-like factor 4/vascular endothelial growth factor A -driven angiogenesis.","authors":"Yunwei Wang, Kuo Shen, Yulin Sun, Peng Cao, Jia Zhang, Wanfu Zhang, Yang Liu, Hao Zhang, Yang Chen, Shaohui Li, Chaolei Xu, Chao Han, Yating Qiao, Qingyi Zhang, Bin Wang, Liang Luo, Yunshu Yang, Hao Guan","doi":"10.1093/burnst/tkad034","DOIUrl":"https://doi.org/10.1093/burnst/tkad034","url":null,"abstract":"<p><strong>Background: </strong>Non-healing wounds are an intractable problem of major clinical relevance. Evidence has shown that dermal papilla cells (DPCs) may regulate the wound-healing process by secreting extracellular vesicles (EVs). However, low isolation efficiency and restricted cell viability hinder the applications of DPC-EVs in wound healing. In this study, we aimed to develop novel 3D-DPC spheroids (tdDPCs) based on self-feeder 3D culture and to evaluate the roles of tdDPC-EVs in stimulating angiogenesis and skin wound healing.</p><p><strong>Methods: </strong>To address the current limitations of DPC-EVs, we previously developed a self-feeder 3D culture method to construct tdDPCs. DPCs and tdDPCs were identified using immunofluorescence staining and flow cytometry. Subsequently, we extracted EVs from the cells and compared the effects of DPC-EVs and tdDPC-EVs on human umbilical vein endothelial cells (HUVECs) <i>in vitro</i> using immunofluorescence staining, a scratch-wound assay and a Transwell assay. We simultaneously established a murine model of full-thickness skin injury and evaluated the effects of DPC-EVs and tdDPC-EVs on wound-healing efficiency <i>in vivo</i> using laser Doppler, as well as hematoxylin and eosin, Masson, CD31 and α-SMA staining. To elucidate the underlying mechanism, we conducted RNA sequencing (RNA-seq) of tdDPC-EV- and phosphate-buffered saline-treated HUVECs. To validate the RNA-seq data, we constructed knockdown and overexpression vectors of Krüppel-like factor 4 (KLF4). Western blotting, a scratch-wound assay, a Transwell assay and a tubule-formation test were performed to detect the protein expression, cell migration and lumen-formation ability of KLF4 and vascular endothelial growth factor A (VEGFA) in HUVECs incubated with tdDPC-EVs after KLF4 knockdown or overexpression. Dual-luciferase reporter gene assays were conducted to verify the activation effect of KLF4 on VEGFA.</p><p><strong>Results: </strong>We successfully cultured tdDPCs and extracted EVs from DPCs and tdDPCs. The tdDPC-EVs significantly promoted the proliferation, lumen formation and migration of HUVECs. Unlike DPC-EVs, tdDPC-EVs exhibited significant advantages in terms of promoting angiogenesis, accelerating wound healing and enhancing wound-healing efficiency both <i>in vitro</i> and <i>in vivo</i>. Bioinformatics analysis and further functional experiments verified that the tdDPC-EV-regulated KLF4/VEGFA axis is pivotal in accelerating wound healing.</p><p><strong>Conclusions: </strong>3D cultivation can be utilized as an innovative optimization strategy to effectively develop DPC-derived EVs for the treatment of skin wounds. tdDPC-EVs significantly enhance wound healing via KLF4/VEGFA-driven angiogenesis.</p>","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2023-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10615254/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71420990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-30eCollection Date: 2023-01-01DOI: 10.1093/burnst/tkad043
Álvaro Sierra-Sánchez, Brice Magne, Etienne Savard, Christian Martel, Karel Ferland, Martin A Barbier, Anabelle Demers, Danielle Larouche, Salvador Arias-Santiago, Lucie Germain
Background: The aim of this in vitro study was to compare side-by-side two models of human bilayered tissue-engineered skin substitutes (hbTESSs) designed for the treatment of severely burned patients. These are the scaffold-free self-assembled skin substitute (SASS) and the human plasma-based skin substitute (HPSS).
Methods: Fibroblasts and keratinocytes from three humans were extracted from skin biopsies (N = 3) and cells from the same donor were used to produce both hbTESS models. For SASS manufacture, keratinocytes were seeded over three self-assembled dermal sheets comprising fibroblasts and the extracellular matrix they produced (n = 12), while for HPSS production, keratinocytes were cultured over hydrogels composed of fibroblasts embedded in either plasma as unique biomaterial (Fibrin), plasma combined with hyaluronic acid (Fibrin-HA) or plasma combined with collagen (Fibrin-Col) (n/biomaterial = 9). The production time was 46-55 days for SASSs and 32-39 days for HPSSs. Substitutes were characterized by histology, mechanical testing, PrestoBlue™-assay, immunofluorescence (Ki67, Keratin (K) 10, K15, K19, Loricrin, type IV collagen) and Western blot (type I and IV collagens).
Results: The SASSs were more resistant to tensile forces (p-value < 0.01) but less elastic (p-value < 0.001) compared to HPSSs. A higher number of proliferative Ki67+ cells were found in SASSs although their metabolic activity was lower. After epidermal differentiation, no significant difference was observed in the expression of K10, K15, K19 and Loricrin. Overall, the production of type I and type IV collagens and the adhesive strength of the dermal-epidermal junction was higher in SASSs.
Conclusions: This study demonstrates, for the first time, that both hbTESS models present similar in vitro biological characteristics. However, mechanical properties differ and future in vivo experiments will aim to compare their wound healing potential.
{"title":"<i>In vitro</i> comparison of human plasma-based and self-assembled tissue-engineered skin substitutes: two different manufacturing processes for the treatment of deep and difficult to heal injuries.","authors":"Álvaro Sierra-Sánchez, Brice Magne, Etienne Savard, Christian Martel, Karel Ferland, Martin A Barbier, Anabelle Demers, Danielle Larouche, Salvador Arias-Santiago, Lucie Germain","doi":"10.1093/burnst/tkad043","DOIUrl":"10.1093/burnst/tkad043","url":null,"abstract":"<p><strong>Background: </strong>The aim of this <i>in vitro</i> study was to compare side-by-side two models of human bilayered tissue-engineered skin substitutes (hbTESSs) designed for the treatment of severely burned patients. These are the scaffold-free self-assembled skin substitute (SASS) and the human plasma-based skin substitute (HPSS).</p><p><strong>Methods: </strong>Fibroblasts and keratinocytes from three humans were extracted from skin biopsies (N = 3) and cells from the same donor were used to produce both hbTESS models. For SASS manufacture, keratinocytes were seeded over three self-assembled dermal sheets comprising fibroblasts and the extracellular matrix they produced (n = 12), while for HPSS production, keratinocytes were cultured over hydrogels composed of fibroblasts embedded in either plasma as unique biomaterial (Fibrin), plasma combined with hyaluronic acid (Fibrin-HA) or plasma combined with collagen (Fibrin-Col) (n/biomaterial = 9). The production time was 46-55 days for SASSs and 32-39 days for HPSSs. Substitutes were characterized by histology, mechanical testing, PrestoBlue™-assay, immunofluorescence (Ki67, Keratin (K) 10, K15, K19, Loricrin, type IV collagen) and Western blot (type I and IV collagens).</p><p><strong>Results: </strong>The SASSs were more resistant to tensile forces (<i>p-</i>value < 0.01) but less elastic (<i>p-</i>value < 0.001) compared to HPSSs. A higher number of proliferative Ki67<sup>+</sup> cells were found in SASSs although their metabolic activity was lower. After epidermal differentiation, no significant difference was observed in the expression of K10, K15, K19 and Loricrin. Overall, the production of type I and type IV collagens and the adhesive strength of the dermal-epidermal junction was higher in SASSs.</p><p><strong>Conclusions: </strong>This study demonstrates, for the first time, that both hbTESS models present similar <i>in vitro</i> biological characteristics. However, mechanical properties differ and future <i>in vivo</i> experiments will aim to compare their wound healing potential.</p>","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2023-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10615253/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71420989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wound healing is a long-term, multi-stage biological process that mainly includes haemostatic, inflammatory, proliferative and tissue remodelling phases. Controlling infection and inflammation and promoting tissue regeneration can contribute well to wound healing. Smart biomaterials offer significant advantages in wound healing because of their ability to control wound healing in time and space. Understanding how biomaterials are designed for different stages of wound healing will facilitate future personalized material tailoring for different wounds, making them beneficial for wound therapy. This review summarizes the design approaches of biomaterials in the field of anti-inflammatory, antimicrobial and tissue regeneration, highlights the advanced precise control achieved by biomaterials in different stages of wound healing and outlines the clinical and practical applications of biomaterials in wound healing.
{"title":"Tailored biomedical materials for wound healing.","authors":"Wenhui Liu, Lihua Zu, Shanzheng Wang, Jingyao Li, Xiaoyuan Fei, Meng Geng, Chunlei Zhu, Hui Shi","doi":"10.1093/burnst/tkad040","DOIUrl":"10.1093/burnst/tkad040","url":null,"abstract":"<p><p>Wound healing is a long-term, multi-stage biological process that mainly includes haemostatic, inflammatory, proliferative and tissue remodelling phases. Controlling infection and inflammation and promoting tissue regeneration can contribute well to wound healing. Smart biomaterials offer significant advantages in wound healing because of their ability to control wound healing in time and space. Understanding how biomaterials are designed for different stages of wound healing will facilitate future personalized material tailoring for different wounds, making them beneficial for wound therapy. This review summarizes the design approaches of biomaterials in the field of anti-inflammatory, antimicrobial and tissue regeneration, highlights the advanced precise control achieved by biomaterials in different stages of wound healing and outlines the clinical and practical applications of biomaterials in wound healing.</p>","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":null,"pages":null},"PeriodicalIF":6.3,"publicationDate":"2023-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10605015/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71410743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Persistent hyperglycaemia in diabetes causes functional abnormalities of human dermal fibroblasts (HDFs), partially leading to delayed skin wound healing. Extracellular vesicles (EVs) containing multiple pro-healing microRNAs (miRNAs) have been shown to exert therapeutic effects on diabetic wound healing. The present study aimed to observe the effects of EVs derived from placental mesenchymal stem cells (P-MSC-EVs) on diabetic wound healing and high glucose (HG)-induced senescent fibroblasts and to explore the underlying mechanisms.
Methods: P-MSC-EVs were isolated by differential ultracentrifugation and locally injected into the full-thickness skin wounds of diabetic mice, to observe the beneficial effects on wound healing in vivo by measuring wound closure rates and histological analysis. Next, a series of assays were conducted to evaluate the effects of low (2.28 x 1010 particles/ml) and high (4.56 x 1010 particles/ml) concentrations of P-MSC-EVs on the senescence, proliferation, migration, and apoptosis of HG-induced senescent HDFs in vitro. Then, miRNA microarrays and real-time quantitative PCR (RT-qPCR) were carried out to detect the differentially expressed miRNAs in HDFs after EVs treatment. Specific RNA inhibitors, miRNA mimics, and small interfering RNA (siRNA) were used to evaluate the role of a candidate miRNA and its target genes in P-MSC-EV-induced improvements in the function of HG-induced senescent HDFs.
Results: Local injection of P-MSC-EVs into diabetic wounds accelerated wound closure and reduced scar widths, with better-organized collagen deposition and decreased p16INK4a expression. In vitro, P-MSC-EVs enhanced the antisenescence, proliferation, migration, and antiapoptotic abilities of HG-induced senescent fibroblasts in a dose-dependent manner. MiR-145-5p was found to be highly enriched in P-MSC-EVs. MiR-145-5p inhibitors effectively attenuated the P-MSC-EV-induced functional improvements of senescent fibroblasts. MiR-145-5p mimics simulated the effects of P-MSC-EVs on functional improvements of fibroblasts by suppressing the expression of cyclin-dependent kinase inhibitor 1A and activating the extracellular signal regulated kinase (Erk)/protein kinase B (Akt) signaling pathway. Furthermore, local application of miR-145-5p agomir mimicked the effects of P-MSC-EVs on wound healing.
Conclusions: These results suggest that P-MSC-EVs accelerate diabetic wound healing by improving the function of senescent fibroblasts through the transfer of miR-145-5p, which targets cyclin-dependent kinase inhibitor 1A to activate the Erk/Akt signaling pathway. P-MSC-EVs are promising therapeutic candidates for diabetic wound treatment.
背景:糖尿病患者持续的高血糖会导致人类真皮成纤维细胞(HDFs)功能异常,部分导致皮肤伤口愈合延迟。含有多种促进愈合的微小RNA(miRNA)的细胞外小泡(EVs)已被证明对糖尿病伤口愈合具有治疗作用。本研究旨在观察来自胎盘间充质干细胞(P-MSC-EVs)的EVs对糖尿病伤口愈合和高糖(HG)诱导的衰老成纤维细胞的影响,并探讨其潜在机制。方法:采用差速超速离心法分离P-MSC-EV,并将其局部注射到糖尿病小鼠全层皮肤伤口中,通过测量伤口闭合率和组织学分析,观察其对体内伤口愈合的有益作用。接下来,进行了一系列测定,以评估低(2.28 x 1010颗粒/ml)和高(4.56 x 1010颗粒g/ml)浓度的P-MSC-EVs对体外HG诱导的衰老HDFs的衰老、增殖、迁移和凋亡的影响。然后,进行miRNA微阵列和实时定量PCR(RT-qPCR)来检测EVs治疗后HDFs中差异表达的miRNA。使用特异性RNA抑制剂、miRNA模拟物和小干扰RNA(siRNA)来评估候选miRNA及其靶基因在P-MSC-EV诱导的HG诱导的衰老HDF功能改善中的作用,具有更好组织的胶原沉积和降低的p16INK4a表达。在体外,P-MSC-EVs以剂量依赖的方式增强HG诱导的衰老成纤维细胞的抗衰老、增殖、迁移和抗凋亡能力。发现MiR-145-5p在P-MSC-EV中高度富集。MiR-145-5p抑制剂有效地减弱了P-MSC-EV诱导的衰老成纤维细胞的功能改善。MiR-145-5p模拟物通过抑制细胞周期蛋白依赖性激酶抑制剂1A的表达和激活细胞外信号调节激酶(Erk)/蛋白激酶B(Akt)信号通路,模拟P-MSC-EVs对成纤维细胞功能改善的影响。此外,miR-145-5p agomir的局部应用模拟了P-MSC-EVs对伤口愈合的影响。结论:这些结果表明,P-MSC-EVs通过转移miR-145-5p改善衰老成纤维细胞的功能,从而加速糖尿病伤口愈合,miR-145-5p靶向细胞周期蛋白依赖性激酶抑制剂1A,激活Erk/Akt信号通路。P-MSC-EV是糖尿病伤口治疗的有前景的候选治疗药物。
{"title":"P-MSC-derived extracellular vesicles facilitate diabetic wound healing via miR-145-5p/ CDKN1A-mediated functional improvements of high glucose-induced senescent fibroblasts.","authors":"Jianlong Su, Qian Wei, Kui Ma, Yaxi Wang, Wenzhi Hu, Hao Meng, Qiankun Li, Yuehou Zhang, Wenhua Zhang, Haihong Li, Xiaobing Fu, Cuiping Zhang","doi":"10.1093/burnst/tkad010","DOIUrl":"https://doi.org/10.1093/burnst/tkad010","url":null,"abstract":"<p><strong>Background: </strong>Persistent hyperglycaemia in diabetes causes functional abnormalities of human dermal fibroblasts (HDFs), partially leading to delayed skin wound healing. Extracellular vesicles (EVs) containing multiple pro-healing microRNAs (miRNAs) have been shown to exert therapeutic effects on diabetic wound healing. The present study aimed to observe the effects of EVs derived from placental mesenchymal stem cells (P-MSC-EVs) on diabetic wound healing and high glucose (HG)-induced senescent fibroblasts and to explore the underlying mechanisms.</p><p><strong>Methods: </strong>P-MSC-EVs were isolated by differential ultracentrifugation and locally injected into the full-thickness skin wounds of diabetic mice, to observe the beneficial effects on wound healing <i>in vivo</i> by measuring wound closure rates and histological analysis. Next, a series of assays were conducted to evaluate the effects of low (2.28 x 10<sup>10</sup> particles/ml) and high (4.56 x 10<sup>10</sup> particles/ml) concentrations of P-MSC-EVs on the senescence, proliferation, migration, and apoptosis of HG-induced senescent HDFs <i>in vitro</i>. Then, miRNA microarrays and real-time quantitative PCR (RT-qPCR) were carried out to detect the differentially expressed miRNAs in HDFs after EVs treatment. Specific RNA inhibitors, miRNA mimics, and small interfering RNA (siRNA) were used to evaluate the role of a candidate miRNA and its target genes in P-MSC-EV-induced improvements in the function of HG-induced senescent HDFs.</p><p><strong>Results: </strong>Local injection of P-MSC-EVs into diabetic wounds accelerated wound closure and reduced scar widths, with better-organized collagen deposition and decreased p16INK4a expression. <i>In vitro</i>, P-MSC-EVs enhanced the antisenescence, proliferation, migration, and antiapoptotic abilities of HG-induced senescent fibroblasts in a dose-dependent manner. MiR-145-5p was found to be highly enriched in P-MSC-EVs. MiR-145-5p inhibitors effectively attenuated the P-MSC-EV-induced functional improvements of senescent fibroblasts. MiR-145-5p mimics simulated the effects of P-MSC-EVs on functional improvements of fibroblasts by suppressing the expression of cyclin-dependent kinase inhibitor 1A and activating the extracellular signal regulated kinase (Erk)/protein kinase B (Akt) signaling pathway. Furthermore, local application of miR-145-5p agomir mimicked the effects of P-MSC-EVs on wound healing.</p><p><strong>Conclusions: </strong>These results suggest that P-MSC-EVs accelerate diabetic wound healing by improving the function of senescent fibroblasts through the transfer of miR-145-5p, which targets cyclin-dependent kinase inhibitor 1A to activate the Erk/Akt signaling pathway. P-MSC-EVs are promising therapeutic candidates for diabetic wound treatment.</p>","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2023-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10583213/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49674555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-16eCollection Date: 2023-01-01DOI: 10.1093/burnst/tkad038
Ruzhen Zhang, Sheng Chen, Zhifan Yang, Ning Zhang, Kenan Guo, Keyi Lv, Zimo Zhou, Meijiao Gao, Xiancheng Hu, Yongping Su, Jianming He, Fengchao Wang
Background: The rapid turnover of the intestinal epithelium is driven by the proliferation and differentiation of intestinal stem cells (ISCs). The dynamics of the F-actin cytoskeleton are critical for maintaining intercellular force and the signal transduction network. However, it remains unclear how direct interference with actin polymerization impacts ISC homeostasis. This study aims to reveal the regulatory effects of the F-actin cytoskeleton on the homeostasis of intestinal epithelium, as well as the potential risks of benproperine (BPP) as an anti-tumor drug.
Methods: Phalloidin fluorescence staining was utilized to test F-actin polymerization. Flow cytometry and IHC staining were employed to discriminate different types of intestinal epithelial cells. Cell proliferation was assessed through bromo-deoxyuridine (BrdU) and 5-ethynyl-2'-deoxyuridine (EdU) incorporation assays. The proliferation and differentiation of intestinal stem cells were replicated in vitro through organoid culture. Epithelial migration was evaluated through BrdU pulse labeling and chasing in mice.
Results: The F-actin content was observed to significantly increase as crypt cells migrated into the villus region. Additionally, actin polymerization in secretory cells, especially in Paneth cells (PCs), was much higher than that in neighboring ISCs. Treatment with the newly identified actin-related protein 2/3 complex subunit 2 (ARPC2) inhibitor BPP led to a dose-dependent increase or inhibition of intestinal organoid growth in vitro and crypt cell proliferation in vivo. Compared with the vehicle group, BPP treatment decreased the expression of Lgr5 ISC feature genes in vivo and in organoid culture. Meanwhile, PC differentiation derived from ISCs and progenitors was decreased by inhibition of F-actin polymerization. Mechanistically, BPP-induced actin polymerization inhibition may activate the Yes1-associated transcriptional regulator pathway, which affects ISC proliferation and differentiation. Accordingly, BPP treatment affected intestinal epithelial cell migration in a dose-dependent manner.
Conclusion: Our findings indicate that the regulation of cytoskeleton reorganization can affect ISC homeostasis. In addition, inhibiting ARPC2 with the Food and Drug Administration-approved drug BPP represents a novel approach to influencing the turnover of intestinal epithelial cells.
{"title":"Actin polymerization inhibition by targeting ARPC2 affects intestinal stem cell homeostasis.","authors":"Ruzhen Zhang, Sheng Chen, Zhifan Yang, Ning Zhang, Kenan Guo, Keyi Lv, Zimo Zhou, Meijiao Gao, Xiancheng Hu, Yongping Su, Jianming He, Fengchao Wang","doi":"10.1093/burnst/tkad038","DOIUrl":"10.1093/burnst/tkad038","url":null,"abstract":"<p><strong>Background: </strong>The rapid turnover of the intestinal epithelium is driven by the proliferation and differentiation of intestinal stem cells (ISCs). The dynamics of the F-actin cytoskeleton are critical for maintaining intercellular force and the signal transduction network. However, it remains unclear how direct interference with actin polymerization impacts ISC homeostasis. This study aims to reveal the regulatory effects of the F-actin cytoskeleton on the homeostasis of intestinal epithelium, as well as the potential risks of benproperine (BPP) as an anti-tumor drug.</p><p><strong>Methods: </strong>Phalloidin fluorescence staining was utilized to test F-actin polymerization. Flow cytometry and IHC staining were employed to discriminate different types of intestinal epithelial cells. Cell proliferation was assessed through bromo-deoxyuridine (BrdU) and 5-ethynyl-2'-deoxyuridine (EdU) incorporation assays. The proliferation and differentiation of intestinal stem cells were replicated <i>in vitro</i> through organoid culture. Epithelial migration was evaluated through BrdU pulse labeling and chasing in mice.</p><p><strong>Results: </strong>The F-actin content was observed to significantly increase as crypt cells migrated into the villus region. Additionally, actin polymerization in secretory cells, especially in Paneth cells (PCs), was much higher than that in neighboring ISCs. Treatment with the newly identified actin-related protein 2/3 complex subunit 2 (ARPC2) inhibitor BPP led to a dose-dependent increase or inhibition of intestinal organoid growth <i>in vitro</i> and crypt cell proliferation <i>in vivo</i>. Compared with the vehicle group, BPP treatment decreased the expression of Lgr5 ISC feature genes <i>in vivo</i> and in organoid culture. Meanwhile, PC differentiation derived from ISCs and progenitors was decreased by inhibition of F-actin polymerization. Mechanistically, BPP-induced actin polymerization inhibition may activate the Yes1-associated transcriptional regulator pathway, which affects ISC proliferation and differentiation. Accordingly, BPP treatment affected intestinal epithelial cell migration in a dose-dependent manner.</p><p><strong>Conclusion: </strong>Our findings indicate that the regulation of cytoskeleton reorganization can affect ISC homeostasis. In addition, inhibiting ARPC2 with the Food and Drug Administration-approved drug BPP represents a novel approach to influencing the turnover of intestinal epithelial cells.</p>","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2023-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10578047/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41232571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Multidrug-resistant (MDR) gram-negative bacteria-related infectious diseases have caused an increase in the public health burden and mortality. Moreover, the formation of biofilms makes these bacteria difficult to control. Therefore, developing novel interventions to combat MDR gram-negative bacteria and their biofilms-related infections are urgently needed. The purpose of this study was to develop a multifunctional nanoassembly (IRNB) based on IR-780 and N, N'-di-sec-butyl-N, N'- dinitroso-1,4-phenylenediamine (BNN6) for synergistic effect on the infected wounds and subcutaneous abscesses caused by gram-negative bacteria.
Methods: The characterization and bacteria-targeting ability of IRNB were investigated. The bactericidal efficacy of IRNB against gram-negative bacteria and their biofilms was demonstrated by crystal violet staining assay, plate counting method and live/dead staining in vitro. The antibacterial efficiency of IRNB was examined on a subcutaneous abscess and cutaneous infected wound model in vivo. A cell counting kit-8 assay, Calcein/PI cytotoxicity assay, hemolysis assay and intravenous injection assay were performed to detect the biocompatibility of IRNB in vitro and in vivo.
Results: Herein, we successfully developed a multifunctional nanoassembly IRNB based on IR-780 and BNN6 for synergistic photothermal therapy (PTT), photodynamic therapy (PDT) and nitric oxide (NO) effect triggered by an 808 nm laser. This nanoassembly could accumulate specifically at the infected sites of MDR gram-negative bacteria and their biofilms via the covalent coupling effect. Upon irradiation with an 808 nm laser, IRNB was activated and produced both reactive oxygen species (ROS) and hyperthermia. The local hyperthermia could induce NO generation, which further reacted with ROS to generate ONOO-, leading to the enhancement of bactericidal efficacy. Furthermore, NO and ONOO- could disrupt the cell membrane, which converts bacteria to an extremely susceptible state and further enhances the photothermal effect. In this study, IRNB showed a superior photothermal-photodynamic-chemo (NO) synergistic therapeutic effect on the infected wounds and subcutaneous abscesses caused by gram-negative bacteria. This resulted in effective control of associated infections, relief of inflammation, promotion of re-epithelization and collagen deposition, and regulation of angiogenesis during wound healing. Moreover, IRNB exhibited excellent biocompatibility, both in vitro and in vivo.
Conclusions: The present research suggests that IRNB can be considered a promising alternative for treating infections caused by MDR gram-negative bacteria and their biofilms.
{"title":"A photoactivatable and phenylboronic acid-functionalized nanoassembly for combating multidrug-resistant gram-negative bacteria and their biofilms.","authors":"Xiaoqing Zhou, Lanlan Dong, Baohua Zhao, Guangyun Hu, Can Huang, Tengfei Liu, Yifei Lu, Mengxue Zheng, Yanlan Yu, Zengjun Yang, Shaowen Cheng, Yan Xiong, Gaoxing Luo, Wei Qian, Rui Yin","doi":"10.1093/burnst/tkad041","DOIUrl":"10.1093/burnst/tkad041","url":null,"abstract":"<p><strong>Background: </strong>Multidrug-resistant (MDR) gram-negative bacteria-related infectious diseases have caused an increase in the public health burden and mortality. Moreover, the formation of biofilms makes these bacteria difficult to control. Therefore, developing novel interventions to combat MDR gram-negative bacteria and their biofilms-related infections are urgently needed. The purpose of this study was to develop a multifunctional nanoassembly (IRNB) based on IR-780 and N, N'-di-sec-butyl-N, N'- dinitroso-1,4-phenylenediamine (BNN6) for synergistic effect on the infected wounds and subcutaneous abscesses caused by gram-negative bacteria.</p><p><strong>Methods: </strong>The characterization and bacteria-targeting ability of IRNB were investigated. The bactericidal efficacy of IRNB against gram-negative bacteria and their biofilms was demonstrated by crystal violet staining assay, plate counting method and live/dead staining <i>in vitro</i>. The antibacterial efficiency of IRNB was examined on a subcutaneous abscess and cutaneous infected wound model <i>in vivo</i>. A cell counting kit-8 assay, Calcein/PI cytotoxicity assay, hemolysis assay and intravenous injection assay were performed to detect the biocompatibility of IRNB <i>in vitro</i> and <i>in vivo</i>.</p><p><strong>Results: </strong>Herein, we successfully developed a multifunctional nanoassembly IRNB based on IR-780 and BNN6 for synergistic photothermal therapy (PTT), photodynamic therapy (PDT) and nitric oxide (NO) effect triggered by an 808 nm laser. This nanoassembly could accumulate specifically at the infected sites of MDR gram-negative bacteria and their biofilms via the covalent coupling effect. Upon irradiation with an 808 nm laser, IRNB was activated and produced both reactive oxygen species (ROS) and hyperthermia. The local hyperthermia could induce NO generation, which further reacted with ROS to generate ONOO<sup>-</sup>, leading to the enhancement of bactericidal efficacy. Furthermore, NO and ONOO<sup>-</sup> could disrupt the cell membrane, which converts bacteria to an extremely susceptible state and further enhances the photothermal effect. In this study, IRNB showed a superior photothermal-photodynamic-chemo (NO) synergistic therapeutic effect on the infected wounds and subcutaneous abscesses caused by gram-negative bacteria. This resulted in effective control of associated infections, relief of inflammation, promotion of re-epithelization and collagen deposition, and regulation of angiogenesis during wound healing. Moreover, IRNB exhibited excellent biocompatibility, both <i>in vitro</i> and <i>in vivo</i>.</p><p><strong>Conclusions: </strong>The present research suggests that IRNB can be considered a promising alternative for treating infections caused by MDR gram-negative bacteria and their biofilms.</p>","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2023-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/7e/7f/tkad041.PMC10578387.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41232570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-04DOI: 10.22141/1608-1706.2.24.2023.940
O. Nekhlopochyn, V. Verbov, I. Cheshuk, M. Karpinsky, O. Yaresko
Background. The area of the thoracolumbar junction is characterized by a significant load that dictates increased requirements to stabilization, which should not only provide a reliable and rigid fixation, but also ensure the maximum uniform distribution of the load on all elements of both the metal structure and the bone tissue to exclude the failure of fixation in the long run. Purpose of the study is to investigate the influence of the transpedicular screw length and the presence of crosslinks on the load distribution during surgical resection of one vertebra from the thoracolumbar junction under the influence of axial compressive load. Materials and methods. We analyzed mathematical finite-element model of the part of thoracolumbar spine (Th9-L5), where the Th12 vertebra was removed and replaced by an interbody implant with additional fixation by a transpedicular system. Four variants of transpedicular fixation were modeled using short and long screws, as well as with and without two crosslinks. The stress-strain state of the models was studied under the influence of a vertical compressive distributed load of 350 N. Results. When using short screws and in the absence of crosslinks, the maximum stresses in the Th10, Th11, L1, and L2 vertebrae are 7.2, 5.3, 4.2, and 14.3 MPa, respectively, when using long screws without crosslinks — 6.5, 4.6, 3.8 and 13.5 MPa. The model with short screws and crosslinks shows 7.1, 4.4, 3.9 and 14.0 MPa, while the application of long screws with crosslinks is 6.3, 4.5, 3.5 and 13.2 MPa, respectively. Conclusions. With a compressive load, the use of long screws allows to reduce the level of stress in the bone elements of the models, the use of crosslinks provides greater rigidity to the posterior support of the transpedicular structure, which leads to an increase in stress on the fixing screws but allows to reduce the level of stress in the bone tissue.
{"title":"Mathematical modeling of variants of thoracolumbar junction transpedicular fixation after resection of Th12 vertebra under compressive load","authors":"O. Nekhlopochyn, V. Verbov, I. Cheshuk, M. Karpinsky, O. Yaresko","doi":"10.22141/1608-1706.2.24.2023.940","DOIUrl":"https://doi.org/10.22141/1608-1706.2.24.2023.940","url":null,"abstract":"Background. The area of the thoracolumbar junction is characterized by a significant load that dictates increased requirements to stabilization, which should not only provide a reliable and rigid fixation, but also ensure the maximum uniform distribution of the load on all elements of both the metal structure and the bone tissue to exclude the failure of fixation in the long run. Purpose of the study is to investigate the influence of the transpedicular screw length and the presence of crosslinks on the load distribution during surgical resection of one vertebra from the thoracolumbar junction under the influence of axial compressive load. Materials and methods. We analyzed mathematical finite-element model of the part of thoracolumbar spine (Th9-L5), where the Th12 vertebra was removed and replaced by an interbody implant with additional fixation by a transpedicular system. Four variants of transpedicular fixation were modeled using short and long screws, as well as with and without two crosslinks. The stress-strain state of the models was studied under the influence of a vertical compressive distributed load of 350 N. Results. When using short screws and in the absence of crosslinks, the maximum stresses in the Th10, Th11, L1, and L2 vertebrae are 7.2, 5.3, 4.2, and 14.3 MPa, respectively, when using long screws without crosslinks — 6.5, 4.6, 3.8 and 13.5 MPa. The model with short screws and crosslinks shows 7.1, 4.4, 3.9 and 14.0 MPa, while the application of long screws with crosslinks is 6.3, 4.5, 3.5 and 13.2 MPa, respectively. Conclusions. With a compressive load, the use of long screws allows to reduce the level of stress in the bone elements of the models, the use of crosslinks provides greater rigidity to the posterior support of the transpedicular structure, which leads to an increase in stress on the fixing screws but allows to reduce the level of stress in the bone tissue.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2023-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73433131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-04DOI: 10.22141/1608-1706.2.24.2023.944
O. Barkov, R.V. Malyk, O. Karpinska
Background. Complications are the main concern of patients and surgeons when considering spine surgery. One of the risk factors for complications in the thoracic and lumbar spinal segments, as well as segments adjacent to those with fusion, is changes in sagittal spinal-pelvic balance. Objective: to determine the effect of muscle changes that occur during surgical access for posterior bisegmental LIV-SI fusion on the load of the iliac crest surface in the sacroiliac joint. Materials and methods. Dynamic motion simulation modeling was performed using OpenSim software with the use of additional programs to calculate loading forces. The complete model of the human musculoskeletal system was taken as a basis. To compare the load force, four models were created: 1 — basic, all spinal motion segments are fully functional, 2 — fixation without changing the anatomical curves of the spine, 3 — fixation in the position of hyperlordosis; 4 — fixation with reproduction of hyperlordosis. For models 2–4, changes in the muscles were made that correspond to the effects of surgical posterior access to the lumbar spine for posterior instrumented fusion LIV-SI. The load on the area of interest was measured as the value of the projection of the force vector depending on the angle of torso inclination as a percentage of body weight. Results. Muscle strength and function were the same for all types of instrumental spinal fusion, and trauma during access was not taken into account. In model 1 (normal) with the upright position, the projection of the load force falls on the center of gravity of the vertebra. When tilted, the load force in the sagittal direction acts exclusively on the anterior ilium with a slight shift of 10 % forward. In normosthenic and hyperlordotic fixation, there is a shift in the projection of the load force on the posterior iliac crest in the upright position and its displacement to the center with the tilt. The displacement of the load center with the upright position in normosthenic fixation is associated with the exclusion of some extensor muscles from the calculation of fibers, which reduces their total strength and leads to sagittal imbalance with an increase in lordosis. Hypolordotic fixation (model 4) slightly shifts the projection of the load force in the upright position (by 3 %) and approaches the normal values of model 1 when tilted. Regarding vertical loads, for all models with muscle integrity impairment (models 2, 3, 4), the load in the upright position is greatly increased — on average by 60 % compared to the norm, with a decrease in body weight by 40–45 % when tilted. Conclusions. It has been proved that the load force on the surface of the iliac crest in the sacroiliac joint depends on the angle of instrumental fusion performed. The greatest changes are observed with the displacement of the load center during upright standing in the sagittal direction. In normosthenic and hyperlordotic fixation with decreased back muscle strength
{"title":"Study of load in the sacroiliac joint during dynamic simulation of movements in the lumbar spine on skeletal muscle models after posterior bisegmental fusion","authors":"O. Barkov, R.V. Malyk, O. Karpinska","doi":"10.22141/1608-1706.2.24.2023.944","DOIUrl":"https://doi.org/10.22141/1608-1706.2.24.2023.944","url":null,"abstract":"Background. Complications are the main concern of patients and surgeons when considering spine surgery. One of the risk factors for complications in the thoracic and lumbar spinal segments, as well as segments adjacent to those with fusion, is changes in sagittal spinal-pelvic balance. Objective: to determine the effect of muscle changes that occur during surgical access for posterior bisegmental LIV-SI fusion on the load of the iliac crest surface in the sacroiliac joint. Materials and methods. Dynamic motion simulation modeling was performed using OpenSim software with the use of additional programs to calculate loading forces. The complete model of the human musculoskeletal system was taken as a basis. To compare the load force, four models were created: 1 — basic, all spinal motion segments are fully functional, 2 — fixation without changing the anatomical curves of the spine, 3 — fixation in the position of hyperlordosis; 4 — fixation with reproduction of hyperlordosis. For models 2–4, changes in the muscles were made that correspond to the effects of surgical posterior access to the lumbar spine for posterior instrumented fusion LIV-SI. The load on the area of interest was measured as the value of the projection of the force vector depending on the angle of torso inclination as a percentage of body weight. Results. Muscle strength and function were the same for all types of instrumental spinal fusion, and trauma during access was not taken into account. In model 1 (normal) with the upright position, the projection of the load force falls on the center of gravity of the vertebra. When tilted, the load force in the sagittal direction acts exclusively on the anterior ilium with a slight shift of 10 % forward. In normosthenic and hyperlordotic fixation, there is a shift in the projection of the load force on the posterior iliac crest in the upright position and its displacement to the center with the tilt. The displacement of the load center with the upright position in normosthenic fixation is associated with the exclusion of some extensor muscles from the calculation of fibers, which reduces their total strength and leads to sagittal imbalance with an increase in lordosis. Hypolordotic fixation (model 4) slightly shifts the projection of the load force in the upright position (by 3 %) and approaches the normal values of model 1 when tilted. Regarding vertical loads, for all models with muscle integrity impairment (models 2, 3, 4), the load in the upright position is greatly increased — on average by 60 % compared to the norm, with a decrease in body weight by 40–45 % when tilted. Conclusions. It has been proved that the load force on the surface of the iliac crest in the sacroiliac joint depends on the angle of instrumental fusion performed. The greatest changes are observed with the displacement of the load center during upright standing in the sagittal direction. In normosthenic and hyperlordotic fixation with decreased back muscle strength","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2023-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79802057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-04DOI: 10.22141/1608-1706.2.24.2023.945
O. Drobotun
Background. Diagnosis and treatment of patients with malignant bone tumors requires continuous improvement of existing methods of diagnosis and treatment. Purpose: to improve the treatment results in patients with tumors of the femur and pelvis through the application of medical imaging technologies, 3D modeling and 3D printing of personalized models of bones and tumors, arthroplasty and bioactive ceramics. Materials and methods. Examination, treatment and monitoring of 28 patients with malignant tumors of the bones of the pelvis, lower extremities and examination of 16 apparently healthy people were performed. Computed tomography (CT) and magnetic resonance imaging (MRI), 3D modeling, biochemical markers of bone metabolism, arthroplasty, biomine were applied. Results. The technology of creating a 3D model of bones affected by malignant tumors has been developed based on the results of MRI, CT and 3D printing. Preoperative planning and training on 3D models reliably reduced intraoperative blood loss, duration of surgery, time of complete recovery of the extremity function, the risk of postoperative complications and, accordingly, increased the duration of the first recurrence-free period. The use of bone resorption and osteosynthesis markers allows to control the osseointegration of endoprosthesis and biomine, to diagnose recurrence/metastasis timely. Conclusions. The application of CT + MRI + 3D modeling + training on 3D models + tumor removal + arthroplasty + biomine algorithm provided functional results after 12 months: excellent — in 57.35 %, good — in 29.41 % of cases. Postoperative complications were observed only in 12.2 % of patients, local recurrences — in 7.3 %.
{"title":"Diagnosis, treatment and monitoring of patients with primary malignant tumors of the bones of the pelvis and lower extremities: promising technologies","authors":"O. Drobotun","doi":"10.22141/1608-1706.2.24.2023.945","DOIUrl":"https://doi.org/10.22141/1608-1706.2.24.2023.945","url":null,"abstract":"Background. Diagnosis and treatment of patients with malignant bone tumors requires continuous improvement of existing methods of diagnosis and treatment. Purpose: to improve the treatment results in patients with tumors of the femur and pelvis through the application of medical imaging technologies, 3D modeling and 3D printing of personalized models of bones and tumors, arthroplasty and bioactive ceramics. Materials and methods. Examination, treatment and monitoring of 28 patients with malignant tumors of the bones of the pelvis, lower extremities and examination of 16 apparently healthy people were performed. Computed tomography (CT) and magnetic resonance imaging (MRI), 3D modeling, biochemical markers of bone metabolism, arthroplasty, biomine were applied. Results. The technology of creating a 3D model of bones affected by malignant tumors has been developed based on the results of MRI, CT and 3D printing. Preoperative planning and training on 3D models reliably reduced intraoperative blood loss, duration of surgery, time of complete recovery of the extremity function, the risk of postoperative complications and, accordingly, increased the duration of the first recurrence-free period. The use of bone resorption and osteosynthesis markers allows to control the osseointegration of endoprosthesis and biomine, to diagnose recurrence/metastasis timely. Conclusions. The application of CT + MRI + 3D modeling + training on 3D models + tumor removal + arthroplasty + biomine algorithm provided functional results after 12 months: excellent — in 57.35 %, good — in 29.41 % of cases. Postoperative complications were observed only in 12.2 % of patients, local recurrences — in 7.3 %.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2023-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81826839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-04DOI: 10.22141/1608-1706.2.24.2023.943
O. D. Karpinskaya, M.Y. Karpinsky, O. Tyazhelov, V. Klymovytskyy, L.D. Goncharova, D. Yurchenko
Background. Dysplastic coxarthrosis is a special medical and social problem in the treatment of adult patients, often leading to disability, limiting the human’s ability to self-care. Arthroplasty for dysplastic coxarthrosis is only a certain stage in the restoration of the patient’s musculoskeletal function. Considering the large number of unsatisfactory results of arthroplasty in dysplastic coxarthrosis, a very important factor is the construction of a rehabilitation prognosis — the estimated probability of achieving the intended goals of rehabilitation or realization of rehabilitation potential, taking into account disease features and the patient’s capabilities. Objective: to determine the significant parameters of the dysplastic hip joint whose change affects the deficit of lower limb muscle strength after arthroplasty and the prospects for rehabilitation potential. Materials and methods. An X-ray examination of 23 dysplastic hip joints was performed. The following radiometric parameters were measured: acetabular depth; floor thickness; acetabular depth index; abductor moment arm; gravity moment arm; height and lateralization of the center of rotation of the femoral head relative to the center of the acetabulum rotation. To objectify the balance of muscle forces required to maintain pelvic balance when standing on one leg, a mathematical model was used created by the authors, which reflects the pelvis with the femur and the action vectors of the muscles of two groups: abductors and adductors of the hip. Results. Using the model of horizontal balance of the pelvis, the level of muscle strength deficit was calculated in patients before and after arthroplasty. It was found that in some of them the muscle strength deficit remained. With a linear regression model, an equation was created to determine the muscle strength deficit. According to the statistical analysis, no difference was found between the results of the regression equation and the mathematical model (p >> 0.05). The regression analysis has shown that the most significant factors for the result are the neck shaft angle, floor thickness, and head height. To determine the limits of radiometric parameters that affect the outcome of arthroplasty, patients were divided into 4 groups according to the level of calculated muscle strength deficit: group I — deficit of more than 20 %, group II — deficit of less than 20 %, group III — surplus of 20 % and group IV — surplus of more than 20 %. In general, patients improve their muscle strength, but the initial deficit greatly affects the outcome after arthroplasty. For patients in group I, pre- and postoperative rehabilitation is necessary to achieve a positive result. In group II, the main direction of rehabilitation is to increase muscle strength. For patients of groups III and IV, general rehabilitation measures can be used. Conclusions. The most important parameter that affects muscle strength after arthroplasty is the patient’s muscle streng
{"title":"Study of changes in the balance of the pelvic girdle muscles in patients with dysplastic coxarthrosis after arthroplasty","authors":"O. D. Karpinskaya, M.Y. Karpinsky, O. Tyazhelov, V. Klymovytskyy, L.D. Goncharova, D. Yurchenko","doi":"10.22141/1608-1706.2.24.2023.943","DOIUrl":"https://doi.org/10.22141/1608-1706.2.24.2023.943","url":null,"abstract":"Background. Dysplastic coxarthrosis is a special medical and social problem in the treatment of adult patients, often leading to disability, limiting the human’s ability to self-care. Arthroplasty for dysplastic coxarthrosis is only a certain stage in the restoration of the patient’s musculoskeletal function. Considering the large number of unsatisfactory results of arthroplasty in dysplastic coxarthrosis, a very important factor is the construction of a rehabilitation prognosis — the estimated probability of achieving the intended goals of rehabilitation or realization of rehabilitation potential, taking into account disease features and the patient’s capabilities. Objective: to determine the significant parameters of the dysplastic hip joint whose change affects the deficit of lower limb muscle strength after arthroplasty and the prospects for rehabilitation potential. Materials and methods. An X-ray examination of 23 dysplastic hip joints was performed. The following radiometric parameters were measured: acetabular depth; floor thickness; acetabular depth index; abductor moment arm; gravity moment arm; height and lateralization of the center of rotation of the femoral head relative to the center of the acetabulum rotation. To objectify the balance of muscle forces required to maintain pelvic balance when standing on one leg, a mathematical model was used created by the authors, which reflects the pelvis with the femur and the action vectors of the muscles of two groups: abductors and adductors of the hip. Results. Using the model of horizontal balance of the pelvis, the level of muscle strength deficit was calculated in patients before and after arthroplasty. It was found that in some of them the muscle strength deficit remained. With a linear regression model, an equation was created to determine the muscle strength deficit. According to the statistical analysis, no difference was found between the results of the regression equation and the mathematical model (p >> 0.05). The regression analysis has shown that the most significant factors for the result are the neck shaft angle, floor thickness, and head height. To determine the limits of radiometric parameters that affect the outcome of arthroplasty, patients were divided into 4 groups according to the level of calculated muscle strength deficit: group I — deficit of more than 20 %, group II — deficit of less than 20 %, group III — surplus of 20 % and group IV — surplus of more than 20 %. In general, patients improve their muscle strength, but the initial deficit greatly affects the outcome after arthroplasty. For patients in group I, pre- and postoperative rehabilitation is necessary to achieve a positive result. In group II, the main direction of rehabilitation is to increase muscle strength. For patients of groups III and IV, general rehabilitation measures can be used. Conclusions. The most important parameter that affects muscle strength after arthroplasty is the patient’s muscle streng","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2023-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79546280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}