ECM hydrogel coating mitigates the chronic inflammatory response to polypropylene mesh

Polypropylene has been used as a surgical mesh material for several decades. This non-degradable synthetic polymer provides mechanical strength, a predictable host response, and its use has resulted in reduced recurrence rates for ventral hernia and pelvic organ prolapse. However, polypropylene and similar synthetic materials are associated with a chronic local tissue inflammatory response and dense fibrous tissue deposition. These outcomes have prompted variations in mesh design to minimize the surface area interface and increase integration with host tissue. In contrast, biologic scaffold materials composed of extracellular matrix (ECM) are rapidly degraded in-vivo and are associated with constructive tissue remodeling and minimal fibrosis. The objective of the present study was to assess the effects of an ECM hydrogel coating on the long-term host tissue response to polypropylene mesh in a rodent model of abdominal muscle injury. At 14 days post implantation, the ECM coated polypropylene mesh devices showed a decreased inflammatory response as characterized by the number and distribution of M1 macrophages (CD86+/CD68+) around mesh fibers when compared to the uncoated mesh devices. At 180 days the ECM coated polypropylene showed decreased density of collagen and amount of mature type I collagen deposited between mesh fibers when compared to the uncoated mesh devices. This study confirms and extends previous findings that an ECM coating mitigates the chronic inflammatory response and associated scar tissue deposition characteristic of polypropylene.     

Subcutaneous low molecular weight heparin administration promotes wound healing in rats.

The influence of subcutaneous low molecular weight heparin (LMWH) compared with physiologic saline on the healing of abdominal wounds with and without prolene mesh was studied in rats. The collagen concentration was determined in the wound tissue and in prolene mesh 14, 21, 28 and 42 days after the skin incision in controls and in two groups of rats treated either with LMWH for 7 (I group) or 14 (II group) days after skin incision and prolene insertion. LMWH administration resulted in a significant increase of collagen content both in wound and in prolene mesh in total dose-dependent manner.     

Expression of non‐mast cell histidine decarboxylase in tumor‐associated microvessels in human esophageal squamous cell carcinomas

Histamine is produced by mast cells and many other types of cells. The role of histamine released from mast cells in promoting tumor angiogenesis has been intensively studied; however, the role of non‐mast cell histamine in regulating tumor angiogenesis has been largely ignored. In this study, tissue specimen sections from 43 patients with esophageal squamous cell carcinoma (ESCC) and normal esophageal biopsies from 17 heath individuals obtained from a high incidence area of north China were used to assess changes in microvessel density (MVD) and non‐mast cell L‐histidine decarboxylase (HDC) (the only rate‐limiting enzyme that catalyzes the formation of histamine from L‐histidine) expression in the tumor microenvironment by immunohistochemistry (IHC). In addition, the cellular characterization of non‐mast cell HDC‐positive cells in microvessels was examined by double IHC combined with HDC/CD34 and HDC/PCNA antibodies. These IHC analyses revealed a significantly increased HDC‐positive MVD in ESCC as compared with normal controls, which accounted for ～61% of CD34‐labeled general MVD in ESCC. Furthermore, IHC in serial sections and double IHC showed that most of these HDC‐positive cells were CD34‐positive endothelial cells in microvessels with an increased proliferative capacity. Thus, our results suggest that non‐mast cell histamine expressed in endothelial cells of microvessels could be an additional cellular source and might play a role in regulating angiogenesis in ESCC.     

Nitric oxide modulates metalloproteinase-2, collagen deposition and adhesion rate after polypropylene mesh implantation in the intra-abdominal wall

Prosthetic meshes are commonly used to correct abdominal wall defects. However, the inflammatory reaction induced by these devices in the peritoneum is not completely understood. We hypothesized that nitric oxide (NO), produced by nitric oxide synthase 2 (NOS2) may modulate the response induced by mesh implants in the abdominal wall and, consequently, affect the outcome of the surgical procedure. Polypropylene meshes were implanted in the peritoneal side of the abdominal wall in wild-type and NOS2-deficient (NOS2^−/−) mice. After 15 days tissues around the mesh implant were collected, and inflammatory markers (the cytokine interleukin 1β (IL-1β) and NO) and tissue remodeling (collagen and metalloproteinases (MMP) 2 and 9) were analyzed. The lack of NOS2-derived NO induced a higher incidence of visceral adhesions at the mesh implantation site compared with wild-type mice that underwent the same procedure (P < 0.05). Additionally, higher levels of IL-1β were present in the mesh-implanted NOS2^−/− animals compared with control and wild-type mice. Mesh implantation induced collagen I and III deposition, but in smaller amounts in NOS2^−/− mice. MMP-9 activity after the surgical procedure was similarly increased in both groups. Conversely, MMP-2 activity was unchanged in mesh-implanted wild-type mice, but was significantly increased in NOS2^−/− mice (P < 0.01), due to decreased S-nitrosylation of the enzyme in these animals. We conclude that NOS2-derived NO is crucial for an adequate response to and integration of polypropylene mesh implants in the peritoneum. NO deficiency results in a prolonged inflammatory reaction to the mesh implant, and reduced collagen deposition may contribute to an increased incidence of visceral adhesions.     

Influence of polyglactin-coating on functional and morphological parameters of polypropylene-mesh modifications for abdominal wall repair

Regarding oversized mechanical properties of most of the currently available materials a new mesh was developed (ETHICON, Norderstedt, Germany) and exactly adopted to the physiology of the human abdominal wall by reducing the amount of polypropylene (weight of <30 g/m2; mesh A). The consecutive increase of pores size as well as the use of multifilaments led to a pronounced increase of flexibility. To improve the handling during operation the initial stiffness of this low-weight large pores mesh was increased by strengthening with different amounts of absorbable polyglactin (combination of glycolide and lactide) in various forms: by coating (mesh B), adding multifilament polyglactin filaments (mesh C, Vypro) or both (mesh D), respectively. To test the consequences of the different supplementary techniques all mesh variants are implanted in a rat model. Over implantation intervals of 3, 7, 14, 21 and 90 days we measured the tensile strength, the resulting stiffness and surveyed the tissue response, particularly in regard to the extent of inflammation and to the induced fibrosis. The results proved a sufficient mechanical stability of the material reduced and pure polypropylene mesh A without restriction of the mobility of the abdominal wall compared with a group that had simple laparotomy and closure. The histological analysis of the interface showed a minor inflammatory reaction and a dense vascularisation. The addition of polyglactin multifilaments (mesh C) reduces the number of macrophages and granulocytes as indicators for acute inflammation, showing generally a scar formation limited merely to the perifilamentary region. The abdominal wall compliance remained unchanged compared with mesh A. The coating of the polypropylene with polyglactin (mesh B and D) appeared to change the tissue reaction remarkably, favouring the formation of a connective tissue capsule around the whole mesh. The mechanical testing revealed an apparent protrusion with an increase of curvature of the artificial abdominal wall at rising intraabdominal pressures. The entire coating of the polypropylene surface with polyglactin induces an all embedding scar plate, filling out the pores and forming a tissue capsule. The complex interaction of tissue and implanted biomaterials with their distinct alterations of the tissue response confirms the necessity of in vivo experiments even after 'minor' modifications. Whereas the addition of polyglactin filaments appears to be favourable, the coating of polypropylene with polyglactin seems to hinder the incorporation of the mesh.     

Attachment of glycosaminoglycans to collagenous matrices modulates the tissue response in rats

Biocompatibility and tissue regenerating capacity are essential characteristics in the design of collagenous biomaterials for tissue engineering. Attachment of glycosaminoglycans (GAGs) to collagen may add to these characteristics by creating an appropriate micro-environment. In this study, porous type I collagen matrices were crosslinked using 1-ethyl-3-(3-dimethyl aminopropyl)carbodiimide, in the presence and absence of chondroitin sulfate and heparan sulfate. The tissue response to these matrices was evaluated after subcutaneous implantation in rats. Biocompatibility of the matrices was established by the induction of a transitional inflammatory response, and the generation of new host tissue. Non-crosslinked collagen was gradually resorbed and replaced by collagenous connective tissue. By contrast, crosslinked matrices, with and without GAGs. retained their scaffold integrity during implantation, and supported the interstitial deposition and organization of extracellular matrix. In addition, crosslinking decreased tissue reactions at late time intervals. No calcification in any of the implants was observed. The presence of GAGs preserved porous lamellar matrix structures. Heparan sulfate in particular promoted angiogenesis at weeks 2 and 4, predominantly at the matrix periphery. The almost complete absence of macrophages and giant cells associated with collagen-GAG matrices, after 10 weeks implantation, indicated a reduced foreign body reaction. It is concluded that attachment of GAGs to collagen matrices modulates the tissue response. The potential of these biocompatible scaffolds for tissue engineering is increased by preserving porous matrix integrity. promoting angiogenesis and reducing foreign body reactions.     

人工补片修复腹部恶性肿瘤体内应用的远期效应

背景：人工补片容易与腹部肠管粘连,甚至出现肠梗阻,为肿瘤复发的再次手术切除带来了巨大困难。 目的：观察腹部恶性肿瘤切除后,应用人工补片修复腹壁缺损所带来的远期临床效应。 方法：回顾性分析因腹部肿瘤切除致腹部缺损患者26例,补片修复腹壁组16例应用聚丙烯类网片、膨体聚四氟乙烯补片和复合补片修复;直接拉拢缝合组10例未用人工补片修复,直接缝合皮下组织及皮肤。比较两组患者的腹壁疝、肠梗阻、再次手术开腹情况。 结果与结论：随访2~10年,补片修复腹壁组16例均未出现腹部疝,6例出现肠梗阻(聚丙烯类网片3例,膨体聚四氟乙烯补片1例,复合补片2例),7例因肿瘤复发再次手术,补片(聚丙烯类网片4例,膨体聚四氟乙烯补片1例,复合补片2例)与肠粘连严重,入腹困难。直接拉拢缝合组10例均出现腹壁疝,4例因肿瘤复发再次手术,肠粘连轻,入腹顺利。提示人工补片修复腹壁缺损能预防切口疝的发生,但容易导致腹腔粘连,严重影响腹部肿瘤复发再次手术。     

Structure of the rat subcutaneous connective tissue in relation to its sliding mechanism

Mammalian skin can extensively slide over most parts of the body. To study the mechanism of this mobility of the skin, the structure of the subcutaneous connective tissue was examined by light microscopy. The subcutaneous connective tissue was observed to be composed of multiple layers of thin collagen sheets containing elastic fibers. These piled-up collagen sheets were loosely interconnected with each other, while the outer and inner sheets were respectively anchored to the dermis and epimysium by elastic fibers. Collagen fibers in each sheet were variable in diameter and oriented in different directions to form a thin, loose meshwork under conditions without mechanical stretching. When a weak shear force was loaded between the skin and the underlying abdominal muscles, each collagen sheet slid considerably, resulting in a stretching of the elastic fibers which anchor these sheets. When a further shear force was loaded, collagen fibers in each sheet seemed to align in a more parallel manner to the direction of the tension. With the reduction or removal of the force, the arrangement of collagen fibers in each sheet was reversed and the collagen sheets returned to their original shapes and positions, probably with the stabilizing effect of elastic fibers. Blood vessels and nerves in the subcutaneous connective tissue ran in tortuous routes in planes parallel to the unloaded skin, which seemed very adaptable for the movement of collagen sheets. These findings indicate that the subcutaneous connective tissue is extensively mobile due to the presence of multilayered collagen sheets which are maintained by elastic fibers.     

Repair and regeneration of the abdominal wall musculofascial defect using silk fibroin-chitosan blend

Reconstructive surgery with synthetic or biological materials is commonly performed to repair abdominal wall musculofascial defects that result from ventral hernias. A study was conducted to investigate the feasibility of using silk fibroin and chitosan blend (SFCS) scaffolds for ventral hernia repair in guinea pigs. We compared SFCS with biodegradable human acellular dermal matrix (HADM) and nonbiodegradable polypropylene mesh by implanting each to repair an incisionally created ventral hernia in the abdominal wall using an inlay technique. At 4 weeks, both HADM and SFCS underwent remodeling by host tissue, but polypropylene mesh resulted in extensive bowel adhesions and scarring. Abdominal wall repairs with SFCS showed tissue remodeling in all 3 dimensions, with seamless integration at the interface with adjacent native tissue. The SFCS repair sites remained intact, and their mechanical strength was similar to that of the native abdominal wall despite greater degradation and remodeling of SFCS than of HADM. The deposition of new extracellular matrix consisting of collagen and ground substance, uniform vascularization, and cellular infiltration in SFCS repair sites contributed to the increase in mechanical strength of the regenerated tissue. Thus, SFCS is a potentially useful material for clinical abdominal wall reconstruction, since it becomes remodeled and integrated into the surrounding abdominal wall and maintains adequate tensile strength.     

A biocompatible polysaccharide hydrogel-embedded polypropylene mesh for enhanced tissue integration in rats

Prosthetic materials are largely used in surgery and tissue engineering. However, many postoperative complications are due to poor integration of the materials, which delays the healing process. The objective of our study was to develop a synthetic scaffold that, according to histopathological and biomechanical criteria, would achieve both tolerance and efficiency. In this study, we evaluated the effect of intramuscular and subcutaneous implantation of a new hybrid mesh (HM) in rats. This HM was composed of clinical grade polypropylene mesh embedded in a polysaccharide hydrogel. Histological and biomechanical studies on the polysaccharide gel alone and on HM were performed 15 and 30 days after implantation, and then compared with two clinically used materials, porcine decellularized small intestinal submucosa and a polypropylene mesh. Results showed that the incorporation of a polypropylene mesh within the polysaccharide hydrogel led to the absence of adverse effects and better tissue organization. Thus, this new synthetic biocompatible HM with suitable properties for tissue repair appears to be a promising material for clinical applications.     

Macrophage polarization in response to ECM coated polypropylene mesh

The host response to implanted biomaterials is a highly regulated process that influences device functionality and clinical outcome. Non-degradable biomaterials, such as knitted polypropylene mesh, frequently elicit a chronic foreign body reaction with resultant fibrosis. Previous studies have shown that an extracellular matrix (ECM) hydrogel coating of polypropylene mesh reduces the intensity of the foreign body reaction, though the mode of action is unknown. Macrophage participation plays a key role in the development of the foreign body reaction to biomaterials, and therefore the present study investigated macrophage polarization following mesh implantation. Spatiotemporal analysis of macrophage polarization was conducted in response to uncoated polypropylene mesh and mesh coated with hydrated and dry forms of ECM hydrogels derived from either dermis or urinary bladder. Pro-inflammatory M1 macrophages (CD86+/CD68+), alternatively activated M2 macrophages (CD206+/CD68+), and foreign body giant cells were quantified between 3 and 35 days. Uncoated polypropylene mesh elicited a dominant M1 response at the mesh fiber surface, which was decreased by each ECM coating type beginning at 7 days. The diminished M1 response was accompanied by a reduction in the number of foreign body giant cells at 14 and 35 days, though there was a minimal effect upon the number of M2 macrophages at any time. These results show that ECM coatings attenuate the M1 macrophage response and increase the M2/M1 ratio to polypropylene mesh in vivo.     

Cytological evaluation of the tissue-implant reaction associated with subcutaneous implantation of polymers coated with titaniumcarboxonitride in vivo

The aim of the present study was to evaluate the influence of titanium-coated polymers on the inflammatory response and remodeling of connective tissue during wound-healing processes. Discs of polyethyleneterephthalate (PET) and silicone as well as high-weight meshes of polypropylene (PP) were coated with a titaniumcarboxonitride (Ti(C,N,O)) layer by a plasma-assisted chemical vapor deposition process (PACVD) and implanted subcutaneously in the dorsal lumbar region of Wistar rats. Light microscopic and histological evaluation of capsule thickness, capsule quality, implant-tissue interface and collagen composition was performed 7, 14, 21 and 28 days post-operatively. All implants were surrounded by a fibrous capsule with decreasing thickness after 2-4 weeks post-implantation. Titaniumcarboxonitride-coated polymers showed no significant differences in capsule thickness and inflammatory cellular response. An increased collagen type III/I ratio, especially for titaniumcarboxonitride-coated materials, was found in week one after implantation remaining elevated up to week 4. This might be associated with disordered collagen metabolism and immature scar reaction. In contrast to previous in vitro experiments, Ti-coating of polymers did not improve biocompatibility after subcutaneous implantation in rats. Material reduction to low-weight meshes and enlargement of pore size may demonstrate a benefit of Ti-coated meshes with an increased biocompatibility.     

The importance of immunohistochemical evaluation of the vascular changes from the decidua and placenta in recurrent pregnancy loss

The angiogenesis is a complex process, incompletely understood, regulated by various stimulating and inhibiting angiogenic factors. In the present study, we proposed to evaluate the angiogenic changes that occur in the cases with recurrent pregnancy loss comparing with a control group represented by women with requested abortion. The evaluation of the changes in the vascular bed was made by immunohistochemical methods, evaluating the answer of the curettage products to the mouse anti-human CD31 and CD34 monoclonal antibodies immunolabeling. The endothelial cells reaction to the CD31 antibody was different, very intense in the normal or slightly congestive vessels. The endothelial cells from the strongly congestive vessels had a light and scratchy reaction. We found intense positive reactions in the control group for CD34 in the vessels from the villous axis and also in the vessels from the spongious decidua. In the study group, we found light positive reaction in the vessels from the decidua situated in the proximity of the necrotic areas; we found a light positive reaction also in the vessels and mesenchymal fibroblasts from some chorial villous axis.     

Revascularization of myocardial scar tissue following prostaglandin E1-therapy in patients with ischemic heart disease

Prostaglandin E1 (PGE-1) treatment has proved to stimulate angiogenesis in vital non-infarcted myocardium of patients with ischemic cardiomyopathy (ICMP). We investigated infarcted myocardial tissue for a possible angiogenic response to PGE-1. Neovascularization was investigated in infarcted areas of 12 hearts explanted from patients with ICMP who had been treated with PGE-1 before heart transplantation (HTX). In transmural sections containing myocardial scar tissue, CD34 and VEGF were immunohistochemically quantified to estimate capillary density and the extent of angiogenesis. To investigate a possible effect of PGE-1 on collagen turnover, the collagen content was determined in myocardial scar tissue by assessing the intensity of the area positively stained with sirius red. PGE-1-treated patients had significantly more CD34- and VEGF-positive cells in infarcted areas, and showed a significant reduction in collagen content as compared with the non-PGE-1 group (CD34: 120.3 +/- 6.1 vs. 47.7 +/- 6.1 capillary profiles/mm2; VEGF: 52.8 +/- 5.6 vs. 24.0 +/- 4.8 capillary profiles/mm2, and collagen content: 2.18 +/- 0.4 eU vs. 3.59 +/- 0.38 eU). Our data demonstrate that PGE-1 stimulates angiogenesis by upregulating VEGF expression, and reduces fibrosis in cardiac scar tissue of ischemic origin. The induction of therapeutic angiogenesis in vital and at sites of putative dead myocardial scar tissue, along with the hemodynamic improvement in patients with severe ICMP, might explain the favorable clinical outcome in PGE-1-treated patients before HTX.     

Camel milk inhibits inflammatory angiogenesis via downregulation of proangiogenic and proinflammatory cytokines in mice

Camel milk has traditionally been used to treat cancer, but this practice awaits scientific scrutiny, in particular its role in tumor angiogenesis, the key step involved in tumor growth and metastasis. We aimed to investigate the effects of camel milk on key components of inflammatory angiogenesis in sponge implant angiogenesis model. Polyester‐polyurethane sponges, used as a framework for fibrovascular tissue growth, were implanted in Swiss albino mice and camel milk (25, 50 and 100 mg/kg/day) was administered for 14 days through installed cannula. The implants collected at day 14 post‐implantation were processed for the assessment of hemoglobin (Hb), myeloperoxidase (MPO), N‐acetylglucosaminidase (NAG), and collagen, which were used as indices for angiogenesis, neutrophil, and macrophage accumulation and extracellular matrix deposition, respectively. Relevant inflammatory, angiogenic, and fibrogenic cytokines were also determined. Camel milk treatment attenuated the main components of the fibrovascular tissue, wet weight, vascularization (Hb content), macrophage recruitment (NAG activity), collagen deposition and the levels of vascular endothelial growth factor (VEGF), interleukin (IL)‐1β, IL‐6, IL‐17, tumor necrosis factor‐α, and transforming growth factor‐β. A regulatory function of camel milk on multiple parameters of the main components of inflammatory angiogenesis has been revealed, giving insight into the potential therapeutic benefit underlying the anti‐cancer actions of camel milk.     

Histopathologic host response to polypropylene-based surgical mesh materials in a rat abdominal wall defect model

Composite polypropylene-based surgical mesh materials including various synthetic polymers and naturally occurring biomaterials have been developed to ameliorate device-associated inflammatory response and associated reduced compliance of pure polypropylene meshes. This study evaluated the histomorphologic response of three composite polypropylene-based surgical meshes, Revive?, a polycarbonate polyurethane reinforced monofilamentous polypropylene scaffold, Assure?, a polycarbonate polyurethane reinforced monofilamentous polypropylene scaffold with a resorbable anti-adhesion layer of lactide caprolactone copolymer, and Proceed?, a polypropylene mesh modified with oxidized cellulose, in a soft tissue repair model in the rat. The host inflammatory response and neotissue formation were evaluated by semiquantitative histologic scoring including the amount of cellular infiltration, angiogenesis, presence of multinucleate giant cells, fibrous connective tissue formation, and host neo-extracellular matrix deposition for up to 26 weeks. All three composite surgical mesh materials showed good integration with host tissue as indicated by rapid cellular infiltration, abundant neo-vascularization, minimal shrinkage, and the lack of visible mesh degradation. The devices elicited a similar inflammatory response and the presence of a mild foreign body response in spite of the different composition and morphology of these composite mesh materials.     

Structural variants of biodegradable polyesterurethane in vivo evoke a cellular and angiogenic response that is dictated by architecture

The aim of this study was to investigate an in vivo tissue response to a biodegradable polyesterurethane, specifically the cellular and angiogenic response evoked by varying implant architectures in a subcutaneous rabbit implant model. A synthetic biodegradable polyesterurethane was synthesized and processed into three different configurations: a non-porous film, a porous mesh and a porous membrane. Glutaraldehyde cross-linked bovine pericardium was used as a control. Sterile polyesterurethane and control samples were implanted subcutaneously in six rabbits (n=12). The rabbits were killed at 21 and 63 days and the implant sites were sectioned and histologically stained using haemotoxylin and eosin (H&E), Masson's trichrome, picosirius red and immunostain CD31. The tissue-implant interface thickness was measured from the H&E slides. Stereological techniques were used to quantify the tissue reaction at each time point that included volume fraction of inflammatory cells, fibroblasts, fibrocytes, collagen and the degree of vascularization. Stereological analysis inferred that porous scaffolds with regular topography are better tolerated in vivo compared to non-porous scaffolds, while increasing scaffold porosity promotes angiogenesis and cellular infiltration. The results suggest that this biodegradable polyesterurethane is better tolerated in vivo than the control and that structural variants of biodegradable polyesterurethane in vivo evoke a cellular and angiogenic response that is dictated by architecture.     

Evaluation of the expression of collagen type I in porous calcium phosphate ceramics implanted in an extra-osseous site

The aim of the present study is to demonstrate the newly formed tissue in calcium phosphate (Ca/P) ceramics after extra-osseous implantation by histological and immunohistochemistry (IHC) methods. Synthesis porous Ca/P ceramics without adding any growth factor and living cell were implanted in the dorsal muscle of dogs for 1 and 2 months. Undecalcified and decalcified sections were stained by hematoxylin and eosin (H&E), and IHC, respectively. The histological results showed the beginning of osteogenesis and angiogenesis after being implanted for 1 month and the obvious new bone formation after being implanted for 2 months. IHC were conducted via the avidin-biotin peroxidase complex (ABC) method and the primary antibody was collagen type I. IHC results indicated that collagen type I was expressed within osteoblast-like cells and newly formed bone-like tissue in Ca/P ceramics after 1 month, and in the mineralized matrix of newly formed bone and osteoblasts, some osteocytes and some lacunae after 2 months. No cartilage and chondrocytes were observed in the histological and IHC-stained sections. Evidence of intramembranous osteogenesis was confirmed.     

The energy density of laser light differentially modulates the skin morphological reorganization in a murine model of healing by secondary intention

This study investigates the influence of gallium–arsenide (GaAs) laser photobiostimulation applied with different energy densities on skin wound healing by secondary intention in rats. Three circular wounds, 10 mm in diameter, were made on the dorsolateral region of 21 Wistar rats weighting 282.12 ± 36.08 g. The animals were equally randomized into three groups: Group SAL, saline solution 0.9%; Group L3, laser GaAs 3 J/cm²; Group L30, laser GaAs 30 J/cm². Analyses of cells, blood vessels, collagen and elastic fibres, glycosaminoglycans and wound contraction were performed on the scar tissue from different wounds every 7 days for 21 days. On day 7, 14 and 21, L3 and L30 showed higher collagen and glycosaminoglycan levels compared to SAL (P < 0.05). At day 21, elastic fibres were predominant in L3 and L30 compared to SAL (P < 0.05). Type‐III collagen fibres were predominant at day 7 in both groups. There was gradual reduction in these fibres and accumulation of type‐I collagen over time, especially in L3 and L30 compared with SAL. Elevated density of blood vessels was seen in L30 on days 7 and 14 compared to the other groups (P < 0.05). On these same days, there was higher tissue cellularity in L3 compared with SAL (P < 0.05). The progression of wound closure during all time points investigated was higher in the L30 group (P < 0.05). Both energy densities investigated increased the tissue cellularity, vascular density, collagen and elastic fibres, and glycosaminoglycan synthesis, with the greater benefits for wound closure being found at the density of 30 J/cm².     

Costunolide suppresses an inflammatory angiogenic response in a subcutaneous murine sponge model

Costunolide is known to possess anti‐inflammatory and antitumor activity, but its role in tumor angiogenesis, the key step involved in tumor growth and metastasis, and the involved molecular mechanism is still unknown. We aimed to investigate the effects of costunolide on key components of inflammatory angiogenesis in the murine cannulated sponge implant angiogenesis model. Polyester‐polyurethane sponges, used as a framework for fibrovascular tissue growth, were implanted in Swiss albino mice and costunolide (5, 10 and 20 mg/kg/day) was administered for 14 days through installed cannula. The implants collected at day 14 post‐implantation were processed for the assessment of hemoglobin (Hb), myeloperoxidase (MPO), N‐acetylglucosaminidase (NAG) and collagen, which were used as indices for angiogenesis, neutrophil and macrophage accumulation, and extracellular matrix deposition, respectively. Relevant inflammatory, angiogenic and fibrogenic cytokines were also determined. Costunolide treatment attenuated the main components of the fibrovascular tissue, wet weight, vascularization (Hb content), macrophage recruitment (NAG activity), collagen deposition, and the levels of vascular endothelial growth factor (VEGF), interleukin (IL)‐1β, IL‐6, IL‐17, tumor necrosis factor (TNF)‐α and transforming growth factor (TGF‐β). Regulatory function of costunolide on multiple parameters of the main components of inflammatory angiogenesis has been revealed giving insight into the potential therapeutic benefit underlying the anti‐angiogenic actions of costunolide.