Study on the Effect and Mechanism of Antibacterial Adhesive Hydrogel on Wound Healing.

Bleeding and infection can cause significant increases in mortalities. Hydrogel sealants have attracted extensive attention for their ability to control bleeding. In this study, the adjuvant treatment with antibacterial adhesive hydrogel dressings was applied to patients with deep second-degree burns/scalds. The traditional medical dressing was regarded as control adjuvant treatment. The results indicated that the total positive rate of bacteria in wound secretions and the pain during dressing change in patients who used antibacterial adhesive hydrogel dressings were significantly reduced. The number of fibroblasts and new capillaries in the granulation tissue of the wound increased, and the patient's wound healing is accelerated. The overall clinical effectiveness has been significantly improved. It is proven that the antibacterial adhesive hydrogel dressing has a significant effect on wound healing.

Morphological and Histological Changes in the Human Anterior Cruciate Ligament after Rupture.

BACKGROUND: Injuries to the anterior cruciate ligament (ACL) are common and complete tears often fail to heal. ACL reconstruction is considered the surgical gold standard of care for ACL injuries in young active patients. OBJECTIVES: To determine the corresponding morphological and histological features of the torn ACL in different time periods after injury. METHODS: The study included 28 remnant specimens of torn ACLs from patients who had ACL reconstruction surgery of the knee. The remnant pathology was evaluated by its morphology during arthroscopy and by histopathologic measurements. RESULTS: At surgery there were three progressive and distinct morphological tear patterns. The first pattern was noticed within the first 3 months from injury and showed no scar tissue. The second pattern appeared later and was characterized by the appearance of scar tissue with adhesion to the femoral wall. The third pattern was characterized by adhesion of the ACL remnant to the posterior cruciate ligament. The histological changes of the first morphological pattern showed abundance of blood vessels and lymphocytes at the torn femoral end with few irregular collagen fibers. The second and third tear patterns showed decrement in the number of blood vessels and lymphocytes with longitudinally oriented collagen fibers. CONCLUSIONS: The morphological features of the ACL remnant in the first 3 months after injury showed no scar tissue and its histological features had the characteristics of a reparative phase. This phase was followed by a prolonged remodeling phase that ended with attachment of the remnant to the posterior cruciate ligament.

Time- and Dose-Dependent Effects of Pulsed Ultrasound on Dermal Repair in Diabetic Mice.

Chronic wounds, including diabetic, leg and pressure ulcers, impose a significant health care burden worldwide. Some evidence indicates that ultrasound can enhance soft tissue repair. However, therapeutic responses vary among individuals, thereby limiting clinical translation. Here, effects of pulsed ultrasound on dermal wound healing were assessed using a murine model of chronic, diabetic wounds. An ultrasound exposure system was developed to provide daily ultrasound exposures to full-thickness, excisional wounds in genetically diabetic mice. Wounds were exposed to 1 MHz ultrasound (2 ms pulse, 100 Hz pulse repetition frequency, 0-0.4 MPa) for 2 or 3 wk. Granulation tissue thickness and wound re-epithelialization increased as a function of increasing ultrasound pressure amplitude. At 2 wk after injury, significant increases in granulation tissue thickness and epithelial ingrowth were observed in response to 1 MHz pulsed ultrasound at 0.4 MPa. Wounds exposed to 0.4 MPa ultrasound for 3 wk were characterized by collagen-dense, revascularized granulation tissue with a fully restored, mature epithelium. Of note, only half of wounds exposed to 0.4 MPa ultrasound showed significant granulation tissue deposition after 2 wk of treatment. Thus, the db+/db+ mouse model may help to identify biological variables that influence individual responses to pulsed ultrasound and accelerate clinical translation.

Negative-Pressure Wound Therapy Promotes Wound Healing by Enhancing Angiogenesis Through Suppression of NLRX1 via miR-195 Upregulation.

Negative-pressure wound therapy (NPWT) is one of the most advanced therapeutic methods in the treatment of various hard-to-heal acute and refractory chronic wounds. Recent emerging evidence points to a role of the microRNA-mediated regulation of angiogenesis in ischemic tissues, and a series of microRNAs associated with angiogenesis have been successively identified. In this study, we found that miR-195 expression was significantly upregulated and the microvessel density (MVD) was increased in granulation tissue collected 7 days after NPWT compared with those in the pre-NPWT tissue. Moreover, the expression of NLRX1, the potential target gene of miR-195, was down-regulated in post-NPWT compared with that in pre-NPWT tissue. Significant negative correlations were detected between miR-195 and NLRX1 expression levels ( r = -.856, P < .001) and between NLRX1 expression and MVD ( r = -.618, P < .05), whereas miR-195 expression was positively correlated with MVD in the granulation tissue ( r = .630, P < .05). In summary, NPWT may suppress NLRX1 expression through the upregulation of miR-195 expression, thus efficaciously promoting angiogenesis in the granulation tissue to enhance wound healing.

Giant arachnoid granulation with a thrombosed dural arteriovenous fistula.

Arachnoid granulations are common incidentally detected small dural lesions which are usually asymptomatic and follow cerebrospinal fluid density/signal intensity on CT/MRI. Such lesions reaching a size of more than 1 cm are termed as giant arachnoid granulations (GAGs) which have been previously reported to cause venous hypertension and headaches. We report a case of GAG involving the proximal half of the superior sagittal sinus in a 45-year-old male patient which was associated with left temporal thrombosed dural arteriovenous fistula (AVF) whose thrombosed draining veins were seen converging towards the site of GAG. The patient presented with three episodes of generalised tonic-clonic seizures and improved with conservative treatment. No reports of such association of GAG with AVF is available in the literature, and we believe it could have occurred due to venous hypertension induced by GAG.

Efficacy of gelatin gel sheets sustaining epidermal growth factor for murine skin defects.

BACKGROUND: Epidermal growth factor (EGF) plays an important role in wound healing. However, EGF must be applied daily due to rapid inactivation in vivo. We investigated the sustained release of EGF from gelatin gel sheets (GGSs) and the efficacy of GGSs impregnated with EGF for promoting wound healing. MATERIALS AND METHODS: GGSs impregnated with EGF were prepared by cross-linking via glutaraldehyde to gelatin solution containing EGF. The sustained release of EGF and the bioactivity of released EGF were evaluated. Then, three kinds of GGSs containing NSS (normal saline solution; NSS group), 2.5 µg of EGF (EGF-L group), or 25 µg of EGF (EGF-H group) were applied to full-thickness skin defects created on the backs of mice. The wounds covered with polyurethane film without GGS were used as a control (PUF group). The wound area, neoepithelium length, regenerated granulation tissue, and newly formed capillaries were evaluated. RESULTS: EGF was sustained and released from GGS as it degraded. The bioactivity of released EGF was confirmed. EGF-L group promoted the neoepithelium length, regenerated granulation tissue, and newly formed capillaries compared with those in the PUF and NSS groups. The area of regenerated granulation tissue in the NSS group (week 1: 2.6 + 0.2 mm(2), week 2: 2.8 + 0.3 mm(2)) was larger than that in the PUF group (week 1: 0.6 + 0.1 mm(2), week 2: 1.0 + 0.1 mm(2)). The area of newly formed capillaries in the EGF-L group (9967 + 1903 µm(2)) was larger than that of the EGF-H group (3485 + 1050 µm(2)). CONCLUSIONS: GGSs impregnated with EGF-L showed promising results regarding wound healing.

Induction of granulation tissue for the secretion of growth factors and the promotion of bone defect repair.

BACKGROUND: The use of the Masquelet technique in the repair of large bone defects has gained increased acceptance in recent years. The core of this technique is the induction of granulation tissue membrane formation and the implantation of an autologous cancellous bone to reconstruct bone defects in the membrane. In this study, we purpose to explore the structure of induced membrane and the content of growth factors as well to compare between the structure and the effects on osteogenesis of induced membranes and the periosteum in animal models. METHODS: Bilateral radial bone defects were generated in 32 healthy adult rabbits. The defects were implanted with bone cement. The induced membranes and periosteum were removed after 2, 4, 6, and 8 weeks. Thereafter, hematoxylin-eosin staining (HE) and an enzyme-linked immunosorbent assay (ELISA) were performed to detect vascular endothelial growth factor (VEGF), angiotensin II (ANG-II), bone morphogenetic protein 2 (BMP2), fibroblast growth factor 2 (FGF2), and prostaglandin E2 (PGE2). Proteins isolated from total cell lysates were cultured with mesenchymal stem cells to test the cell proliferation and alkaline phosphatase activity using epimysium as a control. RESULTS: The induced membrane and periosteum exhibited similar structures and growth factor levels after 4 and 6 weeks. The highest concentration of BMP-2 and VEGF in the induced membranes occurred in week 6, and FGF-2 and ANG-II concentrations peaked in week 4. The thickness and vascular density of induced membranes gradually decreased with time. CONCLUSION: Induced membrane matured between the 4th and the 6th week and secreted growth factors to promote osteogenesis. The matured induced membrane and periosteum had similar structures and abilities to promote the osteogenesis of mesenchymal stem cells. However, the induced membrane was thicker than the periosteum.

[OBJECTIVE CRITERIA OF PATIENT'S READINESS TO FREE AUTOPLASTY IN CASE OF GRANULATING WOUNDS (CRITERIA OF READINESS OF GRANULATING WOUNDS TO OPERATION)].

The article based on the analysis of 84 follow-up of the patients. The authors suggested using the indices of microbiological and immunological investigations and data of laser Doppler ultrasonography to determine the readiness of granulating wound to free autoplasty. The data obtained allowed developing an algorithm of treatment, patient's preparation to surgery and determination of operation terms.

Angiogenic effect of the aqueous extract of Cynodon dactylon on human umbilical vein endothelial cells and granulation tissue in rat.

BACKGROUND: Cynodon dactylon, a valuable medicinal plant, is widely used in Iranian folk medicine for the treatment of various cardiovascular diseases such as heart failure and atherosclerosis. Moreover, its anti-diabetic, anti-cancer and anti-microbial properties have been also reported. Concerning the critical role of angiogenesis in the incidence and progression of tumors and also its protective role in cardiovascular diseases, we investigated the effects of the aqueous extract prepared from the rhizomes of C. dactylon on vascular endothelial growth factor (VEGF) expressions in Human Umbilical Vein Endothelial Cells (HUVECs) and also on angiogenesis in carrageenan induced air-pouch model in rats. METHODS: In the air-pouch model, carrageenan was injected into an air-pouch on the back of the rats and following an IV injection of carmine red dye on day 6, granulation tissue was processed for the assessment of the dye content. Furthermore, in an in vitro study, angiogenic property of the extract was assessed through its effect on VEGF expression in HUVECs. RESULTS: Oral administration of 400 mg/kg/day of the extract significantly increased angiogenesis (p<0.05) and markedly decreased neutrophil (p<0.05) and total leukocyte infiltration (p<0.001) into the granulation tissues. Moreover, the extract increased the expression of total VEGF in HUVECs at a concentration of (100 µl/ml). CONCLUSION: The present study showed that the aqueous extract of C. dactylon promotes angiogenesis probably through stimulating VEGF expression.

Regional disturbances in blood flow and metabolism in equine limb wound healing with formation of exuberant granulation tissue.

As in other fibroproliferative disorders, hypoxia has been suggested to play a key role in the pathogenesis of exuberant granulation tissue (EGT). The purpose of this study was to investigate metabolism and blood flow locally in full-thickness wounds healing with (limb wounds) and without (body wounds) formation of EGT. Microdialysis was used to recover endogenous metabolites from the wounds, and laser Doppler flowmetry was used to measure blood flow. Measurements were performed before wounding and 1-28 days after wounding. Blood flow was consistently lower in limb wounds than in body wounds throughout the study period with no change over time. After wounding and throughout the study period, the glucose concentration was significantly lower in limb wounds than in body wounds, whereas the lactate level showed a significantly higher concentration in limb wounds. The lactate/glucose ratio displayed a significant difference between body and limb wounds. In conclusion, the metabolic disturbances may suggest an inadequate oxygen supply during the wound healing process in equine limb wounds healing with EGT. This may be related to the inherently decreased perfusion in the wound bed of limb wounds.

Natural honey: a new and potent anti-angiogenic agent in the air-pouch model of inflammation.

Despite reports indicating anti-inflammatory effects of honey, the anti-angiogenic effect of honey and its impact on inflammatory mediators in the air pouch model of inflammation have not yet been studied. The aims of present study were to investigate the effects of honey on angiogenesis, inflammatory cytokine vascular endothelial growth factor (VEGF) level as an important marker of angiogenesis and prostaglandin E2 (PGE2) in the rat air pouch model of inflammation. Male Wistar rats were anesthetized, and then 20 ml and 10 ml of sterile air were injected subcutaneously in the back on days 0 and 3, respectively. On day 6, inflammation was induced by injection of 1 ml of carrageenan 1% into pouches. After 72 h, the rats were sacrificed; pouch fluid was collected in order to determine PGE2 concentration and VEGF level. The Pouches were dissected out and weighed. Angiogenesis of granulomatous tissue was assayed using a hemoglobin kit. Honey was able to reduce granulation tissue weight and angiogenesis as well as showing potent inhibitory activities against PGE2 and VEGF in air pouch model of inflammation. The decrease in angiogenesis correlates with the inhibition of PGE2 and VEGF. Honey is potentially useful in the treatment of granulomatous inflammatory conditions. It seems that the anti-angiogenic activities of honey are mediated through modulation of PGE2 and VEGF production.

[Influence of microbial wound dissemination and microcirculation on the results of skin engraftment].

The indices of Doppler laser flowmetery are proposed to be used for determination of the readiness of a granulating wound for free autoplasty. An analysis of capillary blood flow in the groups under test showed the information value of indicators of microcirculation obtained by Doppler laser flowmetery for determination of the granulating wound condition before autotransplantation and prediction of the results of skin engraftment. It is stated, that the disorder of microcirculation has been developed against the background of progression of wound invasive infection. The obtained data can allow the development of an algorithm of treatment and the preparation of the patients to surgery, determination of the terms of operation, the development the strategy of postoperative management of the patients, which can reduce unfavorable results of operations.

Skin wound healing in different aged Xenopus laevis.

Xenopus froglets can perfectly heal skin wounds without scarring. To explore whether this capacity is maintained as development proceeds, we examined the cellular responses during the repair of skin injury in 8- and 15-month-old Xenopus laevis. The morphology and sequence of healing phases (i.e., inflammation, new tissue formation, and remodeling) were independent of age, while the timing was delayed in older frogs. At the beginning of postinjury, wound re-epithelialization occurred in form of a thin epithelium followed by a multilayered epidermis containing cells with apoptotic patterns and keratinocytes stained by anti-inducible nitric oxide synthase (iNOS) antibody. The inflammatory response, early activated by recruitment of blood cells immunoreactive to anti-tumor necrosis factor (TNF)-α, iNOS, transforming growth factor (TGF)-ß1, and matrix metalloproteinase (MMP)-9, persisted over time. The dermis repaired by a granulation tissue with extensive angiogenesis, inflammatory cells, fibroblasts, and anti-α-SMA positive myofibroblasts. As the healing progressed, wounded areas displayed vascular regression, decrease in cellularity, and rearrangement of provisional matrix. The epidermis restored to a prewound morphology while granulation tissue was replaced by a fibrous tissue in a scar-like pattern. The quantitative PCR analysis demonstrated an up-regulated expression of Xenopus suppressor of cytokine signaling 3 (XSOCS-3) and Xenopus transforming growth factor-ß2 (XTGF-ß2) soon after wounding and peak levels were detected when granulation tissue was well developed with a large number of inflammatory cells. The findings indicate that X. laevis skin wound healing occurred by a combination of regeneration (in epidermis) and repair (in dermis) and, in contrast to froglet scarless wound healing, the growth to a more mature adult stage is associated with a decrease in regenerative capacity with scar-like tissue formation.

Phases of the cutaneous angiogenesis process in experimental third-degree skin burns: histological and immunohistochemical study.

Skin burns represent a major problem of public health because of their frequency and because of their seriousness, too. The healing process of the burnt wound is extremely complex, as it requires a well-coordinated collaboration among different tissues and cellular strings. From the morphological point of view, the stages of the repairing process of the skin wounds include processes of inflammation, proliferation and tissular remodeling. Angiogenesis has a role of extreme importance within the healing process of third-degree skin burns. That is because the vascularization remake is necessary for feeding the tissue of granulation with nutritive substances and oxygen. The angiogenesis started relatively fast. Three days after the producing of the burn, there could be identified strings of CD34+ endothelial precursor cells at the edges and deep into the wound, all these having contact with the normal blood vessels or with those lees affected by the thermal aggression. After the lumenization of the newly-formed capillary vessels, there appeared the pericytes within their membrane. The CD34+ endothelial precursor cells (EPc), as well as the pericytes, participate at the synthesis of the base membrane of the angiogenesis vessels. The density of the angiogenesis vessels on the surface unit within the tissue of granulation grew from three to 12 days. After that, they reduced progressively while the tissue of granulation was becoming mature. The angiogenesis vessels go through a process of reshuffling and maturation at the same time with the maturation of the tissue of granulation, but these processes did not appear to be finished when the skin was completely healed, and the epidermis was totally recovered.

Comparison of bacteria and fungus-binding mesh, foam and gauze as fillers in negative pressure wound therapy--pressure transduction, wound edge contraction, microvascular blood flow and fluid retention.

Bacteria- and fungus-binding mesh binds with and inactivates bacteria and fungus, which makes it an interesting alternative, wound filler for negative pressure wound therapy (NPWT). This study was conducted to compare the performance of pathogen-binding mesh, foam and gauze as wound fillers in NPWT with regard to pressure transduction, fluid retention, wound contraction and microvascular blood flow. Wounds on the backs of 16 pigs were filled with pathogen-binding mesh, foam or gauze and treated with NPWT. The immediate effects of 0, -40, -60, -80 and -120 mmHg, on pressure transduction and blood flow were examined in eight pigs using laser Doppler velocimetry. Wound contraction and fluid retention were studied during 72 hours of NPWT at -80 and -120 mmHg in the other eight pigs. Pathogen-binding mesh, gauze and foam provide similar pressure transduction to the wound bed during NPWT. Blood flow was found to decrease 0.5 cm laterally from the wound edge and increase 2.5 cm from the wound edge, but was unaltered 5.0 cm from the wound edge. The increase in blood flow was similar with all wound fillers. The decrease in blood flow was more pronounced with foam than with gauze and pathogen-binding mesh. Similarly, wound contraction was more pronounced with foam, than with gauze and pathogen-binding mesh. Wound fluid retention was the same in foam and pathogen-binding mesh, while more fluid was retained in the wound when using gauze. The blood flow 0.5-5 cm from the wound edge and the contraction of the wound during NPWT were similar when using pathogen-binding mesh and gauze. Wound fluid was efficiently removed when using pathogen-binding mesh, which may explain previous findings that granulation tissue formation is more rapid under pathogen-binding mesh than under gauze. This, in combination with its pathogen-binding properties, makes this mesh an interesting wound filler for use in NPWT.

Influence of oxygen on wound healing dynamics: assessment in a novel wound mouse model under a variable oxygen environment.

INTRODUCTION: Although oxygen is essential for the wound healing process, tissue hypoxia is known to stimulate angiogenesis. To explore these inconsistent findings, we estimated the influence of the oxygen environment on wound healing with our original model. METHODS: Experiment 1 (Establishment of the model): To modify the topical oxygen tension, oxygen impermeable (polyvinylidene chloride) and permeable (polymethylpentene) membranes were applied to symmetrical excisional wounds in ddy mice (n = 6). Oxygen tension under the membrane was quantified with a device using photo-quenching technique. Experiment 2 (Influence of oxygen environment on wound healing): The wound area, granulation thickness and vascular density were analyzed under different oxygen environments (n = 24). RESULTS: Experiment 1: The permeable group maintained equivalent oxygen level to atmosphere (114.1±29.8 mmHg on day 7), while the impermeable group showed extremely low oxygen tension (5.72±2.99 mmHg on day 7). Accordingly, each group was defined as the normoxia group and the hypoxia group. Experiment 2: Percent decrease in wound size was significantly enhanced in the normoxia group (11.1±1.66% on day 7) in comparison with the hypoxia group (27.6±3.47% on day 7). The normoxia group showed significantly thicker granulation tissue than the hypoxia group (491.8±243.2 vs. 295.3±180.9 µm). Contrarily, the vascular density of the hypoxia group significantly increased on day 7 (0.046±0.025 vs. 0.011±0.008 mm(2)/mm(2)). CONCLUSIONS: Our original model successfully controlled local oxygen concentration around the wound, and the hypoxic wounds showed increased angiogenesis but with a smaller amount of granulation tissue and delayed wound closure. Enhanced neovascularization in the hypoxic group likely implies compensative response to an insufficient ambient oxygen supply.

MMP-13 regulates growth of wound granulation tissue and modulates gene expression signatures involved in inflammation, proteolysis, and cell viability.

Proteinases play a pivotal role in wound healing by regulating cell-matrix interactions and availability of bioactive molecules. The role of matrix metalloproteinase-13 (MMP-13) in granulation tissue growth was studied in subcutaneously implanted viscose cellulose sponge in MMP-13 knockout (Mmp13(-/-)) and wild type (WT) mice. The tissue samples were harvested at time points day 7, 14 and 21 and subjected to histological analysis and gene expression profiling. Granulation tissue growth was significantly reduced (42%) at day 21 in Mmp13(-/-) mice. Granulation tissue in Mmp13(-/-) mice showed delayed organization of myofibroblasts, increased microvascular density at day 14, and virtual absence of large vessels at day 21. Gene expression profiling identified differentially expressed genes in Mmp13(-/-) mouse granulation tissue involved in biological functions including inflammatory response, angiogenesis, cellular movement, cellular growth and proliferation and proteolysis. Among genes linked to angiogenesis, Adamts4 and Npy were significantly upregulated in early granulation tissue in Mmp13(-/-) mice, and a set of genes involved in leukocyte motility including Il6 were systematically downregulated at day 14. The expression of Pdgfd was downregulated in Mmp13(-/-) granulation tissue in all time points. The expression of matrix metalloproteinases Mmp2, Mmp3, Mmp9 was also significantly downregulated in granulation tissue of Mmp13(-/-) mice compared to WT mice. Mmp13(-/-) mouse skin fibroblasts displayed altered cell morphology and impaired ability to contract collagen gel and decreased production of MMP-2. These results provide evidence for an important role for MMP-13 in wound healing by coordinating cellular activities important in the growth and maturation of granulation tissue, including myofibroblast function, inflammation, angiogenesis, and proteolysis.

Contrast-enhanced ultrasonography for the detection of joint vascularity in arthritis--subjective grading versus computer-aided objective quantification.

PURPOSE: To compare joint inflammation assessment using subjective grading of power Doppler ultrasonography (PDUS) and contrast-enhanced ultrasonography (CEUS) versus computer-aided objective CEUS quantification. MATERIALS AND METHODS: 37 joints of 28 patients with arthritis of different etiologies underwent B-mode ultrasonography, PDUS, and CEUS using a second-generation contrast agent. Synovial thickness, extent of vascularized pannus and intensity of vascularization were included in a 4-point PDUS and CEUS grading system. Subjective CEUS and PDUS scores were compared to computer-aided objective CEUS quantification using Qontrast® software for the calculation of the signal intensity (SI) and the ratio of SI for contrast enhancement. RESULTS: The interobserver agreement for subjective scoring was good to excellent (κ = 0.8 - 1.0; P < 0.0001). Computer-aided objective CEUS quantification correlated statistically significantly with subjective CEUS (P < 0.001) and PDUS grading (P < 0.05). The Qontrast® SI ratio correlated with subjective CEUS (P < 0.02) and PDUS grading (P < 0.03). Clinical activity did not correlate with vascularity or synovial thickening (P = N. S.) and no correlation between synovial thickening and vascularity extent could be found, neither using PDUS nor CEUS (P = N. S.). CONCLUSION: Both subjective CEUS grading and objective CEUS quantification are valuable for assessing joint vascularity in arthritis and computer-aided CEUS quantification may be a suitable objective tool for therapy follow-up in arthritis.

The effect of dextrin-rhEGF on the healing of full-thickness, excisional wounds in the (db/db) diabetic mouse.

Chronic wounds, such as ulceration of the lower limb, represent a significant clinical challenge in today's ageing society. With the aim of identifying improved therapeutics, we have previously described a bioresponsive, dextrin-recombinant human epidermal growth factor conjugate (dextrin-rhEGF), that (i) protects rhEGF against proteolytic degradation by human chronic wound fluid; and (ii) mediates rhEGF release by α-amylase, capable of stimulating increased proliferation/migration in normal dermal and chronic wound fibroblasts; and keratinocytes, in vitro. The aim of this study was to extend these findings, by investigating the effects of dextrin-rhEGF on wound healing in the (db/db) diabetic mouse, a widely used in vivo model of delayed wound healing. Standardised, full-thickness excisional wounds, created in the dorsal flank skin, were treated topically with succinoylated dextrin (50 µg/mL), rhEGF (10 µg/mL) or dextrin-rhEGF (1 or 10 µg/mL). Treatments were applied immediately after injury and subsequently on post-wounding, days 3 and 8. Wound healing was assessed macroscopically, in terms of initiation of neo-dermal tissue deposition and wound closure (including wound contraction and re-epithelialisation), over a 16 day period. Wound healing was assessed histologically, in terms of granulation tissue formation/maturity; cranio-caudal wound contraction and wound angiogenesis (CD31 immuno-staining), using tissues harvested at day 16. Blood samples were also analysed for α-amylase and rhEGF concentrations. In this established impaired wound healing model, the topically-applied dextrin-rhEGF significantly accelerated wound closure and neo-dermal tissue formation at the macroscopic level; and significantly increased granulation tissue deposition and angiogenesis at the histological level (p<0.05), relative to untreated, succinoylated dextrin and rhEGF alone controls. Overall, these findings support the further development of bioresponsive polymer conjugates, for tissue repair.

Effect of transplantation of bone marrow monomuclears on angiogenesis in rats.

We studied the effect of non-selective intracoronary transplantation of bone marrow mononuclears on day 30 after acute coronary infarction on angiogenesis in rats. On days 14 and 30 after transplantation of mononuclear cells, stable formation of new vessels was observed. The number of venules considerably increased after transplantation of mononuclear cells, which was seen from increased volume density of blood vessels and their caliber. Stable vascularization after transplantation of mononuclear cells improves blood supply, which is essential for reparation of the myocardium.