Keratin Scaffolds Containing Casomorphin Stimulate Macrophage Infiltration and Accelerate Full-Thickness Cutaneous Wound Healing in Diabetic Mice

Impaired wound healing is a major medical challenge, especially in diabetics. Over the centuries, the main goal of tissue engineering and regenerative medicine has been to invent biomaterials that accelerate the wound healing process. In this context, keratin-derived biomaterial is a promising candidate due to its biocompatibility and biodegradability. In this study, we evaluated an insoluble fraction of keratin containing casomorphin as a wound dressing in a full-thickness surgical skin wound model in mice (n = 20) with iatrogenically induced diabetes. Casomorphin, an opioid peptide with analgesic properties, was incorporated into keratin and shown to be slowly released from the dressing. An in vitro study showed that keratin-casomorphin dressing is biocompatible, non-toxic, and supports cell growth. In vivo experiments demonstrated that keratin-casomorphin dressing significantly (p < 0.05) accelerates the whole process of skin wound healing to the its final stage. Wounds covered with keratin-casomorphin dressing underwent reepithelization faster, ending up with a thicker epidermis than control wounds, as confirmed by histopathological and immunohistochemical examinations. This investigated dressing stimulated macrophages infiltration, which favors tissue remodeling and regeneration, unlike in the control wounds in which neutrophils predominated. Additionally, in dressed wounds, the number of microhemorrhages was significantly decreased (p < 0.05) as compared with control wounds. The dressing was naturally incorporated into regenerating tissue during the wound healing process. Applied keratin dressing favored reconstruction of more regular skin structure and assured better cosmetic outcome in terms of scar formation and appearance. Our results have shown that insoluble keratin wound dressing containing casomorphin supports skin wound healing in diabetic mice.     

Acute Ultraviolet Radiation Perturbs Epithelialization but not the Biomechanical Strength of Full‐thickness Cutaneous Wounds

We hypothesized that priming of the skin with ultraviolet radiation (UVR) before being injured would enhance wound healing. Four groups, each comprising 20 immunocompetent hairless mice, were exposed to simulated solar irradiation in escalating UVR doses; 0 standard erythema dose (SED) = control, 1 SED, 3 SED and 5 SED. Twenty‐four hours after UV irradiation, inflammation was quantified by skin reflectance (erythema) and myeloperoxidase (MPO) tissue levels, and two 6 mm full‐thickness excisional wounds and one 3 cm incisional wound were inflicted. Epidermal hyperplasia was assessed by quantitative histology. Five days after wounding, wound coverage by neoepithelium and wound width of the excisional wounds was quantified in hematoxylin–eosin sections, and breaking strength was measured in strips from incisional wounds. Erythema (P < 0.001), MPO levels (P < 0.0005) and epidermal cell layers (P < 0.001) increased dose‐dependently by UV exposure of dorsal skin. In the excisional wounds, epithelial coverage decreased (P = 0.024) by increasing the UVR dose, whereas there was no significant difference (P = 0.765) in wound MPO levels. Neither wound width (P = 0.850) nor breaking strength (P = 0.320) differed among the groups. Solar‐simulated UVR 24 h before wounding impaired epithelialization but was not detrimental for surgical incisional wound healing.     

Preparation of Multi-Functional Quaternary Ammonium Chitosan/Surfactin Hydrogel and its Application in Wound Management

Hydrogel with a 3D network structure can cover the wound to stop the bleeding and support the host tissue infiltration and integration. In this study, an antibacterial hydrogel with hemostasis and the ability to promote wound healing is proposed. This hydrogel comprised surfactin, polyvinylpyrrolidone, and methacrylic anhydride (MA) grafted quaternary ammonium chitosan (CS-MA). The hydrogel formation is triggered by the ultraviolet-initiated polymerization of CS-MA, while the surfactin is complexed with the hydrogel through hydrogen bonding interaction. The results showed that this hydrogel is an adhesive hydrogel with shape adaptability, which can cover the wound surface and promote contact between the hydrogel and the wound surface. More importantly, this hydrogel can simulate the microenvironment of the primary extracellular matrix and increase collagen deposition, and inflammatory factor transformation. The designing of such a multi-functional hydrogel is expected to provide a novel approach to promoting the healing of wounds.     

Enhanced skin wound healing by a sustained release of growth factors contained in platelet-rich plasma

Platelet-rich plasma (PRP) contains growth factors that promote tissue regeneration. Previously, we showed that heparin-conjugated fibrin (HCF) exerts the sustained release of growth factors with affinity for heparin. Here, we hypothesize that treatment of skin wound with a mixture of PRP and HCF exerts sustained release of several growth factors contained in PRP and promotes skin wound healing. The release of fibroblast growth factor 2, platelet-derived growth factor-BB, and vascular endothelial growth factor contained in PRP from HCF was sustained for a longer period than those from PRP, calcium-activated PRP (C-PRP), or a mixture of fibrin and PRP (F-PRP). Treatment of full-thickness skin wounds in mice with HCF-PRP resulted in much faster wound closure as well as dermal and epidermal regeneration at day 12 compared to treatment with either C-PRP or F-PRP. Enhanced skin regeneration observed in HCF-PRP group may have been at least partially due to enhanced angiogenesis in the wound beds. Therefore, this method could be useful for skin wound treatment.     

Dose–Response Relationship of Photobiomodulation Therapy on Matrix Metalloproteinase in Healing Dynamics of Diabetic Neuropathic Ulcers—An in vivo Study

Individuals with diabetic foot ulcers have overlapped the inflammatory, proliferative and remodeling phase, making the tissue vulnerable to delayed healing responses. We aimed to establish the dose–response relationship of photobiomodulation therapy of different doses and matrix metalloproteinases in the healing dynamics of diabetic neuropathic ulcers. Diabetes was induced in 126 Albino Wistar rats, and neuropathy was induced to the hind paw by a sciatic nerve injury method. An excisional wound was created on the neuropathy-induced leg. Photobiomodulation therapy of dosages 4, 6, 8, 10, 12 and 15 J cm⁻² and wavelength 655 nm and 808 nm was irradiated. Photobiomodulation therapy of dosages 4, 6 and 8 J cm⁻² showed better wound healing properties with optimized levels of matrix metalloproteinases-1 and 8. We observed a strong dose response in the experimental group treated with 6 and 8 J cm⁻². The findings from the present study conclude that photobiomodulation therapy of dosages 4, 6 and 8 J cm⁻² is suggestive of usefulness in diabetic neuropathic ulcer healing. Markers like matrix metalloproteinases may give a clear direction on response to the therapy. Based on the findings from the present study, we recommend to validate the findings for safety and efficacy in future through human prospective randomized controlled clinical trials.     

SP600125, a selective JNK inhibitor, aggravates hepatic ischemia-reperfusion injury

c-Jun N-terminal kinase (JNK) is activated during hepatic reperfusion, and JNK inhibitors are known to protect other major organs from ischemia-reperfusion (I/R) injury. We attempted to determine the effect of SP600125, a JNK inhibitor, on hepatic I/R injury using a partial ischemia model in mice. Compared to a vehicle-treated group, the SP600125- treated group showed a greater increase in serum ALT levels 24 h after reperfusion with more severe parenchymal destruction and leukocyte infiltration. Similarly, tissue myeloperoxidase and malondialdehyde levels were higher in the SP600125-treated group, and chemokine expression was also higher in the SP600125-treated group. These data, which are contradictory to previous results, indicate that JNK inhibition by SP600125 may be harmful in hepatic I/R injury. Therefore, care must be taken when investigating the therapeutic use of JNK inhibitors in hepatic I/R injury, especially in the context of the effects of JNK inhibition on inflammatory infiltration.     

Whole wheat flour coating with antioxidant property accelerates tissue remodeling for enhanced wound healing

As a daily food for billions of people for thousands of years,whole grain is rich in phenolic compounds and may have huge potentials to provide natural antioxidants.Herein,owing to the significant biomedical potential,the effect of whole wheat flour solution as antioxidant wound coating for enhanced wound healing has been studied.The results show that the low concentration of whole wheat flour solutions have good biocompatibility and can scavenge radical and intracellular ROS in vitro,accelerating tissue remodeling in vivo to promote wound healing.This kind of whole wheat flour solution has great potential application for cutaneous wound repair.     

Influence of laser photobiomodulation upon connective tissue remodeling during wound healing

The modulation of collagen fibers during experimental skin wound healing was studied in 112 Wistar rats submitted to laser photobiomodulation treatment. A standardized 8mm-diameter wound was made on the dorsal skin of all animals. In half of them, 0.2ml of a silica suspension was injected along the border of the wound in order to enhance collagen deposition and facilitate observation. The others received saline as vehicle. The treatment was carried out by means of laser rays from an aluminum-gallium arsenide diode semiconductor with 9mW applied every other day (total dose=4J/cm(2)) on the borders of the wound. Tissue sections obtained from four experimental groups representing sham-irradiated animals, laser, silica and the association of both, were studied after 3, 7, 10, 15, 20, 30 and 60 days from the laser application. The wounded skin area was surgically removed and submitted to histological, immunohistochemical, ultrastructural, and immunofluorescent studies. Besides the degree and arrangement of collagen fibers and of their isotypes, the degree of edema, the presence of several cell types especially pericytes and myofibroblasts, were described and measured. The observation of Sirius-red stained slides under polarized microscopy revealed to be of great help during the morphological analysis of the collagen tissue dynamic changes. It was demonstrated that laser application was responsible for edema regression and a diminution in the number of inflammatory cells (p<0.05). An evident increase in the number of actin-positive cells was observed in the laser-treated wounds. Collagen deposition was less than expected in silica-treated wounds, and laser treatment contributed to its better differentiation and modulation in all irradiated groups. Thus, laser photobiomodulation was able to induce several modifications during the cutaneous healing process, especially in favoring newly-formed collagen fibers to be better organized and compactedly disposed.     

Animal models of acute photodamage: comparisons of anatomic, cellular and molecular responses in C57BL/6J, SKH1 and Balb/c mice

Human cutaneous photodamage is a major medical problem that includes premature aging and fragility of the skin. Nonxenografted animal models have not been comparatively evaluated for how well they resemble the changes seen in human skin. Here, we sought to identify a suitable mouse model that recapitulates key anatomic, cellular and molecular responses observed in human skin during acute UV exposure. Adult females from three strains of mice, C57BL/6J, SKH1 and Balb/c were exposed to UVB and then evaluated 3 or 20 h after the last irradiation. Skin from UVB-exposed C57BL/6J mice showed features resembling human photodamage, including epidermal thickening, infiltration of the dermis with inflammatory cells, induction of tumor necrosis factor-α (TNF-α) mRNA, accumulation of glycosaminoglycans, particularly hyaluronan in the epidermis and loss of collagen. Hairless SKH1 mouse skin responded similarly, but without any induction of TNF-α mRNA or chondroitin sulfate. Irradiated Balb/c mice were the least similar to humans. Our results in C57BL/6J mice and to a lesser extent in SKH1 mice, show cutaneous responses to a course of UVB-irradiation that mirror those seen in human skin. Proper choice of model is critical for investigating cellular and molecular mechanisms of photodamage and photoaging.     

Sustainable Development of Chitosan/Calotropis procera-Based Hydrogels to Stimulate Formation of Granulation Tissue and Angiogenesis in Wound Healing Applications

The formation of new scaffolds to enhance healing magnitude is necessarily required in biomedical applications. Granulation tissue formation is a crucial stage of wound healing in which granulation tissue grows on the surface of a wound by the formation of connective tissue and blood vessels. In the present study, porous hydrogels were synthesized using chitosan incorporating latex of the Calotropis procera plant by using a freeze–thaw cycle to stimulate the formation of granulation tissue and angiogenesis in wound healing applications. Structural analysis through Fourier transform infrared (FTIR) spectroscopy confirmed the interaction between chitosan and Calotropis procera. Latex extract containing hydrogel showed slightly higher absorption than the control during water absorption analysis. Thermogravimetric analysis showed high thermal stability of the 60:40 combination of chitosan (CS) and Calotropis procera as compared to all other treatments and controls. A fabricated scaffold application on a chick chorioallantoic membrane (CAM) showed that all hydrogels containing latex extract resulted in a significant formation of blood vessels and regeneration of cells. Overall, the formation of connective tissues and blood capillaries and healing magnitude decreased in ascending order of concentration of extract.     

The Unexplored Wound Healing Activity of Urtica dioica L. Extract: An In Vitro and In Vivo Study

Wound healing is a great challenge in many health conditions, especially in non-healing conditions. The search for new wound healing agents continues unabated, as the use of growth factors is accompanied by several limitations. Medicinal plants have been used for a long time in would healing, despite the lack of scientific evidence veryfying their efficacy. Up to now, the number of reports about medicinal plants with wound healing properties is limited. Urtica dioica L. is a well-known plant, widely used in many applications. Reports regarding its wound healing potential are scant and sparse. In this study, the effect of an Urtica dioica L. extract (containing fewer antioxidant compounds compared to methanolic or hydroalcoholic extracts) on cell proliferation, the cell cycle, and migration were examined. Additionally, antioxidant and anti-inflammatory properties were examined. Finally, in vivo experiments were carried out on full-thickness wounds on Wistar rats. It was found that the extract increases the proliferation rate of HEK-293 and HaCaT cells up to 39% and 30% after 24 h, respectively, compared to control cells. The extract was found to increase the population of cells in the G₂/M phase by almost 10%. Additionally, the extract caused a two-fold increase in the cell migration rate of both cell lines compared to control cells. Moreover, the extract was found to have anti-inflammatory properties and moderate antioxidant properties that augment its overall wound healing potential. Results from the in vivo experiments showed that wounds treated with an ointment of the extract healed in 9 days, while wounds not treated with the extract healed in 13 days. Histopathological examination of the wound tissue revealed, among other findings, that inflammation was significantly reduced compared to the control. Urtica dioica L. extract application results in faster wound healing, making the extract ideal for wound healing applications and a novel drug candidate for wound healing.     

Effects of HeNe laser irradiation on experimental paracoccidioidomycotic lesions

Paracoccidioidomycosis (PCM) is the most prevalent human mycosis in Latin America. The infection is thought to take place firstly in the lungs and then may disseminate to other organs and tissues. Treatment by currently available antifungals is lengthy, the drugs may have undesirable side effects, and some are costly. Occasional resistant strains of Paracoccidioides brasiliensis, the causative agent of PCM, have been reported. So, the search for more efficient treatments or adjuvant therapies has to be continued. In this work, we evaluated the effects of HeNe laser irradiation on cutaneous inflammatory lesions caused by the inoculation of 5 x 10(6)/0.1ml yeasts cells into the back footpad of Balb/c mice. HeNe irradiation (lambda=632.8nm, 3mW, incident energy of 3J/cm(2)) was applied at days 7, 8 and 9 post-infection and histological and immunohistochemical analysis were done. Unirradiated animals were used as controls. The results showed that laser-treated mice presented reduction of footpad edema, faster cutaneous wound healing, confluent granuloma, diffuse- and more loosely distributed immunolabeling for TNF-alpha, enhanced labeling of IFN-gamma and any P. brasiliensis form detected, whereas multiple viable fungi were seen in diffuse widespread granulomas obtained from non-treated mice foot-pad. Fungi that were harvested from laser-treated animals presented no capability of growth in vitro as compared to those obtained from non-treated mice. We conclude that HeNe laser irradiation was able to inhibit the progress of inflammatory local reaction produced by P. brasiliensis infection and influence local cytokines production. We suggest that this treatment modality can be a useful coadjuvant tool to be combined with antifungal agents in the treatment of PCM ulcerations. The mechanisms involved in laser therapy of PCM lesions need further investigation.     

Formulation and characterization of a novel cutaneous wound healing ointment by silver nanoparticles containing Citrus lemon leaf: A chemobiological study

IntroductionFormulating new wound-healing ointments by natural compounds is the first research priority in the developing and developed countries. This study was intended to provide green formulation of Ag-NP ointment containing Citrus lemon leaf aqueous extract and examine its capability of healing cutaneous wounds and its antioxidant and cytotoxicity activities under in vitro and in vivo conditions.Materials and methodsDifferent techniques, including UV–Vis and FT-IR spectroscopy, were used to characterize Ag-NPs. MTT assay was used to investigate cytotoxicity property of Ag-NPs. Antioxidant activity of Ag-NPs were examined by DPPH in the presence of butylated hydroxytoluene as positive control. Parameters of cutaneous wound healing were measured both histopathologically and biochemically.ResultsClear peak at 429 nm shown by UV–Vis spectroscopy indicated formation of Ag-NPs. In FT-IR spectroscopy, presence of many antioxidant compounds provided an excellent condition to reduce silver in Ag-NPs. FE-SEM and TEM images showed spherical Ag-NPs with an average size of 25.1 nm. The synthesized silver nanoparticles had excellent cell viability on the HUVECs line and indicated this method was nontoxic. Application of Ag-NP ointment improved wound healing parameters significantly (P ≤ 0.01). Ag-NPs reduced wound areas, total cells, neutrophils and lymphocytes significantly (P ≤ 0.01) and increased wound contracture, vessels, hexosamines, hydroxyl proline, hexuronic acid, fibrocytes, fibroblasts and fibrocyte/ fibroblast ratios significantly (P ≤ 0.01).ConclusionsOnce our results are verified by clinically experimental studies, Ag-NP ointment can be used as a modern one to treat several types of wounds, especially cutaneous ones, in humans.     

Ultrastructural and autoradiographical analysis show a faster skin repair in He-Ne laser-treated wounds

There are evidences that low-intensity red laser radiation is capable to accelerate wound healing. Nowadays, this therapy has been gradually introduced in clinical practice although mechanisms underlying laser effects are poorly understood. To better understand the photobiological effects of laser radiation, this study investigated by electron microscopy, immunohistochemistry and autoradiography the morphological and functional features of irradiated and none irradiated injured mice skin. Full-thickness skin lesions were created on the back of mice and irradiated on days 1, 5, 8, 12, and 15 post-wounding with a He-Ne laser (lambda=632.8nm), dose 1J/cm(2), exposure time 3min. Non-irradiated lesions were used as a control. The mice were inoculated with (3)H-proline and sacrificed one hour after on the 8th, 15th and 22nd days to histological and radioautographical analysis. The irradiated-lesions showed a faster reepithelization compared with control lesions. The irradiated dermis contained a higher number of activated fibroblasts compared to control group and, most of them showed several cytoplasmic collagen-containing phagosomes. In irradiated-lesions, smooth muscle alpha-actin positive cells predominated, which correspond to a higher number of myofibroblasts observed in the electron microscope. Moreover, laser radiation reduced the local inflammation and appears to influence the organization of collagen fibrils in the repairing areas. Quantitative autoradiography showed that the incorporation of (3)H-proline was significantly higher in irradiated-dermis on the 15th day post-wounding (p<0.05). These results suggest that laser radiation may accelerate cutaneous wound healing in a murine model.     

Bioinspired Platelet-Anchored Electrospun Meshes for Tight Inflammation Manipulation and Chronic Diabetic Wound Healing

Tight manipulation of the initial leukocytes infiltration and macrophages plasticity toward the M2 phenotype remain a challenge for diabetic wound healing. Inspired by the platelet function and platelet–macrophage interaction, a platelet-anchored polylactic acid-b-polyethylene glycol-b-polylactic acid (PLA-PEG-PLA) electrospun dressing is developed for inflammatory modulation and diabetic wounds healing acceleration. PLA-PEG-PLA electrospun meshes encapsulated with thymosin β4 (Tβ4) and CaCl₂ is fabricated with electrospinning, followed by immersion of electrospun mesh in platelet-rich plasma to firmly anchor the platelets. It is demonstrated that the anchored platelets on electrospun mesh can enhance the initial macrophage recruitment and control the Tβ4 release from electrospun meshes to facilitate the macrophages polarization to the M2 phenotype. The inflammatory regulation promotes the expression of vascular endothelial growth factor and the migration of vascular endothelial cells for angiogenesis, resulting in accelerated diabetic wounds healing. Therefore, this work paved a new way to design platelet-inspired electrospun meshes for inflammation manipulation and diabetic wound healing.     

Mealworm Oil (MWO) Enhances Wound Healing Potential through the Activation of Fibroblast and Endothelial Cells

Mealworm and mealworm oil (MWO) have been reported to affect antioxidant, anti-coagulation, anti-adipogenic and anti-inflammatory activities. However, the function of MWO in wound healing is still unclear. In this study, we found that MWO induced the migration of fibroblast cells and mRNA expressions of wound healing factors such as alpha-smooth muscle actin (α-SMA), collagen-1 (COL-1) and vascular endothelial growth factor (VEGF) in fibroblast cells. The tube formation and migration of endothelial cells were promoted through the activation of VEGF/VEGF receptor-2 (VEGFR-2)-mediated downstream signals including AKT, extracellular signal-regulated kinase (ERK) and p38 by MWO-stimulated fibroblasts for angiogenesis. Moreover, we confirmed that MWO promoted skin wound repair by collagen synthesis, re-epithelialization and angiogenesis in an in vivo excisional wound model. These results demonstrate that MWO might have potential as a therapeutic agent for the treatment of skin wounds.     

The marriage of sealant agent between structure transformable silk fibroin and traditional Chinese medicine for faster skin repair

Fast skin repair is critical for less infection, less pain and high quality of life, which is still limited with undesirable rehabilitation speed and side effects. Currently, laser-activated silk sealant agent without suture and gauze has been demonstrated promising for fast skin repair taking advantage of its structural transformation after heating. Nevertheless, more efficient healing effects and less side effects of laseractivated silk sealant agent remains challenging due to absence of suita...     

Improvement of dermal burn healing by combining sodium alginate/chitosan-based films and low level laser therapy

This paper aimed to evaluate the improvement of burn wounds healing by sodium alginate/chitosan-based films and laser therapy. Natural polymers with different biological activities are widely used as film dressings to improve wound healing. Lasers arrays accelerate the healing repair of soft tissue injuries. Burn procedures were performed on the backs of 60 male rats assigned into six groups: untreated (CTR), dressed with cellulose films (CL), dressed with sodium alginate/chitosan-based films (SC), laser-irradiated undressed wounds (LT), laser-irradiated wounds with cellulose (CLLT) and sodium alginate/chitosan-based films (SCLT). Laser therapy was applied for 7 days. Animals of each group were euthanised 8 and 14 days after the burn procedures. The inflammatory reaction was significantly more intense in the CTR group than in the irradiated groups after 8 and 14 days. Laser therapy stimulated myofibroblastic differentiation in 8 days, with or without dressing films. Combined laser therapy and both dressings improved epithelisation, blood vessels formation and collagenization, promoted rapid replacement of type III for type I collagen and favored the better arrangement of the newly formed collagen fibres. The combination of laser therapy and sodium alginate/chitosan-based dressing improves burn healing, apparently by modulating the epithelisation, blood vessels formation and collagenization processes.     

Photobiomodulation Therapy on the Guided Bone Regeneration Process in Defects Filled by Biphasic Calcium Phosphate Associated with Fibrin Biopolymer

The aim is to evaluate the effects of photobiomodulation therapy (PBMT) on the guided bone regeneration process (GBR) in defects in the calvaria of rats filled with biphasic calcium phosphate associated with fibrin biopolymer. Thirty male Wistar rats were randomly separated: BMG (n = 10), defects filled with biomaterial and covered by membrane; BFMG (n = 10), biomaterial and fibrin biopolymer covered by membrane; and BFMLG (n = 10), biomaterial and fibrin biopolymer covered by membrane and biostimulated with PBMT. The animals were euthanized at 14 and 42 days postoperatively. Microtomographically, in 42 days, there was more evident bone growth in the BFMLG, limited to the margins of the defect with permanence of the particles. Histomorphologically, an inflammatory infiltrate was observed, which regressed with the formation of mineralized bone tissue. In the quantification of bone tissue, all groups had a progressive increase in new bone tissue with a significant difference in which the BFMLG showed greater bone formation in both periods (10.12 ± 0.67 and 13.85 ± 0.54), followed by BFMG (7.35 ± 0.66 and 9.41 ± 0.84) and BMG (4.51 ± 0.44 and 7.11 ± 0.44). Picrosirius-red staining showed greater birefringence of collagen fibers in yellow-green color in the BFMLG, showing more advanced bone maturation. PBMT showed positive effects capable of improving and accelerating the guided bone regeneration process when associated with biphasic calcium phosphate and fibrin biopolymer.     

Heparin coating of poly(ethylene terephthalate) decreases hydrophobicity, monocyte/leukocyte interaction and tissue interaction

Woven poly(ethylene terephthalate) (PET) is widely used in implantable medical devices. Upon implantation, fibrinogen interacts with the PET and changes conformation, such that the fibrinogen P2 epitope may become exposed. This allows inflammatory cells to interact with the material. In this study we have coated PET with heparin and show that this decreases PET hydrophobicity and the presence of the fibrinogen P2 epitope on the material surface. In addition, we show that heparin-induced reduction of PET hydrophobicity correlates with decreased exposure of the fibrinogen P2 epitope and reduced adhesion of monocytes. Reduction of PET hydrophobicity was furthermore associated with reduced PMN elastase production and decreased interaction between PET and embryonic chicken tissue. We conclude that the heparin coating-induced decrease in PET hydrophobicity is associated with decreased interaction between PET and inflammatory cells. Independent of this interaction, the hydrophobic nature of the heparin coating is related to tissue interaction as demonstrated by a reduction in adhesion, growth and spreading of tissue on PET. The combination of these properties makes heparin coating a candidate for improving biocompatibility of PET.