Figure - available from: Environmental Science and Pollution Research
This content is subject to copyright. Terms and conditions apply.
Immunohistochemistry for collagen in skin wound healing of rats after 14 days of PRP and/or SCH application (Masson’s trichrome, × 200, bars = 50 μm). a The control group showing a low amount of collagen with irregular deposition (arrows). b The PRP-treated group showing an increase in the collagen within the granulation tissue (arrows). c The SCH-treated group showing marked collagen formation with complete remodeling (arrows). d The PRP- and SCH-treated groups showing marked remodeling of collagen tissue (arrows)
Source publication
Platelet-rich plasma (PRP) composites of various cytokines and growth factors which have the potential to activate and speed the process of wound repair. Sildenafil also is a potent stimulator of angiogenesis which favors its potential effects on wound healing in several models. Existing work planned to examine the effectiveness of topical applicat...
Citations
... 23 Indeed, PRP plays an essential role during the inflammatory phase by providing several cytokines involved in the regular healing process. 24 Finally, the polymers forming hydrogels can be also able to influence the different healing stages of injured skin by acting on cell proliferation, migration, maturation and differentiation, angiogenesis, cell signalling and inflammation. 5,15,[25][26][27] In chronic wounds caused by diseases such as diabetes, malignant tumours, infections, and vasculopathy, the physiological cascade of events occurring during the healing process is significantly compromised causing persistent infections, inflammatory response, loss of angiogenic potential, reduced extracellular matrix, and degradation of growth factors. ...
Hydrogels based on various polymeric materials have been successfully developed in recent years for a variety of skin applications. Several studies have shown that hydrogels with regenerative, antibacterial, and antiinflammatory properties can provide faster and better healing outcomes, particularly in chronic diseases where the normal physiological healing process is significantly hampered. Various experimental tests are typically performed to assess these materials' ability to promote angiogenesis, re-epithelialization, and the production and maturation of new extracellular matrix. Immunohistochemistry is important in this context because it allows for the visualization of in situ target tissue factors involved in the various stages of wound healing using antibodies labelled with specific markers detectable with different microscopy techniques. This review provides an overview of the various immunohistochemical techniques that have been used in recent years to investigate the efficacy of various types of hydrogels in assisting skin healing processes. The large number of scientific articles published demonstrates immunohistochemistry's significant contribution to the development of engineered biomaterials suitable for treating skin injuries.
... As a potent stimulator of angiogenesis, sildenafil was also used together with PRP for enhanced wound healing. Gad et al. [65] studied the effectiveness of topical application of PRP and/or sildenafil citrate hydrogel (SCH) in a nonsplinted excision skin wound model. PRP and/or SCH topical treatments caused an enhancement of wound healing parameters, including a rapid switch from the inflammatory phase to the connective tissue stage, as evidenced by less systemic hematological changes and decreased values of interleukin-6 (IL-6), tumor necrosis factor (TNF-α), interleukin (IL-1β), and C-reactive protein (CRP) on the 7th or 14th day. ...
Platelet-rich plasma (PRP), a platelet-rich plasma concentrate obtained from whole blood, has been widely used to treat wounds due to its high contents of growth factors that can not only play a role in the hemostasis, repair, and anti-infection of wounds but also promote cell proliferation, maturation, and angiogenesis. However, after PRP activation, its clinical effect was limited because of burst and uncontrolled release of growth factors and poor mechanical properties of PRP gels. In recent years, increasing attention has been moved to the loading and sustained release of growth factors in PRP by polymeric carriers. Hydrogels, as an interesting carrier, enable controlled delivery of growth factors by structural designs. Moreover, using hydrogels to encapsulate PRP is favorable to controlling the mechanical properties and water maintenance of PRP gels, which can provide a stable and moist wound repair environment to promote coordinated operations of skin tissue cells and cytokines as well as wound healing. In this review, the state of the art of hydrogels that have been used to load PRP for wound treatments is introduced, and further prospects in the research area are proposed.
... Consequently, the mechanisms by which sildenafil confers protection during ischemic diseases requires further investigation, especially when it is used chronically. Recently, it has been demonstrated that sildenafil, as a potent stimulator of angiogenesis, accelerates and better repairs wound healing through the regulation of proinflammatory cytokines and collagen/TGF-β1 pathways [23]. ...
Hypoxia and inflammation play a major role in revascularization following ischemia. Sildenafil inhibits phosphodiesterase-5, increases intracellular cGMP and induces revascularization through a pathway which remains incompletely understood. Thus, we investigated the effect of sildenafil on post-ischemic revascularization. The left femoral artery was ligated in control and sildenafil-treated (25 mg/kg per day) rats. Vascular density was evaluated and expressed as the left/right leg (L/R) ratio. In control rats, L/R ratio was 33 ± 2% and 54 ± 9%, at 7- and 21-days post-ligation, respectively, and was significantly increased in sildenafil-treated rats to 47 ± 4% and 128 ± 11%, respectively. A neutralizing anti-VEGF antibody significantly decreased vascular density (by 0.48-fold) in control without effect in sildenafil-treated animals. Blood flow and arteriolar density followed the same pattern. In the ischemic leg, HIF-1α and VEGF expression levels increased in control, but not in sildenafil–treated rats, suggesting that sildenafil did not induce angiogenesis. PI3-kinase, Akt and eNOS increased after 7 days, with down-regulation after 21 days. Sildenafil induced outward remodeling or arteriogenesis in mesenteric resistance arteries in association with eNOS protein activation. We conclude that sildenafil treatment increased tissue blood flow and arteriogenesis independently of VEGF, but in association with PI3-kinase, Akt and eNOS activation.
... and EPO levels, ICAM-1 in PL of Group 2 were significantly lower compared with Group 4. Gad and coworkers compared PRP and sildenafil (an angiogenesis stimulator) treatment in experimental skin wound healing in rats. They estimated that both components decreased systemic proinflammatory cytokine levels [21]. A comparison of PRP obtained from patients with and without diabetes revealed that patients with diabetes had higher VEGF levels [22]. ...
Platelet lysate contained a wide range of bioactive molecules involved in cell proliferation, migration. The paper analyzes the possibility of using platelet lysate for the treatment of non-healing ulcers. The levels of bioactive molecules were determined by ELISA in platelet lysate. Efficacy of treatment with platelet lysate patients with diabetic foot ulcers, ulcers in patients with peripheral arterial disease and venous insufficiency were analyzed on wound surface area, total epithelialization. Twice injection of platelet lysate with an interval of 5-7 days possess to wound surface area closure on Day 180 at 96% in patients with diabetic foot ulcers, while in patients with peripheral arterial disease and venous insufficiency ulcers wound closure was less. Platelet lysate from patients with non-healing ulcers contained growth factor, cytokine, components of the extracellular matrix, and nitric oxide. Between levels of bioactive molecules in platelet lysate and outcome were found significant correlation. The obtained results indicate that platelet lysate possesses wound healing activity.
Phosphodiesterase type 5 (PDE5) is pivotal in cellular signalling, regulating cyclic guanosine monophosphate (cGMP) levels crucial for smooth muscle relaxation and vasodilation. By targeting cGMP for degradation, PDE5 inhibits sustained vasodilation. PDE5 operates in diverse anatomical regions, with its upregulation linked to various pathologies, including cancer and neurodegenerative diseases. Sildenafil, a selective PDE5 inhibitor, is prescribed for erectile dysfunction and pulmonary arterial hypertension. However, considering the extensive roles of PDE5, sildenafil might be useful in other pathologies. This review aims to comprehensively explore sildenafil’s therapeutic potential across medicine, addressing a gap in the current literature. Recognising sildenafil’s broader potential may unveil new treatment avenues, optimising existing approaches and broadening its clinical application.
This chapter focuses on the research progress of platelet-rich plasma in wound healing, from bench to bedside. Combined with the basic science and clinical application, it reveals the application effect and mechanism of platelet-rich plasma on common clinical wounds, including pressure ulcers, electric injuries, Achilles tendon wounds, venous ulcer of the lower extremity, and chronic refractory wounds and radiotherapy wounds.
Diabetes is generally accompanied by difficult-to-heal wounds, which often lead to permanent disability and even death of patients. Because of the abundance of a variety of growth factors, platelet rich plasma (PRP) has been proven to have great clinical potential for diabetic wound treatment. However, how to suppress the explosive release of its active components while realizing adaptability to different wounds remains important for PRP therapy. Here, an injectable, self-healing, and non-specific tissue-adhesive hydrogel formed by oxidized chondroitin sulfate and carboxymethyl chitosan was designed as an encapsulation and delivery platform for PRP. With a dynamic cross-linking structural design, the hydrogel can meet the clinical demands of irregular wounds with controllable gelation and viscoelasticity. Inhibition of PRP enzymolysis as well as sustained release of its growth factors is realized with the hydrogel, enhancing cell proliferation and migration in vitro. Notably, greatly accelerated healing of full thickness wounds of diabetic skins is enabled by promoting the formation of granulation tissues, collagen deposition and angiogenesis as well as reducing inflammation in vivo. This self-healing and extracellular matrix-mimicking hydrogel provides powerful assistance to PRP therapy, enabling its promising applications for the repair and regeneration of diabetic wounds.
