A systematic literature review of the management of chronic venous ulcers with autologous fibrin matrix with or without growth factors

8 p.Aim: To evaluate available evidence for the effective management of venous leg ulcers with fibrin matrix with or without growth factors. Methods: A systematic review of the literature was performed to evaluate the use of fibrin matrices with or without growth factors for the management of chronic venous ulcers in lower limbs. Article searches were performed in MEDLINE, EMBASE, COCHRANE, LILACS and ongoing clinical trials at ClinicalTrial.gov. Results: The search in MEDLINE and EMBASE identified three articles; one was a pilot study evaluating the use of fibrin matrix and autologous growth factors that included patients with chronic ulcers of different etiology. The second article was a description of the product used in the previous study, and the third consisted of a series case reports of patient treated with cultured keratinocytes in a fibrin matrix. A COCHRANE searched resulted in one study assessing the cost effectiveness of using different fibrin matrices. The search in ClinicalTrial.gov and LILACS did not result in any findings. Conclusion: The study did not provide a conclusive evidence for the use of fibrin matrices in patients with venous leg ulcers

Autologous Platelet-Rich Plasma and Mesenchymal Stem Cells for the Treatment of Chronic Wounds

Emerging autologous cellular therapies, utilizing platelet-rich plasma and mesenchymal stem cell applications, have the potential to play an adjunctive role in a standardized wound care treatment plan in patients suffering from chronic and recalcitrant wounds. The use of platelet-rich plasma growth is based on the fact that platelet growth factors can support the three phases of wound healing and then ultimately contribute to full wound closure. Mesenchymal stem cell-based therapies are also an attractive approach for the treatment of these difficult-to-heal wounds. This field of regenerative medicine focuses primarily on stem cells, which are specialized cells with the ability to self-renew and differentiate into multiple cell types. Mesenchymal stem cells can be isolated from bone marrow and adipose tissue via minimally manipulative and cell-processing techniques, at point of care. Both platelet-rich plasma and mesenchymal stem cell applications have the potential to become an effective and ideal autologous biological cell-based therapy, which can be applied to chronic wounds to effectively change the wound bed microenvironment to enable and accelerate wound closure

Vivostat Platelet-Rich Fibrin® for Complicated or Chronic Wounds-A Pilot Study

Vivostat Platelet-Rich Fibrin® (PRF) is an autologous platelet concentrate used for the local treatment of chronic or complicated wounds. Still, its application for this indication is not evidence-based. Therefore, we performed this monocentric retrospective pilot study investigating the clinical outcome of a local treatment of chronic or complicated wounds in 35 patients (23 male, 12 female, mean age 68.7 years) treated with Vivostat PRF®. This study population is the largest among published studies analyzing the clinical efficacy of Vivostat PRF® on chronic wounds so far. Using the perpendicular method we divided the wounds into three sizes (30 cm2). The clinical efficacy of the Vivostat PRF treatment was the primary endpoint and was divided into three groups of increasing degrees of wound improvement: (1) no improvement of the wound (wound area was not reduced > 10% under Vivostat PRF® treatment), (2) improvement of the wound (reduced area > 10% under Vivostat PRF® treatment) and (3) complete epithelialization (wounds that were completely re-epithelialized after Vivostat PRF® treatment). We included patients' diagnosis and concomitant diseases (peripheral arterial occlusive disease (PAOD)), chronic venous insufficiency (CVI)), diabetic foot syndrome (DFS)) in our data analysis in order to investigate their potential impact on the wound healing capacity of Vivostat PRF®. Our results show that in the entire study population, 13 out of 35 (37.1%) patients experienced wound improvement and 14 out of 35 (40%) patients showed complete epithelialization of their wound under Vivostat PRF® treatment. In summary, 77.1% of the treated patients benefited from the Vivostat PRF® therapy

Leg Ulceration in Sickle Cell Disease: An Early and Visible Sign of End‐Organ Disease

Introduction: Leg ulcers are a frequent and debilitating complication of sickle cell disease (SCD), particularly of the SS genotype. The prevalence of leg ulcers in patients with sickle cell disease (SCD) varies geographically ranging widely from 75% in Jamaica to as low as 1% in Saudi Arabia. The prevalence of leg ulcers in the Cooperative Study of Sickle Cell Disease (CSSCD) in the United States was 5% in SS genotype with the incidence increasing with age. As patients with SCD have increasingly improved survival, the prevalence of leg ulcers is likely to be higher. These ulcers are slow to heal, have a high rate of recurrence, and are associated with severe unremitting pain and depression, thus leading to high healthcare costs. Despite being a well‐recognized complication of SCD, there are no specifically designed evidence‐based guidelines to help clinicians manage these patients

Paracrine factors from aggregates of fibroblasts or bone marrow stromal cells enhance skin wound healing

The skin is the largest organ of the human body. It maintains body homeostasis and provides an essential barrier that protects us from the environment. After injury to the skin, a complex series of tightly controlled responses are initiated to restore its integrity. In large-scale wounds, such as burns, the intrinsic capacity for healing is compromised due to lack of dermal support. Dermal fibroblasts guide crucial re-epithelialization events such as keratinocyte migration and proliferation. Fibroblast-keratinocyte interaction is directed by paracrine factors as well as cell-cell and cell-extracellular matrix contacts. Fibroblasts as well as other mesenchyme-derived cells such as bone marrow stromal cells can produce a vast array of growth factors in vitro. When activated by deprivation of extracellular matrix cell adhesion sites, the cells prefer cell-to-cell contacts, form clusters, and release growth factors. This present work focused on characterizing the use of a combination of growth factors released by mesenchymal cell aggregates, a process designated as nemosis, for treatment of skin wound healing. We used inhibitors of several intracellular signaling pathways to define the migration-inducing mechanisms of nemosis using a keratinocyte wound-healing assay. Model human keratinocytes HaCaT-cells responded to the nemosis-derived conditioned medium with enhanced migration, proliferation, and viability. A c-Met-specific small molecule tyrosine kinase inhibitor as well as an anti-hepatocyte growth factor antibody inhibited these responses. The study aimed to characterize means of improving wound healing by combining biological materials, such as fibrin or recombinant human collagen III with the growth factors to construct a transplantable cell- and growth factor-containing matrix. When we treated porcine partial-thickness wounds with the growth factor-containing fibrin matrix, we observed an increase in the proliferation and migration of hair-follicle and lateral wound-edge keratinocytes. In addition, granulation tissue formation was enhanced when compared with formation on saline-treated wounds. Keratinocyte transplantation in porcine full thickness wounds was feasible with a recombinant human collagen type III matrix. The results presented here indicate that cell-cell contact-activated fibroblasts or bone marrow stromal cells improve keratinocyte transplantation with paracrine factors. Fibrin or recombinant human collagen III can serve as vehicles for delivery of these signals to the target site in acute wounds. Since these factors are also crucial for healing of chronic non-healing wounds, it is likely that our therapeutic approach will be of benefit in their treatment, too.  Ihon ulkopinta, orvaskesi, muodostaa kemiallisen ja fysikaalisen suojan elimistön ja ulkomaailman välille. Vaikeissa ihovaurioissa, kuten laaja-alaisissa palovammoissa ja kroonisissa haavoissa, ihon paranemiskyky on heikentynyt kasvutekijöiden puutteesta. Tiedetään, että kasvutekijät ovat välttämättömiä monitahoisessa paranemisprosessissa. Keskeinen rooli on verinahassa olevilla sidekudossoluilla, fibroblasteilla, jotka tuottavat kasvutekijöitä haavaympäristöön. Ihon sarveissolut reagoivat kasvutekijöihin lisääntymällä ja vaeltamalla haavapintaa pitkin pyrkien palauttamaan orvaskeden suojarakenteen. Vaikeiden haavojen hoitona käytetään tavallisesti iho- tai solusiirtoja toimenpiteen aiheuttaessa potilaalle ihonottohaavan. Sekä ihosiirteen, että ihonottohaavan hidas paraneminen on haitallista ja heikentää vaikeasti palaneiden potilaiden ennustetta ja pidentää merkittävästi sairaalassaoloaikaa. Väitöskirjatutkimuksessa pyrittiin selvittämään fibroblastien ja sarveissolujen kasvutekijävälitteisiä vuorovaikutuksia haavan paranemisessa. Väitöskirjatutkimuksessa osoitettiin, että sidekudossoluja, fibroblasteja ja luuytimen kantasoluja, voidaan soluviljelmissä aktivoida tuottamaan tarkoin määrättyä kasvutekijäyhdistelmää. Soluaktivaatiossa, nemoosissa, soluilta estetään niiden kiinnittyminen viljelymaljaan ja toisiinsa kiinnittyessään ne muodostavat solurykelmän ja vapauttavat muiden tulehdusvälittäjä-aineiden lisäksi suuren määrän HGF-kasvutekijää. Väitöstutkimuksessa havaittiin, että nemoosissa tuotetut aineet tehostivat merkittävästi sarveissolujen jakautumista ja vaeltamista soluviljelymalleissa. HGF-kasvutekijän osuus haavan paranemiseen osoitettiin estämällä sen c-Met reseptorin aktivoituminen lääkeaineilla. Lisäksi selvitettiin HGF-kasvutekijän solusisäistä viestitystä. Porsaan ihohaavamallissa havaitsimme, että kasvutekijäterapia nopeutti haavan paranemista aktivoimalla sarveissoluja ja niiden kantasoluja hiusfollikkeleista. Väitöskirjatyössä pyrittiin edelleen kehittämään käytössä olevia solusiirtomenetelmiä. Nykyisissä menetelmissä käytetään eläinperäisiä soluja ja soluväliaineita, kuten kollageenia, kasvatusalustana ja tukirakenteena. Sovelsimme rekombinanttiteknologian avulla tuotettua ihmisperäistä kollageenia, sekä fibriiniä yhdessä kasvutekijöiden kanssa tehostamaan sarveissolujen siirtoa haavaan. Tämä kokeelliseen kirurgiaan kuuluva väitöskirjatyö tarkentaa käsitystä kasvutekijöiden merkityksestä vaikeiden haavojen hoidossa ja antaa uusia ratkaisuja kliinisten solusiirtoterapioiden tehostamiseksi. Väitöskirjatyön tuloksia hyödynnetään jatkotutkimuksissa, joissa tavoitteena on syventää tietämystä fibroblasti-aktivaation osallisuudesta haavan paranemisen muihin osa-alueisiin

A Comparative study on the Efficacy of Topical Autohemotherapy Versus Topical Autologous Platelet Rich Plasma in Chronic Venous Ulcers

BACKGROUND: Chronic venous ulcers, the most common cause of lower limb ulceration is emerging as a major public health challenge with morbidity and significant impact on the quality of life. Wound healing in these patients is a complex process which is regulated by the interaction between various cell types, extracellular matrix, cytokines and growth factors. Topical autohemotherapy and topical autologous platelet rich plasma (PRP) are simple office based procedure which helps in enhancing the wound healing. AIM OF THE STUDY: To compare the efficacy of topical autohemotherapy and topical autologous platelet rich plasma in the healing of chronic leg ulcers due to venous stasis by estimating the change in the ulcer area and volume after treatment. METHODOLOGY: 36 patients with 40 venous ulcers were randomly divided into two group and each group was treated with topical autohemotherapy and autologous PRP respectively and treatment outcome was measured by percentage of improvement in area and volume of the ulcer. RESULTS: 18 patients with 22 ulcers were treated with autohemotherapy and 18 patients with 18 ulcers were treated with PRP. The median age of the patients was 49.5 years. 34 were males and 2 were females. The mean duration of the ulcers was 4.23 months. The percentage of improvement in the mean area at the end of six weeks following treatment with autohemotherapy and autologous platelet rich plasma was 88.4% and 85% respectively (p=0.45). The percentage of improvement in the mean volume at the end of six weeks following treatment with autohemotherapy and autologous platelet rich plasma was 97.9 % and 88.4% respectively (p=0.1). CONCLUSIONS: Both topical autohemotherapy and topical autologous PRP are safe, office based procedures in treating chronic venous ulcers, Topical autohemotherapy is a simpler, cost effective, less time consuming procedure and does not require sophisticated equipment and hence may be considered as a primary treatment modality in the management of chronic venous ulcers in resource poor settings

Recent Advances in Wound Healing

The human wound-healing process could be divided into four discrete phases, which have also been indicated as the hemostasis, the inflammatory, the proliferation, and the remodeling phase. For a wound to be healed efficaciously, all four phases must sequentially happen at an expected time setting. Numerous aspects can hinder one or more stages of this procedure, thus can cause inappropriate or diminished wound healing. This book reviews the recent literature on the most significant factors that affect wound healing and the potential cellular and/or molecular mechanisms involved. The factors discussed include physiology of wound healing, interferon, stem cells and photobiomodulation, chronic venous ulcer, chronic fistula, bionanomaterials, topical antiseptic agents, including silver and sodium hypochlorite solution, diabetic ulcers, and nutritional supplements such as copper