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BM aspiration from iliac crest. BM, bone marrow. To see this illustration in color, the reader is referred to the web version of this article at www.liebertpub.com/wound
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Introduction: Chronic wounds that are difficult to heal are physical and financial burden to the sufferer and a challenge to the treating physician. Objective: The main purpose of this study was to develop a novel method of using bone marrow (BM) aspirate, either cultured or fresh, as early solution for healing of chronic wounds and further reduce...
Citations
... 46 Hersant et al. showed that a treatment combining PRP and MSCs improves mouse wound closure and proangiogenic properties in wound sites. 75 Furthermore, the addition of 5% activated PRP to normal medium has been shown to promote proliferation of ASCs in vivo and Blanton et al. showed that the addition of PRP to ASCs resulted in synergistically improved wound healing, largely attributed to the large amount of growth factors found in PRP. 76 Interestingly, no effect was seen using neither ASC nor PRP alone. ...
Chronic wounds, characterized by prolonged healing processes, pose a significant medical challenge with multifaceted aetiologies, including local and systemic factors. Here, it explores the complex pathogenesis of chronic wounds, emphasizing the disruption in the normal phases of wound healing, particularly the inflammatory phase, leading to an imbalance in extracellular matrix (ECM) dynamics and persistent inflammation. Senescent cell populations further contribute to impaired wound healing in chronic lesions. Traditional medical management focuses on addressing underlying causes, but many chronic wounds resist to conventional treatments, necessitating innovative approaches. Recent attention has turned to autologous orthobiologics, such as platelet‐rich plasma (PRP), platelet‐rich fibrin (PRF) and mesenchymal stem cells (MSCs), as potential regenerative interventions. These biologically derived materials, including bone marrow aspirate/concentrate (BMA/BMAC) and adipose tissue‐derived stem cells (ADSCs), exhibit promising cytokine content and regenerative potential. MSCs, in particular, have emerged as key players in wound healing, influencing inflammation and promoting tissue regeneration. This paper reviews relevant scientific literature regarding basic science and brings real‐world evidence regarding the use of orthobiologics in the treatment of chronic wounds, irrespective of aetiology. The discussion highlights the regenerative properties of PRP, PRF, BMA, BMAC and SVF, showcasing their potential to enhance wound healing. Despite advancements, further research is essential to elucidate the specific roles of each orthobiologic and determine optimal applications for different wound types. The conclusion underscores the evolving landscape in chronic wound management, with a call for more comprehensive studies to refine treatment strategies and maximize the benefits of regenerative medicine.
... It is within this context that the exploration of stem cell therapy emerges as a promising and potentially transformative approach. Regarding research into the unique regenerative capabilities of stem cells, further research in this domain has the potential to revolutionize wound care and contribute substantially to ameliorating the impact of non-healing wounds on both individuals and the healthcare system [8][9][10][11]. ...
... In a case-control study involving 75 patients with chronic wounds, 50 were treated with autologous bone marrow (BM) aspirate, either fresh or cultured, while 25 received daily saline dressings. Notably, both the fresh and cultured BM aspirate, even without specific identification, isolation, and selective application of stem cells, led to a significant reduction in wound surface area compared to the control group at day 7 and week 4 [11]. Another study by Bonora et al. focused on patients with diabetes and ischemic wounds. ...
Wound healing is an intricate process involving coordinated interactions among inflammatory cells, skin fibroblasts, keratinocytes, and endothelial cells. Successful tissue repair hinges on controlled inflammation, angiogenesis, and remodeling facilitated by the exchange of cytokines and growth factors. Comorbid conditions can disrupt this process, leading to significant morbidity and mortality. Stem cell therapy has emerged as a promising strategy for enhancing wound healing , utilizing cells from diverse sources such as endothelial progenitor cells, bone marrow, adipose tissue, dermal, and inducible pluripotent stem cells. In this systematic review, we comprehensively investigated stem cell therapies in chronic wounds, summarizing the clinical, translational, and primary literature. A systematic search across PubMed, Embase, Web of Science, Google Scholar, and Cochrane Library yielded 22,454 articles, reduced to 44 studies after rigorous screening. Notably, adipose tissue-derived mesenchymal stem cells (AD-MSCs) emerged as an optimal choice due to their abundant supply, easy isolation, ex vivo proliferative capacities, and pro-angiogenic factor secretion. AD-MSCs have shown efficacy in various conditions, including peripheral arterial disease, diabetic wounds, hypertensive ulcers, bullous diabeticorum, venous ulcers, and post-Mohs micrographic surgery wounds. Delivery methods varied, encompassing topical application, scaffold incorporation, combination with plasma-rich proteins, and atelocollagen administration. Integration with local wound care practices resulted in reduced pain, shorter healing times, and improved cosmesis. Stem cell transplantation represents a potential therapeutic avenue, as transplanted stem cells not only differentiate into diverse skin cell types but also release essential cytokines and growth factors, fostering increased angiogenesis. This approach holds promise for intractable wounds, particularly chronic lower-leg wounds, and as a post-Mohs micrographic surgery intervention for healing defects through secondary intention. The potential reduction in healthcare costs and enhancement of patient quality of life further underscores the attractiveness of stem cell applications in wound care. This systematic review explores the clinical utilization of stem cells and stem cell products, providing valuable insights into their role as ancillary methods in treating chronic wounds.
... It is within this context that the exploration of stem cell therapy emerges as a promising and potentially transformative approach. Researching into the unique regenerative capabilities of stem cells, further research in this domain has the potential to revolutionize wound care and contribute substantially to ameliorating the impact of non-healing wounds on both individuals and the healthcare system (8)(9)(10)(11). ...
... In a case-control study involving 75 patients with chronic wounds, 50 were treated with autologous bone marrow (BM) aspirate, either fresh or cultured, while 25 received daily saline dressings. Notably, both fresh and cultured BM aspirate, even without specific identification, isolation, and selective application of stem cells, led to a significant reduction in wound surface area compared to the control group at day 7 and week 4 (11). Another study by Bonora et al. focused on patients with diabetes and ischemic wounds. ...
Introduction: Wound healing is a complex cascade involving the orchestration of inflammatory cells, skin fibroblasts, keratinocytes, and endothelial cells. These cells achieve tissue repair through an interchange of cytokines and growth factors through a controlled inflammation, angiogenesis, and remodeling process. Disruptions in the wound-healing process by comorbid conditions lead to significant morbidity and mortality. Stem cell therapy has emerged as a new strategy to facilitate the wound healing process. Stem cells harvested from different sources can be used for wound repair and regeneration (endothelial progenitor cells, bone marrow, adipose tissue, dermal and inducible pluripotent stem cells). We aimed to review clinical, translational, and primary literature on stem cell therapies in chronic wounds and summarize practical clinical applications to dermatological care. Materials and Methods: A comprehensive search of Pubmed, Embase, Web of Science, Google Scholar, and Cochrane Library was conducted for studies relating to stem cells and wound healing. Duplicate results were removed using Covidence. Titles and abstracts were screened by two independent researchers (BF and KR), with discrepancies resolved through discussion and mutual agreement. Articles were excluded if they were review-type or commentary-type articles. Results: A total of 22,454 articles were retrieved from the search. Deduplication removed 905, and automation removed an additional 18,363 articles. After an initial screening of titles and abstracts, 170 articles remained. Full-text screening resulted in an additional 126 articles being removed, leaving 44 included studies. Discussion: Stem cells used for wound repair and regeneration include endothelial progenitor stem cells and adult stem cells, in the forms of bone marrow-derived mesenchymal stem cells, adipose tissue stem cells, and inducible pluripotent stem cells. Among these sources, adipose tissue-derived mesenchymal stem cells (AD-MSCs) are ideally used due to the abundant supply of fat tissue, ease of isolation, extensive proliferative capacities ex vivo, and their ability to secrete pro-angiogenic factors. AD-MSCs have been used to enhance wound healing in peripheral arterial disease, diabetic wounds, hypertensive ulcers, bullous diabeticorum, venous ulcers, and postsurgical wounds after Mohs micrographic surgery. These cells have been delivered to the tissue topically, with scaffolds, combined with plasma-rich proteins, and through atelocollagen in various human studies. These approaches, when combined with local wound care practices, resulted in decreased pain, shorter wound healing times, and better cosmesis. Conclusions: Stem cell transplantation is a potential therapeutic approach in the wound healing process. Transplanted stem cells do not only differentiate into multiple skin cell types but also provide cytokine and growth factors required for wound healing resulting in increased angiogenesis. Thus, this approach may be regarded as an attractive option for intractable wounds that cause major clinical problems, especially chronic lower leg wounds. It can also be used after Mohs micrographic surgery for defects left to heal by secondary intention. Stem cell application may reduce the overall cost burden on the healthcare system and improve the quality of life for patients.
... In addition, bone marrow contains a variety of the growth factors that initiates and support the process of orthopedic tissues repair such as transforming growth factor-β (TGF-β), fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF), and platelet-derived growth factor (PDGF) (Sugaya et al., 2018). Bone marrow was applied in the repair of wounds (Rodriguez-Menocal et al., 2015;Chittoria et al., 2016;Gupta et al., 2017;Mohammed et al., 2023), cartilage lesions (Fortier et al., 2010;Neubauer et al., 2018), tendon rupture (Imam et al., 2017), bone defects (Pelegrine et al., 2014;U et al., 2019), and meniscal tears (Abdel-Hamid et al., 2005;Duygulu et al., 2012;Koch et al., 2019;Xiao et al., 2021). ...
Repair of meniscal tears in the avascular zone represents an obstacle for orthopedic surgeons. Several therapeutic methods have been suggested to mange these tears including meniscectomy and meniscal allografts; however, their clinical application was restricted due to their disadvantages. These limitations inspired the necessity to develop products that possess the ability to initiate healing in such avascular tears. Hence, the goal of the current study is to assess and compare the regenerative capability of bone marrow aspirate (BMA) and platelet-rich plasma (PRP) to enhance repair of avascular meniscal tears. After preparation of BMA and PRP, meniscal tear was conducted in the inner avascular zones in dogs and left untreated as control or treated with either BMA or PRP. Clinical observation of weight bearing, lameness, pain on manipulation, gait, and functional disability were investigated after 3, 6, 9, and 12 weeks of surgery. In addition, gross and histological evaluations were performed at weeks 4, 8, and 12 after surgery. Both materials demonstrated a positive improvement in clinical observations compared to the control group. Furthermore, repair of meniscal tears was stimulated in tears treated with either BMA or PRP with better gross and histological outcomes in PRP-treated group than BMA-treated group. To conclude, our findings showed that BMA and PRP possess the potential to enhance the healing process of meniscal tears in the inner avascular region with the superiority of PRP.
... The administration of MSCs to either acute or diabetic wounds in rodents accelerates wound closure. Decreased wound size has also been observed when autologous MSCs were applied to human chronic wounds 51 . Injection of allogeneic BM-MSCs around the wound increased re-epithelialization and angiogenesis and subsequently accelerated wound closure in diabetic mice compared to allogeneic neonatal dermal fibroblasts or vehicle control medium 12 . ...
Background:
Diabetes is one of the metabolic diseases characterized by hyperglycemia, with many complications. Diabetic foot ulcer (DFU) is a significant complication of diabetes. Various therapy procedures have been recently described for DFU improvement.
Methods:
Using PubMed, Scopus, Science Direct, and Google Scholar to discover the therapeutic effects of bee products, this review study was conducted in 2018-2019 by searching PubMed, Scopus, Science Direct, and Google Scholar databases.
Results:
Cell therapies with various cell candidates such as mesenchymal stem cells (MSCs) are increasingly introduced into routine medical care to manage skin wounds. The applying of these cells for tissue regeneration was initially based on the capability of MSCs to differentiate into specialized cells within the injured tissue. Paracrine signaling and differentiation mechanisms have both been contributed to improving tissue repair by MCSs. However, the role of MSCs differentiation is less due to the poor survival of these cells at the site of injury.
Conclusion:
At the same time, paracrine signaling or their secretome is the primary mechanism of MSCs that stimulate neovascularization and re-epithelialization and mobilization of inhabitant stem cells. In this review study, we discuss the role of MSCs and their secretome that can improve the use of this new approach in treating ulcers and DFU.
... Поэтому альтернативой могут стать низкозатратные и доступные для базового звена системы здравоохранения методы стимуляции раневого заживления аутологичными аспиратами красного костного мозга [5][6][7]. ...
Цель. Исследовать влияние аутологичных аспиратов красного костного мозга на раневой процесс. Материалы и методы. Выполнено рандомизированное исследование по изучению влияния аутомиелоаспиратов на раневой процесс у 72 пациентов с хирургическими инфекциями кожи и мягких тканей. Пациенты были разделены на основную и контрольную группы. В основной группе для стимуляции раневого заживления применялись аутологичные аспираты красного костного мозга. Стимуляция выполнялась при наличии признаков хронизации раневого процесса. Планиметрию производили с помощью метода А.Н. Лызикова и соавторов (2008) и программного обеспечения Adobe Photoshop (Adobe Systems, США). Для оценки клеточной картины приготовление цитологических отпечатков выполняли с применением метода М.П. Покровской и М.С. Макарова (1942). Скорость раневого заживления рассчитывали по формуле Л.Н. Поповой. Кислотность раневого отделяемого определяли с помощью стерильной универсальной индикаторной бумаги. Иммуногистохимическое окрашивание гистологического материала выполнялось с использованием моноклональных антител anti-Сollagen Type 1 и BondТМ Ki67. Для морфометрической оценки экспресии маркера в образцах применяли программное обеспечение ImageJ 1.45s. Результаты. Скорость заживления ран в основной группе составила 6 [5; 35]% в день, а в контрольной группе - 3 [3; 28]% в день и в 2 раза была достоверно выше при применении аутологичных аспиратов красного костного мозга (р<0,001). Сроки подготовки ран к пластическому закрытию в основной группе составили 5 [3; 7] дней, а в контрольной - 12 [9; 15] дней (р<0,001). Выявлено достоверное увеличение интенсивности экспрессии маркеров COL1 и Ki67 при применении аутомиелоаспиратов. Выводы. Аутологичные аспираты красного костного мозга являются мощными стимуляторами раневого заживления.
Purpose. To study the effect of autologous red bone marrow aspirates on the wound healing process. Materials and methods. A randomized study was carried out to study the effect of automyeloaspirates on the wound healing process in 72 patients with surgical infections of the skin and soft tissues. Patients were divided into main and control groups. In the main group autologous red bone marrow aspirates were used to stimulate wound healing. Stimulation was performed in case of chronic wound healing signs. For planimetry the method of A.N. Lyzikov et al. (2008) and Adobe Photoshop software (Adobe Systems, USA) was used. To estimate the cellular pattern the cytological specimens were prepared with the M.P. Pokrovskaya and M.S. Makarov method (1942). The rate of wound healing was calculated using the formula of L.N. Popova. To determine the acidity of the wound discharge sterile the universal indicator paper was used. Immunohistochemical staining of histological material was performed using anti-Collagen Type 1 and BondTM Ki67 monoclonal antibodies. For morphometric assessment of the samples markers expression the ImageJ 1.45s software was applied. Results. The rate of wound healing in the main group was 6 [5; 35]% per day, and in the control group - 3 [3; 28]% per day and 2 times was significantly higher comparing with autologous red bone marrow aspirates (p<0,001). The duration of the wounds preparation for surgical plastic in the main group was 5 [3; 7] days, and in the control - 12 [9; 15] (p<0,001). A significant increase in the COL1 and Ki67 markers expression intensity was revealed in case of automyeloaspirates the use. Conclusions. Thus, autologous bone marrow aspirates are potent stimulators of wound healing.
... Evidence indicates that stem cells derived from bone marrow (BMSCs) have the potential to treat many disorders given their plasticity and ability to differentiate into various types of cells, including bone cells (Gupta et al., 2017;Badiavas and Falanga, 2013). Inflammatory response seems to be one important step in the bone repair process once it activates bone marrow cells and initiates the cascade of bone healing. ...
This systematic review evaluated the effectiveness of bone marrow aspirate (BMA) to enhance bone repair in humans. Comprehensive survey of ramdomized clinical trials published up to June 2021 and listed in PubMed/MEDLINE, EMBASE, and Cochrane Library databases following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Two reviewers independently searched eligible studies, made a final article selection, and extracted the data of the selected studies to evaluate it qualitatively. Overall, 13 studies were included in the review. Experimental models involved Posttraumatical aseptic nonunions of long bones of the upper limb, alveolar ridges following tooth extraction, atrophic mandibular fracture, benign bone lesions, bilateral tibial lengthening, fracture of intracapsular neck femur, maxillary horizontal ridge augmentation, non-traumatic femoral head necrosis, and sinus maxillary augmentation. The analyses included radiography, tomography, biopsies, and clinical evaluations. Ten studies reported enahanced bone formation (primary outcome) with combined use or not of BMA with other biomaterials and three studies found no benefit resulting from the use of BMA to treat bony defects. Secundary outcomes related to the healing process were also evaluated and positive, such as postoperative complications and pain visual analogue score. Within the limits of the present study, it can be concluded that BMA can improve the early stages of bone healing process.
... Аспират костного мозга включает популяцию стволовых клеток, обладающих не только высокими возможностями регенерации, но и иммунорегуляторным, гемопоэтическим действием, способностью к пролиферации и дифференцировке в различные клетки. Доказано, что в результате их применения происходит стимуляция регенераторных процессов [10][11][12]. ...
The objective of the study was to develop the problem of complex treatment of surgical infections of the skin and soft tissues (SISST).The studies were carried out in 201 patients with SISST who were treated at the Department of Purulent Surgery of the Hospital Surgery Clinic of the EE “Vitebsk State Medical University” in 2017–2020. As a result, it was developed: a protocol for a rational use of antibiotics in the patients with SISST, an effective regimen for use of antiseptic drugs, a method for treating purulent wounds with autologous bone marrow aspirates.For 13 years, there have been significant changes in the etiological structure of gram-negative problematic pathogens in patients with purulent wounds. The share of K.pneumoniae increased approximately 8 times (by 12.25 %; p < 0.05), and A.baumannii ‒ 9 times (by 14.69 %; p < 0.05). The share of MRSA remained virtually unchanged. The resistance of problem microorganisms to almost all antibacterial drugs significantly increased. For MRSA-induced SISST, glycopeptides (vancomycin) should be recommended as a drug of choice, and oxazolidinones (linezolid) and glycylcyclines (tigecycline) should be recommended as a reserve; K. pneumoniae ‒ colistat and tigecycline; P. aeruginosа ‒ carbapenems (doripenem) and colistat; A. baumannii ‒ penicillins or cephalosporins with sulbactam (ampicillin + sulbactam) and colistat.It was found that septomyrin and 0.02 % chlorhexidine bigluconate have the greatest activity against the leading representatives of the microflora of purulent wounds. With a combined use of septomirin and chlorhexidine, the bacterial contamination of wounds decreased below the critical level already on the 2nd day after surgical treatment (p < 0.01).To stimulate wound healing, sternocentesis is performed and automyeloaspirate is taken. The curettage of the wound and the aspirate introduction into the wound edges and the application to the wound surface are performed. It has been established that, along with the pelvic bones, the sternum can be an alternative source of red bone marrow. The myeloaspirate volume obtained by sternal puncture varied from 10 to 140 ml. The developed method allows us to reliably reduce the duration of the 2 phase of the wound process by 7 days (р < 0.01).
... Пациентка 59 лет, посту- Полученные нами данные подтверждают результаты более ранних исследований, которые показали, что аутологичные аспираты костного мозга сами по себе и в комбинации со стволовыми клетками, культурами клеток обладают мощным регенераторным потенциалом и благоприятно влияют на раневое заживление у пациентов с проблемными ранами. Кроме того, наша работа продемонстрировала, что наряду с традиционным использованием тазовых костей для забора костного мозга при лечении ран альтернативным источником аутомиелоаспирата может быть грудина [10,11]. ...
Background: The problem of treating chronic wounds remains topical.Aim: To develop a method for the treatment of chronic wounds, which is based on the use of autoaspirates of the red bone marrow. Material and methods: The sternum was punctured by the needle of I.A. Kassirsky and red bone marrow was collected. The wound surface was treated with a Folkman spoon. An automyeloaspirate was introduced into the edges of the wound and applied to the surface of the wound.The 47 patients with chronic wounds were examined. The main group consisted of 24 patients. The area of the wounds is 87.75+11.51 cm2.The control group consisted of 23 patients. The area of the wounds is 88.52+13.71 cm2.Results: The duration of the phase of formation and maturation of granulation tissue in the main group was 5 (4.75; 7.0) days, and in the control group it was 12 (9.0; 16.0) (p <0.05).Conclusions: The developed method enables to significantly reduce the duration of phase 2 of the wound healing process by 7 days.
... Bone marrow MSCs have been known to differentiate into a wide variety of mesenchymal cell types, including bone, cartilage and fat cells [9-11] and even into cells beyond its originating phenotype, such as cardiomyocytes and neurons [12,13]. In applications to the skin, bone marrow aspirate, bone marrow mononuclear cells, and a combination of cells and biomaterial have been used [14][15][16][17]. In a study utilizing autologous bone marrow aspirate [14], 75 patients with chronic wounds were enrolled. ...
... In applications to the skin, bone marrow aspirate, bone marrow mononuclear cells, and a combination of cells and biomaterial have been used [14][15][16][17]. In a study utilizing autologous bone marrow aspirate [14], 75 patients with chronic wounds were enrolled. Inclusion criteria included wounds that did not respond to traditional treatment for at least 6 weeks, and sized 100 cm 2 or less. ...
