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Sun Y, Zhu M, Qiu L. Efficacy of mesenchymal stem cells and platelet-rich plasma therapies on wound healing: A Systematic Review and meta-analysis. Regen Ther 2025; 30:75-91. [PMID: 40491558 PMCID: PMC12148411 DOI: 10.1016/j.reth.2025.04.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2025] [Revised: 04/02/2025] [Accepted: 04/17/2025] [Indexed: 06/11/2025] Open
Abstract
Background Wound healing is a complex physiological process essential for maintaining tissue integrity and function. This meta-analysis aims to evaluate the efficacy of mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP), and their combination in enhancing wound healing. Methods We conducted a systematic search of PubMed, Web of Science, and Scopus databases for studies published from 2010 to 2024. The inclusion criteria were randomized controlled trials (RCTs) and controlled clinical trials involving human subjects treated with MSCs, PRP, or both. The primary outcomes assessed were wound closure rates and mean healing times, while secondary outcomes included wound size reduction, pain management, infection rates, recurrence, adverse events, and cost-effectiveness. Data were pooled using STATA software version 17.0, with standardized mean differences (SMDs) and risk differences (RDs) calculated. Results A total of 34 studies involving 2458 patients were included. PRP and MSCs significantly reduced wound healing time (PRP: SMD = -1.08, 95 % CI: 1.75 to -0.42, p < 0.001; MSCs: SMD = -1.7195 %, CI: 2.44 to -0.99, p < 0.001). MSCs positively impacted new vessel development (overall SMD = 0.55, 95 % CI: 0.39 to 0.71, p < 0.001). PRP-treated groups had higher ulcer healing rates (72.4 % vs 52.5 %, RD = 0.21, 95 % CI: 0.16 to 0.26, p < 0.001). Infection rates showed no statistically significant difference between PRP and control groups (DR = -0.11, 95 % CI: 0.34 to 0.12, p > 0.05), while rest pain scores were significantly lower in PRP-treated patients (SMD = -4.69, 95 % CI: 0.87 to -0.62, p = 0.02). PRP-treated ulcers had lower recurrence rates (RD = -0.14, 95 % CI: 0.75 to 0.97, p = 0.01). Conclusions The findings from this meta-analysis underscore the promising potential of PRP and MSCs as effective therapeutic strategies for wound healing when used individually.
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Affiliation(s)
- Yunqing Sun
- Department of Pediatrics, Shandong Provincial Third Hospital, Shandong University, No.11 Wuyingshan Middle Road, Tianqiao District, Jinan, Shandong, 250031, China
| | - Ming Zhu
- Department of Pediatrics, Shandong Provincial Third Hospital, Shandong University, No.11 Wuyingshan Middle Road, Tianqiao District, Jinan, Shandong, 250031, China
| | - Lianmei Qiu
- Taian Central Blood Station, No. 9, Yingchun Road, Taishan District, Tai'an City, Shandong, 271000, China
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Riza SM, Porosnicu AL, Sinescu RD. A Comprehensive Literature Review on the Therapeutic Potential of Platelet-Rich Plasma for Diabetic Foot Management: Insights from a Case of a Neglected Deep Plantar Abscess. Healthcare (Basel) 2025; 13:1130. [PMID: 40427966 PMCID: PMC12110965 DOI: 10.3390/healthcare13101130] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2025] [Revised: 04/22/2025] [Accepted: 05/08/2025] [Indexed: 05/29/2025] Open
Abstract
Background: Diabetic foot ulcers (DFUs) remain a major complication of diabetes, characterized by impaired wound healing, high infection risk, and an increased likelihood of limb amputation. Platelet-rich plasma (PRP) has emerged as a promising adjunctive therapy due to its regenerative properties, promoting angiogenesis, modulating inflammation, and accelerating tissue repair. Methods: This literature review explores the current evidence regarding the use of PRP in the management of DFUs. It was conducted using the PubMed database to evaluate the efficacy of PRP in DFUs. The search was restricted to studies published in the last 10 years, including randomized controlled trials, meta-analyses, and systematic reviews. The inclusion criteria focused on studies assessing PRP as a standalone treatment or in combination with other wound care strategies, evaluating key clinical outcomes such as wound healing rates, infection control, tissue regeneration, and amputation prevention. Results: A total of 35 studies met the inclusion criteria, including 11 meta-analyses, 15 review articles, and 9 clinical trials. PRP demonstrated potential benefits in accelerating wound healing, reducing inflammation, and promoting granulation tissue formation. Additionally, PRP combined with negative-pressure wound therapy (NPWT) showed superior outcomes in reducing amputation rates. However, findings varied based on patient characteristics, PRP preparation techniques, and treatment protocols. Conclusions: PRP represents a valuable adjunct in DFU management, contributing to improved healing outcomes and reduced complications. However, the lack of standardized protocols and variability in clinical results highlight the need for further large-scale, multicenter studies to establish its definitive role in diabetic wound care.
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Affiliation(s)
- Stefania-Mihaela Riza
- Department of Plastic Surgery and Reconstructive Microsurgery, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; (S.-M.R.); (R.D.S.)
- Department of Plastic Surgery and Reconstructive Microsurgery, Elias Emergency University Hospital, 011461 Bucharest, Romania
| | - Andrei-Ludovic Porosnicu
- Department of Plastic Surgery and Reconstructive Microsurgery, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; (S.-M.R.); (R.D.S.)
- Department of Plastic Surgery and Reconstructive Microsurgery, Elias Emergency University Hospital, 011461 Bucharest, Romania
| | - Ruxandra Diana Sinescu
- Department of Plastic Surgery and Reconstructive Microsurgery, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; (S.-M.R.); (R.D.S.)
- Department of Plastic Surgery and Reconstructive Microsurgery, Elias Emergency University Hospital, 011461 Bucharest, Romania
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Zhang Z, Liu P, Xue X, Zhang Z, Wang L, Jiang Y, Zhang C, Zhou H, Lv S, Shen W, Yang S, Wang F. The role of platelet-rich plasma in biomedicine: A comprehensive overview. iScience 2025; 28:111705. [PMID: 39898035 PMCID: PMC11787504 DOI: 10.1016/j.isci.2024.111705] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2025] Open
Abstract
Biomedicine has seen significant advancements in the 21st century, with platelet-rich plasma (PRP) playing a crucial role in clinical practice. This blood derivative, enriched with platelet components, has shown great potential for promoting tissue repair and regeneration. Its wide range of applications and the presence of anti-inflammatory and growth-promoting factors make it a valuable tool in the field of biomedicine. The exploration of PRP in clinical settings has been gaining momentum. Despite its cost-effectiveness, safety, and therapeutic efficacy, the widespread clinical adoption of PRP has been hindered by the absence of consistent preparation standards and standardized treatment protocols. This article provides a comprehensive analysis of the clinical uses, physiological roles, molecular mechanisms, and preparation techniques of PRP in biomedicine. The aim is to offer a thorough understanding of the potential applications and benefits of PRP in medical practice.
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Affiliation(s)
- Zhixin Zhang
- Senior Department of Otolaryngology Head and Neck Surgery, the Sixth Medical Center of Chinese PLA General Hospital, Chinese PLA Medical School, Beijing 100853, China
- State Key Laboratory of Hearing and Balance Science, Beijing 100853, China
- National Clinical Research Center for Otolaryngologic Diseases, Beijing 100853, China
- Key Laboratory of Hearing Science, Ministry of Education, Beijing 100853, China
- Beijing Key Laboratory of Hearing Impairment Prevention and Treatment, Beijing 100853, China
- Graduate School of Medicine, Chinese PLA General Hospital, Chinese PLA Medical School, Beijing 100853, China
| | - Peng Liu
- Senior Department of Otolaryngology Head and Neck Surgery, the Sixth Medical Center of Chinese PLA General Hospital, Chinese PLA Medical School, Beijing 100853, China
- State Key Laboratory of Hearing and Balance Science, Beijing 100853, China
- National Clinical Research Center for Otolaryngologic Diseases, Beijing 100853, China
- Key Laboratory of Hearing Science, Ministry of Education, Beijing 100853, China
- Beijing Key Laboratory of Hearing Impairment Prevention and Treatment, Beijing 100853, China
- Graduate School of Medicine, Chinese PLA General Hospital, Chinese PLA Medical School, Beijing 100853, China
| | - Xinmiao Xue
- Senior Department of Otolaryngology Head and Neck Surgery, the Sixth Medical Center of Chinese PLA General Hospital, Chinese PLA Medical School, Beijing 100853, China
- State Key Laboratory of Hearing and Balance Science, Beijing 100853, China
- National Clinical Research Center for Otolaryngologic Diseases, Beijing 100853, China
- Key Laboratory of Hearing Science, Ministry of Education, Beijing 100853, China
- Beijing Key Laboratory of Hearing Impairment Prevention and Treatment, Beijing 100853, China
- Graduate School of Medicine, Chinese PLA General Hospital, Chinese PLA Medical School, Beijing 100853, China
| | - Zhiyu Zhang
- School of Physics and Optoelectronic Engineering Xidian University, Xi’an 710071, China
| | - Li Wang
- Senior Department of Otolaryngology Head and Neck Surgery, the Sixth Medical Center of Chinese PLA General Hospital, Chinese PLA Medical School, Beijing 100853, China
- State Key Laboratory of Hearing and Balance Science, Beijing 100853, China
- National Clinical Research Center for Otolaryngologic Diseases, Beijing 100853, China
- Key Laboratory of Hearing Science, Ministry of Education, Beijing 100853, China
- Beijing Key Laboratory of Hearing Impairment Prevention and Treatment, Beijing 100853, China
- Graduate School of Medicine, Chinese PLA General Hospital, Chinese PLA Medical School, Beijing 100853, China
| | - Yvke Jiang
- Senior Department of Otolaryngology Head and Neck Surgery, the Sixth Medical Center of Chinese PLA General Hospital, Chinese PLA Medical School, Beijing 100853, China
- State Key Laboratory of Hearing and Balance Science, Beijing 100853, China
- National Clinical Research Center for Otolaryngologic Diseases, Beijing 100853, China
- Key Laboratory of Hearing Science, Ministry of Education, Beijing 100853, China
- Beijing Key Laboratory of Hearing Impairment Prevention and Treatment, Beijing 100853, China
- Graduate School of Medicine, Chinese PLA General Hospital, Chinese PLA Medical School, Beijing 100853, China
| | - Chi Zhang
- Senior Department of Otolaryngology Head and Neck Surgery, the Sixth Medical Center of Chinese PLA General Hospital, Chinese PLA Medical School, Beijing 100853, China
- State Key Laboratory of Hearing and Balance Science, Beijing 100853, China
- National Clinical Research Center for Otolaryngologic Diseases, Beijing 100853, China
- Key Laboratory of Hearing Science, Ministry of Education, Beijing 100853, China
- Beijing Key Laboratory of Hearing Impairment Prevention and Treatment, Beijing 100853, China
- Graduate School of Medicine, Chinese PLA General Hospital, Chinese PLA Medical School, Beijing 100853, China
| | - Hanwen Zhou
- Senior Department of Otolaryngology Head and Neck Surgery, the Sixth Medical Center of Chinese PLA General Hospital, Chinese PLA Medical School, Beijing 100853, China
- State Key Laboratory of Hearing and Balance Science, Beijing 100853, China
- National Clinical Research Center for Otolaryngologic Diseases, Beijing 100853, China
- Key Laboratory of Hearing Science, Ministry of Education, Beijing 100853, China
- Beijing Key Laboratory of Hearing Impairment Prevention and Treatment, Beijing 100853, China
| | - Shuhan Lv
- Senior Department of Otolaryngology Head and Neck Surgery, the Sixth Medical Center of Chinese PLA General Hospital, Chinese PLA Medical School, Beijing 100853, China
- State Key Laboratory of Hearing and Balance Science, Beijing 100853, China
- National Clinical Research Center for Otolaryngologic Diseases, Beijing 100853, China
- Key Laboratory of Hearing Science, Ministry of Education, Beijing 100853, China
- Beijing Key Laboratory of Hearing Impairment Prevention and Treatment, Beijing 100853, China
| | - Weidong Shen
- Senior Department of Otolaryngology Head and Neck Surgery, the Sixth Medical Center of Chinese PLA General Hospital, Chinese PLA Medical School, Beijing 100853, China
- State Key Laboratory of Hearing and Balance Science, Beijing 100853, China
- National Clinical Research Center for Otolaryngologic Diseases, Beijing 100853, China
- Key Laboratory of Hearing Science, Ministry of Education, Beijing 100853, China
- Beijing Key Laboratory of Hearing Impairment Prevention and Treatment, Beijing 100853, China
- Graduate School of Medicine, Chinese PLA General Hospital, Chinese PLA Medical School, Beijing 100853, China
| | - Shiming Yang
- Senior Department of Otolaryngology Head and Neck Surgery, the Sixth Medical Center of Chinese PLA General Hospital, Chinese PLA Medical School, Beijing 100853, China
- State Key Laboratory of Hearing and Balance Science, Beijing 100853, China
- National Clinical Research Center for Otolaryngologic Diseases, Beijing 100853, China
- Key Laboratory of Hearing Science, Ministry of Education, Beijing 100853, China
- Beijing Key Laboratory of Hearing Impairment Prevention and Treatment, Beijing 100853, China
- Graduate School of Medicine, Chinese PLA General Hospital, Chinese PLA Medical School, Beijing 100853, China
| | - Fangyuan Wang
- Senior Department of Otolaryngology Head and Neck Surgery, the Sixth Medical Center of Chinese PLA General Hospital, Chinese PLA Medical School, Beijing 100853, China
- State Key Laboratory of Hearing and Balance Science, Beijing 100853, China
- National Clinical Research Center for Otolaryngologic Diseases, Beijing 100853, China
- Key Laboratory of Hearing Science, Ministry of Education, Beijing 100853, China
- Beijing Key Laboratory of Hearing Impairment Prevention and Treatment, Beijing 100853, China
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Perussolo J, Calciolari E, Dereka X, Donos N. Platelet-rich plasma and plasma rich in growth factors in extra-oral wound care. Periodontol 2000 2025; 97:320-341. [PMID: 39056422 PMCID: PMC11808476 DOI: 10.1111/prd.12572] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2023] [Revised: 02/23/2024] [Accepted: 04/15/2024] [Indexed: 07/28/2024]
Abstract
This narrative review evaluates the existing literature on the clinical efficacy and safety of platelet-rich plasma (PRP) and plasma rich in growth factors (PRGFs) in extra-oral wound care, considering their potential benefits and drawbacks. The review specifically focuses on the impact of these treatments on patients' quality of life, pain management, treatment costs, recurrence rates, and potential complications. Given the extensive literature and diverse range of extra-oral wound types in which these autologous platelet concentrates have been applied, this narrative review focuses on the most frequently described wound types, including diabetic foot ulcers, venous leg ulcers, pressure ulcers, surgical wounds, and burns. The use of PRP has been reported in various medical specialties, with a low risk of adverse events. While there is a growing interest in the use of PRGF with promising results, the available literature on this topic is still limited. Only a few studies evaluated patients' perception of the treatment and the relationship between treatment costs and clinical outcomes. Data on recurrence rates and complications also vary across studies. In conclusion, PRP and PRGF show promise as alternatives or as adjunctive therapies to conventional treatments for various extra-oral wounds and ulcers, leading to reduced wound size and accelerated healing time but should be considered on a case-by-case basis, taking into account the type and severity of the wound.
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Affiliation(s)
- Jeniffer Perussolo
- Centre for Oral Clinical Research, Institute of Dentistry, Faculty of Medicine and DentistryQueen Mary University of LondonLondonUK
| | - Elena Calciolari
- Centre for Oral Clinical Research, Institute of Dentistry, Faculty of Medicine and DentistryQueen Mary University of LondonLondonUK
- Department of Medicine and Surgery, Dental SchoolUniversity of ParmaParmaItaly
| | - Xanthippi Dereka
- Department of Periodontology, School of Dentistry, Dental SchoolNational and Kapodistrian University of AthensAthensGreece
| | - Nikolaos Donos
- Centre for Oral Clinical Research, Institute of Dentistry, Faculty of Medicine and DentistryQueen Mary University of LondonLondonUK
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Tong L, Tang L, Tang B, Zhang J. Impacts of stem cells from different sources on wound healing rate in diabetic foot ulcers: a systematic review and meta-analysis. Front Genet 2025; 15:1541992. [PMID: 39935694 PMCID: PMC11811113 DOI: 10.3389/fgene.2024.1541992] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2024] [Accepted: 12/31/2024] [Indexed: 02/13/2025] Open
Abstract
Background Diabetic foot ulcers (DFU) are a significant complication of diabetes, with huge implications on patient morbidity and healthcare costs. The objective of this meta-analysis was to evaluate the impacts of stem cells from different sources on wound healing rate in DFU patients. Methods We systematically retrieved records via key databases PubMed, Cochrane Library, Web of Science, Embase, China National Knowledge Infrastructure (CNKI) and Wanfang from the inception to October 2024. The Stata 16.0 (Stata Corp, TX) software was used to perform the meta-analysis. Risk of bias in all included studies was evaluated by Cochrane Risk of Bias version 2. Results A total of 24 studies involving 1,321 patients were included. There was an increased likelihood of wound healing with peripheral blood-derived stem cells, the most effective cells (odds ratios (OR) = 7.31, 95% CI: 2.90-18.47), followed by adipose-derived stem cells (OR = 5.23, 95% CI: 2.76-9.90), umbilical cord-derived stem cells (OR = 4.94, 95% CI: 0.61-40.03), bone-derived stem cells (OR = 4.36, 95% CI: 2.43-7.85) and other sources stem cells (OR = 3.16, 95% CI: 1.83-5.45). Nevertheless, only umbilical cord-derived stem cells showed statistical significance (p < 0.05). The heterogeneity ranged from non-existent in the adipose and peripheral blood groups (I2 = 0.00%) to moderate in the bone groups (I2 = 26.31%) and other groups (I2 = 30.62%), and substantial in the umbilical cord groups (I2 = 88.37%). Asymmetrical funnel plots pointed to publication bias, but the trim-and-fill method to correct for this brought the effect estimates even lower: based on the pooled OR, corrected OR was 3.40 (95% CI 2.39-4.84). Stem cell therapy was also associated with improvements in several secondary outcomes, suggesting its potential to influence the progression of DFU. Conclusion Our study suggested that stem cells from different sources showed potential in promoting wound healing in DFU, although with some variation in effectiveness. Despite some publication bias and moderate heterogeneity, the overall therapeutic effect remained positive. These findings indicated that stem cell therapy might influence the progression of DFU.
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Affiliation(s)
- Le Tong
- Department of Emergency Medicine, West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, Chengdu, China
- Disaster Medical Center, Sichuan University, Chengdu, China
- Nursing Key Laboratory of Sichuan Province, Chengdu, China
| | - Lin Tang
- Department of Emergency Medicine, West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, Chengdu, China
- Disaster Medical Center, Sichuan University, Chengdu, China
- Nursing Key Laboratory of Sichuan Province, Chengdu, China
| | - Bangli Tang
- Department of Dermatology, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, China
| | - Jianna Zhang
- Department of Emergency Medicine, West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, Chengdu, China
- Disaster Medical Center, Sichuan University, Chengdu, China
- Nursing Key Laboratory of Sichuan Province, Chengdu, China
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Elainein MAA, Whdan MM, Samir M, Hamam NG, Mansour M, Mohamed MAM, Snosy MM, Othman MA, Sobieh AS, Saad MG, Labna MA, Allam S. Therapeutic potential of adipose-derived stem cells for diabetic foot ulcers: a systematic review and meta-analysis. Diabetol Metab Syndr 2025; 17:9. [PMID: 39773633 PMCID: PMC11706097 DOI: 10.1186/s13098-024-01523-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2024] [Accepted: 11/12/2024] [Indexed: 01/11/2025] Open
Abstract
BACKGROUND As the global prevalence of diabetes mellitus increases, the incidence of non-healing wounds in diabetic patients is expected to rise significantly, according to the International Diabetes Federation (IDF), around 537 million adults currently suffer from diabetes mellitus worldwide and 20% to 30% of individuals with diabetes are hospitalized due to diabetic foot ulcers. Conventional treatments such as traditional dressings often fall short in ensuring satisfactory wound healing, this Meta-analysis investigates the therapeutic potential of Adipose-derived Stem Cells (ADSCs) as a promising strategy for addressing this challenge. AIMS To Assess the Therapeutic Potential of Adipose-Derived Stem Cells for Managing Diabetic Foot Ulcers compared to conventional lines of treatments. METHODS The PubMed, SCOPUS, Web of Science Core Collection, Cochrane Library, and ClinicalTrials.gov. databases were searched from January 2000 and December 2023, articles were primarily evaluated regarding their titles and abstracts, then full-text screening was assessed against the inclusion and exclusion criteria by utilizing Rayyan software. The Cochrane risk of bias (RoB 2) assessment tool was used to identify the risk of bias in our included studies. A statistical analysis was performed using Review Manager (RevMan) Version 5 software. Dichotomous data was subjected to risk ratio analysis, while continuous data underwent Mean Difference (MD) evaluation, all was reported with 95% confidence intervals, P value is considered statistically significant if less than 0.05. RESULTS Regarding the total healing state, five studies reported that more participants healed completely at the end of the follow-up period in the ADSCs group (Risk ratio = 1.56, 95% CI [1.32, 1.86], P < 0.00001), for the healing rate the overall effect estimate favors the ADSCs group (pooled effect estimate = 1.84, 95% CI [1.51, 2.89], P < 0.00001), and regarding the healing time the pooled mean difference of the studies demonstrated that the ADSCs group required fewer days to heal than the standard care group. (pooled mean difference = -19.33, 95% CI [-37.36, -1.29], P = 0.04). CONCLUSION ADSCs provide favorable healing results and safety compared to standard care for diabetic foot ulcers.
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Affiliation(s)
| | | | - Mahmoud Samir
- Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Nada G Hamam
- Faculty of Medicine, Cairo University, Cairo, Egypt
| | | | | | | | | | | | | | | | - Salma Allam
- Faculty of Medicine, Galala University, Suez, Egypt.
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Ganesan O, Orgill DP. An Overview of Recent Clinical Trials for Diabetic Foot Ulcer Therapies. J Clin Med 2024; 13:7655. [PMID: 39768578 PMCID: PMC11676782 DOI: 10.3390/jcm13247655] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2024] [Revised: 11/27/2024] [Accepted: 12/12/2024] [Indexed: 01/11/2025] Open
Abstract
Diabetic foot ulcers (DFUs) are a major complication of diabetes, leading to high mortality, reduced quality of life, neuropathy, ischemia, infection, and amputation risks. The prevalence of these ulcers is only on the rise as more people suffer from type 2 diabetes and obesity. The current wound management involves wound dressings, offloading, debridement, and infection control, but more must be done to keep up with the rising prevalence of DFUs and the strain they put on patients and the healthcare system. To find recent therapeutic advances in DFU treatment, we searched PubMed for novel therapeutics from the past 5 years. We found a diversity of promising interventions, including advanced wound dressings and topicals, physical energy-based therapies, regenerative scaffolds, and growth factor- and cell-based therapies. Recent therapies hold significant promise in healing more DFUs faster and more effectively. Providers should consider employing safe, novel therapeutics when standard dressings are not effective.
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Affiliation(s)
- Ovya Ganesan
- Department of Plastic Surgery, Brigham and Women’s Hospital, Boston, MA 02115, USA;
- Geisel School of Medicine at Dartmouth, Hanover, NH 03775, USA
| | - Dennis P. Orgill
- Department of Plastic Surgery, Brigham and Women’s Hospital, Boston, MA 02115, USA;
- Harvard Medical School, Boston, MA 02115, USA
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Ventura C, Bondioli E, de Vita R, Rigotti G, Morigi F, Scarpellini F, Di Fede F, Nanni-Costa A, Melandri D. Autologous Cryopreserved Adipose Tissue Using an Innovative Technique: An In Vitro Biological Characterization. Aesthet Surg J 2024; 45:NP16-NP24. [PMID: 39302643 DOI: 10.1093/asj/sjae192] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2024] [Revised: 08/23/2024] [Accepted: 09/18/2024] [Indexed: 09/22/2024] Open
Abstract
BACKGROUND Utilization of autologous adipose tissue transplantation in plastic and orthopedic surgery such as breast reconstruction and intra-articular injection has become an attractive surgical treatment with satisfactory clinical outcomes. Nevertheless, repeated liposuctions necessary to harvest fatty tissue, normally performed with sedation or general anesthesia, may represent a noteworthy concern. OBJECTIVES The aim of this study was to demonstrate through an in vitro characterization the validity of the surgical option of cryopreserved autologous adipose tissue harvested in a single shot for repeated graft transfer in breast reconstruction without impairment of cell viability and sterility. METHODS Adipose tissue was collected by standard liposuction from patients who needed numerous fat grafting procedures for breast reconstruction. According to an innovative and patented cryopreservation method, autologous adipose tissue was subsequently fractioned in a sterile bag system and frozen at the RER Tissue Bank of the Emilia Romagna Region. Each graft was evaluated for sterility and cell viability immediately after harvesting, and 1, 3, 6, 12, and preliminarily 18 months after cryopreservation and thawing. RESULTS In vitro results showed that after processing, middle-term and long-term cryopreservation, and subsequent thawing, autologous cryopreserved adipose tissue retained absence of bacterial contamination, high cellular viability, and unmodified histomorphological properties, thereby ensuring maintenance of the stromal vascular niche and the filling properties in different multistep surgical procedures. CONCLUSIONS In vitro study and sterility assessment showed that autologous cryopreserved adipose tissue grafting is a safe procedure, making it possible to avoid multiple liposuction surgery. No impairment of sterility, cell viability, or morphology was observed over time.
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Sharifi A, Kouhi A, Patel ZM. Utilization and efficacy of platelet-rich plasma and platelet-rich fibrin in otolaryngology: a systematic evidence-based review. Eur Arch Otorhinolaryngol 2024; 281:5091-5110. [PMID: 38914822 DOI: 10.1007/s00405-024-08763-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Accepted: 05/26/2024] [Indexed: 06/26/2024]
Abstract
PURPOSE To explore utilization and efficacy of platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) in different sub-specialties of otolaryngology. METHODS A systematic search was performed using Cochrane Central Register of Controlled Trials, PubMed, EMBASE, Medline, Clinicaltrials.gov, Scopus, and Google Scholar up to March 2024. English language randomized controlled trials with original data evaluating the use of PRP and PRF in various surgical and non-surgical procedures related to otolaryngologic sub-specialties. Dataset was limited to randomized controlled trials (RCTs) to have the best quality of evidence and possible recommendation. RESULTS Our database search resulted in 591 manuscripts. Four hundred twenty-six studies were primarily excluded after reviewing the title and abstract. The remaining 165 articles were studied completely, and 51 articles met the inclusion criteria. All the studies were RCTs and dated from 2001 to 2024. They included 19 studies related to otology, 10 studies related to rhinology, 7 studies related to facial plastic surgery, 6 studies related to head and neck surgery, 3 studies related to general otolaryngology, 3 studies related to pediatrics, 2 studies related to laryngology, and 1 study related to sleep medicine. CONCLUSION PRP and PRF are safe, easy to use, and potentially effective treatment options for multiple otolaryngology pathologies. As an autologous material, there is no risk of immune reaction, and thus has been selected as a viable treatment option by many otolaryngologists. Larger studies would be helpful to confirm efficacy and allow for optimized patient selection for this treatment option.
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Affiliation(s)
- Alireza Sharifi
- Department of Otolaryngology Head and Neck Surgery, Amir A'lam Hospital, Tehran University of Medical Sciences, Tehran, Iran
- Otorhinolaryngology Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Ali Kouhi
- Department of Otolaryngology Head and Neck Surgery, Amir A'lam Hospital, Tehran University of Medical Sciences, Tehran, Iran
- Otorhinolaryngology Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Zara M Patel
- Department of Otolaryngology - Head and Neck Surgery, Stanford University School of Medicine, 801 Welch Rd, Stanford, CA, 94304, USA.
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OuYang H, Yang J, Wan H, Huang J, Yin Y. Effects of different treatment measures on the efficacy of diabetic foot ulcers: a network meta-analysis. Front Endocrinol (Lausanne) 2024; 15:1452192. [PMID: 39377075 PMCID: PMC11456420 DOI: 10.3389/fendo.2024.1452192] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Accepted: 08/29/2024] [Indexed: 10/09/2024] Open
Abstract
Introduction Through a network meta-analysis, we compared different treatment measures for patients with diabetic foot ulcers (DFU), assessing their impact on the healing of DFU and ranking them accordingly. Methods We searched the PubMed, the China National Knowledge Infrastructure (CNKI), Embase, the WanFang and the WeiPu database. The retrieval time was from database establishment to January 2024, and retrieval entailed subject and free words. Randomized controlled trials (RCTs) with different treatment measures for DFU were included. Data extraction and evaluation were based on the PRISMA guidelines. Meta-analyses using pairwise and network methods were employed to compare and rank the effectiveness of different treatments for DFU. Results Ultimately, we included 57 RCTs involving a total of 4,826 patients with DFU. When it comes to ulcer healing rates, compared to standard of care(SOC),platelet-rich plasma(PRP), hyperbaric oxygen therapy(HBOT), topical oxygen therapy(TOT), acellular dermal matrix(ADM), and stem cells(SCs) in both direct meta-analysis(DMA) and network meta-analysis(NMA) can effectively increase the complete healing rate. For Scs+PRP, a statistically significant improvement was only observed in the NMA. Moreover, when compared to the negative pressure wound therapy(NPWT) group, the PRP+NPWT group was more effective in promoting the complete healing of ulcers. In terms of promoting the reduction of ulcer area, no statistical differences were observed among various treatment measures. When it comes to ulcer healing time, both PRP and NPWT can effectively shorten the healing time compared to SOC. Furthermore, when compared to the NPWT group, the combined treatment of PRP and ultrasonic debridement(UD) with NPWT is more effective in reducing healing time. In terms of amputation rates and adverse reactions, the PRP group effectively reduced the amputation rate and adverse reactions for patients with DFU. Additionally, compared to the NPWT group, the combined treatment of PRP and UD with NPWT reduced the incidence of adverse reactions. However, no significant differences were observed among other treatment measures in terms of amputation rates and adverse reactions. The ranking results showed that the efficacy of PRP+NPWT and UD+NPWT in promoting ulcer healing, reducing ulcer area, shortening healing time, decreasing amputation rates and adverse reactions is superior to that of the alone PRP group, NPWT group, and UD group. Conversely, the SOC group demonstrates the least effective performance in all aspects. Conclusion Due to the particularity of the wound of DFU, the standard of care is not effective, but the new treatment scheme has a remarkable effect in many aspects. And the treatment of DFU is not a single choice, combined with a variety of methods often achieve better efficacy, and will not bring more adverse reactions.
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Affiliation(s)
- Hong OuYang
- Geriatric Diseases Institute of Chengdu, Department of Endocrine and Metabolism, Chengdu Fifth People’s Hospital(The Second Clinical Medical College, Affiliated Fifth People’s Hospital of Chengdu University of Traditional Chinese Medicine), Chengdu, China
| | - Jing Yang
- Geriatric Diseases Institute of Chengdu, Department of Endocrine and Metabolism, Chengdu Fifth People’s Hospital(The Second Clinical Medical College, Affiliated Fifth People’s Hospital of Chengdu University of Traditional Chinese Medicine), Chengdu, China
| | - Haiyan Wan
- Geriatric Diseases Institute of Chengdu, Department of Endocrine and Metabolism, Chengdu Fifth People’s Hospital(The Second Clinical Medical College, Affiliated Fifth People’s Hospital of Chengdu University of Traditional Chinese Medicine), Chengdu, China
| | - Jiali Huang
- Geriatric Diseases Institute of Chengdu, Department of Endocrine and Metabolism, Chengdu Fifth People’s Hospital(The Second Clinical Medical College, Affiliated Fifth People’s Hospital of Chengdu University of Traditional Chinese Medicine), Chengdu, China
| | - Yifan Yin
- Department of Nephrology, Chengdu Third People’s hospital, Chengdu, China
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11
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Xiao Y, Nie M, Xu W, Zhang J, Lei S, Wu D. The efficiency of human fat products in wound healing: A systematic review and meta-analysis. Int Wound J 2024; 21:e70016. [PMID: 39216014 PMCID: PMC11365526 DOI: 10.1111/iwj.70016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2024] [Revised: 07/14/2024] [Accepted: 07/25/2024] [Indexed: 09/04/2024] Open
Abstract
Wound development and healing involve intricate genetic and molecular processes, posing significant clinical management challenges. The objective of this study was to assess commonly used fat extracts' efficacy and safety (autologous fat, stromal vascular fraction and adipose-derived stem cells) in wound healing, particularly for refractory wounds, with the goal of providing evidence in clinical use. After a systematic review, 21 randomised controlled trials were included in our study. Based on the classification of human fat products, our meta-analysis revealed that the use of human fat products could speed healing rate, shorten healing time and achieve more complete healing, with statistically significant differences in outcome indicators when compared to conventional treatments. The analysis of histological findings across various studies indicated that fat extracts can promote epithelialization, collagen deposition and vascularization, thereby facilitating tissue regeneration and reducing inflammatory reactions. There were potential benefits to reducing patient pain levels after using adipose extracts. Furthermore, we analysed and summarised adverse events indicating the safe and effective clinical use of human fat products in wound treatment. Our research findings supported the efficiency of human fat products and demonstrated a high degree of safety in the clinical practice of wound management.
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Affiliation(s)
- Yutian Xiao
- Department of Plastic and Cosmetic Surgery, Xiangya HospitalCentral South UniversityChangshaPR China
- National Clinical Research Center for Geriatric DisordersXiangya HospitalChangshaPR China
| | - Mengqi Nie
- Department of Plastic and Cosmetic Surgery, Xiangya HospitalCentral South UniversityChangshaPR China
- National Clinical Research Center for Geriatric DisordersXiangya HospitalChangshaPR China
| | - Wenqing Xu
- Department of Plastic and Cosmetic Surgery, Xiangya HospitalCentral South UniversityChangshaPR China
- National Clinical Research Center for Geriatric DisordersXiangya HospitalChangshaPR China
| | - Jinglve Zhang
- Department of Plastic and Cosmetic Surgery, Xiangya HospitalCentral South UniversityChangshaPR China
- National Clinical Research Center for Geriatric DisordersXiangya HospitalChangshaPR China
| | - Shaorong Lei
- Department of Plastic and Cosmetic Surgery, Xiangya HospitalCentral South UniversityChangshaPR China
- National Clinical Research Center for Geriatric DisordersXiangya HospitalChangshaPR China
| | - Dingyu Wu
- Department of Plastic and Cosmetic Surgery, Xiangya HospitalCentral South UniversityChangshaPR China
- National Clinical Research Center for Geriatric DisordersXiangya HospitalChangshaPR China
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Rahman E, Rao P, Abu-Farsakh HN, Thonse C, Ali I, Upton AE, Baratikkae SY, Carruthers JDA, Mosahebi A, Heidari N, Webb WR. Systematic Review of Platelet-Rich Plasma in Medical and Surgical Specialties: Quality, Evaluation, Evidence, and Enforcement. J Clin Med 2024; 13:4571. [PMID: 39124838 PMCID: PMC11313071 DOI: 10.3390/jcm13154571] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Revised: 07/25/2024] [Accepted: 07/29/2024] [Indexed: 08/12/2024] Open
Abstract
Background: Platelet-rich plasma (PRP) is widely used in various medical and surgical specialties for its regenerative properties, including aesthetics (facial rejuvenation, hair restoration, and skin tightening) and orthopedics (treatment of tendinitis and osteoarthritis). However, the inconsistent literature on PRP's efficacy and safety leads to critical knowledge gaps. This systematic review evaluates quality control measures in PRP preparation and application and explores the regulatory environment governing its clinical use. Methods: Following PRISMA guidelines, a comprehensive search was conducted across multiple databases, including PubMed, EMBASE, and Web of Science, for studies published from January 2020 to April 2024. The review included randomized controlled trials (RCTs) involving human participants undergoing PRP treatment for aesthetic or regenerative purposes. Key parameters such as the PRP preparation methods, platelet concentration, and quality control measures were analyzed. The study protocol was registered with PROSPERO (ID: CRD42024557669). Results: Out of 75 RCTs involving 5726 patients, the review identified significant variability in PRP preparation methods and application techniques, including differences in centrifugation protocols and platelet concentration levels. A new evidence-based scoring system, the William-Eqram Scoring System for PRP Quality Reporting (WESS-PQR), was proposed to address these inconsistencies. Correlation analysis revealed a strong positive correlation (r = 0.79) between proper temperature control during preparation and PRP efficacy. Initial platelet count assessment showed a moderate positive correlation (r = 0.57) with efficacy. Conclusions: Standardized PRP preparation protocols and robust regulatory frameworks are urgently needed to ensure the safety and efficacy of PRP treatments. The proposed WESS-PQR scoring system can serve as a valuable tool for clinicians and researchers, promoting consistency and reliability in PRP applications.
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Affiliation(s)
- Eqram Rahman
- Research and Innovation Hub, Innovation Aesthetics, London WC2H 9JQ, UK (W.R.W.)
| | - Parinitha Rao
- The Skin Address, Aesthetic Dermatology Practice, Bengaluru 560080, India
| | | | - Chirag Thonse
- Manipal Hospital, Millers Road, Bengaluru 560052, India
| | - Imran Ali
- Integrated Medical Centre, Crawford Street, London WIU 6BE, UK
| | - Alice E. Upton
- Research and Innovation Hub, Innovation Aesthetics, London WC2H 9JQ, UK (W.R.W.)
| | | | - Jean D. A. Carruthers
- Department of Ophthalmology, University of British Columbia, Vancouver, BC V6T 1Z4, Canada
| | - Ash Mosahebi
- Department of Plastic and Reconstructive Surgery, Royal Free Hospital, Hampstead NW3 2QG, UK;
| | - Nima Heidari
- Medical Supercomputation and Machine Learning, European Quantum Medical, London E10 5NP, UK
- Foot, Ankle and Limb Reconstruction, Orthopaedic Surgeon, London W1G 7ET, UK
- Pharmacy, Science and Technology, George Emil Palade University of Medicine, 540142 Targu Mures, Romania
| | - William Richard Webb
- Research and Innovation Hub, Innovation Aesthetics, London WC2H 9JQ, UK (W.R.W.)
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Tseng SL, Kang L, Li ZJ, Wang LQ, Li ZM, Li TH, Xiang JY, Huang JZ, Yu NZ, Long X. Adipose-derived stem cells in diabetic foot care: Bridging clinical trials and practical application. World J Diabetes 2024; 15:1162-1177. [PMID: 38983804 PMCID: PMC11229965 DOI: 10.4239/wjd.v15.i6.1162] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2023] [Revised: 03/03/2024] [Accepted: 04/19/2024] [Indexed: 06/11/2024] Open
Abstract
Diabetic foot ulcers (DFUs) pose a critical medical challenge, significantly im-pairing the quality of life of patients. Adipose-derived stem cells (ADSCs) have been identified as a promising therapeutic approach for improving wound healing in DFUs. Despite extensive exploration of the mechanical aspects of ADSC therapy against DFU, its clinical applications remain elusive. In this review, we aimed to bridge this gap by evaluating the use and advancements of ADSCs in the clinical management of DFUs. The review begins with a discussion of the classification and clinical management of diabetic foot conditions. It then discusses the current landscape of clinical trials, focusing on their geographic distribution, reported efficacy, safety profiles, treatment timing, administration techniques, and dosing considerations. Finally, the review discusses the preclinical strategies to enhance ADSC efficacy. This review shows that many trials exhibit biases in study design, unclear inclusion criteria, and intervention protocols. In conclusion, this review underscores the potential of ADSCs in DFU treatment and emphasizes the critical need for further research and refinement of therapeutic approaches, with a focus on improving the quality of future clinical trials to enhance treatment outcomes and advance the field of diabetic wound care.
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Affiliation(s)
- Song-Lu Tseng
- Department of Plastic and Reconstructive Surgery, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
- Department of Plastic and Reconstructive Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Lin Kang
- Biomedical Engineering Facility, Institute of Clinical Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences Beijing, Beijing 100021, China
| | - Zhu-Jun Li
- Department of Plastic and Reconstructive Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Li-Quan Wang
- Department of Plastic and Reconstructive Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Zi-Ming Li
- Department of Plastic and Reconstructive Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Tian-Hao Li
- Department of Plastic and Reconstructive Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Jie-Yu Xiang
- Department of Plastic and Reconstructive Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Jiu-Zuo Huang
- Department of Plastic and Reconstructive Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Nan-Ze Yu
- Department of Plastic and Reconstructive Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Xiao Long
- Department of Plastic and Reconstructive Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
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14
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Prakash O, Ali SS, Yaseen M, Sudhy IK, Venkateshwar PK, Kishore YR. Utility of Fat Grafting in Chronic Wounds. Indian J Plast Surg 2024; 57:201-207. [PMID: 39139688 PMCID: PMC11319018 DOI: 10.1055/s-0044-1787174] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/15/2024] Open
Abstract
Introduction The history of wounds dates back to the evolution of mankind. Throughout the centuries, management modalities of wounds have undergone drastic changes. With the advent of technology, we have multiple options for wound care, but none of them can be called the gold standard of wound care. Autologous fat grafting (AFG) is one of the most routinely performed procedures in aesthetic surgery. Fat grafting has shown beneficial effects in the healing of wounds. The regenerative potential of autologous fat is contributed by the adipose-derived stem cells present within the stromal vascular fraction, which are capable of differentiating into multiple cell types. This study aims to analyze the usefulness of AFG in cutaneous wound healing. Materials and Methods This prospective, study was conducted in our institute between April 2021 and May 2023. Eighteen patients with nonhealing wounds were included in the study. For assessing wound healing all the patients were first managed with conventional dressing for 2 weeks before surgery. After routine preoperative workup, the procedure was performed under local anesthesia in most cases. Fat was harvested from the lower abdomen and after emulsification, was injected into the edge and floor of the ulcer. The dressing was changed on the third postoperative day and the outcome was assessed. Results Eighteen patients (M:F ratio 8:1), with a mean age of 35.61 ± 12. 64 years (range 10-65 years), were included in this study. The most common etiology was trauma (44%), others being postop infection (17%), veno-lymphatic ulcer (17%), burns (11%), insect bite (5%), and trophic ulcer (5%). Majority of the wounds (95%) healed without the need for any extra intervention. The mean period taken for complete wound healing was 5.05 weeks. Conclusion Complete wound healing was achieved in majority of the patients without any complications. We recommend the usage of AFG for nonhealing wounds, as the procedure is relatively simple and can be performed after basic training. Larger-scale randomized controlled trials should be conducted to prove their efficacy in the management of complicated wounds.
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Affiliation(s)
- Om Prakash
- Department of Plastic Surgery, Jawaharlal Nehru Medical College and Hospital, Aligarh Muslim University, Aligarh, Uttar Pradesh, India
| | - Sheikh Sarfraz Ali
- Department of Plastic Surgery, Jawaharlal Nehru Medical College and Hospital, Aligarh Muslim University, Aligarh, Uttar Pradesh, India
| | - Mohd Yaseen
- Department of Plastic Surgery, Jawaharlal Nehru Medical College and Hospital, Aligarh Muslim University, Aligarh, Uttar Pradesh, India
| | - Indrajith K. Sudhy
- Department of Plastic Surgery, Jawaharlal Nehru Medical College and Hospital, Aligarh Muslim University, Aligarh, Uttar Pradesh, India
| | - Pavan K. Venkateshwar
- Department of Plastic Surgery, Jawaharlal Nehru Medical College and Hospital, Aligarh Muslim University, Aligarh, Uttar Pradesh, India
| | - Y. Ranga Kishore
- Department of Plastic Surgery, Jawaharlal Nehru Medical College and Hospital, Aligarh Muslim University, Aligarh, Uttar Pradesh, India
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15
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Chen P, Vilorio NC, Dhatariya K, Jeffcoate W, Lobmann R, McIntosh C, Piaggesi A, Steinberg J, Vas P, Viswanathan V, Wu S, Game F. Effectiveness of interventions to enhance healing of chronic foot ulcers in diabetes: A systematic review. Diabetes Metab Res Rev 2024; 40:e3786. [PMID: 38507616 DOI: 10.1002/dmrr.3786] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2024] [Accepted: 02/27/2024] [Indexed: 03/22/2024]
Abstract
BACKGROUND It is critical that interventions used to enhance the healing of chronic foot ulcers in diabetes are backed by high-quality evidence and cost-effectiveness. In previous years, the systematic review accompanying guidelines published by the International Working Group of the Diabetic Foot performed 4-yearly updates of previous searches, including trials of prospective, cross-sectional and case-control design. AIMS Due to a need to re-evaluate older studies against newer standards of reporting and assessment of risk of bias, we performed a whole new search from conception, but limiting studies to randomised control trials only. MATERIALS AND METHODS For this systematic review, we searched PubMed, Scopus and Web of Science databases for published studies on randomised control trials of interventions to enhance healing of diabetes-related foot ulcers. We only included trials comparing interventions to standard of care. Two independent reviewers selected articles for inclusion and assessed relevant outcomes as well as methodological quality. RESULTS The literature search identified 22,250 articles, of which 262 were selected for full text review across 10 categories of interventions. Overall, the certainty of evidence for a majority of wound healing interventions was low or very low, with moderate evidence existing for two interventions (sucrose-octasulfate and leucocyte, platelet and fibrin patch) and low quality evidence for a further four (hyperbaric oxygen, topical oxygen, placental derived products and negative pressure wound therapy). The majority of interventions had insufficient evidence. CONCLUSION Overall, the evidence to support any other intervention to enhance wound healing is lacking and further high-quality randomised control trials are encouraged.
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Affiliation(s)
- Pam Chen
- Joondalup Health Campus, Ramsay Healthcare Australia, Joondalup, Western Australia, Australia
- Faculty of Health, University of Tasmania, Hobart, Tasmania, Australia
| | - Nalini Campillo Vilorio
- Department of Diabetology, Diabetic Foot Unit, Plaza de la Salud General Hospital, Santo Domingo, Dominican Republic
| | - Ketan Dhatariya
- Elsie Bertram Diabetes Centre, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, UK
- Norwich Medical School, University of East Anglia, Norwich, UK
| | | | - Ralf Lobmann
- Clinic for Endocrinology, Diabetology and Geriatrics, Klinikum Stuttgart, Stuttgart, Germany
| | | | - Alberto Piaggesi
- Diabetic Foot Section, Department of Medicine, University of Pisa, Pisa, Italy
| | - John Steinberg
- Georgetown University School of Medicine, Washington, District of Columbia, USA
| | - Prash Vas
- King's College Hospital NHS Foundation Trust, London, UK
| | - Vijay Viswanathan
- MV Hospital for Diabetes and Prof M Viswanathan Diabetes Research Center, Chennai, India
| | - Stephanie Wu
- Dr. William M. Scholl College of Podiatric Medicine at Rosalind Franklin University of Medicine and Science, North Chicago, Illinois, USA
| | - Fran Game
- University Hospitals of Derby and Burton NHS Foundation Trust, Derby, UK
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16
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Chen P, Vilorio NC, Dhatariya K, Jeffcoate W, Lobmann R, McIntosh C, Piaggesi A, Steinberg J, Vas P, Viswanathan V, Wu S, Game F. Guidelines on interventions to enhance healing of foot ulcers in people with diabetes (IWGDF 2023 update). Diabetes Metab Res Rev 2024; 40:e3644. [PMID: 37232034 DOI: 10.1002/dmrr.3644] [Citation(s) in RCA: 69] [Impact Index Per Article: 69.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2023] [Accepted: 04/17/2023] [Indexed: 05/27/2023]
Abstract
AIMS Principles of wound management, including debridement, wound bed preparation, and newer technologies involving alternation of wound physiology to facilitate healing, are of utmost importance when attempting to heal a chronic diabetes-related foot ulcer. However, the rising incidence and costs of diabetes-related foot ulcer management necessitate that interventions to enhance wound healing of chronic diabetes-related foot ulcers are supported by high-quality evidence of efficacy and cost effectiveness when used in conjunction with established aspects of gold-standard multidisciplinary care. This is the 2023 International Working Group on the Diabetic Foot (IWGDF) evidence-based guideline on wound healing interventions to promote healing of foot ulcers in persons with diabetes. It serves as an update of the 2019 IWGDF guideline. MATERIALS AND METHODS We followed the GRADE approach by devising clinical questions and important outcomes in the Patient-Intervention-Control-Outcome (PICO) format, undertaking a systematic review, developing summary of judgements tables, and writing recommendations and rationale for each question. Each recommendation is based on the evidence found in the systematic review and, using the GRADE summary of judgement items, including desirable and undesirable effects, certainty of evidence, patient values, resources required, cost effectiveness, equity, feasibility, and acceptability, we formulated recommendations that were agreed by the authors and reviewed by independent experts and stakeholders. RESULTS From the results of the systematic review and evidence-to-decision making process, we were able to make 29 separate recommendations. We made a number of conditional supportive recommendations for the use of interventions to improve healing of foot ulcers in people with diabetes. These include the use of sucrose octasulfate dressings, the use of negative pressure wound therapies for post-operative wounds, the use of placental-derived products, the use of the autologous leucocyte/platelet/fibrin patch, the use of topical oxygen therapy, and the use of hyperbaric oxygen. Although in all cases it was stressed that these should be used where best standard of care was not able to heal the wound alone and where resources were available for the interventions. CONCLUSIONS These wound healing recommendations should support improved outcomes for people with diabetes and ulcers of the foot, and we hope that widescale implementation will follow. However, although the certainty of much of the evidence on which to base the recommendations is improving, it remains poor overall. We encourage not more, but better quality trials including those with a health economic analysis, into this area.
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Affiliation(s)
- Pam Chen
- Joondalup Health Campus, Ramsay Healthcare Australia, Joondalup, Western Australia, Australia
- Faculty of Health, University of Tasmania, Hobart, Tasmania, Australia
| | - Nalini Campillo Vilorio
- Department of Diabetology, Diabetic Foot Unit, Plaza de la Salud General Hospital, Santo Domingo, Dominican Republic
| | - Ketan Dhatariya
- Elsie Bertram Diabetes Centre, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, UK
- Norwich Medical School, University of East Anglia, Norwich, UK
| | | | - Ralf Lobmann
- Clinic for Endocrinology, Diabetology and Geriatrics, Klinikum Stuttgart, Stuttgart, Germany
| | - Caroline McIntosh
- Podiatric Medicine, School of Health Sciences, University of Galway, Galway, Ireland
| | - Alberto Piaggesi
- Diabetic Foot Section, Department of Medicine, University of Pisa, Pisa, Italy
| | - John Steinberg
- Georgetown University School of Medicine, Georgetown, Washington DC, USA
| | - Prash Vas
- King's College Hospital NHS Foundation Trust, London, UK
| | - Vijay Viswanathan
- MV Hospital for Diabetes and Prof M Viswanathan Diabetes Research Center, Chennai, India
| | - Stephanie Wu
- Dr. William M. Scholl College of Podiatric Medicine at Rosalind Franklin University of Medicine and Science, North Chicago, Illinois, USA
| | - Fran Game
- University Hospitals of Derby and Burton NHS Foundation Trust, Derby, UK
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Oley MH, Oley MC, Kepel BJ, Faruk M, Wagiu AMJ, Sukarno I, Tulong MT, Sukarno V. Hyperbaric Oxygen Therapy for Diabetic Foot Ulcers Based on Wagner Grading: A Systematic Review and Meta-analysis. PLASTIC AND RECONSTRUCTIVE SURGERY-GLOBAL OPEN 2024; 12:e5692. [PMID: 38528847 PMCID: PMC10962882 DOI: 10.1097/gox.0000000000005692] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2023] [Accepted: 01/31/2024] [Indexed: 03/27/2024]
Abstract
Background Diabetic foot ulcers (DFUs) are common complications of uncontrolled diabetes mellitus that can result in infection and amputation of the lower extremities. This study compared the benefits and risks of hyperbaric oxygen therapy with those of other DFU treatments, based on the Wagner grading system. Methods Systematic searches for randomly controlled trials using hyperbaric oxygen therapy for DFUs were performed using PubMed, the Cochrane Library, and Embase. Data regarding demographics, wound healing, minor and major amputations, operative debridement, nonhealing wounds, and adverse effects were analyzed based on Wagner grades, using RevMan 5.4.1 and Microsoft Excel. Results Hyperbaric oxygen therapy was significantly superior to other treatments for wound healing rates 8 or more weeks after the final treatment (RR = 2.39; 1.87-3.05; P < 0.00001) minor/distal amputations (RR = 0.58; 0.43-0.80; P < 0.007), and major/proximal amputations (RR = 0.31; 0.18-0.52; P < 0.00001) for the 14 studies analyzed. In addition, this therapy increased the rate of complete wound healing for Wagner grades II (RR = 21.11; 3.05-146.03; P = 0.002), III (RR = 19.58; 2.82-135.94, P = 0.003), and IV (RR = 17.53; 2.45-125.44; P = 0.004); decreased the minor/distal amputation rate for grade III (RR = 0.06; 0.01-0.29; P = 0.0004) and the major/proximal amputation rate on for grade IV (RR = 0.08; 0.03-0.25; P < 0.0001); and decreased the operative debridement rate for Wagner grade II (RR = 0.09; 0.01-0.60; P = 0.01). Conclusions Moderate-quality evidence revealed that adjunctive hyperbaric oxygen therapy improved DFU wound healing for Wagner grades II, III, and IV; prevented minor and major amputations for grades III and IV, respectively; and prevented operative debridement in grade II wounds.
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Affiliation(s)
- Mendy Hatibie Oley
- From the Plastic Reconstructive and Aesthetic Surgery Division, Department of Surgery, Faculty of Medicine, Sam Ratulangi University, Manado, Indonesia
- Plastic Reconstructive and Aesthetic Surgery Division, Department of Surgery, Kandou Hospital, Manado, Indonesia
- Hyperbaric Centre Siloam Hospital, Manado, Indonesia
| | - Maximillian Christian Oley
- Hyperbaric Centre Siloam Hospital, Manado, Indonesia
- Neurosurgery Division, Department of Surgery, Faculty of Medicine, Sam Ratulangi University, Manado, Indonesia
- Neurosurgery Division, Department of Surgery, Kandou Hospital, Manado, Indonesia
| | - Billy Johnson Kepel
- Department of Chemistry, Faculty of Medicine, Sam Ratulangi University, Manado, Indonesia
| | - Muhammad Faruk
- Department of Surgery, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia
| | | | - Irawan Sukarno
- Department of Surgery, Faculty of Medicine, Sam Ratulangi University, Manado, Indonesia
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Mudgal SK, Kumar S, Gaur R, Singh H, Saikia D, Varshney S, Gupta P, Grover A, Varikasuvu SR. Effectiveness of Stem Cell Therapy for Diabetic Foot Ulcers: A Systematic Review and GRADE Compliant Bootstrapped Meta-Analysis of Randomized Clinical Trials. INT J LOW EXTR WOUND 2024:15347346241227530. [PMID: 38298002 DOI: 10.1177/15347346241227530] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2024]
Abstract
Diabetic foot (DF) represents a severe complication of diabetes mellitus, imposing substantial psychological and economic burdens on affected individuals. This investigation sought to assess the therapeutic efficacy of stem cell interventions in the management of DF complications. A comprehensive systematic search across PubMed, Embase, CINAHL, Scopus, and the Cochrane library databases was conducted to identify pertinent studies for meta-analysis. Outcome measures encompassed ulcer or wound healing rates, amputation rates, angiogenesis, ankle-brachial index (ABI), and pain-free walking distance. Dichotomous outcomes were expressed as risk differences (RDs) with 95% confidence intervals (CIs), while continuous data were articulated as standardized mean differences (SMDs) with corresponding 95% CIs. Statistical analyses were executed using RevMan 5.3 and Open Meta, with bootstrapped meta-analysis conducted through OpenMEE software. A total of 20 studies, comprising 24 arms and involving 1304 participants, were incorporated into the meta-analysis. The findings revealed that stem cell therapy exhibited superior efficacy compared to conventional interventions in terms of ulcer or wound healing rate [RD = 0.36 (0.28, 0.43)], pain-free walking distance [SMD = 1.27 (0.89, 1.65)], ABI [SMD = 0.61 (0.33, 0.88)], and new vessel development [RD = 0.48 (0.23, 0.78)], while concurrently reducing the amputation rate significantly [RD = -0.19 (-0.25, -0.12)]. Furthermore, no statistically significant difference in adverse events was observed [RD -0.07 (-0.16, 0.02)]. The Grading of Recommendations, Assessment, Development, and Evaluation assessment indicated varying levels of evidence certainty, ranging from very low to moderate, for different outcomes. Bootstrapping analysis substantiated the precision of the results. The meta-analysis underscores the significant superiority of stem cell therapy over conventional approaches in treating DF complications. Future investigations should prioritize large-scale, randomized, double-blind, placebo-controlled, multicenter trials, incorporating rigorous long-term follow-up protocols. These studies are essential for elucidating the optimal cell types and therapeutic parameters that contribute to the most effective treatment strategies for DF management.
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Affiliation(s)
- Shiv Kumar Mudgal
- All India Institute of Medical Sciences (AIIMS), Deoghar, Jharkhand, India
| | - Subodh Kumar
- All India Institute of Medical Sciences (AIIMS), Deoghar, Jharkhand, India
| | - Rakhi Gaur
- All India Institute of Medical Sciences (AIIMS), Deoghar, Jharkhand, India
| | - Harminder Singh
- All India Institute of Medical Sciences (AIIMS), Deoghar, Jharkhand, India
| | - Dibyajyoti Saikia
- All India Institute of Medical Sciences (AIIMS), Guwahati, Assam, India
| | - Saurabh Varshney
- All India Institute of Medical Sciences (AIIMS), Deoghar, Jharkhand, India
| | - Pratima Gupta
- All India Institute of Medical Sciences (AIIMS), Deoghar, Jharkhand, India
| | - Ashoo Grover
- Indian Council of Medical Research (ICMR), Head Quarters, New Delhi, India
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Peng Y, Wang J, Liu X, Zhou Y, Jia S, Xu J, Zheng C. Efficacy of Platelet-Rich Plasma in the Treatment of Diabetic Foot Ulcers: A Systematic Review and Meta-Analysis. Ann Vasc Surg 2024; 98:365-373. [PMID: 37355015 DOI: 10.1016/j.avsg.2023.05.045] [Citation(s) in RCA: 11] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2023] [Revised: 05/22/2023] [Accepted: 05/26/2023] [Indexed: 06/26/2023]
Abstract
BACKGROUND The probiological healing effect of platelet-rich plasma (PRP) during tissue repair has recently gathered much attention. This study aimed to conduct a systematic review and meta-analysis of patients with diabetic foot ulcer (DFU) receiving PRP or conventional treatment to evaluate their efficacy. METHODS PubMed, Excerpta Medica Database (EMBASE), Cochrane Library, and China National Knowledge Infrastructure (CNKI) databases were comprehensively searched by 2 independent reviewers following PRISMA guidelines for the inclusion of randomized controlled trials (RCTs) comparing PRP with conventional treatments for DFUs. The primary measurements of healing rate and healing time, the methodological quality and extracted data were assessed using Review Manager 5.3. Statistical significance was set at P < 0.05. RESULTS A total of 10 RCTs involving 550 patients were included in this study, PRP was observed to significantly improve the healing rate (risk ratio [RR] = 1.38, 95% confidence interval [CI] 1.05-1.82, P = 0.02) and shorten the healing time (mean difference [MD] = -23.23, 95% CI -45.97 to -0.49, P = 0.05) of patients with DFU when compared to the conventional treatment. CONCLUSIONS Compared to conventional treatment, PRP effectively promoted the healing of patients with DFU by evidently improving the healing rate and healing time.
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Affiliation(s)
- Yundong Peng
- School of Sports Medicine and Rehabilitation, Beijing Sport University, Beijing, China
| | - JiePing Wang
- Laboratory of Exercise Biochemistry, Institute of Sports Sciences, University of Taipei, Taipei, Taiwan
| | - Xinyao Liu
- College of Sports Medicine, Wuhan Sports University, Wuhan, China
| | - Yanqing Zhou
- College of Sports Medicine, Wuhan Sports University, Wuhan, China
| | - Shaohui Jia
- Hubei Key Laboratory of Sport Training and Monitoring, College of Sports Medicine, Wuhan Sports University, Wuhan, China
| | - Jinrong Xu
- Hospital of Central China Normal University, Wuhan, China.
| | - Cheng Zheng
- Department of Sports Medicine, Affiliated Hospital, Wuhan Sports University, Wuhan, China.
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20
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Su YN, Li J, Feng DH, Lu RR, Dong GX, Zhao DY. Efficacy and safety of autologous platelet-rich plasma for diabetic foot ulcers: a systematic review and meta-analysis. J Wound Care 2023; 32:773-786. [PMID: 38060413 DOI: 10.12968/jowc.2023.32.12.773] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2023]
Abstract
OBJECTIVE To investigate the efficacy and safety of autologous platelet-rich plasma (au-PRP) for diabetic foot ulcer (DFU) treatment. METHOD We conducted database searches (MEDLINE, EMBASE, evidence-based medicine reviews: CENTRAL, PubMed, and Web of Science) and reference mining for randomised controlled trials from inception to 23 January 2022. Results were scrutinised, data were extracted and research quality was investigated by two independent authors. Primary outcome was the proportion of complete ulcer healing. Secondary outcomes included both the mean time to complete healing and the incidence of adverse events. Statistical analyses were performed in RevMan 5.4 (Cochrane, UK). Kaplan-Meier curves for time to complete healing were pooled in R software (version 4.1.2) (R Foundation, Austria). RESULTS Of the 231 records identified, 17 studies with a total of 1303 participants (649 randomised to the au-PRP group and 654 to a standard of care (SOC) group) met the eligibility criteria and were included in our study. Compared with SOC, au-PRP appeared to promote the complete healing rate (odds ratio (OR): 2.11; 95% Confidence Interval: 1.55-2.86). Au-PRP also appeared to significantly shorten complete healing time (mean duration: -19.04 days; 95%CI: -20.46--17.61]). There was no significant difference on adverse events. Results were robust on sensitivity analyses. CONCLUSION Based on the findings of this review and meta-analysis, Au-PRP is an effective and safe adjuvant therapy for DFUs.
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Affiliation(s)
- Ya-Na Su
- Department of Health Management, The School of Smart Health and Wellness (Health Medical College), Zhejiang Dongfang Polytechnic, Wenzhou City, Zhejiang Province, PR China
| | - Jing Li
- Department of Evidence-Based Medicine and Clinical Epidemiology, West China Hospital, Sichuan University, Chengdu City, Sichuan Province, PR China
- The Chinese Cochrane Center, Chengdu City, Sichuan Province, PR China
| | - Dai-Hao Feng
- Department of Elderly Services and Management, The School of Smart Health and Wellness (Health Medical College), Zhejiang Dongfang Polytechnic, Wenzhou City, Zhejiang Province, PR China
| | - Ruo-Ruo Lu
- Department of Elderly Services and Management, The School of Smart Health and Wellness (Health Medical College), Zhejiang Dongfang Polytechnic, Wenzhou City, Zhejiang Province, PR China
| | - Guo-Xi Dong
- Department of Nursing Teaching and Research, The School of Smart Health and Wellness (Health Medical College), Zhejiang Dongfang Polytechnic, Wenzhou City, Zhejiang Province, PR China
| | - Ding-Yun Zhao
- Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou City, Zhejiang Province, PR China
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21
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Pixley JN, Cook MK, Singh R, Larrondo J, McMichael AJ. A comprehensive review of platelet-rich plasma for the treatment of dermatologic disorders. J DERMATOL TREAT 2023; 34:2142035. [PMID: 36318219 DOI: 10.1080/09546634.2022.2142035] [Citation(s) in RCA: 28] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
Platelet-rich plasma (PRP) offers anti-inflammatory and regenerative properties through angiogenesis, cell differentiation, and proliferation. Although studied in many dermatologic conditions, its efficacy is not well-understood. Our objective is to review the use and effectiveness of PRP for dermatologic conditions. A literature search was performed through PubMed and yielded 54 articles published between January 2000 and November 2021; articles written in English were reviewed. Intradermal injections were associated with increased hair density in androgenic alopecia. Successful treatment of inflammatory nail diseases with PRP has been reported. Improvement in psoriasis was described, but only two studies were available. PRP was associated with higher patient self-assessment scores of photoaging and fine lines. Treatment with PRP in melasma has been associated with improved subjective satisfaction, but not with objective measures of disease improvement. PRP can serve as a safe and potentially effective adjunct for hair loss, vitiligo, nonhealing wounds, photoaging, and acne scars. An important barrier to interpreting PRP research is lack of standardization of PRP preparation protocols, inconsistent clinical endpoints, and frequent combination treatments. However, PRP is relatively noninvasive, has a well-established safety profile, and patient satisfaction is often high as patients perceive great benefit from treatment with PRP.
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Affiliation(s)
- Jessica N Pixley
- Wake Forest Department of Dermatology, Medical Center Boulevard, Winston-Salem, NC, USA
| | - Madison K Cook
- Wake Forest Department of Dermatology, Medical Center Boulevard, Winston-Salem, NC, USA
| | - Rohan Singh
- Wake Forest Department of Dermatology, Medical Center Boulevard, Winston-Salem, NC, USA
| | - Jorge Larrondo
- Wake Forest Department of Dermatology, Medical Center Boulevard, Winston-Salem, NC, USA
| | - Amy J McMichael
- Wake Forest Department of Dermatology, Medical Center Boulevard, Winston-Salem, NC, USA
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22
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Fang Q, Zhang Y, Tang L, Li X, Zhang X, Gang JJ, Xu G. Clinical Study of Platelet-Rich Plasma (PRP) for Lower Extremity Venous Ulcers: A Meta-Analysis and Systematic Review. INT J LOW EXTR WOUND 2023; 22:641-653. [PMID: 34665051 DOI: 10.1177/15347346211046203] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
To systematically evaluate the clinical effects of platelet-rich plasma in the treatment of lower limb venous ulcers by applying a meta-analysis method. The Pubmed, Cochrance Library, Embase, and OVID EBM Reviews databases were searched for the search terms'platelet-rich plasma" or "Plasma, Platelet-Rich" or "Platelet Rich Plasma" and "lower extremity venous ulcers' or "Leg Ulcers' or "Ulcer, Leg", and a meta-analysis was performed on the published research literature on platelet-rich plasma for lower extremity venous ulcers from January 1900 to April 2021. The outcome indicators were: post-treatment trauma area and healing rate. Revman 5.3 statistical software was applied for meta-analysis. A total of 294 patients with lower extremity venous ulcers were included in six publications, including 148 patients in the experimental group treated with PRP versus 146 patients in the control group treated with conventional therapy. There was a statistically significant difference in the Formula of an ellipse at the end of treatment (CM²) between the experimental group and the control group, with a mean difference of -1.19 (95% CI -1.80 to -0.58, P = .0001; 6 studies, 294 participants moderate quality of evidence). The difference between the healing rate of the experimental group and the control group was statistically significant, with a risk ratio (RR) of 5.73 (95% CI 3.29 - 9.99, P < .00001; 5 studies, 248 participants moderate quality of evidence).There may be publication bias for both Formula of an ellipse at the end of treatment and healing rate. This comprehensive meta-analysis of available evidence suggests that the application of PRP for lower extremity venous ulcers accelerates the wound healing process and improves wound healing rates.
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Affiliation(s)
| | | | - Lijun Tang
- Dalian Medical University, Dalian, China
| | - Xiaomei Li
- Dalian Medical University, Dalian, China
| | - Xiaowei Zhang
- Northern Jiangsu People's Hospital Affiliated to Yangzhou University
| | - Junjun Jin Gang
- Northern Jiangsu People's Hospital Affiliated to Yangzhou University
| | - Gang Xu
- Northern Jiangsu People's Hospital Affiliated to Yangzhou University
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OuYang H, Tang Y, Yang F, Ren X, Yang J, Cao H, Yin Y. Platelet-rich plasma for the treatment of diabetic foot ulcer: a systematic review. Front Endocrinol (Lausanne) 2023; 14:1256081. [PMID: 38169990 PMCID: PMC10760804 DOI: 10.3389/fendo.2023.1256081] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Accepted: 11/23/2023] [Indexed: 01/05/2024] Open
Abstract
Background With the increasing incidence of diabetes, diabetic foot ulcer(DFU) has become one of the most common and serious complications in people with diabetes. DFU is associated with significant morbidity and mortality, and can also result in significant economic, social and public health burdens. Due to peripheral neuropathy, peripheral vascular disease, hyperglycemic environment, inflammatory disorders and other factors, the healing of DFU is impaired or delayed, resulting in the formation of diabetic chronic refractory ulcer. Because of these pathological abnormalities in DFU, it may be difficult to promote wound healing with conventional therapies or antibiotics, whereas platelet-rich plasma(PRP) can promote wound healing by releasing various bioactive molecules stored in platelets, making it more promising than traditional antibiotics. Therefore, the purpose of this systematic review is to summarize and analyze the efficacy of PRP in the treatment of DFU. Methods A literature search was undertaken in PubMed, CNKI, EMB-ASE, the Cochrane Library, the WanFang Database and the WeiPu Database by computer. Included controlled studies evaluating the efficacy of PRP in the treatment of diabetic foot ulcers. The data extraction and assessment are on the basis of PRISMA. Results Twenty studies were evaluated, and nineteen measures for the evaluation of the efficacy of PRP in DFU treatment were introduced by eliminating relevant duplicate measures. The efficacy measures that were repeated in various studies mainly included the rate of complete ulcer healing, the percentage of ulcer area reduction, the time required for ulcer healing, wound complications (including infection rate, amputation rate, and degree of amputation), the rate of ulcer recurrence, and the cost and duration of hospitalization for DFU, as well as subsequent survival and quality of life scores. One of the most important indicators were healing rate, ulcer area reduction and healing time. The meta-analysis found that PRP was significantly improve the healing rate(OR = 4.37, 95% CI 3.02-6.33, P < 0.001) and shorten the healing time(MD = -3.21, 95% CI -3.83 to -2.59,P < 0.001)of patients with DFU when compared to the conventional treatment, but there was no significant difference in reducing the of ulcer area(MD = 5.67, 95% CI -0.77 to 12.11,P =0.08>0.05 ). Conclusion The application of PRP to DFU can improve ulcer healing rate and shorten ulcer healing time, but more clinical data are needed to clarify some efficacy measures. At the same time, a standardized preparation process for PRP is essential.
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Affiliation(s)
- Hong OuYang
- Geriatric Diseases Institute of Chengdu, Department of Endocrine and Metabolism, Chengdu Fifth People’s Hospital (The Second Clinical Medical College, Affiliated Fifth People’s Hospital of Chengdu University of Traditional Chinese Medicine), Chengdu, China
| | - Yi Tang
- Geriatric Diseases Institute of Chengdu, Department of Endocrine and Metabolism, Chengdu Fifth People’s Hospital (The Second Clinical Medical College, Affiliated Fifth People’s Hospital of Chengdu University of Traditional Chinese Medicine), Chengdu, China
| | - Fan Yang
- Geriatric Diseases Institute of Chengdu, Department of Endocrine and Metabolism, Chengdu Fifth People’s Hospital (The Second Clinical Medical College, Affiliated Fifth People’s Hospital of Chengdu University of Traditional Chinese Medicine), Chengdu, China
| | - Xin Ren
- Geriatric Diseases Institute of Chengdu, Department of Endocrine and Metabolism, Chengdu Fifth People’s Hospital (The Second Clinical Medical College, Affiliated Fifth People’s Hospital of Chengdu University of Traditional Chinese Medicine), Chengdu, China
| | - Jing Yang
- Geriatric Diseases Institute of Chengdu, Department of Endocrine and Metabolism, Chengdu Fifth People’s Hospital (The Second Clinical Medical College, Affiliated Fifth People’s Hospital of Chengdu University of Traditional Chinese Medicine), Chengdu, China
| | - Hongyi Cao
- Geriatric Diseases Institute of Chengdu, Department of Endocrine and Metabolism, Chengdu Fifth People’s Hospital (The Second Clinical Medical College, Affiliated Fifth People’s Hospital of Chengdu University of Traditional Chinese Medicine), Chengdu, China
| | - Yifan Yin
- Department of Nephrology, Chengdu Third People’s Hospital, Chengdu, China
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Kress GT, Swerdlow M, Mohan N, Patel K, Shin L. Remission Strategies with Fat Grafting to Prevent Recurrence of Pedal Ulcerations and Pain: A Case Series. PLASTIC AND RECONSTRUCTIVE SURGERY-GLOBAL OPEN 2023; 11:e5232. [PMID: 37662474 PMCID: PMC10473342 DOI: 10.1097/gox.0000000000005232] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2023] [Accepted: 07/12/2023] [Indexed: 09/05/2023]
Abstract
Background Foot deformities and gait abnormalities can result in locally elevated peak pedal pressures or atypical pedal biomechanics. Combined with underlying comorbidities such as neuropathy, stroke, atrophic fat padding and history of ulcerations, this can lead to recurrent ulcerations and pain. Pedal fat grafting (PFG) is a treatment modality that has been shown to reduce peak pressures and accelerate wound healing. This study aimed to investigate the utility of PFG to treat and prevent ulcerations. Methods We retrospectively analyzed medical history, demographics, wound volume at time of procedure, volume of fat injected, surgical outcomes, and presence of new wounds in 15 patients who underwent PFG at Keck Hospital between 2018 and 2023. Results Seventeen feet from 15 patients (63 ± 12 years old, body mass index 30.9 ± 3.1) received PFG with an average volume of fat injected of 10.7 mL and procedure time of 84.6 minutes. At the time of PFG, nine wounds were present on nine feet with an average wound volume of 1.6 ± 2.7 cm3. Average follow-up was 6.9 months (range 1-36 months), with no complications or recurrent ulcerations since the procedure. Conclusions PFG is a promising treatment option for reducing peak pedal pressure and preventing ulcer recurrence in patients with various conditions. Further study is warranted for long-term follow-up.
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Affiliation(s)
- Gavin Thomas Kress
- From Keck School of Medicine of the University of Southern California (USC), Los Angeles, Calif
| | - Mark Swerdlow
- From Keck School of Medicine of the University of Southern California (USC), Los Angeles, Calif
| | - Natasha Mohan
- From Keck School of Medicine of the University of Southern California (USC), Los Angeles, Calif
| | - Ketan Patel
- Department of Plastic and Reconstructive Surgery, Keck School of Medicine of USC, Los Angeles, Calif
- Division of Plastic Surgery, Cedars-Sinai Medical Center, Los Angeles, Calif
| | - Laura Shin
- Southwestern Academic Limb Salvage Alliance (SALSA), Department of Surgery, Keck School of Medicine of University of Southern California, Los Angeles, Calif
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Kunder V, Sharma KC, Rizvi Z, Soubelet R, Ducharme M. The Use of Platelet-Rich Plasma in the Treatment of Diabetic Foot Ulcers: A Scoping Review. Cureus 2023; 15:e43452. [PMID: 37711926 PMCID: PMC10498481 DOI: 10.7759/cureus.43452] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2023] [Accepted: 08/13/2023] [Indexed: 09/16/2023] Open
Abstract
Platelet-rich plasma (PRP) has been recognized as a method of treatment in medicine since the 1980s. It primarily functions by releasing cytokines and growth factors that promote wound healing; these growth-promoting factors released by PRP enact new processes such as angiogenesis, collagen deposition, and tissue formation that can change wound-healing outcomes. Many studies recognize that PRP aids in chronic wound healing, which is advantageous for patients who suffer from chronic diabetic foot ulcers (DFUs). This scoping review aims to examine the literature to identify the efficacy of PRP use in the healing of DFUs. The objective of this study is to explore whether PRP has a beneficial effect on healing completeness and the rate of healing on DFUs. Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we searched randomized-controlled trials involving PRP use in diabetic patients with foot ulcers using PubMed, Medline, CINAHL Complete, and Cochrane Database of Systematic Reviews. We restricted the search to articles published during 2005-2022, full texts in the English language, articles involving patients aged 19 years or older, articles that used PRP specifically on DFUs, articles that included a control group, and articles with human subjects. The initial search yielded 119 articles after removing duplicates. The final analysis for relevance yielded eight articles. In seven of the eight studies, the PRP group showed significant results, with either faster healing, more complete healing, or a larger percentage of healed participants. In the one study that did not give conclusive evidence of accelerated healing with PRP, PRP was used as an adjunct to fat grafting and only used once. Application styles of PRP for treatment were shown to influence the level of healing in patients, with injected PRP appearing to achieve the best results compared to topical PRP application. However, this was not conclusive due to the involvement of several other variables. Two studies additionally found PRP to be useful in healing refractory DFUs, and one study found that PRP use in patients with additional comorbidities was still more effective in healing DFUs than standard wound control. This study used scoping review methodology with randomized-controlled trials to examine the literature regarding PRP use in the healing of DFUs. The evidence suggests that PRP is a useful tool in reducing healing times and improving rates of complete wound healing in DFUs. There is room for further research in the application styles of PRP before conclusive statements can be made on the efficacy of injected versus topical PRP healing, based on the findings in this study. The results of this review provide a baseline for further research on PRP use in patients with diabetes and can be used by physicians and public health experts to guide future treatment options for DFUs.
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Affiliation(s)
- Viktor Kunder
- Osteopathic Medicine, Nova Southeastern University Dr. Kiran C. Patel College of Osteopathic Medicine, Fort Lauderdale, USA
| | - Kiran C Sharma
- Osteopathic Medicine, Nova Southeastern University Dr. Kiran C. Patel College of Osteopathic Medicine, Fort Lauderdale, USA
| | - Zehra Rizvi
- Osteopathic Medicine, Nova Southeastern University Dr. Kiran C. Patel College of Osteopathic Medicine, Fort Lauderdale, USA
| | - Ricardo Soubelet
- Osteopathic Medicine, Nova Southeastern University Dr. Kiran C. Patel College of Osteopathic Medicine, Fort Lauderdale, USA
| | - Monika Ducharme
- Oral and Maxillofacial Surgery, Palm Beach Gardens Medical Center, Palm Beach Gardens, USA
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Thanigaimani S, Jin H, Ahmad U, Anbalagan R, Golledge J. Comparative efficacy of growth factor therapy in healing diabetes-related foot ulcers: A network meta-analysis of randomized controlled trials. Diabetes Metab Res Rev 2023; 39:e3670. [PMID: 37277960 PMCID: PMC10909411 DOI: 10.1002/dmrr.3670] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2022] [Revised: 03/01/2023] [Accepted: 04/26/2023] [Indexed: 06/07/2023]
Abstract
INTRODUCTION This study examined the relative efficacy of growth factor therapies in healing diabetes-related foot ulcers (DFU). METHODS PubMed and Cochrane databases were searched for randomized controlled trials testing growth factor therapies for treating DFU. The primary outcome was complete wound closure. Results were reported as relative risk (RR) ± 95% credible intervals (CrI). The risk of bias was assessed using Cochrane's RoB-2 tool. RESULTS A total of 31 RCTs involving 2174 participants were included. Only 13 of the trials (n = 924) reported on the aetiology of the ulcers (85.4% neuropathic and 14.6% ischaemic). Epidermal growth factor (RR 3.83; 95% CrI 1.81, 9.10), plasma-rich protein (PRP) (RR 3.36; 95% CrI 1.66, 8.03) and platelet-derived growth factor (PDGF) (RR 2.47; 95% CrI 1.23, 5.17) significantly improved the likelihood of complete ulcer healing compared to control. Sub-analyses suggested that PRP (3 trials - RR 9.69; 95% CrI 1.37, 103.37) and PDGF (6 trials - RR 2.22; 95% CrI 1.12, 5.19) significantly improved the likelihood of wound closure amongst trial mainly recruiting participants with neuropathic ulcers. Eleven trials had a low risk of bias, 9 had some concerns and 11 had a high risk of bias. Sub-analysis of trials with a low risk of bias suggested that none of the growth factors significantly improved ulcer healing compared with control. DISCUSSION This network meta-analysis found low-quality evidence that Epidermal growth factor, PRP and PDGF therapy improved DFU healing likelihood compared with control. Larger well-designed trials are needed.
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Affiliation(s)
- Shivshankar Thanigaimani
- Queensland Research Centre for Peripheral Vascular DiseaseCollege of Medicine and DentistryJames Cook UniversityTownsvilleQueenslandAustralia
- The Australian Institute of Tropical Health and MedicineJames Cook UniversityTownsvilleQueenslandAustralia
| | - Harry Jin
- Queensland Research Centre for Peripheral Vascular DiseaseCollege of Medicine and DentistryJames Cook UniversityTownsvilleQueenslandAustralia
| | - Usama Ahmad
- Queensland Research Centre for Peripheral Vascular DiseaseCollege of Medicine and DentistryJames Cook UniversityTownsvilleQueenslandAustralia
| | - Raghuveeran Anbalagan
- Queensland Research Centre for Peripheral Vascular DiseaseCollege of Medicine and DentistryJames Cook UniversityTownsvilleQueenslandAustralia
- The Australian Institute of Tropical Health and MedicineJames Cook UniversityTownsvilleQueenslandAustralia
| | - Jonathan Golledge
- Queensland Research Centre for Peripheral Vascular DiseaseCollege of Medicine and DentistryJames Cook UniversityTownsvilleQueenslandAustralia
- The Australian Institute of Tropical Health and MedicineJames Cook UniversityTownsvilleQueenslandAustralia
- The Department of Vascular and Endovascular SurgeryTownsville University HospitalTownsvilleQueenslandAustralia
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Abdalla MMI, Mohanraj J, Somanath SD. Adiponectin as a therapeutic target for diabetic foot ulcer. World J Diabetes 2023; 14:758-782. [PMID: 37383591 PMCID: PMC10294063 DOI: 10.4239/wjd.v14.i6.758] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 03/25/2023] [Accepted: 04/24/2023] [Indexed: 06/14/2023] Open
Abstract
The global burden of diabetic foot ulcers (DFUs) is a significant public health concern, affecting millions of people worldwide. These wounds cause considerable suffering and have a high economic cost. Therefore, there is a need for effective strategies to prevent and treat DFUs. One promising therapeutic approach is the use of adiponectin, a hormone primarily produced and secreted by adipose tissue. Adiponectin has demonstrated anti-inflammatory and anti-atherogenic properties, and researchers have suggested its potential therapeutic applications in the treatment of DFUs. Studies have indicated that adiponectin can inhibit the production of pro-inflammatory cytokines, increase the production of vascular endothelial growth factor, a key mediator of angiogenesis, and inhibit the activation of the intrinsic apoptotic pathway. Additionally, adiponectin has been found to possess antioxidant properties and impact glucose metabolism, the immune system, extracellular matrix remodeling, and nerve function. The objective of this review is to summarize the current state of research on the potential role of adiponectin in the treatment of DFUs and to identify areas where further research is needed in order to fully understand the effects of adiponectin on DFUs and to establish its safety and efficacy as a treatment for DFUs in the clinical setting. This will provide a deeper understanding of the underlying mechanisms of DFUs that can aid in the development of new and more effective treatment strategies.
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Affiliation(s)
- Mona Mohamed Ibrahim Abdalla
- Department of Physiology, Human Biology Division, School of Medicine, International Medical University, Kuala Lumpur 57000, Malaysia
| | - Jaiprakash Mohanraj
- Department of Biochemistry, Human Biology Division, School of Medicine, International Medical University, Kuala Lumpur 57000, Malaysia
| | - Sushela Devi Somanath
- Department of Microbiology, School of Medicine, International Medical University, Kuala Lumpur 57000, Malaysia
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Yin XL, Hu L, Li T, Zou Y, Li HL. A meta-analysis on the efficacy of vacuum sealing drainage combined with autologous platelet-rich plasma in the treatment of Grade 2 and Grade 3 diabetic foot ulcers. Int Wound J 2023; 20:1033-1041. [PMID: 36111514 PMCID: PMC10031232 DOI: 10.1111/iwj.13956] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2022] [Revised: 08/25/2022] [Accepted: 08/26/2022] [Indexed: 11/29/2022] Open
Abstract
This meta-analysis aims to systemically evaluate the efficacy of vacuum sealing drainage (VSD) combined with autologous platelet-rich plasma (PRP) in the treatment of diabetic foot ulcers (DFU). The China HowNet, China Biomedical Literature, VIP periodical resource integration service platform, Wanfang, Embase, Cochrane Central, and PubMed databases were retrieved using the computer. The retrieval period was up to July 2021. Randomised controlled trials on VSD combined with PRP in the treatment of DFU were collected. Those trials that met the inclusion criteria were included for meta-analysis using RevMan 5.3 software. A total of 13 articles were included. In the trial group, 477 patients with DFU were treated with VSD combined with PRP, while in the control group, 482 patients with DFU were treated with conventional dressings and/or VSD. The meta-analysis showed that, compared with the control group, VSD combined with PRP has significant advantages in shortening healing time (standardised mean difference [SMD] = -0.87, 95% confidence interval [CI]: -1.07 to -0.67, P < .00001), improving ulcer healing rates (odds ratio = 4.01, 95% CI: 2.95 ~ 5.46, P < .00001), and reducing hospital stays (mean difference = -15.29, 95% CI: -16.05 to -14.54, P < .00001), but the differences in dressing change times (SMD = -1.27, 95% CI: -2.71 to 0.17, P = .08) and hospitalisation expenses (SMD = -0.16, 95% CI: -13.40 to 13.07, P = .98) were not statistically significant. VSD combined with autologous PRP has good curative efficacy in the treatment of DFU and is a better treatment option. However, this treatment is limited in patients with platelet dysfunction, thrombocytopenia, leukaemia, and poor general condition.
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Affiliation(s)
- Xiao-Ling Yin
- Department of Endocrinology, The First Hospital of Nanchang (The Third Affiliated Hospital of Nanchang University), Nanchang, Jiangxi, China
| | - Ling Hu
- Department of Endocrinology, The First Hospital of Nanchang (The Third Affiliated Hospital of Nanchang University), Nanchang, Jiangxi, China
| | - Ting Li
- Department of Endocrinology, The First Hospital of Nanchang (The Third Affiliated Hospital of Nanchang University), Nanchang, Jiangxi, China
| | - Yi Zou
- Department of Endocrinology, The First Hospital of Nanchang (The Third Affiliated Hospital of Nanchang University), Nanchang, Jiangxi, China
| | - Hong-Lin Li
- Department of Biochemistry, Medical College of Georgia, Augusta, Georgia, USA
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The Efficacy of Platelet-Rich Plasma Injection Therapy in the Treatment of Patients with Achilles Tendinopathy: A Systematic Review and Meta-Analysis. J Clin Med 2023; 12:jcm12030995. [PMID: 36769643 PMCID: PMC9918262 DOI: 10.3390/jcm12030995] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2022] [Revised: 01/21/2023] [Accepted: 01/24/2023] [Indexed: 01/31/2023] Open
Abstract
BACKGROUND Over the past few years, many studies have been conducted to evaluate the effectiveness of platelet-rich plasma (PRP) in treating musculoskeletal conditions. However, there is controversy about its benefits for patients with Achilles tendinopathy. OBJECTIVE This study aimed to investigate whether platelet-rich plasma injections can improve outcomes in patients with Achilles tendinopathy. METHODS A comprehensive literature search was conducted in PubMed, Embase, Cochrane Library, Web of Science, China Biomedical CD-ROM, and Chinese Science and Technology Journal databases to identify randomised controlled clinical trials that compared the efficacy of PRP injection in patients with Achilles tendinopathy (AT) versus placebo, published between 1 January 1966 and 1 December 2022. Review Manager 5.4.1 software was used for the statistical analysis, and the Jadad score was used to assess the included literature. Only 8 of the 288 articles found met the inclusion criteria. RESULTS Our work suggests that: The PRP treatment group had a slightly higher VISA-A score than the placebo group at 6 weeks [MD = 1.92, 95% CI (-0.54, 4.38), I2 = 34%], at 12 weeks [MD = 0.20, 95% CI (-2.65 3.05), I2 = 60%], and 24 weeks [MD = 2.75, 95% CI (-2.76, 8.26), I2 = 87%]). However, the difference was not statistically significant. The Achilles tendon thickness was higher at 12 weeks of treatment in the PRP treatment group compared to the control group [MD = 0.34, 95% CI (-0.04, 0.71), p = 0.08], but the difference was not statistically significant. The VAS-improvement results showed no significant difference at 6 and 24 weeks between the two groups, respectively (MD = 6.75, 95% CI = (-6.12, 19.62), I2 = 69%, p = 0.30), and (MD = 10.46, 95% CI = (-2.44 to 23.37), I2 = 69%, p = 0.11). However, at 12 weeks of treatment, the PRP injection group showed a substantial VAS improvement compared to the control group (MD = 11.30, 95% CI = (7.33 to 15.27), I2 = 0%, p < 0.00001). The difference was statistically significant. The return to exercise rate results showed a higher return to exercise rate in the PRP treatment group than the placebo group [RR = 1.11, 95% CI (0.87, 1.42), p = 0.40]; the difference was not statistically significant. CONCLUSION There is no proof that PRP injections can enhance patient functional and clinical outcomes for Achilles tendinopathy. Augmenting the frequency of PRP injections may boost the outcomes, and additionally, more rigorous designs and standardised clinical randomised controlled trials are needed to produce more reliable and accurate results.
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Wang Y, Liu B, Pi Y, Hu L, Yuan Y, Luo J, Tao Y, Li P, Lu S, Song W. Risk factors for diabetic foot ulcers mortality and novel negative pressure combined with platelet-rich plasma therapy in the treatment of diabetic foot ulcers. Front Pharmacol 2022; 13:1051299. [PMID: 36588684 PMCID: PMC9800930 DOI: 10.3389/fphar.2022.1051299] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2022] [Accepted: 11/30/2022] [Indexed: 12/23/2022] Open
Abstract
The purpose of this study was to assess the risk factors for morbidity and mortality of diabetic foot ulcers (DFUs). For the treatment of diabetic foot ulcers, negative pressure wound therapy (NPWT) combined with platelet-rich plasma-fibrin glue (PRP) was also investigated. There were 653 patients in the diabetic foot ulcer group and 510 patients in the diabetic patients without foot ulceration (NFU) group, for a total of 1163 patients in the study samples after individuals without follow-up were excluded. The patients were randomized into two groups: the negative pressure wound therapy group and the negative pressure wound therapy combined with the PRP group. The findings of the univariate analysis revealed the blood indicators for predicting diabetic foot ulcer morbidity risk factors, such as C-reactive protein, albumin, creatinine, alkaline phosphatase, procalcitonin, platelets, 25-hydroxyvitamin D, β-2-microglobulin, monocyte ratio, low-density protein cholesterol (LDL), triglyceride, alanine aminotransferase (ALT), aminotransferase (AST), creatine kinase (CK) and total cholesterol. Using logistic regression analysis revealed only albumin and age to be independent predictors of diabetic foot ulcer mortality. Our study also revealed that, compared to negative pressure wound therapy alone, negative pressure wound therapy combined with PRP accelerated wound healing and reduced the mortality rate. According to the findings of this pilot study, new risk factors for diabetic foot ulcer morbidity and mortality have been found, and negative pressure wound therapy combined with PRP therapy may provide the first information that it is an effective adjunct treatment for diabetic foot ulcers.
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Affiliation(s)
- Yanling Wang
- Changsha Maternal and Child Health Hospital Affiliated to Hunan Normal University, Changsha, China
| | - Bang Liu
- Changsha Maternal and Child Health Hospital Affiliated to Hunan Normal University, Changsha, China
| | - Yinzhen Pi
- The First Hospital of Changsha, Changsha, China
| | - Li Hu
- The First Hospital of Changsha, Changsha, China
| | - Yeling Yuan
- Department of Pediatrics, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Jiao Luo
- Changsha Maternal and Child Health Hospital Affiliated to Hunan Normal University, Changsha, China
| | - Yixiao Tao
- Changsha Maternal and Child Health Hospital Affiliated to Hunan Normal University, Changsha, China
| | - Ping Li
- Changsha Maternal and Child Health Hospital Affiliated to Hunan Normal University, Changsha, China
| | - Shan Lu
- Changsha Maternal and Child Health Hospital Affiliated to Hunan Normal University, Changsha, China
| | - Wei Song
- National & Local Joint Engineering Research Center of High-Throughput Drug Screening Technology, College of Health Science and Engineering, Hubei University, Wuhan, China,*Correspondence: Wei Song,
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Kerstan A, Dieter K, Niebergall-Roth E, Klingele S, Jünger M, Hasslacher C, Daeschlein G, Stemler L, Meyer-Pannwitt U, Schubert K, Klausmann G, Raab T, Goebeler M, Kraft K, Esterlechner J, Schröder HM, Sadeghi S, Ballikaya S, Gasser M, Waaga-Gasser AM, Murphy GF, Orgill DP, Frank NY, Ganss C, Scharffetter-Kochanek K, Frank MH, Kluth MA. Translational development of ABCB5 + dermal mesenchymal stem cells for therapeutic induction of angiogenesis in non-healing diabetic foot ulcers. Stem Cell Res Ther 2022; 13:455. [PMID: 36064604 PMCID: PMC9444095 DOI: 10.1186/s13287-022-03156-9] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Accepted: 06/25/2022] [Indexed: 11/15/2022] Open
Abstract
Background While rapid healing of diabetic foot ulcers (DFUs) is highly desirable to avoid infections, amputations and life-threatening complications, DFUs often respond poorly to standard treatment. GMP-manufactured skin-derived ABCB5+ mesenchymal stem cells (MSCs) might provide a new adjunctive DFU treatment, based on their remarkable skin wound homing and engraftment potential, their ability to adaptively respond to inflammatory signals, and their wound healing-promoting efficacy in mouse wound models and human chronic venous ulcers. Methods The angiogenic potential of ABCB5+ MSCs was characterized with respect to angiogenic factor expression at the mRNA and protein level, in vitro endothelial trans-differentiation and tube formation potential, and perfusion-restoring capacity in a mouse hindlimb ischemia model. Finally, the efficacy and safety of ABCB5+ MSCs for topical adjunctive treatment of chronic, standard therapy-refractory, neuropathic plantar DFUs were assessed in an open-label single-arm clinical trial. Results Hypoxic incubation of ABCB5+ MSCs led to posttranslational stabilization of the hypoxia-inducible transcription factor 1α (HIF-1α) and upregulation of HIF-1α mRNA levels. HIF-1α pathway activation was accompanied by upregulation of vascular endothelial growth factor (VEGF) transcription and increase in VEGF protein secretion. Upon culture in growth factor-supplemented medium, ABCB5+ MSCs expressed the endothelial-lineage marker CD31, and after seeding on gel matrix, ABCB5+ MSCs demonstrated formation of capillary-like structures comparable with human umbilical vein endothelial cells. Intramuscularly injected ABCB5+ MSCs to mice with surgically induced hindlimb ischemia accelerated perfusion recovery as measured by laser Doppler blood perfusion imaging and enhanced capillary proliferation and vascularization in the ischemic muscles. Adjunctive topical application of ABCB5+ MSCs onto therapy-refractory DFUs elicited median wound surface area reductions from baseline of 59% (full analysis set, n = 23), 64% (per-protocol set, n = 20) and 67% (subgroup of responders, n = 17) at week 12, while no treatment-related adverse events were observed. Conclusions The present observations identify GMP-manufactured ABCB5+ dermal MSCs as a potential, safe candidate for adjunctive therapy of otherwise incurable DFUs and justify the conduct of a larger, randomized controlled trial to validate the clinical efficacy. Trial registration: ClinicalTrials.gov, NCT03267784, Registered 30 August 2017, https://clinicaltrials.gov/ct2/show/NCT03267784 Supplementary Information The online version contains supplementary material available at 10.1186/s13287-022-03156-9.
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Affiliation(s)
- Andreas Kerstan
- Department of Dermatology, Venereology and Allergology, University Hospital Würzburg, Würzburg, Germany
| | | | | | - Sabrina Klingele
- TICEBA GmbH, Im Neuenheimer Feld 517, 69120, Heidelberg, Germany
| | - Michael Jünger
- Department of Dermatology, University Hospital Greifswald, Greifswald, Germany
| | | | - Georg Daeschlein
- Department of Dermatology, University Hospital Greifswald, Greifswald, Germany.,Clinic of Dermatology, Immunology and Allergology, Medical University Brandenburg "Theodor Fontane" Medical Center Dessau, Dessau, Germany
| | - Lutz Stemler
- Diabetologikum DDG Ludwigshafen, Ludwigshafen, Germany
| | | | | | | | | | - Matthias Goebeler
- Department of Dermatology, Venereology and Allergology, University Hospital Würzburg, Würzburg, Germany
| | | | | | | | - Samar Sadeghi
- TICEBA GmbH, Im Neuenheimer Feld 517, 69120, Heidelberg, Germany
| | - Seda Ballikaya
- TICEBA GmbH, Im Neuenheimer Feld 517, 69120, Heidelberg, Germany
| | - Martin Gasser
- Department of Surgery, University Hospital Würzburg, Würzburg, Germany
| | - Ana M Waaga-Gasser
- Department of Surgery, University Hospital Würzburg, Würzburg, Germany.,Division of Renal (Kidney) Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - George F Murphy
- Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Dennis P Orgill
- Division of Plastic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Natasha Y Frank
- Department of Medicine, VA Boston Healthcare System, Boston, MA, USA.,Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.,Transplant Research Program, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.,Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA
| | - Christoph Ganss
- RHEACELL GmbH & Co. KG, Heidelberg, Germany.,TICEBA GmbH, Im Neuenheimer Feld 517, 69120, Heidelberg, Germany
| | | | - Markus H Frank
- Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.,Transplant Research Program, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.,Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA.,School of Medical and Health Sciences, Edith Cowan University, Perth, Australia
| | - Mark A Kluth
- RHEACELL GmbH & Co. KG, Heidelberg, Germany. .,TICEBA GmbH, Im Neuenheimer Feld 517, 69120, Heidelberg, Germany.
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Gardikiotis I, Cojocaru FD, Mihai CT, Balan V, Dodi G. Borrowing the Features of Biopolymers for Emerging Wound Healing Dressings: A Review. Int J Mol Sci 2022; 23:ijms23158778. [PMID: 35955912 PMCID: PMC9369430 DOI: 10.3390/ijms23158778] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2022] [Revised: 08/02/2022] [Accepted: 08/05/2022] [Indexed: 12/02/2022] Open
Abstract
Wound dressing design is a dynamic and rapidly growing field of the medical wound-care market worldwide. Advances in technology have resulted in the development of a wide range of wound dressings that treat different types of wounds by targeting the four phases of healing. The ideal wound dressing should perform rapid healing; preserve the body’s water content; be oxygen permeable, non-adherent on the wound and hypoallergenic; and provide a barrier against external contaminants—at a reasonable cost and with minimal inconvenience to the patient. Therefore, choosing the best dressing should be based on what the wound needs and what the dressing does to achieve complete regeneration and restoration of the skin’s structure and function. Biopolymers, such as alginate (ALG), chitosan (Cs), collagen (Col), hyaluronic acid (HA) and silk fibroin (SF), are extensively used in wound management due to their biocompatibility, biodegradability and similarity to macromolecules recognized by the human body. However, most of the formulations based on biopolymers still show various issues; thus, strategies to combine them with molecular biology approaches represent the future of wound healing. Therefore, this article provides an overview of biopolymers’ roles in wound physiology as a perspective on the development of a new generation of enhanced, naturally inspired, smart wound dressings based on blood products, stem cells and growth factors.
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Affiliation(s)
- Ioannis Gardikiotis
- Advanced Research and Development Center for Experimental Medicine (CEMEX), Grigore T. Popa University of Medicine and Pharmacy of Iasi, 9-13 Kogalniceanu Street, 700454 Iasi, Romania
| | - Florina-Daniela Cojocaru
- Advanced Research and Development Center for Experimental Medicine (CEMEX), Grigore T. Popa University of Medicine and Pharmacy of Iasi, 9-13 Kogalniceanu Street, 700454 Iasi, Romania
- Biomedical Sciences Department, Faculty of Medical Bioengineering, Grigore T. Popa University of Medicine and Pharmacy of Iasi, 9-13 Kogalniceanu Street, 700454 Iasi, Romania
- Correspondence: (F.-D.C.); (G.D.)
| | - Cosmin-Teodor Mihai
- Advanced Research and Development Center for Experimental Medicine (CEMEX), Grigore T. Popa University of Medicine and Pharmacy of Iasi, 9-13 Kogalniceanu Street, 700454 Iasi, Romania
| | - Vera Balan
- Biomedical Sciences Department, Faculty of Medical Bioengineering, Grigore T. Popa University of Medicine and Pharmacy of Iasi, 9-13 Kogalniceanu Street, 700454 Iasi, Romania
| | - Gianina Dodi
- Advanced Research and Development Center for Experimental Medicine (CEMEX), Grigore T. Popa University of Medicine and Pharmacy of Iasi, 9-13 Kogalniceanu Street, 700454 Iasi, Romania
- Correspondence: (F.-D.C.); (G.D.)
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Hasiba-Pappas SK, Tuca AC, Luze H, Nischwitz SP, Zrim R, Geißler JC, Lumenta DB, Kamolz LP, Winter R. Platelet-Rich Plasma in Plastic Surgery: A Systematic Review. Transfus Med Hemother 2022; 49:129-142. [PMID: 35813605 PMCID: PMC9210026 DOI: 10.1159/000524353] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2021] [Accepted: 03/21/2022] [Indexed: 11/16/2023] Open
Abstract
INTRODUCTION Platelet-rich plasma (PRP) is gaining popularity and is applied in a variety of clinical settings. This review aims to present and evaluate available evidence regarding the use of PRP in various applications in plastic surgery. METHODS PubMed, Web of Science, Medline, and Embase were searched using predefined MeSH terms to identify studies concerning the application of PRP alone or in combination with fat grafting for plastic surgery. The search was limited to articles in English or German. Animal studies, in vitro studies, case reports, and case series were excluded. RESULTS Of 50 studies included in this review, eleven studies used PRP for reconstruction or wound treatment, eleven for cosmetic procedures, four for hand surgery, two for burn injuries, five for craniofacial disorders, and 17 as an adjuvant to fat grafting. Individual study characteristics were summarized. Considerable variation in preparation protocols and treatment strategies were observed. Even though several beneficial effects of PRP therapy were described, significance was not always demonstrated, and some studies yielded conflicting results. Efficacy of PRP was not universally proven in every field of application. CONCLUSION This study presents an overview of current PRP treatment options and outcomes in plastic surgery. PRP may be beneficial for some indications explored in this review; however, currently available data are insufficient and systematic evaluation is limited due to high heterogeneity in PRP preparation and treatment regimens. Further randomized controlled trials employing standardized protocols are warranted.
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Affiliation(s)
- Sophie K. Hasiba-Pappas
- Research Unit for Tissue Regeneration, Repair and Reconstruction, Division of Plastic, Aesthetic and Reconstructive Surgery, Department of Surgery, Medical University of Graz, Graz, Austria
| | - Alexandru Cristian Tuca
- Research Unit for Tissue Regeneration, Repair and Reconstruction, Division of Plastic, Aesthetic and Reconstructive Surgery, Department of Surgery, Medical University of Graz, Graz, Austria
| | - Hanna Luze
- Research Unit for Tissue Regeneration, Repair and Reconstruction, Division of Plastic, Aesthetic and Reconstructive Surgery, Department of Surgery, Medical University of Graz, Graz, Austria
| | - Sebastian P. Nischwitz
- Research Unit for Tissue Regeneration, Repair and Reconstruction, Division of Plastic, Aesthetic and Reconstructive Surgery, Department of Surgery, Medical University of Graz, Graz, Austria
| | - Robert Zrim
- Research Unit for Tissue Regeneration, Repair and Reconstruction, Division of Plastic, Aesthetic and Reconstructive Surgery, Department of Surgery, Medical University of Graz, Graz, Austria
| | - Judith C.J. Geißler
- Research Unit for Tissue Regeneration, Repair and Reconstruction, Division of Plastic, Aesthetic and Reconstructive Surgery, Department of Surgery, Medical University of Graz, Graz, Austria
| | - David Benjamin Lumenta
- Research Unit for Tissue Regeneration, Repair and Reconstruction, Division of Plastic, Aesthetic and Reconstructive Surgery, Department of Surgery, Medical University of Graz, Graz, Austria
| | - Lars-P. Kamolz
- Research Unit for Tissue Regeneration, Repair and Reconstruction, Division of Plastic, Aesthetic and Reconstructive Surgery, Department of Surgery, Medical University of Graz, Graz, Austria
- COREMED − Cooperative Centre for Regenerative Medicine, Joanneum Research GmbH, Graz, Austria
| | - Raimund Winter
- Research Unit for Tissue Regeneration, Repair and Reconstruction, Division of Plastic, Aesthetic and Reconstructive Surgery, Department of Surgery, Medical University of Graz, Graz, Austria
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Bellei B, Migliano E, Picardo M. Research update of adipose tissue-based therapies in regenerative dermatology. Stem Cell Rev Rep 2022; 18:1956-1973. [PMID: 35230644 DOI: 10.1007/s12015-022-10328-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/01/2022] [Indexed: 12/09/2022]
Abstract
Mesenchymal stromal/stem cells (MSCs) have a spontaneous propensity to support tissue homeostasis and regeneration. Among the several sources of MSCs, adipose-derived tissue stem cells (ADSCs) have received major interest due to the higher mesenchymal stem cells concentration, ease, and safety of access. However, since a significant part of the natural capacity of ADSCs to repair damaged tissue is ascribable to their secretory activity that combines mitogenic factors, cytokines, chemokines, lipids, and extracellular matrix components, several studies focused on cell-free strategies. Furthermore, adipose cell-free derivatives are becoming more attractive especially for non-volumizing purposes, such as most dermatological conditions. However, when keratinocytes, fibroblasts, melanocytes, adipocytes, and hair follicle cells might not be locally sourced, graft of materials containing concentrated ADSCs is preferred. The usage of extracellular elements of adipose tissue aims to promote a self-autonomous regenerative microenvironment in the receiving area restoring physiological homeostasis. Hence, ADSCs or their paracrine activity are currently being studied in several dermatological settings including wound healing, skin fibrosis, burn, and aging.The present work analyzing both preclinical and clinical experiences gives an overview of the efficacy of adipose tissue-derivatives like autologous fat, the stromal vascular fraction (SVF), purified ADSCs, secretome and extracellular matrix graft in the field of regenerative medicine for the skin.
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Affiliation(s)
- Barbara Bellei
- Laboratory of Cutaneous Physiopathology and Integrated Center of Metabolomics Research, San Gallicano Dermatological Institute, IRCCS, Via Elio Chianesi 53, 00144, Rome, Italy.
| | - Emilia Migliano
- Department of Plastic and Reconstructive Surgery, San Gallicano Dermatological Institute, IRCCS, Via Elio Chianesi 53, 00144, Rome, Italy
| | - Mauro Picardo
- Laboratory of Cutaneous Physiopathology and Integrated Center of Metabolomics Research, San Gallicano Dermatological Institute, IRCCS, Via Elio Chianesi 53, 00144, Rome, Italy
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Tsou YA, Tien VHC, Chen SH, Shih LC, Lin TC, Chiu CJ, Chang WD. Autologous Fat Plus Platelet-Rich Plasma versus Autologous Fat Alone on Sulcus Vocalis. J Clin Med 2022; 11:jcm11030725. [PMID: 35160180 PMCID: PMC8836483 DOI: 10.3390/jcm11030725] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2021] [Revised: 01/22/2022] [Accepted: 01/27/2022] [Indexed: 11/16/2022] Open
Abstract
Sulcus vocalis is a frequent cause of glottic insufficiency that leads to incomplete vocal fold closure during phonation. Type II sulcus vocalis is defined as a partial defect of the lamina propria (LP). Treatment with fillers, such as fat or hyaluronic acid (HA), in the vocal folds is widely used, but the duration of effect is variable. Platelet-rich plasma (PRP) can enhance the survival of autologous fat in fat grafting, and also is used to treat sulcus vocalis. This study aimed to compare the effectiveness of autologous fat graft versus fat graft plus PRP to treat type II sulcus vocalis. Thirty-four patients with a voice handicap index (VHI) ≥ 11 were randomized to two groups, which received LP injections of fat graft (n = 17) or fat graft plus PRP (n = 17). At 1 month and 6 months after injection, the VHI decreased significantly in both groups. The fat plus PRP group had better Jitter, Shimmer, and noise to harmonic ratio (NHR) in 1 month and 6 months after surgery. The fat plus PRP group resulted in lower VHI scores one month after surgery, and stroboscopy revealed sustained smaller gaps after six months. These results indicate that a combination of fat graft plus PRP is safe and effective for treating sulcus vocalis type II and associated vocal atrophy.
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Affiliation(s)
- Yung-An Tsou
- Department of Otolaryngology-Head and Neck Surgery, China Medical University Hospital, Taichung 40402, Taiwan; (Y.-A.T.); (V.H.-C.T.); (L.-C.S.); (T.-C.L.); (C.-J.C.)
- School of Medicine, China Medical University, Taichung 40402, Taiwan
- Department of Otolaryngology Head and Neck Surgery, Asia University Hospital, Taichung 40402, Taiwan
- Department of Audiology and Speech-Language Pathology, Asia University, Taichung 41354, Taiwan;
| | - Vincent Hui-Chi Tien
- Department of Otolaryngology-Head and Neck Surgery, China Medical University Hospital, Taichung 40402, Taiwan; (Y.-A.T.); (V.H.-C.T.); (L.-C.S.); (T.-C.L.); (C.-J.C.)
- Department of Otolaryngology Head and Neck Surgery, Asia University Hospital, Taichung 40402, Taiwan
- Department of Audiology and Speech-Language Pathology, Asia University, Taichung 41354, Taiwan;
| | - Sheng-Hwa Chen
- Department of Audiology and Speech-Language Pathology, Asia University, Taichung 41354, Taiwan;
| | - Liang-Chun Shih
- Department of Otolaryngology-Head and Neck Surgery, China Medical University Hospital, Taichung 40402, Taiwan; (Y.-A.T.); (V.H.-C.T.); (L.-C.S.); (T.-C.L.); (C.-J.C.)
- Graduate Institute of Biomedical Sciences, China Medical University, Taichung 40402, Taiwan
| | - Tzu-Chieh Lin
- Department of Otolaryngology-Head and Neck Surgery, China Medical University Hospital, Taichung 40402, Taiwan; (Y.-A.T.); (V.H.-C.T.); (L.-C.S.); (T.-C.L.); (C.-J.C.)
| | - Chien-Jen Chiu
- Department of Otolaryngology-Head and Neck Surgery, China Medical University Hospital, Taichung 40402, Taiwan; (Y.-A.T.); (V.H.-C.T.); (L.-C.S.); (T.-C.L.); (C.-J.C.)
| | - Wen-Dien Chang
- Department of Sport Performance, National Taiwan University of Sport, Taichung 404401, Taiwan
- Correspondence: ; Tel.: +886-4-2221-3108
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Chiang KJ, Chiu LC, Kang YN, Chen C. Autologous Stem Cell Therapy for Chronic Lower Extremity Wounds: A Meta-Analysis of Randomized Controlled Trials. Cells 2021; 10:3307. [PMID: 34943815 PMCID: PMC8699089 DOI: 10.3390/cells10123307] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2021] [Revised: 11/19/2021] [Accepted: 11/23/2021] [Indexed: 12/15/2022] Open
Abstract
Lower extremity chronic wounds (LECWs) commonly occur in patients with diabetes mellitus (DM) and peripheral arterial disease (PAD). Autologous stem cell therapy (ASCT) has emerged as a promising alternative treatment for those who suffered from LECWs. The purpose of this study was to assess the effects of ASCT on LECWs. Two authors searched three core databases, and independently identified evidence according to predefined criteria. They also individually assessed the quality of the included randomized controlled trials (RCTs), and extracted data on complete healing rate, amputation rate, and outcomes regarding peripheral circulation. The extracted data were pooled using a random-effects model due to clinical heterogeneity among the included RCTs. A subgroup analysis was further performed according to etiology, source of stem cells, follow-up time, and cell markers. A total of 28 RCTs (n = 1096) were eligible for this study. The pooled results showed that patients receiving ASCT had significantly higher complete healing rates (risk ratio (RR) = 1.67, 95% confidence interval (CI) 1.28-2.19) as compared with those without ASCT. In the CD34+ subgroup, ASCT significantly led to a higher complete healing rate (RR = 2.70, 95% CI 1.50-4.86), but there was no significant difference in the CD34- subgroup. ASCT through intramuscular injection can significantly improve wound healing in patients with LECWs caused by either DM or critical limb ischemia. Lastly, CD34+ is an important cell marker for potential wound healing. However, more extensive scale and well-designed studies are necessary to explore the details of ASCT and chronic wound healing.
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Affiliation(s)
- Kuan-Ju Chiang
- School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan; (K.-J.C.); (L.-C.C.)
| | - Li-Cheng Chiu
- School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan; (K.-J.C.); (L.-C.C.)
| | - Yi-No Kang
- Department of Health Care Management, College of Health Technology, National Taipei University of Nursing Health Sciences, Taipei 112, Taiwan
- Evidence-Based Medicine Center, Wan Fang Hospital, Taipei Medical University, Taipei 116, Taiwan
- Research Center of Big Data and Meta-Analysis Center, Wan Fang Hospital, Taipei Medical University, Taipei 116, Taiwan
- Cochrane Taiwan, Taipei Medical University, Taipei 110, Taiwan
- Institute of Health Policy & Management, College of Public Health, National Taiwan University, Taipei 100, Taiwan
| | - Chiehfeng Chen
- Evidence-Based Medicine Center, Wan Fang Hospital, Taipei Medical University, Taipei 116, Taiwan
- Cochrane Taiwan, Taipei Medical University, Taipei 110, Taiwan
- Division of Plastic Surgery, Department of Surgery, Wan Fang Hospital, Taipei Medical University, Taipei 116, Taiwan
- Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
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Chen J, Wan Y, Jiang H. The effect of platelet-rich plasma injection on chronic Achilles tendinopathy and acute Achilles tendon rupture. Platelets 2021; 33:339-349. [PMID: 34346853 DOI: 10.1080/09537104.2021.1961712] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Several clinical trials exploring the effect of platelet-rich plasma (PRP) on Achilles tendon rupture (ATR) or Achilles tendinopathy (AT) have been published. However, current evidence is limited to small-sized trials. This study aims to evaluate whether PRP improves the outcomes of ATR or AT. PubMed, Web of Science, EMBASE, and Cochrane Library databases were searched to identify randomized controlled trials comparing PRP injection versus placebo for ATR or AT. Eleven studies with 574 patients were included. Quantitative synthesis suggested that compared with placebo, AT patients in PRP group had higher VISA-A score improvement at six-week follow-up (mean difference (MD) = 2.64; 95% CI) = 1.12 to 4.15). However, there was no significant difference between two groups for VISA-A score improvement at three-month follow-up (MD = 0.93; 95% CI = -2.75 to 4.62), or 6-month follow-up (MD = 5.46; 95% CI = -1.19 to 12.11). In ATR patients, quantitative synthesis suggested that no significant difference was seen between PRP and control group at 3-month, 6-month, and 1-year follow-up. In addition, no significant difference was detected between the two groups in improving tendon thickness and pain for AT patients, and no significant difference was seen in improving heel-rise work, maximum heel-rise height, dorsal and plantar flexion, rate of returning to sports activities, and complication for ATR patients. To conclude, no evidence indicates that PRP injection can improve the patient-reported/clinical/functional outcomes of AT or ATR. The increasing times of PRP injection could improve the outcomes, and further clinical randomized controlled trials are expected to be conducted to verify this hypothesis.
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Affiliation(s)
- Jianguo Chen
- Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yingying Wan
- Xi Yuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Haiyue Jiang
- Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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Nolan GS, Smith OJ, Heavey S, Jell G, Mosahebi A. Histological analysis of fat grafting with platelet-rich plasma for diabetic foot ulcers-A randomised controlled trial. Int Wound J 2021; 19:389-398. [PMID: 34169656 PMCID: PMC8762540 DOI: 10.1111/iwj.13640] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Revised: 05/26/2021] [Accepted: 05/31/2021] [Indexed: 11/28/2022] Open
Abstract
Diabetic foot ulcers are often unresponsive to conventional therapy and are a leading cause of amputation. Animal studies have shown stem cells and growth factors can accelerate wound healing. Adipose‐derived stem cells are found in fat grafts and mixing them with platelet‐rich plasma (PRP) may improve graft survival. This study aimed to establish the histological changes when diabetic foot ulcers are treated with fat grafts and PRP. A three‐armed RCT was undertaken of 18 diabetic foot ulcer patients: fat grafting; fat grafting with PRP; and routine podiatry care. Biopsies were obtained at week 0, 1, and 4, and underwent quantitative histology/immunohistochemistry (H&E, CD31, and Ki67). Treatment with fat and PRP increased mean microvessel density at 1 week to 1645 (SD 96) microvessels/mm2 (+32%‐45% to other arms, P = .035). PRP appeared to increase vascularity surrounding fat grafts, and histology suggested PRP may enhance fat graft survival. There was no clinical difference between arms. This study demonstrates PRP with fat grafts increased neovascularisation and graft survival in diabetic foot ulcers. The histology was not, however, correlated with wound healing time. Future studies should consider using apoptosis markers and fluorescent labelling to ascertain if enhanced fat graft survival is due to proliferation or reduced apoptosis. Trial registration NCT03085550.
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Affiliation(s)
- Grant Switzer Nolan
- Division of Surgery & Interventional Science, University College London, Royal Free Hospital, London, United Kingdom
| | - Oliver John Smith
- Division of Surgery & Interventional Science, University College London, Royal Free Hospital, London, United Kingdom
| | - Susan Heavey
- Division of Surgery & Interventional Science, University College London, Royal Free Hospital, London, United Kingdom
| | - Gavin Jell
- Division of Surgery & Interventional Science, University College London, Royal Free Hospital, London, United Kingdom
| | - Afshin Mosahebi
- Division of Surgery & Interventional Science, University College London, Royal Free Hospital, London, United Kingdom
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Chen J, Wan Y, Lin Y, Jiang H. Current art of combination therapy with autologous platelet-rich plasma for stable vitiligo: A meta-analysis. Int Wound J 2020; 18:251-260. [PMID: 33245822 PMCID: PMC8243985 DOI: 10.1111/iwj.13524] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2020] [Accepted: 11/08/2020] [Indexed: 12/17/2022] Open
Abstract
Presently, there is an explosion in various uses of platelet‐rich plasma (PRP). Several trials comparing combination therapy with PRP vs monotherapy for vitiligo have been published. However, evidence‐based information is not enough for making well‐informed decisions. This study aimed to evaluate several combination therapy strategies for vitiligo. EMBASE, PubMed, Web of Science, Cochrane Library and Google Scholar databases were searched to identify randomised controlled trials comparing combination therapy with PRP vs monotherapy for vitiligo. Eleven studies with 670 cases were included. Compared with monotherapy, clinical improvement of repigmentation was significantly higher in 308‐nm excimer laser combined with PRP (odds rate for response rate of 50%‐100% repigmentation, 4.47; 95% CI, 2.47‐8.10; P < .00001) and in fractional carbon dioxide laser combined with PRP (mean difference for mean improvement grades of repigmentation, 1.61; 95% CI, 0.24‐2.99; P = .02), respectively. Compared to monotherapy, there is no higher clinical improvement in strategies of PRP combined with narrowband‐ultraviolet B or non‐cultured epidermal cell suspension. Trivial adverse events were reported. This meta‐analysis summarises current evidence that PRP combined with 308‐nm excimer laser or fractional carbon dioxide laser is effective and safe for vitiligo. This systematic review and meta‐analysis aims to evaluate the effectiveness and safety of several combination therapy strategies with PRP in the treatment of vitiligo. The response rate of repigmentation and mean improvement grades of repigmentation were mainly used for qualitative assessment. PRP combined with 308‐nm excimer laser or fractional carbon dioxide laser is effective and safe for vitiligo due to its healing and regenerative properties.
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Affiliation(s)
- Jianguo Chen
- Department of Plastic and Reconstructive Surgery, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yingying Wan
- Department of Internal Medicine, Xi Yuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Yan Lin
- Department of Plastic and Reconstructive Surgery, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Haiyue Jiang
- Department of Plastic and Reconstructive Surgery, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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Smith OJ, Leigh R, Kanapathy M, Macneal P, Jell G, Hachach-Haram N, Mann H, Mosahebi A. Fat grafting and platelet-rich plasma for the treatment of diabetic foot ulcers: A feasibility-randomised controlled trial. Int Wound J 2020; 17:1578-1594. [PMID: 32633854 DOI: 10.1111/iwj.13433] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2020] [Revised: 05/30/2020] [Accepted: 06/02/2020] [Indexed: 12/16/2022] Open
Abstract
Chronic, nonhealing diabetic foot ulcers (DFU) are increasing in prevalence and are often unresponsive to conventional therapy. Adipose tissue, containing adipose-derived stem cells, and platelet rich plasma (PRP) are regenerative therapies rich in growth factors which may provide a solution to chronic wound healing. This study aimed to assess the feasibility of conducting a definitive randomised controlled trial (RCT) to investigate the efficacy of these therapies for the treatment of DFU. This was a single centre, feasibility, three-arm, parallel group RCT. Eligible DFU patients were randomised on a 1:1:1 basis to three intervention arms: control (podiatry); fat grafting; fat grafting with PRP. The intervention was delivered once and patients were followed-up for 12 weeks. The primary objective was to assess measures of trial feasibility. Clinical outcomes and health-related quality of life (HRQoL) were also evaluated. Three hundred and thirty four patients were screened and 32 patients (9.6%) were deemed eligible with 18 enrolled in the trial (6 per arm) over 17 months. All participants completed the trial with no withdrawals or crossover. Participant engagement was high with most HRQoL questionnaires returned and only 4.8% follow-up appointments missed. There were five adverse events (AEs) related to the trial with no serious AEs. Five (28%) of the wounds healed. There was no difference between any of the groups in terms of clinical outcomes. This feasibility study demonstrated that a multi-centre RCT is safe and feasible with excellent patient engagement. We have highlighted crucial information regarding methodology and recruitment, which will guide future trial design. Registration number: NCT03085550 clinicaltrials.gov. Registered 01/03/2017.
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Affiliation(s)
- Oliver J Smith
- Department of Plastic Surgery, Royal Free Hospital, London, UK.,Division of Surgery and Interventional Science, University College London, London, UK
| | - Richard Leigh
- Department of Podiatry, Royal Free Hospital, London, UK
| | | | - Peter Macneal
- Department of Plastic Surgery, St George's Hospital, London, UK
| | - Gavin Jell
- Division of Surgery and Interventional Science, University College London, London, UK
| | | | - Haroon Mann
- Department of Trauma and Orthopaedics, Royal Free Hospital, London, UK
| | - Ash Mosahebi
- Department of Plastic Surgery, Royal Free Hospital, London, UK.,Division of Surgery and Interventional Science, University College London, London, UK
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