Research progress in microenvironmentally responsive hydrogel materials for chronic refractory wounds / 国际生物医学工程杂志

Chronic refractory wounds have been a challenge for clinical treatment because of their diverse causative factors and complex pathological processes, long healing times, and high treatment costs. The microenvironment of the wound surface includes the external microenvironment of the periwound surface, the internal microenvironment of the wound surface, and subsurface physiological structures. Research on clinical treatment strategies based on the microenvironment of chronic refractory wounds continues to innovate and make progress. Hydrogels have the advantages of high-water content, adjustable performance, good biocompatibility, and similarity to extracellular matrix. The ability of hydrogels to load drugs and their modification to confer excellent tissue adhesion, antibacterial, antioxidant, and modulation of inflammatory factor expression can be used to achieve a multi-factor response and modulation of the physical, chemical, and biological aspects of the trauma microenvironment. Therefore, hydrogels have outstanding advantages and clinical application prospects in the repair of chronic, difficult-to-heal wounds. In this review paper, the characteristics and etiology of chronic refractory wounds were introduced, and the classification of microenvironment-responsive hydrogels for chronic refractory wounds and their application in the repair of refractory wounds were reviewed. Besides, the shortcomings of current hydrogels were discussed, and an outlook was proposed.

Effects of autologous platelet-rich plasma combined with negative pressure wound therapy for chronic refractory wounds: a Meta-analysis / 中国输血杂志

【Objective】 To systematically evaluate the therapeutic efficacy of autologous platelet-rich plasma combined with negative pressure wound therapy on chronic refractory wounds, and to provide reference for clinical treatment. 【Methods】 Randomized controlled trials of autologous platelet-rich plasma combined with negative pressure wound therapy for the treatment of chronic refractory wounds were included in the databases of CNKI, Wan fang, VIP, PubMed, Embase and Cochrane Library from the time of database construction to November 2022. After literature screening, data extraction and quality evaluation, Meta analysis was performed using Stata 15.1 software. 【Results】 After screening, a total of 11 Chinese literatures that met the criteria of this paper were retrieved, involving a total of 359 patients with chronic refractory wounds. The observation group was treated with autologous platelet-rich plasma combined with negative pressure wound therapy, and the control group was treated with negative pressure wound therapy alone. Meta-analysis suggested that compared with negative pressure wound therapy alone, autologous platelet-rich plasma combined with negative pressure wound therapy shortened wound healing time [WMD=-6.08, 95%CI (-7.77, -4.40), P<0.05]. The hospitalization was shortened [WMD=-8.24, 95%CI (-11.55, -4.94), P<0.05], the pain score was decreased [WMD=-1.73, 95%CI (-2.06, -1.40), P<0.05], and the positive rate of bacterial culture on the wound was decreased [RR=0.28, 95%CI(0.16, 0.49), P<0.05], the wound treatment effect was good [RR=1.28, 95%CI(1.17, 1.41), P<0.05]. 【Conclusion】 Based on current studies, compared with the negative pressure wound therapy alone, autologous platelet-rich plasma combined with negative pressure wound therapy can effectively promote the healing of chronic refractory wounds, shorten the hospital stay, reduce pain and infection, and the clinical treatment effect is better.

Progress in clinical researches of platelet-rich plasma in the treatment of chronic refractory wounds / 中国输血杂志

Cutaneous chronic wounds are a major global health burden in continuous growth due to population aging and the higher incidence of chronic diseases, such as diabetes. In the process of spontaneous wound healing, growth factors play a vital role. Thanks to the high content of growth factors in platelet rich plasma(PRP), more and more PRP has been used to treat chronic refractory wounds, including diabetic ulcer, pressure ulcer, venous ulcer, and burns, etc., and has achieved significant results. Given the short duration of local growth factor release in the wound when PRP is applied alone, some studies have combined PRP with different tissue biology materials, such as hyaluronic acid, chitosan, and chitosan derivatives, to achieve better therapeutic results. In this paper, the preparation method of PRP, the mechanism of growth factors, the effect of PRP on wound repair, the combined application of PRP with repair materials and the advantages and disadvantages of PRP are reviewed.

The clinical application of platelet-rich plasma to repair chronic refractory wounds: A retrospective study and literature retrieval evidence analysis / 中国组织工程研究

BACKGROUND: Autologous platelet-rich plasma (PRP) has a certain repair effect on refractory wounds, which can accelerate the healing of soft tissue. The PRP gel can prevent the loss of platelets, make platelets survive for a long time and secrete growth factors, which is conducive to wound healing. OBJECTIVE: To observe the effects of PRP on the healing of chronic refractory wounds and analyze the research status. METHODS: Twenty-two patients with refractory wounds, including eight cases of diabetic ulcer, three cases of traumatic ulcer, three cases of traumatic bone ununion, two cases of bone exposure after electric burn, and six cases of radiation ulcer, were treated with PRP gel after surgical debridement. Dressing and PRP gel were regularly changed, and wound healing was observed. The first author retrieved WanFang for the literature addressing the treatment of chronic refractory wounds with autologous PRP gel published in recent 10 years, and analyzed the research status. RESULTS AND CONCLUSION: (1) In all of chronic wounds (22 cases), complete healing was observed In 11 cases as well as in 5 cases after skin flap transfer, and the remaining 6 cases were subjected to skin grafting. There was no disease transmission or immune rejection. The results indicate that the use of PRP gel is a safe and effective method for chronic refractory wounds. (2) Thirty-two relevant literatures were enrolled in literature retrieval. Although the number of relevant articles published from 2016 to 2018 increased yearly, there is no convincing evidence for autologous PRP in the treatment of chronic refractory wounds. There is lack of large-scale, multicenter, prospective, randomized controlled studies. How to standardize PRP preparation and use to ensure a curative effect with high stability remains to be elucidated.

Effect of mebt/mebo on expression of mmp-2 and mmp-9 in chronic refractory wounds / 中国药理学通报

Aim To investigate the mechanism of MEBT/MEBO in promoting chronic wound healing by MMP-2 and MMP-9. Methods Ninety Wistar rats were randomly divided into five groups: MEBO group, rb-bFGF group, chronic wound group, acute wound group and blank group. Eighteen rats in each group were modeled as chronic refractory wounds. The ex-pression of MMP-2 and MMP-9 in wound tissues, on 3rd and 14th day, was detected by ELISA, Western blot and qRT-PCR. Results ( 1 ) Compared with chronic wound group, the time of wound healing was obviously shorter and the rate of wound healing was higher in MEBO group and rb-bFGF group ( P < 0. 05) ; meanwhile, the growth of wounds and the pathological changes of wounds were better in MEBO group and rb-bFGF group. (2) On 3rd day, the ex pression of MMP-2 and MMP-9 in MEBO group and rb-bFGF group was higher than that in chronic wound group (P <0. 05) ; however, on 14th day, the expression of MMP-2 and MMP-9 in MEBO group and rb-bF-GF group also decreased (P < 0. 05). (3) Compared with chronic wound group, the expression of MMP-2 and MMP-9 in MEBO group and rb-bFGF group increased on 3rd day (P <0. 05) , while the expression of MMP-2 and MMP-9 decreased in MEBO group and rb-bFGF group on 14th day (P <0.05). Conclusions MEBT/MEBO promoting chronic wound healing may be associated with regulating MMP-2 and MMP-9 to participate in the degradation and remodeling of ECM.

Characteristics of patients with tuberculous wounds and non-tuberculous chronic refractory wounds in single center / 中华烧伤杂志

Objective@#To explore the characteristics of patients with tuberculous wounds and non-tuberculous chronic refractory wounds in single center.@*Methods@#From January 2010 to June 2017, 43 patients with tuberculous wounds and 44 patients with non-tuberculous chronic refractory wounds admitted to the Department of Burns and Plastic Surgery of the Eighth Medical Center of the General Hospital of the Chinese People′s Liberation Army were conforming to the inclusion criteria. The patients were assigned to tuberculous wound group and non-tuberculous wound group, respectively, and their clinical records were retrospectively analyzed. The gender, place of residence, history of trauma, time of wound formation, time of wound diagnosis, number and length of hospital stay, age, wound site, wound area, sinus occurrence, number of dressing change, number of operation, vacuum sealing drainage (VSD) treatment, recovery, source of medical expense, expense paid by social basic medical insurance and the self-payment of patients in the 2 groups were investigated. Data were processed with independent sample t test and chi-square test.@*Results@#(1) Except for gender (χ2=0.019, P>0.05), there were significantly statistical differences in place of residence, history of trauma, time of wound formation, time of wound diagnosis, number and length of hospital stay between patients in tuberculous wound group and non-tuberculous wound group (χ2=4.535, 27.651, t=7.252, 16.131, 4.663, 7.416, P<0.05 or P<0.01). (2) There was no statistically significant difference in the composition ratio of age between patients in tuberculous wound group and non-tuberculous wound group (χ2=11.522, P>0.05). (3) The wounds of patients in tuberculous wound group were more common in the chest, and the wounds of patients in non-tuberculous wound group were more common in the lower limbs. There was statistically significant difference in the composition ratio of the wound sites between patients in the two groups (χ2=28.450, P<0.01). (4) There were statistically significant differences in wound area, sinus occurrence, number of dressing change, number of operation between patients in tuberculous wound group and non-tuberculous wound group (t=-8.524, 9.846, -15.426, 4.663, P<0.01). There were no statistically significant differences in VSD treatment and recovery between patients in the two groups (χ2=0.032, 0.111, P>0.05). (5) The medical expenses of patients in tuberculous wound group from social basic medical insurance, free medical service, the self-paid, and military medical services accounted for 48.8% (21/43), 7.0% (3/43), 39.5% (17/43), and 4.7% (2/43), respectively. The medical expenses of patients in non-tuberculous wound group from social basic medical insurance, free medical service, the self-paid, and military medical services accounted for 59.1% (26/44), 4.5% (2/44), 29.5% (13/44), and 6.8% (3/44), respectively. There was no statistically significant difference in the composition ratio of sources of medical expense between patients in the two groups (χ2=1.154, P>0.05). (6) There were statistically significant differences in expenses for diagnosis, medicine, surgery, examination, laboratory test, and bed, and total expenses paid by social basic medical insurance and the self-payment between patients in tuberculous wound group and non-tuberculous wound group (t=45.051, 39.995, 64.212, 32.584, 8.754, 43.991, 15.671, 17.640, 65.155, 35.546, 35.903, -4.329, 3.344, 12.984, P<0.01).@*Conclusions@#Compared with those of patients with non-tuberculous chronic refractory wounds, the tuberculous wounds of patients have longer formation time, the diagnosis and treatment of the wounds are difficult, their wounds are mostly distributed in the chest and often accompanied by sinus formation, and patients with the wounds have long hospital stay and high medical expenses. Besides, the medical expenses for treating wounds of patients in the two groups are mainly paid by social basic medical insurance and the patients themselves.

Analysis of differential gene expressions of inflammatory and repair-related factors in chronic refractory wounds in clinic / 中华烧伤杂志

Objective@#To compare the tissue morphology and gene expressions of inflammatory and repair-related factors in chronic refractory wound tissue including pressure ulcers and diabetic feet.@*Methods@#During August 2016 to September 2017, 10 samples of prepuce were collected after circumcision of 10 urological patients [all male, aged (38±4) years old] admitted in the First Affiliated Hospital of Nanchang University and included in normal skin group, samples of tissue around the edge of wounds with blood supply were collected from 9 heat or electric burn patients [6 male patients, 3 female patients, aged (51±8) years old], 13 pressure ulcer patients [9 male patients, 4 female patients, aged (51±14) years old] and 10 diabetic foot patients [8 male patients, 2 female patients, aged (61±10) years old] during the operations. The samples were divided into burn wound group (9 samples), pressure ulcer group (13 samples), and diabetic foot group (10 samples). Ten slices were taken from pressure ulcer group and diabetic foot group respectively, and 5 slices in each group were used to observe the tissue morphology and expressions of Ki67 and CD31 of wounds respectively with immunofluorescence method. Ten samples from normal skin group, 9 samples from burn wound group, 13 samples from pressure ulcer group, and 10 samples from diabetic foot group were collected for analysis of mRNA expressions of vascular endothelial growth factor 192 (VEGF192), transforming growth factor β (TGF-β), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) , interleukin-1β (IL-1β), IL-6, and tumor necrosis factor α (TNF-α) by real time fluorescent quantitative reverse transcription polymerase chain reaction. Data were processed with Mann-Whitney U test and Kruskal-Wallis rank-sum test.@*Results@#(1) The expression level of Ki67 in diabetic foot group (390±100) was higher than that of pressure ulcer group (182±14, Z=-2.611, P<0.01). (2) Although there were a large number of vascular endothelial cells (CD31 positive cells) in wounds of diabetic foot group, their distribution was disordered and failed to form intact lumen. There were less vascular endothelial cells in wounds of pressure ulcer group than those of diabetic foot group, but the complete lumen was formed. (3) The mRNA expression levels of VEGF192 in wounds of burn wound group, pressure ulcer group, and diabetic foot group were significantly lower than the level in normal skin group (H=13.72, 30.50, 15.20, P<0.05 or P<0.01), and the level was the lowest in pressure ulcer group. The mRNA expression level of VEGF192 in wounds of pressure ulcer group was significantly lower than that of diabetic foot group (H=15.30, P<0.01). Compared with that of normal skin group, the mRNA expression level of TGF-β in wounds of burn wound group showed no significant difference (H=-9.50, P>0.05), while the mRNA expression levels of TGF-β in wounds of pressure ulcer group and diabetic foot group were significantly decreased (H=18.04, 14.50, P<0.01). The mRNA expression level of TGF-β in wounds of pressure ulcer group was similar to that of diabetic foot group (H=3.54, P>0.05). (4) Compared with those of normal skin group, the mRNA expression levels of VCAM-1 in wounds of burn wound group and pressure ulcer group were significantly increased (H=-22.50, -11.50, P<0.05 or P<0.01), and there was no significant difference in the mRNA expression level of VCAM-1 in wounds of diabetic foot group (H=10.00, P>0.05); the mRNA expression level of ICAM-1 in wounds of burn wound group showed no significant difference (H=-9.50, P>0.05), and the levels of ICAM-1 in wounds of pressure ulcer group and diabetic foot group were significantly decreased (H=16.50, 16.50, P<0.01). The mRNA expression level of VCAM-1 in wounds of pressure ulcer group was significantly higher than that of diabetic foot group (H=-21.50, P<0.01), the mRNA expression level of ICAM-1 in wounds of pressure ulcer group was similar to that of diabetic foot group (H=0, P>0.05). (5) Compared with those of normal skin group, except for the mRNA expression level of IL-1β in wounds of diabetic foot group showed no significant difference (H=-10.00, P>0.05), the mRNA expression levels of IL-1β in wounds of burn wound group and pressure ulcer group were significantly increased (H=-32.50, -21.50, P<0.01); the mRNA expression levels of IL-6 were significantly increased in wounds of burn wound group, pressure ulcer group, and diabetic foot group (H=-17.50, -30.50, -11.80, P<0.05 or P<0.01); except for the mRNA expression level of TNF-α in wounds of burn wound group showed no significant difference (H=-9.50, P>0.05), the mRNA expression levels of TNF-α in wounds of pressure ulcer group and diabetic foot group were significantly decreased (H=18.04, 14.50, P<0.01). The mRNA expression levels of IL-1β and TNF-α in wounds of pressure ulcer group were significantly lower than those of burn wound group (H=11.00, 27.54, P<0.05 or P<0.01), while the mRNA expression level of IL-6 was significantly higher (H=-13.00, P<0.05). The mRNA expression levels of IL-1β and TNF-α in wounds of diabetic foot group were significantly lower than those of burn wound group (H=22.50, 24.00, P<0.01), while the mRNA expression level of IL-6 showed no significant difference (H=5.70, P>0.05).@*Conclusions@#The phenotypes of diabetic foot and pressure ulcer vary from the expressions levels of proliferating cell nuclear antigen and blood vessels forming ability to the expression levels of growth factors, cell adhesion factors, and inflammatory cytokines.

Thoughts and principles of diagnosis and treatment of chronic refractory wounds in China / 中华烧伤杂志

The correct thoughts and principles of diagnosis and treatment of chronic refractory wounds need to be formulated. Through the relevant domestic and international consensus and based on clinical experience, the Thoughts and principles of diagnosis and treatment of chronic refractory wounds in China is proposed. It is considered that in the diagnosis and treatment of chronic refractory wounds, in the case of fully understanding the patient′s medical history, the following thoughts and principles should be complied in order. (1) Pay attention to the cleanliness of the wound after being cleaned. (2) Reasonably perform debridement to avoid being " excessive" or " not thorough". (3) Reasonably perform examination, diagnosis, and differential diagnosis of pathogenic factors. (4) Treat according to etiology. (5) Find comorbidities and prevent adverse outcomes. (6) Select the correct wound treatment method reasonably and timely. When the conservative wound care treatment is considered, pay attention to embodying the concept of etiological treatment, treat the wound according to the principles of safety, phase, selectivity, and effectiveness, and make a reasonable choice of continuing conservative treatment or surgical treatment in time after completing the preparation of the wound bed. When surgical treatment is considered, pay attention to the selection of reasonable surgical method and donor site, pay attention to the healing rate of surgical wound site and the outcome of donor site, and give reasonable protection to the wound site after surgery. (7) Carry out rehabilitation treatment after wound healing and related health education.