富血小板血浆促进慢性创面愈合研究进展

Normal wound healing is a well-orchestrated process of inflammatory response,cell proliferation,and tissue remodeling.However,this orderly and precise process is impaired in chronic wounds.A series of ...     

Effect of platelet rich plasma gel in a physiologically relevant platelet concentration on wounds in persons with spinal cord injury

The objective of the study was to investigate the use of a 1·3 times normal platelet concentration platelet-rich plasma (PRP) gel to move chronic wounds towards healing in persons with spinal cord injury (SCI). The study design was a case series of 20 persons with SCI with non healing wounds. The outcome measures were, in wound area, volume, undermining and sinus tracts/tunnels (ST/Ts), calculated average, (i) percent of change from baseline, (ii) change per day from baseline, (iii) number of treatments and (iv) number of weeks. In a mean of 4·0, after treatments over 3·4 weeks, the wounds closed on an average of 47·9% in area and 56·0% in volume. Undermining closed on an average of 31·4% using 3·5 treatments over 2·6 weeks. ST/Ts closed on an average of 26·1% after 2·3 treatments over 1·5 weeks. Clinical relevance by percent of positive responders and their response: in area, 90·0% of the subjects responded positively, the average reduction was 53·8%. In volume, 90·0% responded, with an average reduction of 67·3%. Of four subjects with undermining, 75% closed 47·0% on average. Of the three with ST/Ts, 100% closed 26·1% on average. Average haemoglobin and haematocrit levels were below normal. To conclude, 1·3× PRP gel appears to progress chronic, non healing wounds in SCI patients into the granulation phase of healing quickly. Review of the literature shows these results may not be applied to all PRP preparations.     

Topical application of platelet-rich plasma for diabetic foot ulcers: a systematic review

AIM To determine if topical application of platelet-rich plasma(PRP) to diabetic foot ulcers(DFUs) results in superior healing rates. METHODS A systematic review was registered with PROSPERO and performed using PRISMA guidelines. Level Ⅰ-Ⅳ investigations of topical PRP application in DFUs were sought in multiple databases including: MEDLINE, Web of Science, and Cochrane Central Register of Controlled Trials. The search terms used were "platelet rich plasma", "diabetes", "ulcers", and "wound". The Modified Coleman Methodology Score(MCMS) was used to analyze study methodological quality. Study heterogeneity and a mostly non-comparative nature of evidence precluded meta-analysis. Only the outcome measurements used by more than 50% of the studies were included in the data synthesis to increase power of the measurement over that of individual studies. A weighted mean of healing rate per week between PRP group vs controls were compared using two-sample z-tests using P-value of less than 0.05 for significance.RESULTS One thousand two hundred and seventeen articles were screened. Eleven articles(322 PRP subjects, 126 controls, PRP subject mean age 58.4 ± 7.2 years, control mean age 58.7 ± 5.9 years) were analyzed. Six articles were level Ⅱ evidence, four were level Ⅲ, and one article was level Ⅳ. The mean MCMS was 61.8 ± 7.3. Healing rate was significantly faster with PRP application compared to controls(0.68 ± 0.56 cm2/wk vs 0.39 ± 0.09 cm2/wk; P 0.001). Mean heal time to 90% of the original ulcer area was 7.8 ± 2.7 wk and 8.3 ± 3.7 wk for patients in the PRP group and control groups, respectively(P = 0.115). There were significantly lower adverse effects reported with PRP application compared to controls(7 wound infections, 1 contact dermatitis vs 14 wound infections, 1 maceration; P 0.001).CONCLUSION The topical application of PRP for DFUs results in statistically superior healing rates and lower complication rates compared to controls.     

The clinical use of platelet-rich plasma in the promotion of bone healing: A systematic review

Platelet-rich plasma has been shown in several in vitro and animal studies to play a role in promoting new bone formation. A systematic literature review was conducted to identify the current relevant evidence base, searching across multiple sources including Medline, Embase and the Cochrane Library, and finding five clinically relevant articles. Only one was a randomised controlled trial, but this was underpowered for the outcome measure defined. Three studies exclusively concerned children, and included those with congenital limb deformities. Two other reports were case series. Early clinical results suggest that the use of platelet-rich plasma is safe and feasible, but that at present there is no clinical evidence of benefit in either acute or delayed fracture healing.     

The effectiveness of intralesional injection of platelet‐rich plasma in accelerating the healing of chronic ulcers: an experimental and clinical study

The purpose of this prospective experimental and clinical study is to evaluate the effectiveness of the intralesional injection of platelet‐rich plasma (PRP), in the management of non‐healing chronic wounds. Skin defects were created in the ears of 20 white New Zealand rabbits. In the study group, autologous PRP was injected intralesionally. The control group was treated conservatively. Nineteen out of 20 cases of the study group healed within a mean time of 24·9 days. In the control group, seven defects healed within a mean period of 26·7 days, seven ulcers did not heal at day 28 and in six cases a full thickness ear defect was recorded. For a 3‐year period, 26 patients with chronic ulcers underwent surgical debridement and intralesional injection of PRP. A histological study was performed before and 7 days after PRP injection. Ten patients healed within a mean period of 7 weeks. In 16 cases, PRP prepared the wound bed for the final and simpler reconstructive procedure. Intralesional injection is a newly described method for application of PRP and represents an effective therapeutic option when dealing with non‐healing wounds.     

The use of fat grafting and platelet‐rich plasma for wound healing: A review of the current evidence

Fat grafting is becoming a common procedure in regenerative medicine because of its high content of growth factors and adipose derived stem cells (ADSCs) and the ease of harvest, safety, and low cost. The high concentration of ADSCs found in fat has the potential to differentiate into a wide range of wound‐healing cells including fibroblasts and keratinocytes as well as demonstrating proangiogenic qualities. This suggests that fat could play an important role in wound healing. However retention rates of fat grafts are highly variable due in part to inconsistent vascularisation of the transplanted fat. Furthermore, conditions such as diabetes, which have a high prevalence of chronic wounds, reduce the potency and regenerative potential of ADSCs. Platelet‐rich plasma (PRP) is an autologous blood product rich in growth factors, cell adhesion molecules, and cytokines. It has been hypothesised that PRP may have a positive effect on the survival and retention of fat grafts because of improved proliferation and differentiations of ADSCs, reduced inflammation, and improved vascularisation. There is also increasing interest in a possible synergistic effect that PRP may have on the healing potential of fat, although the evidence for this is very limited. In this review, we evaluate the evidence in both in vitro and animal studies on the mechanistic relationship between fat and PRP and how this translates to a benefit in wound healing. We also discuss future directions for both research and clinical practice on how to enhance the regenerative potential of the combination of PRP and fat.     

Comparison of the effects of topical fusidic acid and rifamycin on wound healing in rats

Wound healing is an active and dynamic process that begins from the moment of injury. Any delay in the initiation of the response to injury can prolong the healing process. The aim of this study was to investigate the effects of topically applied fusidic acid and rifamycin on wound healing in a full‐thickness wound model. Ten female Sprague‐Dawley rats, aged 4 months and weighing 200–250 g, were used. Four rifamycin (R), four fusidic acid (F) and four control (K) areas were generated on their backs by using a 5‐mm punch biopsy pen. On the 4th, 7th, 14th and 21st days, biopsies were taken from each wound area of all the rats. Fusidic acid group demonstrated a statistically significant increase of collagen and intensity of fibroblast proliferation on the 21st day of wound healing, whereas in the rifamycin group, healing time was, as expected, similar to physiological wound‐healing phases. Despite the limited number of subjects, topical fusidic acid was found to delay wound healing by prolonging fibroblast proliferation.     

Systematic review of the efficacy of fat grafting and platelet‐rich plasma for wound healing

Adipose‐derived stem cells found in fat grafts may have significant healing properties. When fat is combined with autologous platelet‐rich plasma (PRP), there may be enhanced healing effects due to the pro‐angiogenic and anti‐inflammatory effects of PRP. This study aimed to evaluate the current evidence on fat grafting in combination with PRP for wound healing to establish the efficacy of this technique. A comprehensive search in the MEDLINE, EMBASE, CENTRAL, Science Citation Index, and Google Scholar databases (to March 2017) was conducted to identify studies on fat grafting and PRP for wound healing. Case series of less than 3 cases and studies only describing harvest technique were excluded. The database identified 571 articles, of which 3 articles that used a combination of fat and PRP for wound healing (1 RCT and 2 case series) were included in this review. A total of 69 wounds in 64 patients were treated with an average wound size of 36.32cm². Of these, 67% of wounds achieved complete healing. When reported, the mean time to healing was 7.5 weeks for those who underwent a single treatment. There were no significant complications in any patients. The combination of fat grafting and PRP may achieve adequate wound healing with relatively quick wound healing time compared with standard wound management options. However, evidence is extremely limited, and further studies are required to evaluate its efficacy for wound healing.     

Efficacy of topical platelet-rich plasma and chitosan co-administration on Candida albicans-infected partial thickness burn wound healing

This study aims to evaluate the effects of topical sole and co-administration of Platelet-rich plasma (PRP) and chitosan on the infected burn wounds model by Candida albicans in Wistar rats. A circle partial thickness contact burn wound model occurred via brass a size of 8 mm diameter between the shoulders and after that, 50 μl of a suspension containing C. albicans yeast (5 × 10⁷) colony forming unit was poured on the surface of the wound. The experimental groups included Control, Clotrimazole, PRP and Chitosan+PRP that received any agent, Clotrimazole®, PRP and Chitosan + PRP to treat the wound, respectively. To assess the healing rate, wound size rate, tissue yeast count (TYC) and immunohistochemical staining for heat shock protein 70 (HSP70), HSP 90 and proliferating cell nuclear antigen (PCNA) were conducted. Moreover, enzymatic activity of glutathione peroxidase (GPx), superoxide dismutase (SOD) and malondialdehyde (MDA) rate were evaluated. The results demonstrated that the co-administration of Chitosan + PRP drastically (P < 0.05) decreased the wound size and TYC rate comparing to other groups (P < 0.05). Immunohistochemical results for HSP 70, HSP 90 and PCNA showed positive reactions and increased intensity in all the treated groups comparing to the control group. Activities of GPx and SOD were higher and the level of MDA was lower all treated groups compared to the control group. A topical use of PRP and chitosan can be advantageous in the infected burn wounds healing.     

Quantifying the effects of wound healing risk and potential on clinical measurements and outcomes of severely burned patients: A data-driven approach

IntroductionGiven recent advances in computational power, the goal of this study was to quantify the effects of wound healing risk and potential on clinical measurements and outcomes of severely burned patients, with the hope of providing more insight on factors that affect wound healing.MethodsThis retrospective study involved patients who had at least 10% TBSA% “burned” and three burn mappings each. To model risk to wounds, we defined the variable θ, a hypothetical threshold for TBSA% “open wound” used to demarcate “low-risk” from “high-risk” patients. Low-risk patients denoted those patients whose actual TBSA% “open wound” ≤θ, whereas high-risk patients denoted those patients whose actual TBSA% “open wound” >θ. To consider all possibilities of risk, 100 sub analyses were performed by (1) varying θ from 100% to 1% in decrements of 1%, (2) grouping all patients as either “low-risk” or “high-risk” for each θ, and (3) comparing all means and deviations of variables and outcomes between the two groups for each θ. Hence, this study employed a data-driven approach to capture trends in clinical measurements and outcomes. Plots and tables were also obtained.ResultsFor 303 patients, median age and weight were 43 [29–59] years and 85 [72–99] kg, respectively. Mean TBSA% “burned” was 25 [17–39] %, with a full-thickness burn of 4 [0–15] %. Average crystalloid volumes were 4.25 ± 2.27 mL/kg/TBSA% “burned” in the first 24 h. Importantly, for high-risk patients, decreasing θ was matched by significant increases in PaO2-FiO2 ratio, platelet count, Glasgow coma score (GCS), and MAP. On the other hand, increasing their risk θ was also matched by significant increases in creatinine, bilirubin, lactate, blood, estimated blood loss, and 24-h and total fluid volumes. As expected, for low-risk patients, clinical measurements were more stable, despite decreasing or increasing θ. At a θ of 80%, statistical tests indicated much disparity between high-risk and low-risk patients for TBSA% “burned”, full thickness burn, bilirubin (1.66 ± 1.16 mg/dL versus 0.83 ± 0.65 mg/dL, p = 0.005), GCS (7 ± 2 versus 12 ± 3, p < 0.001), MAP (42 ± 22 mm Hg versus 59 ± 22 mm Hg, p = 0.004), 24-h blood, estimated blood loss, 24-h fluid, total fluid, and ICU length of stay (81 ± 113 days versus 24 ± 27 days, p = 0.002). These differences were all statistically significant and remained significant down to θ = 10%.ConclusionWound healing risk and potential may be forecasted by many different clinical measurements and outcomes and has many implications on multi-organ function. Future work will be needed to further explain and understand these effects, in order to facilitate development of new predictive models for wound healing.     

Platelet-rich plasma versus platelet-poor plasma in the management of chronic diabetic foot ulcers: a comparative study

Non healing diabetic foot ulcers and the resulting potential amputations present significant costs to the health care system and reduce patient quality of life. The goal of diabetic foot ulcer treatment is to obtain wound closure as expeditiously as possible. The use of platelet-rich plasma (PRP) to enhance wound healing has increased dramatically over the last decade. However, controversies exist in the literature regarding the added benefit of this procedure. The aim of this study is to investigate the efficiency of platelet releasate on the healing of chronic diabetic ulcers in comparison with platelet-poor plasma (PPP). This study included 24 patients with chronic diabetic ulcers. They were systematically randomised into two groups: PRP group (n = 12) and PPP group (n = 12). The results showed that healing in PRP group was significantly faster (P < 0·005). PRP enhances healing of chronic diabetic foot ulcers.     

Effect of Acticoat® and Cutinova Hydro® on wound healing

In this study, the effects of the wound‐covering materials, Acticoat^® and Cutinova Hydro^®, on wound healing have been studied in rabbit models with open and tissue‐lost wounds with full‐thickness flank excisions. Rabbits were used as subjects with three groups of four rabbits each, and trial periods of 7, 14 and 21{\uns}days. Four circular wounds, of 1.5 cm diameter were made two on the right (one of them control) and two on the left (one of them control) of the dorsal sides of the abdomen. Acticoat^® and Cutinova Hydro^® were applied on the wounds with suture for a period of 21 days and one each placed on the right and left sides as control with gauze. Biopsy specimens were taken from the animals at the end of the research period to check the length of the epithelium, epithelial thickness, size of wounds, wound granulation tissue formation and histopathological evaluation for clarity. The Acticoat^® group showed better healing and scar formation compared to the Cutinova Hydro^® group by macroscopic examination. Epithelial wound length and clarity in terms of statistical difference occurred on day 21 (P <0.05); while the length of the wound epithelium decreased patency, epithelial thickness on days~7, 14 and 21, showed no statistical differences (P >0.05). As a result, the Acticoat^® wound dressing was determined as a more reliable for the early wound healing. This study has shown the short‐term clinical benefits of hydroactive, polyurethane dressings in the management of acute wounds. However, longer periods of wound healing procedure should be planned for reliable and safe results of wound dressing. It has also been concluded that microbiological analyses should be included for more robust and reliable comparisons.     

Relationship between maceration and wound healing on diabetic foot ulcers in Indonesia: a prospective study

The aim of this study was to clarify the relationship between maceration and wound healing. A prospective longitudinal design was used in this study. The wound condition determined the type of dressings used and the dressing change frequency. A total of 62 participants with diabetic foot ulcers (70 wounds) were divided into two groups: non‐macerated (n = 52) and macerated wounds (n = 18). Each group was evaluated weekly using the Bates–Jensen Wound Assessment Tool, with follow‐ups until week 4. The Mann–Whitney U test showed that the changes in the wound area in week 1 were faster in the non‐macerated group than the macerated group (P = 0·02). The Pearson correlation analysis showed a moderate correlation between maceration and wound healing from enrolment until week 4 (P = 0·002). After week 4, the Kaplan–Meier analysis showed that the non‐macerated wounds healed significantly faster than the macerated wounds (log‐rank test = 19·378, P = 0·000). The Cox regression analysis confirmed that maceration was a significant and independent predictor of wound healing in this study (adjusted hazard ratio, 0·324; 95% CI, 0·131–0·799; P = 0·014). The results of this study demonstrated that there is a relationship between maceration and wound healing. Changes in the wound area can help predict the healing of wounds with maceration in clinical settings.     

Comparative study of conventional and topical heparin treatment in second degree burn patients for burn analgesia and wound healing

Objective

To compare clinical outcome of topical conventional with topical heparin treatment in 2nd degree or partial thickness (PTB) burn patients.

The effect of a new wound dressing on wound healing: Biochemical and histopathological evaluation

Electrospinning process has gained importance in the production of wound dressings in recent years. The wound dressings prepared by electrospinning method provide many advantages over conventional wound dressings. The aim of this study was to assess the histological, biochemical, and immunohistochemical evaluation of collagen/doxycycline loaded nanofiber wound dressing in both acute and chronic wound healing. Full-thickness wound model was created on rats and rats were divided in two main groups: normoglycemic (acute) and hyperglycemic (chronic) groups. Each group was divided into three sub groups: not treated (control) group, treated with nanofiber wound dressing group and treated with commercial product group. Wound closure rates were measured. Oxidative events were investigated by biochemical analyses. In addition to histological studies, matrix metalloproteinase, tissue inhibitor of metalloproteinase, vascular endothelial growth factor, basic-fibroblast growth factor, and von Willebrand factor levels were investigated with immunohistochemical studies. According to the biochemical analyses, it was concluded that the nanofiber wound dressing helps to increase antioxidant capacity and decrease lipid peroxidation. Immunohistochemical studies showed that nanofiber wound dressing enhanced angiogenesis and shortened the inflammatory phase. It was concluded that an effective and safe prototype nanofiber wound dressing, which has similar wound healing effect to the commercial product, has been developed to be used in acute or chronic wound treatment.     

Comparative analysis of leucocyte poor vs leucocyte rich platelet-rich plasma in the management of lateral epicondylitis: Systematic review & meta-analysis of randomised controlled trials

Study designSystematic Review & Meta-analysis.ObjectivesWe aim to comparatively analyse the efficacy and safety of using leucocyte-poor platelet rich plasma (LP-PRP) against leucocyte-rich platelet rich plasma (LR-PRP) in the management of lateral epicondylitis.Materials and methodsWe conducted independent and duplicate electronic database searches including PubMed, Embase, Web of Science and Cochrane Library till September 2020 for randomised controlled trials analyzing the efficacy and safety of LP-PRP and LR-PRP in the management of lateral epicondylitis. Visual Analog Score(VAS) for pain, Disabilities of the Arm, Shoulder and Hand (DASH) Score, Patient Reported Tennis-Elbow Evaluation (PRETEE) Score, Mayo Elbow Performance Score(MEPS) and adverse events were the outcomes analyzed. Analysis was performed in R-platform using OpenMeta[Analyst] software.ResultsWe performed a single arm meta-analysis of 26 studies involving 2034 patients. On analysis it was noted that significant improvement was noted in the VAS for pain (p < 0.001), DASH score (p < 0.001), PRETEE score (p < 0.001) and MEPS (p < 0.027) compared to their pre-operative state. No significant increase in adverse events were noted compared to the control group (p = 0.170). While stratifying the results based on the type of PRP used, no significant difference was noted between the use of LP-PRP or LR-PRP in any of the above-mentioned outcome measures.ConclusionPRP is a safe and effective treatment option for lateral epicondylitis with clinical improvements in pain and functional scores and both types of PRP (LR-PRP & LP-PRP) offer similar results.     

Effect of opium dependency on secondary intention wound healing in a rat model: an experimental study

Opium dependency is a social and health problem in some middle eastern countries like Iran. Many of these people may require surgery. This study investigates the effects of opium dependency on histological parameters of secondary intention wound healing in rat. A full‐thickness wound (2 × 2 cm in diameters) was created on the dorsum of two groups of rats, a normal control group and a second group of rat depended to opium (Badawy's method). Several times during 14 days postwounding, the wound was excised with peripheral margins of normal skin and was evaluated for cellular population, reepithelialisation and revascularisation. Results are presented as the mean ± standard error. Data were compared by an unpaired t‐test or analysis of variance. Histological examination of the wound tissue showed evidence of increased population of fibroblasts, decreased recruitment of neutrophile and plateau of macrophage cells in opium depended animals comparing with control group. In the depended animals, reepithelialisation was seen to be enhanced significantly, while prohibiting progression of revascularisation. This study shows that opium dependency enhances reepitheliazation as well as tissue recruitment of fibroblasts; thereby probable enhancement of secondary intention wound healing.     

Platelet-rich plasma for the treatment of patellar tendinopathy: clinical and imaging findings at medium-term follow-up

Purpose

The purpose of this study was to evaluate the efficacy of multiple platelet-rich plasma (PRP) injections on the healing of chronic refractory patellar tendinopathy, and report the quality and duration of the clinical improvement up to a medium-term follow-up.

Methods

Forty-three patients (mean age, 30.6 years; mean BMI, 24.7; 42 men, one woman) affected by chronic patellar proximal tendinopathy were enrolled in this trial. Eleven patients were affected by bilateral tendinopathy. They underwent three ultrasound guided intra-tendinous injections of five millilitres PRP, two weeks apart from each other. Patients were prospectively evaluated initially, then after two, six, and up to mean 48.6 ± 8.1 months of follow-up (minimum evaluation at 36 months). The following evaluation tools were used: Blanzina, VISA-P, EQ-VAS for general health, and Tegner scores. Patients’ overall satisfaction and time to return to sport were also reported.

Results

Good and stable results were documented over time, with the VISA-P score increasing from 44.1 ± 15.6 at baseline to 61.4 ± 22.2 at two months, 76.6 ± 25.4 at six months, and 84.3 ± 21.6 at four years’ follow-up. The same trend was confirmed by the other scores used, and 80 % of the patients were satisfied and returned to previous sports activities. Significantly poorer results were obtained in patients with a longer history of symptoms, and poor results were also observed in bilateral lesions. No correlation between ultrasonographic and clinical findings could be found.

Conclusions

Multiple injections of PRP provided a good clinical outcome for the treatment of chronic recalcitrant patellar tendinopathy with stable results up to medium-term follow-up. Patients affected by bilateral pathology and presenting a long history of pain obtained significantly poorer results.