Autologous platelet-rich gel for treatment of diabetic chronic refractory cutaneous ulcers: A prospective, randomized clinical trial.

The purpose of the study is to examine the safety and effectiveness of topical autologous platelet-rich gel (APG) application on facilitating the healing of diabetic chronic refractory cutaneous ulcers. The study was designed as a prospective, randomized controlled trial between January 1, 2007 and December 31, 2011. Eligible inpatients at the Diabetic Foot Care Center of West China Hospital, Sichuan University (China) were randomly prescribed with a 12-week standard treatment of ulcers (the control group) or standard treatment plus topical application APG (the APG group). The wound healing grades (primary endpoint), time to complete healing, and healing velocity within 12 weeks were monitored as short-term effectiveness measurements, while side effects were documented safety endpoints. The rates of survival and recurrence within the follow up were recorded as long-term effectiveness endpoints. Analysis on total diabetic ulcers (DUs) (n = 117) and subgroup analysis on diabetic foot ulcers (DFUs) (n = 103) were both conducted. Standard treatment plus APG treatment was statistically more effective than standard treatment (p < 0.05 in both total DUs and subgroup of DFUs). The subjects defined as healing grade 1 were 50/59 (84.8%) in total DUs and 41/48 (85.4%) in DFUs in the APG group compared with 40/58 (69.0%) and 37/55 (67.3%) in the control group from intent to treat population. The Kaplan-Meier time-to-healing were significantly different between the two groups (p < 0.05 in both total DUs and subgroup of DFUs). No side effects were identified after topical APG application. The long-term survival and recurrence rates were comparative between groups (p > 0.05). This study shows that topical APG application plus standard treatment is safe and quite effective on diabetic chronic refractory cutaneous ulcers, compared with standard treatment.

[Study on the mechanism of autologous platelet-rich gel to treat the refractory diabetic dermal ulcers].

OBJECTIVE: To investigate the mechanism of autologous platelet-rich gel (APG)in the treatment of refractory diabetic dermal ulcers. METHODS: After the treatment of refractory diabetic dermal ulcers with APG at 0, 3, 6, 9, 15 days, the protein levels of PDGF-BB, VEGF, IGF-1, EGF and TGF-beta1 in the granulation tissue were detected by ELISA, while the dimensions of ulcer area were measured at the same time. RESULTS: The areas of ulcers were obviously reduced at the third and fifteen day after APG treatment (P < 0.05). The concentrations of these 5 growth factors in the granulation tissue were began to increase after 3 days treatment, the peak of PDGF-BB emerged at the third day (P < 0.05), and the peaks of VEGF, IGF-1, TGF-beta1 were found at the ninth day (P < 0.05). The concentration of VEGF increased 2.1-fold, IGF-1 increased 1.95-fold, EGF increased 1.75-fold, PDGF-BB increased 1.89-fold and TGF-beta1 increased 1.67-fold. CONCLUSION: The expression of multiple growth factors are increased in granulation tissue of refractory diabetic dermal ulcers after the treatment of APG,which might be one of the mechanism of APG to treat refractory diabetic dermal ulcer.

[The preliminary application of autologous platelet-rich gel used to treat refractory diabetic dermal ulcer].

OBJECTIVE: To assess the effectiveness and security of autologous platelet-rich gel (APG) in the treatment of refractory diabetic dermal ulcers. METHODS: Thirteen diabetic patients with refractory skin lesions were enrolled for this study, and APG was produced by platelet (PLT)-rich plasma (PRP) with thrombin and calcium gluconate. APG treatment consisted of wound dressed with APG, followed by topical washing and cleaning. The APG was then covered with Vaseline gauze and left for 48 to 72 hours, after which the wounds were treated conventionally until the next PLT-gel treatment. The clinical endpoints of the study were the healing rate. RESULTS: A total of 13 patients entered the pilot study. There were no drop-outs in the study. 69.2% ulcers were cured, and especially the ulcer areas were reduced significantly in the first 3 weeks; no adverse reactions were observed. CONCLUSION: Topical therapy with APG may be considered as an effective adjuvant method to treating refractory diabetic dermal ulcer.

[Clinical study on topical bismuth subgallate/borneol (Suile) dressing for treatment of diabetic foot ulcers].

OBJECTIVE: To evaluate the efficacy and safety of Bismuth Subgallate/Borneol (Suile) (BSB) dressing in the treatment of diabetic foot ulcers. METHODS: A two-center, randomized controlled parallel-group comparison study was conducted. Between September 2005 and November 2006, 35 patients with nonhealing diabetic foot ulcer (Wagner 2-3 grade) were recruited and divided randomly into the test group (BSB group, n = 25) and control group (IG group, n = 10). There was no significant difference in general data between 2 groups (P > 0.05). Based on the comprehensive therapy of diabetic foot, ulcers were topically treated by Suile dressing and Intrasite gel in the BSB group and IG group, respectively. The ulcer area was measured once a week. Ulcer bleeding was observed and acceptance of the dressing was inquired each week. RESULTS: Of the patients, 22 patients in the BSB group and 8 in the IG group completed the clinical trial. Intention to treat (ITT) analysis indicated that the results were excellent in 19 (76%) cases, good in 3 cases (12%), fair in 1 case (4%), and poor in 2 cases (8%) in the BSB group. In the IG group, the results were excellent in 8 cases (80%) cases, fair in 1 case (10%), and poor in 1 case (10%). Per-protocol (PP) analysis showed that the results were excellent in 19 cases (86%) and good in 3 cases (14%) in the BSB group, and were excellent in 8 cases (100%) in the IG group. The results of ITT and PP analysis all showed no significant difference between 2 groups (P > 0.05). The change trend of ulcer areas in the BSB group was similar to that in the IG group. There was no significant difference in the hemostatic effect between 2 groups (P > 0.05) and the patients were more likely to accept BSB dressings. CONCLUSION: BSB dressings is an effective, safe, and generally well-tolerated therapy dressing in the treatment of diabetic foot ulcers.

[A comparison of digital planimetry and transparency tracing based methods for measuring diabetic cutaneous ulcer surface area].

OBJECTIVE: To assess the reliability of diabetic cutaneous ulcer surface area (DCUSA) measurement using digital planimetry method (A) and transparency tracing method (B). METHODS: Images of diabetic cutaneous ulcers from 35 inpatients with diabetic skin ulcers from September 2005 to April 2007 were taken by a digital camera once a week or twice a week over a period of 12 weeks, resulting in 305 photographs; the ulcers were traced on a grid with acetate wound tracings, simultaneously. A total of 305 pairs of DCUSA which were calculated respectively throughout digital camera combined with Image J medical imaging software and transparency tracing with grid sheet by two independent observers sequentially were obtained. The intraclass correlation coefficients (ICCs, one-way random effect model) was used as an indicator of chance-corrected agreement to estimate the relative reliability for the interobserver data. Multiple linear regression analysis was also used to measure the relationship of these two methods. RESULTS: DCUSA obtained from method A and obtained from method B was (4.84 +/- 7.73) cm2 and (5.03 +/- 7.89) cm2, respectively; no significant difference was found (P > 0.05). ICCs was high (ICCs = 0.949 for method B and 0.965 for method A), indicating that the relative reliability for the interobserver was excellent. The method A were highly correlated with measurements obtained from method B (r = 0.957, P < 0.05). CONCLUSION: The digital planimetry method described in this study represents a simple, practical, without any wound damage and contamination, and inexpensive technique to accurately evaluate the areas of diabetic cutaneous ulcers. The photographic technique combined with Image J medical imaging software should be considered for wound measurement.

[Preparation of autologous platelet-rich gel for diabetic refractory dermal ulcer and growth factors analysis from it].

OBJECTIVE: To compare the platelet enrichment ratio of platelet-rich plasma (PRP) prepared by different centrifuge methods and to compare the concentration of growth factors released from autologous platelet-rich gel (APG) with the whole blood. METHODS: Thirteen diabetic patients with refractory skin lesions were enrolled in APG treatment. (1) Three kinds of centrifuge methods were selected for PRP by 11 diabetic patients: A (n = 6): 529 x g for 4 minutes in the first centrifuge and 854 x g for 6 minutes in the second centrifuge; B (n = 5): 313 x g for 4 minutes in the first centrifuge and 1,252 x g for 6 minutes in the second centrifuge; C (n = 5): 176 x g for 5 minutes in the first centrifuge and 1,252 x g for 5 minutes in the second centrifuge. Platelet counted on the whole blood and PRP was determined. The APG, produced by combining the PRP with thrombin and calcium gluconate (10:1) was used by patients. (2) PDGF-BB, TGF-beta1, VEGF, EGF, and IGF-1 were measured in the APG and the whole blood using the enzyme-linked immunosorbent assay method. RESULTS: (1) The average platelet concentration was higher in group B [(1,363.80 +/- 919.74) x 10(9)/L] than in groups A [(779.67 +/- 352.39) x 10(9)/L)] and C [(765.00 +/- 278.78) x 10(9)/L] and the platelet recovery rate was 75.2% +/- 21.0% in group B. (2) The concentration of growth factors all increased with the increasing platelet number. On average, for the whole blood as compared with APG, the PDGF-BB concentration increased from (145.94 +/- 133.24) pg/mL to (503.81 +/- 197.86) pg/mL (P < 0.05); TGF-beta1 concentration increased from (3.31 +/- 2.27) ng/mL to (5.67 +/- 4.80) ng/mL (P < 0.05); IGF-1 concentration increased from (14.54 +/- 35.34) ng/mL to (110.56 +/- 84.36) ng/mL (P < 0.05); and EGF concentration increased from (160.73 +/- 71.10) pg/mL to (265.95 +/- 138.43) pg/mL (P < 0.05). No increase was found for VEGF (P > 0.05). (3) There was positive correlation between the platelet concentration and PDGF-BB and TGF-beta1 (r = 0.627, r = 0.437, P < 0.05). (4) Thirteen diabetic repractory dermal ulcers received APG treatment for 18 times, 9 ulcers (69.2%) and 10 sinuses (88.3%) were cured at the end of 12-week treatment. CONCLUSION: The method of group B is the best centrifuge method. A variety of growth factors are detected and released from the platelets at significant levels in APG. There is positive correlation between the platelet concentration and PDGF-BB and TGF-beta1.

[Application of autologous platelet-rich gel to refractory chronic diabetic cutaneous ulcers].

OBJECTIVE: To review and evaluate the clinical application of autologous platelet-rich gel (APG) in refractory chronic diabetic cutaneous ulcers. METHODS: The latest literature was extensively reviewed, and the potential mechanism of APG for healing diabetic cutaneous ulcers was discussed. RESULTS: APG accelerated the ulcer healing, especially in healing the refractory diabetic cutaneous ulcers, and the high-level growth factors from the platelet releasate were thought to be the major potential mechanism of the APG action. CONCLUSION: APG can promote the healing of refractory chronic diabetic cutaneous ulcers. Topical haemotherapy with APG may be considered an adjuvant treatment of a multidisciplinary process and may be useful to the effective therapy of cutaneous ulcers.