Efficacy of platelets in bone healing: A systematic review on animal studies

In presence of large bone defects, delayed bone union, non-union, fractures, and implant surgery, bone reconstruction may be necessary. Different strategies have been employed to enhance bone healing among which the use of autologous platelet concentrates. Due to the high content of platelets and platelet-derived bioactive molecules (e.g., growth factors, antimicrobial peptides), they are promising candidates to increase bone healing. However, a high heterogeneity of both preclinical and clinical studies resulted in contrasting results. Aim of the present systematic review was to evaluate the efficacy of platelet concentrates in animal models of bone regeneration, considering the possible factors which might affect the outcome. An electronic search was performed on MEDLINE and SCOPUS databases. Animal studies with a minimum follow up of 2 weeks and a sample size of five subjects per group, using platelet concentrates for bone regeneration, were included. Articles underwent risk of bias assessment and further quality evaluation was done. Sixty studies performed on six animal species (rat, rabbit, dog, sheep, goat, and mini-pig) were included. The present part of the review considers only studies performed on rats and rabbits (35 articles). The majority of the studies were considered at medium risk of bias. Animal species, healthy models, platelet, growth factors and leukocytes concentration, and type of bone defect seemed to influence the efficacy of platelet concentrates in bone healing. However, final conclusions were not be drawn, since only few included studies evaluated leukocyte, growth factor content, or presence of other bioactive molecules in platelet concentrates. Further studies with a standardized protocol including characterization of the final products will provide useful information for clinical application of platelet concentrates in bone surgery

Efficacy of platelet concentrates in bone healing: A systematic review on animal studies – Part B: Large-size animal models

In the presence of large bone defects, delayed bone union, or nonunion and fractures, bone reconstruction may be necessary. Different strategies have been employed to enhance bone healing among which the use of autologous platelet concentrates (APCs). Due to the high content of platelets and platelet-derived bioactive molecules (e.g., growth factors, antimicrobial peptides), they are promising candidates to enhance bone healing. However, both preclinical and clinical studies produced contrasting results, mainly due to a high heterogeneity in study design, objectives, techniques adopted, and outcomes assessed. The aim of the present systematic review was to evaluate the efficacy of APCs in animal models of bone regeneration, considering the possible factors that might affect the outcome. An electronic search was performed on MEDLINE and Scopus databases. Comparative animal studies with a minimum follow up of 2 weeks, at least five subjects per group and using APCs for regeneration of bone defects were included. Articles underwent risk of bias assessment and quality evaluation. Fifty studies performed on six animal species (rat, rabbit, dog, sheep, goat, mini-pig) were included. The present part of the review considers studies performed on small ruminants, dogs, and mini-pigs (14 articles). The majority of the studies were considered at low risk of bias. In general, APCs’ adjunct positively affected bone regeneration. Animal species, platelet and growth factors concentration, type of bone defect and of platelet concentrate used seemed to influence their efficacy in bone healing. However, sound conclusions were not drawn since too few studies for each large-size animal model were included. In addition, characterization of APCs’ content was performed only in a few studies. Further studies with a standardized protocol including characterization of the final products will provide useful information for translating the results to clinical application of APCs in bone surgery

Platelet-rich plasma to treat experimentally-induced skin wounds in animals: A systematic review and meta-analysis

<div><p>The objective of the study was to review current literature to determine whether the topical application of platelet-rich plasma (PRP) promotes healing in experimentally-induced full-thickness skin wounds in animals. The hypothesis was that the adjunct of PRP has a positive effect on wound healing. An electronic search was carried out on the following databases: Web of Science, Cochrane Library, PubMed, Research Gate, Cochrane Wounds Group, Veterinary Information Network. No publication date nor language restrictions were applied. Randomised and not randomised controlled clinical trials comparing PRP with placebo or with other treatments were included. The reduction of open wound area in PRP-treated (test) wounds compared to control wounds was the primary outcome. Secondary outcomes were healing time and number of healed cases in test group compared to control. The following effect sizes were calculated: the Hedges’ g for continuous variables; the odds ratio for binary data. Eighteen controlled clinical trials were included in the qualitative and quantitative synthesis, with a total of 661 wounds. All studies were published in the period 2007–2016. Eight studies were carried out on rodent/lagomorph mammals and 10 on non-rodent/lagomorph mammals. In all included studies, control wounds underwent placebo or were left untreated. The PRP group showed a better healing performance than the control group in each outcome. The effect size was statistically significant considering the primary outcome and the overall aggregation of the three outcomes. The effect size, although in favour of the treatment with PRP, was not significant considering the healing time and the number of healings. The overall heterogeneity was mild or moderate. Five studies reported a high risk of selection bias. The publication bias was always mild or absent. The results support the hypothesis of the positive effects of the PRP when compared to control groups in the treatment of experimentally-induced full-thickness skin wounds in animals. PRP can therefore be considered an effective adjunctive therapy in stimulating second intention healing of acute wounds in healthy animals.</p></div

Concours pour l'agrégation (1906-1907) [section de pathologie interne et de médecine légale]. Titres et travaux scientifiques du Dr Charles Lesieur,...

<p>Heterogeneity analysis: Q = 50.87; df = 17; P = 0.000; I² = 66.58; T² = 0.16; T = 0.40. (ES: effect size; 95%CI: confidence interval; W: weight; V: variance; SE: standard error; Sig: statistical significance (p-value); N: total sample size; Q, I₂, T₂ and T: indexes of heterogeneity; df: degrees of freedom).</p

Publication bias analysis, funnel plot, meta-analysis 2: Healing time.

<p>Trim and fill analysis: trimmed studies = 0. Overall effect size (observed): ES = 0.10; LL = -0.68; UL = 0.89; P = 0.795; V = 0.16; SE = 0.40. Overall effect size (estimated): ES = 0.10; LL = -0.68; UL = 0.89; P = 0.795; V = 0.16; SE = 0.40. Egger’s linear regression test: intercept = -21.36; t = -2.66; P = 0.117.</p

Publication bias analysis, funnel plot, meta-analysis 1: Reduction of open wound area.

<p>Trim and fill analysis: trimmed studies = 0. Overall effect size (observed): ES = 0.40; LL = 0.16; UL = 0.65; P = 0.001; V = 0.02; SE = 0.13. Overall effect size (estimated): ES = 0.40; LL = 0.16; UL = 0.65; P = 0.001; V = 0.02; SE = 0.13. Egger’s linear regression test: intercept = 0.60; t = 0.52; P = 0.611.</p

Selection of primary studies: PRISMA flow diagram.

<p>Selection of primary studies: PRISMA flow diagram.</p

Assessment of the moderators’ effect on the combined overall outcome.

<p>Assessment of the moderators’ effect on the combined overall outcome.</p

Sensitivity analysis, meta-analysis 4: Combination of all outcomes.

<p>(ES: effect size; 95%CI: confidence interval; W: weight; V: variance; SE: standard error; Sig: statistical significance (p-value); N: total sample size; N1: sample size PRP group; N2: sample size control group).</p

Characteristics of excluded studies in alphabetical order.

<p>Characteristics of excluded studies in alphabetical order.</p