Use Of Autologous Growth Factors Research Articles

Comparison of platelet-rich plasma vs hyaluronic acid injections in patients with knee osteoarthritis: A protocol for a systematic review and meta-analysis.

Background:Knee osteoarthritis (KOA) is a progressive joint disease involving intraarticular and periarticular structures. In recent years, there has been increasing interest in the use of autologous growth factors, such as intraarticular injections of platelet-rich plasma (PRP), to treat KOA. It is necessary to update the research and reevaluate the efficacy and safety of PRP to provide up-to-date evidence for KOA management. Therefore, we provide a protocol for a systematic review of PRP for KOA.Methods:The aim of this study was to retrieve papers on the topic of PRP treatment for KOA in electronic databases including PubMed, Embase, and the Cochrane Library. The search will include studies that were published from the time the databases were established until April 2018. The entire process will include study selection, data extraction, risk of bias assessment, and meta-analyses.Results:The literature will provide a high-quality analysis of the current evidence supporting PRP for KOA based on various comprehensive assessments including the Western Ontario and McMaster Universities Osteoarthritis Index, visual analog scale scores, International Knee Documentation Committee scores, Lequesne index scores, and adverse events.Conclusion:This proposed systematic review will provide up-to-date evidence to assess the effect of PRP treatment for patients with KOA.PROSPERO registration number:CRD42018108825.

To evaluate the role of platelet-rich plasma in healing of acute diaphyseal fractures of the femur

PurposeNew research is focusing on the use of autologous growth factors to increase the effect of bone fracture healing while decreasing the amount of healing time for the patient. Platelets have been demonstrated to be the natural storage vessel for several growth factors and cytokines that promote blood coagulation, tissue repair, and the process of bone mineralization. The present study aims to evaluate the role of platelet-rich plasma (PRP) in healing of acute femoral shaft fractures radiologically. We hypothesize that it provides artificial hematoma and releases various growth factors. MethodsThis prospective randomized study was carried out in 72 patients of traumatic fracture of the femoral shaft operated with interlocking nails (closed or open). Patients were divided into two groups: study group A (n = 33) treated with intramedullary nailing & PRP injection/gel application in the same setting; and control group B (n = 39) treated with intramedullary nailing without PRP application. Both groups were further divided into two subgroups. Study group included subgroup A1 (n = 14) operated with closed intramedullary nailing and PRP injection at the fracture site under radiological control, and subgroup A2 (n = 19) operated with open intramedullary nailing and PRP gel along with fibrin membrane application at the fracture site; while control group included subgroup B1 (n = 16) operated with closed intramedullary nailing, and subgroup B2 (n = 23) operated with open intramedullary nailing. Radiological assessment of fracture healing was done by measuring the cortex to callus ratio every month till union at 6 months. ResultsMeasurements of mean cortex to callus ratio revealed significant difference between the groups A & B at third and fourth months. Measurements of mean cortex to callus ratio did not reveal significant difference between the subgroups at first and sixth months. A statistically significant difference was observed between subgroups A1 & B2 and B1 & B2 at the second month; between subgroups A1 & B2, A2 & B2 and B1 & B2 at the third month; and between subgroups A1 & B2 at fourth and fifth months. ConclusionPRP has no effect on femoral shaft fracture healing treated with closed intramedullary nailing. However, PRP and matrix scaffold provided by fibrin membrane may provide an artificial hematoma effect in the initial phase of healing in open or failed closed intramedullary nailing.

Bone substitutes and expanders in Spine Surgery: A review of their fusion efficacies.

A narrative review of literature. This manuscript intends to provide a review of clinically relevant bone substitutes and bone expanders for spinal surgery in terms of efficacy and associated clinical outcomes, as reported in contemporary spine literature. Ever since the introduction of allograft as a substitute for autologous bone in spinal surgery, a sea of literature has surfaced, evaluating both established and newly emerging fusion alternatives. An understanding of the available fusion options and an organized evidence-based approach to their use in spine surgery is essential for achieving optimal results. A Medline search of English language literature published through March 2016 discussing bone graft substitutes and fusion extenders was performed. All clinical studies reporting radiological and/or patient outcomes following the use of bone substitutes were reviewed under the broad categories of Allografts, Demineralized Bone Matrices (DBM), Ceramics, Bone Morphogenic proteins (BMPs), Autologous growth factors (AGFs), Stem cell products and Synthetic Peptides. These were further grouped depending on their application in lumbar and cervical spine surgeries, deformity correction or other miscellaneous procedures viz. trauma, infection or tumors; wherever data was forthcoming. Studies in animal populations and experimental in vitro studies were excluded. Primary endpoints were radiological fusion rates and successful clinical outcomes. A total of 181 clinical studies were found suitable to be included in the review. More than a third of the published articles (62 studies, 34.25%) focused on BMP. Ceramics (40 studies) and Allografts (39 studies) were the other two highly published groups of bone substitutes. Highest radiographic fusion rates were observed with BMPs, followed by allograft and DBM. There were no significant differences in the reported clinical outcomes across all classes of bone substitutes. There is a clear publication bias in the literature, mostly favoring BMP. Based on the available data, BMP is however associated with the highest radiographic fusion rate. Allograft is also very well corroborated in the literature. The use of DBM as a bone expander to augment autograft is supported, especially in the lumbar spine. Ceramics are also utilized as bone graft extenders and results are generally supportive, although limited. The use of autologous growth factors is not substantiated at this time. Cell matrix or stem cell-based products and the synthetic peptides have inadequate data. More comparative studies are needed to evaluate the efficacy of bone graft substitutes overall.

Extraction Socket Management Utilizing Platelet Rich Fibrin: A Proof-of-Principle Study of the "Accelerated-Early Implant Placement" Concept.

Dental implants are widely accepted as the golden standard for the rehabilitation of an edentulous site following the extraction of a tooth. The ideal time for implant placement is dependent on the time required for partial or complete tissue healing and the adequacy of socket dimensions. The use of autologous growth factors is a promising new concept that aids clinicians in minimizing treatment time and increasing patient satisfaction. The purpose of this paper is to introduce a protocol for "accelerated-early" implant placement. In this protocol, platelet rich fibrin is employed to accelerate soft and hard tissue healing and to provide a better-healed recipient site for accelerated, early implant placement. Histological analysis revealed that at 6 weeks postextraction, the application of our approach resulted in delicate newly formed bone showing intense osteoblastic activity surrounded by connective tissue as well as areas of mineralized tissue. The present study is a proof-of-principle study of the acceleration of the physiologic postextraction healing sequelae with the use of autologous growth factors. The accelerated-early implant placement concept is a bioengineered protocol that may aid clinicians to achieve increased primary stability, by placing implants in ridges in an advanced stage of bone healing, while offering patients the benefits associated with early implant placement. Controlled studies are warranted to verify the reproducibility of this treatment concept and identify specific indications where the use of the presented technique can lead to significant clinical results.

The growing evidence for the use of platelet-rich plasma on diabetic chronic wounds: A review and a proposal for a new standard care.

Nonhealing chronic wounds and exposed tendons, bones and joints are very challenging to cure specially for diabetic patients. Plastic surgeons have a new weapon to enhance wound healing with the use of autologous growth factors. Recently, the process of fabrication of platelet-rich plasma (PRP) has been simplified. The goal of this literature review is to summarize the evidenced-based body of knowledge regarding the treatment of diabetic chronic wounds by PRP. A PubMed and Cochrane search (1978-2015) was performed and all studies assessing the clinical effect of PRP on the healing of diabetic chronic wounds were included. The screening retrieved 7,555 articles and 12 studies were included. On six randomized studies included, five found significant benefits for the use of PRP on diabetic chronic foot ulcers and the sixth randomized study did not publish a statistical analysis but found favorable outcomes. The two other controlled studies included found significant benefits regarding the healing rate and the four uncontrolled studies included showed high rates of healing with the adjunction of PRP. Regarding the method of use, PRP was applied on the wound as a gel twice a week (41.7% of studies) or once a week (33.3% of studies). In conclusion, 87.5% of controlled studies found a significant benefit for the adjunction of PRP to treat chronic diabetic wounds. As PRP may be beneficial, we suggest using PRP on diabetic ulcers which remain unhealed after standard treatment.

Use of autologous growth factors in aging tendon and chronic tendinopathy

Aging tendons or chronic tendinopathy are frequent conditions responsible for handicap in middle-aged and aging populations. Current therapies fail to relieve handicap. Medical treatment can sometimes be efficient, but surgical procedures often fail to restore tendon function. Cell therapy with platelets, based on tendon histological modifications and the capacity of such tissue to respond to growth factors, is an ever-expanding field of clinical research. In the current review, we compare the histological properties of normal tendons, aging tendons and chronic tendinopathy. We explain the natural healing process of such tendons and the rationale for using, or not, autologous growth factors. We review current clinical studies exploring the effect of concentrated autologous growth factor injection in chronic lesions and attempt to explain why, to date, all clinical studies have demonstrated no effect of such therapies.

Tissue engineering applications in the management of bone loss

Several conditions in Orthopaedics and Traumatology are characterized by a bone loss. Bone auto- or allo-grafting was considered sufficient to fullfill the defects decades ago; however, large bone defects were challenging for the Surgeons, particularly in case of necessity of structural and biological properties. Bioindusrty proposed over the years synthetic biomaterials, as Demineralized Bone Matrix, bioactive surfaces for implant coponents, and recently recombinant Bone Morphogenetic Proteins. At the same time, the concept of the "biological chamber" and "diamond concept" allowed the scientific community to consider the need of a more complex interaction between scaffolds (matrix), cells (mesenchymal cells), and signaling (growth factors) in order to induce bone regeneration and also to fill small or large bone defects. A brief overview is made on the processes of a physiologic bone metabolism (induction, conduction, osteogenesis), on the latest therapeutical procedures, based on the use of autologous growth factors and cells, and the recent prosthetic or synthetic scaffolds, and the common clinical conditions that may beneficiate of these modern approaches.

The Use of Platelet-Rich Plasma in Sports Medicine—the International Olympic Committee Opinion

i Acute and chronic musculoskeletal injuries in sports are common and problematic for both athletes and cliniians. A significant proportion of these injuries remain diffiult to treat, and many athletes suffer from decreased perforance and long-standing pain and discomfort.1 In 2008, the International Olympic Committee (IOC) published a consensus document on the importance of molecular mechanisms in connective tissue and skeletal muscle injury and healing.2 This document predicted an increase in the use of autologous growth factors, as has indeed happened following that publication. Platelet-rich plasma (PRP, also referred to as platelet rich in growth factors, platelet-rich fibrin matrix, platelet-rich fibrin, fibrin sealant, platelet concentrate) is now being widely used to treat musculoskeletal injuries in sports and draws widespread media attention, despite the absence of robust clinical studies to support its use.3 Of the few studies published on he effectiveness of PRP in clinical settings, only very few are f sufficient methodological quality that would enable evience-based decision making. On January 1, 2011, the orld Anti-Doping Agency eased the restrictions on PRP, iting that there was no evidence that the procedure enanced performance. PRP and its variant forms were originally used in clinical ractice as an adjunct to surgery to assist in the healing of arious tissues. Initially, PRP was mainly used in oral surery.4,5 Subsequently, PRP has also been used at the time of urgery, involving shoulder,6 hip,7 and knee joint procedures,8,9 including anterior cruciate ligament reconstruction,10 and it has been used to improve bone healing.11 More recently, PRP in an injectable form has been used for the

IOC consensus paper on the use of platelet-rich plasma in sports medicine : editor's choice

Acute and chronic musculoskeletal injuries in sports are common and problematic for both athletes and clinicians. A significant proportion of these injuries remain difficult to treat, and many athletes suffer from decreased performance and longstanding pain and discomfort.1 In 2008, the International Olympic Committee (IOC) published a consensus document on the importance of molecular mechanisms in connective tissue and skeletal muscle injury and healing.2 This document predicted an increase in the use of autologous growth factors, as it has indeed happened following that publication. Platelet-rich plasma (PRP) (also referred to as platelet-rich in growth factors, platelet-rich fibrin matrix, platelet-rich fibrin, fibrin sealant, platelet concentrate) is now being widely used to treat musculoskeletal injuries in sports and draws widespread media attention despite the absence of robust clinical studies to support its use.3 Of the few studies on the effectiveness of PRP in clinical settings published, very few are of sufficient methodological quality that would enable evidence-based decision-making. PRP and its variant forms were originally used in clinical practice as an adjunct to surgery to assist in the healing of various tissues. PRP has also been used in prosthetic surgery to promote tissue healing and implant integration, and to control blood loss.4 5 Furthermore, the application of activated PRP has an effect on pain and pain medication use following open subacromial decompression surgery.5 Initially, PRP was mainly used in oral surgery.6 7 Subsequently, PRP has also been used at the time of surgery involving shoulder,8 hip9 and knee joint procedures,10 11 including anterior cruciate ligament (ACL) reconstruction,12 and it has been used to improve bone healing. 13 More recently, PRP in an injectable form has been used for the management of common muscle,14 tendon15 and cartilage injuries.16 As predicted by the 2008 IOC consensus document on the molecular mechanisms in connective tissue and skeletal muscle injury and healing,2 there is significant anecdotal evidence that the use of PRP for treating musculoskeletal injuries has increased in recent times. Currently, PRP is not considered as a drug or a therapeutic substance, and so it does not have the usual regulatory requirements that would generally be needed for a substance used in regular clinical practice.

Improved treatment of mandibular odontogenic cysts with platelet-rich gel

Platelets play a central role in hemostasis and healing processes. By concentrating platelets, platelet-rich plasma (PRP) with higher levels of growth factors can be obtained, which might stimulate healing processes. After platelet degranulation, massive release of growth factors and active substances occurs and gelatinous matrix-platelet-rich gel (PRG) is formed. In this double-blind study, we report the influence of PRG on healing of mandibular odontogenic cysts. We examined 23 cases divided into control (no PRG treatment) and experimental (PRG-treated) groups. Each participant was followed on a regular basis with clinical examinations, roentgenograms, and dual-energy x-ray absorptiometry (DEXA) examinations. Clinical observations showed that oral mucosa healed faster in patients treated with PRG compared with cases where gel was not added. Roentgenograms and DEXA examinations showed considerable enhancement of bone regeneration beginning from the 5th week and continuing during subsequent periods after implantation of PRG in the experimental group compared with the control group. In our opinion, PRG possesses inductive properties that could stimulate the healing processes. The use of autologous growth factors from platelet gel seems to be one of the most promising methods of treatment of bone, cartilage, and soft tissue defects.

Spinal fusion using an autologous growth factor gel and a porous resorbable ceramic.

Augmenting healing through a single application of an exogenous growth factor or bone morphogenetic protein is not a new concept. The use of autologous growth factors through platelet isolation and concentration provides multiple endogenous growth factors to the healing site. A posterolateral fusion model in aged sheep (5- to 6-year-old ewes) was used to examine the effects of the addition of growth factors through autologous platelet isolation on the biomechanic and histologic properties of the fusion using a resorbable coral bone graft substitute. At 6 months the combination of autologous growth factors to the Pro Osteon 500R plus aspirated bone marrow resulted in the greatest bending stiffness but not ultimate load. Autologous growth factors can be isolated from platelets and concentrated to provide multiple growth factors to the fusion site to aid in spinal fusion.

Use of autologous growth factors in lumbar spinal fusion

The results of spinal fusion, especially posteriorly above the lumbosacral junction, have been mixed. Autologous growth factor concentrate (AGF) prepared by ultraconcentration of platelets contains multiple growth factors having a chemotactic and mitogenic effect on mesenchymal stem cells and osteoblasts and may play a role in initiating bone healing. The purpose of this retrospective study is to review our results with AGF in lumbar spinal fusions. To date, AGF has been used in 39 patients having lumbar spinal fusion. The study group consisted of the first 19 consecutive cases to allow at least 6 months follow-up. The average follow-up was 13 months (range 6 to 18 months). Follow-up compliance was 91%. There were 7 men and 12 women. Average age was 52 years (range 30–72 years). Nine patients had prior back surgery. There were 8 smokers. AGF was used in posterior (n = 15) or anterior intradiscal (n = 4) fusions. AGF was used with autograft and coraline hydroxyapatite in all posterior fusions, and autograft, coral, and intradiscal spacer (carbon fiber spinal fusion cages or Synthes femoral ring) in intradiscal fusions. Posterior stabilization was used in all cases. Eight cases were single-level fusions, 6 were two-level, and 1 was a three-level fusion. Autologous iliac crest bone graft was taken in 14 cases and local autograft used in 5 cases. Posteriorly, a total of 23 levels were fused; of these, nine were at L5–S1, eight at L4–L5, five at L3–L4, and one at L2–L3. No impending pseudoarthroses were noted on plain radiographic examination at last follow-up visit. Solid fusion was confirmed in 3 patients having routine hardware removal, and in 2 patients who had surgery at an adjacent level. There was one posterior wound infection, which was managed without sequelae. When used as an adjunct to autograft, AGF offers theoretical advantages that need to be examined in controlled studies. Further study is necessary to determine whether coralline hydroxyapatite used as a bone graft extender in lumbar spinal fusion may help to obviate the need for secondary site graft harvesting.