The effects of local platelet rich plasma delivery on diabetic fracture healing

Background: The therapeutic use of autologously prepared, platelet-leukocyte-enriched gel (PLG) is a relatively new technology for the stimulation and acceleration of soft tissue and bone healing. The effectiveness of this procedure lies in the delivery of a wide range of platelet growth factors mimicking the physiologic wound healing and reparative tissue processes. Despite an increase in PLG applications, the structures and kinetics of this autogenously derived biologic material have not been observed. Methods: A review of the most recent literature was performed to evaluate the use of PLG in various surgical disciplines. Results: The review showed that the application of PLG has been extended to various surgical disciplines including orthopedics, cardiac surgery, plastic and maxillofacial surgery, and recently also endoscopic surgery. Conclusion: This review demonstrates the usefulness of PLG in a wide range of clinical applications for improvement of healing after surgical procedures.Key words: Growth factors -Leukocytes -Platelet gel -Wound healing Soft tissue wound healing and bone growth involve physiologic cascades in which cellular and hormonal factors play pivotal roles [1,2]. Some of these cascade components can be isolated from autologously drawn whole blood. Point-of-care devices can intraoperatively fractionate the autologous blood into platelet-poor plasma, platelet-leukocyte-rich plasma (P-LRP), and red blood cells [3,4]. The P-LRP fraction, a mixture of concentrated platelets and leukocytes, can be activated by (autologous) thrombin to create a viscous solution known as platelet-leukocyte gel (PLG). This platelet coagulum can be exogenously applied to soft wound tissues, bone, or synthetic bone as a spray or as a solid, clotted, gelatinous mass. The rationale for applying platelet gel is based on the delivery of platelet growth factors to tissues and on the fact that platelet a-granules, found inside the platelets, contain a variety of growth factors [5]. Platelet gel growth factors are peptides that promote cell proliferation, differentiation, chemotaxis, and the migration of various cells involved in both wound healing and bone growth [6,7].Recently, numerous P-LRP devices have become available for therapeutic use to stimulate and accelerate soft tissue and bone healing and to control postoperative wound bleeding. The rationale for applying PLG lies in the mimicking and accelerating of physiologic wound healing and reparative tissue processes.This article provides information on the results of electron microscopic imaging used to evaluate the content of PLG. Furthermore, because the use of PLG is a relatively new per-and/or perioperative biotechnological application, new and additional indications for the use of PLG are defined. New PLG applications are reviewed for different applications including cardiac surgery, general surgery, orthopedics and traumatology, cosmetic surgery, maxillofacial surgery, sports medicine, and endoscopic surgical procedures. Defining platelet-leukocyte-rich...

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“…Normalized cellular proliferation and chondrogenesis, with improved mechanical strength, were observed when PLG was injected in this model [46].…”

Section: Bone Growthmentioning

confidence: 64%

The use of autologous platelet–leukocyte gels to enhance the healing process in surgery, a review

et al. 2007

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“…8 Following fracture, a lateral incision was made above the fracture site and the underlying muscle bluntly dissected to expose the fracture. Matrix combined with rhPDGF-BB was then applied directly to the fracture site with minimal perturbation of the periosteum.…”

Section: Fracture Modelmentioning

confidence: 99%

“…11 Degranulation of the a-granules releases multiple growth factors, including platelet derived growth factor (PDGF) and transforming growth factor b (TGF-b), into the fracture site. Previous studies in diabetic rats, however, have demonstrated that at early time points after fracture (2, 4, and 7 days), levels of PDGF, TGF-b, insulin-like growth factor I (IGF-I), and vascular endothelial growth factor (VEGF) are reduced, 6,8 and correspondingly cellular proliferation is decreased at the fracture site. These observations suggest that diabetes-impaired fracture healing occurs secondarily to a deficiency in an early phase of bone healing, potentially as a result of either inadequate biological signals or a discordant growth factor signaling cascade.…”

mentioning

confidence: 99%

“…4 Furthermore, chemically induced and spontaneous diabetic animal models also have demonstrated impairments in fracture healing. [5][6][7][8] In various fracture healing models, diabetes correlated with a reduction in fracture callus cellular proliferation, collagen synthesis, and biomechanical properties. 2,7,9,10 The mechanism by which diabetes impairs fracture healing is unknown.…”

mentioning

confidence: 99%

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Recombinant human platelet‐derived growth factor BB (rhPDGF‐BB) and beta‐tricalcium phosphate/collagen matrix enhance fracture healing in a diabetic rat model

Al-Zube

Breitbart

O’Connor

et al. 2009

Journal Orthopaedic Research

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Diabetes mellitus is a common systemic disease that has been associated with poor fracture healing outcomes. The mechanism through which diabetes impairs bone regeneration is unknown. One possible mechanism may be related to either decreased or uncoordinated release of local growth factors at the fracture site. Indeed, previous studies have found reduced platelet-derived growth factor (PDGF) levels in the fracture callus of diabetic rats, suggesting that local application of PDGF may overcome the negative effects of diabetes and promote fracture healing. To test this hypothesis, low (22 mg) and high (75 ug) doses of recombinant human PDGF-BB (rhPDGF-BB) were applied directly to femur fracture sites in BB Wistar diabetic rats that were then compared to untreated or vehicle-treated animals. rhPDGF-BB treatment significantly increased early callus cell proliferation compared to that in control specimens. Low dose rhPDGF-BB treatment significantly increased callus peak torque values (p < 0.05) at 8 weeks after fracture as compared to controls. High dose rhPDGF-BB treatment increased callus bone area at 12 weeks postfracture. These data indicate that rhPDGF-BB treatment ameliorates the effects of diabetes on fracture healing by promoting early cellular proliferation that ultimately leads to more bone formation. Local application of rhPDGF-BB may be a new therapeutic approach to treat diabetes-impaired fracture healing. ß

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“…It has the additional advantage of using the host as a donor source, which avoids bone graft donor site morbidity. Animal studies have yielded variable results (Gandhi et al, 2006;Gerard et al, 2006;Sarkar et al, 2006). Unfortunately, clinical studies have not seen the same success with the use of PRP as has been seen with other osteoinductive products such as BMPs (Carreon et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

The role of bone marrow aspirate cells in the management of atrophic mandibular fractures by mini-invasive surgical approach: Single-institution experience

Mannelli

Arcuri

Conti

et al. 2017

Journal of Cranio-Maxillofacial Surgery

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Elderly patients management Bone marrow aspirate cells Min-invasive surgical approach a b s t r a c t Purpose: The treatment of fractures involves addressing the biology of fracture repair and the mechanical stability of fracture fixation. Traditionally it has included the addition of bone graft to enhance healing. New advances in the understanding of the cellular and molecular mechanisms of fracture repair have led to the use of growth factors to accelerate bone healing. This study aimed to assess the advantages of autologous stem cell use for atrophic mandibular fracture treatment in comparison to standard technique. Materials and methods: A total of 35 patients (14 male and 21 female) were treated for fractures of atrophic mandibles between January 2011 and December 2014. Surgical technique provided miniinvasive open reduction with or without immediate homologous bone graft, while selected patients received autologous bone marrow aspirate cell grafts in addition to the standard treatment. Demographic data and details of treatment and outcomes were recorded. Results: Patients were categorized according to the use of autologous stem cells, leaving 17 patients treated with standard technique and autologous stem cells (Group A) and 18 treated with standard osteosynthesis only (Group B). Of the 35 patients, 26 had bilateral fractures; most patients had significant medical co-morbidities. Immediate bone graft was used in 37.1% of patients (7 in group A and 6 in group B). Complications occurred in 5 patients (14.3%). Two patients in group B (11.1%) showed non-union of the fracture. One patient in group A (5.8%) and one patient in group B (5.5%) showed wound dehiscence and were treated conservatively; one patient in group B had a local infection (5.5%), one out of 35 (2.8%), that was managed by prolonged antibiotic treatment. Conclusions: Despite the advanced age and medical co-morbidities of the vast majority of patients, miniinvasive open approach with autologous bone graft ensures a fast and excellent recovery. Moreover, the management of atrophic mandibular fractures by bone marrow aspirate cells is a safe and useful procedure which has a lower complication rate when compared to standard technique.

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The effects of local platelet rich plasma delivery on diabetic fracture healing

Cited by 157 publications

References 56 publications

The use of autologous platelet–leukocyte gels to enhance the healing process in surgery, a review

The use of autologous platelet–leukocyte gels to enhance the healing process in surgery, a review

Recombinant human platelet‐derived growth factor BB (rhPDGF‐BB) and beta‐tricalcium phosphate/collagen matrix enhance fracture healing in a diabetic rat model

The role of bone marrow aspirate cells in the management of atrophic mandibular fractures by mini-invasive surgical approach: Single-institution experience

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