Platelet rich plasma enhances tissue incorporation of biologic mesh

Fernandez-Moure, Joseph; Eps, Jeffrey L. Van; Menn, Zachary K.; Cabrera, Fernando; Tasciotti, Ennio; Weiner, Bradley K.; Ellsworth, Warren A.

doi:10.1016/j.jss.2015.06.034

Cited by 29 publications

(37 citation statements)

References 32 publications

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“…Despite the key role of PLTs in the maintenance of hemostasis, they were shown to regulate multiple processes such as angiogenesis, cell differentiation, cell migration, immune responses and tissue remodeling (25)(26)(27). More recently, those PLT unique features have been exploited in the development of novel therapies such as in supporting wound healing, tissue regeneration or as drug carriers (28)(29)(30)(31). Due to the population aging, a significant increase on PLT demand for all those therapeutic approaches is expected.…”

Section: Hla-universal Mks Generate Plts In a Refractoriness Mouse Modelmentioning

confidence: 99%

Generation of HLA-Universal iPSC-Derived Megakaryocytes and Platelets for Survival Under Refractoriness Conditions

Börger

Eicke

Wolf

et al. 2016

Mol Med

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Platelet (PLT) transfusion is indispensable to maintain homeostasis in thrombocytopenic patients. However, PLT transfusion refractoriness is a common life-threatening condition observed in multitransfused patients. The most frequent immune cause for PLT transfusion refractoriness is the presence of alloantibodies specific for human leukocyte antigen (HLA) class I epitopes. Here, we have silenced the expression of HLA class I to generate a stable HLA-universal induced pluripotent stem cell (iPSC) line that can be used as a renewable cell source for the generation of low immunogenic cell products. The expression of HLA class I was silenced by up to 82% and remained stable during iPSC cultivation. In this study, we have focused on the generation of megakaryocytes (MK) and PLTs from a HLA-universal iPSC source under feeder-and xeno-free conditions. On d 19, differentiation rates of MKs and PLTs with means of 58% and 76% were observed, respectively. HLA-universal iPSC-derived MKs showed polyploidy with DNA contents higher than 4n and formed proPLTs. Importantly, differentiated MKs remained silenced for HLA class I expression. HLA-universal MKs produced functional PLTs. Notably, iPSC-derived HLA-universal MKs were capable to escape antibody-mediated complement-and cellular-dependent cytotoxicity. Furthermore, HLA-universal MKs were able to produce PLTs after in vivo transfusion in a mouse model indicating that they might be used as an alternative to PLT transfusion. Thus, in vitro produced low immunogenic MKs and PLTs may become an alternative to PLT donation in PLT-based therapies and an important component in the management of severe alloimmunized patients.

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Section: Hla-universal Mks Generate Plts In a Refractoriness Mouse Modelmentioning

confidence: 99%

Generation of HLA-Universal iPSC-Derived Megakaryocytes and Platelets for Survival Under Refractoriness Conditions

Börger

Eicke

Wolf

et al. 2016

Mol Med

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“…The use of concentrated platelet solutions or platelet lysate in soft tissue wound healing has been investigated . Although PRP has been studied in oral maxillofacial, orthopedic, and plastic surgical applications, there remains conflicting evidence and a glaring lack of consensus regarding its clinical benefit .…”

Section: Discussionmentioning

confidence: 99%

“…In order to further validate that the correct Plt concentration was attained, Plt number was quantified using a Multisizer Coulter Counter (Beckman Coulter, CA). PRP samples were standardized to an effective dose final concentration of 1 × 10 6 platelets per microliter of plasma according to prior studies . Prior to application in surgery, 200 µL of PRP was activated using 10% calcium solution and thrombin (1,000 U/mL; Sigma‐Aldrich, St. Louis, MO) as previously described …”

Section: Methodsmentioning

confidence: 99%

“…We have previously reported on the angiogenic cell factors—vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF)—contained within the biologic milieu of PRP . Multiple reports have demonstrated that augmentation with PRP improves cellular migration, proliferation, extracellular matrix (ECM) deposition, wound healing/contraction and neovascularization . When used as an adjuvant to chronic VHR with non–cross‐linked porcine ADM, PRP was found to enhance incorporation, preserve ADM from immunologic degradation and reduce recurrence .…”

mentioning

confidence: 99%

“…9 Multiple reports have demonstrated that augmentation with PRP improves cellular migration, proliferation, extracellular matrix (ECM) deposition, wound healing/contraction and neovascularization. [10][11][12] When used as an adjuvant to chronic VHR with non-cross-linked porcine ADM, PRP was found to enhance incorporation, preserve ADM from immunologic degradation and reduce recurrence. 11,13 Additionally, when used with collagen matrices, PRP has been shown to improve wound healing, cellular adhesion, and migration into the scaffold.…”

mentioning

confidence: 99%

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Cross‐linking of porcine acellular dermal matrices negatively affects induced neovessel formation using platelet‐rich plasma in a rat model of hernia repair

Fernandez-Moure

Eps

Peterson

et al. 2017

Wound Repair Regeneration

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The degree of cross-linking within acellular dermal matrices (ADM) seems to correlate to neovascularization when used in ventral hernia repair (VHR). Platelet-rich plasma (PRP) enhances wound healing through several mechanisms including neovascularization, but research regarding its effect on soft tissue healing in VHR is lacking. We sought to study the effect of cross-linking on PRP-induced neovascularization in a rodent model of bridging VHR. We hypothesized that ADM cross-linking would negatively affect PRP-induced neovessel formation. PRP was extracted and characterized from pooled whole blood. Porcine cross-linked (cADM) and non-cross-linked ADMs (ncADM) were implanted in a rat model of chronic VHR after treatment with saline (control) or PRP. Neovascularization of samples at 2, 4, and 6 weeks was assessed by hematoxylin and eosin and immunohistochemical staining of CD 31. Adhesion severity at necropsy was compared using a previously validated scale. Addition of PRP increased neovascularization in both cADM and ncADM at 2- and 4-week time points but appeared to do so in a dependent fashion, with significantly greater neovascularization in the PRP-treated ncADMs compared to cADMs. Omental adhesions were increased in all PRP-treated groups. Results indicate that, for 2-week measurements when compared with the cADM group without PRP therapy, the mean change in neovascularization due to ncADM was 3.27 (Z = 2.75, p = 0.006), PRP was 17.56 (Z = 14.77, p < 0.001), and the combined effect of ncADM and PRP was 9.41 (Z = 5.6, p < 0.001). The 4-week data indicate that the average neovascularization change due to ncADM was 0.676 (Z = 0.7, p = 0.484), PRP was 7.69 (Z = 7.95, p < 0.001), and combined effect of ncADM and PRP was 5.28 (Z = 3.86, p < 0.001). These findings validate PRP as a clinical adjunct to enhance the native tissue response to implantable biomaterials and suggest that ncADM is more amenable than cADM to induced neovascularization. PRP use could be advantageous in patients undergoing VHR where poor incorporation is anticipated and early-enhanced neovascularization is desired.

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Platelet‐rich plasma enhances mechanical strength of strattice in rat model of ventral hernia repair

Fernandez-Moure

Eps

Scherba

et al. 2021

J Tissue Eng Regen Med

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Incisional hernia is a common complication of hernia repair despite the development of various synthetic and bio‐synthetic repair materials. Poor long‐term mechanical strength, leading to high recurrence rates, has limited the use of acellular dermal matrices (ADMs) in ventral hernia repair (VHR). Biologically derived meshes have been an area of increasing interest. Still these materials bring the risk of more aggressive immune response and fibrosis in addition to the mechanical failures suffered by the synthetic materials. Platelet‐rich plasma (PRP), a growth‐factor‐rich autologous blood product, has been shown to improve early neovascularization, tissue deposition, and to decrease the rates of recurrence. Here, we demonstrate that PRP promotes the release of growth factors stromal derived factor (SDF)‐1, transforming growth factor‐beta, and platelet‐derived growth factor in a dose‐dependent manner. Additionally, we utilize an aortic ring angiogenesis assay to show that PRP promotes angiogenesis in vitro. A rat model of VHR using StratticeTM ADM demonstrates similar findings in vivo, corresponding with the increased expression of vascular endothelial growth factor and collagen type 1 alpha 1. Finally, we show that the molecular and cellular activity initiated by PRP results in an increased mechanical stiffness of the hernia repair mesh over time. Collectively, these data represent an essential step in demonstrating the utility and the mechanism of platelet‐derived plasma in biomaterial‐aided wound healing and provide promising preclinical data that suggest such materials may improve surgical outcomes.

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Platelet rich plasma enhances tissue incorporation of biologic mesh

Cited by 29 publications

References 32 publications

Generation of HLA-Universal iPSC-Derived Megakaryocytes and Platelets for Survival Under Refractoriness Conditions

Generation of HLA-Universal iPSC-Derived Megakaryocytes and Platelets for Survival Under Refractoriness Conditions

Cross‐linking of porcine acellular dermal matrices negatively affects induced neovessel formation using platelet‐rich plasma in a rat model of hernia repair

Platelet‐rich plasma enhances mechanical strength of strattice in rat model of ventral hernia repair

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