Treatment of bisphosphonate-related osteonecrosis using platelet-rich plasma: microtomographic, microscopic, and immunohistochemical analyses

Cardoso, Camila Lopes; Curra, Cláudia; Curi, Marcos Martins; Matsumoto, Mariza Akemi; Argentino, Camila Dionísio; Franzolin, Solange de Oliveira Braga; Constantino, Dulce Helena Jardim; Barbosa, Daniela Nicolielo; Júnior, Osny Ferreira

doi:10.1590/1807-3107bor-2019.vol33.0050

Cited by 12 publications

(8 citation statements)

References 32 publications

(42 reference statements)

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“…FBS, fetal bovine serum; tPRP, thrombin-activated platelet-rich plasma [Colour figure can be viewed at wileyonlinelibrary.com] driven by a higher density of osteoprogenitors in the constructs. A superiority of PRP over FBS in terms of bone formation in an osteonecrosis model was already reported elsewhere also, but only when applied directly, that is, without cells and compared with no treatment (Cardoso et al, 2019). It has also been shown that culture of adipose-derived stromal cells with PRP increased not only their proliferation capacity but also the direct osteogenic differentiation of the progenitor cells present in the SVF (Hong et al, 2019).…”

Section: Bone Formationsupporting

confidence: 58%

Platelet‐rich plasma and stromal vascular fraction cells for the engineering of axially vascularized osteogenic grafts

Ismail

Lunger

Haumer

et al. 2020

J Tissue Eng Regen Med

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Avascular necrosis of bone (AVN) leads to sclerosis and collapse of bone and joints. We have previously shown that axially vascularized osteogenic constructs, engineered by combining human stromal vascular fraction (SVF) cells and a ceramic scaffold, can revitalize necrotic bone of clinically relevant size in a rat model of AVN. For a clinical translation, the fetal bovine serum (FBS) used to generate such grafts should be substituted by a nonxenogeneic culture supplement. Human thrombin‐activated platelet‐rich plasma (tPRP) was evaluated in this context. SVF cells were cultured inside porous hydroxyapatite scaffolds with a perfusion‐based bioreactor system for 5 days. The culture medium was supplemented with either 10% FBS or 10% tPRP. The resulting constructs were inserted into devitalized bovine bone cylinders to mimic the treatment of a necrotic bone. A ligated vascular bundle was inserted into the constructs upon subcutaneous implantation in the groin of nude rats. After 1 and 8 weeks, constructs were harvested, and vascularization, host cell recruitment, and bone formation were analyzed. After 1 week in vivo, constructs were densely vascularized, with no difference between tPRP‐ and FBS‐based ones. After 8 weeks, bone formation and vascularization was found in both tPRP‐ and FBS‐precultured constructs. However, the amount of bone and the vessel density were respectively 2.2‐ and 1.8‐fold higher in the tPRP group. Interestingly, the density of M2, proregenerative macrophages was also significantly higher (6.9‐fold) following graft preparation with tPRP than with FBS. Our findings indicate that tPRP is a suitable substitute for FBS to generate vascularized, osteogenic grafts from SVF cells and could thus be implemented in protocols for clinical translation of this strategy towards the treatment of bone loss and AVN.

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Section: Bone Formationsupporting

confidence: 58%

Platelet‐rich plasma and stromal vascular fraction cells for the engineering of axially vascularized osteogenic grafts

Ismail

Lunger

Haumer

et al. 2020

J Tissue Eng Regen Med

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“… 13 To effectively prevent patients from BRONJ after tooth extraction, clinical operations such as early wound closure after tooth extraction, hyperbaric oxygen therapy, stem cell therapy, and growth factor are mostly used, but there are few clinical data and it is difficult to reach a consensus. 14 – 17 Therefore, at this stage, the clinic advocates prevention for BRONJ.…”

Section: Introductionmentioning

confidence: 99%

Tetrahedral framework nucleic acid carrying angiogenic peptide prevents bisphosphonate-related osteonecrosis of the jaw by promoting angiogenesis

et al. 2022

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The significant clinical feature of bisphosphonate-related osteonecrosis of the jaw (BRONJ) is the exposure of the necrotic jaw. Other clinical manifestations include jaw pain, swelling, abscess, and skin fistula, which seriously affect the patients’ life, and there is no radical cure. Thus, new methods need to be found to prevent the occurrence of BRONJ. Here, a novel nanoparticle, tFNA-KLT, was successfully synthesized by us, in which the nanoparticle tetrahedral framework nucleic acid (tFNA) was used for carrying angiogenic peptide, KLT, and then further enhanced angiogenesis. TFNA-KLT possessed the same characteristics as tFNA, such as simple synthesis, stable structure, and good biocompatibility. Meanwhile, tFNA enhanced the stability of KLT and carried more KLT to interact with endothelial cells. First, it was confirmed that tFNA-KLT had the superior angiogenic ability to tFNA and KLT both in vitro and in vivo. Then we apply tFNA-KLT to the prevention of BRONJ. The results showed that tFNA-KLT can effectively prevent the occurrence of BRONJ by accelerating angiogenesis. In summary, the prepared novel nanoparticle, tFNA-KLT, was firstly synthesized by us. It was also firstly confirmed by us that tFNA-KLT significantly enhanced angiogenesis and can effectively prevent the occurrence of BRONJ by accelerating angiogenesis, thus providing a new avenue for the prevention of BRONJ and a new choice for therapeutic angiogenesis.

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“…Several studies have focused on the regenerative potentialities and translational applications of PRP ( Cardoso et al., 2019 ; Inchingolo et al., 2017 ) associated with the choice of the best scaffold seeded with different SCs such as dental-derived SCs ( Ballini et al., 2017 ), mesenchymal SCs ( Cantore et al., 2018 ), and adipose-derived SCs ( Barba-Recreo et al., 2015 ) in the regenerative medicine such as the management of medication-related osteonecrosis of the jaw ( Boccaccio et al., 2018 ; Crincoli et al., 2015 ). Since the pathogenesis of BRONJ as well as its prevention and treatment has not been established, this study was aimed to investigate the success of applying PRP + collagen scaffold and collagen scaffold alone in prevention of zoledronic acid-induced BRONJ grossly, histologically, and radiographically in the rat animal model.…”

Section: Discussionmentioning

confidence: 99%

Application of a collagen scaffold saturated with platelet-rich plasma in prevention of bisphosphonate-related osteonecrosis of the jaw in the rat animal model

Razmara

Bayat

Shirian

et al. 2021

Heliyon

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Background: Among the myriad adverse events of drugs in the oral cavity, Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is one of the most detrimental drug reactions that have ever been known. Objective: This study was aimed to investigate the success of applying collagen scaffold alone and platelet-rich plasma (PRP)þcollagen scaffold in prevention of zoledronic acid-induced BRONJ in the rat. Methods: A total of 17 male Wistar-rats were treated with 4 weekly doses of zoledronic acid. All rats were undergone bilateral tooth extraction of mandibular first molars and divided into three groups of scaffold þ PRP þ suture, scaffold þ suture, and suture only. All rats were scarified and clinical, radiological, histological and histomorphomerical evaluations were made on week 8 post-treatment. The soft tissue healing, bone mineralized density (BMD), number of osteoclasts and osteoblasts, necrotic bone (NB), intensity of inflammation and new bone formation (NBF) were analyzed. Results: BMD, number of osteoblasts and NBF variables proved to be statistically were higher in the treatment groups than the control group. In addition, the PRP þ scaffold group showed the better results in terms of BMD, number of osteoblasts and NBF than that of the scaffold alone group. Number of osteoclasts, inflammation intensity and osteonecrosis were also significantly different in the PRP þ scaffold group compared to the scaffold alone and the control groups. Conclusion: Application of a PRP-enriched collagen scaffold appeared to be a successful preventive treatment for BRONJ by effecting of the number of osteoblasts and osteoclasts, BMD, NBF, inflammation, and osteonecrosis.

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Treatment of bisphosphonate-related osteonecrosis using platelet-rich plasma: microtomographic, microscopic, and immunohistochemical analyses

Abstract: Camila Lopes CARDOSO (a) Cláudia CURRA (a) Marcos Martins CURI (b) Mariza Akemi MATSUMOTO (c) Camila Dionísio ARGENTINO (a) Solange de Oliveira Braga FRANZOLIN (d) Dulce CONSTANTINO (d) Daniela Nicolielo BARBOSA (d) Osny FERREIRA JÚNIOR (e)

Cited by 12 publications

References 32 publications

Platelet‐rich plasma and stromal vascular fraction cells for the engineering of axially vascularized osteogenic grafts

Platelet‐rich plasma and stromal vascular fraction cells for the engineering of axially vascularized osteogenic grafts

Tetrahedral framework nucleic acid carrying angiogenic peptide prevents bisphosphonate-related osteonecrosis of the jaw by promoting angiogenesis

Application of a collagen scaffold saturated with platelet-rich plasma in prevention of bisphosphonate-related osteonecrosis of the jaw in the rat animal model

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