In vivo evaluation of the biocompatibility and biodegradation of a new denatured plasma membrane combined with liquid PRF (Alb-PRF)

Gheno, Ezio; Mourão, Carlos Fernando de Almeida Barros; Mello-Machado, Rafael Coutinho; Lourenço, Emanuele Stellet; Miron, Richard J.; Catarino, Karoline Ferreira Farias; Alves, Adriana Terezinha Neves Novellino; Alves, Gutemberg Gomes; Calasans-Maia, Mônica Diuana

doi:10.1080/09537104.2020.1775188

Cited by 34 publications

(55 citation statements)

References 31 publications

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“…This research was prompted by the recently established PRF formulation consisting of heat-coagulated PPP mixed with the liquid cell-rich buffy coat C-PRF to serve as a long-term stable autologous and injectable matrix [13,20]. Previous reports clearly demonstrated that TGF-β is among the growth factors supporting the formation of a fibrous extracellular matrix [29,30,34].…”

Section: Discussionmentioning

confidence: 99%

“…Thus, the viscous injectable PRF mixture consists of a gel prepared from heated PPP and the non-heated liquid buffy coat C-PRF fraction (Alb-PRF). Following subcutaneous implantation in nude mice, Alb-PRF, but not traditional L-PRF and H-PRF, remains stable over at least 21 days, ideally supporting medical procedures which require a long-lasting scaffold [13].…”

Section: Introductionmentioning

confidence: 93%

“…More recently, PRF protocols prepared via horizontal centrifugation using plain glass tubes without clot activators to prepare H-PRF have been shown to lead to more favorable accumulation of platelets and leukocytes in the upper plasma layers [ 4 , 12 ]. Nevertheless, L-PRF and H-PRF membranes undergo spontaneous fibrinolysis within a 3 week period upon subcutaneous implantation in immunocompromised rodents [ 13 ], and thus are not ideal for clinical application requiring long-term volume stability serving as dermal fillers [ 14 , 15 ] or as a replacement for soft tissue grafts in dentistry [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

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Liquid Platelet-Rich Fibrin and Heat-Coagulated Albumin Gel: Bioassays for TGF-β Activity

et al. 2020

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Liquid platelet-rich fibrin (PRF) can be prepared by high centrifugation forces separating the blood into a platelet-poor plasma (PPP) layer and a cell-rich buffy coat layer, termed concentrated PRF (C-PRF). Heating the liquid PPP was recently introduced to prepare an albumin gel (Alb-gel) that is later mixed back with the concentrated liquid C-PRF to generate Alb-PRF. PRF is a rich source of TGF-β activity; however, the overall TGF-β activity in the PPP and the impact of heating the upper plasma layer remains unknown. Here, we investigated for the first time the in vitro TGF-β activity of all fractions of Alb-PRF. We report that exposure of oral fibroblasts with lysates of PPP and the buffy coat layer, but not with heated PPP, provoked a robust increase in the TGF-β target genes interleukin 11 and NADPH oxidase 4 by RT-PCR, and for IL11 by immunoassay. Consistent with the activation of TGF-β signaling, expression changes were blocked in the presence of the TGF-β receptor type I kinase inhibitor SB431542. Immunofluorescence and Western blot further confirmed that lysates of PPP and the buffy coat layer, but not heated PPP, induced the nuclear translocation of Smad2/3 and increased phosphorylation of Smad3. The immunoassay further revealed that PPP and particularly BC are rich in active TGF-β compared to heated PPP. These results strengthen the evidence that not only the cell-rich C-PRF but also PPP comprise a TGF-β activity that is, however, heat sensitive. It thus seems relevant to mix the heated PPP with the buffy coat C-PRF layer to regain TGF-β activity, as proposed during the preparation of Alb-PRF.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

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Liquid Platelet-Rich Fibrin and Heat-Coagulated Albumin Gel: Bioassays for TGF-β Activity

et al. 2020

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“…However, as shown in other studies [ 20 , 21 ], this model enables the assessment of the membranes’ safety (biocompatibility) and degradation (time the membrane remains in place). Thus, according to the ISO Standard [ 22 ], this study gave details on the recruitment of inflammatory cells, the formation of fibrous tissue and fatty infiltrate, and the degradation of membranes. Understanding how the tissue responds to the presence of membranes facilitates the knowledge of the biodegradation process.…”

Section: Discussionmentioning

confidence: 99%

In Vivo Comparative Evaluation of Biocompatibility and Biodegradation of Bovine and Porcine Collagen Membranes

et al. 2020

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Mechanical barriers prevent the invasion of the surrounding soft tissues within the bone defects. This concept is known as Guided Bone Regeneration (GBR). The knowledge about the local tissue reaction and the time of degradation of absorbable membranes favors the correct clinical indication. This study aimed to evaluate the biocompatibility and biodegradation of a bovine collagen membrane (Lyostypt®, São Gonçalo, Brazil) and compare it to a porcine collagen membrane (Bio-Gide®) implanted in the subcutaneous tissue of mice, following ISO 10993-6:2016. Thirty Balb-C mice were randomly divided into three experimental groups, LT (Lyostypt®), BG (Bio-Gide®), and Sham (without implantation), and subdivided according to the experimental periods (7, 21, and 63 days). The BG was considered non-irritant at seven days and slight and moderate irritant at 21 and 63 days, respectively. The LT presented a small irritant reaction at seven days, a mild reaction after 21, and a reduction in the inflammatory response at 63 days. The biodegradation of the LT occurred more rapidly compared to the BG after 63 days. This study concluded that both membranes were considered biocompatible since their tissue reactions were compatible with the physiological inflammatory process; however, the Bio-Gide® was less degraded during the experimental periods, favoring the guided bone regeneration process.

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“…In this study, they changed the name to Alb-PRF to distinguish this method from liquid PRF [87,88]. They also performed an in vivo study, in which they observed biodegradation in mice, and observed the Alb-PRF membrane after 21 days in subcutaneous tissue, indicating its slow degradation and the potential use of this blood by-product as a barrier [89]. Although further studies will be needed to assess the behavior of these autologous barriers, the development of such a highly functionalized PRF matrix will facilitate the discussion of the controlled release of growth factors from PRFs in vivo and its clinical significance.…”

Section: Controlled Release Of Growth Factors Retained In Prf Matricesmentioning

confidence: 99%

The Platelet Concentrates Therapy: From the Biased Past to the Anticipated Future

2020

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The ultimate goal of research on platelet concentrates (PCs) is to develop a more predictable PC therapy. Because platelet-rich plasma (PRP), a representative PC, was identified as a possible therapeutic agent for bone augmentation in the field of oral surgery, PRP and its derivative, platelet-rich fibrin (PRF), have been increasingly applied in a regenerative medicine. However, a rise in the rate of recurrence (e.g., in tendon and ligament injuries) and adverse (or nonsignificant) clinical outcomes associated with PC therapy have raised fundamental questions regarding the validity of the therapy. Thus, rigorous evidence obtained from large, high-quality randomized controlled trials must be presented to the concerned regulatory authorities of individual countries or regions. For the approval of the regulatory authorities, clinicians and research investigators should understand the real nature of PCs and PC therapy (i.e., adjuvant therapy), standardize protocols of preparation (e.g., choice of centrifuges and tubes) and clinical application (e.g., evaluation of recipient conditions), design bias-minimized randomized clinical trials, and recognize superfluous brand competitions that delay sound progress. In this review, we retrospect the recent past of PC research, reconfirm our ultimate goals, and discuss what will need to be done in future.

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In vivo evaluation of the biocompatibility and biodegradation of a new denatured plasma membrane combined with liquid PRF (Alb-PRF)

Cited by 34 publications

References 31 publications

Liquid Platelet-Rich Fibrin and Heat-Coagulated Albumin Gel: Bioassays for TGF-β Activity

Liquid Platelet-Rich Fibrin and Heat-Coagulated Albumin Gel: Bioassays for TGF-β Activity

In Vivo Comparative Evaluation of Biocompatibility and Biodegradation of Bovine and Porcine Collagen Membranes

The Platelet Concentrates Therapy: From the Biased Past to the Anticipated Future

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