The effect of experimental diabetes and glycaemic control on guided bone regeneration: histology and gene expression analyses

Retzepi, M; Calciolari, Elena; Wall, Ivan; Lewis, Mark P.; Donos, Nikolaos

doi:10.1111/clr.13031

Cited by 28 publications

(27 citation statements)

References 70 publications

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“…BMP-4, which belongs to the TGF-β superfamily, can directly induce osteogenic differentiation of BMSCs and osteoblasts through the Smad signaling pathway [ 38 ]. Recently, many studies have reported that the expression of BMP-4 is decreased in the serum of patients with DM and the calvarial defects of a DM rat model [ 39 , 40 ]. In addition, Martínez et al and Valencia et al reported that BMP-4 could induce macrophages to the M2 type by enhancing the secretion of IL-10 [ 41 , 42 ].…”

Section: Introductionmentioning

confidence: 99%

Three-dimensional bioprinting of multicell-laden scaffolds containing bone morphogenic protein-4 for promoting M2 macrophage polarization and accelerating bone defect repair in diabetes mellitus

Sun

Zhao

et al. 2021

Bioactive Materials

118

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Critical-sized bone defect repair in patients with diabetes mellitus remains a challenge in clinical treatment because of dysfunction of macrophage polarization and the inflammatory microenvironment in the bone defect region. Three-dimensional (3D) bioprinted scaffolds loaded with live cells and bioactive factors can improve cell viability and the inflammatory microenvironment and further accelerating bone repair. Here, we used modified bioinks comprising gelatin, gelatin methacryloyl (GelMA), and 4-arm poly (ethylene glycol) acrylate (PEG) to fabricate 3D bioprinted scaffolds containing BMSCs, RAW264.7 macrophages, and BMP-4-loaded mesoporous silica nanoparticles (MSNs). Addition of MSNs effectively improved the mechanical strength of GelMA/gelatin/PEG scaffolds. Moreover, MSNs sustainably released BMP-4 for long-term effectiveness. In 3D bioprinted scaffolds, BMP-4 promoted the polarization of RAW264.7 to M2 macrophages, which secrete anti-inflammatory factors and thereby reduce the levels of pro-inflammatory factors. BMP-4 released from MSNs and BMP-2 secreted from M2 macrophages collectively stimulated the osteogenic differentiation of BMSCs in the 3D bioprinted scaffolds. Furthermore, in calvarial critical-size defect models of diabetic rats, 3D bioprinted scaffolds loaded with MSNs/BMP-4 induced M2 macrophage polarization and improved the inflammatory microenvironment. And 3D bioprinted scaffolds with MSNs/BMP-4, BMSCs, and RAW264.7 cells significantly accelerated bone repair. In conclusion, our results indicated that implanting 3D bioprinted scaffolds containing MSNs/BMP-4, BMSCs, and RAW264.7 cells in bone defects may be an effective method for improving diabetic bone repair, owing to the direct effects of BMP-4 on promoting osteogenesis of BMSCs and regulating M2 type macrophage polarization to improve the inflammatory microenvironment and secrete BMP-2.

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Section: Introductionmentioning

confidence: 99%

Three-dimensional bioprinting of multicell-laden scaffolds containing bone morphogenic protein-4 for promoting M2 macrophage polarization and accelerating bone defect repair in diabetes mellitus

Sun

Zhao

et al. 2021

Bioactive Materials

118

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“…In bone augmentation procedures, diabetes is also associated with a significantly increased risk of intraoral bone block graft failure (Schwartz‐Arad, Levin, & Sigal, 2005). Similarly, diabetes affects the osteogenesis process in the early phase of guided bone regeneration (Retzepi, Calciolari, Wall, Lewis, & Donos, 2018). In addition, the periodontal therapy and a careful plaque control have been associated with improved glycemic control in type 2 diabetes mellitus (Stewart, Wager, Friedlander, & Zadeh, 2001).…”

Section: Introductionmentioning

confidence: 99%

Platelet‐rich plasma counteracts detrimental effect of high‐glucose concentrations on mesenchymal stem cells from Bichat fat pad

D’Esposito

Lecce

Marenzi

et al. 2020

J Tissue Eng Regen Med

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Diabetic patients display increased risk of periodontitis and failure in bone augmentation procedures. Mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP) represent a relevant advantage in tissue repair process and regenerative medicine. We isolated MSCs from Bichat's buccal fat pad (BFP) and measured the effects of glucose and PRP on cell number and osteogenic differentiation potential. Cells were cultured in the presence of 5.5-mM glucose (low glucose [LG]) or 25-mM glucose (high glucose [HG]). BFP-MSC number was significantly lower when cells were cultured in HG compared with those in LG. Following osteogenic differentiation procedures, calcium accumulation, alkaline phosphatase activity, and expression of osteogenic markers were significantly lower in HG compared with LG. Exposure of BFP-MSC to PRP significantly increased cell number and osteogenic differentiation potential, reaching comparable levels in LG and in HG. Thus, high-glucose concentrations impair BFP-MSC growth and osteogenic differentiation. However, these detrimental effects are largely counteracted by PRP. K E Y W O R D S Bichat's buccal fat pad, bone reconstruction, diabetes, mesenchymal stem cells, platelet-rich plasma Vittoria D'Esposito and Manuela Lecce equally contributed to this work.

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“…The use of a barrier membrane to promote the selective repopulation of a periodontal/bone defect by cells with regenerative, rather than reparative, potential has been successfully applied for more than 40 years . In particular, in guided bone regeneration (GBR), the surgical placement of a tissue‐occlusive membrane has been applied for the predictable treatment of atrophic ridges and peri‐implant defects, for socket preservation and for de novo bone formation in healthy and medically compromised conditions (for review see refs ). An ideal barrier for GBR should combine biocompatibility and tissue occlusiveness with clinical manageability, space maintenance and the possibility to resorb gradually over time …”

Section: Introductionmentioning

confidence: 99%

Degradation pattern of a porcine collagen membrane in an in vivo model of guided bone regeneration

Calciolari

Ravanetti

Strange

et al. 2018

J of Periodontal Research

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The collagen membrane investigated was biocompatible and able to promote bone regeneration. However, pronounced signs of degradation were observed starting from day 30. Since successful regeneration is obtained only when cell occlusion and space maintenance exist for the healing time needed by the bone progenitor cells to repopulate the defect, the suitability of collagen membranes in cases where long-lasting barriers are needed needs to be further reviewed.

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The effect of experimental diabetes and glycaemic control on guided bone regeneration: histology and gene expression analyses

Cited by 28 publications

References 70 publications

Three-dimensional bioprinting of multicell-laden scaffolds containing bone morphogenic protein-4 for promoting M2 macrophage polarization and accelerating bone defect repair in diabetes mellitus

Three-dimensional bioprinting of multicell-laden scaffolds containing bone morphogenic protein-4 for promoting M2 macrophage polarization and accelerating bone defect repair in diabetes mellitus

Platelet‐rich plasma counteracts detrimental effect of high‐glucose concentrations on mesenchymal stem cells from Bichat fat pad

Degradation pattern of a porcine collagen membrane in an in vivo model of guided bone regeneration

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