TGF-β1 and BMP-4 carried by liposomes enhance the healing process in alveolar bone

Ferreira, Cynthia Lopes; Abreu, Fernando Antônio Mauad de; Silva, Gerluza Aparecida Borges; Silveira, Frank Ferreira; Barreto, Luana Beatriz Araújo; Paulino, Tony de Paiva; Miziara, Melissa Nunes; Alves, José Bento

doi:10.1016/j.archoralbio.2012.11.013

Cited by 21 publications

(18 citation statements)

References 66 publications

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“…The components of the ECM, such as collagen type I and III, play vital roles in the formation of new blood vessels [ 50 , 51 ]. Type I collagen is the main component of bone tissue, and type III collagen is expressed at high levels during remodeling of injured tissue [ 50 , 52 ]. Type III collagen is also abundant in blood vessels, where it contributes to the strength and elasticity of capillaries.…”

Section: Discussionmentioning

confidence: 99%

Prevascularization promotes endogenous cell-mediated angiogenesis by upregulating the expression of fibrinogen and connective tissue growth factor in tissue-engineered bone grafts

Cheng¹,

Li²,

Gao³

et al. 2018

Stem Cell Res Ther

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BackgroundVascularization is one of the most important processes in tissue-engineered bone graft (TEBG)-mediated regeneration of large segmental bone defects. We previously showed that prevascularization of TEBGs promoted capillary vessel formation within the defected site and accelerated new bone formation. However, the precise mechanisms and contribution of endogenous cells were not explored.MethodsWe established a large defect (5 mm) model in the femur of EGFP+ transgenic rats and implanted a β-tricalcium phosphate (β-TCP) scaffold seeded with exogenous EGFP− cells; the femoral vascular bundle was inserted into the scaffold before implantation in the prevascularized TEBG group. Histopathology and scanning electron microscopy were performed and connective tissue growth factor (CTGF) and fibrin expression, exogenous cell survival, endogenous cell migration and behavior, and collagen type I and III deposition were assessed at 1 and 4 weeks post implantation.ResultsWe found that the fibrinogen content can be increased at the early stage of vascular bundle transplantation, forming a fibrin reticulate structure and tubular connections between pores of β-TCP material, which provides a support for cell attachment and migration. Meanwhile, CTGF expression is increased, and more endogenous cells can be recruited and promote collagen synthesis and angiogenesis. By 4 weeks post implantation, the tubular connections transformed into von Willebrand factor-positive capillary-like structures with deposition of type III collagen, and accelerated angiogenesis of endogenous cells.ConclusionsThese findings demonstrate that prevascularization promotes the recruitment of endogenous cells and collagen deposition by upregulating fibrinogen and CTGF, directly resulting in new blood vessel formation. In addition, this molecular mechanism can be used to establish fast-acting angiogenesis materials in future clinical applications.Electronic supplementary materialThe online version of this article (10.1186/s13287-018-0925-y) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Prevascularization promotes endogenous cell-mediated angiogenesis by upregulating the expression of fibrinogen and connective tissue growth factor in tissue-engineered bone grafts

Cheng¹,

Li²,

Gao³

et al. 2018

Stem Cell Res Ther

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“…Two of its members constitute the only osteoinductive growth factors approved by the FDA for clinical use, commercialized as INFUSE (rhBMP-2, Medtronic) and OP-1 Putty (rhBMP-7/OP-1, Stryker) (Cahill et al, 2015 ). To date, over 20 BMPs have been identified, and several have been shown to play important roles in the induction of osteogenesis, including BMP-2, 4, 5, 6, and 7 (Ferreira et al, 2013 ; Fischerauer et al, 2013 ). Clinically, BMPs have been utilized to heal open tibial fractures and nonunions (Kanakaris et al, 2008 ), form new bone in the disc spaces for spinal fusion procedures (Brandoff et al, 2008 ), and induce the formation of new bone in dental procedures (Lan et al, 2007 ).…”

Section: Bone Tissue Engineeringmentioning

confidence: 99%

Tissue Engineering and Cell-Based Therapies for Fractures and Bone Defects

Perez

Kouroupis

et al. 2018

Front. Bioeng. Biotechnol.

285

198

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Bone fractures and segmental bone defects are a significant source of patient morbidity and place a staggering economic burden on the healthcare system. The annual cost of treating bone defects in the US has been estimated to be $5 billion, while enormous costs are spent on bone grafts for bone injuries, tumors, and other pathologies associated with defective fracture healing. Autologous bone grafts represent the gold standard for the treatment of bone defects. However, they are associated with variable clinical outcomes, postsurgical morbidity, especially at the donor site, and increased surgical costs. In an effort to circumvent these limitations, tissue engineering and cell-based therapies have been proposed as alternatives to induce and promote bone repair. This review focuses on the recent advances in bone tissue engineering (BTE), specifically looking at its role in treating delayed fracture healing (non-unions) and the resulting segmental bone defects. Herein we discuss: (1) the processes of endochondral and intramembranous bone formation; (2) the role of stem cells, looking specifically at mesenchymal (MSC), embryonic (ESC), and induced pluripotent (iPSC) stem cells as viable building blocks to engineer bone implants; (3) the biomaterials used to direct tissue growth, with a focus on ceramic, biodegradable polymers, and composite materials; (4) the growth factors and molecular signals used to induce differentiation of stem cells into the osteoblastic lineage, which ultimately leads to active bone formation; and (5) the mechanical stimulation protocols used to maintain the integrity of the bone repair and their role in successful cell engraftment. Finally, a couple clinical scenarios are presented (non-unions and avascular necrosis—AVN), to illustrate how novel cell-based therapy approaches can be used. A thorough understanding of tissue engineering and cell-based therapies may allow for better incorporation of these potential therapeutic approaches in bone defects allowing for proper bone repair and regeneration.

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“…A number of powerful GFs have been used to induce differentiation in cells. For example, bone morphogenetic proteins (BMPs), including bone morphogenetic protein-2 (BMP-2) 40, 42 BMP-4, 24 BMP-6, 85 and BMP-7 10 have been used to promote osteogenic and chondrogenic differentiation of cells on scaffolds. Fibroblast growth factor-2 (FGF-2) 101 and vascular endothelial growth factor (VEGF) 119 have been used to enhanced tissue and vascular growth in ceramic scaffolds.…”

Section: Tissue Engineering Approaches For Vascularized Bone Repairmentioning

confidence: 99%

Vascularization in Bone Tissue Engineering Constructs

et al. 2015

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Vascularization of large bone grafts is one of the main challenges of bone tissue engineering (BTE), and has held back the clinical translation of engineered bone constructs for two decades so far. The ultimate goal of vascularized BTE constructs is to provide a bone environment rich in functional vascular networks to achieve efficient osseointegration and accelerate restoration of function after implantation. To attain both structural and vascular integration of the grafts, a large number of biomaterials, cells, and biological cues have been evaluated. This review will present biological considerations for bone function restoration, contemporary approaches for clinical salvage of large bone defects and their limitations, state-of-the-art research on the development of vascularized bone constructs, and perspectives on evaluating and implementing novel BTE grafts in clinical practice. Success will depend on achieving full graft integration at multiple hierarchical levels, both between the individual graft components as well as between the implanted constructs and their surrounding host tissues. The paradigm of vascularized tissue constructs could not only revolutionize the progress of bone tissue engineering, but could also be readily applied to other fields in regenerative medicine for the development of new innovative vascularized tissue designs.

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TGF-β1 and BMP-4 carried by liposomes enhance the healing process in alveolar bone

Cited by 21 publications

References 66 publications

Prevascularization promotes endogenous cell-mediated angiogenesis by upregulating the expression of fibrinogen and connective tissue growth factor in tissue-engineered bone grafts

Prevascularization promotes endogenous cell-mediated angiogenesis by upregulating the expression of fibrinogen and connective tissue growth factor in tissue-engineered bone grafts

Tissue Engineering and Cell-Based Therapies for Fractures and Bone Defects

Vascularization in Bone Tissue Engineering Constructs

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