BMP and TGFβ use and release in bone regeneration

Abstract

A fracture that does not unite in nine months is defined as nonunion. Nonunion is common in fragmented fractures and large bone defects where vascularization is impaired. The distal third of the tibia, the scaphoid bone or the talus fractures are furthermore prone to nonunion. Open fractures and spinal fusion cases also need special monitoring for healing. Bone tissue regeneration can be attained by autografts, allografts, xenografts and synthetic materials, however their limited availability and the increased surgical time as well as the donor site morbidity of autograft use, and lower probability of success, increased costs and disease transmission and immunological reaction probability of allografts oblige us to find better solutions and new grafts to overcome the cons. A proper biomaterial for regeneration should be osteoinductive, osteoconductive, biocompatible and mechanically suitable. Cytokine therapy, where growth factors are introduced either exogenously or triggered endogenously, is one of the commonly used method in bone tissue engineering. Transforming growth factor β (TGFβ) superfamily, which can be divided structurally into two groups as bone morphogenetic proteins (BMPs), growth differentiation factors (GDFs) and TGFβ, activin, Nodal branch, Mullerian hormone, are known to be produced by osteoblasts and other bone cells and present already in bone matrix abundantly, to take roles in bone homeostasis. BMP family, as the biggest subfamily of TGFβ superfamily, is also reported to be the most effective growth factors in bone and development, which makes them one of the most popular cytokines used in bone regeneration. Complications depending on the excess use of growth factors, and pleiotropic functions of BMPs are however the main reasons of why they should be approached with care. In this review, the Smad dependent signaling pathways of TGFβ and BMP families and their relations and the applications in preclinical and clinical studies will be briefly summarized.

Innovative Concepts and Recent Breakthrough for Engineered Graft and Constructs for Bone Regeneration: A Literature Systematic Review

“…Its use has led to results comparable to those of autologous grafts in terms of bone volume and density and even reduced the risk of infection and the time of hospitalization [ 113 ]. It has been reported that bone repair could be produced by BMP-2, but this ability is dose-dependent [ 114 ], while a high dosage could give unwanted effects [ 115 , 116 ]. In the tooth matrix, the BMP is found in physiological quantities and therefore adequate for the patient.…”

Autologous regenerative stimulants for bone allograft implantation

“…По данным разных литературных источников, вероятность иммунной реакции после имплантации таких материалов составляет около 10% [9]. Деминерализованный костный матрикс (ДМК) -это высокоочищенный, производный аллогенной кости, материал, лишенный (более чем на 40%) минерального компонента при сохранении коллагена и неколлагеновых белков-индукторов [10], определяющих остеоиндуктивность. Обладая пластичностью и высокой степенью биодеградации в сравнении с недеминерализованными костными материалами, процесс остеоинтеграции и ремоделирования имплантированного ДМК происходит интенсивнее [4].…”

The Cross-Talks Among Bone Morphogenetic Protein (BMP) Signaling and Other Prominent Pathways Involved in Neural Differentiation

“…The human genome contains more than 20 types of heterodimer or homodimer BMPs. According to the sequence homology of their amino acids, structures, and functions, they are divided into four separate subfamilies: (1) BMP2 and 4; (2) BMP5, 6, 7, 8a, and 8b; (3) BMP9 and 10; and (4) BMP12, 13, 14 (Bal et al, 2020 ). BMPs are involved in biological activities such as embryogenesis (epidermal induction and inhibiting ectodermal fate), developmental processes (cell proliferation, differentiation, and apoptosis), and also the maintenance of adult tissue homeostasis (Wang et al, 2014 ; Biniazan et al, 2021 ).…”

“…(2) BMP5,6,7,8a,and 8b; (3) BMP9 and 10; and (4) BMP12, 13, 14 (Bal et al, 2020). BMPs are involved in biological activities such as embryogenesis (epidermal induction and inhibiting ectodermal fate), developmental processes (cell proliferation, differentiation, and apoptosis), and also the maintenance of adult tissue homeostasis (Wang et al, 2014;Biniazan et al, 2021).…”