Large scale segmental bone defect healing through the combined delivery of VEGF and BMP‐2 from biofunctionalized cortical allografts

Sharmin, Farzana; O’Sullivan, Michael; Malinowski, Seth; Lieberman, Jay R.; Khan, Yusuf

doi:10.1002/jbm.b.34193

Cited by 33 publications

(27 citation statements)

References 42 publications

(67 reference statements)

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“…It is notable that approaches to enhance vascularity are now at the forefront of tissue engineering strategies to repair large bone defects, as it is assumed that poor vascularization may be one factor associated with poor healing of large bone defects. Particularly co‐delivery of angiogenic and osteogenic factors is highly topical . As this field moves forward it will be essential to examine potential bone regeneration therapeutics in vascular compromised models.…”

Section: Comorbidities Influencing Fracture Healingmentioning

confidence: 99%

Review of Animal Models of Comorbidities in Fracture‐Healing Research

Haffner‐Luntzer¹,

Hankenson

Ignatius³

et al. 2019

Journal Orthopaedic Research

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There is clinical evidence that patient-specific comorbidities like osteoporosis, concomitant tissue injury, and ischemia may strongly interfere with bone regeneration. However, underlying mechanisms are still unclear. To study these mechanisms in detail, appropriate animal models are needed. For decades, bone healing has been studied in large animals, including dogs, rabbits, pigs, or sheep. However, large animal models display a limited ability to study molecular pathways and cellular functions. Therefore in recent years, mice and rats have become increasingly popular as a model organism for fracture healing research due to the availability of molecular analysis tools and transgenic models. Both large and small animals can be used to study comorbidities and risk factors, modelling the human clinical situation. However, attention has to be paid when choosing an appropriate model due to species differences between large animals, rodents, and humans. This review focuses on large and small animal models for the common comorbidities ischemic injury/reduced vascularization, osteoporosis, and polytrauma, and critically discusses the translational and molecular aspects of these models. Here, we review material which was presented at the workshop "Animal

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Section: Comorbidities Influencing Fracture Healingmentioning

confidence: 99%

Review of Animal Models of Comorbidities in Fracture‐Healing Research

Haffner‐Luntzer¹,

Hankenson

Ignatius³

et al. 2019

Journal Orthopaedic Research

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“…The BMP-2 + BCP results at the end of 4 weeks were better than the BMP-2 + FGF-2 + BCP results, whereas the BMP-2 + FGF-2 + BCP group results were better at the end of 8 weeks [11]. Similarly, Sharmin et al reported that the combination of vascular endothelial growth factor and BMP was superior to BMP-2 alone [60].…”

Section: Discussionmentioning

confidence: 91%

Evaluation of the effects of bone morphogenetic protein-2 on the healing of bone calvarial defects in ovariectomized rats

Kadiroğlu¹,

Karayürek²,

Akbalık³

2020

Turk J Vet Anim Sci

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Introduction Inadequate bone support for oral surgery and periodontal regeneration is a major problem for surgical applications. Additional graft materials are needed in dentistry to repair missing bone tissue. Currently, due to their osteogenic, osteoinductive, and osteoconductive effects, autogenous bone grafts are considered the gold standard under certain conditions [1]. However, other conditions, such as the presence of a second surgical site and the failure to obtain the desired amount of material, limit the use of autogenous bone grafts [2]. Because of this, many researchers have attempted to find an alternative to autografts. For instance, allografts have been used in dentistry for a long time. Allografts have osteoconductive and osteoinductive effects [3]. Regrettably, the devitalization process used to suppress the host immune response and prevent possible disease transmission in cadaveric allografts causes the loss of the mechanical, osteoinductive, and osteoconductive properties of the graft [4,5]. In addition, the maturation times of allografts are longer in defect regions than those of autografts [6,7]. Bone morphogenetic proteins (BMPs) are well known to induce osteogenic effects. Allografts typically contain BMPs that accelerate mesenchymal cell migration and attachment [3]. In both in vitro and in vivo studies of BMP-2, which is a type of BMP, the contribution of BMP-2 to ossification could be shown. BMP-2 promotes periodontal and bone regeneration in some animal models [8,9] and also induces differentiation of preosteoblast cells and thereby increases ossification [10,11]. Fundamentally, BMPs are types of growth factors and belong to the transforming growth factor (TGF-β) family [12]. There are variant BMPs that support bone regeneration, such as BMP-2,-4,-5,-6, and-7 [13]. Recombinant human bone morphogenetic protein-2 (rhBMP-2), generated by recombinant DNA technology from mammalian cells, is known to induce differentiation of osteoblasts at a cellular level and to induce osteogenesis in animal models [14]. Bone graft materials and osteoinductive agents have a synergistic effect [15]. The synergistic effect of BMPs and bone grafts on bone regeneration has been demonstrated in animal studies [11].

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“…Previous studies reported that co-delivery of VEGF with BMP-2 enhanced the bone healing effect of BMP-2 by interacting with BMP-2 and regulating its biological activity. [25,[32][33][34][35]In particular, sequential delivery of VEGF followed by BMP-2 improved bone healing compared to simultaneous VEGF and BMP-2 delivery. [25,35] In contrast, other studies demonstrated insignificant effects of VEGF and BMP-2 on bone healing.…”

Section: Smart Delivery System Enables Tunable Delivery Of Multiple Growth Factorsmentioning

confidence: 99%

Effects of controlled dual growth factor delivery on bone regeneration following composite bone-muscle injury

Subbiah¹,

Cheng

Ruehle³

et al. 2020

Acta Biomaterialia

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Highlights• We developed a smart growth factor delivery system using heparin microparticles and alginate that facilitates tunable delivery of VEGF and BMP-2 in a simultaneous or sequential manner by merely varying the loading strategy.• In vitro, both VEGF and BMP-2 alone promoted vascular growth; however, VEGF was significantly more potent, and there was no detectable benefit of co-delivery.• In vivo, both BMP-2 alone and co-delivery of VEGF and BMP-2 promoted bone formation in the challenging bone/muscle polytrauma model; however, none of the treatment groups restored biomechanical properties to that of uninjured bone.

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Large scale segmental bone defect healing through the combined delivery of VEGF and BMP‐2 from biofunctionalized cortical allografts

Cited by 33 publications

References 42 publications

Review of Animal Models of Comorbidities in Fracture‐Healing Research

Review of Animal Models of Comorbidities in Fracture‐Healing Research

Evaluation of the effects of bone morphogenetic protein-2 on the healing of bone calvarial defects in ovariectomized rats

Effects of controlled dual growth factor delivery on bone regeneration following composite bone-muscle injury

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