BMP delivery systems for bone regeneration: Healthy vs osteoporotic population. Review

González, Enrique; García-García, Patricia; Évora, Carmen; Delgado, Araceli

doi:10.1016/j.jddst.2017.05.014

Cited by 16 publications

(16 citation statements)

References 114 publications

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“…Several carriers have been proposed for the delivery of bone active molecules for critical defect healing. A majority of them often involve tedious fabrication strategies, and the preparation in the operating room remains a challenge due to practical reasons (24). The goal of this study was to use a clinically tested CaS/HA biomaterial that could provide an easy-to-implement single-stage platform for the delivery of the bone active molecules such as rhBMP-2 and ZA in a clinically relevant critical bone defect model in rats.…”

Section: Introductionmentioning

confidence: 99%

A facile one-stage treatment of critical bone defects using a calcium sulfate/hydroxyapatite biomaterial providing spatiotemporal delivery of bone morphogenic protein–2 and zoledronic acid

et al. 2020

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Bone morphogenic proteins (BMPs) are the only true osteoinductive molecules. Despite being tremendously potent, their clinical use has been limited for reasons including supraphysiological doses, suboptimal delivery systems, and the pro-osteoclast effect of BMPs. Efforts to achieve spatially controlled bone formation using BMPs are being made. We demonstrate that a carrier consisting of a powder of calcium sulfate/hydroxyapatite (CaS/HA) mixed with bone active molecules provides an efficient drug delivery platform for critical femoral defect healing in rats. The bone-active molecules were composed of osteoinductive rhBMP-2 and the bisphosphonate, and zoledronic acid (ZA) was chosen to overcome BMP-2–induced bone resorption. It was demonstrated that delivery of rhBMP-2 was necessary for critical defect healing and restoration of mechanical properties, but codelivery of BMP-2 and ZA led to denser and stronger fracture calluses. Together, the CaS/HA biomaterial with rhBMP-2 and/or ZA can potentially be used as an off-the-shelf alternative to autograft bone.

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Section: Introductionmentioning

confidence: 99%

A facile one-stage treatment of critical bone defects using a calcium sulfate/hydroxyapatite biomaterial providing spatiotemporal delivery of bone morphogenic protein–2 and zoledronic acid

et al. 2020

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“…Furthermore, the ability to control the release rate of BMP‐2 post‐implantation represents a distinct advantage over existing systems which frequently demonstrate BMP release as a “burst release” immediately following implantation rather than a sustained release over time. This release profile differs greatly from the physiologic processes in normal bone healing and results in the formation of poor quality bone 26 . Slower, more sustained release kinetics are more biologically accurate and are reported to result in an enhanced bone healing response 4,27–29 .…”

Section: Discussionmentioning

confidence: 99%

Hydroxyapatite sonosensitization of ultrasound‐triggered, thermally responsive hydrogels: An on‐demand delivery system for bone repair applications

et al. 2021

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While bones have the innate capability to physiologically regenerate, in certain cases regeneration is suboptimal, too slow, or does not occur. Biomaterials‐based growth factor delivery systems have shown potential for the treatment of challenging bone defects, however, achieving controlled growth factor release remains a challenge. The objective of this study was to develop a thermally responsive hydrogel for bone regeneration capable of ultrasound‐triggered on‐demand delivery of therapeutic agents. Furthermore, it was hypothesized that incorporation of hydroxyapatite (HA) into the hydrogel could increase sonosensitization, augmenting ultrasound sensitivity to enable controlled therapeutic release to the target tissue. Alginate thermally responsive P(Alg‐g‐NIPAAm) hydrogels were fabricated and varying quantities of HA (1, 3, 5, and 7% wt./vol.) incorporated. All hydrogels were highly injectable (maximum injection force below 6.5 N) and rheological characterization demonstrated their ability to gel at body temperature. The study demonstrated the ultrasound‐triggered release of sodium fluorescein (NaF), bovine serum albumin (BSA), and bone morphogenetic protein 2 (BMP‐2) from the hydrogels. Release rates of BSA and BMP‐2 were significantly enhanced in the HA containing hydrogels, confirming for the first time the role of HA as a son sensitizer. Together these results demonstrate the potential of these ultrasound‐triggered thermally responsive hydrogels for on‐demand delivery of therapeutic agents for bone regeneration.

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“…A controlled elution of BMP‐2 for longer time periods is required for optimal bone healing . It is important to note that both in vitro and in vivo release kinetics profiles differ from each other to a great extent because in in vivo the cellular activity, blood circulation, and scaffold degradation, lead to a more pronounced and accelerated release . Commercially, Medtronic has been using a hollow titanium cage filled with rhBMP‐2 adsorbed collagen sponge (trademarked as INFUSE‐ACS) to treat interbody spinal fusions, which shows a burst release of BMP‐2 and >95% of release after 2 weeks of post in vivo implantation .…”

Section: Discussionmentioning

confidence: 99%

Interplay of topographical and biochemical cues in regulating osteoblast cellular activity in BMP‐2 eluting three‐dimensional cellular titanium alloy mesh structures

Nune

Misra

Bai

et al. 2018

J Biomedical Materials Res

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The objective of this study is to elucidate the elution response of bone morphogenetic protein (BMP-2) in tuning cellular functions on 3D-printed titanium alloy mesh scaffolds subjected to microarc/plasma electrolytic oxidation process. The microtopographical cues enabled strong interaction with BMP-2 protein, which led to controlled release. Furthermore, the interaction of BMP-2 with the surface microtopographical cue regulated osteoblast cellular activity by contributing to the early phase differentiation and mineralization of osteoblasts. The in vitro BMP-2 release kinetics showed an initial burst of BMP-2 after day 1, followed by a controlled release on plasma electrolytic oxidized mesh structure. The profile represented that the rate of release decreased with increase in time on both as-fabricated and plasma electrolytic oxidized mesh structures after 24 h, with relatively higher degree on plasma electrolytic oxidized mesh structure. Furthermore, the in vitro osteoblast cellular activity indicated enhanced osteogenic induction on BMP-2 adsorbed plasma electrolytic oxidized mesh structure. Cells penetrated into micropores through several filopodia-like cellular extensions by increasing the area of contact, leading to stronger cell adhesion on BMP-2 adsorbed plasma electrolytic oxidized mesh structure. The up-regulation of biochemical markers and quantification of the expression level of cell secreted proteins underscored the determining role of BMP-2 eluting 3D mesh structure in modulating osteoblasts functions. The study emphasizes the potential of BMP-2 in rendering plasma electrolytic oxidized 3D-printed titanium alloy mesh structure osteoinductive and controlled delivery of BMP-2.

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BMP delivery systems for bone regeneration: Healthy vs osteoporotic population. Review

Cited by 16 publications

References 114 publications

A facile one-stage treatment of critical bone defects using a calcium sulfate/hydroxyapatite biomaterial providing spatiotemporal delivery of bone morphogenic protein–2 and zoledronic acid

A facile one-stage treatment of critical bone defects using a calcium sulfate/hydroxyapatite biomaterial providing spatiotemporal delivery of bone morphogenic protein–2 and zoledronic acid

Hydroxyapatite sonosensitization of ultrasound‐triggered, thermally responsive hydrogels: An on‐demand delivery system for bone repair applications

Interplay of topographical and biochemical cues in regulating osteoblast cellular activity in BMP‐2 eluting three‐dimensional cellular titanium alloy mesh structures

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