Sustained BMP-2 delivery and injectable bone regeneration using thermosensitive polymeric nanoparticle hydrogel bearing dual interactions with BMP-2

Seo, Bo-Bae; Choi, Hyung-Seok; Koh, Jeong‐Tae; Song, Soo‐Chang

doi:10.1016/j.jconrel.2015.04.023

Cited by 96 publications

(86 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In recent studies thermo-sensitive DDSs have been used for: co-delivery of drugs and genes, 94 induced therapeutic angiogenesis in peripheral vascular disease, 95 allowed ophthalmic drug delivery with enhanced corneal permeation and retention capacity, 96 produced a new intelligent dermatological formulation, 97 allowed mucoadhesive-thermogel-based vaginal delivery, 98 protein delivery in tissue engineering 99 and for bone regeneration. 100 Other applications have been reported in cutaneous protein delivery, 101 delivery to the uterus for efficacious therapy of uterine diseases ( e.g. bovine reproductive disorders), 102 therapy of inflammatory bowel disease with enhanced colonic retention of drugs, 103 real-time image-guided theranostic drug delivery in cancer chemotherapy, 104 efficient mild hyperthermia with increased tumor retention and high specificity toward cancer and angiogenic cells, 105 and treatment of hypoxic hepatocellular carcinoma.…”

Section: Different Stimuli-responsive Mnpsmentioning

confidence: 99%

Smart micro/nanoparticles in stimulus-responsive drug/gene delivery systems

et al. 2016

View full text Add to dashboard Cite

New achievements in the realm of nanoscience and innovative techniques of nanomedicine have moved micro/nanoparticles (MNPs) to the point of becoming actually useful for practical applications in the near future. Various differences between the extracellular and intracellular environments of cancerous and normal cells and the particular characteristics of tumors such as physicochemical properties, neovasculature, elasticity, surface electrical charge, and pH have motivated the design and fabrication of inventive “smart” MNPs for stimulus-responsive controlled drug release. These novel MNPs can be tailored to be responsive to pH variations, redox potential, enzymatic activation, thermal gradients, magnetic fields, light, and ultrasound (US), or can even be responsive to dual or multi-combinations of different stimuli. This unparalleled capability has increased their importance as site-specific controlled drug delivery systems (DDSs) and has encouraged their rapid development in recent years. An in-depth understanding of the underlying mechanisms of these DDS approaches is expected to further contribute to this groundbreaking field of nanomedicine. Smart nanocarriers in the form of MNPs that can be triggered by internal or external stimulus are summarized and discussed in the present review, including pH-sensitive peptides and polymers, redox-responsive micelles and nanogels, thermo- or magnetic-responsive nanoparticles (NPs), mechanical- or electrical-responsive MNPs, light or ultrasound-sensitive particles, and multi-responsive MNPs including dual stimuli-sensitive nanosheets of graphene. This review highlights the recent advances of smart MNPs categorized according to their activation stimulus (physical, chemical, or biological) and looks forward to future pharmaceutical applications.

show abstract

Section: Different Stimuli-responsive Mnpsmentioning

confidence: 99%

Smart micro/nanoparticles in stimulus-responsive drug/gene delivery systems

et al. 2016

View full text Add to dashboard Cite

show abstract

“…As is well known, the key for effectively rhBMP-2-induced bone regeneration lies in localization and continuous osteogenic stimulation at defected sites 41 From this viewpoint, one major advantage of this delivery system is that this novel AHbased tethering system could support a sustainably controlled release of rhBMP-2 as illustrated in the in vitro and in vivo release proles (Fig. 5B and 7A) while maintaining high bioactivity locally as demonstrated by the enhanced alkaline phosphatase activity and ectopic bone formation aer implantation in vivo (Fig.…”

Section: Discussionmentioning

confidence: 99%

Tethering of rhBMP-2 upon calcium phosphate cement via alendronate/heparin for localized, sustained and enhanced osteoactivity

et al. 2017

View full text Add to dashboard Cite

Localized, continuous and effective osteogenic stimulation to defected sites is still a great challenge for recombinant human bone morphogenetic protein-2 (rhBMP-2) in clinical bone regeneration. In this study, a novel delivery system was engineered to tether rhBMP-2 onto the surface of calcium phosphate cement (CPC) based on the high affinity between alendronate and CPC, as well as the strong binding of heparin and rhBMP-2. Alendronate was first grated to heparin via the EDC/NHS reaction and then the resultant alendronate-heparin (AH) was adsorbed onto the CPC surface. RhBMP-2 was further anchored onto the CPC-AH surface. The results from in vitro release and in vivo fluorescence-labeled traces all indicated that the AH-tethered rhBMP-2 exhibited a more stable and stronger adherence to the CPC surface than the CPC-adsorbed and heparin-anchored ones. Moreover, based on the results of the alkaline phosphatase (ALP) activity in skeletal myoblasts (C2C12) in vitro and osteogenic efficacy in vivo, it could be seen that rhBMP-2-induced osteogenic bioactivity was also significantly enhanced on the CPC-AH surface. These results demonstrated that the tethering of rhBMP-2 onto calcium phosphate surface via AH presented an effective method to achieve a localized and sustained exposure to targeted cells, and consequently to promote bone regeneration.

show abstract

“…This family includes, among others, five isoforms of TGF-β (1-5), bone morphogenetic proteins (BMPs) and growth differentiation factors (GDFs), which participate in a complex series of molecular events that lead to mesenchymal precursors during bone morphogenesis [25,29,33,36]. They originate from high molecular weight precursors and are activated by proteolytic enzymes.…”

Section: Transforming Growth Factor-beta (Tgf-β) Superfamilymentioning

confidence: 99%

Regenerative Medicine: A New Paradigm in Bone Regeneration

Chaparro¹,

Linero²

2016

Advanced Techniques in Bone Regeneration

View full text Add to dashboard Cite

Bone defects are the cause of functional disability and the restoration of skeletal function remains an important challenge on orthopedics, neurosurgery and oral and maxillofacial surgery. Because of the limitations of the currently used techniques for the reconstruction of bone defects and the difficulties for the implementation of new therapeutic strategies, a new paradigm in the field of reconstructive surgery has arisen, leading to tissue engineering and regenerative medicine. Mesenchymal stem cells (MSC) have emerged as a promising alternative for the treatment of bone lesions. It was postulated that the therapeutic action was the result of proliferation and differentiation of MSCs, replacing injured tissue. However, recent studies have shown that MSCs secrete a number of trophic factors that have a strong effect during repair and tissue regeneration. This represents a shift from a paradigm centered on MSC proliferation and differentiation to a new paradigm in which the MSCs exert their beneficial effect by the secretion of paracrine factors that induce endogenous repair mechanisms. This chapter will bring together basic and clinical aspects, focused on novel findings on MSC paracrine effect and the development of new therapeutic strategies based on growth factors, cytokines and signaling molecules involved in bone regeneration.

show abstract

Sustained BMP-2 delivery and injectable bone regeneration using thermosensitive polymeric nanoparticle hydrogel bearing dual interactions with BMP-2

Cited by 96 publications

References 29 publications

Smart micro/nanoparticles in stimulus-responsive drug/gene delivery systems

Smart micro/nanoparticles in stimulus-responsive drug/gene delivery systems

Tethering of rhBMP-2 upon calcium phosphate cement via alendronate/heparin for localized, sustained and enhanced osteoactivity

Regenerative Medicine: A New Paradigm in Bone Regeneration

Contact Info

Product

Resources

About