Ectopic bone formation via rhBMP-2 delivery from porous bioabsorbable polymer scaffolds

Whang, Kyumin; Tsai, D. C.; Nam, Ellis K.; Aitken, M.E.; Sprague, Stuart M.; Patel, Parth; Healy, Kevin E.

doi:10.1002/(sici)1097-4636(19981215)42:4<491::aid-jbm3>3.0.co;2-f

Cited by 192 publications

(78 citation statements)

References 29 publications

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“…Several researchers have utilized this well-characterized copolymer for encapsulation and release of a wide variety of bioactive molecules and drugs including TGF-b, BMPs, IGFs, VEGF, NGF, DNA, vancomycin, gentamysin, cisplatin, and others. [261][262][263][264][265][266][267][268] To successfully fabricate and encapsulate PLGA scaffold with these molecules, a wide variety of creative approaches have been taken such as emulsion freeze-drying, 269 nano and microparticle encapsulation, [270][271][272] double emulsion solvent extraction, 273 electrospinning, [274][275][276] compression molding, 277 and others. As mentioned earlier, a fundamental problem with utilizing growth factors is their characteristic short half life in physiological environments.…”

Section: Common Copolymers In Bone Engineeringmentioning

confidence: 99%

Bone tissue engineering: A review in bone biomimetics and drug delivery strategies

Porter

Ruckh

Popat

2009

Biotechnology Progress

671

499

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Critical‐sized defects in bone, whether induced by primary tumor resection, trauma, or selective surgery have in many cases presented insurmountable challenges to the current gold standard treatment for bone repair. The primary purpose of a tissue‐engineered scaffold is to use engineering principles to incite and promote the natural healing process of bone which does not occur in critical‐sized defects. A synthetic bone scaffold must be biocompatible, biodegradable to allow native tissue integration, and mimic the multidimensional hierarchical structure of native bone. In addition to being physically and chemically biomimetic, an ideal scaffold is capable of eluting bioactive molecules (e.g., BMPs, TGF‐βs, etc., to accelerate extracellular matrix production and tissue integration) or drugs (e.g., antibiotics, cisplatin, etc., to prevent undesired biological response such as sepsis or cancer recurrence) in a temporally and spatially controlled manner. Various biomaterials including ceramics, metals, polymers, and composites have been investigated for their potential as bone scaffold materials. However, due to their tunable physiochemical properties, biocompatibility, and controllable biodegradability, polymers have emerged as the principal material in bone tissue engineering. This article briefly reviews the physiological and anatomical characteristics of native bone, describes key technologies in mimicking the physical and chemical environment of bone using synthetic materials, and provides an overview of local drug delivery as it pertains to bone tissue engineering is included. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009

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Section: Common Copolymers In Bone Engineeringmentioning

confidence: 99%

Bone tissue engineering: A review in bone biomimetics and drug delivery strategies

Porter

Ruckh

Popat

2009

Biotechnology Progress

671

499

View full text Add to dashboard Cite

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“…The most widely used poly(α-hydroxy ester) polymers for particle-based strategies are polylactide (PLA), polyglycolide (PGA) and their co-polymers (poly-DL-lactide-coglycolide) (PLGA) (Brekke, 1996;Hollinger and Leong, 1996;Whang et al, 1998). Their widespread use stems from the ability of these materials to serve a multitude of purposes and applications.…”

Section: Incorporation and Releasementioning

confidence: 99%

Materials in particulate form for tissue engineering. 1. Basic concepts

Silva

Ducheyne

Reis

2007

J Tissue Eng Regen Med

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For biomedical applications, materials small in size are growing in importance. In an era where 'nano' is the new trend, micro-and nano-materials are in the forefront of developments. Materials in the particulate form aim to designate systems with a reduced size, such as micro-and nanoparticles. These systems can be produced starting from a diversity of materials, of which polymers are the most used. Similarly, a multitude of methods are to produce particulate systems, and both materials and methods are critically reviewed here. Among the varied applications that materials in the particulate form can have, drug delivery systems are probably the most prominent, as these have been in the forefront of interest for biomedical applications. The basic concepts pertaining to drug delivery are summarized, and the role of polymers as drug delivery systems conclude this review. JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE R E V I E W A R T I C L E

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“…[25][26][27] In addition to the direct application of recombinant BMP proteins, numerous reports have confirmed the ability of adenoviral or retroviral vector-mediated gene transfer of several BMPs to induce bone formation in animal models. 18,20,21,23,[28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44] Although a plethora of studies have demonstrated the ability of several BMPs, mostly BMP-2 and BMP-7, to promote osteogenesis, it is unclear whether or not BMPs other than those currently being tested in clinical trials are more potent stimulators of new bone formation. Thus, it is important to conduct a comprehensive comparative analysis of the in vivo osteogenic activity of all BMPs.…”

Section: Introductionmentioning

confidence: 99%

Characterization of the distinct orthotopic bone-forming activity of 14 BMPs using recombinant adenovirus-mediated gene delivery

et al. 2004

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Efficacious bone regeneration could revolutionize the clinical management of bone and musculoskeletal disorders. Although several bone morphogenetic proteins (BMPs) (mostly BMP-2 and BMP-7) have been shown to induce bone formation, it is unclear whether the currently used BMPs represent the most osteogenic ones. Until recently, comprehensive analysis of osteogenic activity of all BMPs has been hampered by the fact that recombinant proteins are either not biologically active or not available for all BMPs. In this study, we used recombinant adenoviruses expressing the 14 types of BMPs (AdBMPs), and demonstrated that, in addition to currently used BMP-2 and BMP-7, BMP-6 and BMP-9 effectively induced orthotopic ossification when either AdBMP-transduced osteoblast progenitors or the viral vectors were injected into the quadriceps of athymic mice. Radiographic and histological evaluation demonstrated that BMP-6 and BMP-9 induced the most robust and mature ossification at multiple time points. BMP-3, a negative regulator of bone formation, was shown to effectively inhibit orthotopic ossification induced by BMP-2, BMP-6, and BMP-7. However, BMP-3 exerted no inhibitory effect on BMP-9-induced bone formation, suggesting that BMP-9 may transduce osteogenic signaling differently. Our findings suggest that BMP-6 and BMP-9 may represent more effective osteogenic factors for bone regeneration.

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Ectopic bone formation via rhBMP-2 delivery from porous bioabsorbable polymer scaffolds

Cited by 192 publications

References 29 publications

Bone tissue engineering: A review in bone biomimetics and drug delivery strategies

Bone tissue engineering: A review in bone biomimetics and drug delivery strategies

Materials in particulate form for tissue engineering. 1. Basic concepts

Characterization of the distinct orthotopic bone-forming activity of 14 BMPs using recombinant adenovirus-mediated gene delivery

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