Stabilizing insulin-like growth factor-I in poly(d,l-lactide-co-glycolide) microspheres

Meinel, Lorenz; Illi, O. E.; Zapf, J.; Malfanti, Marco; Merkle, Hans P.; Gander, Bruno

doi:10.1016/s0168-3659(00)00352-7

Cited by 154 publications

(82 citation statements)

References 25 publications

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“…However, the tests we employed are commonly used and give sufficient evidence that osteogenesis occurred and to what extent. Indeed, our encapsulation efficiency for BMP-2 is lower than some other values reported in the literature for GFs [ 9,24,34]. However, many of the reported encapsulation methods include the use of high temperatures and considerable amounts of toxic organic solvents without using a carrier protein to protect the GFs.…”

Section: Discussionmentioning

confidence: 58%

“…For the microparticles to be loaded with BMP-2, a coencapsulation process was performed by using bovine serum albumin (BSA) (C 96%; Sigma-Aldrich). BSA protects bioactive molecules such as GFs and peptides from inactivation (eg, as a result of exposure to harsh organic solvents) by binding them [22,34,47]. BSA (200 mg) and BMP-2 (10 lg) were mixed and added to the SPCL solution just before addition to the stirring polyvinyl alcohol emulsification medium.…”

Section: Methodsmentioning

confidence: 99%

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Starch-poly-є-caprolactone Microparticles Reduce the Needed Amount of BMP-2

Balmayor

Feichtinger

Azevedo

et al. 2009

Clin Orthop Relat Res

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BMP-2 is currently administered clinically using collagen matrices often requiring large amounts of BMP-2 due to burst release over a short period of time. We developed and tested a novel injectable drug delivery system consisting of starch-poly-e-caprolactone microparticles for inducing osteogenesis and requiring smaller amounts of BMP-2. We evaluated BMP-2 encapsulation efficiency and the in vitro release profile by enzyme-linked immunosorbent assay. BMP-2 was rapidly released during the first 12 hours, followed by sustained release for up to 10 days. We then evaluated the osteogenic potential of dexamethasone (standard osteogenic induction agent) and BMP-2 after incorporation and during release using an osteo/myoblast cell line (C2C12). Alkaline phosphatase activity was increased by released BMP-2. Mineralization occurred after stimulation with BMP-2-loaded microparticles. A luciferase assay for osteocalcin promoter activity showed high levels of activity upon treatment with BMP-2-loaded microparticles. In contrast, no osteogenesis occurred in C2C12 cells using dexamethasone-loaded microparticles. However, human adipose stem cells exposed to the microparticles produced high amounts of alkaline phosphatase. The data suggest starch-poly-e-caprolactone microparticles are suitable carriers for the incorporation and controlled release of glucocorticoids and growth factors. Specifically, they reduce the amount of BMP-2 needed and allow more sustained osteogenic effects.

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Section: Discussionmentioning

confidence: 58%

Section: Methodsmentioning

confidence: 99%

Starch-poly-є-caprolactone Microparticles Reduce the Needed Amount of BMP-2

Balmayor

Feichtinger

Azevedo

et al. 2009

Clin Orthop Relat Res

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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

685

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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“…Furthermore PEG 400 promoted sufficient release of entrapped NGF. Subsequently, this compound was co-encapsulated with insulin like growth factor I [29], L-asparaginase enzyme [5] or non glycosylated GDNF [30] to prepare particles by conventional multiple emulsion solvent evaporation method.…”

Section: Microsphere Preparation and Characterizationmentioning

confidence: 99%