Biocompatibility testing of novel starch-based materials with potential application in orthopaedic surgery: a preliminary study

Mendes, Sofia Silva; Reis, Rui L.; Bovell, Y. P.; Cunha, António M.; Blitterswijk, Clemens A. van; Bruijn, Joost D. de

doi:10.1016/s0142-9612(00)00395-1

Cited by 185 publications

(128 citation statements)

References 20 publications

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“…Thus, ours appeared a more efficient method, needing less GF for encapsulation purposes. We chose SPCL blend materials to encapsulate DEX and BMP-2 because of their known biocompatibility [32,35,47] and proven biodegradability [1,2,4]. Moreover, the combination of a hydrophilic natural material (starch) with a hydrophobic synthetic polymer (polycaprolactone) in a single blended material constitutes the major advantage of these microparticles.…”

Section: Discussionmentioning

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: 99%

“…In summary, starch-based materials are able to enhance cell attachment and proliferation of several cell types [32,35,45,47]. Therefore, we tested the suitability of the combination of a microparticle system made of SPCL with bioactive molecules to induce osteogenesis.…”

Section: Discussionmentioning

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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“…Starch-based polymers have been studied and proposed in the last decade by Reis and coworkers [13,[15][16][17][18][19][20][21] for several biomedical applications, such as drug delivery carrier systems, hydrogels and partially degradable bone cements, materials for bone replacement/fixation or fillers for bone defects, and porous structures to be used as scaffolds in tissue engineering of bone and cartilage. These materials were found to be biocompatible [16,[22][23], noncytotoxic, biodegradable [24][25][26][27] and have shown a great processing versatility [13].…”

Section: Introductionmentioning

confidence: 99%

Preparation and characterization of starch-poly-ε-caprolactone microparticles incorporating bioactive agents for drug delivery and tissue engineering applications

et al. 2009

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One limitation associated with the delivery of bioactive agents concerns the short half-life of these molecules when administered intravenously, which results in their loss from the desired site. Incorporation of bioactive agents into depot vehicles provides a means to increase their persistence at the disease site. Major issues are involved in the development of a proper carrier system able to deliver the correct drug, at the desired dose, place and time. In this work, starch-poly-e-caprolactone (SPCL) microparticles were developed for use in drug delivery and tissue engineering (TE) applications. SPCL microparticles were prepared by using an emulsion solvent extraction/evaporation technique, which was demonstrated to be a successful procedure to obtain particles with a spherical shape (particle size between 5 and 900 lm) and exhibiting different surface morphologies. Their chemical structure was confirmed by Fourier transform infrared spectroscopy. To evaluate the potential of the developed microparticles as a drug delivery system, dexamethasone (DEX) was used as model drug. DEX, a well-known component of osteogenic differentiation media, was entrapped into SPCL microparticles at different percentages up to 93%. The encapsulation efficiency was found to be dependent on the polymer concentration and drug-to-polymer ratio. The initial DEX release seems to be governed mainly by diffusion, and it is expected that the remaining DEX will be released when the polymeric matrix starts to degrade. In this work it was demonstrated that SPCL microparticles containing DEX can be successfully prepared and that these microparticular systems seem to be quite promising for controlled release applications, namely as carriers of important differentiation agents in TE.

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“…These materials have shown promising properties in terms of cytocompatibility [21][22][23] which leads their evaluation further on to consider their immunogenic potential. The aim of the present study was to investigate the contribution of various types of starchbased materials and composites and respective changes in their chemical and physical properties in leukocyte adhesion and activation, namely in promoting differentiation of different subsets of macrophages in order to demonstrate the effect of these materials in terms of an immunogenic response.…”

Section: Introductionmentioning

confidence: 99%

The effect of starch-based biomaterials on leukocyte adhesion and activation in vitro

Marques

Reis

Hunt

2005

J Mater Sci: Mater Med

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Leukocyte adhesion to biomaterials has long been recognised as a key element to determine their inflammatory potential. Results regarding leukocyte adhesion and activation are contradictory in some aspects of the material's effect in determining these events. It is clear that together with the wettability or hydrophilicity/hydrophobicity, the roughness of a substrate has a major effect on leukocyte adhesion. Both the chemical and physical properties of a material influence the adsorbed proteins layer which in turn determines the adhesion of cells.In this work polymorphonuclear (PMN) cells and a mixed population of monocytes/macrophages and lymphocytes (mononuclear cells) were cultured separately with a range of starch-based materials and composites with hydroxyapatite (HA). A combination of both reflected light microscopy and scanning electron microscopy (SEM) was used in order to study the leukocyte morphology. The quantification of the enzyme lactate dehydrogenase (LDH) was used to determine the number of viable cells adhered to the polymers. Cell adhesion and activation was characterised by immunocytochemistry based on the expression of several adhesion molecules, crucial in the progress of an inflammatory response.This work supports previous in vitro studies with PMN and monocytes/macrophages, which demonstrated that there are several properties of the materials that can influence and determine their biological response. From our study, monocytes/macrophages and lymphocytes adhere in similar amounts to more hydrophobic (SPCL) and to moderately hydrophilic (SEVA-C) surfaces and do not preferentially adhere to rougher substrates (SCA). Contrarily, more hydrophilic surfaces (SCA) induced higher PMN adhesion and lower activation. In addition, the hydroxyapatite reinforcement induces changes in cell behaviour for some materials but not for others.

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Biocompatibility testing of novel starch-based materials with potential application in orthopaedic surgery: a preliminary study

Cited by 185 publications

References 20 publications

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

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

Preparation and characterization of starch-poly-ε-caprolactone microparticles incorporating bioactive agents for drug delivery and tissue engineering applications

The effect of starch-based biomaterials on leukocyte adhesion and activation in vitro

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