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Antonios G Mikos - One of the best experts on this subject based on the ideXlab platform.

  • dual growth factor delivery from degradable oligo poly ethylene glycol fumarate hydrogel scaffolds for cartilage tissue engineering
    Journal of Controlled Release, 2005
    Co-Authors: Theresa A Holland, Yasuhiko Tabata, Antonios G Mikos
    Abstract:

    Abstract This work describes the development of a non-invasive means of simultaneously delivering insulin-like growth factor-1 (IGF-1) and transforming growth factor-β1 (TGF-β1) to injured cartilage tissue in a controlled manner. This novel delivery technology employs the water-soluble polymer, oligo(poly(ethylene glycol) fumarate) (OPF), in the fabrication of biodegradable hydrogels which encapsulate gelatin Microparticles. Release studies first examined the effect of gelatin isoelectric point (IEP) and crosslinking extent on IGF-1 release from these Microparticles. In the presence of collagenase, highly crosslinked, acidic gelatin (IEP=5.0) provided sustained release of IGF-1, 95.2±2.9% cumulative release at day 28, while less crosslinked Microparticles and Microparticles of alternate IEP exhibited similar release values after only 6 days. Encapsulation of these highly crosslinked Microparticles in a network of OPF provided a means to further control release, reducing final cumulative release to 70.2±4.7% in collagenase-containing PBS. Final release values from OPF–gelatin Microparticle composites could be altered by incorporating less crosslinked, non-loaded Microparticles within these constructs. Finally, this technology was extended to the dual delivery of IGF-1 and TGF-β1 by loading these growth factors into either the OPF hydrogel phase or gelatin Microparticle phase of composites. Release profiles were successfully manipulated by altering the phase of growth factor loading and Microparticle crosslinking extent. For instance, by loading TGF-β1 into the gelatin Microparticle phase, a burst release of 10.8±0.7% was achieved, while loading this growth factor into the OPF hydrogel phase resulted in a burst release of 25.2±1.5%. With either system, simultaneous, slow release of IGF-1 over a 4-week period was accomplished by selectively loading this protein into highly crosslinked, encapsulated Microparticles. These results demonstrate the utility of these systems in future studies to assess the interplay and time course of multiple growth factors in cartilage repair.

  • dual growth factor delivery from degradable oligo poly ethylene glycol fumarate hydrogel scaffolds for cartilage tissue engineering
    Journal of Controlled Release, 2005
    Co-Authors: Theresa A Holland, Yasuhiko Tabata, Antonios G Mikos
    Abstract:

    This work describes the development of a non-invasive means of simultaneously delivering insulin-like growth factor-1 (IGF-1) and transforming growth factor-beta1 (TGF-beta1) to injured cartilage tissue in a controlled manner. This novel delivery technology employs the water-soluble polymer, oligo(poly(ethylene glycol) fumarate) (OPF), in the fabrication of biodegradable hydrogels which encapsulate gelatin Microparticles. Release studies first examined the effect of gelatin isoelectric point (IEP) and crosslinking extent on IGF-1 release from these Microparticles. In the presence of collagenase, highly crosslinked, acidic gelatin (IEP=5.0) provided sustained release of IGF-1, 95.2+/-2.9% cumulative release at day 28, while less crosslinked Microparticles and Microparticles of alternate IEP exhibited similar release values after only 6 days. Encapsulation of these highly crosslinked Microparticles in a network of OPF provided a means to further control release, reducing final cumulative release to 70.2+/-4.7% in collagenase-containing PBS. Final release values from OPF-gelatin Microparticle composites could be altered by incorporating less crosslinked, non-loaded Microparticles within these constructs. Finally, this technology was extended to the dual delivery of IGF-1 and TGF-beta1 by loading these growth factors into either the OPF hydrogel phase or gelatin Microparticle phase of composites. Release profiles were successfully manipulated by altering the phase of growth factor loading and Microparticle crosslinking extent. For instance, by loading TGF-beta1 into the gelatin Microparticle phase, a burst release of 10.8+/-0.7% was achieved, while loading this growth factor into the OPF hydrogel phase resulted in a burst release of 25.2+/-1.5%. With either system, simultaneous, slow release of IGF-1 over a 4-week period was accomplished by selectively loading this protein into highly crosslinked, encapsulated Microparticles. These results demonstrate the utility of these systems in future studies to assess the interplay and time course of multiple growth factors in cartilage repair.

  • transforming growth factor beta 1 release from oligo poly ethylene glycol fumarate hydrogels in conditions that model the cartilage wound healing environment
    Journal of Controlled Release, 2004
    Co-Authors: Theresa A Holland, Yasuhiko Tabata, Joerg Tessmar, Antonios G Mikos
    Abstract:

    This research demonstrates that controlled material degradation and transforming growth factor-beta1 (TGF-beta1) release can be achieved by encapsulation of TGF-beta1-loaded gelatin Microparticles within the biodegradable polymer oligo(poly(ethylene glycol) fumarate) (OPF), so that these Microparticles function as both a digestible porogen and a delivery vehicle. Release studies performed with non-encapsulated Microparticles confirmed that at normal physiological pH, TGF-beta1 complexes with acidic gelatin, resulting in slow release rates. At pH 4.0, this complexation no longer persists, and TGF-beta1 release is enhanced. However, by encapsulating TGF-beta1-loaded Microparticles in a network of OPF, release at either pH can be diffusionally controlled. For instance, after 28 days of incubation at pH 4.0, final cumulative release from non-encapsulated Microparticles crosslinked in 10 and 40 mM glutaraldehyde (GA) was 75.4+/-1.6% and 76.6+/-1.1%, respectively. However, when either Microparticle formulation was encapsulated in an OPF hydrogel (noted as OPF-10 mM and OPF-40 mM, respectively), these values were reduced to 44.7+/-14.6% and 47.4+/-4.7%. More interestingly, release studies, in conditions that model the expected collagenase concentration of injured cartilage, demonstrated that by altering the Microparticle crosslinking extent and loading within OPF hydrogels, TGF-beta1 release, composite swelling, and polymer loss could be systematically altered. Composites encapsulating less crosslinked Microparticles (OPF-10 mM) exhibited 100% release after only 18 days and were completely degraded by day 24 in collagenase-containing phosphate-buffered saline (PBS). Hydrogels encapsulating 40 mM GA Microparticles did not exhibit 100% release or polymer loss until day 28. Hydrogels with no Microparticle component demonstrated only 79.3+/-9.2% release and 89.2+/-3.4% polymer loss after 28 days in enzyme-containing PBS. Accordingly, these studies confirm that the rate of TGF-beta1 release and material degradation can be controlled by altering key parameters of these novel, in situ crosslinkable biomaterials, so that TGF-beta1 release and scaffold degradation may be tailored to optimize cartilage repair.

Theresa A Holland - One of the best experts on this subject based on the ideXlab platform.

  • dual growth factor delivery from degradable oligo poly ethylene glycol fumarate hydrogel scaffolds for cartilage tissue engineering
    Journal of Controlled Release, 2005
    Co-Authors: Theresa A Holland, Yasuhiko Tabata, Antonios G Mikos
    Abstract:

    Abstract This work describes the development of a non-invasive means of simultaneously delivering insulin-like growth factor-1 (IGF-1) and transforming growth factor-β1 (TGF-β1) to injured cartilage tissue in a controlled manner. This novel delivery technology employs the water-soluble polymer, oligo(poly(ethylene glycol) fumarate) (OPF), in the fabrication of biodegradable hydrogels which encapsulate gelatin Microparticles. Release studies first examined the effect of gelatin isoelectric point (IEP) and crosslinking extent on IGF-1 release from these Microparticles. In the presence of collagenase, highly crosslinked, acidic gelatin (IEP=5.0) provided sustained release of IGF-1, 95.2±2.9% cumulative release at day 28, while less crosslinked Microparticles and Microparticles of alternate IEP exhibited similar release values after only 6 days. Encapsulation of these highly crosslinked Microparticles in a network of OPF provided a means to further control release, reducing final cumulative release to 70.2±4.7% in collagenase-containing PBS. Final release values from OPF–gelatin Microparticle composites could be altered by incorporating less crosslinked, non-loaded Microparticles within these constructs. Finally, this technology was extended to the dual delivery of IGF-1 and TGF-β1 by loading these growth factors into either the OPF hydrogel phase or gelatin Microparticle phase of composites. Release profiles were successfully manipulated by altering the phase of growth factor loading and Microparticle crosslinking extent. For instance, by loading TGF-β1 into the gelatin Microparticle phase, a burst release of 10.8±0.7% was achieved, while loading this growth factor into the OPF hydrogel phase resulted in a burst release of 25.2±1.5%. With either system, simultaneous, slow release of IGF-1 over a 4-week period was accomplished by selectively loading this protein into highly crosslinked, encapsulated Microparticles. These results demonstrate the utility of these systems in future studies to assess the interplay and time course of multiple growth factors in cartilage repair.

  • dual growth factor delivery from degradable oligo poly ethylene glycol fumarate hydrogel scaffolds for cartilage tissue engineering
    Journal of Controlled Release, 2005
    Co-Authors: Theresa A Holland, Yasuhiko Tabata, Antonios G Mikos
    Abstract:

    This work describes the development of a non-invasive means of simultaneously delivering insulin-like growth factor-1 (IGF-1) and transforming growth factor-beta1 (TGF-beta1) to injured cartilage tissue in a controlled manner. This novel delivery technology employs the water-soluble polymer, oligo(poly(ethylene glycol) fumarate) (OPF), in the fabrication of biodegradable hydrogels which encapsulate gelatin Microparticles. Release studies first examined the effect of gelatin isoelectric point (IEP) and crosslinking extent on IGF-1 release from these Microparticles. In the presence of collagenase, highly crosslinked, acidic gelatin (IEP=5.0) provided sustained release of IGF-1, 95.2+/-2.9% cumulative release at day 28, while less crosslinked Microparticles and Microparticles of alternate IEP exhibited similar release values after only 6 days. Encapsulation of these highly crosslinked Microparticles in a network of OPF provided a means to further control release, reducing final cumulative release to 70.2+/-4.7% in collagenase-containing PBS. Final release values from OPF-gelatin Microparticle composites could be altered by incorporating less crosslinked, non-loaded Microparticles within these constructs. Finally, this technology was extended to the dual delivery of IGF-1 and TGF-beta1 by loading these growth factors into either the OPF hydrogel phase or gelatin Microparticle phase of composites. Release profiles were successfully manipulated by altering the phase of growth factor loading and Microparticle crosslinking extent. For instance, by loading TGF-beta1 into the gelatin Microparticle phase, a burst release of 10.8+/-0.7% was achieved, while loading this growth factor into the OPF hydrogel phase resulted in a burst release of 25.2+/-1.5%. With either system, simultaneous, slow release of IGF-1 over a 4-week period was accomplished by selectively loading this protein into highly crosslinked, encapsulated Microparticles. These results demonstrate the utility of these systems in future studies to assess the interplay and time course of multiple growth factors in cartilage repair.

  • transforming growth factor beta 1 release from oligo poly ethylene glycol fumarate hydrogels in conditions that model the cartilage wound healing environment
    Journal of Controlled Release, 2004
    Co-Authors: Theresa A Holland, Yasuhiko Tabata, Joerg Tessmar, Antonios G Mikos
    Abstract:

    This research demonstrates that controlled material degradation and transforming growth factor-beta1 (TGF-beta1) release can be achieved by encapsulation of TGF-beta1-loaded gelatin Microparticles within the biodegradable polymer oligo(poly(ethylene glycol) fumarate) (OPF), so that these Microparticles function as both a digestible porogen and a delivery vehicle. Release studies performed with non-encapsulated Microparticles confirmed that at normal physiological pH, TGF-beta1 complexes with acidic gelatin, resulting in slow release rates. At pH 4.0, this complexation no longer persists, and TGF-beta1 release is enhanced. However, by encapsulating TGF-beta1-loaded Microparticles in a network of OPF, release at either pH can be diffusionally controlled. For instance, after 28 days of incubation at pH 4.0, final cumulative release from non-encapsulated Microparticles crosslinked in 10 and 40 mM glutaraldehyde (GA) was 75.4+/-1.6% and 76.6+/-1.1%, respectively. However, when either Microparticle formulation was encapsulated in an OPF hydrogel (noted as OPF-10 mM and OPF-40 mM, respectively), these values were reduced to 44.7+/-14.6% and 47.4+/-4.7%. More interestingly, release studies, in conditions that model the expected collagenase concentration of injured cartilage, demonstrated that by altering the Microparticle crosslinking extent and loading within OPF hydrogels, TGF-beta1 release, composite swelling, and polymer loss could be systematically altered. Composites encapsulating less crosslinked Microparticles (OPF-10 mM) exhibited 100% release after only 18 days and were completely degraded by day 24 in collagenase-containing phosphate-buffered saline (PBS). Hydrogels encapsulating 40 mM GA Microparticles did not exhibit 100% release or polymer loss until day 28. Hydrogels with no Microparticle component demonstrated only 79.3+/-9.2% release and 89.2+/-3.4% polymer loss after 28 days in enzyme-containing PBS. Accordingly, these studies confirm that the rate of TGF-beta1 release and material degradation can be controlled by altering key parameters of these novel, in situ crosslinkable biomaterials, so that TGF-beta1 release and scaffold degradation may be tailored to optimize cartilage repair.

Yasuhiko Tabata - One of the best experts on this subject based on the ideXlab platform.

  • dual growth factor delivery from degradable oligo poly ethylene glycol fumarate hydrogel scaffolds for cartilage tissue engineering
    Journal of Controlled Release, 2005
    Co-Authors: Theresa A Holland, Yasuhiko Tabata, Antonios G Mikos
    Abstract:

    Abstract This work describes the development of a non-invasive means of simultaneously delivering insulin-like growth factor-1 (IGF-1) and transforming growth factor-β1 (TGF-β1) to injured cartilage tissue in a controlled manner. This novel delivery technology employs the water-soluble polymer, oligo(poly(ethylene glycol) fumarate) (OPF), in the fabrication of biodegradable hydrogels which encapsulate gelatin Microparticles. Release studies first examined the effect of gelatin isoelectric point (IEP) and crosslinking extent on IGF-1 release from these Microparticles. In the presence of collagenase, highly crosslinked, acidic gelatin (IEP=5.0) provided sustained release of IGF-1, 95.2±2.9% cumulative release at day 28, while less crosslinked Microparticles and Microparticles of alternate IEP exhibited similar release values after only 6 days. Encapsulation of these highly crosslinked Microparticles in a network of OPF provided a means to further control release, reducing final cumulative release to 70.2±4.7% in collagenase-containing PBS. Final release values from OPF–gelatin Microparticle composites could be altered by incorporating less crosslinked, non-loaded Microparticles within these constructs. Finally, this technology was extended to the dual delivery of IGF-1 and TGF-β1 by loading these growth factors into either the OPF hydrogel phase or gelatin Microparticle phase of composites. Release profiles were successfully manipulated by altering the phase of growth factor loading and Microparticle crosslinking extent. For instance, by loading TGF-β1 into the gelatin Microparticle phase, a burst release of 10.8±0.7% was achieved, while loading this growth factor into the OPF hydrogel phase resulted in a burst release of 25.2±1.5%. With either system, simultaneous, slow release of IGF-1 over a 4-week period was accomplished by selectively loading this protein into highly crosslinked, encapsulated Microparticles. These results demonstrate the utility of these systems in future studies to assess the interplay and time course of multiple growth factors in cartilage repair.

  • dual growth factor delivery from degradable oligo poly ethylene glycol fumarate hydrogel scaffolds for cartilage tissue engineering
    Journal of Controlled Release, 2005
    Co-Authors: Theresa A Holland, Yasuhiko Tabata, Antonios G Mikos
    Abstract:

    This work describes the development of a non-invasive means of simultaneously delivering insulin-like growth factor-1 (IGF-1) and transforming growth factor-beta1 (TGF-beta1) to injured cartilage tissue in a controlled manner. This novel delivery technology employs the water-soluble polymer, oligo(poly(ethylene glycol) fumarate) (OPF), in the fabrication of biodegradable hydrogels which encapsulate gelatin Microparticles. Release studies first examined the effect of gelatin isoelectric point (IEP) and crosslinking extent on IGF-1 release from these Microparticles. In the presence of collagenase, highly crosslinked, acidic gelatin (IEP=5.0) provided sustained release of IGF-1, 95.2+/-2.9% cumulative release at day 28, while less crosslinked Microparticles and Microparticles of alternate IEP exhibited similar release values after only 6 days. Encapsulation of these highly crosslinked Microparticles in a network of OPF provided a means to further control release, reducing final cumulative release to 70.2+/-4.7% in collagenase-containing PBS. Final release values from OPF-gelatin Microparticle composites could be altered by incorporating less crosslinked, non-loaded Microparticles within these constructs. Finally, this technology was extended to the dual delivery of IGF-1 and TGF-beta1 by loading these growth factors into either the OPF hydrogel phase or gelatin Microparticle phase of composites. Release profiles were successfully manipulated by altering the phase of growth factor loading and Microparticle crosslinking extent. For instance, by loading TGF-beta1 into the gelatin Microparticle phase, a burst release of 10.8+/-0.7% was achieved, while loading this growth factor into the OPF hydrogel phase resulted in a burst release of 25.2+/-1.5%. With either system, simultaneous, slow release of IGF-1 over a 4-week period was accomplished by selectively loading this protein into highly crosslinked, encapsulated Microparticles. These results demonstrate the utility of these systems in future studies to assess the interplay and time course of multiple growth factors in cartilage repair.

  • transforming growth factor beta 1 release from oligo poly ethylene glycol fumarate hydrogels in conditions that model the cartilage wound healing environment
    Journal of Controlled Release, 2004
    Co-Authors: Theresa A Holland, Yasuhiko Tabata, Joerg Tessmar, Antonios G Mikos
    Abstract:

    This research demonstrates that controlled material degradation and transforming growth factor-beta1 (TGF-beta1) release can be achieved by encapsulation of TGF-beta1-loaded gelatin Microparticles within the biodegradable polymer oligo(poly(ethylene glycol) fumarate) (OPF), so that these Microparticles function as both a digestible porogen and a delivery vehicle. Release studies performed with non-encapsulated Microparticles confirmed that at normal physiological pH, TGF-beta1 complexes with acidic gelatin, resulting in slow release rates. At pH 4.0, this complexation no longer persists, and TGF-beta1 release is enhanced. However, by encapsulating TGF-beta1-loaded Microparticles in a network of OPF, release at either pH can be diffusionally controlled. For instance, after 28 days of incubation at pH 4.0, final cumulative release from non-encapsulated Microparticles crosslinked in 10 and 40 mM glutaraldehyde (GA) was 75.4+/-1.6% and 76.6+/-1.1%, respectively. However, when either Microparticle formulation was encapsulated in an OPF hydrogel (noted as OPF-10 mM and OPF-40 mM, respectively), these values were reduced to 44.7+/-14.6% and 47.4+/-4.7%. More interestingly, release studies, in conditions that model the expected collagenase concentration of injured cartilage, demonstrated that by altering the Microparticle crosslinking extent and loading within OPF hydrogels, TGF-beta1 release, composite swelling, and polymer loss could be systematically altered. Composites encapsulating less crosslinked Microparticles (OPF-10 mM) exhibited 100% release after only 18 days and were completely degraded by day 24 in collagenase-containing phosphate-buffered saline (PBS). Hydrogels encapsulating 40 mM GA Microparticles did not exhibit 100% release or polymer loss until day 28. Hydrogels with no Microparticle component demonstrated only 79.3+/-9.2% release and 89.2+/-3.4% polymer loss after 28 days in enzyme-containing PBS. Accordingly, these studies confirm that the rate of TGF-beta1 release and material degradation can be controlled by altering key parameters of these novel, in situ crosslinkable biomaterials, so that TGF-beta1 release and scaffold degradation may be tailored to optimize cartilage repair.

Claudia Flores - One of the best experts on this subject based on the ideXlab platform.

  • gentamicin loaded poly lactic co glycolic acid Microparticles for the prevention of maxillofacial and orthopedic implant infections
    Materials Science and Engineering: C, 2016
    Co-Authors: Claudia Flores, Stephanie Degoutin, Feng Chai, G Raoul, Jeanchritophe Hornez, Bernard Martel
    Abstract:

    Abstract Trauma and orthopedic surgery can cause infections as any open surgical procedures. Such complications occur in only1 to 5% of the cases, but the treatment is rather complicated due to bacterial biofilm formation and limited drug access to the site of infection upon systemic administration. An interesting strategy to overcome this type of complications is to prevent bacterial proliferation and biofilm formation via the local and controlled release of antibiotic drugs from the implant itself. Obviously, the incorporation of the drug into the implant should not affect the latter's biological and mechanical properties. In this context, we optimized the preparation process for gentamicin-loaded poly(lactic-co-glycolic acid) (PLGA) Microparticles, which can be incorporated in the macropores of calcium phosphate-based bone substitutes. Microparticles were prepared using a double emulsion solvent extraction/evaporation technique. The processing parameters were optimized in order to provide an average Microparticle size of about 60 μm, allowing for incorporation inside the macropores (100 μm) of the hydroxyapatite scaffold. Gentamicin-loaded PLGA Microparticles showed a sustained release for 25–30 days and a rapid antibacterial activity due to a burst effect, the extent of which was controlled by the initial loading of the Microparticles. SEM pictures revealed a highly porous Microparticle structure, which can help to reduce the micro environmental pH drop and autocatalytic effects. The biological evaluation showed the cytocompatibility and non-hemolytic property of the Microparticles, and the antibacterial activity against Staphylococcus aureus under the given conditions.

Joerg Tessmar - One of the best experts on this subject based on the ideXlab platform.

  • transforming growth factor beta 1 release from oligo poly ethylene glycol fumarate hydrogels in conditions that model the cartilage wound healing environment
    Journal of Controlled Release, 2004
    Co-Authors: Theresa A Holland, Yasuhiko Tabata, Joerg Tessmar, Antonios G Mikos
    Abstract:

    This research demonstrates that controlled material degradation and transforming growth factor-beta1 (TGF-beta1) release can be achieved by encapsulation of TGF-beta1-loaded gelatin Microparticles within the biodegradable polymer oligo(poly(ethylene glycol) fumarate) (OPF), so that these Microparticles function as both a digestible porogen and a delivery vehicle. Release studies performed with non-encapsulated Microparticles confirmed that at normal physiological pH, TGF-beta1 complexes with acidic gelatin, resulting in slow release rates. At pH 4.0, this complexation no longer persists, and TGF-beta1 release is enhanced. However, by encapsulating TGF-beta1-loaded Microparticles in a network of OPF, release at either pH can be diffusionally controlled. For instance, after 28 days of incubation at pH 4.0, final cumulative release from non-encapsulated Microparticles crosslinked in 10 and 40 mM glutaraldehyde (GA) was 75.4+/-1.6% and 76.6+/-1.1%, respectively. However, when either Microparticle formulation was encapsulated in an OPF hydrogel (noted as OPF-10 mM and OPF-40 mM, respectively), these values were reduced to 44.7+/-14.6% and 47.4+/-4.7%. More interestingly, release studies, in conditions that model the expected collagenase concentration of injured cartilage, demonstrated that by altering the Microparticle crosslinking extent and loading within OPF hydrogels, TGF-beta1 release, composite swelling, and polymer loss could be systematically altered. Composites encapsulating less crosslinked Microparticles (OPF-10 mM) exhibited 100% release after only 18 days and were completely degraded by day 24 in collagenase-containing phosphate-buffered saline (PBS). Hydrogels encapsulating 40 mM GA Microparticles did not exhibit 100% release or polymer loss until day 28. Hydrogels with no Microparticle component demonstrated only 79.3+/-9.2% release and 89.2+/-3.4% polymer loss after 28 days in enzyme-containing PBS. Accordingly, these studies confirm that the rate of TGF-beta1 release and material degradation can be controlled by altering key parameters of these novel, in situ crosslinkable biomaterials, so that TGF-beta1 release and scaffold degradation may be tailored to optimize cartilage repair.