- Email: [email protected]
Injectable mineralized collagen-based bone repair materials
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Abstracts / Journal of Controlled Release 172 (2013) e125–e149
the macroinitiator PNIPAAm–NH2 was obtained and used to initiate the ROP of BLG-NCA to get the ultimate block polymer PNIPAAm-b-PBLG. All the polymers were characterized and confirmed by 1H NMR successfully. The molecular weight (PDI) of PNIPAAm-TTC, PNIPAAm–NH–Boc, PNIPAAm–NH2 and PNIPAAm-b-PBLG are 9810 g/mol (1.23), 4192 g/mol (1.27), 4264 g/mol (1.24) and 10295 g/mol (1.37) respectively. The MALDI-TOF mass spectrum of PNIPAAm-NH-Boc reveals the peaks corresponding to the PNIPAAm with a NH-Boc end group, proving the successful end-group transformation. Finally, micelles were obtained by a dialysis method, and the mean diameter and polydispersity determined by DLS (θ = 90°) are 167.6 nm and 0.141 respectively, proving the acquisition of the PNIPAAm-b-PBLG indirectly. In conclusion, we obtained a new approach for the synthesis of polypeptide-based diblock copolymers, which can be used for the preparation of stimuli-responsive drug delivery systems.
and bimodal mesoporous channels of BMMs, the obtained materials were noted as LHMS-X (X: 0.1, 0.25, 0.5, 1, 3, 10, and 20) due to the different amounts of 4-NH2-NA. The emission spectra which were obtained on a LS45 luminescence spectrometer show that the wavelength ranges from 501 to 518 nm for the different hybrids, With increasing gradual additive loading amount of 4-NH2-NA, sample (a) shows one peak centered at around 501 nm, after that, a red-shifted emission is observed for sample (b) at 502 nm, sample (c) at 509 nm, sample (d) at 514 nm, sample (e) at 515 nm, sample (f) at 516 nm, and sample (g) at 518 nm along with an increase in the fluorescence intensity (Fig. 1). Excellent photoluminescent performance is shown for this LHMS material, which could be applied for optical sensors and so on.
Scheme 1. A new pathway for producing block copolymers via the combination of RAFT polymerization, ROP and thiol-ene click reactions (the yellow sphere represents the NH2 group).
Keywords: Stimuli-responsive, Thiol-ene, Polypeptides, PNIPAAm-bPBLG Acknowledgements This work was supported by the National Natural Science Foundation of China (Grant No. 50873048, 51073080). References [1] X. Zhang, J. Li, W. Li, A. Zhang, Synthesis and characterization of thermo- and pHresponsive double-hydrophilic diblock copolypeptides, Biomacromolecules 8 (2007) 3557–3567. [2] A. Gregory, M.H. Stenzel, Complex polymer architectures via RAFT polymerization: from fundamental process to extending the scope using click chemistry and nature's building blocks, Prog. Polym. Sci. 37 (2012) 38–105.
doi:10.1016/j.jconrel.2013.08.241
Synthesis and characterization of novel luminescent hybrid materials via grafting 4-amino-1,8-Naphthalic Anhydride(4-NH2-NA) into the channels of bimodal mesoporous materials Yuzhen Lia, Jihong Sunb,⁎ College of Environmental Science and Engineering, Taiyuan University of Technology, Taiyuan 030027, China b College of Environmental & Energy Engineering, Beijing University of Technology, Beijing 100124, China E-mail address: [email protected] (J. Sun).
a
Since the discovery of mesoporous silicas in 1992 [1], mesostructured silicas have been studied extensively as drug-delivery vehicles [2]. In the progress of drug carriers, how to track and even diagnose the effectiveness of the drug delivery has also attracted much attention. By using 4-amino-1, 8-Naphthalic anhydride(4-NH2-NA) as fluorescent molecule, the aim of this work is to immobilize it on the mesoporous silica, and hope to obtain uniform monodisperse luminescent molecules, which could have many potential applications in related fields of drug carriers. In the present work, we report the synthesis and characterization of luminescent hybrid materials (LHMS) by combining the 4-NH2-NA
Fig. 1. The emission spectra of samples (a) LHMS-0.1, (b) LHMS-0.25, (c) LHMS-0.5, (d) LHMS-1, (e) LHMS-3, (f) LHMS-10, and (g) LHMS-20.
Keywords: Bimodal mesoporous silicas, Fluorescent signaling, Covalent anchoring Acknowledgement This work was supported by the State Basic Research Project (2009CB930200). References [1] C.T. Kresge, M.E. Leonowicz, W.G. Roth, J.C. Vartuli, J.C. Beck, Ordered mesoporous molecular sieves synthesized by a liquid–crystal template mechanism, Nature 359 (1992) 710–712. [2] M. Vallet-Regi, A. Ramila, R.P. del Real, J. Perez-Pariente, A new property of MCM-41: drug delivery system, Chem. Mater. 13 (2001) 309–311.
doi:10.1016/j.jconrel.2013.08.242
Injectable mineralized collagen-based bone repair materials Zonggang Chena, Huanye Liub, Xi Liuc, Zhongwu Guoa, Fu-Zhai Cuic,⁎ a National Glycoengineering Research Center, Shandong University, Jinan 250100, China b School of Stomatology, China Medical University, Shenyang 11000, China c Department of Materials Science and Engineering, Tsinghua University, Beijing 100084, China E-mail addresses: [email protected] (Z. Chen), [email protected] (F.-Z. Cui).
Abstracts / Journal of Controlled Release 172 (2013) e125–e149
The nHAC composites, which are the mineralized fibrils of nanosized hydroxyapatite and collagen, have the same features as natural bone in the main hierarchical microstructure and composition, so it is a bioactive osteoconductor, which has been successfully used for tens of thousands of cases in clinical applications [1]. However, the materials lack handling characteristics because of its solid-preformed block shape. Herein, calcium sulfate hemihydrate (CSH) was introduced into nHAC to develop injectable bone repair materials, and calcium sulfate dihydrate (CSD) was selected as setting accelerator. The morphology, injectability, setting time, mechanical properties and degradation ratios of materials were examined in in vitro cellular activities and in vivo implantation experiments were performed by seeding cells on the materials and implanting the materials into a 13 mm × 10 mm box defect in the mandible of rabbits, respectively. The nHAC/CSH composites have favorable injectability under appropriate conditions. When mixed with water, the materials were transformed into nHAC/CSD composites after final setting. The rod-like crystal structure of CSH was transformed into the sheet crystal structure of CSD. CSD as setting accelerator has a significant accelerating effect on the setting properties of nHAC/CSH composites. The self-setting time of nHAC/CSH composites can be regulated from more than 100 min to 30 min and even less than 20 min by adding various amounts of setting accelerator. The average compressive strength and modulus of materials after final setting range from about 2.0 to nearly 20 MPa and about 100 to 750.0 MPa with the difference of L/S ratio, setting accelerator content and nHAC content, respectively, which are similar to the mechanical properties of cancellous bone. The degradation rate of the materials matches that of tissue formation. The excellent interactions between the materials and cells imply that the composites as a scaffold can provide a satisfactory biological environment for cell adhesion, migration, and proliferation (Fig. 1A). Its good efficacy in bone regeneration as bone
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materials strongly supports that the composites can offer adequate stimulus for new bone growth and bone regeneration in the implants (Fig. 1B and C). As injectable bone materials, the nHAC/CSD composites can not only provide a satisfactory biological environment for facilitating cell adhesion, migration, and proliferation but also offer adequate stimulus for growing new bone and bone regeneration in the implants.
Fig. 1. SEM result of 2-day cultured cells on the composites: (A), histology photographs of Masson staining results of implanted composites: (B) at 4 weeks; (C) at 8 weeks.
Keywords: injectable, mineralized collagen, self-setting property, bone repair materials Acknowledgements This work was supported by the National Basic Research Program of China (2011CB606205 and 2012CB822102) and the National Natural Science Foundation of China (50830102). Reference [1] W. Zhang, S.S. Liao, F.Z. Cui, Hierarchical self-assembly of nano-fibrils in mineralized collagen, Chem. Mater. 15 (2010) 3221–3226.
doi:10.1016/j.jconrel.2013.08.243
Abstracts / Journal of Controlled Release 172 (2013) e125–e149
the macroinitiator PNIPAAm–NH2 was obtained and used to initiate the ROP of BLG-NCA to get the ultimate block polymer PNIPAAm-b-PBLG. All the polymers were characterized and confirmed by 1H NMR successfully. The molecular weight (PDI) of PNIPAAm-TTC, PNIPAAm–NH–Boc, PNIPAAm–NH2 and PNIPAAm-b-PBLG are 9810 g/mol (1.23), 4192 g/mol (1.27), 4264 g/mol (1.24) and 10295 g/mol (1.37) respectively. The MALDI-TOF mass spectrum of PNIPAAm-NH-Boc reveals the peaks corresponding to the PNIPAAm with a NH-Boc end group, proving the successful end-group transformation. Finally, micelles were obtained by a dialysis method, and the mean diameter and polydispersity determined by DLS (θ = 90°) are 167.6 nm and 0.141 respectively, proving the acquisition of the PNIPAAm-b-PBLG indirectly. In conclusion, we obtained a new approach for the synthesis of polypeptide-based diblock copolymers, which can be used for the preparation of stimuli-responsive drug delivery systems.
and bimodal mesoporous channels of BMMs, the obtained materials were noted as LHMS-X (X: 0.1, 0.25, 0.5, 1, 3, 10, and 20) due to the different amounts of 4-NH2-NA. The emission spectra which were obtained on a LS45 luminescence spectrometer show that the wavelength ranges from 501 to 518 nm for the different hybrids, With increasing gradual additive loading amount of 4-NH2-NA, sample (a) shows one peak centered at around 501 nm, after that, a red-shifted emission is observed for sample (b) at 502 nm, sample (c) at 509 nm, sample (d) at 514 nm, sample (e) at 515 nm, sample (f) at 516 nm, and sample (g) at 518 nm along with an increase in the fluorescence intensity (Fig. 1). Excellent photoluminescent performance is shown for this LHMS material, which could be applied for optical sensors and so on.
Scheme 1. A new pathway for producing block copolymers via the combination of RAFT polymerization, ROP and thiol-ene click reactions (the yellow sphere represents the NH2 group).
Keywords: Stimuli-responsive, Thiol-ene, Polypeptides, PNIPAAm-bPBLG Acknowledgements This work was supported by the National Natural Science Foundation of China (Grant No. 50873048, 51073080). References [1] X. Zhang, J. Li, W. Li, A. Zhang, Synthesis and characterization of thermo- and pHresponsive double-hydrophilic diblock copolypeptides, Biomacromolecules 8 (2007) 3557–3567. [2] A. Gregory, M.H. Stenzel, Complex polymer architectures via RAFT polymerization: from fundamental process to extending the scope using click chemistry and nature's building blocks, Prog. Polym. Sci. 37 (2012) 38–105.
doi:10.1016/j.jconrel.2013.08.241
Synthesis and characterization of novel luminescent hybrid materials via grafting 4-amino-1,8-Naphthalic Anhydride(4-NH2-NA) into the channels of bimodal mesoporous materials Yuzhen Lia, Jihong Sunb,⁎ College of Environmental Science and Engineering, Taiyuan University of Technology, Taiyuan 030027, China b College of Environmental & Energy Engineering, Beijing University of Technology, Beijing 100124, China E-mail address: [email protected] (J. Sun).
a
Since the discovery of mesoporous silicas in 1992 [1], mesostructured silicas have been studied extensively as drug-delivery vehicles [2]. In the progress of drug carriers, how to track and even diagnose the effectiveness of the drug delivery has also attracted much attention. By using 4-amino-1, 8-Naphthalic anhydride(4-NH2-NA) as fluorescent molecule, the aim of this work is to immobilize it on the mesoporous silica, and hope to obtain uniform monodisperse luminescent molecules, which could have many potential applications in related fields of drug carriers. In the present work, we report the synthesis and characterization of luminescent hybrid materials (LHMS) by combining the 4-NH2-NA
Fig. 1. The emission spectra of samples (a) LHMS-0.1, (b) LHMS-0.25, (c) LHMS-0.5, (d) LHMS-1, (e) LHMS-3, (f) LHMS-10, and (g) LHMS-20.
Keywords: Bimodal mesoporous silicas, Fluorescent signaling, Covalent anchoring Acknowledgement This work was supported by the State Basic Research Project (2009CB930200). References [1] C.T. Kresge, M.E. Leonowicz, W.G. Roth, J.C. Vartuli, J.C. Beck, Ordered mesoporous molecular sieves synthesized by a liquid–crystal template mechanism, Nature 359 (1992) 710–712. [2] M. Vallet-Regi, A. Ramila, R.P. del Real, J. Perez-Pariente, A new property of MCM-41: drug delivery system, Chem. Mater. 13 (2001) 309–311.
doi:10.1016/j.jconrel.2013.08.242
Injectable mineralized collagen-based bone repair materials Zonggang Chena, Huanye Liub, Xi Liuc, Zhongwu Guoa, Fu-Zhai Cuic,⁎ a National Glycoengineering Research Center, Shandong University, Jinan 250100, China b School of Stomatology, China Medical University, Shenyang 11000, China c Department of Materials Science and Engineering, Tsinghua University, Beijing 100084, China E-mail addresses: [email protected] (Z. Chen), [email protected] (F.-Z. Cui).
Abstracts / Journal of Controlled Release 172 (2013) e125–e149
The nHAC composites, which are the mineralized fibrils of nanosized hydroxyapatite and collagen, have the same features as natural bone in the main hierarchical microstructure and composition, so it is a bioactive osteoconductor, which has been successfully used for tens of thousands of cases in clinical applications [1]. However, the materials lack handling characteristics because of its solid-preformed block shape. Herein, calcium sulfate hemihydrate (CSH) was introduced into nHAC to develop injectable bone repair materials, and calcium sulfate dihydrate (CSD) was selected as setting accelerator. The morphology, injectability, setting time, mechanical properties and degradation ratios of materials were examined in in vitro cellular activities and in vivo implantation experiments were performed by seeding cells on the materials and implanting the materials into a 13 mm × 10 mm box defect in the mandible of rabbits, respectively. The nHAC/CSH composites have favorable injectability under appropriate conditions. When mixed with water, the materials were transformed into nHAC/CSD composites after final setting. The rod-like crystal structure of CSH was transformed into the sheet crystal structure of CSD. CSD as setting accelerator has a significant accelerating effect on the setting properties of nHAC/CSH composites. The self-setting time of nHAC/CSH composites can be regulated from more than 100 min to 30 min and even less than 20 min by adding various amounts of setting accelerator. The average compressive strength and modulus of materials after final setting range from about 2.0 to nearly 20 MPa and about 100 to 750.0 MPa with the difference of L/S ratio, setting accelerator content and nHAC content, respectively, which are similar to the mechanical properties of cancellous bone. The degradation rate of the materials matches that of tissue formation. The excellent interactions between the materials and cells imply that the composites as a scaffold can provide a satisfactory biological environment for cell adhesion, migration, and proliferation (Fig. 1A). Its good efficacy in bone regeneration as bone
e149
materials strongly supports that the composites can offer adequate stimulus for new bone growth and bone regeneration in the implants (Fig. 1B and C). As injectable bone materials, the nHAC/CSD composites can not only provide a satisfactory biological environment for facilitating cell adhesion, migration, and proliferation but also offer adequate stimulus for growing new bone and bone regeneration in the implants.
Fig. 1. SEM result of 2-day cultured cells on the composites: (A), histology photographs of Masson staining results of implanted composites: (B) at 4 weeks; (C) at 8 weeks.
Keywords: injectable, mineralized collagen, self-setting property, bone repair materials Acknowledgements This work was supported by the National Basic Research Program of China (2011CB606205 and 2012CB822102) and the National Natural Science Foundation of China (50830102). Reference [1] W. Zhang, S.S. Liao, F.Z. Cui, Hierarchical self-assembly of nano-fibrils in mineralized collagen, Chem. Mater. 15 (2010) 3221–3226.
doi:10.1016/j.jconrel.2013.08.243