Co-reporter:Yanpeng Liu, Xiaobin Chen, Sheyu Li, Qiang Guo, Jing Xie, Lin Yu, Xinyuan Xu, Chunmei Ding, Jianshu Li, and Jiandong Ding
ACS Applied Materials & Interfaces July 19, 2017 Volume 9(Issue 28) pp:23428-23428
Publication Date(Web):June 22, 2017
DOI:10.1021/acsami.7b05740
Effective antiosteopenia therapy can be achieved by designing long-term protein/peptide drug delivery systems for bone trabecula restoration. Here we show that a complex of salmon calcitonin and oxidized calcium alginate (sCT-OCA) was prepared and loaded into a thermosensitive copolymer hydrogel for long-term antiosteopenia treatment. The triblock copolymer, poly(d,l-lactic acid-co-glycolic acid)-b-poly(ethylene glycol)-b-poly(d,l-lactic acid-co-glycolic acid) (PLGA-PEG-PLGA) exhibited sol–gel transition at body temperature. The sustained release of sCT from the in situ gelling system was determined by both the degradation of the hydrogel and the decomposition of the sCT-OCA complex. This system showed sustained effects in reducing serum calcium and bone trabecula reconstruction in the treatment of glucocorticoid-induced osteopenia in rats for approximately 30 days after a single subcutaneous injection, which may shed light on antiosteopenia therapy in the future.Keywords: controlled release; osteoporosis; peptide drug; salmon calcitonin; thermosensitive hydrogel;
Co-reporter:Xiao Yang, Fuhui Huang, Xinyuan Xu, Yanpeng Liu, Chunmei Ding, Kefeng Wang, Anran Guo, Wei Li, and Jianshu Li
Chemistry of Materials July 11, 2017 Volume 29(Issue 13) pp:5663-5663
Publication Date(Web):June 9, 2017
DOI:10.1021/acs.chemmater.7b01465
Manipulation of the surface properties of biominerals is very important for their biomedical applications. However, the straightforward preparation of a multifunctional and stable coating on biominerals remains a challenge. Herein we report a rapid and universal method for the preparation of multifunctional coatings on various biominerals using a salivary acquired pellicle (SAP) inspired dendrimer. The dendrimer has a highly branched structure and an external surface modified with DDDEEKC peptide. It mimics the adsorption function of statherin, which is one of the main components of SAP, to endow the coating with a universal capability for adhesion on various biominerals such as hydroxyapatite, tertiary calcium phosphate, calcium carbonate, pearls, enamel, dentin, and bone. The coating can be formed by a simple dip-coating method on the surface of biominerals within 10 min, and is stable for more than 1 month. The coating can also provide a general platform for secondary modifications. For example, we use pregrafting or postgrafting methods to introduce functional molecules such as fluorescein isothiocyanate, heptadecafluoroundecanoyl chloride, and collagen to the surface of the coatings, thus these biomineral surfaces can be applied for different applications such as for protein crystallization by forming superhydrophobic surface, or promoting cell adhesion and proliferation by immobilizing collagen.
Co-reporter:Qin Huang, Jing Xie, Yanpeng Liu, Anna Zhou, and Jianshu Li
Bioconjugate Chemistry April 19, 2017 Volume 28(Issue 4) pp:944-944
Publication Date(Web):January 23, 2017
DOI:10.1021/acs.bioconjchem.6b00665
The fibrillation of protein is harmful and impedes the use of protein drugs. It also relates to various debilitating diseases such as Alzheimer’s diseases. Thus, investigating the protein fibrillation process is necessary. In this study, poly(amido amine) dendrimers (PAMAM) of generation 3 (G3) and generation 4 (G4) were synthesized and conjugated with 4-aminobiphenyl, an aggregation-induced emission (AIE) moiety, at varied grafting ratios. Among them, one fluorescence probe named G3-biph-3 that was grafted average 3.25 4-aminobiphenyl to the G3, can detect the transformations both from native insulin to oligomers and from oligomers to fibrils. The size difference of native insulin, oligomers, and fibrils was proposed to be the main factor leading to the detection of the above transformations. Different molecular weights of sodium polyacrylate (PAAS) were also applied as a model to interact with G3-biph-3 to further reveal the mechanism. The results indicated that PAMAM with a certain generation and grafted with appropriate AIE groups can detect the oligomer formation and transformation during the insulin fibrillation process.
Co-reporter:Shuqin Cao, Yanpeng Liu, Hui Shang, Sheyu Li, Jian Jiang, Xiaofeng Zhu, Peng Zhang, Xianlong Wang, Jianshu Li
Journal of Controlled Release 2017 Volume 256(Volume 256) pp:
Publication Date(Web):28 June 2017
DOI:10.1016/j.jconrel.2017.04.014
Salmon calcitonin (sCT) is a therapeutic polypeptide drug widely used to treat bone diseases such as osteoporosis (more than 200 million patients all over the world). The half-life of sCT is very short (~ 1 h), thus various delivery systems have been developed for sCT in order to avoid frequent injections. However, most delivery systems use polymeric materials, which may limit their applications in clinic formulations due to the biocompatibility issue. We observed that a very simple dipeptide (Asp-Phe, DF) was co-assembled with sCT into supramolecular nanoparticles. These nanoparticles can significantly prolong the acting time of sCT to beyond one month after just a single subcutaneous injection. The assembling and releasing mechanisms were thoroughly investigated by both in vitro and in vivo methods, as well as by molecular dynamics simulations. This work provides an alternative strategy of designing protein/peptide drug delivery systems with long-lasting therapeutic effects.Supramolecular dipeptide-calcitonin nanoparticles are prepared to prolong the acting time of calcitonin in rats to beyond one month after a single subcutaneous injection (the original half-life is about 40 min).Download high-res image (152KB)Download full-size image
Co-reporter:Yuchen Jiang, Yuling Su, Lili Zhao, Fancui Meng, Quanxin Wang, Chunmei Ding, Jianbin Luo, Jianshu Li
Colloids and Surfaces B: Biointerfaces 2017 Volume 156(Volume 156) pp:
Publication Date(Web):1 August 2017
DOI:10.1016/j.colsurfb.2017.05.030
•PMCP modified surfaces with different architectures were prepared by SI-ATRP.•Antifouling activities of CP modified surface against bacteria was studied.•A synergetic fouling resistant properties of PHEMA and PMCP is observed.•Decreased platelet adhesion and activation is observed for CP containing surfaces.Choline phosphate (CP) containing polymers modified surfaces have been shown good resist to the adhesion of proteins while prompt the attaching of mammalian cells due to the dipole pairing between the CP groups of the polymer and the phosphorylcholine (PC) groups on the cell membrane. However, the antifouling activities of CP modified surface against microbes have not been investigated at present. In addition, CP containing polymers modified surface with different molecular architectures has not been prepared and studied. To this end, glass slides surface modified with two different 2-(meth-acryloyloxy)ethyl cholinephosphate (MCP) containing polymer (PMCP) structures, i.e. brush-like (Glass-PMCP) and bottle brush-like (Glass-PHEMA-g-PMCP) architectures, were prepared in this work by surface-initiated atom transfer radical polymerization (SI-ATRP). The surface physichemical and antifouling properties of the prepared surfaces were characterized and studied. The Glass-PMCP shows improved antifouling properties against proteins and bacteria as compared to pristine glass slides (Glass-OH) and glass slides grafted with poly(2-hydroxyethyl methacrylate) (Glass-PHEMA). Notably, a synergetic fouling resistant properties of PHEMA and PMCP is presented for Glass-PHEMA-g-PMCP, which shows superior antifouling activities over Glass-PHEMA and Glass-PMCP. Furthermore, glass slides containing PMCP, i.e. Glass-PMCP and Glas-PHEMA-g-PMCP, decrease platelet adhesion and prevent their activation significantly. Therefore, the combination of antifouling PHEMA and PMCP into one system holds potential for prevention of bacterial fouling and biomaterial-centered infections.Download high-res image (130KB)Download full-size image
Co-reporter:Xinyuan Xu;Libang He;Bengao Zhu;Jiyao Li
Polymer Chemistry (2010-Present) 2017 vol. 8(Issue 5) pp:807-823
Publication Date(Web):2017/01/31
DOI:10.1039/C6PY01957A
Over the past decade, polymeric materials for clinical dental applications have been developed with excellent properties and various functionalities. This review outlines the present understanding and design of polymeric dental materials based on structure–property–function relationships. First, the chemistry/microstructure of polymeric materials will be reviewed. Then, the resultant properties such as mechanical, thermal, visco-elastic, and water solution properties, as well as additional bio-functionalities such as antibacterial capabilities, remineralization, and bioactive-delivery properties, will be reviewed for specific dental applications. Finally, perspectives and challenges regarding the rational design and application of polymeric dental materials will be discussed.
Co-reporter:Wei Wu;Zaifu Lin;Yanpeng Liu;Xinyuan Xu;Chunmei Ding
Journal of Materials Chemistry B 2017 vol. 5(Issue 3) pp:428-434
Publication Date(Web):2017/01/18
DOI:10.1039/C6TB02657E
A type of four-arm star-shaped copolymer (star-PAA(PEA)-PNIPAM), consisting of the thermoresponsive block (poly(N-isopropylacrylamide), PNIPAM) and the phosphorylated functional block O-phosphoethanolamine (PEA) grafted poly(acrylic acid) (PAA(PEA)), is synthesized by atom transfer radical polymerization (ATRP) and subsequent modification. Owing to the unique superiority of the star-shaped structure, star-PAA(PEA)-PNIPAM can transform from the sol to gel state in response to the physiological temperature (37 °C) at a relatively low polymer concentration (>0.5 wt%). In addition, because of the enriched phosphorylated functional groups, the hydrogel formed by star-PAA(PEA)-PNIPAM can mimic the acidic extracellular matrix protein to adsorb calcium ions and mineralize in situ, both in in vitro and in in vivo experiments. Meanwhile, it is favorable for cell adhesion and proliferation due to its appropriate three-dimensional interspace. Thus, the biocompatible star-PAA(PEA)-PNIPAM hydrogel has great potential for bone repair applications.
Co-reporter:Yaping Gou;Xiao Yang;Libang He;Xinyuan Xu;Yanpeng Liu;Yuebo Liu;Yuan Gao;Qin Huang;Kunneng Liang;Chunmei Ding;Jiyao Li;Changsheng Zhao
Polymer Chemistry (2010-Present) 2017 vol. 8(Issue 29) pp:4264-4279
Publication Date(Web):2017/07/25
DOI:10.1039/C7PY00811B
Bacterial colonization on implanted biomaterials remains a clinically significant problem. In order to achieve relatively long-term antibacterial activity and reduce the incidence of infections associated with the use of biomaterials, a salivary statherin protein (SSP) inspired poly(amidoamine) dendrimer (SSP-PAMAM-NH2) was synthesized and characterized. PAMAM-NH2 has numerous peripheral amino groups, and thus possesses effective antibacterial activity. The SSP bio-inspired peptide sequence DDDEEKC was conjugated to PAMAM-NH2 since it has a strong capability of adsorbing on hydroxyapatite (HA). Moreover, SSP-PAMAM-NH2 is a zwitterionic polymer possessing cationic amino groups and anionic carboxylic groups, thus it can form aggregates by intermolecular electrostatic interactions, thereby promoting its adsorption on HA. Adsorption tests by ATR-IR, UV, QCM-D, and CLSM, all indicated that SSP-PAMAM-NH2 can tightly adsorb on the HA surface. We found that even after being incubated in PBS for 4 weeks, the SSP-PAMAM-NH2 treated HA disks still retained stable antibacterial activity, while the inhibitory impact of PAMAM-NH2 treated disks had disappeared. Animal experiments also demonstrated that SSP-PAMAM-NH2 could significantly reduce infection of HA implanted into the medullary cavity of rats.
Co-reporter:Hui Shang, Xiaobin Chen, Yanpeng Liu, Lin Yu, Jianshu Li, Jiandong Ding
International Journal of Pharmaceutics 2017 Volume 527, Issues 1–2(Issue 1) pp:
Publication Date(Web):15 July 2017
DOI:10.1016/j.ijpharm.2017.05.006
Conventional formulations of human calcitonin (hCT), a peptide drug, normally suffer from limited therapeutic efficacy with low stability and short half-life. We have found that the fibrillation of highly amyloidogenic hCT can be inhibited by cucurbit[7] (CB[7]), an amphiphilic small molecule. Meanwhile, a thermogelling copolymer was found to be a suitable candidate for sustained delivery of peptide/protein drugs. Herein, we report a long-term delivery formulation composed of hCT-CB[7] complex and biodegradable thermogel of poly(D,L-lactic acid-co-glycolic acid)-b-poly(ethylene glycol)-b-poly(D,L-lactic acid −co-glycolic acid) (PLGA-PEG-PLGA). A 20 wt% PLGA-PEG-PLGA solution exhibited a temperature-sensitive sol-gel transition at 35 °C in phosphate buffer solution and slowly degraded over one month at neutral pH. Both the mass fraction of PLGA-PEG-PLGA copolymer and the complexation of hCT-CB[7] moderated the release process. hCT was sustainedly released over three weeks in the 20 wt% hydrogel with hCT-CB[7] complex at the ratio of 1:10 or 1:25. Further considering its low cytotoxicity, the delivery system is potential for the clinical application of hCT.Biodegradable and biocompatible PLGA-PEG-PLGA thermogel system was developed and loaded with hCT-CB[7] complex for sustained release.Download high-res image (152KB)Download full-size image
Co-reporter:Chunmei Ding;Zhuoxin Chen
Biomaterials Science (2013-Present) 2017 vol. 5(Issue 8) pp:1435-1449
Publication Date(Web):2017/07/26
DOI:10.1039/C7BM00247E
Enamel, dentin and bone are calcified hard tissues in the human body that play significant roles in food mastication and movement support. Generally, hard tissues lack the ability of self-repair, except for the regeneration ability of bone for small-scale defects. Fabrication of man-made repair materials is therefore highly demanded. In this review, following a bioinspired strategy, we describe the composition and multiscale structures of different hard tissues, and highlight the key points for the reconstruction of hard tissues. Finally, bioinspired tissue repair techniques ranging from molecule-induced mineralization, to microscale assembly to macroscaffold fabrication are summarised.
Co-reporter:Shuai Li, Zhouxiang Zhao, Wei Wu, Chunmei Ding and Jianshu Li
Polymer Chemistry 2016 vol. 7(Issue 12) pp:2202-2208
Publication Date(Web):18 Feb 2016
DOI:10.1039/C6PY00177G
The development of pH-sensitive micelles with a tumor-acidity-activated surface charge-conversional property has a great benefit to tumor-targeted therapy. In this study, diblock copolymers, i.e., poly(2-diisopropylaminoethyl methacrylate)-b-poly(2-aminoethyl methacrylate hydrochloride) (PDPA-b-PAMA) and poly(ethylene glycol)-b-poly(2-aminoethyl methacrylate hydrochloride) (PEG-b-PAMA), are synthesized via atom transfer radical polymerization (ATRP). Then pH-sensitive core–shell composite micelles are prepared based on a cationic PDPA-b-PAMA nanoparticle core, which is coated with a 2,3-dimethylmaleic anhydride (DMMA) modified PEG-b-PAMA (PEG-b-PAMA/DMMA) shell. The cationic PDPA-b-PAMA nanoparticle core can effectively enhance cellular uptake and intracellular drug release. Meanwhile, the negatively charged PEG-b-PAMA/DMMA shell could also efficiently prolong the blood circulation time and allow for better accumulation in the tumor area. The molecular structure of the copolymers is confirmed by 1H NMR. The charge-conversional behavior of PEG-b-PAMA/DMMA@PDPA-b-PAMA micelles in a slightly acidic environment is observed by dynamic light scattering (DLS). Transmission electron microscopy (TEM) clearly confirmed that PEG-b-PAMA/DMMA@PDPA-b-PAMA micelles could effectively encapsulate drugs. The drug loading and encapsulation efficiencies of doxorubicin (DOX)-loaded micelles are 14.1% and 82.1%, respectively. The results of cumulative in vitro release indicate that under pH 7.4 and 6.8 conditions, the micellar structure of drug carriers is relatively stable and the drug release is relatively slow. While at pH 5.0, DOX-loaded micelles rapidly disassemble to release the drug due to the protonation of PDPA blocks. In addition, the micellar system also presents distinct cytotoxic behavior to HeLa cells when loaded with DOX. These results imply that pH-responsive PEG-b-PAMA/DMMA@PDPA-b-PAMA micelles with the tumor-acidity-activated surface charge-conversional property are highly promising drug carriers for tumor therapy.
Co-reporter:Tianchan Chen, Wei Wu, Hong Xiao, Yanxiao Chen, Min Chen, and Jianshu Li
ACS Macro Letters 2016 Volume 5(Issue 1) pp:55
Publication Date(Web):December 16, 2015
DOI:10.1021/acsmacrolett.5b00765
Mesoporous silica nanoparticles (MSNs) exhibit significant advantages for efficient drug/gene delivery but it is hard for simple MSNs to deliver the loaded drug to the target sites of disease. Considering that there are some well-known pH differences in the body, it is a useful strategy to modify the exterior surface of MSNs with stimuli-responsive gatekeepers to realize open–close transformation of their mesopores. In this work, multifunctional pH-sensitive MSNs were designed with mixed polymeric coatings, that is, poly(ethylene glycol) (PEG) as a dispersity-enhancer and poly(2-(pentamethyleneimino)ethyl methacrylate) (PPEMA) as an ultra-pH-sensitive gatekeeper. Enhanced dispersity, high drug loading capacity, long-circulation time, pH-triggered targeting, and better cellular uptake of the multifunctional MSNs make them potential candidates for pH-sensitive drug delivery such as tumor therapy.
Co-reporter:Rui-Quan Li, Wei Wu, Hai-Qing Song, Yanli Ren, Ming Yang, Jianshu Li, Fu-Jian Xu
Acta Biomaterialia 2016 Volume 41() pp:282-292
Publication Date(Web):1 September 2016
DOI:10.1016/j.actbio.2016.06.006
Abstract
Nucleic acid-based gene therapy is a promising treatment option to cure numerous intractable diseases. For non-viral gene carriers, low-molecular-weight polymeric vectors generally demonstrate poor transfection performance, but benefit their final removals from the body. Recently, it was reported that aminated poly(glycidyl methacrylate) (PGMA) is one potential gene vector. Based on ethylenediamine (ED)-functionalized low-molecular-weight PGMA (denoted by PGED), a flexible strategy was herein proposed to design new well-defined reducible cationic nanogels (denoted by PGED-NGs) with friendly crosslinking reagents for highly efficient nucleic acid delivery. α-Lipoic acid (LA), one natural antioxidant in human body, was readily introduced into ED-functionalized PGMA and crosslinked to produce cationic PGED-NGs with plentiful reducible lipoyl groups. PGED-NGs could effectively complex plasmid DNA (pDNA) and short interfering RNA (siRNA). Compared with pristine PGED, PGED-NGs exhibited much better performance of pDNA transfection. PGED-NGs also could efficiently transport MALAT1 siRNA (siR-M) into hepatoma cells and significantly suppressed the cancer cell proliferation and migration. The present work indicated that reducible cationic nanogels involving LA crosslinking reagents are one kind of competitive candidates for high-performance nucleic acid delivery systems.
Statement of Significance
Recently, the design of new types of high-performance nanoparticles is of great significance in delivering therapeutics. Nucleic acid-based therapy is a promising treatment option to cure numerous intractable diseases. A facile and straightforward strategy to fabricate safe nucleic acid delivery nanovectors is highly desirable. In this work, based on ethylenediamine-functionalized low-molecular-weight poly(glycidyl methacrylate), a flexible strategy was proposed to design new well-defined reducible cationic nanogels (denoted by PGED-NGs) with α-Lipoic acid, one friendly crosslinking reagent, for highly efficient nucleic acid delivery. Such PGED-NGs possess plentiful reducible lipoyl groups, effectively encapsulated pDNA and siRNA and exhibited excellent abilities of nucleic acid delivery. The present work indicated that reducible cationic nanogels involving α-lipoic acid crosslinking reagents are one kind of competitive candidates for high-performance nucleic acid delivery systems.
Co-reporter:Xingyu Chen, Tianchan Chen, Zaifu Lin, Xian'e Li, Wei Wu and Jianshu Li
Chemical Communications 2015 vol. 51(Issue 3) pp:487-490
Publication Date(Web):07 Nov 2014
DOI:10.1039/C4CC08681C
A choline phosphate (CP) modified surface is designed to resist protein adsorption due to its zwitterionic properties and simultaneously promote cell adhesion though its universal interaction with phosphate choline (PC) headgroups of the cell membrane. This work provides a new approach to obtain a cell-adhesive surface with a non-biofouling ‘background’, which has a potential for tissue engineering.
Co-reporter:Xiao Yang, Hui Shang, Chunmei Ding and Jianshu Li
Polymer Chemistry 2015 vol. 6(Issue 5) pp:668-680
Publication Date(Web):01 Dec 2014
DOI:10.1039/C4PY01537A
Nowadays, the bioinspired strategy has become a prevalent guide for the design and fabrication of various novel materials. Due to their unique steric structures and rich peripheral functional groups, dendritic polymers can be designed for various bioinspired functions. This review begins with a brief introduction on the preparation of dendritic polymers, followed by the discussion of their physicochemical and biological properties. Then, a detailed review will focus on their bioinspired applications such as artificial proteins, virus, enzymes, cellular structures and light harvesting antenna, including our own studies. This review highlights the structure–function relationship of dendritic polymers to their bioinspired applications. Finally, an outlook will be proposed about the developing trends and challenges in this field.
Co-reporter:Xingyu Chen, Hui Shang, Shuqin Cao, Hong Tan and Jianshu Li
RSC Advances 2015 vol. 5(Issue 93) pp:76216-76220
Publication Date(Web):28 Aug 2015
DOI:10.1039/C5RA16883J
Choline phosphate (CP) contains amino and phosphate groups in the reverse order in which they are present in phosphate choline (PC), which is the headgroup of phospholipids in all eukaryotic cell membranes. Here we used HeLa and L929 cells to study the general interaction between CP-modified surfaces and cells/proteins. The results of cell counting kit-8 (CCK-8), confocal laser scanning (CLSM) and scanning electron microscopy (SEM) indicated that CP-modified surfaces could improve cell adhesion by almost three times than unmodified surfaces through a unique CP–PC interaction with PC headgroups of the cell membrane. The mechanism for this interaction was the formation of a quadrupole from two quaternary nitrogen–phosphorus pairs. Moreover, the results of fibrinogen and fetal bovine serum protein adsorption experiments indicated that CP-modified surfaces could also resist nonspecific protein adsorption due to the zwitterionic property of the CP group. Therefore, this surface offers a general strategy for the preparation of biomaterials with both cell-adhesive and protein-resistant properties.
Co-reporter:Hui Zhang, Jiaojiao Yang, Kunneng Liang, Jiyao Li, Libang He, Xiao Yang, Shuangjuan Peng, Xingyu Chen, Chunmei Ding, Jianshu Li
Colloids and Surfaces B: Biointerfaces 2015 Volume 128() pp:304-314
Publication Date(Web):1 April 2015
DOI:10.1016/j.colsurfb.2015.01.058
•Fourth generation phosphate-terminated polyamidoamine dendrimer is successfully synthesized by one-step modification.•As the analog of dentin phosphophoryn, it achieves effective remineralization on the demineralized human dentin.•The regenerated mineral layers are thicker than 10 μm both in vitro and in vivo.In clinic, it calls for effective and simple materials to repair etched dentin. Bioinspired by the natural mineralization process guided by noncollagenous proteins (NCPs), in this work, we synthesized the fourth generation phosphate-terminated polyamidoamine dendrimer (G4-PO3H2) by one-step modification. We used FT-IR and 1H NMR to characterize the structure of G4-PO3H2, and MTT assay to prove its biocompatibility. It was applied as the analog of dentin phosphophoryn (DPP: a type of NCPs) to repair dentin, due to its similar dimensional scale, topological architecture and peripheral functionalities to that of DPP. By the characterization of SEM and XRD, the effective regeneration of human dentin induced by G4-PO3H2 is characterized and illustrated both in vitro (artificial saliva) and in vivo (oral cavity of rats). It is noted that the thickness of the regenerated mineral layers are more than 10 μm both in vitro and in vivo. The design strategy of G4-PO3H2 may be valuable for researchers in the fields of material science, stomatology and medicine to prepare various promising restorative nano-materials for biomineralized hard tissues such as bone and teeth.
Co-reporter:Jianyu Xin, Tianchan Chen, Zaifu Lin, Ping Dong, Hong Tan and Jianshu Li
Chemical Communications 2014 vol. 50(Issue 49) pp:6491-6493
Publication Date(Web):02 May 2014
DOI:10.1039/C4CC00617H
Dendronized poly(amido amine)s (DPs) bearing tri-phosphate or bis-phosphonate peripheral groups are synthesized. These worm-like DPs can template the formation of BMSCs adhesive hydroxylapatite (HA) on the nano-scale, or self-assemble into mineral-collecting microfibers on the micro-scale, exhibiting similar functions of non-collagenous proteins (NCPs) in the natural biomineralization process of HA.
Co-reporter:Wei Wu, Qiujing Zhang, Jiantao Wang, Miao Chen, Shuai Li, Zaifu Lin and Jianshu Li
Polymer Chemistry 2014 vol. 5(Issue 19) pp:5668-5679
Publication Date(Web):30 May 2014
DOI:10.1039/C4PY00575A
Development of nanocarriers, which can selectively accumulate and remain within the tumor tissue matrix, is beneficial for non-invasive cancer diagnosis and therapy. In this study, a well-defined pH-sensitive block copolymer, i.e., succinic anhydride (SA)-modified poly(2-diisopropylaminoethyl methacrylate)-block-poly(2-aminoethyl methacrylate hydrochloride) (PDPA-b-PAMA/SA), was prepared by a two-step atom transfer radical polymerization (ATRP) and subsequent amidation. The low critical micelle concentration (CMC, 40.7 × 10−4 mg mL−1) of PDPA-b-PAMA/SA investigated in pH 7.4 aqueous solution confirmed the adequate thermodynamic stability of its self-assembly. In addition, the pH-sensitive aggregation behaviors of blank and drug-loaded PDPA-b-PAMA/SA were systematically studied at typical pH conditions (7.4 and 6.5) using dynamic light scattering (DLS) and transmission electron microscopy (TEM). Compared with the control sample, i.e., poly(D,L-lactide)-block-poly(2-aminoethyl methacrylate hydrochloride (PLA-b-PAMA/SA), both blank and drug-loaded PDPA-b-PAMA/SA (PDPA-b-PAMA/SA@DOX·HCl) exhibited obvious aggregation through electric interaction between the positive charge of the protonated PDPA block and the negative charge of the PAMA/SA block at tumor sites under slightly acidic condition. Moreover, the drug-loaded nanocarriers exhibited accelerated drug release profiles in response to the acidic condition due to the electric repulsion between the protonated PDPA block and positive DOX·HCl. Cytotoxicity assay results demonstrated that the pH-sensitive block copolymer did not demonstrate obvious cytotoxicity, even at a concentration up to 100 μg mL−1. The enhanced intracellular DOX·HCl distribution in nuclei was also confirmed by confocal laser scanning microscopy (CLSM). Thus, these results suggest that PDPA-b-PAMA/SA provides a feasible platform for efficient tumor-targeted therapy.
Co-reporter:Mei Chen, Jiaojiao Yang, Jiyao Li, Kunneng Liang, Libang He, Zaifu Lin, Xingyu Chen, Xiaokang Ren, Jianshu Li
Acta Biomaterialia 2014 Volume 10(Issue 10) pp:4437-4446
Publication Date(Web):October 2014
DOI:10.1016/j.actbio.2014.05.016
Abstract
In the bioinspired repair process of tooth enamel, it is important to simultaneously mimic the organic-matrix-induced biomineralization and increase the binding strength at the remineralization interface. In this work, a fourth-generation polyamidoamine dendrimer (PAMAM) is modified by dimethyl phosphate to obtain phosphate-terminated dendrimer (PAMAM-PO3H2) since it has a similar dimensional scale and peripheral functionalities to that of amelogenin, which plays important role in the natural development process of enamel. Its phosphate group has stronger affinity for calcium ion than carboxyl group and can simultaneously provide strong hydroxyapatite (HA)-binding capability. The MTT assay demonstrates the low cytotoxicity of PAMAM-PO3H2. Adsorption tests indicate that PAMAM-PO3H2 can be tightly adsorbed on the human tooth enamel. Scanning electron microscopy and X-ray diffraction are used to analyze the remineralization process. After being incubated in artificial saliva for 3 weeks, there is a newly generated HA layer of 11.23 μm thickness on the acid-etched tooth enamel treated by PAMAM-PO3H2, while the thickness for the carboxyl-terminated one (PAMAM-COOH) is only 6.02 μm. PAMAM-PO3H2 can regulate the remineralization process to form ordered new crystals oriented along the Z-axis and produce an enamel prism-like structure that is similar to that of natural tooth enamel. The animal experiment also demonstrates that PAMAM-PO3H2 can induce significant HA regeneration in the oral cavity of rats. Thus PAMAM-PO3H2 shows great potential as a biomimetic restorative material for human tooth enamel.
Co-reporter:Wei Wu;Jiantao Wang;Zaifu Lin;Xiuhua Li
Macromolecular Rapid Communications 2014 Volume 35( Issue 19) pp:1679-1684
Publication Date(Web):
DOI:10.1002/marc.201400362
Co-reporter:Wei Wu, Miao Chen, Jiantao Wang, Qiujing Zhang, Shuai Li, Zaifu Lin and Jianshu Li
RSC Advances 2014 vol. 4(Issue 58) pp:30780-30783
Publication Date(Web):03 Jul 2014
DOI:10.1039/C4RA05270F
Block polymers are synthesized to prepare nanocarriers with dual pH-sensitivity, which are expected to prolong blood circulation time, reduce systemic toxicity, enhance tumor cell uptake and accelerate intracellular drug release for efficient anti-cancer therapy.
Co-reporter:Wei Wu;Weigang Wang;Shuai Li;Jiantao Wang;Qiujing Zhang
Journal of Polymer Research 2014 Volume 21( Issue 7) pp:
Publication Date(Web):2014 July
DOI:10.1007/s10965-014-0494-4
In order to develop polymeric self-assembly with an intelligent morphological transition property under appropriate stimuli, a series of pH-sensitive amphiphilic block copolymers have been prepared via atom transfer radical polymerization (ATRP). Due to the delicately designed macromolecular structure, poly(ethylene glycol)44-b-poly(2-diisopropylaminoethyl methacrylate)15 (PEG44-b-PDPA15) could form self-assemblies with a controllable morphological transition in response to the physiological pH changes. As demonstrated by the results of dynamic light scattering (DLS) records and transmission electron microscopy (TEM) micrographs, PEG44-b-PDPA15 could self-assemble into toruloid aggregates arranged by several single micelles at pH 7.4, but the morphology changed into uniform single micelles at pH 6.5. With a further decrease of pH value to 5.5, PEG-b-PDPA became double hydrophilic and could not self-assemble into any nanostructure. Therefore, this block copolymer provides a feasible approach to construct a nanoscale smart self-assembly with adjustable morphologies, which exhibits its potential for biomedical applications with specific physiological pH stimuli, such as intracellular delivery and tumor therapy.
Co-reporter:Shuai Li, Qin He, Tianchan Chen, Wei Wu, Kening Lang, Zhong-Ming Li, Jianshu Li
Colloids and Surfaces B: Biointerfaces 2014 Volume 123() pp:486-492
Publication Date(Web):1 November 2014
DOI:10.1016/j.colsurfb.2014.09.049
•We have successfully developed a core-stabilized mixed micellar system with β-CD-PLA-mPEG and TA-PLA-mPEG for the co-delivery of DOX and FA.•DOX can be loaded within the hydrophobic segment of PLA and FA may form stable complexation with β-CD in the core.•The mixed micelles are based on well-accepted medical materials and can be easily cross-linked by adding 1,4-dithio-d,l-threitol (DTT), which are highly promising for intracellular co-delivery of multiple drugs.The combination of multiple drugs within a single nanocarrier can provide significant advantages for disease therapy and it is desirable to introduce a second drug based on host–guest interaction in these co-delivery systems. In this study, a core-stabilized mixed micellar system consisting of β-cyclodextrin-conjugated poly(lactic acid)-b-poly(ethylene glycol) (β-CD-PLA-mPEG) and DL-Thioctic acid (TA) terminated PLA-mPEG (TA-PLA-mPEG) was developed for the co-delivery of DOX and fluorescein isothiocyanate labeled adamantane (FA). DOX can be loaded within the hydrophobic segment of PLA and FA may form stable complexation with β-CD in the core. The mixed micelles (MM) are based on well-accepted medical materials and can be easily cross-linked by adding 1,4-dithio-d,l-threitol (DTT), which can enhance the stability of the system. Drug-loaded MM system was characterized in terms of particle size, morphology, drug loading and in vitro release profile. Cytotoxicity test showed that blank MM alone showed negligible cytotoxicity whereas the drug-loaded MM remained relatively high cytotoxicity for HeLa cancer cells. Confocal laser scanning microscopy (CLSM) demonstrated that the MM could efficiently deliver and release DOX and FA in the same tumor cells to effectively improve drugs’ bioavailability. These results suggested that the core-stabilized MM are highly promising for intracellular co-delivery of multiple drugs.We construct mixed micelles by cyclodextrin-conjugated and cross-linked copolymers for effectively intracellular co-delivery of multiple drugs.
Co-reporter:Jianyu Xin, Ping Dong, Lu Pu, Hong Tan, Jianshu Li
Colloids and Surfaces A: Physicochemical and Engineering Aspects 2014 450() pp: 25-35
Publication Date(Web):
DOI:10.1016/j.colsurfa.2014.03.003
Co-reporter:Yan Zhou, Jiaojiao Yang, Zaifu Lin, Jiyao Li, Kunneng Liang, He Yuan, Sheyu Li, Jianshu Li
Colloids and Surfaces B: Biointerfaces 2014 Volume 115() pp:237-243
Publication Date(Web):1 March 2014
DOI:10.1016/j.colsurfb.2013.11.045
•We have successfully prepared and characterized a group of triclosan-loaded carboxyl-terminated PAMAM dendrimers.•The dendrimer can induce in situ remineralization on the dentine and release anti-bacterial drug for local treatment at the same time.•The newly generated crystals are similar to the natural dentine in terms of shape, size and orientation degree.•This system is proved to be low cytotoxicity by MTT assay.•The drug release profiles are controlled by both dendrimer encapsulation capability and the mineralization degree.In order to treat dental caries of damaged dentine, triclosan-loaded carboxyl-terminated poly(amido amine) dendrimer (PAMAM-COOH) is prepared and characterized. While being incubated in artificial saliva, triclosan-loaded PAMAM-COOH formulation can induce in situ remineralization of hydroxyapatite (HA) on etched dentine, and the regenerated HA has a similar crystal structure with natural dentine. It can also release the encapsulated triclosan for a long period. The interesting drug release profiles are controlled by both dendrimer encapsulation capability and the mineralization degree, which are ideal to obtain multifunctional properties of long-term release of anti-bacterial drug for local treatment during the remineralization process. The triclosan-loaded G4-COOH provides a general strategy to cure dental caries and repair damaged dentine at the same time, which forms a potential restorative material for dental repair.
Co-reporter:K.M. Xiu, J.J. Yang, N.N. Zhao, J.S. Li, F.J. Xu
Acta Biomaterialia 2013 Volume 9(Issue 1) pp:4726-4733
Publication Date(Web):January 2013
DOI:10.1016/j.actbio.2012.08.020
Abstract
Controlled β-cyclodextrin (β-CD) core-based cationic star polymers have attracted considerable attention as non-viral gene carriers. Atom transfer radical polymerization (ATRP) could be readily used to produce the star-shaped polymers. The precise control of the number of initiation sites on the multifunctional core was of crucial importance to the investigation of the structure–property relationship of the functional star gene carriers. Herein, the controlled multiarm star polymers consisting of a β-CD core and various arm lengths of poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) were prepared via ATRP from the chloroacetylated β-CD with well-designed initiation sites. Generally, these star polycations can condense plasmid DNA into 100–150 nm nanoparticles with positive zeta potentials of 30–40 mV at N/P ratios (star polymer to DNA ratios) of 17 or higher. The effects of arm numbers and lengths on gene delivery were investigated in detail. With a fixed length of the PDMAEMA arm, the fewer the number of arms, the lower the toxicity. The star polycations with suitable arm numbers possess the best transfection ability. On the other hand, with the fixed molecular weights, the shorter the arms, the lower the toxicity. The polymers with 21 arms possess the lowest transfection efficiency.
Co-reporter:Jiaojiao Yang, Shuqin Cao, Jiahui Li, Jianyu Xin, Xingyu Chen, Wei Wu, Fujian Xu and Jianshu Li
Soft Matter 2013 vol. 9(Issue 31) pp:7553-7559
Publication Date(Web):05 Jun 2013
DOI:10.1039/C3SM51510A
In this work, the PAMAM dendrimer self-assembles into macroscopic aggregates with a microribbon structure in aqueous solution containing ferric chloride, which are millimeters in length and micrometers in width. The microribbons have a stable structure with the thickness approaching 5 μm. Their self-assembly process and final morphology are pretty similar to those of the supramolecular assembly of amelogenin. The method opens a new avenue for fabricating novel and well-defined materials to mimic the assembly process of proteins and their biological functionalizations as protein analogues for wide applications.
Co-reporter:Jiaojiao Yang;Shuqin Cao;Jianyu Xin;Xingyu Chen;Wei Wu
Journal of Polymer Research 2013 Volume 20( Issue 6) pp:
Publication Date(Web):2013 June
DOI:10.1007/s10965-013-0157-x
Layer-by-layer (LbL) systems constructed via electrostatic attraction or other forces can be used as templates in biomimetic mineralization. In this work, 21-arm star poly(acrylic acid) (star-PAA) and 21-arm star poly[2-(dimethylamino)ethyl methacrylate] (star-PDMAEMA) were successfully synthesized from a cyclodextrin core via atom transfer radical polymerization (ATRP). The star polymers were used to construct three kinds of LbL systems: negatively charged star-PAA with positively charged chitosan (CHI) as a model of unconfined space for mineralization, and positively charged star-PDMAEMA with negatively charged poly(styrene sulfonic acid) sodium salt (PSS), which had acid-etched holes or constructed within a porous polycarbonate filters, as two different models of confined space for mineralization. Different crystal forms of calcium carbonate were obtained using the three systems, so these LbL systems assembled from star polymers could be new tools for developing functional materials and investigating fundamental aspects of the mineralization process.
Co-reporter:Zaifu Lin, Shuqin Cao, Xingyu Chen, Wei Wu, and Jianshu Li
Biomacromolecules 2013 Volume 14(Issue 7) pp:
Publication Date(Web):June 13, 2013
DOI:10.1021/bm4003442
A series of thermoresponsive and biocompatible ABA triblock copolymers in which the outer A blocks comprise poly(N-isopropylacrylamide) and the central B block consists of O-phosphoethanolamine (PEA) grafted poly(acrylic acid) (PAA(PEA)) are achieved by atom transfer radical polymerization (ATRP) and subsequent modification. At a relatively low concentration (2 w/v% in phosphate buffered saline), the triblock copolymers can form free-standing gels at 37 °C. Using a combination of variable-temperature 1H NMR, dynamic light scattering, and rheological measurements, it is demonstrated that the gelation behavior is highly dependent on both the length of A blocks and the substitution degree of phosphate group. To examine the potential application as scaffold for bone tissue engineering, the physical gels are incubated in the simulated body fluid (SBF) for 2 weeks. Obvious nucleation and growth of hydroxyapatite are found in the gels, as indicated by the scanning electron microscope, energy dispersive spectroscopy, and X-ray diffraction measurements. The triblock copolymers also exhibit low cytotoxicity in cell viability test. Thus the triblock copolymers have great potential for bone tissue engineering.
Co-reporter:Jiahui Li, JiaoJiao Yang, Jiyao Li, Liang Chen, Kunneng Liang, Wei Wu, Xingyu Chen, Jianshu Li
Biomaterials 2013 34(28) pp: 6738-6747
Publication Date(Web):
DOI:10.1016/j.biomaterials.2013.05.046
Co-reporter:Duo Wu, Jiaojiao Yang, Jiyao Li, Liang Chen, Bei Tang, Xingyu Chen, Wei Wu, Jianshu Li
Biomaterials 2013 34(21) pp: 5036-5047
Publication Date(Web):
DOI:10.1016/j.biomaterials.2013.03.053
Co-reporter:Xingyu Chen, Jun Luo, Wei Wu, Hong Tan, Fujian Xu, Jianshu Li
Acta Biomaterialia 2012 Volume 8(Issue 12) pp:4380-4388
Publication Date(Web):December 2012
DOI:10.1016/j.actbio.2012.08.014
Abstract
Insulin, glucose oxidase and positively charged star polymers were incorporated into multilayer films by the layer-by-layer (LbL) assembly method. It is interesting to find that the arrangement sequence of the three components could significantly affect the glucose-responsive controlled release behaviors. The insulin release in vitro could be tuned to linear release and obtain desired “on–off” sensitivity in response to stepwise glucose challenge, just by rearranging the assembly sequence of LbL building blocks. Further, the controlled release of insulin in vivo, as well as the hypoglycemic effect, could be obviously prolonged from 17 days to 36 days by this simple strategy without changing the dosage of all the LbL components. In addition to provide a potential glucose-responsive delivery system for insulin, the strategy described in this paper could be valuable for various drug-incorporated LbL systems with three or more components.
Co-reporter:Jun Luo, Shuqin Cao, Xingyu Chen, Shuning Liu, Hong Tan, Wei Wu, Jianshu Li
Biomaterials 2012 33(33) pp: 8733-8742
Publication Date(Web):
DOI:10.1016/j.biomaterials.2012.08.041
Co-reporter:Jiahui Li;Jiaojiao Yang;Fujian Xu;Jiazhuang Xu
Journal of Polymer Research 2012 Volume 19( Issue 8) pp:
Publication Date(Web):2012 August
DOI:10.1007/s10965-012-9941-2
A simple approach to tune the fluorescent properties of star polymers was reported via only adjusting the arm numbers. Atom transfer radical polymerization (ATRP) using β-CD-based initiators was utilized to synthesize star-shaped poly(N-vinyl carbazole) (star PVK) consisting of β-cyclodextrin (β-CD) core and different arm numbers (3, 7, and 14). The conversion ratio was nearly 100 % characterized by 1H-NMR. Fluorescent properties of star PVKs could be modulated by varying the arm number at the same mass concentration of fluorescent groups. Fluorescence intensity declined with the increase of arm number and displayed “sandwich-like excimer” emission rather than “higher-energy excimer” emission. The unique structure of star polymer might effectively inhibit the formation of “random coil”, which often happened in linear polymer systems. In addition, all of the star PVKs with different arm numbers had the same emission peak centered at 395 nm and excimer band at 420 nm, respectively, which differed from their linear counterparts and demonstrated that the intramolecular interaction was not dominant in this system.
Co-reporter:Xingyu Chen, Wei Wu, Zhizhang Guo, Jianyu Xin, Jianshu Li
Biomaterials 2011 32(6) pp: 1759-1766
Publication Date(Web):
DOI:10.1016/j.biomaterials.2010.11.002
Co-reporter:Zhizhang Guo, Xingyu Chen, Xiao Zhang, Jianyu Xin, Jianshu Li, Huining Xiao
Tetrahedron Letters 2010 Volume 51(Issue 17) pp:2351-2353
Publication Date(Web):28 April 2010
DOI:10.1016/j.tetlet.2010.02.140
Selective chloroacetylations at per-2,3- and per-3-positions of β-cyclodextrin have been achieved via protection–deprotection methods. The reaction condition of pH >4 controlled by appropriate proton scavenger is essential for obtaining designed chloroacetylation degree under effective protection, as well as for high yield with less side-products. The β-cyclodextrin derivatives with 14 or 7 chloroacetyl groups are useful initiators for synthesizing star polymers with well-defined structure by atom transfer radical polymerization.
Co-reporter:Lan Huang;Jianyu Xin;Yuchao Guo
Journal of Applied Polymer Science 2010 Volume 115( Issue 3) pp:1371-1379
Publication Date(Web):
DOI:10.1002/app.30775
Abstract
This work describes a new oral pharmaceutical formulation of insulin that is complexed with cationic β-cyclodextrin polymers (CPβCDs), and then encapsulated into alginate/chitosan microspheres, which are prepared by ionotropic pregelation/polyelectrolyte method. CPβCDs were synthesized through a one-step polymerization of β-cyclodextrin (βCD), epichlorohydrin, and choline chloride. CPβCDs have enhanced ability to complex with insulin due to the assistance of their polymeric chains, as well as the electrostatic interactions between insulin (negatively charged while pH>5.3) and quaternary ammonium groups of CPβCDs. The noncovalent inclusion complex formed between CPβCDs and insulin was analyzed by Fourier transform infrared and fluorescence emission spectra. With the increase of zeta potential of CPβCDs from 1.8 to 14.2 mV, the insulin association efficiency (AE) of current system was increased from 55.2 to 71.8%, whereas the AE of insulin-loaded microspheres at the same condition was only 50.7%. The cumulative insulin release in simulated intestinal fluid was also higher than that of the insulin-loaded microspheres and βCD-insulin encapsulated microspheres. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010
Co-reporter:Zhizhang Guo, Xingyu Chen, Jianyu Xin, Duo Wu, Jianshu Li, and Chenlong Xu
Macromolecules 2010 Volume 43(Issue 21) pp:9087-9093
Publication Date(Web):October 14, 2010
DOI:10.1021/ma1013429
The influence of molecular weight and arm number of star polymers on the buildup and pH-dependent morphology changes of multilayer films assembled from star poly[2-(dimethylamino)ethyl methacrylate] (PDMAEMA) and linear poly(styrenesulfonate) (PSS) was systematically investigated. Well-defined star PDMAEMA, consisting of β-cyclodextrin (CD) core and different arm number (21, 14, and 7) were successfully synthesized via atom transfer radical polymerization (ATRP). It is found that star polymers with certain arm number deposit more mass with the increase of molecular weight. As for the star polymers with almost the same arm length but different arm number, film assembled from 14-arm star PDMAEMA exhibits the fastest growth and the most significant morphology changes upon the pH 2.75 treatment. It is assumed that the interdiffusion of PSS controlled by star PDMAEMA with different structures should be responsible for the different buildup and pH-dependent morphology changes of the multilayer films.
Co-reporter:R. H. True;P. G. Agnew
Science 1919 Vol 49(1273) pp:487-489
Publication Date(Web):23 May 1919
DOI:10.1126/science.49.1273.487
Co-reporter:Xingyu Chen, Tianchan Chen, Zaifu Lin, Xian'e Li, Wei Wu and Jianshu Li
Chemical Communications 2015 - vol. 51(Issue 3) pp:NaN490-490
Publication Date(Web):2014/11/07
DOI:10.1039/C4CC08681C
A choline phosphate (CP) modified surface is designed to resist protein adsorption due to its zwitterionic properties and simultaneously promote cell adhesion though its universal interaction with phosphate choline (PC) headgroups of the cell membrane. This work provides a new approach to obtain a cell-adhesive surface with a non-biofouling ‘background’, which has a potential for tissue engineering.
Co-reporter:Jianyu Xin, Tianchan Chen, Zaifu Lin, Ping Dong, Hong Tan and Jianshu Li
Chemical Communications 2014 - vol. 50(Issue 49) pp:NaN6493-6493
Publication Date(Web):2014/05/02
DOI:10.1039/C4CC00617H
Dendronized poly(amido amine)s (DPs) bearing tri-phosphate or bis-phosphonate peripheral groups are synthesized. These worm-like DPs can template the formation of BMSCs adhesive hydroxylapatite (HA) on the nano-scale, or self-assemble into mineral-collecting microfibers on the micro-scale, exhibiting similar functions of non-collagenous proteins (NCPs) in the natural biomineralization process of HA.
Co-reporter:Chunmei Ding, Zhuoxin Chen and Jianshu Li
Biomaterials Science (2013-Present) 2017 - vol. 5(Issue 8) pp:NaN1449-1449
Publication Date(Web):2017/07/10
DOI:10.1039/C7BM00247E
Enamel, dentin and bone are calcified hard tissues in the human body that play significant roles in food mastication and movement support. Generally, hard tissues lack the ability of self-repair, except for the regeneration ability of bone for small-scale defects. Fabrication of man-made repair materials is therefore highly demanded. In this review, following a bioinspired strategy, we describe the composition and multiscale structures of different hard tissues, and highlight the key points for the reconstruction of hard tissues. Finally, bioinspired tissue repair techniques ranging from molecule-induced mineralization, to microscale assembly to macroscaffold fabrication are summarised.
Co-reporter:Wei Wu, Zaifu Lin, Yanpeng Liu, Xinyuan Xu, Chunmei Ding and Jianshu Li
Journal of Materials Chemistry A 2017 - vol. 5(Issue 3) pp:NaN434-434
Publication Date(Web):2016/12/22
DOI:10.1039/C6TB02657E
A type of four-arm star-shaped copolymer (star-PAA(PEA)-PNIPAM), consisting of the thermoresponsive block (poly(N-isopropylacrylamide), PNIPAM) and the phosphorylated functional block O-phosphoethanolamine (PEA) grafted poly(acrylic acid) (PAA(PEA)), is synthesized by atom transfer radical polymerization (ATRP) and subsequent modification. Owing to the unique superiority of the star-shaped structure, star-PAA(PEA)-PNIPAM can transform from the sol to gel state in response to the physiological temperature (37 °C) at a relatively low polymer concentration (>0.5 wt%). In addition, because of the enriched phosphorylated functional groups, the hydrogel formed by star-PAA(PEA)-PNIPAM can mimic the acidic extracellular matrix protein to adsorb calcium ions and mineralize in situ, both in in vitro and in in vivo experiments. Meanwhile, it is favorable for cell adhesion and proliferation due to its appropriate three-dimensional interspace. Thus, the biocompatible star-PAA(PEA)-PNIPAM hydrogel has great potential for bone repair applications.
