Co-reporter:Tera M. Filion;Jordan D. Skelly;Henry Huang
Stem Cell Research & Therapy 2017 Volume 8( Issue 1) pp:65
Publication Date(Web):11 March 2017
DOI:10.1186/s13287-017-0521-6
Poor bone quality, increased fracture risks, and impaired bone healing are orthopedic comorbidities of type 1 diabetes (T1DM). Standard osteogenic growth factor treatments are inadequate in fully rescuing retarded healing of traumatic T1DM long bone injuries where both periosteal and bone marrow niches are disrupted. We test the hypotheses that osteogenesis of bone marrow-derived stromal cells (BMSCs) and periosteum-derived cells (PDCs), two critical skeletal progenitors in long bone healing, are both impaired in T1DM and that they respond differentially to osteogenic bone morphogenetic proteins (BMPs) and/or insulin-like growth factor-1 (IGF-1) rescue.BMSCs and PDCs were isolated from Biobreeding Diabetes Prone/Worcester rats acquiring T1DM and normal Wistar rats. Proliferation, osteogenesis, and adipogenesis of the diabetic progenitors were compared with normal controls. Responses of diabetic progenitors to osteogenesis rescue by rhBMP-2/7 heterodimer (45 or 300 ng/ml) and/or rhIGF-1 (15 or 100 ng/ml) in normal and high glucose cultures were examined by alizarin red staining and qPCR.Diabetic BMSCs and PDCs proliferated slower and underwent poorer osteogenesis than nondiabetic controls, and these impairments were exacerbated in high glucose cultures. Osteogenesis of diabetic PDCs was rescued by rhBMP-2/7 or rhBMP-2/7 + rhIGF-1 in both normal and high glucose cultures in a dose-dependent manner. Diabetic BMSCs, however, only responded to 300 ng/nl rhBMP-2/7 with/without 100 ng/ml rhIGF-1 in normal but not high glucose osteogenic culture. IGF-1 alone was insufficient in rescuing the osteogenesis of either diabetic progenitor. Supplementing rhBMP-2/7 in high glucose osteogenic culture significantly enhanced gene expressions of type 1 collagen (Col 1), osteocalcin (OCN), and glucose transporter 1 (GLUT1) while suppressing that of adipogenic marker peroxisome proliferator-activated receptor gamma (PPARγ) in diabetic PDCs. The same treatment in high glucose culture only resulted in a moderate increase in Col 1, but no significant changes in OCN or GLUT1 expressions in diabetic BMSCs.This study demonstrates more effective osteogenesis rescue of diabetic PDCs than BMSCs by rhBMP-2/7 with/without rhIGF-1 in a hyperglycemia environment, underscoring the necessity to tailor biochemical therapeutics to specific skeletal progenitor niches. Our data also suggest potential benefits of combining growth factor treatment with blood glucose management to optimize orthopedic therapeutic outcomes for T1DM patients.
Co-reporter:Ben Zhang, Janae E. DeBartolo, and Jie Song
ACS Applied Materials & Interfaces 2017 Volume 9(Issue 5) pp:
Publication Date(Web):January 26, 2017
DOI:10.1021/acsami.6b14167
Maintaining adequate or enhancing mechanical properties of shape memory polymers (SMPs) after shape recovery in an aqueous environment are greatly desired for biomedical applications of SMPs as self-fitting tissue scaffolds or minimally invasive surgical implants. Here we report stable temporary shape fixing and facile shape recovery of biodegradable triblock amphiphilic SMPs containing a poly(ethylene glycol) (PEG) center block and flanking poly(lactic acid) or poly(lactic-co-glycolic acid) blocks in warm water, accompanied by concomitant enhanced mechanical strengths. Differential scanning calorimetry (DSC), wide-angle X-ray diffraction (WXRD), and small-angle X-ray scattering (SAXS) analyses revealed that the unique stiffening of the amphiphilic SMPs upon hydration was due to hydration-driven microphase separation and PEG crystallization. We further demonstrated that the chemical composition of degradable blocks in these SMPs could be tailored to affect the persistence of hydration-induced stiffening upon subsequent dehydration. These properties combined open new horizons for these amphiphilic SMPs for smart weight-bearing in vivo applications (e.g., as self-fitting intervertebral discs). This study also provides a new material design strategy to strengthen polymers in aqueous environment in general.Keywords: amphiphilic biodegradable polymers; hydration-induced stiffening effect; minimal invasive surgery; shape memory; weight-bearing implantation;
Co-reporter:Pingsheng Liu
Journal of Polymer Science Part A: Polymer Chemistry 2016 Volume 54( Issue 9) pp:1268-1277
Publication Date(Web):
DOI:10.1002/pola.27969
ABSTRACT
The combination of atom transfer radical polymerization (ATRP) and click chemistry has created unprecedented opportunities for controlled syntheses of functional polymers. ATRP of azido-bearing methacrylate monomers (e.g., 2-(2-(2-azidoethyoxy)ethoxy)ethyl methacrylate, AzTEGMA), however, proceeded with poor control at commonly adopted temperature of 50 °C, resulting in significant side reactions. By lowering reaction temperature and monomer concentrations, well-defined pAzTEGMA with significantly reduced polydispersity were prepared within a reasonable timeframe. Upon subsequent functionalization of the side chains of pAzTEGMA via Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) click chemistry, functional polymers with number-average molecular weights (Mn) up to 22 kDa with narrow polydispersity (PDI < 1.30) were obtained. Applying the optimized polymerization condition, we also grafted pAzTEGMA brushes from Ti6Al4 substrates by surface-initiated ATRP (SI-ATRP), and effectively functionalized the azide-terminated side chains with hydrophobic and hydrophilic alkynes by CuAAC. The well-controlled ATRP of azido-bearing methacrylates and subsequent facile high-density functionalization of the side chains of the polymethacrylates via CuAAC offers a useful tool for engineering functional polymers or surfaces for diverse applications. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016, 54, 1268–1277
Co-reporter:Artem B. Kutikov, Jordan D. Skelly, David C. Ayers, and Jie Song
ACS Applied Materials & Interfaces 2015 Volume 7(Issue 8) pp:4890
Publication Date(Web):February 19, 2015
DOI:10.1021/am508984y
Effective repair of critical-size long bone defects presents a significant clinical challenge. Electrospun scaffolds can be exploited to deliver protein therapeutics and progenitor cells, but their standalone application for long bone repair has not been explored. We have previously shown that electrospun composites of amphiphilic poly(d,l-lactic acid)-co-poly(ethylene glycol)-co-poly(d,l-lactic acid) (PELA) and hydroxyapatite (HA) guide the osteogenic differentiation of bone marrow stromal cells (MSCs), making these scaffolds uniquely suited for evaluating cell-based bone regeneration approaches. Here we examine whether the in vitro bioactivity of these electrospun scaffolds can be exploited for long bone defect repair, either through the participation of exogenous MSCs or through the activation of endogenous cells by a low dose of recombinant human bone morphogenetic protein-2 (rhBMP-2). In critical-size rat femoral segmental defects, spiral-wrapped electrospun HA–PELA with preseeded MSCs resulted in laminated endochondral ossification templated by the scaffold across the longitudinal span of the defect. Using GFP labeling, we confirmed that the exogenous MSCs adhered to HA–PELA survived at least 7 days postimplantation, suggesting direct participation of these exogenous cells in templated bone formation. When loaded with 500 ng of rhBMP-2, HA–PELA spirals led to more robust but less clearly templated bone formation than MSC-bearing scaffolds. Both treatment groups resulted in new bone bridging over the majority of the defect by 12 weeks. This study is the first demonstration of a standalone bioactive electrospun scaffold for templated bone formation in critical-size long bone defects.Keywords: amphiphilic polymer; BMP (bone morphogenetic protein); bone marrow derived stromal cells; bone tissue engineering; electrospinning; hydroxyapatite
Co-reporter:Artem B. Kutikov and Jie Song
ACS Biomaterials Science & Engineering 2015 Volume 1(Issue 7) pp:463
Publication Date(Web):May 26, 2015
DOI:10.1021/acsbiomaterials.5b00122
Biodegradable tissue engineering scaffolds have great potential for delivering cells/therapeutics and supporting tissue formation. Polyesters, the most extensively investigated biodegradable synthetic polymers, are not ideally suited for diverse tissue engineering applications due to limitations associated with their hydrophobicity. This review discusses the design and applications of amphiphilic block copolymer scaffolds integrating hydrophilic poly(ethylene glycol) (PEG) blocks with hydrophobic polyesters. Specifically, we highlight how the addition of PEG results in striking changes to the physical properties (swelling, degradation, mechanical, handling) and biological performance (protein and cell adhesion) of the degradable synthetic scaffolds in vitro. We then perform a critical review of how these in vitro characteristics translate to the performance of biodegradable amphiphilic block copolymer-based scaffolds in the repair of a variety of tissues in vivo including bone, cartilage, skin, and spinal cord/nerve. We conclude the review with recommendations for future optimizations in amphiphilic block copolymer design and the need for better-controlled in vivo studies to reveal the true benefits of the amphiphilic synthetic tissue scaffolds.Keywords: amphiphilic polymers; biodegradable; block copolymers; poly(ethylene glycol) (PEG); tissue engineering scaffolds
Co-reporter:Jianwen Xu ; Ellva Feng
Journal of the American Chemical Society 2014 Volume 136(Issue 11) pp:4105-4108
Publication Date(Web):March 5, 2014
DOI:10.1021/ja4130862
Hydrogels with predictable degradation are highly desired for biomedical applications where timely disintegration of the hydrogel (e.g., drug delivery, guided tissue regeneration) is required. However, precisely controlling hydrogel degradation over a broad range in a predictable manner is challenging due to limited intrinsic variability in the degradation rate of liable bonds and difficulties in modeling degradation kinetics for complex polymer networks. More often than not, empirical tuning of the degradation profile results in undesired changes in other properties. Here we report a simple but versatile hydrogel platform that allows us to formulate hydrogels with predictable disintegration time from 2 to >250 days yet comparable macroscopic physical properties. This platform is based on a well-defined network formed by two pairs of four-armed polyethylene glycol macromers terminated with azide and dibenzocyclooctyl groups, respectively, via labile or stable linkages. The high-fidelity bioorthogonal reaction between the symmetric hydrophilic macromers enables robust cross-linking in water, phosphate-buffered saline, and cell culture medium to afford tough hydrogels capable of withstanding >90% compressive strain. Strategic placement of labile ester linkages near the cross-linking site within this superhydrophilic network, accomplished by adjustments of the ratio of the macromers used, enables broad tuning of the disintegration rates precisely matching with the theoretical predictions based on first-order linkage cleavage kinetics. This platform can be exploited for applications where a precise degradation rate is targeted.
Co-reporter:Pingsheng Liu, Erin Emmons and Jie Song
Journal of Materials Chemistry A 2014 vol. 2(Issue 43) pp:7524-7533
Publication Date(Web):01 Oct 2014
DOI:10.1039/C4TB01046A
Cationic and anionic residues of the extracellular matrices (ECM) of bone play synergistic roles in recruiting precursor ions and templating the nucleation, growth and crystalline transformations of calcium apatite in natural biomineralization. We previously reported that zwitterionic sulfobetaine ligands can template extensive 3-dimensional (3-D) hydroxyapatite (HA)-mineralization of photo-crosslinked polymethacrylate hydrogels. Here, we compared the potency of two other major zwitterionic ligands, phosphobetaine and carboxybetaine, with that of the sulfobetaine in mediating 3-D mineralization using a crosslinked polymethacrylate hydrogel platform. We confirmed that all three zwitterionic hydrogels were able to effectively template 3-D mineralization, supporting the general ability of zwitterions to mediate templated mineralization. Among them, however, sulfobetaine and phosphobetaine hydrogels templated denser 3-D mineralization than the carboxybetaine hydrogel, likely due to their higher free water fractions and better maintenance of zwitterionic nature throughout the pH-changes during the in vitro mineralization process. We further demonstrated that the extensively mineralized zwitterionic hydrogels could be exploited for efficient retention (e.g. 99% retention after 24 h incubation in PBS) of osteogenic growth factor recombinant bone morphogenetic protein-2 (rhBMP-2) and subsequent sustained local release with retained bioactivity. Combined with the excellent cytocompatibility of all three zwitterionic hydrogels and the significantly improved cell adhesive properties of their mineralized matrices, these materials could find promising applications in bone tissue engineering.
Co-reporter:Pingsheng Liu, Emily Domingue, David C. Ayers, and Jie Song
ACS Applied Materials & Interfaces 2014 Volume 6(Issue 10) pp:7141
Publication Date(Web):May 14, 2014
DOI:10.1021/am501967y
Osteoconductive mineral coatings are beneficial for improving the osteointegration of metallic orthopedic/dental implants, but achieving adequate structural integration between the surface minerals and underlying metallic substrates has been a significant challenge. Here, we report covalent grafting of zwitterionic poly(sulfobetaine methacrylate) (pSBMA) brushes on the Ti6Al4V substrates to promote the surface-mineralization of hydroxyapatite with enhanced surface mineral coverage and mineral-substrate interfacial adhesion. We first optimized the atom transfer radical polymerization (ATRP) conditions for synthesizing pSBMA polymers in solution. Well-controlled pSBMA polymers (relative molecular weight up to 26kD, PDI = 1.17) with high conversions were obtained when the ATRP was carried out in trifluoroethanol/ionic liquid system at 60 °C. Applying identical polymerization conditions, surface-initiated atom transfer radical polymerization (SI-ATRP) was carried out to graft zwitterionic pSBMA brushes (PDI < 1.20) from the Ti6Al4V substrates, generating a stable superhydrophilic and low-fouling surface coating without compromising the bulk mechanic property of the Ti6Al4V substrates. The zwitterionic pSBMA surface brushes, capable of attracting both cationic and anionic precursor ions during calcium phosphate apatite mineralization, increased the surface mineral coverage from 32% to 71%, and significantly reinforced the attachment of the apatite crystals on the Ti6Al4V substrate. This facile approach to surface modification of metallic substrates can be exploited to generate multifunctional polymer coatings and improve the performance of metallic implants in skeletal tissue engineering and orthopedic and dental care.Keywords: calcium phosphate apatite; mineralization; SI-ATRP; surface modification; Ti6Al4V; zwitterionic brush;
Co-reporter:Pingsheng Liu, Jordan D. Skelly, Jie Song
Acta Biomaterialia 2014 Volume 10(Issue 10) pp:4296-4303
Publication Date(Web):October 2014
DOI:10.1016/j.actbio.2014.06.024
Abstract
Zwitterions are well known for their anti-biofouling properties. Past investigations of zwitterionic materials for biomedical uses have been centered on exploiting their ability to inhibit non-specific adsorption of proteins. Here, we report that zwitterionic motifs, when presented in three dimensions (e.g. in crosslinked hydrogels), could effectively sequester osteogenic bone morphogenetic protein-2 (rhBMP-2). The ionic interactions between rhBMP-2 and the 3-D zwitterionic network enabled dynamic sequestering and sustained release of the protein with preserved bioactivity. We further demonstrated that the zwitterionic hydrogel confers high-efficiency in vivo local delivery of rhBMP-2. It can template the functional healing of critical-size femoral segmental defects in rats with rhBMP-2 at a loading dose substantially lower than those required for current natural or synthetic polymeric carriers. These findings reveal a novel function of zwitterionic materials beyond their commonly perceived anti-biofouling property, and may establish 3-D zwitterionic matrices as novel high-efficiency vehicles for protein/ionic drug therapeutic delivery.
Co-reporter:Jing Zhang, Jie Song
Acta Biomaterialia 2014 Volume 10(Issue 7) pp:3079-3090
Publication Date(Web):July 2014
DOI:10.1016/j.actbio.2014.02.051
Abstract
Controlled delivery of the angiogenic factor sphingosine 1-phosphate (S1P) represents a promising strategy for promoting vascularization during tissue repair and regeneration. In this study, we developed an amphiphilic biodegradable polymer platform for the stable encapsulation and sustained release of S1P. Mimicking the interaction between amphiphilic S1P and its binding proteins, a series of polymers with hydrophilic poly(ethylene glycol) core and lipophilic flanking segments of polylactide and/or poly(alkylated lactide) with different alkyl chain lengths were synthesized. These polymers were electrospun into fibrous meshes, and loaded with S1P in generally high loading efficiencies (>90%). Sustained S1P release from these scaffolds could be tuned by adjusting the alkyl chain length, blockiness and lipophilic block length, achieving 35–55% and 45–80% accumulative releases in the first 8 h and by 7 days, respectively. Furthermore, using endothelial cell tube formation assay and chicken chorioallantoic membrane assay, we showed that the different S1P loading doses and release kinetics translated into distinct pro-angiogenic outcomes. These results suggest that these amphiphilic polymers are effective delivery vehicles for S1P and may be explored as tissue engineering scaffolds where the delivery of lipophilic or amphiphilic bioactive factors is desired.
Co-reporter:Jianwen Xu;Ellva Feng
Journal of Applied Polymer Science 2014 Volume 131( Issue 5) pp:
Publication Date(Web):
DOI:10.1002/app.39822
ABSTRACT
Aliphatic polycarbonates (APCs) were discovered a long time ago, with their conventional applications mostly limited to low-molecular-weight oligomeric intermediates for copolymerization with other prepolymers or small molecules. Recent developments in polymerization techniques have overcome the difficulty in preparing high-molecular-weight APCs. These in turn, along with new functional monomers, have enabled the preparation of a wide range of APCs with diverse chemical compositions and structures. This review summarizes the latest polymerization techniques for preparing well-defined functional APCs and the new applications of those APCs, especially in the biomedical field. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2014, 131, 39822.
Co-reporter:Artem B. Kutikov;Kevin A. Reyer
Macromolecular Chemistry and Physics 2014 Volume 215( Issue 24) pp:
Publication Date(Web):
DOI:10.1002/macp.201400340
Co-reporter:Artem B. Kutikov, Jie Song
Acta Biomaterialia 2013 Volume 9(Issue 9) pp:8354-8364
Publication Date(Web):September 2013
DOI:10.1016/j.actbio.2013.06.013
Abstract
Electrospun polymer/hydroxyapatite (HA) composites combining biodegradability with osteoconductivity are attractive for skeletal tissue engineering applications. However, most biodegradable polymers such as poly(lactic acid) (PLA) are hydrophobic and do not blend with adequate interfacial adhesion with HA, compromising the structural homogeneity, mechanical integrity and biological performance of the composite. To overcome this challenge, we combined a hydrophilic polyethylene glycol (PEG) block with poly(d,l-lactic acid) to improve the adhesion of the degradable polymer with HA. The amphiphilic triblock copolymer PLA–PEG–PLA (PELA) improved the stability of HA–PELA suspension at 25 wt.% HA content, which was readily electrospun into HA–PELA composite scaffolds with uniform fiber dimensions. HA–PELA was highly extensible (failure strain >200% vs. <40% for HA–PLA), superhydrophilic (∼0° water contact angle vs. >100° for HA–PLA), and exhibited an 8-fold storage modulus increase (unlike deterioration for HA–PLA) upon hydration, owing to the favorable interaction between HA and PEG. HA–PELA also better promoted osteochondral lineage commitment of bone marrow stromal cells in unstimulated culture and supported far more potent osteogenic gene expression upon induction than HA–PLA. We demonstrate that the chemical incorporation of PEG is an effective strategy to improve the performance of degradable polymer/HA composites for bone tissue engineering applications.
Co-reporter:Pingsheng Liu, Jie Song
Biomaterials 2013 34(10) pp: 2442-2454
Publication Date(Web):
DOI:10.1016/j.biomaterials.2012.12.029
Co-reporter:Pingsheng Liu, Jonathan Smits, David C. Ayers, Jie Song
Acta Biomaterialia 2011 Volume 7(Issue 9) pp:3488-3495
Publication Date(Web):September 2011
DOI:10.1016/j.actbio.2011.05.025
Abstract
Titanium alloys are prevalently used as orthopedic prosthetics. Inadequate bone–implant interactions can lead to premature prosthetic loosening and implant failure. Local delivery of osteogenic therapeutics promoting osteointegration of the implant is an attractive strategy to address this clinical challenge. Given the affinity of calcium apatites for bone matrix proteins we hypothesize that titanium alloys surface mineralized with calcium apatites should be explored for the retention and local delivery of osteogenic recombinant human bone morphogenetic protein-2 (rhBMP-2). Using a heterogeneous surface nucleation and growth process driven by the gradual pH elevation of an acidic solution of hydroxyapatite via thermal decomposition of urea, Ti6Al4V substrates were surface mineralized with calcium apatite domains exhibiting good affinity for the substrate. The microstructures, size and surface coverage of the mineral domains as a function of the in vitro mineralization conditions were examined by light and scanning electron microscopy and the surface calcium ion content quantified. An optimal mineralization condition was identified to rapidly (<10 h) achieve surface mineral coverage far superior to those accomplished by week long incubation in simulated body fluids. In vitro retention–release profiles of rhBMP-2 from the mineralized and unmineralized Ti6Al4V, determined by an enzyme-linked immunosorbent assay, supported a higher degree of retention of rhBMP-2 on the mineralized substrate. The rhBMP-2 retained on the mineralized substrate after 24 h incubation in phosphate-buffered saline remained bioactive, as indicated by its ability to induce osteogenic transdifferentiation of C2C12 myoblasts attached to the substrate. This mineralization technique could also be applied to the surface mineralization of calcium apatites on dense tantalum and titanium and porous titanium substrates.
Co-reporter:Tera M. Filion, Artem Kutikov, Jie Song
Bioorganic & Medicinal Chemistry Letters 2011 Volume 21(Issue 17) pp:5067-5070
Publication Date(Web):1 September 2011
DOI:10.1016/j.bmcl.2011.04.032
Cellulose and sulfated cellulose fibrous meshes exhibiting robust structural and mechanical integrity in water were fabricated using a combination of electrospinning, thermal–mechanical annealing and chemical modifications. The sulfated fibrous mesh exhibited higher retention capacity for human recombinant bone morphogenetic protein-2 than the cellulose mesh, and the retained proteins remained biologically active for at least 7 days. The sulfated fibrous mesh also more readily supported the attachment and osteogenic differentiation of rat bone marrow stromal cells in the absence of osteogenic growth factors. These properties combined make the sulfated cellulose fibrous mesh a promising bone tissue engineering scaffold.
Co-reporter:Jianwen Xu, Fioleda Prifti, and Jie Song
Macromolecules 2011 Volume 44(Issue 8) pp:2660-2667
Publication Date(Web):March 23, 2011
DOI:10.1021/ma200021m
Despite the increasing demands for functional degradable biomaterials, strategies for generating materials with modular compositions and well-defined functionalities from common building blocks are still lacking. Here we report an azido-functionalized cyclic carbonate monomer, AzDXO, that exhibited controlled/“living” ring-opening polymerization kinetics under the catalysis of 1,8-diazabicyclo[5.4.0]undec-7-ene. Homopolymerization of AzDXO and copolymerization of AzDXO with lactide resulted in polycarbonate and poly(ester−carbonates) with well-defined composition and narrow polydispersity. Further side-chain functionalizations of these polymers were accomplished under facile conditions via copper-catalyzed or copper-free strain-promoted azido−alkyne cyclcoaddition. This versatile monomer building block, obtainable in two steps without tedious purifications, provides a practical solution to the preparation of well-defined functional polycarbonates and poly(ester−carbonates).
Co-reporter:Tera M. Filion, Jianwen Xu, Manju L. Prasad, Jie Song
Biomaterials 2011 32(4) pp: 985-991
Publication Date(Web):
DOI:10.1016/j.biomaterials.2010.10.012
Co-reporter:Dr. Jianwen Xu;Tera M. Filion;Fioleda Prifti ; Jie Song
Chemistry – An Asian Journal 2011 Volume 6( Issue 10) pp:2730-2737
Publication Date(Web):
DOI:10.1002/asia.201100411
Abstract
Strategies to encapsulate cells in cytocompatible three-dimensional hydrogels with tunable mechanical properties and degradability without harmful gelling conditions are highly desired for regenerative medicine applications. Here we reported a method for preparing poly(ethylene glycol)-co-polycarbonate hydrogels through copper-free, strain-promoted azide–alkyne cycloaddition (SPAAC) click chemistry. Hydrogels with varying mechanical properties were formed by “clicking” azido-functionalized poly(ethylene glycol)-co-polycarbonate macromers with dibenzocyclooctyne-functionalized poly(ethylene glycol) under physiological conditions within minutes. Bone marrow stromal cells encapsulated in these gels exhibited higher cellular viability than those encapsulated in photo-cross-linked poly(ethylene glycol) dimethacrylate. The precise control over the macromer compositions, cytocompatible SPAAC cross-linking, and the degradability of the polycarbonate segments make these hydrogels promising candidates for scaffold and stem cell assisted tissue repair and regeneration.
Co-reporter:Jianwen Xu
PNAS 2010 Volume 107 (Issue 17 ) pp:7652-7657
Publication Date(Web):2010-04-27
DOI:10.1073/pnas.0912481107
Smart materials that can respond to external stimuli are of widespread interest in biomedical science. Thermal-responsive
shape memory polymers, a class of intelligent materials that can be fixed at a temporary shape below their transition temperature
(Ttrans) and thermally triggered to resume their original shapes on demand, hold great potential as minimally invasive self-fitting
tissue scaffolds or implants. The intrinsic mechanism for shape memory behavior of polymers is the freezing and activation
of the long-range motion of polymer chain segments below and above Ttrans, respectively. Both Ttrans and the extent of polymer chain participation in effective elastic deformation and recovery are determined by the network
composition and structure, which are also defining factors for their mechanical properties, degradability, and bioactivities.
Such complexity has made it extremely challenging to achieve the ideal combination of a Ttrans slightly above physiological temperature, rapid and complete recovery, and suitable mechanical and biological properties
for clinical applications. Here we report a shape memory polymer network constructed from a polyhedral oligomeric silsesquioxane
nanoparticle core functionalized with eight polyester arms. The cross-linked networks comprising this macromer possessed a
gigapascal-storage modulus at body temperature and a Ttrans between 42 and 48 °C. The materials could stably hold their temporary shapes for > 1 year at room temperature and achieve
full shape recovery ≤ 51 °C in a matter of seconds. Their versatile structures allowed for tunable biodegradability and biofunctionalizability.
These materials have tremendous promise for tissue engineering applications.
Co-reporter:Jie Song;Jianwen Xu;Tera Filion;Eduardo Saiz;Antoni P. Tomsia;Jane B. Lian;Gary S. Stein;David C. Ayers;Carolyn R. Bertozzi
Journal of Biomedical Materials Research Part A 2009 Volume 89A( Issue 4) pp:1098-1107
Publication Date(Web):
DOI:10.1002/jbm.a.32110
Abstract
The design of synthetic bone grafts that mimic the structure and composition of bone and possess good surgical handling characteristics remains a major challenge. We report the development of poly(2-hydroxyethyl methacrylate) (pHEMA)-hydroxyapatite (HA) composites termed “FlexBone” that possess osteoconductive mineral content approximating that of human bone yet exhibit elastomeric properties enabling the press-fitting into a defect site. The approach involves crosslinking pHEMA hydrogel in the presence of HA using viscous ethylene glycol as a solvent. The composites exhibit excellent structural integration between the apatite mineral component and the hydroxylated hydrogel matrix. The stiffness of the composite and the ability to withstand compressive stress correlate with the microstructure and content of the mineral component. The incorporation of porous aggregates of HA nanocrystals rather than compact micrometer-sized calcined HA effectively improved the resistance of the composite to crack propagation under compression. Freeze-dried FlexBone containing 50 wt % porous HA nanocrystals could withstand hundreds-of-megapascals compressive stress and >80% compressive strain without exhibiting brittle fractures. Upon equilibration with water, FlexBone retained good structural integration and withstood repetitive moderate (megapascals) compressive stress at body temperature. When subcutaneously implanted in rats, FlexBone supported osteoblastic differentiation of the bone marrow stromal cells pre-seeded on FlexBone. Taken together, the combination of high osteoconductive mineral content, excellent organic-inorganic structural integration, elasticity, and the ability to support osteoblastic differentiation in vivo makes FlexBone a promising candidate for orthopedic applications. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
Co-reporter:Pingsheng Liu, Erin Emmons and Jie Song
Journal of Materials Chemistry A 2014 - vol. 2(Issue 43) pp:NaN7533-7533
Publication Date(Web):2014/10/01
DOI:10.1039/C4TB01046A
Cationic and anionic residues of the extracellular matrices (ECM) of bone play synergistic roles in recruiting precursor ions and templating the nucleation, growth and crystalline transformations of calcium apatite in natural biomineralization. We previously reported that zwitterionic sulfobetaine ligands can template extensive 3-dimensional (3-D) hydroxyapatite (HA)-mineralization of photo-crosslinked polymethacrylate hydrogels. Here, we compared the potency of two other major zwitterionic ligands, phosphobetaine and carboxybetaine, with that of the sulfobetaine in mediating 3-D mineralization using a crosslinked polymethacrylate hydrogel platform. We confirmed that all three zwitterionic hydrogels were able to effectively template 3-D mineralization, supporting the general ability of zwitterions to mediate templated mineralization. Among them, however, sulfobetaine and phosphobetaine hydrogels templated denser 3-D mineralization than the carboxybetaine hydrogel, likely due to their higher free water fractions and better maintenance of zwitterionic nature throughout the pH-changes during the in vitro mineralization process. We further demonstrated that the extensively mineralized zwitterionic hydrogels could be exploited for efficient retention (e.g. 99% retention after 24 h incubation in PBS) of osteogenic growth factor recombinant bone morphogenetic protein-2 (rhBMP-2) and subsequent sustained local release with retained bioactivity. Combined with the excellent cytocompatibility of all three zwitterionic hydrogels and the significantly improved cell adhesive properties of their mineralized matrices, these materials could find promising applications in bone tissue engineering.
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