Synthesis and characterization of cinnamated Type I collagen and its related mechanical properties after photomediated crosslinking were investigated in detail. Using an EDC/NHS conjugation method, collagen was chemically modified to incorporate a photosensitive cinnamate moiety. The cinnamated collagen was fully characterized by 1H NMR, UV-vis, and circular dichroism (CD) spectroscopy, as well as by rheological and mechanical analyses. Cinnamated collagens with varying degrees of derivatization retained collagen triple helical structure. The rheological spectra of collagen solutions demonstrate that the storage modulus decreases with increasing cinnamate content, owing to a decrease in physical crosslinking. The kinetics of the crosslinking process in both hydrated gels and dry films were monitored by UV-vis spectroscopy and confirmed that crosslinking was complete within 60 min of irradiation. The uniaxial stress-strain behavior of crosslinked collagen films, including Young's modulus and ultimate tensile strength, was comparable to values reported for glutaraldehyde-crosslinked monomeric collagen films. These data demonstrate that derivatization of collagen with photosensitive cinnamate moieties provides a facile route for solid-state crosslinking, thereby improving the mechanical properties of collagen and enhancing the potential applicability of collagen-based materials in tissue engineering and drug delivery.

Both well defined star-shaped poly(3-caprolactone) having four arms (4sPCL) and six arms (6sPCL) and linear PCL having one arm (LPCL) and two arms (2LPCL) were synthesized and then used for the investigation of physical properties, isothermal and nonisothermal crystallization kinetics, and spherulitic growth. The maximal melting point, the cold crystallization temperature, and the degree of crystallinity of these PCL polymers decrease with the increasing number of polymer arms, and they have similar crystalline structure. The isothermal crystallization rate constant (K) of these PCL polymers is in the order of K2LPCLOKLPCLOK4sPCLOK6sPCL. Notably, the K of linear PCL decreases with the increasing molecular weight of polymer while that of star-shaped PCL inversely increases. The variation trend of K over the number of polymer arms or the molecular weight of polymer is consistent with the analyses of both nonisothermal crystallization kinetics and the spherulitic growth rate. These results indicate that both the number of polymer arms and the molecular weight of polymer mainly controlled the isothermal and nonisothermal crystallization rate constants, the spherulitic growth rate, and the spherulitic morphology of these PCL polymers.

Glycopolymer-polypeptide triblock copolymers of the structure, poly(L-alanine)-b-poly(2-cryloyloxyethyllactoside)-b-poly(L-alanine)(AGA), have been synthesized by sequential atom transfer radical polymerization (ATRP) and ring-opening polymerization (ROP). Controlled free radical polymerization of 2-O-acryloyloxyethoxyl-(2,3,4,6-tetra-O-acetyl-â-D-galactopyranosyl)-(1-4)-2,3,6-tri-O-acetyl-â-D-glucopyranoside (AEL) by ATRP with a dibromoxylene (DBX)/CuBr/bipy complex system was used to generate a central glycopolymer block. Telechelic glycopolymers with diamino end groups were obtained by end group transformation and subsequently used as macroinitiators for ROP of L-alanine N-carboxyanhydride monomers (Ala-NCA). Gel permeation chromatography (GPC) and nuclear magnetic resonance (NMR) spectroscopy analysis demonstrated that copolymer molecular weight and composition were controlled by both the molar ratios of the Ala-NCA monomer to macroinitiator and monomer conversion and exhibited a narrow distribution (Mw/Mn) 1.06-1.26). FT-IR spectroscopy of triblock copolymers revealed that the ratio of R-helix/â-sheet increased with poly(L-alanine) block length. Of note, transmission electron microscopy (TEM) demonstrated that selected amphiphilic glycopolymer-polypeptide triblock copolymers self-assemble in aqueous solution to form nearly spherical aggregates of several hundreds nanometer in diameter. Significantly, the sequential application of ATRP and ROP techniques provides an effective method for producing triblock copolymers with a central glycopolymer block and flanking polypeptide blocks of defined architecture, controlled molecular weight, and low polydispersity.

A series of derivatized arylamine initiators were used to generate chain-end functionalized glycopolymers by cyanoxyl-mediated free-radical polymerization. Significant features of this strategy include the capacity to produce polymers of low polydispersity (PDI < 1.5) under aqueous conditions using unprotected monomers bearing a wide range of functional groups. In addition, the presence of a phenyl ring simplifies calculation of polymer saccharide content and molar mass by 1H NMR. It is particularly noteworthy, however, that derivatized arylamine initiators in conjunction with the presence of a terminal cyanate group provide a convenient approach for synthesizing polymers with a variety of distinct functional groups at R and ö chain ends. In the process, the capacity to label glycopolymers or otherwise conjugate them to proteins or other molecules is greatly enhanced.

A new class of dendron-like polypeptide/linear poly(ε-caprolactone) block copolymers with asymmetrical topology (i.e., dendron-like poly(γ-benzyl-L-glutamate)/linear PCL copolymers having 2m PBLG branches, m) 0, 1, 2, and 3; denoted as PCL-Dm-PBLG) was for the first time synthesized via the combination of controlled ringopening polymerization (ROP) of ε-caprolactone, click chemistry, and the ROP of γ-benzyl-L-glutamate N-carboxyanhydride (BLG-NCA). The linear hydroxyl-terminated PCL (PCL-OH) was synthesized by controlled ROP of ε-caprolactone and then transformed into clickable azide-terminated PCL (PCL-N3). The PCL-N3 precursor was further click conjugated with propargyl focal point PAMAM-typed dendrons (i.e., Dm having 2m primary amine groups) to generate PCL-dendrons (PCL-Dm) using CuBr/PMDETA as catalyst in dimethylformamide solution at 35℃. Finally, PCL-Dm was used as macroinitiator for the ROP of BLG-NCA monomer to produce the targeted PCL-Dm-PBLG block copolymers. Their molecular structures and physical properties were characterized in detail by FT-IR, NMR, matrix assisted laser desorption ionization time-of-flight mass spectrometry, gel permeation chromatography, differential scanning calorimetry, and wide-angle X-ray diffraction. To the best of our knowledge, this is the first report that describes the synthesis of dendron-like polypeptide/linear PCL block copolymers with asymmetrical topology via the combination of ROP and click chemistry. Consequently, this provides a versatile strategy for the synthesis of biodegradable and biomimetic dendron-like polypeptide-based biohybrids.

Dendron-like/linear/dendron-like poly(ε-caprolactone)-b-poly(ethylene glycol)-b-poly(ε-caprolactone) triblock copolymers with controlled molecular weights (Mn) 9550-30 460) and low polydispersities were synthesized by a click conjugation between dendron-like poly(ε-caprolactone) and bifunctional azide-terminated poly(ethylene glycol)(copolymer yield) 56-89%). Their molecular structures and physicochemical and self-assembly properties were thoroughly characterized by means of FT-IR, 1H NMR, multiangle laser light scattering coupled with gel permeation chromatography, differential scanning calorimetry, wide-angle X-ray diffraction, dynamic light scattering, and transmission electron microscopy. Using a nanoprecipitation method, these triblock copolymers self-assembled into spherical flower-like micelles with an average diameter of less than 50 nm in aqueous solution, and both the copolymer composition and the dendritic topology of the hydrophobic core had no apparent influence on the morphology of nanoparticles. The critical aggregation concentrations of these copolymers ranged from 0.034 to 0.048mg/mL. However, the anticancer doxorubicin-loaded nanoparticles showed worm-like micelles similar to blank nanoparticles fabricated by a dialysis method, and the loaded doxorubicin drug hardly affected the final morphology of nanoparticles. Moreover, the doxorubicin-loaded nanoparticles fabricated from the dumbbell copolymer showed a higher drug loading efficiency of 18% and a longer drug-release time of 45 days than the linear counterpart. Consequently, this provides a versatile strategy not only for the synthesis of biodegradable and biocompatible dendron-like/linear/dendron-like triblock copolymers with dumbbell topology by using click chemistry but also for fabricating worm-like doxorubicin-loaded nanoparticles for anticancer drug release.

Star poly(amido amine)-b-poly(ε-caprolactone)-b-poly(D-gluconamidoethyl methacrylate)(PAMAM- PCL-PGAMA) block copolymers with a dendrimer core were synthesized from the ring-opening polymerization of ε-caprolactone using a hydroxyl-terminated dendrimer poly(amido amine) initiator followed by the direct atom transfer radical polymerization of unprotected glycomonomer. The selfassembly and the biomolecular binding of PAMAM-PCL-PGAMA with Concanavalin A (Con A) were investigated by NMR, UV-vis, dynamic light scattering, and transmission electron microscopy, respectively. Multivalent sugar-installed vesicles and large compound aggregates were self-assembled from these dendritic copolymers in aqueous solution, demonstrating thermodynamically more stable than those self-assembled from linear counterpart. Moreover, these copolymers presented specific biomolecular binding with Con A lectin compared with bovine serum albumin, while both the lower mobility and the higher spatial hindrance within dendritic copolymers, to some extent, limited the clustering between sugar and Con A. Furthermore, these star copolymer nanoparticles showed a higher drugloading efficiency and less burst release compared with linear counterpart. This work provides a method not only for the synthesis of star PCL/glycopolymer biohybrid with a dendrimer core but also for the fabrication of sugar-installed nanoparticles with tunable clustering ability, good druloading efficiency, and controlled drug-release profile useful for targeted drug delivery system.

Dendron-like poly(γ-benzyl-L-glutamate)/linear poly(ethylene oxide) block copolymers with both asymmetrical and symmetrical topologies (i.e., ABn type Dm-PBLG-b-PEO and BnABn type Dm-PBLG-b-PEOb- Dm-PBLG; n) 2m, m) 0, 1, 2, and 3; Dm are the propargyl focal point poly(amido amine) type dendrons having 2m terminal primary amine groups) were synthesized via the combination of ring-opening polymerization (ROP) of γ-benzyl-L-glutamate N-carboxyanhydride (BLG-NCA) and click chemistry according to the "armfirst" and "core-first" strategies. In the arm-first method, the propargyl focal point dendrons Dm having 2m terminal primary amine groups were first used for initiating the ROP of BLG-NCA, generating "clickable" dendron-like Dm-PBLG homopolymers having 2m branches, which were then click conjugated with azide-terminated PEO (PEO-N3) to produce asymmetrical Dm-PBLG-b-PEO. In the core-first strategy, the propargyl focal point Dm was first click conjugated with PEO-N3 to generate primary amine-terminated PEO dendrons, which were further used as the macroinitiators for the ROP of BLG-NCA to produce the targeted copolymers with both asymmetrical and symmetrical topologies. Their molecular structures and physical properties were characterized in detail by FT-IR, NMR, gel permeation chromatography, differential scanning calorimetry, and wide-angle X-ray diffraction. Both spherical and wormlike micelles self-assembled from these Dm-PBLG-b-PEO copolymers in aqueous solution, and mainly the PBLG composition controlled the morphology of nanostructures.

Two types of three-arm or four-arm star-shaped hydroxy-terminated poly(-caprolactone) (PCL) were successfully synthesized via the ring-opening polymerization of caprolactone (CL) with multifunctional initiator, such as trimethylolpropane (TMP) or pentaerythritol (PTOL), and stannous octoate (SnOct2) catalyst in bulk at 110℃. The number-average molecular weight of PCL is proportional to the molar ratio of monomer to initiator. 1H NMR spectroscopy of the resulting PCL indicates that it contains a primary hydroxy end group in each arm. The star-shaped PCL with hydroxy end groups can be used as a macroinitiator for block copolymerization with DL-3-methylglycolide (MG) using SnOctcatalyst in bulk at 115℃. 1H NMR spectra of the resulting block copolymers show that the molecular weights and the unit compositions of the block copolymers were controlled by the molar ratios of MG monomer to hydroxy groups of PCL and MG to CL in feed, respectively. Moreover, the molecular weights of the resulting block copolymers linearly increased with the increase of the molar ratios of MG to CL in feed. The molecular weight distributions of the block copolymers were rather narrow (Mw/Mn) 1.09-1.26). 13C NMR spectra of the resulting block copolymers clearly show their diblock structures, that is, PCL as the first block and poly(DL-lactic acid-alt-glycolic acid) (DL-PLGA50) with alternating structures of lactyl and glycolyl units as the second block. Therefore, two types of three-arm or four-arm star-shaped diblock copolyesters comprising the first block PCL and the second block DL-PLGA50 were successfully synthesized via the sequential ring-opening polymerization of CL with multifunctional initiator and Snoctcatalyst and then followed by copolymerization with MG.

A new class of linear-dendron-like poly(ε-caprolactone)-b-poly(ethylene oxide) (PCL-b-PEO) copolymers with unsymmetrical topology was synthesized via controlled ring-opening polymerization (ROP) of ε-caprolactone (CL) followed by a click conjugation with azide-terminated PEO (PEO-N3). The dendron-like PCL terminated with a clickable alkyne group (Dm-PCL, m) 0, 1, 2, and 3) was for the first time synthesized from the ROP of CL monomer using a propargyl focal point dendrons Dm with primary amine groups as the initiators and stannous octoate as catalyst in bulk at 130℃. Then, the linear-dendron-like Dm-PCL-b-PEO copolymers were obtained by the click conjugation of Dm-PCL with PEO-N3 using PMDETA/CuBr as catalyst in DMF solution at 35℃. Their molecular structures and physical properties were in detail characterized by FT-IR, NMR, MALLS-GPC, DSC, and WAXD. Both DLS and TEM analyses demonstrated that the biodegradable micelles and vesicles with different sizes (less than 100 nm) self-assembled from these Dm-PCL-b-PEO copolymers in aqueous solution, and both the PEO composition and the linear-dendron-like architecture of copolymers controlled the morphology and the average size of nanoparticles. To the best of our knowledge, this is the first report that describes the synthesis of linear-dendron-like PCL-b-PEO block copolymers via the combination of ROP and click chemistry. Consequently, this provides a versatile strategy not only for the synthesis of biodegradable and amphiphilic block copolymers with linear-dendron-like architecture but also for fabricating biocompatible nanoparticles with suitable size for controlled drug release.