Kinetic degradation and biocompatibility evaluation of polycaprolactone-based biologics delivery matrices for regenerative engineering of the rotator cuff.

Whereas synthetic biodegradable polymers have been successfully applied for the delivery of biologics in other tissues, the anatomical complexity, poor blood supply, and reduced clearance of degradation byproducts in the rotator cuff create unique design challenges for implantable biomaterials. Here, we investigated lower molecular weight poly-lactic acid co-epsilon-caprolactone (PLA-CL) formulations with varying molecular weight and film casting concentrations as potential matrices for the therapeutic delivery of biologics in the rotator cuff. Matrices were fabricated with target footprint dimensions to facilitate controlled and protected release of model biologic (Bovine Serum Albumin), and anatomically-unhindered implantation under the acromion in a rodent model of acute rotator cuff repair. The matrix obtained from the highest polymeric-film casting concentration showed a controlled release of model biologics payload. The tested matrices rapidly degraded during the initial 4 weeks due to preferential hydrolysis of the lactide-rich regions within the polymer, and subsequently maintained a stable molecular weight due to the emergence of highly-crystalline caprolactone-rich regions. pH evaluation in the interior of the matrix showed minimal change signifying lesser accumulation of acidic degradation byproducts than seen in other bulk-degrading polymers, and maintenance of conformational stability of the model biologic payload. The context-dependent biocompatibility evaluation in a rodent model of acute rotator cuff repair showed matrix remodeling without eliciting excessive inflammatory reaction and is anticipated to completely degrade within 6 months. The engineered PLA-CL matrices offer unique advantages in controlled and protected biologic delivery, non-toxic biodegradation, and biocompatibility overcoming several limitations of commonly-used biodegradable polyesters.

First-principles studies of spontaneous polarization in mixed poly(vinylidene fluoride)/2,3,3,3-tetrafluoropropene polymer crystals.

Spontaneous polarization P of mixed polymer crystals based on ß poly(vinylidene fluoride) (PVDF, -CH2-CF2-) and 2,3,3,3-tetrafluoropropene (TFP, -CH2-CF(CF3)-) was evaluated for ß-PVDF/iso-PTFP, ß-PVDF/P(VDF-alt-iso-TFP) and ß-PVDF/syndio-PTFP. A plane-wave-based density-functional theory (DFT) approach, combined with the Modern Theory of Polarization formalism utilizing maximally-localized Wannier functions for calculating P, indicates that all systems exhibit similarly high or even slightly larger polarization than that of perfectly crystalline ß-PVDF (0.18 C m-2). These properties stem from the substantial dipole moment of the TFP unit, which is estimated to be ∼2.3 D in an isolated chain, but is enhanced to ∼2.8 D in the crystal.

Photomediated Controlled Radical Polymerization and Block Copolymerization of Vinylidene Fluoride.

This review summarizes recent research on novel photochemical methods for the initiation and control of the polymerization of main chain fluorinated monomers as exemplified by vinylidene fluoride (VDF) and for the synthesis of their block copolymers. Such reactions can be carried out at ambient temperature in glass tubes using visible light. Novel, original protocols include the use of hypervalent iodide carboxylates alone or in conjunction with molecular iodine, as well as the use of photoactive transition metal carbonyls in the presence of alkyl, fluoroalkyl, and perfluoroalkyl halides. An in-depth study of the reaction parameters highlights the use of dimethyl carbonate as a preferred polymerization solvent and outlines the structure-property relationship for hypervalent iodide carboxylates and halide initiators in both the free radical and iodine degenerative transfer controlled radical polymerization (IDT-CRP) of VDF. Finally, the rational selection of metal carbonyls that are successful not only as IDT mediators but, more importantly, in the quantitative activation of both PVDF-CH2-CF2-I and PVDF-CF2-CH2-I chain ends toward the synthesis of well-defined PVDF block copolymers is presented.

Visible-light hypervalent iodide carboxylate photo(trifluoro)methylations and controlled radical polymerization of fluorinated alkenes.

IFAB-ulous trifluoromethylation: (CX3COO)2I(III) h (X=F, H) and (CH3COO)3I(V)(C6H4COO) are introduced as CX3·/CX3I precursors for metal-free, visible-light, radical (trifluoro)(iodo)methylations of alkenes, illustrated by their use as photoinitiators for the controlled radical polymerization of vinylidene fluoride with external (I(CF2)6I) and in situ generated (CF3I) iodine chain transfer agents, and for block copolymer synthesis.

Stabilization of graphene sheets by a structured benzene/hexafluorobenzene mixed solvent.

Applications requiring pristine graphene derived from graphite demand a solution stabilization method that utilizes an easily removable media. Using a combination of molecular dynamics simulations and experimental techniques, we investigate the solublization/suspension of pristine graphene sheets by an equimolar mixture of benzene and hexafluorobenzene (C(6)H(6)/C(6)F(6)) that is known to form an ordered structure solidifying at 23.7 °C. Our simulations show that the graphene surface templates the self-assembly of the mixture into periodic layers extending up to 30 Å from both sides of the graphene sheet. The solvent structuring is driven by quadrupolar interactions and consists of stacks of alternating C(6)H(6)/C(6)F(6) molecules rising from the surface of the graphene. These stacks result in density oscillations with a period of about 3.4 Å. The high affinity of the 1:1 C(6)H(6)/C(6)F(6) mixture with graphene is consistent with observed hysteresis in Wilhelmy plate measurements using highly ordered pyrolytic graphite (HOPG). AFM, SEM, and TEM techniques verify the state of the suspended material after sonication. As an example of the utility of this mixture, graphene suspensions are freeze-dried at room temperature to produce a sponge-like morphology that reflects the structure of the graphene sheets in solution.

Mild-temperature Mn2(CO)10-photomediated controlled radical polymerization of vinylidene fluoride and synthesis of well-defined poly(vinylidene fluoride) block copolymers.

By contrast to typical high-temperature (100-250 °C) telo-/polymerizations of gaseous fluorinated monomers, carried out in high-pressure metal reactors, the visible light, Mn(2)(CO)(10)-photomediated initiation of vinylidene fluoride (bp = -83 °C) polymerization occurs readily from a variety of alkyl, semifluorinated, and perfluorinated halides at 40 °C, in low-pressure glass tubes and in a variety of solvents, including water and alkyl carbonates. Perfluorinated alkyl iodide initiators also induce a controlled radical polymerization via iodine degenerative transfer (IDT). While IDT proceeds with accumulation of the less reactive P(m)-CF(2)-CH(2)-I vs the P(n)-CH(2)-CF(2)-I chain ends, Mn(2)(CO)(10) enables their subsequent quantitative activation toward the synthesis of well-defined poly(vinylidene fluoride) block copolymers with a variety of other monomers.

Imaging and thermal studies of wheat gluten/poly(vinyl alcohol) and wheat gluten/thiolated poly(vinyl alcohol) blends.

The morphology of wheat protein (WG) blends with polyvinyl alcohol (PVA) and respectively with thiolated polyvinyl alcohol (TPVA) was investigated by atomic force (AFM) and transmission electron microscopy (TEM) as well as by modulated dynamic scanning calorimetry (MDSC). Thiolated additives based on PVA and other substrates were previously presented as effective means of improving the strength and toughness of compression molded native WG bars via disulfide-sulfhydryl exchange reactions. Consistent with our earlier results, AFM and TEM imaging clearly indicate that the addition of just a few mole percent of thiol to PVA was sufficient to dramatically change its compatibility with wheat protein. Thus, TPVA is much more compatible with WG and phase separates into much smaller domains than in the case of PVA, although there are still two phases in the blend: one WG-rich phase and another TPVA-rich phase. The WG/TPVA blend has phase domains ranging in size from 0.01 to 0.1 microm, which are roughly 10 times smaller than those of the WG/PVA blend. MDSC further illustrates the compatibilization of the protein with TPVA via the dependence of the transition temperatures on composition.

Wheat gluten-thiolated poly(vinyl alcohol) blends with improved mechanical properties.

A multifunctional macromolecular thiol (TPVA) obtained by esterification of poly(vinyl alcohol) (PVA) with 3-mercaptopropionic acid was characterized by a combination of NMR, IR, transmission electron microscopy (TEM), and differential scanning calorimetry (DSC), and was used as a wheat gluten (WG) reactive modifier. The effect of TPVA molecular weight (M(w) = 2000, 9500, 50 000, and 205 000) and blend composition (5, 20, and 40% w/w TPVA/WG) on the mechanical properties of compression-molded bars indicates that TPVA/WG blends increase the fracture strength by up to 76%, the elongation by 80%, and the modulus by 25% above WG. In contrast, typical WG additives such as glycerol and sorbitol improve flexibility but decrease modulus and strength. Preliminary investigations of suspension rheology, water uptake, molecular weight distribution and electron microscopy of TPVA/WG and PVA/WG blends illustrate the different protein interactions with PVA and TPVA. Further work is underway to determine whether TPVA and WG form protein conjugates or microphase-separated morphologies.

TiCp2Cl-catalyzed living radical polymerization of styrene initiated by oxirane radical ring opening.

Epoxides and paramagnetic early transition metal complexes are introduced as two new classes of initiators and catalysts, respectively, for living radical polymerizations. Thus, Ti(III)Cp2Cl synthesized in situ from the reduction of TiCp2Cl2 with Zn catalyzes the radical ring opening of oxiranes to initiate the radical polymerization of styrene. A linear dependence of molecular weight on conversion, low polydispersity, and reinitiation of the polymerization in the presence of fresh monomer indicates that the polymerization is living and that it most likely occurs by the reversible endcapping of the macroradical with Ti(III). Moreover, epoxides provide convenient access to alcohol chain ends, suitable for further transformations.

Aqueous room temperature metal-catalyzed living radical polymerization of vinyl chloride.

This paper describes the room-temperature living radical polymerization (LRP) of vinyl chloride in H2O/THF in the presence of Cu0 or CuI salts as catalysts, tren or PEI as ligands, and iodoform as initiator. The disproportionation reaction 2CuI + L --> Cu0 + CuII(L) is the crucial step, as it continuously provides the active species for both the initiation (Cu0) and the reversible termination step (CuII). Mn was found to increase linearly with conversion and is in good agreement with Mth, with the Mw/Mn being approximately 1.5.