Semi-synthetic degradable notochordal cell-derived matrix hydrogel for use in degenerated intervertebral discs: Initial in vitro characterization

Low back pain is the leading cause of disability worldwide, but current therapeutic interventions are palliative or surgical in nature. Loss of notochordal cells (NCs) and degradation of the healthy matrix in the nucleus pulposus (NP), the central tissue of intervertebral discs (IVDs), has been associated with onset of degenerative disc changes. Recently, we established a protocol for decellularization of notochordal cell derived matrix (NCM) and found that it can provide regenerative cues to nucleus pulposus cells of the IVD. Here, we combined the biologically regenerative properties of decellularized NCM with the mechanical tunability of a poly(ethylene glycol) hydrogel to additionally address biomechanics in the degenerate IVD. We further introduced a hydrolysable PEG-diurethane crosslinker for slow degradation of the gels in vivo. The resulting hydrogels were tunable over a broad range of stiffness's (0.2 to 4.5 kPa), matching that of NC-rich and -poor NP tissues, respectively. Gels formed within 30 min, giving ample time for handling, and remained shear-thinning post-polymerization. Gels also slowly released dNCM over 28 days as measured by GAG effusion. Viability of encapsulated bone marrow stromal cells after extrusion through a needle remained high. Although encapsulated NCs stayed viable over two weeks, their metabolic activity decreased, and their phenotype was lost in physiological medium conditions in vitro. Overall, the obtained gels hold promise for application in degenerated IVDs but require further tuning for combined use with NCs

Discrete oligodimethylsiloxane-oligomethylene di- and triblock co-oligomers: synthesis, self-assembly and molecular organisation

A new class of discrete-length block co-oligomers comprising oligodimethylsiloxane (oDMS) and oligomethylene (oM) is presented. For this, oM blocks containing up to 69 backbone carbons are synthesised via an iterative, Wittig reaction-based strategy. Ligation with oDMS hydrides permits the formation of a library of block co-oligomers (BCOs) in which the block configuration, MW, and composition can be tuned. Differential scanning calorimetry and small-angle X-ray scattering show that all BCOs exhibit microphase separation into well-ordered lamellar morphologies, driven by the crystallisation of the oM blocks. Pre-melting order-order transitions are present for a number of BCOs, resulting in an alteration of the oM crystal packing as well as in changes of the overall microphase-segregated structure. As a result of the discrete nature of the BCO chains, we propose models that describe the molecular organisation within the microphase-segregated structures by evaluating the changes in the lamellar thickness upon varying the BCO architecture

Discrete oligodimethylsiloxane-oligomethylene di- and triblock co-oligomers:synthesis, self-assembly and molecular organisation

\u3cp\u3eA new class of discrete-length block co-oligomers comprising oligodimethylsiloxane (oDMS) and oligomethylene (oM) is presented. For this, oM blocks containing up to 69 backbone carbons are synthesised via an iterative, Wittig reaction-based strategy. Ligation with oDMS hydrides permits the formation of a library of block co-oligomers (BCOs) in which the block configuration, MW, and composition can be tuned. Differential scanning calorimetry and small-angle X-ray scattering show that all BCOs exhibit microphase separation into well-ordered lamellar morphologies, driven by the crystallisation of the oM blocks. Pre-melting order-order transitions are present for a number of BCOs, resulting in an alteration of the oM crystal packing as well as in changes of the overall microphase-segregated structure. As a result of the discrete nature of the BCO chains, we propose models that describe the molecular organisation within the microphase-segregated structures by evaluating the changes in the lamellar thickness upon varying the BCO architecture.\u3c/p\u3

Dispersity under scrutiny:phase behavior differences between disperse and discrete low molecular weight block co-oligomers

\u3cp\u3eAn experimental study is presented in which we compare the bulk phase behavior of discrete and (partially) disperse diblock co-oligomers (BCOs) with high χ-low N. To this end, oligomers of dimethylsiloxane (oDMS) and lactic acid (oLA) were synthesized, each having either a discrete number of repeat units or a variable block length. Ligation of the blocks resulted in oDMS-oLA BCOs with dispersities ranging from <1.00001 to 1.09, as revealed by mass spectroscopy and size exclusion chromatography. The phase behavior of all BCOs was investigated by differential scanning calorimetry and small-angle X-ray scattering. Compared to the well-organized lamellae formed by discrete oDMS-oLA, we observe that an increase in the dispersity of these BCOs results in (1) an increase of the stability of the microphase-segregated state, (2) a decrease of the overall degree of ordering, and (3) an increase of the domain spacing.\u3c/p\u3

Stereocomplexes of discrete, isotactic lactic acid oligomers conjugated with oligodimethylsiloxanes

Discrete length block co-oligomers (BCOs) comprised of a crystalline and an amorphous block are a new class of materials that gives highly ordered lamellar morphologies at small length scales. Here, we show the preparation of discrete, isotactic oligo l- and d-lactic acid (olLA and odLA) homoblocks followed by ligation to oligodimethylsiloxane (oDMS), affording a library of crystalline-amorphous BCOs that vary in molecular weight and composition. Mixing the two enantiomeric BCOs or homoblocks results in the formation of the corresponding stereocomplex. The properties and phase behavior of the isotactic (block co)oligomers and the stereocomplexes thereof are studied using differential scanning calorimetry and small-angle X-ray scattering. A systematic study of the isotactic homoblock lengths and crystal structure confirmed the formation of a 10 3 helix with a monomeric rise of 0.3 nm, whereas the stereocomplex adopts a 3 1 helix. The same type of crystal structure was found for the isotactic and stereocomplex of BCOs giving rise to the formation of lamellar morphologies at room temperature as a result of crystallization of the oLA blocks. Distorted lamellar structures were found in BCOs that preorganize into nonlamellar morphologies prior to crystallization. The stereocomplex BCOs shows more crystal defects and a loss of long-range ordering in the microstructure due to the larger driving force for crystallization. Hence, the balance between chain length, block volume, and the crystallization strength are of major importance for the formation of the final structure with the least defects

Amplifying (im)perfection:the impact of crystallinity in discrete and disperse block co-oligomers

\u3cp\u3eCrystallinity is seldomly utilized as part of the microphase segregation process in ultralow-molecular-weight block copolymers. Here, we show the preparation of two types of discrete, semicrystalline block co-oligomers, comprising an amorphous oligodimethylsiloxane block and a crystalline oligo-l-lactic acid or oligomethylene block. The self-assembly of these discrete materials results in lamellar structures with unforeseen uniformity in the domain spacing. A systematic introduction of dispersity reveals the extreme sensitivity of the microphase segregation process toward chain length dispersity in the crystalline block.\u3c/p\u3

Synthesis and self-assembly of discrete dimethylsiloxane-lactic acid diblock co-oligomers:The dononacontamer and its shorter homologues

\u3cp\u3eMost of the theoretical and computational descriptions of the phase behavior of block copolymers describe the chain ensembles of perfect and uniform polymers. In contrast, experimental studies on block copolymers always employ materials with disperse molecular makeup. Although most polymers are so-called monodisperse, they still have a molecular weight dispersity. Here, we describe the synthesis and properties of a series of discrete length diblock co-oligomers, based on oligo-dimethylsiloxane (oDMS) and oligo-lactic acid (oLA), diblock co-oligomers with highly noncompatible blocks. By utilizing an iterative synthetic protocol, co-oligomers with molar masses up to 6901 Da, ultralow molar mass dispersities (Đ ≤ 1.00002), and unique control over the co-oligomer composition are synthesized and characterized. This specific block co-oligomer required the development of a new divergent strategy for the oDMS structures by which both bis- and monosubstituted oDMS derivatives up to 59 Si-atoms became available. The incompatibility of the two blocks makes the final coupling more demanding the longer the blocks become. These optimized synthetic procedures granted access to multigram quantities of most of the block co-oligomers, useful to study the lower limits of block copolymer phase segregation in detail. Cylindrical, gyroid, and lamellar nanostructures, as revealed by DSC, SAXS, and AFM, were generated. The small oligomeric size of the block co-oligomers resulted in exceptionally small feature sizes (down to 3.4 nm) and long-range organization.\u3c/p\u3

Stereocomplexes of discrete, isotactic lactic acid oligomers conjugated with oligodimethylsiloxanes

\u3cp\u3e Discrete length block co-oligomers (BCOs) comprised of a crystalline and an amorphous block are a new class of materials that gives highly ordered lamellar morphologies at small length scales. Here, we show the preparation of discrete, isotactic oligo l- and d-lactic acid (olLA and odLA) homoblocks followed by ligation to oligodimethylsiloxane (oDMS), affording a library of crystalline-amorphous BCOs that vary in molecular weight and composition. Mixing the two enantiomeric BCOs or homoblocks results in the formation of the corresponding stereocomplex. The properties and phase behavior of the isotactic (block co)oligomers and the stereocomplexes thereof are studied using differential scanning calorimetry and small-angle X-ray scattering. A systematic study of the isotactic homoblock lengths and crystal structure confirmed the formation of a 10 \u3csub\u3e3\u3c/sub\u3e helix with a monomeric rise of 0.3 nm, whereas the stereocomplex adopts a 3 \u3csub\u3e1\u3c/sub\u3e helix. The same type of crystal structure was found for the isotactic and stereocomplex of BCOs giving rise to the formation of lamellar morphologies at room temperature as a result of crystallization of the oLA blocks. Distorted lamellar structures were found in BCOs that preorganize into nonlamellar morphologies prior to crystallization. The stereocomplex BCOs shows more crystal defects and a loss of long-range ordering in the microstructure due to the larger driving force for crystallization. Hence, the balance between chain length, block volume, and the crystallization strength are of major importance for the formation of the final structure with the least defects. \u3c/p\u3

Triggering activity of catalytic rod-like supramolecular polymers

Supramolecular polymers based on benzene-1,3,5- tricarboxamides (BTAs) functionalized with an L- or D-proline moiety display high catalytic activity towards aldol reactions in water. High turnover frequencies (TOF) of up to 27 × 10-4 s-1 and excellent stereoselectivities (up to 96% de, up to 99% ee) were observed. In addition, the catalyst could be reused and remained active at catalyst loadings and substrate concentrations as low as 0.1 mol% and 50 mm, respectively. A temperature-induced conformational change in the supramolecular polymer triggers the high activity of the catalyst. The supramolecular polymer's helical sense in combination with the configuration of the proline (L- or D) is responsible for the observed selectivity