The regulatory effects of proteoglycans on collagen fibrillogenesis and morphology investigated using biomimetic proteoglycans.

Collagen is one of the leading components in extracellular matrix (ECM), providing durability, structural integrity, and functionality for many tissues. Regulation of collagen fibrillogenesis and degradation is important for treating several diseases from orthopedic injuries to genetic deficiencies. In vivo, this process is generally regulated by proteoglycans (PGs), a family of molecules that contain both protein and glycosaminoglycan components. Recently, novel, biocompatible, semi-synthetic biomimetic proteoglycans (BPGs) were developed, which consist of an enzymatically resistant synthetic polymer core and natural chondroitin sulfate (CS) bristles. It was demonstrated that BPGs affect type I collagen fibrillogenesis in vitro, as reflected by their impact delaying the kinetic formation of gels similar to native PGs. To elucidate the interaction and the effect of BPGs on the quality of collagen fibrils, a histological technique, electron tomography, was adapted and utilized to image nano-scale structures in 2D and 3D within the tissue model. BPGs were found to aid in lateral growth and enhance fibril banding periodicity resulting in structures resembling those in native tissue. BPGs attached to collagen despite the lack of a protein core. This interaction was mediated by the CS bristle regions of the BPGs, implying that CS itself is sufficient for PG-type I tropocollagen interactions, in the absence of the protein core, with the overall nanoarchitecture of the molecule serving to affect ECM kinetics. Synthetic mimics are a tool to study non-proteinaceous PG interactions in collagen assembly and warrant exploration as a viable pathway to augmenting molecular repair in collagen type I-rich tissues.

Synthesis of macromolecular mimics of small leucine-rich proteoglycans with a poly(ethylene glycol) core and chondroitin sulphate bristles.

Small leucine-rich proteoglycans (SLRPs) are a class of molecules prevalent in almost all tissues types and are thought to be responsible for collagen organization and macro-scale biological properties. However, when they are dysfunctional or degraded, severe pathological phenotypes are observed. Here we investigate macromolecular mimics to SLRPs using poly(ethylene glycol) (PEG) as a core (replacing the protein core of natural SLRPs) and chondroitin sulphate (CS) bristle(s) in an end-on attachment (via epoxide-amine reactions), mimicking the physical structure of the natural SLRPs. Poly(ethylene glycol)-diglycidyl ether (PEG-DEG) and ethylene glycol-diglycidyl ether (EG-DGE) monomers were used to incorporate CS bristles into a macromolecule that closely mimics the SLRP biglycan structure in a grafting-to strategy. The kinetics of these reactions was studied along with the specific viscosity and cytocompatibility of resulting CS macromolecules. Structures were found to incorporate two CS chains (similar to biglycan) on average and exhibited cytocompatibility equivalent to or better than CS-only controls.

Co-precipitation of rare-earth-doped Y2O3 and MgO nanocomposites for mid-infrared solid-state lasers.

Mid-infrared, solid-state laser materials face three main challenges: (1) need to dissipate heat generated in lasing; (2) luminescence quenching by multiphonon relaxation; and (3) trade-off in high thermal conductivity and small maximum phonon energy. We are tackling these challenges by synthesizing a ceramic nanocomposite in which multiple phases will be incorporated into the same structure. The undoped majority species, MgO, will be the main carrier of high thermal conductivity, and the minority species, Er:Y2O3, will have low maximum phonon energy. There is also an inherent challenge in attempting to make a translucent part from a mixture of two different materials with two different indexes of refraction. A simple, co-precipitation technique has been developed in which both components are synthesized in situ to obtain intimate mixing. These powders compare well to commercially available ceramics, including their erbium spectroscopy, even when mixed as a composite, and can be air-fired to ∼96% of theoretical density, yielding translucent parts. As the amount of Er:Y2O3 increases, the translucency decreases as the number of scattering sites start to coalesce into large patches. If the amount of Er:Y2O3 is sufficiently small and dispersed, the yttria grains will be pinned as individuals in a sea of MgO, leading to optimal translucency.