Long term outcomes of biomaterial-mediated repair of focal cartilage defects in a large animal model.

The repair of focal cartilage defects remains one of the foremost issues in the field of orthopaedics. Chondral defects may arise from a variety of joint pathologies and left untreated, will likely progress to osteoarthritis. Current repair techniques, such as microfracture, result in short-term clinical improvements but have poor long-term outcomes. Emerging scaffold-based repair strategies have reported superior outcomes compared to microfracture and motivate the development of new biomaterials for this purpose. In this study, unique composite implants consisting of a base porous reinforcing component (woven poly(ε-caprolactone)) infiltrated with 1 of 2 hydrogels (self-assembling peptide or thermo-gelling hyaluronan) or bone marrow aspirate were evaluated. The objective was to evaluate cartilage repair with composite scaffold treatment compared to the current standard of care (microfracture) in a translationally relevant large animal model, the Yucatan minipig. While many cartilage-repair studies have shown some success in vivo, most are short term and not clinically relevant. Informed by promising 6-week findings, a 12-month study was carried out and those results are presented here. To aid in comparisons across platforms, several structural and functionally relevant outcome measures were performed. Despite positive early findings, the long-term results indicated less than optimal structural and mechanical results with respect to cartilage repair, with all treatment groups performing worse than the standard of care. This study is important in that it brings much needed attention to the importance of performing translationally relevant long-term studies in an appropriate animal model when developing new clinical cartilage repair approaches.

New dinuclear cobalt(II) and zinc(II) complexes of a carboxylate-rich dinucleating ligand: synthesis, structure, spectroscopic characterization, and their interactions with sugars.

Sugar-metal ion interactions in aqueous medium are involved in many biochemical processes such as the transport and storage of metals, the function and regulation of sugar-metabolizing metalloenzymes, the mechanism of action of metal-containing pharmaceuticals, and toxic metal metabolism. To understand such interactions we synthesized and fully characterized two new dinuclear cobalt(II) and zinc(II) complexes as carbohydrate binding models for xylose/glucose isomerases (XGI). Synthesis of the dicobalt complex, Na3[Co2(ccdp)(µ-HCO2)]BF4·9H2O·2CH3OH (1), was performed in methanol with stoichiometric amounts of Co(BF4)2·6H2O and the dinucleating ligand, H5ccdp (H5ccdp = N,N'-bis[2-carboxybenzomethyl]-N,N'-bis[carboxymethyl]-1,3-diaminopropan-2-ol), in the presence of NaOH at ambient temperature in an argon glovebox. Similarly, the dizinc complex, [NMe4]2[Zn2(ccdp)(µ-OAc)]·CH3OH (2), was synthesized from Zn(OAc)2·2H2O and H5ccdp in the presence of NMe4OH at ambient temperature in methanol. Binding of the complexes with carbohydrates was investigated under different reaction conditions. In aqueous alkaline media, complexes 1 and 2 showed chelating ability towards the biologically important sugars, d-glucose and d-xylose, and a polyalcohol enzyme inhibitor (xylitol). In solution, each complex forms a 1:1 complex-substrate bound product with specific binding constant values. Synthesis, characterization details, and substrate binding using spectroscopic techniques and single-crystal X-ray diffraction are reported.

Synthesis and characterization of mono- and micro6-sulfato hexanuclear zinc complexes of a new symmetric dinucleating ligand.

Zinc complexes of a new symmetric dinucleating ligand, N,N'-Bis[2-carboxybenzomethyl]-N,N'-Bis[carboxymethyl]-1,3-diaminopropan-2-ol (H5ccdp) with mixed donating groups, have been studied in the solid state as well as in solution. In methanol, the reaction of stoichiometric and substoichiometric amounts of Zn(ClO4)2 x 6H2O and the ligand H5ccdp, in the presence of K2CO3 or Et3N, afforded a mononuclear zinc complex, [Zn(H2O)6][Zn(H2ccdp)(H2O)2]2 x 12H2O (1). The solid state structure of 1 contains two units of the zinc-ligand anion, [Zn(H2ccdp)(H2O)2]-, and one [Zn(H2O)6]2+ counter cation. The Zn(II) center of the anion is in a distorted octahedral geometry. However, in methanol, the reaction of ZnSO4 x 7H2O and the ligand Hsccdp in the presence of NaOH afforded a unique micro6-sulfato hexanuclear zinc complex, Na6[Zn6(ccdp)3(micro6-SO4)](OH) x 10.5H2O (2). The structure of 2 contains a [ZnII6(micro6-SO4)] core unit which is held together by three heptadentate bridging ligands, ccdp5-. Three of the Zn(II) centers are in highly distorted square pyramidal geometry, the other three Zn(II) centers are in a distorted octahedral geometry.

Bis(tetra-methyl-ammonium) tetra-chlorido-zincate(II), phase VI.

Phase VI of bis-(tetra-methyl-ammonium) tetra-chloro-zincate(II), (C(4)H(12)N)(2)[ZnCl(4)], contains three formula units per asymmetric unit. Several short C-H⋯Cl contacts [2.70 (3) and 2.72 (4) Å] are observed, but they are believed to participate only in van der Waals inter-actions. The crystal studied exhibited inversion twinning.