In the current investigation, we report osseous regeneration in critical-size rat calvarial defects using recombinant human bone morphogenetic protein-2 (rhBMP-2) and novel delivery systems based on biomaterials. The novel systems combine rhBMP-2 with dry powder microparticles of poly(D,L-lactide-co-glycolide) (PLGA). The mixture of rhBMP-2 with PLGA microparticles is added to an aqueous solution of biopolymer to yield a semisolid paste. The biopolymers tested include autologous blood clot, hydroxypropyl methylcellulose, and sodium alginate cross-linked with calcium ion. Insoluble collageneous bone matrix was also studied as a control. Test articles were made at 0-, 10-, and 30-micrograms doses of rhBMP-2 and imiplanted in 8-mm-diameter rat calvarial defects (which will not heal if left untreated). The animals were examined 21 days after implantation by radiography, radiomorphometry, histology, and histomorphometry. All tested materials containing rhBMP-2 restored radiopacity and normal contouring to the calvarial defects. Samples without added rhBMP-2 yielded only soft tissue within the defects. Histology showed restoration of inner and outer bone tables plus marrow constituents. The PLGA microparticles were significantly resorbed at the 21-day time point. Although small differences between delivery systems were evident at 0- and 10-micrograms rhBMP-2 doses, all test articles performed essentially equivalently at the 30-micrograms dose. Thus, novel delivery systems for rhBMP-2 offer the promise of combining the intrinsic bioactivity of the osteoinductive protein with pharmaceutically acceptable biomaterials.
strong O1 2' and a weak OH" ligand in the axial direction and that the strong O2" ligand is preferable to the 5 = 1 spin state of the central metal ion.
Y) Y (Z) Flgure 1. Axis system in C=O and N-0 bonds: X = C, N.atoms, as compared with the values for otherwise similar but non-hydrogen-bonded atoms.7 The experimental data presented here corroborate the theoretical results (see also Figure 2 of ref 7 ) .In addition to the direct study of hydrogen bonding in the form of geometrical interpretation of the I7O NQR data, the results presented here and in the previous paper facilitate the analysis of the electronic effects that are reflected in the I7O NQR data. For example, the carbonyl group in 4(1H)-pyridinone is structurally similar to that in p-benzoquinone, but has a quite different quadrupole coupling constant, 8.33 vs. 11.51 MHz.14 A large portion of the difference in the values of the quadrupole coupling constant is probably due to the effect of hydrogen bonding in 4(1H)-pyridinone, although the solid-state structure of this compound is not known. If we assume that the length of the hydrogen bond is the same as is found in 2(1H)-pyridinone (2.77 A),'5 then we can estimate the effect of hydrogen bonding on the 170 quadrupole coupling constant to be about 1.0 MHz. Because this still leaves a large difference of 2.2 MHz between the two oxygen sites, one can infer that there exists a significant difference in the electronic environment of the two carbonyl groups. The lower quadrupole coupling constant in 4( 1H)-pyridinone suggests a much larger oxygen 2p, population.In summary, we have presented 1 7 0 NQR data for several hydrogen-bonded systems. The experimental data support the results of a previous theoretical study. The results demonstrate that hydrogen bonding in the solid state is amenable to study by 170 NQR techniques. Secondly, the effects of hydrogen bonding upon the electric field gradient can be estimated, thus aiding in the further analysis of intramolecular electronic effects on the 1 7 0 NQR data. ~ ~~~~~ (14) Hsieh,Y.; Koo, J. C.; Hahn, E. L.The reactions of OH with benzene, toluene, 1,4-dimethylbenzene, and 1,3,5-trimethylbenzene have been investigated in a discharge flow system at total pressures of 6-12 torr. In the presence of NO, NOz, and O2 the intermediate radicals are converted quantitatively to stable products from which two major reaction pathways are identified. Abstraction of a hydrogen atom from the methyl group by OH leads primarily to the corresponding aldehyde, and addition to the aromatic ring by OH gives primarily the corresponding phenols. Nitro substitution of the aromatics via the OH adduct competes with phenol formation; however, the amount depends on the ratio of NOz/Oz. In the case for toluene, the ratio of rate constants, kNOf/kol, for the two processes is (4 f 2) X lo3. The isomer distributions for OH addition to toluene were determined to be 0.806 f 0.022 ortho, 0.051 f 0,009 meta, 0.143 & 0.019 para, and <0.008 ipso. The contributions of methyl attack (k,) relative to total reaction (kl + k2) are 0.15 f 0.02 for toluene, 0.15 f 0.02 for 1,4-dirnethylbenzene, and 0.021 f 0.006 for 1,3,5-trimethylbenzene. IntroductionArom...
As an extension of an earlier investigation (J. Med. Chem. 1984, 27, 1431), we prepared a series of 3-substituted 5-[(hydroxyimino)methyl]-1,2,4-oxadiazoles and the corresponding 5-thiocarbohydroximic acid 2-(N,N-dialkylamino)ethyl S-esters. The compounds were evaluated in vitro as reactivators of phosphonylated electric eel and human erythrocyte (RBC) acetylcholinesterases (AChE). The compounds were characterized with respect to (hydroxyimino)methyl acid dissociation constant, nucleophilicity, octanol/buffer partition coefficient, reversible AChE inhibition, and kinetics of reactivating ethyl methylphosphonylated AChE. One compound was also tested for effectiveness in preventing AChE phosphonylation. All of the tested compounds significantly reactivate ethyl methylphosphonylated AChE: the 3-n-octyl- and 3-(1-naphthyl)-substituted aldoximes are as reactive (within a factor of 5-10) toward the inhibited enzymes as the benchmark pyridinium reactivators, 2-PAM and HI-6. All of the substituted thiocarbohydroximic acid S-esters are powerful reversible inhibitors of AChE's: the 3-n-octyl- and 3-(1-naphthyl)-substituted thiocarbohydroximates inhibit eel AChE to 50% initial activity at concentrations less than 5 microM. When added to an eel AChE solution at concentrations between 5 and 50 microM, the 3-phenyl-substituted thiocarbohydroximate effectively antagonizes AChE inhibition by ethyl p-nitrophenyl methylphosphonate (EPMP), suggesting the potential utility of this compound for preventing anti-AChE-agent poisoning.
Trauma, disease, developmental deformities, and tumor resection frequently cause bone defects that seriously challenge the skills of orthopedic and maxillofacial surgeons. Currently, repairing osseous deficiencies involves various medical surgical techniques, including autogenous grafts, allografts, internal and external fixation devices, electrical stimulation, and alloplastic implants. The existing technology, though effective in many cases, still is beset with numerous difficulties and disadvantages. A critical need for improved treatment methods exists today. Biotechnology now provides access to new bone repair concepts via administration of protein growth and morphogenic factors. Implantable device and drug delivery system technologies also have advanced. The converging biopharmaceutical, device, and delivery technologies represent an opportunity to improve the quality of health care for individuals with orthopedic and maxillofacial deficiencies. This report reviews current concepts in fracture healing and bone repair and examines existing treatment modalities. It also addresses novel protein drugs that stimulate osseous regeneration and delivery systems for these drugs.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.