Modular, tissue-specific, and biodegradable hydrogel cross-linkers for tissue engineering.

Synthetic hydrogels are investigated extensively in tissue engineering for their tunable physicochemical properties but are bioinert and lack the tissue-specific cues to produce appropriate biological responses. To introduce tissue-specific biochemical cues to these hydrogels, we have developed a modular hydrogel cross-linker, poly(glycolic acid)-poly(ethylene glycol)-poly(glycolic acid)-di(but-2-yne-1,4-dithiol) (PdBT), that can be functionalized with small peptide-based cues and large macromolecular cues simply by mixing PdBT in water with the appropriate biomolecules at room temperature. Cartilage- and bone-specific PdBT macromers were generated by functionalization with a cartilage-associated hydrophobic N-cadherin peptide, a hydrophilic bone morphogenetic protein peptide, and a cartilage-derived glycosaminoglycan, chondroitin sulfate. These biofunctionalized PdBT macromers can spontaneously cross-link polymers such as poly(N-isopropylacrylamide) to produce rapidly cross-linking, highly swollen, cytocompatible, and hydrolytically degradable hydrogels suitable for mesenchymal stem cell encapsulation. These favorable properties, combined with PdBT's modular design and ease of functionalization, establish strong potential for its usage in tissue engineering applications.

Synthesis and properties of photocross-linked poly(propylene fumarate) scaffolds.

The photocross-linking of poly(propylene fumarate) (PPF) to form porous scaffolds for bone tissue engineering applications was investigated. PPF was cross-linked using the photoinitiator bis(2,4,6-trimethylbenzoyl) phenylphosphine oxide (BAPO) and exposure to 30 min of long wavelength ultraviolet (UV) light. The porous photocross-linked PPF scaffolds (6.5 mm diameter cylinders) were synthesized by including a NaCl porogen (70, 80, and 90 wt% at cross-linking) prior to photocross-linking. After UV exposure, the samples were placed in water to remove the soluble porogen, revealing the porous PPF scaffold. As porogen leaching has not been used often with cross-linked polymers, and even more rarely with photoinitiated cross-linking, a study of the efficacy of this strategy and the properties of the resulting material was required. Results show that the inclusion of a porogen does not significantly alter the photoinitiation process and the resulting scaffolds are homogeneously cross-linked throughout their diameter. It was also shown that porosity can be generally controlled by porogen content and that scaffolds synthesized with at least 80 wt% porogen possess an interconnected pore structure. Compressive mechanical testing showed scaffold strength to decrease with increasing porogen content. The strongest scaffolds with interconnected pores had an elastic modulus of 2.3+/-0.5 MPa and compressive strength at 1% yield of 0.11+/-0.02 MPa. This work has shown that a photocross-linking/porogen leaching technique is a viable method to form porous scaffolds from photoinitiated materials.

Strongly UV absorbing bifunctional azoalkanes.

[structure: see text] Two new anthracene-containing azoalkanes (1 and 2) absorb UV light 600 times more strongly than simple azoalkanes. Intramolecular energy transfer from excited singlet anthracene to the azo group is nearly complete, but despite the close proximity of the two chromophores, 1 and 2 continue to exhibit anthracene fluorescence. Thermolysis of these compounds in the presence of monomers affords fluorescent labeled polymers. Compounds 1 and 2 are the first azoalkanes to undergo induced decomposition in solution.

Thermolysis of free-radical initiators: tert-butylazocumene and its 1,3- and 1,4-bisazo and 1,3,5-trisazo analogues.

Four tert-butylazocumenes (4-7) were prepared from the corresponding cyanobenzenes, and their nitrogen evolution kinetics and products were analyzed. In combination with TEMPO, the simplest compound, tert-butylazocumene (4), shows promise as a "one-radical" initiator of styrene polymerization. The ABNO-trapped cumyl radical 29 is a particularly stable trialkylhydroxylamine, whose thermolysis half-life is 2.1 h at 150 degrees C. Taking advantage of this stability, we trapped the cumyl radical centers from 7 to afford tris adduct 32a. While the behavior of the meta bisazoalkane 6 can be mostly predicted from that of 4, the para isomer 5 exhibits both unusual products and kinetics, attributed to the formation of quinodimethane 33 via azo-containing radical 34. In fact, flash vacuum pyrolysis of 5 allowed observation of the (1)H and (13)C NMR spectra of 33, whose persistence even at ambient temperature showed that this quinodimethane is far more stable than the parent 36. Finally, evidence is presented that 7 is an initiator of star polymerization.

An open-label evaluation of the efficacy and safety of Stadol NS with ibuprofen in the treatment of pain after removal of impacted wisdom teeth.

PURPOSE: This study evaluated the efficacy and safety of transnasal butorphanol tartrate (Stadol NS; Bristol-Myers Squibb, New York, NY) in the treatment of patients with moderate to severe pain after oral surgery for the removal of impacted third molars. PATIENTS AND METHODS: In this open-label study, third molar extraction was performed on 25 male and 25 female patients. These patients were given Stadol NS nasal spray, 1 mg, administered in a single dose every 4 hours as needed. However, patients were allowed to remedicate 60 to 90 minutes after the initial dose, if necessary. They also took ibuprofen (400 mg) as concomitant medication every 4 to 6 hours for the first 48 hours. Patients recorded pain intensity on a visual analog scale, with 0 representing no pain, to 10 representing the most severe pain. RESULTS: Stadol NS significantly reduced pain (by 50%) after third molar extraction within 15 minutes after administration. It had a high level of patient acceptance, 81% on day 1, and was well tolerated. CONCLUSION: The rapid onset of analgesia and long duration of action shown by Stadol NS in this study, as well as its ease of administration and high level of patient acceptance, suggest that this drug would be an excellent primary choice for the management of pain after third molar extraction and oral surgery in general.

Injectable biodegradable polymer composites based on poly(propylene fumarate) crosslinked with poly(ethylene glycol)-dimethacrylate.

New injectable, in situ crosslinkable biodegradable polymer composites were investigated consisting of poly(propylene fumarate) (PPF), poly(ethylene glycol)-dimethacrylate (PEG-DMA), and beta-tricalcium phosphate (beta-TCP). We examined the effects of the PEG-DMA/PPF double-bond ratio and beta-TCP content on the crosslinking characteristics of the composites including the maximum crosslinking temperature and the gel point, as well as the properties of the crosslinked composites such as the compressive strength and modulus, and the water-holding capacity. The maximum crosslinking temperature was constant averaging 39.7 degrees C for the composite formulations tested. The gel points varied from 8.0 +/- 1.0 to 12.6 +/- 2.5 min and were not affected by the relative amounts of PEG-DMA. The compressive strength at yield of PEG-DMA/PPF composites without beta-TCP increased from 5.9 +/- 1.0 to 11.2 +/- 2.2 MPa as the double-bond ratio of PEG-DMA/PPF increased from 0.38 to 1.88. An increase in compressive modulus was also observed from 30.2 +/- 3.5 to 58.4 +/- 6.2 MPa for the same range of the PEG-DMA/PPF double-bond ratio. Also, the addition of beta-TCP (33 wt%) enhanced the mechanical properties of all composites. The equilibrium water content of networks without beta-TCP increased from 21.7 +/- 0.2 to 30.6 +/- 0.2% for a double-bond ratio of PEG-DMA/PPF ranging from 0.38 to 1.88. However, the mechanical properties of the swollen composites under compression were smaller than the dry ones. These data demonstrate the feasibility of fabricating injectable biodegradable polymer composites with engineered mechanical properties for orthopedic tissue engineering.

Synthetic biodegradable polymers for orthopaedic applications.

Synthetic biodegradable polymers offer an alternative to the use of autografts, allografts, and nondegradable materials for bone replacement. They can be synthesized with tailored mechanical and degradative properties. They also can be processed to porous scaffolds with desired pore morphologic features conducive to tissue ingrowth. Moreover, functionalized polymers can modulate cellular function and induce tissue ingrowth. This review focuses on four classes of polymers that hold promise for orthopaedic applications: poly alpha-hydroxy esters, polyphosphazenes, polyanhydrides, and polypropylene fumarate crosslinked networks.

Synthesis of poly(propylene fumarate) by acylation of propylene glycol in the presence of a proton scavenger.

To synthesize high molecular weight poly(propylene fumarate) (PPF), fumaryl chloride and propylene glycol were reacted in the presence of potassium carbonate, which serves as a proton scavenger. Transesterification of the resulting low molecular weight oligomer led to a polymer with greater molecular weight than those from previous reaction methods without requiring the use of a catalyst. According to two-dimensional NMR, the backbone structure of this polymer was as expected and contained no byproducts formed by acid catalyzed addition across the fumarate double bond. Kinetic studies of the transesterification showed that the molecular weight reached a final Mn of 4900 (+/-700) and Mw of 9100 (+/-1300) after 16 h, while the polydispersity index remained below 1.8 throughout the reaction. Thus the PPF synthesized by the new method is of higher molecular weight and greater purity than our previously prepared material.

Alveolar distraction osteogenesis: a new alternative to bone grafts. Report of three cases.

Case reports of distraction osteogenesis of the alveolar bone, case selection, methods and follow-up of patients seen in the Oral Surgery Group office, New Brunswick, NJ.

Characterization of partially saturated poly(propylene fumarate) for orthopaedic application.

A partially saturated linear polyester based on poly(propylene fumarate) (PPF) was synthesized for potential application in filling skeletal defects. The synthesis was carried out according to a two-step reaction scheme. Propylene glycol and fumaryl chloride were first combined to form an intermediate fumaric diester. The intermediate was then subjected to a transesterification to form the PPF-based polymer. This method allowed for production of a polymer with a number average molecular weight up to 1500 and a polydispersity index of 2.8 and below. The polymeric backbone structure was investigated through the use of FTIR and NMR. Kinetic studies of the transesterification allowed mapping of the molecular weight increase with reaction time. The final product was also characterized by thermal and solubility analysis.

Magnetic stirrer with no external moving parts.

This note describes a variable speed stirrer which is based upon a rotating magnetic field produced electronically. Digital circuitry is used to generate two stepped functions which approximate sine waves differing in phase by 90 degrees . The signals are amplified to drive sets of perpendicular coils such that a magnet situated between the coils rotates at the chosen speed.