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.

Matrix-assisted laser desorption mass spectrometric analysis of a pegylated recombinant protein.

Matrix-assisted laser desorption ionization mass spectrometry (MALDI) has been investigated as a technique for the characterization of recombinant stem cell factor that had been covalently modified with polyethylene glycol (PEG) chains. The attachment of PEG chains produces a heterogeneous mixture of protein species that differ by 6000 Da. These differences in molecular weight could be readily determined by MALDI. The potential of MALDI as a general strategy for characterizing PEG-modified proteins is discussed.

Polyethylene wear after total hip arthroplasty: the effect of a modular femoral head with an extended flange-reinforced neck.

The use of modular components in total hip arthroplasty has been thought to contribute to accelerated polyethylene wear. Specifically, a modular femoral head with a flange extension and a longer neck may cause increased wear. The purpose of the current study was to evaluate the effect of a flange extension on polyethylene wear. Ninety-one patients who had had a total of 100 primary total hip arthroplasties were evaluated after an intermediate duration of follow-up. All of the acetabular components consisted of a hemispherical titanium-alloy fiber-mesh porous-coated shell with a nonelevated modular polyethylene liner; they were inserted without cement and with use of supplemental screws through the dome after so-called line-to-line reaming. All of the femoral components consisted of a modular head with a diameter of twenty-eight millimeters and either a long neck (with a flange extension) or a short or medium neck (without a flange extension). The study group comprised sixty-two patients (sixty-six hips) who had had radiographic evaluation that was adequate to allow the valid measurement of polyethylene wear. Thirty-two hips were in men, and thirty-four were in women. The mean age of the patients was fifty-six years, the mean weight was seventy-three kilograms, and the mean duration of follow-up was 6.1 years (range, four to eight years). The rate of polyethylene wear in the eleven hips in which the femoral component had a flange extension was significantly greater than that in the fifty-five in which the femoral component did not have a flange extension (mean, 0.17 compared with 0.11 millimeter per year; p = 0.009). Multivariate analysis showed that the presence of a flange extension was associated with increased polyethylene wear to a greater degree (F = 2.86) than were all other variables that were measured, including a younger age (F = 1.72), a more vertical angle of the acetabular component (F = 0.49), a heavier weight (F = 0.14), male gender (F = 0.11), and a smaller initial thickness of the polyethylene (F = 0.02). These data support an association between the presence of a modular femoral head with a flange extension and an accelerated rate of polyethylene wear. The presumed mechanism is an increase in peripheral, or so-called rim, impingement of the flange-reinforced neck on the acetabulum due to a decrease in the ratio between the diameters of the femoral head and neck.

Effect of povidone-iodine on in vitro locomotion of equine neutrophils.

Incubation of equine neutrophils with povidone-iodine solutions of greater than or equal to 0.2 per cent resulted in total inhibition of migration under agarose. This was caused by the cytotoxic effects of the solutions as shown by pyknosis and cell lysis. Lower concentrations of povidone-iodine, however, did not adversely affect neutrophil viability or locomotion.

Macrophage clearance of 125I-labelled polyvinyl pyrrolidone in the horse: effect of ovarian steroids and persistent endometritis.

The rate of clearance of 125I-labelled polyvinyl pyrrolidone (PVP) from blood was measured in mares as an indicator of macrophage function. In three out of four cycling mares, PVP clearance was slower during oestrus than dioestrus. Similarly, administration of oestrogen to four ovariectomised mares tended to depress PVP clearance compared with clearance from the same mares before they received oestrogen. However, the effect of oestrogen was not statistically significant. Mares susceptible to persistent endometritis had rates of PVP clearance which were similar to those of genitally normal mares.

The Harris-Galante Porous acetabular component at intermediate follow-up.

Outcome of the acetabular component in 90 consecutive primary noncemented total hip arthroplasties (THAs) was prospectively studied. The acetabular cup consisted of a hemispherical titanium alloy shell with a titanium fiber-mesh porous coating and a modular polyethylene liner (Harris-Galante Porous-1, Zimmer, Warsaw, Ind). The cup was implanted using line-to-line reaming with adjunctive dome screw fixation. The femoral component consisted of a titanium alloy stem with titanium fiber-mesh porous coating and a 28-mm cobalt-chrome modular head. Mean patient age was 53 years (range: 27-75 years); male:female ratio was 48:42; and mean follow-up was 6 years (range: 4.5-8 years). One acetabular component was revised for aseptic loosening. Of 81 unrevised hips available for follow-up, mean Harris hip score was 57 preoperatively and 96 at final follow-up (72% excellent, 15% good, 1 3% fair, and none poor). Of 61 unrevised hips with adequate radiographic follow-up, radiographic failure (complete periprosthetic radiolucency) was evident in 3 (4.9%) and periacetabular osteolysis in none. Radiographic failure did not correlate with poor clinical outcome. Linear polyethylene wear rate (mean: 0.13 mm/year) did not correlate with age, gender, weight, outcome, or cup abduction angle, but did correlate with the presence of femoral periprosthetic osteolysis (0.18 mm/year with femoral osteolysis versus 0.11 mm/year without; P= .01). This series of porous-coated hemispherical cups demonstrated excellent intermediate-term clinical and radiographic outcome, comparable with similarly favorable results reported by the prosthesis designers. A potentially adverse effect of polyethylene wear on the longevity of a THA was supported by a positive correlation between polyethylene wear rate and femoral osteolysis.

The measurement of mandibular cortical bone height in osteoporotic vs. non-osteoporotic postmenopausal women.

The asymptomatic progression of osteoporosis, in conjunction with the possibility of catastrophic disability, makes this disorder a major public health priority. Various body sites, including the mandible, have shown susceptibility to decreasing bone density. In 1986, Benson et al. proposed a radiomorphometric technique called the Panoramic Mandibular Index (PMI) as an inexpensive noninvasive dental technique for osteoporosis screening, although no osteoporotic subjects were included in their study. The purpose of our study was to determine whether osteoporotic postmenopausal women would show a decrease in mandibular cortical bone height, as measured by the PMI index, when compared with nonosteoporotic postmenopausal women. Seventy-two Caucasian females (33 cases/39 controls), aged 54-71 years old, were selected through records and screening via a dual-energy x-ray absorptiometry scan (LUNAR-DEXA). ANOVA analysis indicated no differences in the mean PMI between case and control groups (0.37 +/- 0.15 and 0.38 +/- 0.13, respectively; p = 0.69). Other techniques, such as computer digitized radiography should be explored to test the validity of the PMI.

Population pharmacokinetic modeling for dose setting of nonacog beta pegol (N9-GP), a glycoPEGylated recombinant factor IX.

BACKGROUND: nonacog beta pegol (N9-GP) is a glycoPEGylated recombinant factor IX (rFIX) molecule with a prolonged half-life. OBJECTIVES: To provide information on potential dose regimens for N9-GP for phase 3 pivotal and surgery trials. METHODS: A population pharmacokinetic model was developed from single-dose data derived from the first human-dose trial with N9-GP in hemophilia B patients, and was used to extrapolate to steady-state conditions for different N9-GP dose regimens for prophylaxis. The model was also used to compare prophylaxis using N9-GP with standard prophylactic regimens using rFIX or plasma-derived (pd) FIX (40 IU kg(-1) every third day). Plasma activity following dosing with N9-GP, rFIX and pdFIX for surgery and on-demand treatment of bleeds was also simulated. RESULTS: A linear two-compartmental model best described the pharmacokinetic profiles of N9-GP, rFIX and pdFIX. A prophylactic regimen of 10 U kg(-1) N9-GP once weekly predicted mean peak and trough levels of 18 and 4.2 U dL(-1) , while 40 U kg(-1) once weekly predicted values of 72 and 17 U dL(-1) , respectively. Standard prophylactic regimens with rFIX and pdFIX predicted mean peak and trough levels of 34 and 3.9 IU dL(-1) for rFIX, and mean values of 43 and 2.1 IU dL(-1) for pdFIX. Additional simulations predicted significantly reduced dosing frequency and factor concentrate consumption for N9-GP vs. rFIX and pdFIX for surgery and the treatment of bleeds. CONCLUSIONS: N9-GP may allow prophylaxis, surgical dosing regimens and on-demand treatment of bleeding episodes with less frequent injections and lower factor concentrate consumption; this possibility is being investigated in prospective clinical trials.

The oral health status of adults with a visual impairment, their dental care and oral health information needs.

AIM There is little information available concerning the impact of visual impairment upon oral health. The present study sought to identify the oral health and experiences of adults with a visual impairment together with the nature, source and access to oral health information. In addition the study evaluated the oral health status of a group of individuals with a visual impairment with respect to oral health markers, treatment choice and attendance patterns in comparison to a reference group from the general population in the United Kingdom. METHOD One hundred adults with a visual impairment were examined and completed a questionnaire concerning their experience of oral health care and available information sources. The information collected was directly compared with data from the Adult Dental Health Survey 1998 for the south region of England. RESULTS The present group of individuals with a visual impairment had better oral hygiene practices, and similar levels of oral hygiene and hard tissue disease to those of a comparable group of the Adult Dental Health Survey 1998 (ADHS 1998). However 24% of those with a visual impairment were not registered with a dentist and 26% of the patients wished for appropriate information concerning oral health care. CONCLUSIONS There is a need to develop oral health promotion that ensures patients with a visual impairment have appropriate information regarding oral health care and its provision.

Human oral epithelial cell culture I. Improved conditions for reproducible culture in serum-free medium.

Gingival tissue from healthy adult human donors was used as a source of epithelial cells for culture. An overnight incubation of this tissue with dispase facilitated the mechanical separation of the surface epithelium from the underlying fibrous connective tissue. This step minimized culture contamination with fibroblasts. The epithelium was then trypsinized to prepare a single cell suspension. The cell pellets were collected by centrifugation and resuspended in keratinocyte growth medium, incubated at 37 degrees C and 5% CO2 in a humid atmosphere. Primary cultures grew in small islands that coalesced at confluency. Immunohistochemistry demonstrated uniform staining of the cells with antibodies to keratins of stratified squamous epithelium. Ultrastructurally, the cells contained distinct intermediate filaments. When cells were grown in media with low calcium (0.15 mM), cell-to-cell contacts were via interlacing papillary projections with no desmosomes. However, when cells were grown under physiologic calcium (1.2 mM), desmosomes were prominent and well developed. Cells were maintained in culture for over 100 d (7 passages).

Case record analysis: biopsied lesions in a high-risk white and African American Community.

OBJECTIVES: The purpose of this secondary data analysis was to characterize biopsied intraoral lesions documented from neighborhood health center records in a lower socioeconomic biracial community over an eight year period, (1982-1989.) METHODS: A thorough intraoral examination, which included radiographs, was completed by either a general dentist or an oral surgeon. Questionable lesions were referred to and biopsied in the Department of Pathology at Johns Hopkins Medical Center. Biopsied lesions were classified into three groups for analysis: benign, malignant/premalignant, and dental-related. RESULTS: Of 13,317 recorded dental visits, 10,819 (81.2%) visits were made by African Americans. There were 341 lesions biopsied, representing 69 different histologic diagnoses. Of identified lesions, 76.5% were in African Americans; 41.6% were in males, ranging in age from 41 to 94 years old (a mean age of 73 +/- 7 years). Approximately 50% of identified lesions in African American and Whites were benign. Among African Americans, 11.9% of the lesions were malignant premalignant, while 16.3% were among Whites. Within the malignant/premalignant category, squamous cell carcinoma was the most frequently identified malignant lesion. Hyperkeratosis was the most common premalignant lesion type. CONCLUSIONS: Neighborhood health centers can provide a valuable screening service identifying intraoral lesions in vulnerable communities. Future research should explore how socioeconomic factors affect differences in the prevalence of intraoral pathologies among White and African American subgroups as well as other subpopulations.