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A model is presented for enhancement of fluid flow through bone matrix and any porous tissue engineering scaffold implanted within it. The mechanism of enhancement is the skeletal muscle pump in compartments adjacent to the bone. Pressure waves from muscle pump contractions aided by increased blood pressure during exercise coupled with temporary occlusion of arteries leading to and veins from the bone, increase hydraulic pressure in cortical bone capillaries so as to amplify capillary filtration. It is proposed that capillary filtration increase is sufficiently convective to contribute to bone fluid flow and associated percolation through tissue engineered scaffold matrix implants. Importance of this contribution is its relative role in maintaining seeded cells in bioreactor scaffolds. Validation of the hypothesis starts at a minimum level of demonstrating that capillary filtration is convective. At a maximum level confirmation of the hypothesis requires demonstration that capillary filtration-based interstitial flow is sufficient to stimulate not only host bone cells (as proposed in part I of the hypothesis) but bioreactor-seeded cells as well. Preliminary data is presented supporting the prediction that skeletal muscle contraction generates convective capillary filtration.

Presents several commentaries on the article "L-Arginine Availability Is Not Limiting for Nitric Oxide Generation from Recombinant Endothelial Nitric Oxide Synthase," by Mohacsi, et al, published in the 1999 issue of the "Journal of Vascular Research." Involvement of nitric oxide and cyclic guanylic acid pathway in atherosclerosis; Role of L-arginine in nitric oxide production; Efficiency of L-arginine to restore endothelium-dependent relaxation.

The direct and indirect effects of muscle contraction on bone microcirculation and fluid flow are neither well documented nor explained. However, skeletal muscle contractions may affect the acquisition and maintenance of bone via stimulation of bone circulatory and interstitial fluid flow parameters. The purposes of this study were to assess the effects of transcutaneous electrical neuromuscular stimulation (TENS)-induced muscle contractions on cortical bone blood flow and bone mineral content, and to demonstrate that alterations in blood flow could occur independently of mechanical loading and systemic circulatory mechanisms. Bone chamber implants were used in a rabbit model to observe real-time blood flow rates and TENS-induced muscle contractions. Video recording of fluorescent microspheres injected into the blood circulation was used to calculate changes in cortical blood flow rates. TENS-induced repetitive muscle contractions uncoupled from mechanical loading instantaneously increased cortical microcirculatory flow, directly increased bone blood flow rates by 130%, and significantly increased bone mineral content over 7 weeks. Heart rates and blood pressure did not significantly increase due to TENS treatment. Our findings suggest that muscle contraction therapies have potential clinical applications for improving blood flow to cortical bone in the appendicular skeleton., (Copyright 2008 Orthopaedic Research Society)

Birefringence variations in circularly polarized light (CPL) images of thin plane-parallel sections of cortical bone can be used to quantify regional differences in predominant collagen fiber orientation (CFO). Using CPL images of equine third metacarpals (MC3s), R.B. Martin, V.A. Gibson, S.M. Stover, J.C. Gibeling, and L.V. Griffin. (40) described six secondary osteon variants ('morphotypes') and suggested that differences in their regional prevalence affect fatigue resistance and toughness. They devised a numerical osteon morphotype score (MTS) for quantifying regional differences in osteon morphotypes. We have observed that a modification of this score could significantly improve its use for interpreting load history. We hypothesized that our modified osteon MTS would more accurately reveal differences in osteon MTSs between opposing "tension" and "compression" cortices of diaphyses of habitually bent bones. This was tested using CPL images in transverse sections of calcanei from sheep, deer, and horses, and radii from sheep and horses. Equine MC3s and sheep tibiae were examined as controls because they experience comparatively greater load complexity that, because of increased prevalence of torsion/shear, would not require regional mechanical enhancements provided by different osteon morphotypes. Predominant CFO, which can reliably reflect adaptation for a regionally prevalent strain mode, was quantified as mean gray levels from birefringence of entire images (excluding pore spaces) in anterior, posterior, medial, and lateral cortices. Results showed that, in contrast to the original scoring scheme of Martin et al., the modified scheme revealed significant anterior/posterior differences in osteon MTSs in nearly all "tension/compression" bones (p<0.0001), but not in equine MC3s (p=0.30) and sheep tibiae (p=0.35). Among habitually bent bones, sheep radii were the exception; relatively lower osteon populations and the birefringence of the primary bone contributed to this result. Correlations between osteon MTSs using the scoring scheme of Martin et al. with CFO data from all regions of each bone invariably demonstrated weak-to-moderate negative correlations. This contrasts with typically high positive correlations between modified osteon MTSs and regional CFO. These results show that the modified osteon MTS can be a strong correlate of predominant CFO and of the non-uniform strain distribution produced by habitual bending.

The Society for Biomaterials (SFB) aims to serve its members through acting as a forum for the exchange of information and ideas. To aid in the practical development of the SFB and more specifically biomaterials education, all active, associate, and student members were surveyed. In general, the survey asked questions regarding respondent demographics, experiences and activities with the SFB, and opinions about biomaterials education. Perceptions and needs of biomaterials-related education and career-related training practices were a specific focus of the survey. A total of 140 individuals responded to the survey for a response rate of 18%. Members from industry felt that new hires, in general, should be better trained in product development, regulatory issues for new materials and devices, and in the relevant testing required. When asked what was missing from their professional education, many respondents commented that business training in areas such as negotiations, management, and understanding the needs outside of academia was lacking. Also, many respondents seemed to have trouble identifying with what they were supposed to know and felt a "lack of set professional knowledge." This study has raised many ideas and questions that require further discussion. The results should ultimately be useful for helping the SFB decide how best to focus future efforts in biomaterials education., (Copyright 2004 Wiley Periodicals, Inc.)

The purpose of the study reported here was to use an in vivo rabbit model to evaluate the rate of bone ingrowth into remodelable calcium phosphate bone cement. We evaluated an in vivo bone chamber placed in a rabbit tibia with its ingrowth compartment filled with absorbable calcium phosphate bone cement (Norian Skeletal Repair System; Norian Corp, Cupertino, Calif). Five New England white rabbits had a single bone chamber implanted into the proximal right tibia. Observations were made and photomicrographs taken on a weekly basis. Results of morphological analysis showed sequential loss of cement and subsequent bone ingrowth over a testing period of up to 30 weeks. Resorption of bone cement was complete in 1 rabbit. The other rabbits had significant bone ingrowth, which reaffirms the biocompatibility of this material. Results of this study showed that using in vivo microscopy with the rabbit bone chamber model was useful in evaluating bone ingrowth and replacement of absorbable bone cement. This model may make it possible to evaluate various combinations of bone cement and bone growth factors, which could serve as an alternative to autogenous bone grafting.

A non-destructive ultrasonic longitudinal wave pulse-echo technique was utilized to monitor the degradation process of three biodegradable polymers: poly(glycolic acid) (PGA), poly(L-lactic acid) (PLLA) and 50:50 poly(D,L-lactide-co-glycolide) (PDLLG). The degradation processes of PGA and PLLA, which have different molecular structure, were also studied by differential scanning calorimetry (DSC). The degradation processes of PDLLG specimens prepared by different methods were characterized by the ultrasonic wave technique and gel permeation chromatography (GPC). The resulting acoustic and thermal properties indicate that PLLA and PGA exhibit distinctly different degradation behavior, whereas the acoustic properties and molecular weight of PDLLG are sensitive with preparation methods. The present study demonstrates that ultrasonic wave technique provides a powerful tool in detecting the property changes of biodegradable polymers prepared with different manufacturing process and that the degradation behavior of biodegradable polymers can be closely monitored by ultrasonic technique.

This study examines relationships between bone morphology and mechanically mediated strain/fluid-flow patterns in an avian species. Using mid-diaphyseal transverse sections of domestic turkey ulnae (from 11 subadults and 11 adults), we quantified developmental changes in predominant collagen fiber orientation (CFO), mineral content (%ash), and microstructure in cortical octants or quadrants (i.e., %ash). Geometric parameters were examined using whole mid-diaphyseal cross-sections. The ulna undergoes habitual bending and torsion, and demonstrates nonuniform matrix fluid-flow patterns, and high circumferential strain gradients along the neutral axis (cranial-caudal) region at mid-diaphysis. The current results showed significant porosity differences: 1) greater osteocyte lacuna densities (N.Lac/Ar) (i.e., "non-vascular porosity") in the caudal and cranial cortices in both groups, 2) greater N.Lac/Ar in the pericortex vs. endocortex in mature bones, and 3) greater nonlacunar porosity (i.e., "vascular porosity") in the endocortex vs. pericortex in mature bones. Vascular and nonvascular porosities were not correlated. There were no secondary osteons in subadults. In adults, the highest secondary osteon population densities and lowest %ash occurred in the ventral-caudal, caudal, and cranial cortices, where shear strains, circumferential strain gradients, and fluid displacements are highest. Changes in thickness of the caudal cortex explained the largest proportion of the age-related increase in cranial-caudal breadth; the thickness of other cortices (dorsal, ventral, and cranial) exhibited smaller changes. Only subadult bones exhibited CFO patterns corresponding to habitual tension (ventral) and compression (dorsal). These CFO variations may be adaptations for differential mechanical requirements in "strain-mode-specific" loading. The more uniform oblique-to-transverse CFO patterns in adult bones may represent adaptations for shear strains produced by torsional loading, which is presumably more prevalent in adults. The micro- and ultrastructural heterogeneities may influence strain and fluid-flow dynamics, which are considered proximate signals in bone adaptation., (Copyright 2003 Wiley-Liss, Inc.)

The effects of recombinant human fibroblast growth factor-2 in the presence of eroding 50:50 poly(DL-lactide-co-glycolide) on angiogenesis during acute bone defect healing were studied in the optical bone chamber. Bone chambers were loaded with disks of poly(DL-lactide-co-glycolide) surrounded by one of four doses of recombinant human fibroblast growth factor-2. Fifty-two female rabbit right tibias were implanted. Commencing with the third postimplantation week, healing into the bone chamber compartment was observed weekly, with use of intravital microscopy, until week 8. The treatment groups were as follows: unloaded, loaded with polymer only, and loaded with polymer plus-0.5, -1.0, and -10 microg recombinant human fibroblast growth factor-2. Videotaped and photographed bone images were measured and analyzed with a frame-grabber digitizing system. Comparison with controls or polymer alone revealed that angiogenesis rates were significantly above normal in rabbits loaded with polymer plus either of the two highest recombinant human fibroblast growth factor-2 doses. The effects of these doses were not, however, significantly different from each other, indicating a plateauing rather than monotonically increasing response. It was concluded that recombinant human fibroblast growth factor-2 in the dose- range studied can effectively overcome the retarding effects of eroding polymer on angiogenesis in bone, which has been reported previously by this laboratory. In contrast to these results, no statistically significant differences in angiogenesis rate as a function of time could be detected. It is suggested that this apparent lack of variation is linked to observed alterations in vessel patterns from week-to-week. The clinical relevance of these results is that inhibitory carrier effects can be compensated for by increasing the dose of loaded agent where the effect being inhibited is the one being treated, or by adding an agent specific for the inhibited effect. In either case, geometry of the carrier must be considered when programming for delivery rate.

Neovascularization across a gap defect in a rabbit tibial cortex was monitored using the optical bone chamber implant (BCI). Cortical bone growing by apposition as trabeculae was observed weekly as it penetrated a slit into a tissue space in vivo and in situ. Each rabbit was viewed weekly with an intravital microscope from 3 to 8 weeks postimplantation. The constant field of view was the slit-gap tissue space, which was 100 microns thick and 2 mm in diameter. Vessels were imaged with epi-illuminated fluorescence microscopy as they carried FITC-dextran 70 that had been injected into an aural vein. Observations were videotaped and photographed. Videotape frames were analyzed with a digital image processing system to obtain measures of vessel length per unit volume (L/V) of fibroblastic granular tissue and trabeculae, caliber C, and flow velocity u, all as functions of time. Observations supported the conclusions that (1) neovascularization precedes neo-osteogenesis, (2) major vessels tend to align with the tibial axis, (3) bone apposition-generated destruction of fibrous granular tissue vessels stimulates fibrous granular tissue angiogenesis, which keeps its L/V constant, (4) L/V in trabeculae increases with time, and (5) blood supply (Q) and nutrient exchange in healing trabeculae are not positively correlated. Thus, O2 supply to the trabeculum cannot be predicted from Q alone because the nutrient exchange area is not constant. It was noted that an increase in the potential nutrient exchange area occurred in both fibrous granular tissue and osseous vessels and the volume fraction of blood decreased in the fibrous granular tissue and remained constant in the trabeculae.

Human sperm motility response to three mechanical stimuli, gravity, fluid flow shear and rigid boundaries, was measured in a tube of 310 X 400 microns calibre. Data were gathered by cine recordings at various focussing levels d across the tube and analysed with a computerized image analysis system. The most influential stimulus was the tube wall near (more than 'at') which the swimmers tended to accumulate, leaving the fluid beyond 100 microns from the wall (d = 100) vacant of motile spermatozoa. The boundary effect was evident as soon as the spermatozoa could be viewed after loading, and accumulation, measured as frequency, as a function of d did not change with time t. This response was not significantly altered by the addition of laminar flow with a centre line velocity of about 400 microns/sec. In flow shear, spermatozoa aligned positively (in the flow direction) at the wall but negatively by about 30 microns from the wall where the velocity gradient (= shear rate) was about 3.5 sec-1. The response to gravity was relatively weak with 11 spermatozoa positive (swimming downwards) for each 9 negative. Neither the boundary effect nor the 'rheotaxic' effect were influenced by gravity as there was no statistical difference in orientation or distribution patterns between vertically and horizontally flowing suspensions. It is suggested that the boundary effect cannot be ignored in in-vitro manipulations, particularly when spermatozoa are observed or extracted. Its importance in vivo lies in the degree to which the tubes transporting motile spermatozoa seem to have mechanisms for reversing the wall accumulation tendency.