Influence of in vitro maturation of engineered cartilage on the outcome of osteochondral repair in a goat model.

This study was designed to determine if the maturation stage of engineered cartilage implanted in a goat model of cartilage injury influences the repair outcome. Goat engineered cartilage was generated from autologous chondrocytes cultured in hyaluronic acid scaffolds using 2 d, 2 weeks or 6 weeks of pre-culture and implanted above hydroxyapatite/hyaluronic acid sponges into osteochondral defects. Control defects were left untreated or treated with cell-free scaffolds. The quality of repair tissues was assessed 8 weeks or 8 months post implantation by histological staining, modified O'Driscoll scoring and biochemical analyses. Increasing pre-culture time resulted in progressive maturation of the grafts in vitro. After 8 weeks in vivo, the quality of the repair was not improved by any treatment. After 8 months, O'Driscoll histology scores indicated poor cartilage architecture for untreated (29.7 ± 1.6) and cell-free treated groups (24.3 ± 5.8). The histology score was improved when cellular grafts were implanted, with best scores observed for grafts pre-cultured for 2 weeks (16.3 ± 5.8). As compared to shorter pre-culture times, grafts cultured for 6 weeks (histology score: 22.3 ± 6.4) displayed highest type II/I collagen ratios but also inferior architecture of the surface and within the defect, as well as lower integration with native cartilage. Thus, pre-culture of engineered cartilage for 2 weeks achieved a suitable compromise between tissue maturity and structural/integrative properties of the repair tissue. The data demonstrate that the stage of development of engineered cartilage is an important parameter to be considered in designing cartilage repair strategies.

Interleukin-1ß enhances cartilage-to-cartilage integration.

The failure of cartilages to fuse, particularly in the case of articular cartilage under conditions of repair is due to morphological and structural constraints of the tissue. Factors that impede integration include, non-vascularisation, low cellularity, and proteoglycan in the surrounding extracellular matrix acting as a natural barrier to cellular migration. We hypothesised that brief activation of a catabolic cascade by cytokines followed by culture under anabolic conditions would promote tissue fusion in a ring-disk model of cartilage integration. Our results show that transient exposure to 10 ng mL(-1) interleukin-1ß, followed by two weeks post-culture under anabolic conditions, enhanced cartilage-cartilage integration compared to untreated explants. Quantitative PCR analysis of catabolism-related genes ADAMTS4 and MMP13 showed both were transiently upregulated and these findings correlated with evidence of extracellular matrix remodelling. At the level of histology, we observed chondrocytes readily populated the interfacial matrix between fused explants in interleukin-1ß treated explants, whereas in control explants this region was relatively acellular in comparison. Catabolic cytokine treated explants exhibited 29-fold greater adhesive strength (0.859 MPa versus 0.028 MPa, P 〈 0.05) than untreated counterparts. Collectively, our results demonstrate that a single short catabolic pulse followed by an anabolic response is sufficient to generate mechanically robust, integrative cartilage repair.

Regulation of osteoarthritis by omega-3 (n-3) polyunsaturated fatty acids in a naturally occurring model of disease.

OBJECTIVE: To examine effects of high omega-3 (n-3) polyunsaturated fatty acid (PUFA) diets on development of osteoarthritis (OA) in a spontaneous guinea pig model, and to further characterise pathogenesis in this model. Modern diets low in n-3 PUFAs have been linked with increases in inflammatory disorders, possibly including OA. However, n-3 is also thought to increases bone density, which is a possible contributing factor in OA. Therefore we aim to determine the net influence of n-3 in disease development. METHOD: OA-prone Dunkin-Hartley (DH) Guinea pigs were compared with OA-resistant Bristol Strain-2s (BS2) each fed a standard or an n-3 diet from 10 to 30 weeks (10/group). We examined cartilage and subchondral bone pathology by histology, and biochemistry, including collagen cross-links, matrix metalloproteinases (MMPs), alkaline phosphatase, glycosaminoglycan (GAG), and denatured type II collagen. RESULTS: Dietary n-3 reduced disease in OA-prone animals. Most cartilage parameters were modified by n-3 diet towards those seen in the non-pathological BS2 strain - significantly active MMP-2, lysyl-pyridinoline and total collagen cross-links - the only exception being pro MMP-9 which was lower in the BS2, yet increased with n-3. GAG content was higher and denatured type II lower in the n-3 group. Subchondral bone parameters in the DH n-3 group also changed towards those seen in the non-pathological strain, significantly calcium:phosphate ratios and epiphyseal bone density. CONCLUSION: Dietary n-3 PUFA reduced OA in the prone strain, and most disease markers were modified towards those of the non-OA strain, though not all significantly so. Omega-3 did not increase markers of pathology in either strain.

Type II and VI collagen in nasal and articular cartilage and the effect of IL-1alpha on the distribution of these collagens.

The distribution of type II and VI collagen was immunocytochemically investigated in bovine articular and nasal cartilage. Cartilage explants were used either fresh or cultured for up to 4 weeks with or without interleukin 1alpha (IL-1alpha). Sections of the explants were incubated with antibodies for both types of collagen. Microscopic analyses revealed that type II collagen was preferentially localized in the interchondron matrix whereas type VI collagen was primarily found in the direct vicinity of the chondrocytes. Treatment of the sections with hyaluronidase greatly enhanced the signal for both types of collagen. Also in sections of explants cultured with IL-1alpha a higher level of labeling of the collagens was found. This was apparent without any pre-treatment with hyaluronidase. Under the influence of IL-1alpha the area positive for type VI collagen that surrounded the chondrocytes broadened. Although the two collagens in both types of cartilage were distributed similarly, a remarkable difference was the higher degree of staining of type VI collagen in articular cartilage. Concomitantly we noted that digestion of this type of cartilage hardly occurred in the presence of IL-1alpha whereas nasal cartilage was almost completely degraded within 18 days of culture. Since type VI collagen is known to be relatively resistant to proteolysis we speculate that the higher level of type VI collagen in articular cartilage is important in protecting cartilage from digestion.

The effect of growth factor treatment on meniscal chondrocyte proliferation and differentiation on polyglycolic acid scaffolds.

The aim of this investigation was to determine the effect of growth factor treatment on ovine meniscal chondrocyte (OMC) proliferation in vitro and on the production of matrix proteins by OMCs grown within a polyglycolic acid (PGA) scaffold. Analysis of 72-h monolayer cultures using the mean transit time (MTT) assay revealed a greater increase in OMC numbers in the presence of platelet-derived growth factor (PDGF)-AB, PDGF-BB, insulin-like growth factor (IGF)-I, transforming growth factor-beta1 (TGF-beta1) and basic fibroblast growth factor (bFGF) than in untreated controls. In contrast, IGF-II and bone morphogenetic protein-2 had no effect on OMC proliferation at the concentrations tested. The growth factors that elicited the greatest proliferative response (PDGF-AB, PDGF-BB, TGF-beta1, and IGF-I) were subsequently tested for their ability to enhance OMC proliferation and differentiation within PGA scaffolds. Biochemical analysis revealed less glycosaminoglycan (GAG) production in the presence of all growth factors tested compared to untreated control samples. In contrast, all of the growth factors increased collagen type I production by OMCs within the scaffolds at day 20, and all except PDGF-BB resulted in an increase at day 39, when compared to appropriate control samples. With the exception of IGF-I, none of the growth factors tested had any significant effect on collagen type II production. Histological staining of sections from OMC-PGA scaffolds did not reveal any difference in GAG or collagen production between the treatment groups. However, immunohistochemical analysis demonstrated an increase in collagen type I expression and a decrease in collagen type II at day 39 in all growth factortreated constructs, concomitant with a high infiltration of cells. This suggests that PDGF-AB, PDGF-BB, TGF-beta1, and IGF-1 may be useful in future tissue engineering studies for promoting meniscal cell proliferation and differentiation within scaffolds.

The individual relationship between heart rate and oxygen uptake in people with a tetraplegia during exercise.

STUDY DESIGN: Descriptive study. OBJECTIVE: To examine the individual heart rate-oxygen uptake (HR-VO(2)) relationship during exercise in persons with tetraplegia (TP). SETTING: Rehabilitation Centre Heliomare, Wijk aan Zee, The Netherlands. METHODS: The HR-VO(2) relationship was determined in untrained subjects with motor complete TP (C5 or C6, n=10 and C7 or C8, n=10) during a discontinuous graded exercise hand cycle test. The mean HR and VO(2) of the final 60 s of 2-min exercise blocks were used for calculation of the individual correlation coefficient and the standard error of the estimate (SEE). RESULTS: Two subjects of the C5-C6 group were not able to complete the test. Individual Pearson's correlation coefficients (r) ranged from 0.68 to 0.97 and SEE from 2.6 to 22.4% VO(2)-Reserve (VO(2)R). The mean Pearson's r and SEE were 0.81+/-0.12 and 10.6+/-5.6% VO(2)R in the C5-C6 group and 0.91+/-0.07 and 7.0+/-3.2% VO(2)R in the C7-C8 group, respectively. Two subjects of the C5-C6 group and six subjects of the C7-C8 group attained a linear HR-VO(2) relationship with an acceptable SEE (< or =6.0%) and r (>0.90). CONCLUSIONS: The HR-VO(2) relationship appeared linear in only eight out of 18 subjects. An individual analysis of the HR-VO(2) relationship is necessary to determine whether HR can be used to quantify exercise intensity. The use of HR to prescribe training intensity should be reconsidered in persons with TP. SPONSORSHIP: This study is supported from a grant by ZON-MW.

Cartilage tissue engineering by expanded goat articular chondrocytes.

In this study we investigated whether expanded goat chondrocytes have the capacity to generate cartilaginous tissues with biochemical and biomechanical properties improving with time in culture. Goat chondrocytes were expanded in monolayer with or without combinations of FGF-2, TGF-beta1, and PDGFbb, and the postexpansion chondrogenic capacity assessed in pellet cultures. Expanded chondrocytes were also cultured for up to 6 weeks in HYAFF-M nonwoven meshes or Polyactive foams, and the resulting cartilaginous tissues were assessed histologically, biochemically, and biomechanically. Supplementation of the expansion medium with FGF-2 increased the proliferation rate of goat chondrocytes and enhanced their postexpansion chondrogenic capacity. FGF-2-expanded chondrocytes seeded in HYAFF-M or Polyactive scaffolds formed cartilaginous tissues with wet weight, glycosaminoglycan, and collagen content, increasing from 2 days to 6 weeks culture (up to respectively 2-, 8-, and 41-fold). Equilibrium and dynamic stiffness measured in HYAFF M-based constructs also increased with time, up to, respectively, 1.3- and 16-fold. This study demonstrates the feasibility to engineer goat cartilaginous tissues at different stages of development by varying culture time, and thus opens the possibility to test the effect of maturation stage of engineered cartilage on the outcome of cartilage repair in orthotopic goat models.

Human nasal cartilage responds to oncostatin M in combination with interleukin 1 or tumour necrosis factor alpha by the release of collagen fragments via collagenases.

BACKGROUND: The synergistic degradation of cartilage by oncostatin M (OSM) in combination with either interleukin 1 (IL1) or tumour necrosis factor alpha (TNFalpha) has been previously demonstrated using bovine nasal cartilage (BNC). OBJECTIVES: (a) To investigate if human nasal cartilage (HNC) responds in the same way as BNC to these cytokine combinations, particularly in collagen degradation. (b) To compare the response of human nasal and articular cartilages. METHODS: Collagen release was assessed by measuring the hydroxyproline content of culture supernatants and proteoglycan release by the dimethylmethylene blue assay. Matrix metalloproteinase (MMP)-1, MMP-13, and tissue inhibitor of metalloproteinase 1 release were measured by specific enzyme linked immunosorbent assays (ELISAs), and collagenolytic activity was measured by a bioassay using radiolabelled collagen. RESULTS: OSM in combination with either IL1 or TNFalpha acted synergistically to induce collagenolysis from HNC, with a maximum of 79% collagen release. This degradation strongly correlated with MMP-1 and MMP-13 levels and collagenolytic activity. CONCLUSION: Collagen release from human cartilage is marked and implicates both MMP-1 and MMP-13 in the synergistic degradation of human cartilage by OSM in combination with either IL1 or TNFalpha. HNC responds in the same way as BNC, thus validating the bovine cartilage degradation assay as a model relevant to human disease.

Polymer scaffolds fabricated with pore-size gradients as a model for studying the zonal organization within tissue-engineered cartilage constructs.

The zonal organization of cells and extracellular matrix (ECM) constituents within articular cartilage is important for its biomechanical function in diarthroidal joints. Tissue-engineering strategies adopting porous three-dimensional (3D) scaffolds offer significant promise for the repair of articular cartilage defects, yet few approaches have accounted for the zonal structural organization as in native articular cartilage. In this study, the ability of anisotropic pore architectures to influence the zonal organization of chondrocytes and ECM components was investigated. Using a novel 3D fiber deposition (3DF) technique, we designed and produced 100% interconnecting scaffolds containing either homogeneously spaced pores (fiber spacing, 1 mm; pore size, about 680 microm in diameter) or pore-size gradients (fiber spacing, 0.5-2.0 mm; pore size range, about 200-1650 microm in diameter), but with similar overall porosity (about 80%) and volume fraction available for cell attachment and ECM formation. In vitro cell seeding showed that pore-size gradients promoted anisotropic cell distribution like that in the superficial, middle, and lower zones of immature bovine articular cartilage, irrespective of dynamic or static seeding methods. There was a direct correlation between zonal scaffold volume fraction and both DNA and glycosaminoglycan (GAG) content. Prolonged tissue culture in vitro showed similar inhomogeneous distributions of zonal GAG and collagen type II accumulation but not of GAG:DNA content, and levels were an order of magnitude less than in native cartilage. In this model system, we illustrated how scaffold design and novel processing techniques can be used to develop anisotropic pore architectures for instructing zonal cell and tissue distribution in tissue-engineered cartilage constructs.

Influence of task complexity on mechanical efficiency and propulsion technique during learning of hand rim wheelchair propulsion.

OBJECTIVE: To investigate the consequence of task complexity on gross mechanical efficiency and propulsion technique during the learning process of hand rim wheelchair propulsion. METHODS: Three groups of unimpaired subjects (N=10 each) received a 3-week wheelchair practice period (3 week(-1), nine practice trials) with different levels of complexity, i.e. propelling a stationary wheelchair ergometer, wheelchair propulsion on a motor-driven treadmill or at a circular wheelchair track. During practice trials 1 and 9, gross mechanical efficiency and propulsion technique variables (work per cycle, cycle frequency, push and cycle time, effective force) were measured. RESULTS: Using multi-level regression analysis, no differences in the development over time in mechanical efficiency and propulsion technique could be discerned between the three conditions of task complexity. Only the percentage push time during the cycle decreased significantly more in the group that practiced on the ergometer compared to the treadmill-practice group. For all three groups a change over time was shown for cycle frequency, push time and cycle time. DISCUSSION: Under the current experimental conditions, task complexity does not have an influence on gross mechanical efficiency and propulsion technique during the learning process of wheelchair propulsion. The 3-week practice period had a favorable practice effect on timing regardless of the task complexity.

Effect of matrix depleting agents on the expression of chondrocyte metabolism by equine chondrocytes.

This study was carried out to investigate the effect of two enzymes (collagenase and chondroitinase) and two cytokines/metabolites (interleukin-1beta and retinoic acid) of known catabolic activity on the expression of cartilage metabolism/phenotype in equine articular cartilage. Articular cartilage explants from 11 horses (5-13 years old) were treated for 48 h and assayed for total sulphated glycosaminoglycan (GAG), the incorporation of 35S-sulphate, collagen degradation and mRNA expression of the proteoglycans collagen II, collagen IIA, collagen III, collagen IX, collagen X, collagen XI and glyceraldehyde-3-phosphate (GAPDH). Purified collagenase and retinoic acid were responsible for increased GAG loss from the tissues. Chondroitinase, responsible for catalysing the elimination of glucuronate residues from chondroitin A, B and C (Chondroitinase ABC) and retinoic acid treatment induced an inhibition of proteoglycan synthesis, whereas collagenase treatment did not. Collagenase activity was correlated with increased appearance of the CB11B epitope and type II collagen denaturation. By RT-PCR there was evidence of expression of altered collagen type IIA in purified collagenase treated tissues.

Effect of wheelchair stroke pattern on mechanical efficiency.

OBJECTIVE: To investigate the effect of different wheelchair stroke patterns on efficiency and propulsion technique (force application and timing). DESIGN: Inexperienced, able-bodied subjects were randomly divided into two velocity groups (1.11 m/sec [n = 13] and 1.39 m/sec [n = 11]). An external (medium) load was set at 0.23 N/kg. Subjects performed four 4-min exercise blocks on a wheelchair ergometer. The first block was performed with a freely chosen movement pattern of the hand. Thereafter, the pumping, semicircular, or single-looping over propulsion pattern were performed in a counterbalanced order. Gross mechanical efficiency and propulsion technique variables were measured with Oxycon Alpha and an instrumented wheelchair ergometer. RESULTS: A significant difference was found for mechanical efficiency, with pumping showing the highest efficiency and semicircular the lowest efficiency, regardless of velocity. Timing variables and negative power deflections before and after the push phase showed significant differences between the stroke patterns. CONCLUSIONS: Pumping is the energetically most efficient stroke pattern in contrast to the semicircular pattern in this subject group. Propulsion technique could not explain the difference in efficiency.

The effects of 11 weeks whole body vibration training on jump height, contractile properties and activation of human knee extensors.

The purpose of the present study was to investigate whether 11 weeks of whole body vibration (WBV) training applied in a way that is commonly seen in practice, i.e. without additional loads, would improve muscle activation and/or contractile properties of the knee extensor muscles and counter movement jump height in healthy subjects. Ten subjects belonging to the experimental group trained three times a week and stood bare-foot with a 110 degrees knee angle on a vibration platform (30 Hz, 8 mm amplitude). They underwent five to eight sets of 1-min vibration with 1 min rest in between. Ten control subjects followed the same training programme but stood (110 degrees knee angle) beside the platform. Before, during and following the training period the subjects were tested. Values [mean (SEM)] obtained in the last test were expressed as percentages of the baseline value and presented for control and experimental groups. Quadriceps femoris isometric muscle force [105.4 (6.2)%, 99.9 (2.0)%; P=0.69], voluntary activation [107.1 (6.0)%, 101.1 (2.3)%; P=0.55] and maximal rate of voluntary force rise [95.4 (6.0)%, 103.3 (7.7)%; P=0.57] did not improve. The maximal rate of force rise during electrical stimulation was increased [102.3 (4.5)%, 123.6 (7.5)%; P=0.02]. Counter movement jump height was not affected by WBV [103.7 (1.8)%, 103.0 (2.8)%; P=0.71]. In conclusion, 11 weeks of standard two-legged WBV training without additional training loads did not improve functional knee extensor muscle strength in healthy young subjects.

Adaptations in physiology and propulsion techniques during the initial phase of learning manual wheelchair propulsion.

OBJECTIVE: The purpose of this study was to analyze adaptations in gross mechanical efficiency and wheelchair propulsion technique in novice able-bodied subjects during the initial phase of learning hand-rim wheelchair propulsion. DESIGN: Nine able-bodied subjects performed three 4-min practice blocks on a wheelchair ergometer. The external power output and velocity of all blocks was, respectively, 0.25 W/kg and 1.11 m/sec. Gross mechanical efficiency, force application, timing, and intercycle variability were measured. RESULTS: No change in gross mechanical efficiency was found. However, a decrease in push frequency occurred, which was accompanied by an increase in work per cycle and a decrease in percentage push time. The increase in work per cycle was associated with a higher peak torque. No changes in intercycle variability were visible over time. CONCLUSIONS: The timing variables had already changed during the initial phase of learning manual wheelchair propulsion. However, for other variables, such as force production, gross mechanical efficiency, and intercycle variability, a longer practice period might be necessary to induce a change. The effective force direction seemed to be optimized from the start of the learning process onward.

Short-term adaptations in co-ordination during the initial phase of learning manual wheelchair propulsion.

The purpose of this study was to analyse adaptations in kinematics and muscle activity/co-contraction in novice able-bodied subjects during the initial phase of learning hand rim wheelchair propulsion. Nine able-bodied subjects performed three 4-min practice blocks on a wheelchair ergometer. The external power output and velocity were constant for all blocks, respectively 0.25 W x kg(-1) and 1.11 m x s(-1). Electromyography of 16 arm, shoulder, back and chest muscles and kinematics were measured. Some small changes in the segmental movement pattern were seen during the practice period. Moreover, an increase in muscle activity and co-contraction of several muscles was found over time. The hypothesis that subjects instinctively search for an optimum frequency, in which the recovery phase is related to the eigenfrequency of the arms and, therefore, the least muscle activity, could not be supported. Since co-contraction of antagonist pairs remained the same or even increased, the hypothesis that there would be a decrease in muscle co-contraction as a result of practice, was not confirmed. This study was probably too short for the novice subjects to explore this new task of wheelchair propulsion completely and reach an optimum in terms of cycle frequency and muscle activity/co-contraction.

Short-term effects of whole-body vibration on maximal voluntary isometric knee extensor force and rate of force rise.

Whole-Body vibration (WBV) may lead to muscle contractions via reflex activation of the primary muscle spindle (Ia) fibres. WBV has been reported to increase muscle power in the short term by improved muscle activation. The present study set out to investigate the acute effects of a standard WBV training session on voluntary activation during maximal isometric force production (MVC) and maximal rate of force rise (MRFR) of the knee extensors. Twelve students underwent a single standard WBV training session: 5x1 min vibration (frequency 30 Hz, amplitude 8 mm) with 2 min rest in between. During vibration, subjects stood barefoot on the vibration platform with their knees at an angle of 110 degrees. At 90 s following vibration, maximal voluntary knee extensor force was reduced to 93 (5)% [mean (SD), P<0.05] of baseline value and recovered within the next 3 h. Voluntary activation remained significantly depressed (2-4%). Neither the electrically induced MRFR nor voluntary MRFR were significantly affected by WBV. In addition, six WBV training sessions in 2 weeks ( n=10) did not enhance either voluntary muscle activation during MVC [99 (2)% of the baseline value] or voluntary MRFR [98 (9)% of the baseline value]. It is concluded that in the short term, WBV training does not improve muscle activation during maximal isometric knee extensor force production and maximal rate of force rise in healthy untrained students.

Differences in leg muscle activity during running and cycling in humans.

Delta (delta) efficiency is defined as the ratio of an increment in the external mechanical power output to the increase in metabolic power required to produce it. The purpose of the present study was to investigate whether differences in leg muscle activity between running and cycling can explain the observed difference in delta efficiency between the two activities. A group of 11 subjects performed incremental submaximal running and cycling tests on successive days. The delta efficiencies during running and cycling were based on five exercise stages. Electromyograph (EMG) measurements were made of three leg muscles (gastrocnemius, vastus lateralis and biceps femoris). Kendall's correlation coefficients between the mean EMG activity and the load applied were calculated for each muscle, for both running and cycling. As expected, the mean delta efficiency during running (42%) was significantly greater than that during cycling (25%). For cycling, all muscles showed a significant correlation between mean EMG activity and the load applied. For running, however, only the gastrocnemius muscle showed a significant, but low correlation ( r=0.33). The correlation coefficients of the vastus lateralis and biceps femoris muscles were not significantly different from 0. The results were interpreted as follows. In contrast to cycling, which includes only concentric contractions, during running up inclines eccentric muscle actions play an important role. With steeper inclines, more concentric contractions must be produced to overcome the external force, whereas the amount of eccentric muscle actions decreases. This change in the relative contribution of concentric and eccentric muscle actions, in combination with the fact that eccentric muscle actions require much less metabolic energy than concentric contractions, can explain the difference between the running and cycling delta efficiency.

Consequence of feedback-based learning of an effective hand rim wheelchair force production on mechanical efficiency.

OBJECTIVE: Investigation of the effect of visual feedback on effective hand rim wheelchair force production and the subsequent effect on gross mechanical efficiency. DESIGN: Ten subjects in an experimental group and 10 subjects in a control group practised three weeks (3.wk(-1), i.e., a pre-test and 8 trials) on a computer-controlled wheelchair ergometer. Every trial consisted of two blocks of 4 min at 0.15 and 0.25 W.kg(-1) at 1.11 m.s(-1). On three trials an additional block at 0.40 W.kg(-1) was performed. The experimental group practised with and the control group practised without visual feedback on the effectiveness of force production. BACKGROUND: In mechanical terms, the low gross mechanical efficiency of hand rim wheelchair propulsion may be the result of ineffective force production. METHODS: During all trials oxygen uptake, power output, forces and torque on the hand rims were measured. RESULTS: In comparison with the control group, the experimental group at trial 8 had a significantly more effective force production compared to the control group (90-97% vs. 79-83%, respectively), but showed a significantly lower mechanical efficiency (5.5-8.5% vs. 5.9-9.9%, respectively). CONCLUSION: Findings indicate that the most effective force production from a mechanical point of view is not necessarily the most efficient way--in terms of energy cost-- from a biological point of view and that force direction is based on an optimization of cost and effect. RELEVANCE: Learning a more effective force production by visual feedback is not useful for increasing the mechanical efficiency of hand rim wheelchair propulsion.

Matrix turnover in human cartilage repair tissue in autologous chondrocyte implantation.

OBJECTIVE: Autologous chondrocyte implantation (ACI) is a form of tissue engineering that is being used increasingly to treat damaged articular cartilage. What happens at the graft site subsequent to the transplantation of chondrocytes beneath a periosteal flap has largely remained a matter of conjecture. We examined biopsy samples from the graft site using a panel of specific antibodies to investigate the cellular mechanisms involved and to determine whether remodeling of the matrix occurs. METHODS: Ten full-depth core biopsy samples were obtained from patients who had undergone ACI 9-30 months previously (ages 28-53 years), in addition to 6 "control" biopsy samples. Cryosections were evaluated by standard histologic examination using polarized light and immunohistochemistry. Antibodies specific for type II collagen (CIIC1) were used, as well as antibodies against the C-propeptide of type II collagen (R160) and its denaturation product (Col2-3/4m), as indicators of anabolism or catabolism. In addition, antibodies to the matrix proteinase-generated neoepitopes of the aggrecan core protein were used to demonstrate either aggrecanase (BC-3 and BC-13) or matrix metalloproteinase (MMP) (BC-4 and BC-14) activity. RESULTS: All biopsy samples stained for type II collagen, even in areas of fibrocartilaginous morphology. There was evidence of newly synthesized type II collagen in addition to denatured collagen. MMP and aggrecanase activity on the proteoglycan population was evident, with aggrecanase being more active in fibrocartilaginous areas. CONCLUSION: The findings of this study indicate that ACI is capable of not only cartilage repair but, in some cases, regeneration. This may be achieved by the turnover and remodeling of an initial fibrocartilaginous matrix via enzymatic degradation and synthesis of newly formed type II collagen.

Delta efficiencies of running and cycling.

PURPOSE: The purpose of the present study was to compare delta efficiencies of running with cycling, while several factors that can possibly influence delta efficiency were excluded. METHODS: Twelve subjects performed a submaximal running and cycling test on subsequent days. Delta efficiencies of running and cycling were compared at equal metabolic intensities. Furthermore, rest periods were included in the protocol to avoid fatigue. Pedaling and stride frequencies were held constant during the tests. Finally, the influence of two ways of applying extra external load (inclination of treadmill and horizontal impeding forces) on the delta efficiency of running and cycling was investigated. RESULTS: The results of the present study show that the mean delta efficiency of running (45.5%) is still significantly higher than the mean delta efficiency of cycling (25.7%). The way extra external load is applied does not influence delta efficiency. CONCLUSION: The way of loading and the difference in metabolic intensity can be excluded as causes for the observed difference in delta efficiency between running and cycling. It is suggested that a different contribution in the metabolic load attributable to muscular activity of the arms and/or trunk that does not directly contribute to the work needed to overcome the amount of applied external load may be a relevant factor.