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Biomedical subjects

David L Butler

Publications and source records attributed to David L Butler.

15 recordsLinked to original sources
PubMed2006

The effect of gamma irradiation on anterior cruciate ligament allograft biomechanical and biochemical properties in the caprine model at time zero and at 6 months after surgery.

BACKGROUND: High levels of gamma irradiation are required to eliminate the risk of bacterial and viral transmission during implantation of musculoskeletal allografts. The effects of high levels of gamma irradiation on anterior cruciate ligament allograft biomechanics are still not known. HYPOTHESIS: High-dose gamma irradiation (4 Mrad) adversely affects anterior cruciate ligament allograft biomechanics at surgery and at 6 months after surgery and affects biochemistry at 6 months. STUDY DESIGN: Controlled laboratory study. METHODS: Bilateral anterior cruciate ligament reconstructions were performed in 18 adult goats, with one knee receiving an irradiated patellar tendon allograft (4 Mrad) and the other receiving a frozen control allograft (0 Mrad). In 6 recipients (time zero group), graft pairs were tested immediately after sacrifice, and load relaxation of the femur-allograft-tibia preparation was measured during cyclic anterior displacement. Twelve recipients received bilateral anterior cruciate ligament reconstructions, staged 2 months apart, and were sacrificed a mean of 6 months postoperatively. Load relaxation and tensile failure testing were performed, followed by allograft biochemistry assessment. RESULTS: At time zero, irradiated grafts showed less load relaxation than did contralateral controls, but by 6 months, the trend had reversed because of decreases in control graft relaxation, with no changes in irradiated graft relaxation. By 6 months, irradiated grafts showed lower stiffness and maximum force compared to controls but no differences in modulus, maximum stress, or biochemistry. CONCLUSION: High levels of gamma irradiation affect anterior cruciate ligament allograft subfailure viscoelastic and structural properties but not material or biochemical properties over time. CLINICAL RELEVANCE: Although high levels of gamma irradiation may inactivate infectious agents, this treatment is not a feasible clinical option because of altered allograft biomechanics.

Animals↗
PubMed2006

Effects of cell seeding density and collagen concentration on contraction kinetics of mesenchymal stem cell-seeded collagen constructs.

Our group has been engineering cell-scaffold constructs to improve tendon repair by contracting mesenchymal stem cells (MSCs) in collagen gels and then evaluating their repair potential in wound sites in rabbits. Because the construct's initial conditions may influence the ultimate repair outcome, this two-part study sought to distinguish which factors most influence contraction kinetics in culture. (1)We optically determined if varying cell-to-collagen ratio significantly affected construct contraction. Temporal changes in construct area were monitored up to 168 h for 4 cell-to-collagen ratios (HK = 0.04, LK = 0.08, HM = 0.4, and LM = 0.8, where H, L = 2.6, 1.3 mg/mL collagen and K,M = 0.1, 1 million cells/mL, respectively).A mathematical model was created with terms that represent the different combinations of cell densities and collagen concentrations in order to predict the contraction kinetics as a function of time. Highly significant differences in construct areas were found among all 4 ratios after 8 h of contraction with the exception of the LK (0.08) vs. HM(0.4) conditions. This similar pattern raised the question of whether cell density or collagen concentration more influenced these events. (2) To isolate these effects, the contraction kinetics of the HM construct were compared to those of a new construct (L5K) with equivalent cell-to-collagen ratio (0.4) but half the cell density (500 K MSCs/mL) and half the collagen concentration (1.3 mg/mL). The L5K construct contracted significantly faster and more completely than the HM construct but no differently than the LM construct. These results indicate that above a threshold value of cell density, percentage reductions in collagen concentration influence contraction kinetics more than equivalent percentage increases in cell seeding density. The fact that our model successfully predicted intermediate time points of contraction suggests its utility for examining other cell and collagen densities. Controlling scaffold as well as cellular initial conditions will be critical in achieving our goal of functional tissue engineering (FTE) a successful tendon repair.

Animals↗
PubMed2006

Effects of mechanical stimulation on the biomechanics and histology of stem cell-collagen sponge constructs for rabbit patellar tendon repair.

The objective of this study was to determine how mechanical stimulation affects the biomechanics and histology of stem cell-collagen sponge constructs used to repair central rabbit patellar tendon defects. Autogenous tissue-engineered constructs were created for both in vitro and in vivo analyses by seeding mesenchymal stem cells from 10 adult rabbits at 0.14x10(6) cells/construct in type I collagen sponges. Half of these constructs were mechanically stimulated once every 5 min for 8 h/day to a peak strain of 4% for 2 weeks. The other half remained in an incubator without mechanical stimulation for 2 weeks. Samples allocated for in vitro testing revealed that mechanically stimulated constructs had 2.5 times the linear stiffness of nonstimulated constructs. The remaining paired constructs for in vivo studies were implanted in bilateral full-thickness, full-length defects in the central third of rabbit patellar tendons. Twelve weeks after surgery, repair tissues were assigned for biomechanical (7 pairs) and histologic (3 pairs) analyses. Maximum force, linear stiffness, maximum stress, and linear modulus for the stimulated (vs. nonstimulated) repairs averaged 70% (vs. 55%), 85% (vs. 55%), 70% (vs. 50%), and 50% (vs. 40%) of corresponding values for the normal central third of the patellar tendons. The average force-elongation curve for the mechanically stimulated repairs also matched the corresponding curve for the normal patellar tendons, up to 150% of the peak in vivo force values recorded in a previous study. Construct and repair linear stiffness and linear modulus were also positively correlated (r = 0.6 and 0.7, respectively). Histologically both repairs showed excellent cellular alignment and mild staining for decorin and collagen type V, and moderate staining for fibronectin and collagen type III. This study shows that mechanical stimulation of stem cell-collagen sponge constructs can significantly improve tendon repair biomechanics up to and well beyond the functional limits of in vivo loading.

Animals↗
PubMed2006

The effect of autologous mesenchymal stem cells on the biomechanics and histology of gel-collagen sponge constructs used for rabbit patellar tendon repair.

The objective of this study was to introduce mesenchymal stem cells (MSCs) into a gel-sponge composite and examine the effect the cells have on repair biomechanics and histology 12 weeks postsurgery. We tested two related hypotheses-adding MSCs would significantly improve repair biomechanics and cellular organization, and would result in higher failure forces than peak in vivo patellar tendon (PT) forces recorded for an inclined hopping activity. Autogenous tissue-engineered constructs were created by seeding MSCs from 15 adult rabbits at 0.1 x 10(6) cells/mL in 2.6 mg/mL of collagen gel in collagen sponges. Acellular constructs were created using the same concentration of collagen gel in matching collagen sponges. These cellular and acellular constructs were implanted in bilateral full-thickness, full-length defects in the central third of patellar tendons. At 12 weeks after surgery, repair tissues were assigned for biomechanical (n = 12 pairs) and histological (n = 3 pairs) analyses. Maximum force and maximum stress for the cellular repairs were about 60 and 50% of corresponding values for the normal central third of the PT, respectively. Likewise, linear stiffness and linear modulus for these cellular repairs averaged 75 and 30% of normal PT values, respectively. By contrast, the acellular repairs exhibited lower percentages of normal PT values for maximum force (40%), maximum stress (25%), linear stiffness (30%), and linear modulus (20%). Histologically, both repairs showed strong staining for collagen types III and V, fibronectin, and decorin. The cellular repairs also showed cellular alignment comparable to that of normal tendon. This study shows that introducing autogenous mesenchymal stem cells into a gel-collagen sponge composite significantly improves tendon repair compared to the use of a gel-sponge composite alone in the range of in vivo loading.

Animals↗
PubMed2006

Effects of cell-to-collagen ratio in stem cell-seeded constructs for Achilles tendon repair.

The objective of the present study was to test the hypotheses that implantation of cell-seeded constructs in a rabbit Achilles tendon defect model would 1) improve repair biomechanics and matrix organization and 2) result in higher failure forces than measured in vivo forces in normal rabbit Achilles tendon (AT) during an inclined hopping activity. Autogenous tissue-engineered constructs were fabricated in culture between posts in the wells of silicone dishes at four cell-to-collagen ratios by seeding mesenchymal stem cells (MSC) from 18 adult rabbits at each of two seeding densities (0.1 x 10(6) and 1 x 10(6) cell/mL) in each of two collagen concentrations (1.3 and 2.6 mg/mL). After 5 days of contraction, constructs having the two highest ratios (0.4 and 0.8 M/mg) were damaged by excessive cell traction forces and could not be used in subsequent in vivo studies. Constructs at the lower ratios (0.04 and 0.08 M/mg) were implanted in bilateral, 2 cm long gap defects in the rabbit's lateral Achilles tendon. At 12 weeks after surgery, both repair tissues were isolated and either failed in tension (n = 13) to determine their biomechanical properties or submitted for histological analysis (n = 5). No significant differences were observed in any structural or mechanical properties or in histological appearance between the two repair conditions. However, the average maximum force and maximum stress of these repairs achieved 50 and 85% of corresponding values for the normal AT and exceeded the largest peak in vivo forces (19% of failure) previously recorded in the rabbit AT. Average stiffness and modulus were 60 and 85% of normal values, respectively. New constructs with lower cell densities and higher scaffold stiffness that do not excessively contract and tear in culture and that further improve the repair stiffness needed to withstand various levels of expected in vivo loading are currently being investigated.

Achilles Tendon↗
PubMed2005

Meniscal material properties are minimally affected by matrix stabilization using glutaraldehyde and glycation with ribose.

Knee meniscus replacement holds promise, but current allografts are susceptible to biodegradation. Matrix stabilization with glutaraldehyde, a crosslinking agent used clinically to fabricate cardiovascular bioprostheses, or with glycation, a process of crosslinking collagen with sugars such as ribose, is a potential means of rendering tissue resistant to such degradation. However, stabilization should not significantly alter meniscal material properties, which could disturb normal function in the knee. Our objective was to evaluate the effects of glutaraldehyde- and glycation-induced matrix stabilization on the material properties of porcine meniscus. Normal untreated meniscus specimens were tested in confined compression at one of three applied stresses (0.069, 0.208, 0.347 MPa), subjected to either a glutaraldehyde or glycation stabilization treatment, and then re-tested to measure changes in tissue aggregate modulus, permeability, and compressive strain at equilibrium. Changes in these properties significantly increased with glutaraldehyde concentration and exposure time to ribose. One glutaraldehyde and three glycation treatments did not alter aggregate modulus or compressive strain at equilibrium compared to controls (p > 0.10). However, all treatments increased permeability by at least 108% compared to controls (p < 0.001). This study reveals a dose-dependent relationship between meniscal material properties and certain stabilization conditions and identifies treatments that minimally affect these properties. Further research is necessary to determine whether these treatments prevent enzymatic degradation before and after surgical implantation in the knee.

Animals↗
PubMed2004

Characterization of in vivo Achilles tendon forces in rabbits during treadmill locomotion at varying speeds and inclinations.

The objective of this study was to test the hypothesis that increasing the speed and inclination of the treadmill increases the peak Achilles tendon forces and their rates of rise and fall in force. Implantable force transducers (IFT) were inserted in the confluence of the medial and lateral heads of the left gastrocnemius tendon in 11 rabbits. IFT voltages were successfully recorded in 8 animals as the animals hopped on a treadmill at each of two speeds (0.1 and 0.3 mph) and inclinations (0 degrees and 12 degrees). Instrumented tendons were isolated shortly after sacrifice and calibrated. Contralateral unoperated tendons were failed in uniaxial tension to determine maximum or failure force, from which safety factor (ratio of maximum force to peak in vivo force) was calculated for each activity. Peak force and the rates of rise and fall in force significantly increased with increasing treadmill inclination (p<0.001). Safety factors averaged 30.8+/-7.5 for quiet standing, 7.0+/-2.9 for level hopping, and 5.2+/-0.7 for inclined hopping (mean+/-SEM). These in vivo force parameters will help tissue engineers better design functional tissue engineered constructs for rabbit Achilles tendon and other tendon repairs. Force patterns can also serve as input data for mechanical stimulation of tissue-engineered constructs in culture. Such approaches are expected to help accelerate tendon repair after injury.

Achilles Tendon↗
PubMed2004

Functional tissue engineering parameters toward designing repair and replacement strategies.

Abnormal joint kinematics and loads induced after soft tissue injuries are assumed to contribute to long-term degenerative joint disease and osteoarthritis. Controlling abnormal kinematics after repair and reconstruction of these injured structures would seem to be important for limiting wear of the articular cartilage surfaces. In this paper, we propose to expand the paradigm of functional tissue engineering to more fully characterize normal joint function and to establish design parameters for soft tissue repair and reconstruction to ultimately protect joint surfaces after surgery. Structure-function relationships are examined for tissues of increasing complexity, from tendons to menisci. Emphasis is placed on understanding normal in vivo function of tissues by conducting biomechanical experiments in vitro that better mimic in vivo conditions. This process yields nine classes of functional tissue engineering parameters: differential fiber length, in vivo force and displacement, variations in relative attachment site locations, loading from adjacent structures, fiber interactions, types of insertion, regional variations in material properties, nonparallel fiber orientations, and complex loading within the structure. These functional tissue engineering parameters are useful not only for understanding the function of normal tissues but for more effectively designing their repair and replacement. This paper concludes with a discussion of research directions that investigators might take to establish tissue-specific functional tissue engineering parameters for improving joint function and reducing articular surface degradation and osteoarthritis.

Humans↗
PubMed2004

Functional efficacy of tendon repair processes.

Despite various attempts to repair and replace injured tendon, an understanding of the repair processes and a systematic approach to achieving functional efficacy remain elusive. In this review the epidemiology of tendon injury and repair is first examined. Using a traditional paradigm for repair assessment, the biology and biomechanics of normal tendon, natural healing, and repair are then explored. New treatment strategies such as functional tissue engineering are discussed, including a functional approach to treatment that involves the development of in vivo functional design parameters to judge the acceptability of a repair outcome. The paper concludes with future directions.

Biomechanical Phenomena↗
PubMed2003

Effects of matrix stabilization when using glutaraldehyde on the material properties of porcine meniscus.

Meniscus transplantation frequently is one of the only options available for treating symptomatic younger patients with tibiofemoral pain and early arthrosis after a prior meniscectomy. However, clinical results indicate that current meniscal allografts may undergo degenerative changes due to enzymatic degradation during the remodeling phase. The objective of this study was to evaluate the effects of glutaraldehyde-induced matrix stabilization on the material properties of porcine meniscus prior to surgical implantation. Protocols for fabricating heart-valve replacements were examined, followed by an exploration of the effects of reducing glutaraldehyde concentration and exposure time. Cylindrical meniscus specimens were tested in uniaxial confined compression under a 0.196 MPa compressive stress, and aggregate modulus (H(A)), permeability (k), and compressive strains at equilibrium (epsilon(eq)) were calculated from the creep response. Compared to controls, the mean values for H(A) and k increased, on average, by 213 and 709%, respectively, and epsilon(eq) decreased by 57% for all "heart-valve" treatments. Reducing tissue exposure time to glutaraldehyde had little effect, but decreasing glutaraldehyde concentration to 0.02% resulted in tissues with material properties no different from the untreated controls. We conclude that minimal concentrations of glutaraldehyde (less than 0.2%) should be used in future studies to preserve normal meniscus properties.

Animals↗
PubMed2003

In vivo forces used to develop design parameters for tissue engineered implants for rabbit patellar tendon repair.

Previous studies in tissue engineering have shown that suspending undifferentiated mesenchymal stem cells in collagen gels and wrapping them about a suture causes alignment of cells and contraction of constructs in culture in a form that is suitable for implantation for tendon repair. Little is known about the patterns of these in vivo signals that might improve tendon repair biomechanics. Three hypotheses were tested in this study using the rabbit patellar tendon (PT) model: (1) peak in vivo forces and the rates of rise and fall in these forces will increase significantly with increasing levels of activity; (2) the PTs safety factor for all activities will be in the range of values found for tendons (2.5-3); (3) rabbits will not "favor" the operated limb at the time of evaluation but maintain similar vertical ground reaction forces in both limbs during quiet standing (QS). In vivo rabbit PT forces were measured during QS and while the animal hopped on a treadmill whose speed (0.04 and 0.13 m/s) and inclination (0 degrees and 12 degrees) were controlled. Implantable force transducers were surgically placed in one PT and data collected three days post surgery in each of eight New Zealand White rabbits. Peak tensile forces increased significantly with inclination of the treadmill and the rates of rise and fall in tendon force increased significantly with both speed and inclination (p<0.001). Such design criteria should be useful in mechanically stimulating cell-gel constructs for tendon repair.

Animals↗
PubMed2003

Repair of patellar tendon injuries using a cell-collagen composite.

Collagen gels were seeded with rabbit bone marrow-derived mesenchymal stem cells (MSCs) and contracted onto sutures at initial cell densities of 1, 4, and 8 million cells/ml. These MSC-collagen composites were then implanted into full thickness, full length, central defects created in the patellar tendons of the animals providing the cells. These autologous repairs were compared to natural repair of identical defects on the contralateral side. Biomechanical, histological, and morphometric analyses were performed on both repair tissue types at 6, 12, and 26 weeks after surgery. Repair tissues containing the MSC-collagen composites showed significantly higher maximum stresses and moduli than natural repair tissues at 12 and 26 weeks postsurgery. However, no significant differences were observed in any dimensional or mechanical properties of the repair tissues across seeding densities at each evaluation time. By 26 weeks, the repairs grafted with MSC-collagen composites were one-fourth of the maximum stress of the normal central portion of the patellar tendon with bone ends. The modulus and maximum stress of the repair tissues grafted with MSC-collagen composites increased at significantly faster rates than did natural repairs over time. Unexpectedly, 28% of the MSC-collagen grafted tendons formed bone in the regenerating repair site. Except for increased repair tissue volume, no significant differences in cellular organization or histological appearance were observed between the natural repairs and MSC-collagen grafted repairs. Overall, these results show that surgically implanting tissue engineered MSC-collagen composites significantly improves the biomechanical properties of tendon repair tissues, although greater MSC concentrations produced no additional significant histological or biomechanical improvement.

Animals↗
PubMedDate not supplied

Structural and mechanical properties of the glenohumeral joint posterior capsule.

The purpose of this study was to quantify regional variations in material properties of the glenohumeral joint posterior capsule and to compare these data with the anterior band of the inferior glenohumeral ligament (AB-IGHL). Mechanical properties were determined for individual bands of the AB-IGHL, superior posterior capsule (SUP-PC), middle posterior capsule (MID-PC), and inferior posterior capsule (INF-PC). Significant differences in tissue thickness were found among the 3 posterior capsular regions and the AB-IGHL. The AB-IGHL was thicker than the MID-PC (P=.03) and INF-PC (P=.01), and the SUP-PC was thicker than the INF-PC (P=.02). Except for significant differences in failure strains, material properties were not significantly different among the 4 tissue regions. There were no significant differences between tissue bands in modulus (P=.2), maximum stress (P=.46), or strain energy density (P=.62). Specimens failed primarily near the glenoid insertion (75%), with 4 specimens failing at the humeral insertion and 2 others failing in the tissue's mid substance.

Aged↗
PubMedDate not supplied

Effects of cell-to-collagen ratio in mesenchymal stem cell-seeded implants on tendon repair biomechanics and histology.

Autogenous tissue-engineered constructs were fabricated at four cell-to-collagen ratios (0.08, 0.04, 0.8, and 0.4 M/mg) by seeding mesenchymal stem cells (MSCs) from 16 adult rabbits at one of two seeding densities (0.1 x 10(6) and 1 x 10(6) cells/mL) in one of two collagen concentrations (1.3 and 2.6 mg/mL). The highest two ratios (0.4 and 0.8 M/mg) were damaged by excessive cell contraction and could not be used in subsequent in vivo studies. The remaining two sets of constructs were implanted into bilateral full-thickness, full-length defects created in the central third of the patellar tendon (PT). At 12 weeks after surgery, repair tissues were assigned for biomechanical (n = 13) and histological (n = 3) analyses. A second group of rabbits (n = 6) received bilateral acellular implants with the same two collagen concentrations. At 12 weeks, repair tissues were also assigned for biomechanical (n = 4) and histological (n = 2) analyses. No significant differences were observed in any structural or material properties or in histological appearance among the two cell-seeded and two acellular repair groups. Average maximum force and maximum stress of the repairs were approximately 30% of corresponding values for the central one-third of normal PT and higher than peak in vivo forces measured in rabbit PT from one of our previous publications. However, average repair stiffness and modulus were only 30 and 20% of normal PT values, respectively. Current repairs achieved higher maximum forces than in previous studies and without ectopic bone, but will need to achieve sufficient stiffness as well to be effective in the in vivo range of loading.

Animals↗