Autograft rejection, temporary transplantation of autografts to allogeneic and xenogeneic hosts within and without diffusion chambers.
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Patellar tendon graft has been the most frequently used material in anterior cruciate ligament (ACL) reconstruction, but the hamstring tendons have been increasingly used as well; however, which graft is to be preferred is not adequately supported by existing clinical studies. In this prospective randomized clinical trial, the study hypothesis was that the hamstring tendons are equally good graft material as the patellar tendon in ACL reconstruction. Ninety-nine patients with laxity due to a torn ACL underwent arthroscopically assisted reconstruction with graft randomization according to their birth year to either patellar tendon with metal interference screw fixation or double looped semitendinosus and gracilis tendons with fixation similar to the Endobutton technique using a titanium metal plate suspension proximally and screw-washer postdistally. Excluding preoperative Lysholm knee score, there were no significant differences between the two groups in the preoperative and operative data. A standard rehabilitation regimen was used for all the patients, including immediate postoperative mobilization without a knee brace, protected weight bearing for 2 weeks, and return to full activity at 6-12 months postoperatively. Forty patients in the patellar tendon group and 39 patients in the hamstring tendon group were available for clinical evaluation at median 5 years after surgery (ranges 3 years 11 months-6 years 7 months). The results revealed no statistically significant differences with respect to clinical and instrumented laxity testing, isokinetic muscle torque measurements, International Knee Documentation Committee ratings, Lysholm (knee score), Tegner (activity level) and Kujala patellofemoral knee scores. There was an enlargement of the drill tunnels, statistically more in the hamstring tendon group, but no increase from 2 to 5 years in either group. Narrowing of the joint spaces (IKDC measurement method) from 2 to 5 years postoperatively was seen in both the groups, however, without difference between the two groups.
In order to compare the healing of tendon to bone and the healing of bone to bone in a rabbit model, the lateral 4 mm of patellar tendons were detached from their insertion into the tibia either subperiosteally (group I) or with a bone block (group II) and implanted into drill holes in the proximal articular surface of the tibia. The histological and biomechanical features of the graft incorporation were observed at 2, 4, 8 and 12 weeks. Histological patterns similar to normal tendon-bone attachment were seen at the tendon-bone interface in group I by 12 weeks, while direct bony union was seen in group II by 8 weeks. The maximum tensile load and stiffness were significantly greater in group II at 4 and 8 weeks while the difference between the two groups was not significant at 2 and 12 weeks. These findings show that more rapid incorporation of the graft occurs in group II although no significant difference in biomechanical parameters was noted once healing was complete.
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An ideal replacement for the scapholunate ligament (SLL) has not been found. The carpometacarpal bone-ligament-bone complex at the base of the second and third metacarpal is proposed as a replacement for the SLL in this study. A cadaveric study of matched SLL, second metacarpal-trapezoid ligament, third metacarpal-capitate ligament, and dorsal periosteal retinaculum was performed. Stiffness and strength were obtained from fresh-frozen specimens tested to failure with a hydraulic distractor. The second metacarpal-trapezoid ligament and the third metacarpal-capitate ligament most closely approximated the stiffness and strength of the SLL. The dorsal periosteal retinaculum was significantly less stiff and was significantly weaker than the SLL. This study indicates that the second or third carpometacarpal ligaments are grafts that approximate the mechanical properties of the SLL.
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BACKGROUND AND AIMS OF THE STUDY: The Ross operation was first performed as a root replacement in 1974, and only limited mid- and long-term results assessing durability and adaptation of the pulmonary root to systemic pressures are available. We reviewed our experience to assess function of the autograft valve and the autograft pulmonary root, and its adaptation to systemic pressures. METHODS: A total of 244 operative survivors (median age 22 years; range: 1 week to 62 years) were reviewed. Clinical follow up (within one year) was available on 98% of cases, and echocardiographic assessment within one year on 93%. Autograft and homograft valve function, aortic annulus diameter, autograft root sinus diameter and ascending aortic diameter were determined on the most recent echocardiogram. RESULTS: Actuarial freedom from autograft valve degeneration (non-endocarditis autograft valve reoperation or severe autograft valve insufficiency or valve-related death) was 95 +/- 3% at 5 years and 93 +/-4% at 10 years. Actuarial freedom from all valve-related complications (autograft valve degeneration, autograft valve reoperation, homograft valve reoperation or valve-related death) was 90 +/- 4% at 5 years and 83 +/-6% at 10 years. Actuarial freedom from autograft valve replacement was 98 +/- 2% at 5 years and 96 +/- 4% at 10 years. Actuarial survival rate was 98 +/- 2% at 5 years and 86 +/- 9% at 10 years. Aneurysmal dilation of the autograft root occurred in two patients; this was not associated with autograft valve degeneration, and these patients were followed closely. CONCLUSIONS: At 10 years, the Ross root replacement has a low risk of valve degeneration, valve-related complications and autograft valve replacement, and patient survival is excellent. Autograft valve reoperation and homograft valve reoperation have been the only significant late valve-related complications. Techniques to reduce autograft reoperation have been introduced, and hopefully methods to mediate the immunological response to the homograft valve will reduce the incidence of failure. Significant aneurysmal dilation of the pulmonary autograft root is rare.
This study compares the acinar cell regenerative response in submandibular gland (SMG) autografts that were cultured before grafting to the rat tongue with the acinar cell regenerative response in direct SMG autografts to the tongue. In addition, the effects of isoproterenol on direct SMG autografts were studied. A portion of the left SMG was excised from each rat and cut into fragments which were autografted either immediately into the middle one-third of the rat's tongue; or were cultured for 1, 4, or 7 days and then autografted to the donor's tongue. After 8 weeks the rats were killed and the tongues were removed and processed for light microscopic study. The histologic preparations showed evidence of cytodifferentiation into acinar cells in four of the previously cultured SMG autografts. Some of the direct SMG autografts did not contain acinar cells, whereas other direct SMG autografts contained numerous acinar cells and even striated ducts. In the SMG autografts that were cultured for 1 day before autografting and in the direct SMG autografts, the most pronounced regenerative responses were seen in autografts that contained ductlike structures that were apparently connected to the epithelial surface of the tongue. Lastly, isoproterenol appeared to accelerate the regenerative response in some of the direct SMG autografts, and the drug caused acinar cell hypertrophy in two of the direct SMG autografts.
This morphologic study compares the regenerative response in submandibular gland (SMG) autografts placed in the tongues of previously sympathectomized rats to autografts placed in tongues of sham-sympathectomized rats. We hypothesized that sympathectomy would alter the process of cellular proliferation and inhibit cytodifferentiation in regenerating SMG autografts. Either 1 week, or 8 to 11 weeks following the SMG autografting procedure, the rats were sacrificed and their tongues were removed and sectioned in a cryostat. Frozen tissue sections containing the SMG autografts were either reacted for cholinesterase activity, treated with a glyoxylic acid mixture to induce histofluorescence, or stained for histologic examination. In addition, 3H-thymidine labeled and unlabeled cells were counted in autoradiographs of 1-week autografts, and these counts were used to calculate labeling indices. The 1-week SMG autografts from both the sympathectomized and the sham-sympathectomized rats were similar in histologic appearance, and neither group of autografts contained cholinesterase-positive or monoaminergic nerve fibers. The 8- to 11-week autografts from sympathectomized and sham-sympathectomized rats contained cholinesterase-positive fibers, but monoaminergic fibers were present in the autografts only from the sham-operated rats. Acinar cells were observed in one-third of the 8- to 11-week autografts of both the sympathectomized and sham-sympathectomized rats. This finding suggests that sympathectomy did not prelude cytodifferentiation in the autografts. The autoradiographic data revealed no statistically significant difference between the mean labeling indices of the 1-week autografts from the sympathectomized and sham-sympathectomized rats, which suggests that sympathectomy also did not alter the level of cellular proliferation in the autografts.
STUDY DESIGN: A review of 66 consecutive patients at a single institution who underwent one-level anterior cervical discectomy and fusion (ACDF) with rigid anterior plate fixation with allograft or autograft. OBJECTIVES: To address the efficacy of allograft to autograft with primary respect to fusion rate and secondary attention to risk factors and clinical outcome in patients undergoing one-level ACDF with rigid anterior plate fixation. SUMMARY OF BACKGROUND DATA: Although autograft is considered the gold standard in achieving optimal fusion, when compared with allograft in noninstrumented one-level ACDF and in plated and nonplated multilevel ACDF, the efficacy of allograft to autograft in one-level ACDF with rigid anterior plate fixation is not thoroughly understood. METHODS: Sixty-six consecutive patients (mean age, 45 years) at a single institution who underwent one-level ACDF with rigid anterior plate fixation with allograft (n = 35) or autograft (n = 31) were reviewed for radiographic fusion (mean, 12 months), risk factors, and clinical outcome (mean, 17 months). Smokers entailed 33.3% of the patients, and 45.5% of all patients presented with a work-related injury. An independent blinded observer reviewed at last follow-up lateral neutral and flexion/extension plain radiographs for radiographic fusion and instrumentation integrity. Clinical outcome was assessed on last follow-up and rated according to the Odom criteria. The threshold for statistical significance was established at P < 0.05. RESULTS: Solid fusion was achieved in 63 patients (95.5%). Fusion was noted in 100% of the allograft patients, whereas 90.3% of the autograft cases achieved fusion. No statistically significant difference was noted between allograft to autograft with regard to fusion rate (P > 0.05). Three patients developed nonunions (1 smoker; 2 nonsmokers) and entailed Orion instrumentation. In the one patient who was a nonsmoker with a nonunion, slight screw penetration into the involved and uninvolved interbody spaces was noted. No other intraoperative, postoperative, or radiographic complication was noted. All of the nonunions occurred early in the series. Postoperatively, excellent results were reported in 19.7%, good results in 71.2%, and fair results in 9.1% of the patients. Satisfactory clinical outcome was noted in all nonunion patients. A nonstatistically significant difference was noted with regard to clinical outcome of fused and nonfused patients, demographics, and the presence of a work-related injury (P > 0.05). The impact of smoking was not a factor influencing fusion or clinical outcome in this series (P > 0.05). A statistically significant difference was noted in plate-type on fusion rate (P < 0.05). CONCLUSION: A 100% and 90.3% radiographic fusion rate was obtained for allograft and autograft in one-level ACDF procedures with rigid anterior plate fixation, respectively. Although autograft achieved a higher incidence of nonunion than allograft, this may be attributed to the use of autograft early in the experience of plate application and fixation in this series. The effects of smoking were not found to be a significant factor influencing fusion in these plated patients. In 90.9% of the patients, excellent and good clinical outcome results were reported. The use of allograft in one-level ACDF with rigid plate fixation yields similar and high fusion rates as autograft. The use of allograft bone eliminates complications and pitfalls associated with autologous donor site harvesting. However, the use of autograft is a viable alternative to avoid the risk of infection, disease transmission, and histocompatibility differences associated with allograft. The use of allograft or autograft bone in properly selected patients for one-level ACDF with rigid anterior plate fixation can result in high fusion rates with excellent and good clinical outcomes.
To test the hypothesis that loading conditions can be used to "engineer" ligament autograft behaviors, the effect of cyclic tension on the mRNA levels of matrix molecules and collagenase in in-vivo immobilized and mobilized 6-week rabbit medial collateral ligament (MCL) autografts was examined using an in-vitro system. Femur-[autograft MCL]-tibia complexes were subjected to a tensile stress of 4 MPa at 0.5 Hz for 1 min, followed by 14 min of rest. This 15-min testing cycle was repeated for 4 h. Semi-quantitative reverse transcrip-tase polymerase chain reaction (RT-PCR) was performed on RNA from mechanically treated MCL autografts, using rabbit-specific primer sets for types I and III collagen, biglycan, decorin, fibromodulin, lumican, versican, matrix metalloproteinase-1 (MMP-1, collagenase-1), MMP-13 (collagenase-3), and a housekeeping gene, glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Interestingly, 4 h of culture of normal control MCLs led to increased mRNA levels for MMP-1 (P < 0.05), but there were no significant changes in MMP-13 mRNA levels. Total RNA levels in that normal MCL tissue were, however, decreased after culture (P < 0.05). In-vitro tensile loading of in-vivo mobilized autografts resulted in a significant increase in total RNA (185% of in-vitro non-loaded autografts). On the other hand, in-vitro tensile loading of in-vivo immobilized autografts resulted in no significant changes in total RNA levels compared with levels in non-loaded control grafts. MMP-1 mRNA levels in both the in-vivo mobilized (47% of non-loaded autograft) and in-vivo immobilized (38% of non-loaded autograft) MCL autografts were significantly lower than those in non-loaded control tissue following in-vitro tensile loading, but there were no significant changes in the mRNA levels for the seven other matrix molecules assessed. These results show that it is possible to selectively inhibit MMP-1 mRNA levels in autograft ligaments by supplying mechanical stimuli in vitro. The results also demonstrate that in-vivo immobilization leads to a decrease in the effects of subsequent in-vitro mechanical loading in such autografts with respect to total RNA levels. Collectively, these results demonstrate that both in-vivo and in-vitro loading have implications in the engineering of an ideal ligament graft.
STUDY DESIGN: This study analyzed the fusion results of an allograft-demineralized bone matrix composite versus autograft in a prospective series of patients undergoing surgery for cervical disc disease. OBJECTIVES: To determine the fusion rates of allograft-demineralized bone matrix composite in anterior cervical fusion as compared with the gold standard autograft. SUMMARY OF BACKGROUND DATA: For the anterior cervical fusion, the use of freeze-dried allograft is well documented in the literature, citing its effectiveness and inferior fusion rates. The use of demineralized bone matrix in conjunction with freeze-dried allograft in anterior cervical fusion has not been reported. METHODS: This study was done in a prospective fashion in two medical centers. One group received autograft from the anterior iliac crest, whereas others received freeze-dried allograft augmented with demineralized bone matrix (Grafton, Osteotech, Inc., Shrewsbury, New Jersey). For the autograft group, the standard Smith-Robinson grafting technique was used. For the allograft composite group, demineralized bone matrix was pasted onto the freeze-dried allograft and into the disc space before graft insertion. The autograft group consisted of 38 patients with age ranging 26-71 years (mean, 46.1 years) and follow-up periods of 12-33 months (mean, 18.4 months). There were 19 one-level, 17 two-level, and two three-level fusions. Similarly, the allograft group consisted of 39 patients with age ranging 28-80 years (mean, 48.0 years) with follow-up period of 12-31 months (mean, 17.5 months). There were 19 one-level, 16 two-level, and four three-level fusions. Clinical and radiographic follow-up evaluations were completed at 3-month intervals. Radiographs taken 12 months after surgery were analyzed blindly. RESULTS: Pseudarthrosis developed in 46.2% of patients (33.3% of levels) in the allograft-demineralized bone matrix group compared with 26.3% (22% of levels) in the autograft group (P = 0.11 for patients, P = 0.23 for levels). For patients undergoing two-level fusions, 37.5% of allograft-demineralized bone matrix failed compared with 23.5% of autografts. For single-level fusions, 47.4% of allograft patients developed a pseudarthrosis compared with 26.3% in the autograft group. Graft collapse of > or = 3 mm was noted in 11% of the autograft group versus 19% in the allograft-demineralized bone matrix group (P = 0.32). Graft collapse of > or = 2 mm occurred in 24.4% of autograft patients compared with 39.7% of the allograft-demineralized bone matrix group (P = 0.09). Smokers had an increased rate of pseudarthrosis (47.1%) compared with nonsmokers (27.9%, P = 0.13). CONCLUSIONS: The study revealed that the allograft-demineralized bone matrix construct gives a higher rate of graft collapse and pseudarthrosis when compared with autograft in a prospective series, although the differences were not statistically significant. The pseudarthrosis rate in the series may be high because of the large percentage of smokers and radiographic evaluation techniques. For the purpose of solid radiographic fusion, the use of autograft is recommended in anterior cervical surgery until other acceptable osteoinductive materials are developed.
OBJECTIVES: We established an in vitro model to investigate the effect of size mismatch between the aortic and pulmonary root on the hydrodynamic performance and leaflet motion of the pulmonary autograft. METHODS: Ten fresh porcine pulmonary roots (annulus diameter: 19-25 mm) were tested in a pulsatile flow simulator. The autografts then were implanted in fresh porcine aortic roots (annulus diameter: 19-30 mm) and retested in the flow simulator. Three roots were oversized by 21-39%, three were undersized by 32-45% and there were four size for size implantations. The external diameter of the roots and autografts was measured at the sinotubular junction at hydrostatic pressures of 0 - 120 mmHg. The transvalvular gradient and regurgitation were also measured and the effective orifice area was calculated. The leaflet motion was recorded on video. RESULTS: The fresh pulmonary roots were more compliant than the fresh aortic roots (46 +/- 8.4% vs. 35 +/- 7.8% dilatation from 0 to 120 mmHg). The group of matching size autografts dilated by 43 +/- 4.9% in the same pressure range. The external diameter of the undersized autografts was 10 +/- 2.1% bigger than before implantation at 0 pressure and then the dilatation was 40 +/- 5.3% at 120 mmHg. The oversized implantation made the autografts 11 +/- 9.4% smaller in their relaxed state, but then they dilated by 65 +/- 11% as the pressure increased to 120 mmHg, resulting in a net dilatation of 54% over the original undilated state. The under or oversizing had little effect on the pressure gradient measured across the valves (5.6 +/- 2.57 mmHg before, 6.3 +/- 3.27 mmHg after implantation). Only the oversized valves showed significantly higher gradients than the native pulmonary valves. The effective orifice area of the undersized autografts was slightly bigger and the oversized autografts was slightly smaller after implantation, although the differences were not significant. The size mismatch did not cause regurgitation on the valves. The video images showed very low-open leaflet-bending deformation, both on the fresh pulmonary and the autograft valves. CONCLUSION: Under or oversizing the pulmonary autograft up to 40% of the annulus diameter did not affect the hydrodynamic parameters significantly. The compliance of the autograft root was able to compensate for the size mismatch without adversely influencing the valve performance.
BACKGROUND CONTEXT: Recent studies have documented increased fusion success afforded by bone morphogenetic proteins versus autogenous graft for posterolateral spinal arthrodesis. PURPOSE: The current study was designed to investigate the time-course maturation processes of lumbar posterolateral arthrodeses performed with Osteogenic Protein-1 (Stryker Biotech, Inc., Hopkinton, MA, USA) (rhOP-1) versus "gold standard" autograft. STUDY DESIGN: The primary focus of this study was to compare the histologic mechanisms of posterolateral osseointegration produced by "hot topic" growth factors. METHODS: A total of 36 coonhounds were equally divided into one of four postoperative time periods of 4, 8, 12 and 24 weeks (nine animals per period). Posterolateral arthrodesis treatments included 1) autograft alone, 2) autograft plus rhOP-1, or 3) rhOP-1 alone. The treatments and animals were divided such that a value of n=6 was obtained for each treatment group per time period and no one animal received the same treatment at both operative sites. Functional spinal unit (FSU) fusion status was assessed using radiographic analysis, biomechanical testing and undecalcified histopathologic and histomorphometric analyses. RESULTS: Radiographic differences in fusion maturation between the treatment groups were evident as early as the 4-week time interval and continued through the 24-week time period. The Osteogenic Protein-1 treatments demonstrated an accelerated rate of radiographic fusion by 4 weeks, which plateaued after the 8-week time period (22% autograft, 88% autograft/rhOP-1 and 66% rhOP-1). In contradistinction, the so-called "gold standard" autograft alone treatments reached a maximum of 50% fusion by the 6-month interval. Biomechanical testing of the FSUs indicated lower flexion-extension and axial rotation range of motion levels for both rhOP-1 treatments versus autograft alone at the 8- and 12-week time periods, respectively (p<.05). Histomorphometric analysis yielded no difference in the posterolateral trabecular bone area (mm(2)) between the three treatments (p>.05), and histopathology indicated no significant histopathologic changes. The most distinctive finding in this study deals with the mechanisms of posterolateral ossification. Based on plain and polarized light microscopy, bone induction and development for the rhOP-1 treatments, with and without autograft, was the result of intramembranous ossification, whereas the process of osseointegration for autograft alone was endochondral bone formation. By the 24-week interval, no discernable differences in trabecular histomorphology were evident based on the different mechanisms of ossification. CONCLUSIONS: This serves as the first study to document the mechanisms of bone induction and fusion maturation between posterolateral arthrodeses treated with autograft versus rhOP-1. The histological data served to corroborate the radiographic and biomechanical findings, because the rhOP-1 treatments consistently demonstrated increased fusion rates and lower range of motion levels compared with the autograft group, particularly at the 8-week postoperative time period. The improvements in these fusion criteria for Osteogenic Protein-1 versus autograft were considered secondary to the differing mechanisms of bone induction. When implanted for posterolateral arthrodesis, rhOP-1 induces an intramembranous healing response, obviating the need for the cartilage intermediate phases found in endochondral bone development. The mechanism of increased speed and incidence of fusion using growth factors (rhOP-1) is delineated by this comprehensive study of preferential intramembranous ossification.
We treated 14 patients with Ph-chromosome-positive chronic myeloid leukaemia still in chronic phase by autografting with blood-derived haemopoietic stem cells. Eleven patients were autografted electively after cytoreductive treatment with busulphan (16 mg/kg) and melphalan (60 mg/m2) and three were autografted after marrow cells from HLA-identical sibling donors had failed to engraft. In 13 patients haemopoiesis recovered; one failed to engraft and died 114 d after autografting. Two other patients became pancytopenic and received further stem cell transfusions at 3 and 40 months respectively after first autografting. One patient entered lymphoid transformation and died 14 months after autografting. Twelve patients survive at a median of 41 months (range 24-53) after autografting. Nine of the survivors have required further chemotherapy after autografting and four of the nine were electively autografted on a second occasion. Three patients surviving after autografting for 28, 43 and 53 months respectively have not required further chemotherapy. In two of these patients haemopoiesis is now predominantly Ph-negative. We conclude that autografting in chronic phase might prolong survival in some cases by reducing the size of the leukaemic stem cell population. The fact that initially successful grafts failed in two patients suggests that blood-derived stem cells may have a finite potential for self-replication.
Fifty extensor digitorium longus muscles of 25 cats were autografted, 33 with and 17 without prior denervation. After 50 days, no significant differences were observed between predenervated and nonpredenervated autografts. Autografted muscles weighed 48% of the weight of control muscles. Few original muscle fibers survived and within 2 wk autografts contained regenerating muscle fibers. The mean cross-sectional area of muscle fibers in the autografts reached 125% of the value for control nontransplanted muscles. The mean percentage of fibers classified high oxidative in autografted muscles was 67% of values for control muscles. SDH activity of autografted muscle homogenates reached 55% of control values. Up to 60 days after surgery autografts had only fast-twitch fibers. At 170 days autografts remained 95% fast twitch in composition. Revascularization began within 4 days, but the capillary to fiber ratio of long term autografts reached only 60% of control values. Although fiber hypertrophy suggests that cats use autografted muscles, lower than control succinate dehydrogenase activity may result from altered recruitment.