Kiss, Marc-Olivier; Levasseur, Annie; Petit, Yvan; Lavigne, Patrick
Osteochondral autografts in mosaicplasty are inserted in a press-fit fashion, and hence, patients are kept nonweightbearing for up to 2 months after surgery to allow bone healing and prevent complications. Very little has been published regarding alternative fixation techniques of those grafts. Osteochondral autografts stabilized with a resorbable osteoconductive bone cement would have a greater load-bearing capacity than standard press-fit grafts. Controlled laboratory study. Biomechanical testing was conducted on 8 pairs of cadaveric bovine distal femurs. For the first 4 pairs, 6 single osteochondral autografts were inserted in a press-fit fashion on one femur. On the contralateral femur, 6 grafts were stabilized with a calcium triglyceride osteoconductive bone cement. For the 4 remaining pairs of femurs, 4 groups of 3 adjacent press-fit grafts were inserted on one femur, whereas on the contralateral femur, grafts were cemented. After a maturation period of 48 hours, axial loading was applied on all single grafts and on the middle graft of each 3-in-a-row series. For the single-graft configuration, median loads required to sink the press-fit and cemented grafts by 2 and 3 mm were 281.87 N versus 345.56 N (P = .015) and 336.29 N versus 454.08 N (P = .018), respectively. For the 3-in-a-row configuration, median loads required to sink the press-fit and cemented grafts by 2 and 3 mm were 260.31 N versus 353.47 N (P = .035) and 384.83 N versus 455.68 N (P = .029), respectively. Fixation of osteochondral grafts using bone cement appears to improve immediate stability over the original mosaicplasty technique for both single- and multiple-graft configurations. Achieving greater primary stability of osteochondral grafts could potentially accelerate postoperative recovery, allowing early weightbearing and physical therapy.
Ma, D. H.; See, L.; Liau, S.; Tsai, R. J.
AIM—To study the efficacy and safety of amniotic membrane graft as an adjunctive therapy after removal of primary pterygium, and to compare the clinical outcome with conjunctival autograft and topical mitomycin C. METHODS—80 eyes of 71 patients with primary pterygia were treated with excision followed by amniotic membrane graft. The result was compared retrospectively with 56 eyes of 50 patients receiving conjunctival autograft, and 54 eyes of 46 patients receiving topical mitomycin C. Patients were followed for at least 6 months, and the averaged follow up periods for the three groups were 13.8, 22.8, and 18.4 months, respectively. RESULTS—There were three recurrences (3.8%) in the amniotic membrane graft group, three recurrences (5.4%) in the conjunctival autograft group, and two recurrences (3.7%) in the topical mitomycin C group. There was no significant difference in recurrence rate among the three groups (p = 0.879). No major complications occurred in the amniotic membrane graft group or the conjunctival autograft group. One case of infectious scleritis due to scleral ischaemia occurred in the topical mitomycin C group. CONCLUSION—This study showed that amniotic membrane graft was as effective as conjunctival autograft and mitomycin C in preventing pterygium recurrence, and can be considered as a preferred grafting procedure for primary pterygium. PMID:10966947
Jia, Zhen-Yu; Zhang, Chen; Cao, Shi-Qi; Xue, Chen-Chen; Liu, Tian-Ze; Huang, Xuan; Xu, Wei-Dong
Critically evaluation and summarization for the outcomes between autografts and artificial grafts using in anterior cruciate ligament (ACL) reconstruction have not been performed currently. The purpose of this study is to compare the clinical outcomes between artificial ligaments and autografts at a short- to mid-term follow-up. A computerized search of the databases was conducted including Medline, Embase, and the Cochrane library. Only prospective or retrospective comparative studies with a minimum 2-year follow-up and a minimum sample size of 15 for each group were considered for inclusion. Two independent reviewers performed data extraction and methodological quality assessment. A Mantel-Haenszel analysis was used for pooling of results. Sensitivity analysis was performed in order to maintain the stability of results. Seven studies were included in this study. The total sample size was 403 (autograft group: 206 patients; synthetic graft group: 197 patients). Four studies were randomized controlled trials. Two studies were retrospective comparative studies and one study was non-randomized prospective comparative study. In terms of instrumented laxity, patient-oriented outcomes and complications, no significant difference was occurred between new artificial ligaments and autografts. But the results of IKDC grades and instrumented laxity were worsen in early artificial ligaments compared to autografts. The outcomes of new generation of artificial ligaments are similar to autografts at a short- to mid-term follow-up. However, the early artificial ligaments are not suggested for ACL reconstruction compared to autografts.
Afshari, Natalie A; Duncan, Scott M; Tanhehco, Tasha Y; Azar, Dimitri T
To calculate clinical guidelines for the optimal location and size of a rotational autokeratoplasty. The ideal graft size and trephine decentration for a rotational autograft were calculated based on scar location using geometric models. Mathematical variables were set to maximize postoperative visual acuity and for generalization of the geometric model. This model was used in a rotational autokeratoplasty of a patient with a history of a corneal scar and diplopia. An 8-mm autograft was decentered 0.5 mm superiorly and rotated 180 degrees to relocate the scar to the superior aspect of the cornea, out of the patient's vision. For cases that satisfy the given variables, a graft diameter of 8 mm with a decentration of 0.5 mm balances maximization of scar removal and scar movement superiorly, with minimization of discrepancy in corneal thickness after rotation. For scars that are alpha degrees from horizontal, the graft should be rotated 180 - alpha degrees . By using these calculations, the autograft in this case successfully resolved the diplopia and improved visual acuity. A rotational autograft can be an effective alternative to standard penetrating keratoplasty for some patients with corneal scars. We establish a mathematical model for most clinical instances of a rotational autograft, in which an 8-mm graft with a decentration of 0.5 mm best satisfies the goals of surgery.
Tuchman, Alexander; Brodke, Darrel S.; Youssef, Jim A.; Meisel, Hans-Jörg; Dettori, Joseph R.; Park, Jong-Beom; Yoon, S. Tim; Wang, Jeffrey C.
Study Design Systematic review. Objective To compare the effectiveness and safety between iliac crest bone graft (ICBG) and local autologous bone and allograft in the lumbar spine. Methods A systematic search of multiple major medical reference databases identified studies evaluating spinal fusion in patients with degenerative joint disease using ICBG, local autograft, or allograft in the thoracolumbar spine. Results Six comparative studies met our inclusion criteria. A “low” strength of the overall body of evidence suggested no difference in fusion percentages in the lumbar spine between local autograft and ICBG. We found no difference in fusion percentages based on low evidence comparing allograft with ICBG autograft. There were no differences in pain or functional results comparing local autograft or allograft with ICBG autograft. Donor site pain and hematoma/seroma occurred more frequently in ICBG autograft group for lumbar fusion procedures. There was low evidence around the estimate of patients with donor site pain following ICBG harvesting, ranging from 16.7 to 20%. With respect to revision, low evidence demonstrated no difference between allograft and ICBG autograft. There was no evidence comparing patients receiving allograft with local autograft for fusion, pain, functional, and safety outcomes. Conclusion In the lumbar spine, ICBG, local autograft, and allograft have similar effectiveness in terms of fusion rates, pain scores, and functional outcomes. However, ICBG is associated with an increased risk for donor site-related complications. Significant limitations exist in the available literature when comparing ICBG, local autograft, and allograft for lumbar fusion, and thus ICBG versus other fusion methods necessitates further investigation. PMID:27556001
Akhter, Waseem; Tayyab, Ali; Kausar, Ayisha; Masrur, Amena
To compare the recurrence of pterygium between free conjunctival auto-graft and conjunctival rotation flap following simple surgical excision of pterygium. Quasi-experimental study. Shifa Foundation Community Health Clinic, Shifa College of Medicine, Islamabad, from January to November 2012. Fifty seven cases aged above 18 years, with a pterygium corneal encroachment of ³ 2 mm which was responsible for visual disability or was cosmetically undesirable were recruited for the study and randomly assigned to conjunctival auto-graft group and conjunctival rotation flap group. Cases with a history of glaucoma or glaucoma suspect, prior pterygium surgery, pterygium with concurrent ocular surface and lid disease, conjunctival inflammation and scarring, pseudo-pterygium or collagen vascular disease were excluded. After simple pterygium excision conjunctival auto-graft group (n=26) cases received a free conjunctival flap was transplanted, while conjunctival rotation flap group (n=31) cases received a conjunctival rotation flap. All cases were followed-up for 6 months after surgery for recurrence and complications. Frequency distribution and significance of association of recurrence using Fisher's exact test and Mann-Whitney U-test was carried out using Statistical Package for Social Sciences (SPSS) version 20. The median (and inter-quartile range) age and surgery duration in conjunctival auto-graft group and conjunctival rotation flap group were 60 (51.50-63.00) and 57 (45.00-60.00) years, 28.50 (27.00-30.50) and 16.00 (15.00-17.00) minutes respectively. Recurrence was seen in 2 (7.96%) and 3 (9.76%) cases in auto-graft and rotation flap groups respectively. No significant difference was seen in postoperative complications between the two groups (p=0.60). The surgical time for conjunctival rotation flap procedure is less as compared to free auto-graft, while their recurrence and complications are comparable.
Maharaj, Monish M.; Phan, Kevin
Background Patient dissatisfaction with donor site morbidity has led to the search for alternative grafting options and techniques. This report compares patient satisfaction rates between autograft and graft substitutes for anterior cervical discectomy and fusion (ACDF). Methods This study was performed with the approval of the local area health network ethics committee. Over a 9-year period, the author performed 574 ACDF procedures (697 levels). Of these, 22 patients had previous surgery with autograft, with a subsequent ACDF procedure performed using a graft substitute. Patients rated their satisfaction with pain, recovery, and preference of autograft versus a bone graft substitute. Graft substitutes used include: tricalcium phosphate/hydroxyapatite (TCP/HA) composite and iFactor placed within a polyetheretherketone (PEEK) cage. Results Results demonstrated that 21/22 patients achieved a solid fusion with the graft substitute. A total of 20/22 patients rated the autograft incision more painful than the anterior cervical incision, and 21/22 preferred the graft substitute. Three patients had adjacent segment disc replacement performed after autograft/ACDF. All patients reported preference for the total disc replacement (TDR) procedure in terms of recovery and postoperative pain. Conclusions Patient satisfaction with bone graft substitutes is very high compared with autograft with all but one (21/22) preferring the graft substitute option. The author questions the traditional recommendation that autograft is the “gold standard” for ACDF. In modern age of graft substitutes, autograft should not be considered the gold standard, but an index option between other options for comparison. PMID:27683706
Pennock, Andrew T; Ho, Brian; Parvanta, Kristina; Edmonds, Eric W; Chambers, Henry G; Roocroft, Joanna H; Bastrom, Tracey P
Small-diameter hamstring tendons are frequently encountered during anterior cruciate ligament (ACL) reconstructions in patients with short stature or those who are skeletally immature. The role of augmenting these small-diameter autografts with allograft is unclear. To assess clinical outcomes and failure rates in adolescent patients with small hamstring tendon autografts (<7 mm) that were either augmented with soft tissue allograft or accepted "as is" and not augmented. Cohort study; Level of evidence, 3. A retrospective chart review of all primary ACL reconstructions performed with hamstring autografts identified 385 patients, of whom 50 (13%) had a quadrupled (semitendinosus-gracilis) graft size less than 7 mm. Patients were grouped based on the surgeon's preference either to augment these grafts with allograft (augmented group; n = 26) or to accept the smaller autograft (nonaugmented group; n = 24). Preoperative demographic, injury, and intraoperative data were documented. All patients were contacted to obtain information about outcome scores, subsequent procedures, and complications. Forty patients (20 in each group) were available for 2-year follow-up. The mean age of the entire cohort was 15.7 years (range, 12-18 years), and 38% were male. No between-group differences were found with respect to any of the preoperative or intraoperative variables except extremity side. The mean graft size for the augmented group was 8.9 mm and for the nonaugmented group was 6.4 mm. At a mean follow-up of 3 years, 6 (30%) of the patients in the augmented group had a graft failure, whereas only 1 (5%) in the nonaugmented group had a failure ( P = .04). Five of the 6 augmented failures occurred within 1 year of surgery, whereas the single failure in the nonaugmented group occurred 2.7years postoperatively. No differences were noted in the reported outcomes between patients in the augmented and nonaugmented groups who did not experience graft failure (Lysholm score, 88 vs 92
Buser, Zorica; Brodke, Darrel S; Youssef, Jim A; Meisel, Hans-Joerg; Myhre, Sue Lynn; Hashimoto, Robin; Park, Jong-Beom; Tim Yoon, S; Wang, Jeffrey C
The purpose of this review was to compare the efficacy and safety of synthetic bone graft substitutes versus autograft or allograft for the treatment of lumbar and cervical spinal degenerative diseases. Multiple major medical reference databases were searched for studies that evaluated spinal fusion using synthetic bone graft substitutes (either alone or with an autograft or allograft) compared with autograft and allograft. Randomized controlled trials (RCT) and cohort studies with more than 10 patients were included. Radiographic fusion, patient-reported outcomes, and functional outcomes were the primary outcomes of interest. The search yielded 214 citations with 27 studies that met the inclusion criteria. For the patients with lumbar spinal degenerative disease, data from 19 comparative studies were included: 3 RCTs, 12 prospective, and 4 retrospective studies. Hydroxyapatite (HA), HA+collagen, β-tricalcium phosphate (β-TCP), calcium sulfate, or polymethylmethacrylate (PMMA) were used. Overall, there were no differences between the treatment groups in terms of fusion, functional outcomes, or complications, except in 1 study that found higher rates of HA graft absorption. For the patients with cervical degenerative conditions, data from 8 comparative studies were included: 4 RCTs and 4 cohort studies (1 prospective and 3 retrospective studies). Synthetic grafts included HA, β-TCP/HA, PMMA, and biocompatible osteoconductive polymer (BOP). The PMMA and BOP grafts led to lower fusion rates, and PMMA, HA, and BOP had greater risks of graft fragmentation, settling, and instrumentation problems compared with iliac crest bone graft. The overall quality of evidence evaluating the potential use and superiority of the synthetic biological materials for lumbar and cervical fusion in this systematic review was low or insufficient, largely due to the high potential for bias and small sample sizes. Thus, definitive conclusions or recommendations regarding the use of these
Cookson, S J; Clemente Moreno, M J; Hevin, C; Nyamba Mendome, L Z; Delrot, S; Magnin, N; Trossat-Magnin, C; Ollat, N
Although grafting is widely used in the agriculture of fruit-bearing crops, little is known about graft union formation in particular when two different species are grafted together. It is fascinating that two different plant species brought together can develop harmoniously as one organism for many decades. The objective of this study was to determine whether grafting two different grapevine genotypes alters gene expression at the graft interface in comparison to the presumably wound-like gene expression changes induced in autografts. Gene expression at the graft interface was studied 3, 7, 14, and 28 d after grafting in hetero- and autografts of grapevine (Vitis spp.). Genes differentially expressed between the hetero- and autografts during graft union formation were identified. These genes were clustered according to their expression profile over the time course. MapMan and Gene Ontology enrichment analysis revealed the coordinated upregulation of genes from numerous functional categories related to stress responses in the hetero- compared to the autografts. This indicates that heterografting with nonself rootstocks upregulates stress responses at the graft interface, potentially suggesting that the cells of the graft interface can detect the presence of a nonself grafting partner. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology.
Cookson, S. J.
Although grafting is widely used in the agriculture of fruit-bearing crops, little is known about graft union formation in particular when two different species are grafted together. It is fascinating that two different plant species brought together can develop harmoniously as one organism for many decades. The objective of this study was to determine whether grafting two different grapevine genotypes alters gene expression at the graft interface in comparison to the presumably wound-like gene expression changes induced in autografts. Gene expression at the graft interface was studied 3, 7, 14, and 28 d after grafting in hetero- and autografts of grapevine (Vitis spp.). Genes differentially expressed between the hetero- and autografts during graft union formation were identified. These genes were clustered according to their expression profile over the time course. MapMan and Gene Ontology enrichment analysis revealed the coordinated upregulation of genes from numerous functional categories related to stress responses in the hetero- compared to the autografts. This indicates that heterografting with nonself rootstocks upregulates stress responses at the graft interface, potentially suggesting that the cells of the graft interface can detect the presence of a nonself grafting partner. PMID:24692649
Samuelsen, Brian T; Webster, Kate E; Johnson, Nick R; Hewett, Timothy E; Krych, Aaron J
Bone-patellar tendon-bone (bone-tendon-bone) and four-strand hamstring tendon grafts (hamstring) are the most commonly utilized autografts for primary anterior cruciate ligament (ACL) reconstruction. Existing clinical trials, registry studies, and meta-analyses offer conflicting opinions regarding the most favorable graft choice. Which graft type for ACL reconstruction (bone-tendon-bone or hamstring) has a higher risk of (1) graft rupture and/or (2) graft laxity? We performed a meta-analysis of randomized controlled trials (RCTs), prospective cohort studies, and high-quality national registry studies to compare the outcomes of primary ACL reconstruction with bone-tendon-bone autograft or hamstring autograft. Studies that compared these graft types were identified through a comprehensive search of electronic databases (PubMed, MEDLINE, EMBASE, and the Cochrane Library). Two independent reviewers utilized the Jadad scale for RCT study quality and the Modified Coleman Methodology Score for prospective comparative and registry study quality. The included studies were analyzed for the primary outcome measure of graft rupture with or without revision ACL surgery. In surviving grafts, secondary outcomes of graft laxity were quantified by KT1000/2000™ testing, a positive pivot shift test, and a positive Lachman test. Meta-analysis was performed with Review Manager. A total of 47,613 ACL reconstructions (39,768 bone-tendon-bone and 7845 hamstring) from 14 RCTs, 10 prospective comparative studies, and one high-quality national registry study were included in this meta-analysis. Mean age was 28 years in both groups. Sixty-three percent of patients in the bone-tendon-bone cohort were men versus 57% of patients in the hamstring cohort. Mean followup was 68 ± 55 months. Two hundred twelve of 7560 (2.80%) bone-tendon-bone grafts ruptured compared with 1123 of 39,510 (2.84%) in the hamstring group (odds ratio = 0.83, 95% confidence interval, 0.72-0.96; p = 0.01). The number
Alsbjoern, B.F.S.; Sorensen, B.
Extensively burned patients suffer from lack of sufficient autologous donor skin. Meshing and wide expansion of the obtained split skin has met the requirement to a large degree. However, the wider the expansion, the less chance of a proper take. By covering widely expanded autografts with viable cadaver split skin, the take has been improved. If the epidermal Langerhans cells in the cadaver split skin are depressed by ultraviolet B light and glucocorticosteroids before grafting, a prolonged allograft take can be achieved and the healing of the underlying autografts is ensured for an extended period. Grafting results in 6 patients with extensive burns are reported.
Leo, Brian M; Krill, Michael; Barksdale, Leticia; Alvarez-Pinzon, Andres M
To compare the revision rate and subjective outcome measures of autograft hamstring versus a soft tissue hybrid graft combining both autograft hamstring and tibialis allograft for isolated anterior cruciate ligament (ACL) reconstruction. A single-center retrospective, nonrandomized, comparative study of isolated ACL reconstruction revision rates for subjects who underwent arthroscopic reconstruction of the ACL using autograft hamstring or a soft tissue hybrid graft using both autograft hamstring and tibialis allograft was performed. Patients with isolated ACL tears were included and underwent anatomic single-bundle reconstruction using an independent tunnel drilling technique and a minimum of 24 months' follow-up. The primary outcome assessed was the presence or absence of ACL rerupture. Secondary clinical outcomes consisted of the International Knee Documentation Committee, University of California at Los Angeles (UCLA) ACL quality of life assessment, and the visual analog pain scale. Between February 2010 and April 2013, 95 patients with isolated ACL tears between ages 18 and 40 met the inclusion criteria and were enrolled. Seventy-one autograft hamstring and 24 soft tissue hybrid graft ACL reconstructions were performed during the course of this study. The follow-up period was 24 to 32 months (mean 26.9 months). There were no statistically significant differences in patient demographics or Outerbridge classification. No statistically significant differences in ACL retears (5.6% auto, 4.2% hybrid; P = .57) were found between groups. Clinical International Knee Documentation Committee and UCLA ACL quality of life assessment improvement scores revealed no statistically significant differences in autograft and hybrid graft reconstructions (41 ± 11, 43 ± 13; P = .65) (38 ± 11, 40 ± 10; P = .23). The mean pain level decreased from 8.1 to 2.8 in the autograft group and 7.9 to 2.5 in the hybrid group (P = .18). The use of a hybrid soft tissue graft has a
Glatter, R D; Goldberg, J S; Schomacker, K T; Compton, C C; Flotte, T J; Bua, D P; Greaves, K W; Nishioka, N S; Sheridan, R L
OBJECTIVE: To compare the long-term clinical and histologic outcome of immediate autografting of full-thickness burn wounds ablated with a high-power continuous-wave CO2 laser to sharply débrided wounds in a porcine model. SUMMARY BACKGROUND DATA: Continuous-wave CO2 lasers have performed poorly as tools for burn excision because the large amount of thermal damage to viable subeschar tissues precluded successful autografting. However, a new technique, in which a high-power laser is rapidly scanned over the eschar, results in eschar vaporization without significant damage to underlying viable tissues, allowing successful immediate autografting. METHODS: Full-thickness paravertebral burn wounds measuring 36 cm2 were created on 11 farm swine. Wounds were ablated to adipose tissue 48 hours later using either a surgical blade or a 150-Watt continuous-wave CO2 laser deflected by an x-y galvanometric scanner that translated the beam over the tissue surface, removing 200 microm of tissue per scan. Both sites were immediately autografted and serially evaluated clinically and histologically for 180 days. RESULTS: The laser-treated sites were nearly bloodless. The mean residual thermal damage was 0.18+/-0.05 mm. The mean graft take was 96+/-11% in manual sites and 93+/-8% in laser sites. On postoperative day 7, the thickness of granulation tissue at the graft-wound bed interface was greater in laser-debrided sites. By postoperative day 180, the manual and laser sites were histologically identical. Vancouver scar assessment revealed no differences in scarring at postoperative day 180. CONCLUSIONS: Long-term scarring, based on Vancouver scar assessments and histologic evaluation, was equivalent at 6 months in laser-ablated and sharply excised sites. Should this technology become practical, the potential clinical implications include a reduction in surgical blood loss without sacrifice of immediate engraftment rates or long-term outcome. Images Figure 1. Figure 2. Figure 3
Verbeke, Fei; Binst, Dominique; Stegen, Ludo; Waelbers, Tim; de Rooster, Hilde; Van Goethem, Bart
A sizeable right atrial hemangiosarcoma in a 6-year-old Bordeaux dog, World Health Organization (WHO) stage 2, was excised using total venous inflow occlusion. The defect was restored with a non-vascularized pericardial auto-graft. The dog had a disease-free interval of 7 mo. The dog was euthanized 9 months later, at which time there were distant metastases but no indication of local recurrence. PMID:23543933
Ma, Yong; Murawski, Christopher D; Rahnemai-Azar, Amir Ata; Maldjian, Catherine; Lynch, Andrew D; Fu, Freddie H
The purpose of this study was to report the potential differences associated with graft maturity measured on magnetic resonance imaging (MRI) between quadriceps tendon with bone block and hamstring tendon autografts 6 months after ACL reconstruction. Twenty-six patients (15 male, 11 female; mean age 29.4 ± 17 years, range 13-46 years) who had undergone anatomic SB ACL reconstruction with either hamstring or quadriceps tendon with bone block autografts and had postoperative MRI 6 months after surgery. In 12 cases, the quadriceps tendon with bone block was used and hamstring in 14 cases. The signal/noise quotient was calculated to compare the difference between quadriceps tendon with bone block and hamstring autografts. Mean signal/noise quotient is lesser in quadriceps tendon with bone block (1.74 ± 0.39) compared with HS (2.44 ± 0.61) autografts (p = 0.020). For hamstring autograft, the distal region showed a significantly lower mean signal/noise quotient value compared with middle region, and the mean signal/noise quotient value in proximal region was the highest (distal vs middle p < 0.001; middle vs proximal p = 0.007; proximal vs distal p < 0.001). The mean signal/noise quotient of proximal region in quadriceps tendon with bone block autograft was lesser than that in hamstring. The middle region of the quadriceps tendon with bone block graft demonstrated the greatest signal/noise quotient [distal vs middle p = 0.001; middle vs proximal p = 0.027; proximal vs distal (n.s.)]. The maturity of quadriceps tendon with bone block was better in comparison with hamstring 6 months after anatomic SB ACL reconstruction. This study is clinically relevant in that modifying the individual rehabilitation according to the extent of graft maturity may be necessary to optimize patient function and prevent re-injury of the ACL graft.
Matthews, Peter B; Jhun, Choon-Sik; Yaung, Stephanie; Azadani, Ali N; Guccione, Julius M; Ge, Liang; Tseng, Elaine E
Pulmonary autograft dilatation requiring reoperation is an Achilles' heel of the Ross procedure, as exposure to systemic pressure increases autograft wall stress, which may in turn lead to tissue remodeling and aneurysmal pathology. However, the magnitude of autograft wall stress with the Ross procedure is unknown. The study aim was to develop a realistic finite element (FE) model of the autograft, and to perform simulations at systemic pressure to determine wall stress distribution immediately after the Ross operation. The porcine pulmonary root geometry was generated from high-resolution microcomputed tomography (microCT) images to create a mesh composed of hexahedral elements. Previously defined constitutive equations were used to describe the regional material properties of the native porcine pulmonary root. The anterior and posterior pulmonary arteries, and each of the pulmonary sinuses, were best described by non-linear, anisotropic Fung strain energy functions, and input individually into the model. Autograft dilatation and wall stress distribution during pulmonary and systemic loading prior to remodeling were determined using explicit FE analysis in LS-DYNA. The autograft was highly compliant in the low-strain region, and the majority of dilation occurred with < 30 mmHg of pressurization. During pulmonic loading, a typical inflation/deflation was observed between systole and diastole, but the autograft remained almost completely dilated throughout the cardiac cycle at systemic pressure. Although the systolic blood pressure was 380% greater in the aortic than in the pulmonary position, the peak systolic diameter was increased by only 28%. The maximum principal wall stress increased approximately 10-fold during systole and 25-fold during diastole, and was greater in the sinus than the distal artery for all simulations. Under systemic loading conditions, the pulmonary autograft remained fully dilated and experienced large wall stresses concentrated in the
Vizesi, F.; Cornwall, G. B.; Bell, D.; Oliver, R.; Yu, Y.
Choosing the appropriate graft material to participate in the healing process in posterolateral spinal fusion continues to be a challenge. Combining synthetic graft materials with bone marrow aspirate (BMA) and autograft is a reasonable treatment option for surgeons to potentially reduce or replace the need for autograft. FormaGraft, a bone graft material comprising 12% bovine-derived collagen and 88% ceramic in the form of hydroxyapatite (HAp) and beta tricalcium phosphate (β-TCP) was evaluated in three possible treatment modalities for posterior spinal fusion in a standard rabbit model. These three treatment groups were FormaGraft alone, FormaGraft soaked in autogenous BMA, and FormaGraft with BMA and iliac crest autograft. No statistically demonstrable benefits or adverse effects of the addition of BMA were found in the current study based on macroscopic, radiology or mechanical data. This may reflect, in part, the good to excellent results of the collagen HA/TCP composite material alone in a well healing bony bed. Histology did, however, reveal a benefit with the use of BMA. Combining FormaGraft with autograft and BMA achieved results equivalent to autograft alone. The mineral and organic nature of the material provided a material that facilitated fusion between the transverse processes in a standard preclinical posterolateral fusion model. PMID:19475437
Gelse, Kolja; Riedel, Dominic; Pachowsky, Milena; Hennig, Friedrich F; Trattnig, Siegfried; Welsch, Götz H
The purpose of this study was to investigate integration and cellular outgrowth of native cartilage autografts transplanted into articular cartilage defects. Native cartilage autografts were applied into chondral defects in the femoral condyle of adult sheep. Within the defects, the calcified cartilage layer was either left intact or perforated to induce bone marrow stimulation. Empty defects served as controls. The joints were analyzed after 6 and 26 weeks by macroscopic and histological analysis using the ICRS II Score and Modified O'Driscoll Scores. Non-treated defects did not show any endogenous regenerative response and bone marrow stimulation induced fibrous repair tissue. Transplanted native cartilage grafts only insufficiently integrated with the defect borders. Cell death and loss of proteoglycans were present at the margins of the grafts at 6 weeks, which was only partially restored at 26 weeks. Significant cellular outgrowth from the grafts or defect borders could not be observed. Bonding of the grafts could be improved by additional bone marrow stimulation providing ingrowing cells that formed a fibrous interface predominantly composed of type I collagen. Transplanted native cartilage grafts remain as inert structures within cartilage defects and fail to induce integrative cartilage repair which rather demands additional cells provided by additional bone marrow stimulation. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.
Mariani, P P; Adriani, E; Maresca, G
During arthroscopic posterior cruciate ligament (PCL) reconstruction, passage of the graft into the knee joint may be difficult, especially when using the patellar tendon. Because of the angle of passage, the bone block ends may become entangled or caught on the superior edge of the posterior tibial tunnel when passing the graft from the tibia to the femur. The use of a blunt trocar through the posteromedial portal avoids impingement of the bone block against the edge of the tibial tunnel. This method uses the pulley principle and permits the graft to pass freely into the knee. This method has been used successfully by the authors in more than 40 PCL arthroscopic reconstructions.
Clearfield, Elizabeth; Muthappan, Valliammai; Wang, Xue; Kuo, Irene C
Database (LILACS) (1982 to November 2015), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com) (last searched 21 November 2014), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic search for trials. We last searched the electronic databases on 23 November 2015. Selection criteria We included in this review randomized controlled trials that had compared conjunctival autograft surgery (with or without adjunctive therapy) with amniotic membrane graft surgery (with or without adjunctive therapy) in people with primary or recurrent pterygium. Data collection and analysis Two review authors independently screened search results and assessed full-text reports from among the potentially eligible trials. Two review authors independently extracted data from the included trials and assessed the trial characteristics and risk of bias. The primary outcome was the risk of recurrence of pterygium at 3 months and 6 months after surgery. We combined results from individual studies in meta-analyses using random-effects models. Risk of recurrence of pterygium was reported using risk ratios to compare conjunctival autograft with amniotic membrane transplant. Main results We identified 20 studies that had analyzed a total of 1947 eyes of 1866 participants (individual studies ranged from 8 to 346 participants who were randomized). The studies were conducted in eight different countries: one in Brazil, three in China, three in Cuba, one in Egypt, two in Iran, two in Thailand, seven in Turkey, and one in Venezuela. Overall risk of bias was unclear, as many studies did not provide information on randomization methods or masking to prevent performance and detection bias. The risk ratio for recurrence of pterygium using conjunctival autograft versus amniotic membrane transplant was 0.87 (95
Nemoto, Hitoshi; Watson, Deborah; Masuda, Koichi
Tissue engineering holds great promise for cartilage repair with minimal donor-site morbidity. The in vivo maturation of a tissue-engineered construct can be tested in the subcutaneous tissues of the same species for autografts or of immunocompromised animals for allografts or xenografts. This section describes detailed protocols for the surgical transplantation of a tissue-engineered construct into an animal model to assess construct validity.
Irvine, James N; Arner, Justin W; Thorhauer, Eric; Abebe, Ermias S; D'Auria, Jennifer; Schreiber, Verena M; Harner, Christopher D; Tashman, Scott
Bone-patellar tendon-bone (BTB) grafts are generally believed to heal more quickly than soft tissue grafts after anterior cruciate ligament (ACL) reconstruction, but little is known about the time course of healing or motion of the grafts within the bone tunnels. Graft-tunnel motion will be greater in hamstring (HS) grafts compared with BTB grafts and will be less at 1 year than at 6 weeks. Controlled laboratory study. Twelve patients underwent anatomic single-bundle ACL reconstruction using HS or BTB autografts (6 per group) with six 0.8-mm tantalum beads embedded in each graft. Dynamic stereo x-ray images were collected at 6 weeks and 1 year during treadmill walking and stair descent and at 1 year during treadmill running. Tibiofemoral kinematics and bead positions were evaluated. Graft-tunnel motion was based on bead range of motion during the loading response phase (first 10%) of the gait cycle. During treadmill walking, there was no difference in femoral tunnel or tibial tunnel motion between BTB or HS grafts at 6 weeks (BTB vs HS: 2.00 ± 1.05 vs 1.25 ± 0.67 mm [femoral tunnel]; 1.20 ± 0.63 vs 1.27 ± 0.71 mm [tibial tunnel]), or 1 year (BTB vs HS: 1.62 ± 0.76 vs 1.08 ± 0.26 mm [femoral tunnel]; 1.58 ± 0.75 vs 1.68 ± 0.53 mm [tibial tunnel]). During stair descent, there was no difference in femoral or tibial tunnel motion between BTB and HS grafts at 6 weeks or 1 year. With running, there was no difference between graft types at 1 year. For all results, P values were > .05. Knee kinematics were consistent with the literature. During walking and stair descent, ACL reconstruction using suspensory fixation yielded no difference between graft types in femoral or tibial tunnel motion at 6 weeks or 1 year. All subjects were asymptomatic with knee kinematics similar to that of the literature. The significance of persistent, small (1 to 3 mm) movements at 1 year for healing or graft performance is unknown. These study results may have significant implications
Feng, Yong; Wang, Shanzhi; Jin, Dongxu; Sheng, Jiagen; Chen, Shengbao; Cheng, Xiangguo; Zhang, Changqing
The aim of this study was to compare the safety and efficacy of OsteoSet®2 DBM with autologous cancellous bone in free vascularised fibular grafting for the treatment of large osteonecrotic lesions of the femoral head. Twenty-four patients (30 hips) with large osteonecrotic lesions of the femoral head (stage IIC in six hips, stage IIIC in 14, and stage IVC in ten, according to the classification system of Steinberg et al.) underwent free vascularised fibular grafting with OsteoSet®2 DBM. This group was retrospectively matched to a group of 24 patients (30 hips) who underwent free vascularised fibular grafting with autologous cancellous bone during the same time period according to the aetiology, stage, and size of the lesion and the mean preoperative Harris hip score. A prospective case-controlled study was then performed with a mean follow-up duration of 26 months. The results show no statistically significant differences between the two groups in overall clinical outcome or the radiographic assessment. Furthermore, no adverse events related to the use of the OsteoSet®2 DBM were observed. The results demonstrate that OsteoSet®2 DBM combined with autograft bone performs equally as well as that of autologous bone alone. Therefore, OsteoSet®2 DBM can be used as a safe and effective graft extender in free vascularised fibular grafting for large osteonecrotic lesions of the femoral head.
Chen, Wen-Jer; Tsai, Tsung-Ting; Chen, Lih-Huei; Niu, Chi-Chien; Lai, Po-Liang; Fu, Tsai-Sheng; McCarthy, Kevin
A prospective study. To compare the efficacy of calcium sulfate pellets plus laminectomy bone chips with a fresh autologous iliac bone graft for short-segment lumbar fusion. Bone graft substitute material can be used to expand an existing quantity of available laminectomy bone chips. Seventy-four patients underwent surgery for instrumented one- or two-segment fusion with decompression. Autologous iliac crest bone graft was placed in one posterolateral gutter, while on the other side, an equal quantity of autogenous laminectomy bone supplemented with calcium sulfate was placed. Radiographic assessment included radiographs alone; this was performed every 3 months (3 months to 12 months), then annually. The status of fusion and the relative size of the fusion bone mass on either side of the vertebra were compared. Using iliac crest bone graft (control side) versus autograft laminectomy bone with calcium sulfate (test side), there was no significant difference between the fusion rate and sizes of the fusion bone mass (P > 0.05). Follow-up periods ranged from 30 months to 34 months, averaging 32.5 months. For the 39 patients who received single-segment fusion, 34 patients (87.2%) exhibited bone fusion on the test side, and 35 patients (89.7%) had evidence of fusion on the control side. For the 35 patients who received two-segment fusion, 29 patients (82.9%) exhibited bone fusion on the test side and 30 patients (85.7%) demonstrated complete fusion on the control side. The fusion rate and fusion size between the two groups are similar. Calcium sulfate pellets may play a role as a bone graft extender in short-segment spinal fusion.
Autograft - bone; Allograft - bone; Fracture - bone graft; Surgery - bone graft; Autologous bone graft ... Fuse joints to prevent movement Repair broken bones (fractures) that have bone loss Repair injured bone that ...
Tudorache, Igor; Theodoridis, Karolina; Baraki, Hassina; Sarikouch, Samir; Bara, Christoph; Meyer, Tanja; Höffler, Klaus; Hartung, Dagmar; Hilfiker, Andres; Haverich, Axel; Cebotari, Serghei
Pulmonary autografts (PAs) represent the substitute of choice for aortic valve (AV) replacement, especially in children and young adults. Similarly, decellularized aortic valve allografts (DAVAs) have shown excellent mid-term function when implanted in the systemic circulation. The aim of this study was to compare the performance of DAVAs with that of pulmonary autografts after a Ross procedure in the growing sheep model. AV root replacement was performed in female lambs (25 ± 3.4 kg) using either DAVAs (n = 5) or pulmonary autografts (n = 5) as in the Ross procedure. Sheep undergoing the Ross procedure received a decellularized pulmonary allograft in place of pulmonary valve. Haemodynamics was investigated by echocardiography and magnetic resonance imaging. The roots were explanted at 20 months and examined by histology to determine the degree of repopulation and quality of the extracellular matrix, and by immunohistochemistry to characterize the repopulating cells. The mean valve diameter increased from 16 to 21 and from 16 to 25 mm in DAVAs and PAs, respectively. At explantation, one PA and one DAVA exhibited moderate insufficiency. Significant differences in transvalvular gradient were only found in PAs between implantation and prior to explantation. The cusps of all implants were soft, pliable and showed no major signs of degeneration. In the decellularized allografts, cell repopulation occurred at the wall and cusp level with a well-maintained, three-layered cusp structure. Ventricular cusp surface of decellularized allografts was more strongly repopulated than the arterial surface. Cusps were covered with cells positive for endothelial markers and were also repopulated by interstitial cells. DAVAs and PAs provide adequate haemodynamics after AV replacement in the growing sheep. While decellularized grafts are repopulated by endothelial and interstitial cells, autografts maintain in general their native cell distribution. Maintenance of valvular competence
Knothe Tate, Melissa L.; Dolejs, Scott; McBride, Sarah; Miller, R. Matthew; Knothe, Ulf
The link between mechanics and biology in generation and adaptation of bone has been studied for more than a century in the context of skeletal development and fracture healing. However, the interplay between mechanics and biology in de novo generation of bone in postnatal defects as well as healing of morcellized bone graft or massive cortical bone autografts is less well understood. To address this, here we integrate insights from our previously published studies describing the mechanobiology on both de novo bone generation and graft healing in a common ovine femoral defect model. Studying these effects in a common experimental model provides a unique opportunity to elucidate factors conducive to harnessing the regenerative power of the periosteum and ultimately to provide mechanistic insights into the multiscale mechanobiology of bone generation, remodeling and adaptation. Taken together, the studies indicate that, as long as adequate, directional transport of cells and molecules can be insured (e.g. with peristeum in situ or a delivery device), biological factors intrinsic to the periosteum suffice to bridge critical sized bone defects, even in the absence of a patent blood supply. Furthermore, mechanical stimuli are crucial for the success of periosteal bone generation and bone graft healing. Interestingly, areas of highest periosteal strain around defects correlate with highest areas albeit less mineralized areas of new bone. This may indicate a role for convection enhanced transport of cells and molecules in modulation of tissue generation by pluripotent cells that ingress into the defect center, away from the peristeum and toward the surface of the intramedullary nail that fills the medullary cavity. These insights bring us much closer to understanding the mechanobiological environment and stimuli that stimulate the proliferation and differentiation of periosteum derived progenitor cells and ultimately drive the generation of new bone tissue. Furthermore
van Zuijlen, P P; van Trier, A J; Vloemans, J F; Groenevelt, F; Kreis, R W; Middelkoop, E
Survival of the autograft and objective parameters for scar elasticity were evaluated after dermal substitution for acute burns and reconstructive surgery. The dermal substitute, which was based on bovine type I collagen and elastin-hydrolysate, was evaluated by intraindividual comparison in a clinical trial. The substitute was applied in a one-step procedure in combination with a split-thickness autograft. This treatment was compared with the conventional treatment, the split-thickness antograft. After 1 week, the percentage of autograft survival was assessed. The Cutometer SEM 474 was used to obtain objective measurements of skin elasticity parameters 3 to 4 months postoperatively. Forty-two pairs of wounds (31 patients, age 32.9 +/- 19.3 years; burned surface area, 19.8 +/- 14.5 percent) were treated because of acute burns. Reconstructive surgery was performed on 44 pairs of wounds (31 patients, age 33.9 +/- 17.5 years). Autograft survival was not altered by the substitute for reconstructive wounds, although a slight but significant reduction (p = 0.015) was established in the burn category for substituted compared with nonsubstituted wounds. However, the necessity for regrafting was not increased by substitution. Cutometer measurements of reconstructive wounds with a dermal substitute demonstrated a significant increase of pliability (50 percent, p < 0.001), elasticity (defined as immediate extension, 33 percent, p = 0.04), maximal extension (33 percent, p = 0.002), and immediate retraction (31 percent, p = 0.01), as compared with nonsubstituted wounds. After burn surgery, no improvement was found for the different elasticity parameters. Dermal substitution in a one-stage grafting model seems feasible with respect to graft survival. Skin elasticity was considerably improved by the collagen/elastin dermal substitute after reconstructive surgery.
Wohl, Greg; Goplen, Gordon; Ford, Jason; Novak, Kelli; Hurtig, Mark; McPherson, Roger; McGann, Locksley; Schachar, Norman; Zernicke, Ronald F.
Objective To assess the influence of osteochondral graft preservation techniques on post-transplant biomechanics of graft and host subchondral bone in the knee joint. Design An experimental animal model (sheep), specifically the weight-bearing articular surface of the medial femoral condyle of the knee joints. Intervention Each sheep received, in the ipsilateral knee, an allograft that was (a) frozen without dimethyl sulfoxide (DMSO), (b) snap-frozen in liquid nitrogen or (c) frozen with DMSO. The contralateral knee received an autograft that was (a) snap-frozen, (b) treated with DMSO or (c) left untreated (fresh). Main outcome measures Mechanical and material properties of bone, including maximal compression stress, modulus of elasticity and bone mineral ash content of subchondral bone cores (from the graft centre and surrounding host bone). Results No significant differences were found in the mechanical properties of the subchondral bone under the graft, but there were significant changes in surrounding bone. Bone surrounding the grafts that were snap-frozen or frozen without DMSO was significantly stronger than the normal control bone. However, bone surrounding fresh autografts and cryoprotected allografts was not significantly different from normal control bone. Conclusions The changes in the mechanical behaviour of the host bone may be associated with graft cell viability. The greater stiffness of the subchondral host bone may have consequences for long-term graft integrity and for the development of degenerative osteoarthritis. PMID:9627549
Nelson, Ian R; Chen, Jason; Love, Rebecca; Davis, Brent R; Maletis, Gregory B; Funahashi, Tadashi T
Anterior cruciate ligament reconstructions (ACLRs) in skeletally immature patients are increasing. The purpose of this study is to describe the demographics, graft usage, revision, and re-operation rates in skeletally immature ACLRs in the Kaiser Permanente healthcare system. Skeletally immature patients (<17.0 years old with open physes) were identified using the Kaiser Permanente ACLR registry. Multi-ligament reconstructions and physeal-sparing ACLRs were excluded. Aseptic revision and same-knee re-operation were the outcomes of interest. Exposure of interest was graft type; bone-patellar-tendon-bone (BPTB) autograft, hamstring autograft, and any type of allograft. Age, gender, body mass index (BMI), and race were evaluated as confounders. Cox proportional hazard models stratified by surgeon were used to analyse the risk of revision and re-operation. A total of 534 primary ACLR cases were evaluated with a mean follow-up of 2.9 years. The majority were hamstring autografts (n = 388, 72.7%), male (n = 339, 63.9%), and White (n = 232, 43.4%). Median age was 14.9 years, and median BMI was 21.9 kg/m(2). There were 44 (8.2%) aseptic revisions and 48 (9.0%) same-knee re-operations. The incidence rate for revision was BPTB autograft 5.5%, hamstring autograft 7.5%, and allograft 13.2%. After adjusting for confounders and surgeon clustering effect, the risk of aseptic revision and revision between allograft and hamstring autograft did not reach statistical significance. Graft selection differs in skeletally immature patients with a preponderance of surgeries being performed with hamstring tendon autografts. High revision rates were identified for all graft types used, though differences in revision rates across different graft types did not reach statistical significance. Surgeons should be aware of high rates of revision in this skeletally immature young population, although type of graft used did not appear to make a difference. III.
Snyder‐Mackler, Lynn; Axe, Michael J.; Buchanan, Thomas S.
Purpose/Background: The semitendinosus‐gracilis tendon autograft is often used to reconstruct the anterior cruciate ligament. Tendon regeneration appears to occur for most individuals in the short term, but little is known about the long‐term effects of graft harvest. The purpose of this study was to describe the effect of semitendinosis‐gracilis tendon graft harvest on muscle and tendon morphology at least five years following reconstruction in a case series. Methods: Magnetic resonance images were taken of the knees of three subjects at least five years following anterior cruciate ligament reconstruction. These subjects represented the different regeneration patterns at the time of return‐to‐sport. Muscle and tendon morphology were analyzed by calculating the volume, peak cross‐sectional area, and length of the knee flexors. Muscle and tendon morphological changes were analyzed individually, and then in combination as defined as a knee flexor group. Results: Muscle and tendon regeneration continued in those tendons that had begun regeneration at the time of return‐to‐sports in two subjects. There was significant additional muscle degeneration in those muscles whose tendons had not regenerated at the time of return‐to‐sports, in the remaining subject. Compensatory hypertrophy of the remaining knee flexors restored the knee flexor group to near preoperative peak cross‐sectional area and volume across the each of the three case subjects. Conclusions: Knee flexor morphology at the time of return‐to‐sports foreshadowed the long‐term outcome in the three studied subjects. Preservation of the tendon sheath in situ may play a role in tendon regeneration. When tendon regeneration did not occur, fatty infiltration of the muscle may be a worst‐case outcome. Semitendinosus‐gracilis muscle synergists demonstrated hypertrophy, perhaps in an effort to compensate for knee flexor group morphology deficits that existed after Semitendinosus gracilis
Branski, Ludwik K.; Mittermayr, Rainer; Herndon, David N.; Norbury, William B.; Masters, Oscar E.; Hofmann, Martina; Traber, Daniel L.; Redl, Heinz; Jeschke, Marc G.
Acute burn wounds often require early excision and adequate coverage to prevent further hypothermia, protein and fluid losses, and the risk of infection. Meshed autologous skin grafts are generally regarded as the standard treatment for extensive full-thickness burns. Graft take and rate of wound healing, however, depend on several endogenous factors. This paper describes a standardized reproducible porcine model of burn and skin grafting which can be used to study the effects of topical treatments on graft take and re-epithelialization. Procedures provide a protocol for successful porcine burn wound experiments with special focus on pre-operative care, anesthesia, burn allocation, excision and grafting, postoperative treatment, dressing application, and specimen collection. Selected outcome measurements include percent area of wound closure by planimetry, wound assessment using a clinical assessment scale, and histological scoring. The use of this standardized model provides burn researchers with a valuable tool for the comparison of different topical drug treatments and dressing materials in a setting that closely mimics clinical reality. PMID:18617332
Branski, Ludwik K; Mittermayr, Rainer; Herndon, David N; Norbury, William B; Masters, Oscar E; Hofmann, Martina; Traber, Daniel L; Redl, Heinz; Jeschke, Marc G
Acute burn wounds often require early excision and adequate coverage to prevent further hypothermia, protein and fluid losses, and the risk of infection. Meshed autologous skin grafts are generally regarded as the standard treatment for extensive full-thickness burns. Graft take and rate of wound healing, however, depend on several endogenous factors. This paper describes a standardized reproducible porcine model of burn and skin grafting which can be used to study the effects of topical treatments on graft take and re-epithelialization. Procedures provide a protocol for successful porcine burn wound experiments with special focus on pre-operative care, anesthesia, burn allocation, excision and grafting, postoperative treatment, dressing application, and specimen collection. Selected outcome measurements include percent area of wound closure by planimetry, wound assessment using a clinical assessment scale, and histological scoring. The use of this standardized model provides burn researchers with a valuable tool for the comparison of different topical drug treatments and dressing materials in a setting that closely mimics clinical reality.
Acellular allogeneic nerve grafting combined with bone marrow mesenchymal stem cell transplantation for the repair of long-segment sciatic nerve defects: biomechanics and validation of mathematical models
Li, Ya-jun; Zhao, Bao-lin; Lv, Hao-ze; Qin, Zhi-gang; Luo, Min
We hypothesized that a chemically extracted acellular allogeneic nerve graft used in combination with bone marrow mesenchymal stem cell transplantation would be an effective treatment for long-segment sciatic nerve defects. To test this, we established rabbit models of 30 mm sciatic nerve defects, and treated them using either an autograft or a chemically decellularized allogeneic nerve graft with or without simultaneous transplantation of bone marrow mesenchymal stem cells. We compared the tensile properties, electrophysiological function and morphology of the damaged nerve in each group. Sciatic nerves repaired by the allogeneic nerve graft combined with stem cell transplantation showed better recovery than those repaired by the acellular allogeneic nerve graft alone, and produced similar results to those observed with the autograft. These findings confirm that a chemically extracted acellular allogeneic nerve graft combined with transplantation of bone marrow mesenchymal stem cells is an effective method of repairing long-segment sciatic nerve defects. PMID:27651781
García-Graz, Nestor Jaime; Galindo-Ibarra, José Luis; García-Soto, Gabriel; Mejía-Arreguín, Hugo; Trejo-Suárez, José; Ramírez-Salas, Miguel Angel
Vascular autografts are commonly used to repair damage to blood vessels; however, they can be used only with small-caliber vessels. Although synthetic vascular grafts are good options, there may be a high likelihood of thrombus formation. An experimental animal model was used in order to evaluate feasibility and viability of a vascular autograft. Under inhalatory anesthesia, seven mongrel dogs were operated on. A 4-cm vascular autograft was created with the posterior rectus aponeurosis with subjacent peritoneum, leaving the second one as the internal sheath. A 2-cm-long portion of the abdominal aorta was removed and the vascular autograft was inserted by end-end surgical anastomosis. Animals were observed for 7 weeks, evaluating clinical data of vascular insufficiency (intensity of pulse, temperature and trophic changes of the legs). At the end of the experiment, aortography under fluoroscopic visualization was performed. Dogs were sacrificed and autograft removed in order to evaluate permeability. All dogs survived until the end of the procedure. Vascular autograft was easy to create. During surgery, no evidence of bleeding of the anastomosis or the graft suture was noted. At the end of the procedure, no clinical signs of vascular insufficiency were noted; radiographic evaluation of the autograft showed no dye leakage at any level. Autografts were removed and no signs of thrombus formation were noticed. Feasibility of the vascular autograft was demonstrated with good permeability and no thrombogenicity.
Gifstad, Tone; Foss, Olav A; Engebretsen, Lars; Lind, Martin; Forssblad, Magnus; Albrektsen, Grethe; Drogset, Jon Olav
A number of studies have found comparable results after anterior cruciate ligament (ACL) reconstruction with patellar tendon autografts and hamstring autografts; however, few studies have been large enough to reveal differences in risk of revision with regard to clinical and demographic factors. To present the distribution of grafts for ACL reconstruction based on data in the Scandinavian ACL registries and to compare the risk of revision between patellar tendon autografts and hamstring autografts. Potential associations with other clinical and demographic factors were also explored. Cohort study; Level of evidence, 2. A total of 45,998 primary ACL reconstructions, including 6736 patellar tendon autografts and 38,666 hamstring autografts, were identified in the Scandinavian ACL registries. The overall median follow-up time was 3 years (range, 0-8 years). To compare the risk of revision between groups of patients, univariate Kaplan-Meier analysis (with log-rank test) and the Cox proportional hazard regression model were applied. The hazard rate ratio with 95% CI was reported as a measure of effect. Patellar tendon and hamstring autografts were used in 14.6% and 84.1% of the patients, respectively. The remaining patients received allografts, direct sutures, or other graft types (1.3%). The primary ACL injury occurred during soccer, team handball, or alpine activities in 67.5% of the patients in the patellar tendon group and 66.2% in the hamstring group. A total of 156 patients in the patellar tendon group and 1042 patients in the hamstring group underwent revision. The overall risk of revision was significantly lower in the patellar tendon group versus the hamstring group (hazard rate ratio = 0.63; 95% CI, 0.53-0.74), and it decreased with increasing age at surgery, although not strictly linearly. The lower risk of revision in the patellar tendon group was consistently observed across subgroups of patient sex, age, and concomitant cartilage injury (P > .05, test for
Enjo, Mitsuhiro; Terada, Shinichi; Uehara, Maki; Itani, Yoshihito; Isogai, Noritaka
Approaches to auricular reconstruction have shown improved outcome when a basic fibroblast growth factor (bFGF) slow-release system and fibrin spraying are combined with biodegradable polymers. More complex, three-dimensional structures, such as those that replicate the human auricle, are often lost because of biodegradation of the synthetic scaffold. To improve the mechanical strength of regenerated cartilage, the authors grafted canine autologous chondrocytes after seeding onto scaffolds made of a complex of polyglycolic acid and polypropylene, incorporating a slow-release bFGF system with a fibrin spray coating. Five weeks after grafting, thicker cartilage with increased bending stress was obtained with the slow-release bFGF. In a three-polyglycolic acid-layer construct sandwiched around polypropylene, simulating a three-dimensional auricular structure, greater cartilage regeneration and angiogenesis were found around the implant. Sox5-positive cells were identified, indicative of maturation of neocartilage with chondroblast proliferation. These results support the usefulness of combining absorbable and nonabsorbable materials (polyglycolic acid and polypropylene) in composite scaffolds for autologous cartilage regeneration in a large-animal autograft model.
Rose, Lloyd F.; Wu, Jesse C.; Tucker, David I.; Chan, Maren M.; Christy, Robert J.; Hale, Robert G.; Leung, Kai P.
Background: Texture, color, and durability are important characteristics to consider for skin replacement in conspicuous and/or mobile regions of the body such as the face, neck, and hands. Although autograft thickness is a known determinant of skin quality, few studies have correlated the subjective and objective characters of skin graft healing with their associated morphologic and cellular profiles. Defining these relationships may help guide development and evaluation of future skin replacement strategies. Methods: Six-centimeter-diameter full-thickness wounds were created on the back of female Yorkshire pigs and covered by autografts of variable thicknesses. Skin quality was assessed on day 120 using an observer scar assessment score and objective determinations for scar contraction, erythema, pigmentation, and surface irregularities. Histological, histochemical, and immunohistochemical assessments were performed. Results: Thick grafts demonstrated lower observer scar assessment score (better quality) and decreased erythema, pigmentation, and surface irregularities. Histologically, thin grafts resulted in scar-like collagen proliferation while thick grafts preserves the dermal architecture. Increased vascularity and prolonged and increased cellular infiltration were observed among thin grafts. In addition, thin grafts contained predominately dense collagen fibers, whereas thick grafts had loosely arranged collagen. α-Smooth muscle actin staining for myofibroblasts was observed earlier and persisted longer among thinner grafts. Conclusions: Graft thickness is an important determinant of skin quality. High-quality skin replacements are associated with preserved collagen architecture, decreased neovascularization, and decreased inflammatory cellular infiltration. This model, using autologous skin as a metric of quality, may give a more informative analysis of emerging skin replacement strategies. PMID:26301157
Efficacy of i-Factor Bone Graft versus Autograft in Anterior Cervical Discectomy and Fusion: Results of the Prospective, Randomized, Single-blinded Food and Drug Administration Investigational Device Exemption Study.
Arnold, Paul M; Sasso, Rick C; Janssen, Michael E; Fehlings, Michael G; Smucker, Joseph D; Vaccaro, Alexander R; Heary, Robert F; Patel, Ashvin I; Goulet, Benoit; Kalfas, Iain H; Kopjar, Branko
A prospective, randomized, controlled, parallel, single-blinded noninferiority multicenter pivotal FDA IDE trial. The objective of this study was to investigate efficacy and safety of i-Factor Bone Graft (i-Factor) compared with local autograft in single-level anterior cervical discectomy and fusion (ACDF) for cervical radiculopathy. i-Factor is a composite bone substitute material consisting of the P-15 synthetic collagen fragment adsorbed onto anorganic bone mineral and suspended in an inert biocompatible hydrogel carrier. P-15 has demonstrated bone healing efficacy in dental, orthopedic, and nonhuman applications. Patients randomly received either autograft (N = 154) or i-Factor (N = 165) in a cortical ring allograft. Study success was defined as noninferiority in fusion, Neck Disability Index (NDI), and Neurological Success endpoints, and similar adverse events profile at 12 months. At 12 months (follow-up rate 87%), both i-Factor and autograft subjects demonstrated a high fusion rate (88.97% and 85.82%, respectively, noninferiority P = 0.0004), significant improvements in NDI (28.75 and 27.40, respectively, noninferiority P < 0.0001), and high Neurological Success rate (93.71% and 93.01%, respectively, noninferiority P < 0.0001). There was no difference in the rate of adverse events (83.64% and 82.47% in the i-Factor and autograft groups, respectively, P = 0.8814). Overall success rate consisting of fusion, NDI, Neurological Success and Safety Success was higher in i-Factor subjects than in autograft subjects (68.75% and 56.94%, respectively, P = 0.0382). Improvements in VAS pain and SF-36v2 scores were clinically relevant and similar between the groups. A high proportion of patients reported good or excellent Odom outcomes (81.4% in both groups). i-Factor has met all four FDA mandated noninferiority success criteria and has demonstrated safety and efficacy in single-level ACDF for cervical radiculopathy. i-Factor and autograft
Csomos, Rebecca A; Hardie, Robert J; Schmiedt, Chad W; Delaney, Fern A; McAnulty, Jonathan F
OBJECTIVE To assess the effect of cold storage (CS) on immediate posttransplantation function of renal autografts in cats. ANIMALS 15 healthy 1-year-old cats. PROCEDURES Cats were assigned to 2 groups and underwent autotransplantation of the left kidney followed by nephrectomy of the right kidney. The left kidney was autotransplanted either immediately (IT group; n = 6) or after being flushed with a cold sucrose phosphate solution and stored on ice while the implant site was prepared (CS group; 9). Serum creatinine and BUN concentrations were monitored daily and autografts were ultrasonographically examined intermittently for 14 days after surgery. RESULTS Mean duration of CS was 24 minutes for the CS group. Posttransplantation serum creatinine and BUN concentrations for the CS group had lower peak values, returned to the respective reference ranges quicker, and were generally significantly lower than those for the IT group. Mean posttransplantation autograft size for the CS group was smaller than that for the IT group. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that immediate posttransplantation function of renal autografts following a short period of CS was better than that of renal autografts that did not undergo CS, which suggested CS protected grafts from ischemic injury and may decrease perioperative complications, speed recovery, and improve the long-term outcome for cats with renal transplants. IMPACT FOR HUMAN MEDICINE Cats metabolize immunosuppressive drugs in a manner similar to humans; therefore, renal transplantation in cats may serve as a desirable model for investigating the effects of renal transplantation in human patients.
Ge, Yunshen; Li, Hong; Tao, Hongyue; Hua, Yinghui; Chen, Jiwu; Chen, Shiyi
The purpose of the study is to compare tendon-bone healing between autograft tendons and allograft tendons after anterior cruciate ligament (ACL) reconstruction using 3.0T magnetic resonance imaging. A total of 36 participants (18 with autograft and 18 with allograft reconstruction) underwent MRI scans at least 2 years after the ACL reconstruction operation. Oblique axial images were obtained on three-dimensional dual-echo steady-state images and imported into solid modelling software for three-dimensional model reconstruction of the bone tunnel. The graft signal intensity in the tunnel, tendon-bone interface, tunnel morphology, and tunnel area was analysed using the Siemens software packages to determine the tendon-bone healing between the groups. For the tunnel morphology, both groups exhibited bone tunnel enlargement either at the femoral or tibial tunnel aperture. For the tendon-bone interface, one patient in the autograft group and two patients in the allograft group exhibited a significant fibrous scar tissue bands at the tendon-bone interface. The graft signal/noise quotient values of the allograft group were higher than the autograft group. However, there was no significant difference in the tunnel area between the allograft group and the autograft group. Although the autograft tendons exhibited a better remodelling effect than did the allograft tendons in the bone tunnel, there was no significant difference in the tendon-bone healing between the autograft tendons and the allograft tendons postoperatively. These findings indicate that the biomechanical effect of graft motion may play a significant role in the tunnel aperture. III.
Singer, Adam J; Toussaint, Jimmy; Chung, Won Taek; McClain, Steve A; Raut, Vivek; Rosenberg, Lior
The standard of care for full-thickness burns is tangential excision followed by skin autografting; however, the timing of excision and grafting is subject to debate. The authors compared early (2 days) versus delayed (14 days) excision and grafting in a porcine full-thickness burn model. Full-thickness burns (n = 12) were created on the backs of two anesthetized pigs and assigned randomly to no excision, tangential excision followed by skin autografting 2 days after injury, or tangential excision followed by skin autografting 14 days after injury. Digital images and full-thickness biopsy specimens were taken at 16, 21, 28, and 42 days after injury to determine percentage reepithelialization and scar depth. At day 16, all burns that were excised early were completely reepithelialized, whereas only eight of 11 nonexcised burns (72.7 percent) were reepithelialized (p = 0.02). By day 21, all burns were completely reepithelialized. Scar thickness was greatest at 42 days in nonexcised burns (7.5 ± 2.1 mm); scars were thinner after early excision than after late excision (2.2 ± 1.8 mm versus 4.0 ± 1.1 mm; p < 0.001, analysis of variance). Wounds treated with early or late tangential excision followed by skin autografting were flat and minimally contracted, whereas all nonexcised burns were red, contracted, and slightly raised. Scar contraction at 28 and 42 days was greatest in nonexcised control wounds compared with early and late excised wounds. Both early and late excision followed by autografting reduce scarring in a full-thickness porcine burn model. However, early excision (2 days after injury) reduces scar thickness to a greater extent than later (after 14 days) excision.
Naves, Lucas B; Dhand, Chetna; Almeida, Luis; Rajamani, Lakshminarayanan; Ramakrishna, Seeram
In this review, we present a brief introduction of the skin structure, a concise compilation of skin-related disorders, and a thorough discussion of different in vitro skin models, artificial skin substitutes, skin grafts, and dermal tissue engineering protocols. The advantages of the development of in vitro skin disorder models, such as UV radiation and the prototype model, melanoma model, wound healing model, psoriasis model, and full-thickness model are also discussed. Different types of skin grafts including allografts, autografts, allogeneic, and xenogeneic are described in detail with their associated applications. We also discuss different tissue engineering protocols for the design of various types of skin substitutes and their commercial outcomes. Brief highlights are given of the new generation three-dimensional printed scaffolds for tissue regeneration applications. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.
In a Level III, single center, retrospective, nonrandomized observational study, anterior cruciate ligament reconstruction revision rates and patient-reported outcomes were found to be similar at 2-year follow-up when using autograft hamstrings versus a hybrid graft (autograft and nonirradiated allograft), with both groups reporting low levels of revisions and excellent outcomes. Despite previous published data that were cause for concern, a study in this issue provides support for use of a hybrid graft technique when encountering the challenging situation of a diminutive hamstring autograft when performing anterior cruciate ligament reconstruction. Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.
Walterscheid, Zakk; O'Neill, Conor; Ochs, Alex; D'Averso, Adrian; Dew, Christopher; Huntington, Alyssa; Ma, Grace; Behrend, Caleb; De Vita, Rafaella; Carmouche, Jonathan
Anterior cervical discectomy with fusion is an effective treatment for patients having cervical radiculopathy and myelopathy. To reduce morbidity associated with autograft taken from the iliac crest without sacrificing high fusion rates, a novel technique that harvests bone from the vertebral body adjacent to the operative disc space has been proposed. The effects of square and round bone graft harvest techniques on the mechanical stability of the osteopenic donor vertebrae are unknown. We analyzed the biomechanical implications of the technique by subjecting osteopenic models to uniaxial compression to compare yield strengths of surgically altered and unaltered specimens. Biomechanical grade polyurethane foam was cut into 60 different 12 mm × 17 mm × 20 mm blocks. The foam had a density of 10 pounds per cubic foot, simulating osteoporotic bone. Rectangular prism (4 mm × 4 mm × 6 mm) and cylindrical cores (r = 2 mm, h = 8 mm) were removed from 20 blocks per group. Twenty samples were left intact as a control group. Anterior plate screws were applied to the models and a Polyether ether ketone (PEEK) interbody spacer was placed on top. Samples underwent uniaxial compression at 0.1 mm/s until mechanical failure. Points of structural failure were determined using a 0.1% offset on a force-displacement curve and compared to determine the reductions in compressive strength. The mean force eliciting structural failure for intact samples was 450.6 N. Average failure forces for rectangular prisms and cylindrical cores removed were 383.2 and 395.4 N, respectively. Removal of a rectangular prismatic core of the necessary volume resulted in a 15.0% reduction in compressive strength, while removal of a cylindrical core of comparable volume facilitated a reduction of 12.2%. Local autograft harvested from adjacent vertebrae reduces morbidity associated with a second surgical site while minimally reducing the compressive strength of the donor vertebra in an osteopenic model
Fang, P; Engrav, L H; Gibran, N S; Honari, S; Kiriluk, D B; Cole, J K; Fleckman, Philip; Heimbach, D M; Bauer, G J; Matsumura, H; Warner, P
Using the INTEGRA Dermal Regeneration Template requires the outer silastic layer to be replaced with an autograft. We followed the manufacturer's directions for epidermal autografting and frequently obtained shredded, useless grafts, therefore, it seemed important to determine the proper dermatome setting. We evaluated dermatome settings from 0.002 to 0.012 inches. First, with feeler gauges, we verified the dermatome settings. Second, we harvested skin at various dermatome settings and measured the thickness histologically. We found that 1) the dermatome settings are reasonably accurate; 2) harvesting useful sheets at 0.002 and 0.004 inches is virtually impossible; 3) the variability of histologic graft thickness is enormous; and 4) a dermatome setting of 0.006 inches yields useful grafts. We no longer use the term epidermal autografting but rather ultrathin split-thickness grafting. To harvest these grafts, we now merely set the dermatome to 0.006 inches and make whatever midcourse corrections are necessary to obtain translucent grafts.
Mills, R P; Cree, I A
Histological studies have been carried out on six cortical bone autografts and three ossicular grafts removed between 6 and 232 months after implantation in ossicular reconstructions. Both types of graft consisted mainly of dead bone, with some areas of viable osteocytes. Four out of six cortical bone grafts showed evidence of new bone formation and only one had reduced in size during the period in the middle ear. Fibrosis and inflammation were also noted in some specimens. In most cases cortical bone autografts appear to survive as well as ossicular grafts in the middle ear.
Qin, Lingfeng; Yu, Luyang; Min, Wang
Graft arteriosclerois (GA), also called allograft vasculopathy, is a pathologic lesion that develops over months to years in transplanted organs characterized by diffuse, circumferential stenosis of the entire graft vascular tree. The most critical component of GA pathogenesis is the proliferation of smooth muscle-like cells within the intima. When a human coronary artery segment is interposed into the infra-renal aortae of immunodeficient mice, the intimas could be expand in response to adoptively transferred human T cells allogeneic to the artery donor or exogenous human IFN-γ in the absence of human T cells. Interposition of a mouse aorta from one strain into another mouse strain recipient is limited as a model for chronic rejection in humans because the acute cell-mediated rejection response in this mouse model completely eliminates all donor-derived vascular cells from the graft within two-three weeks. We have recently developed two new mouse models to circumvent these problems. The first model involves interposition of a vessel segment from a male mouse into a female recipient of the same inbred strain (C57BL/6J). Graft rejection in this case is directed only against minor histocompatibility antigens encoded by the Y chromosome (present in the male but not the female) and the rejection response that ensues is sufficiently indolent to preserve donor-derived smooth muscle cells for several weeks. The second model involves interposing an artery segment from a wild type C57BL/6J mouse donor into a host mouse of the same strain and gender that lacks the receptor for IFN-γ followed by administration of mouse IFN-γ (delivered via infection of the mouse liver with an adenoviral vector. There is no rejection in this case as both donor and recipient mice are of the same strain and gender but donor smooth muscle cells proliferate in response to the cytokine while host-derived cells, lacking receptor for this cytokine, are unresponsive. By backcrossing additional
Recipient wound bed characteristics affect scarring and skin graft contraction Lloyd F. Rose, PhD; Jesse C. Wu, MS; Anders H. Carlsson, PhD; David I...use of autograft skin is essential in the treatment of full thickness burns and large cutaneous defects. Both autograft thickness and condition of the... skin grafting onto hypodermis vs. onto fascia. Compared to autografts grafted onto fascia, identical thickness autografts grafted onto fat demonstrated
Han, Songfeng; Hoffman, Michael D; Proctor, Ashley R; Vella, Joseph B; Mannoh, Emmanuel A; Barber, Nathaniel E; Kim, Hyun Jin; Jung, Ki Won; Benoit, Danielle S W; Choe, Regine
Vascular infiltration and associated alterations in microvascular blood flow are critical for complete bone graft healing. Therefore, real-time, longitudinal measurement of blood flow has the potential to successfully predict graft healing outcomes. Herein, we non-invasively measure longitudinal blood flow changes in bone autografts and allografts using diffuse correlation spectroscopy in a murine femoral segmental defect model. Blood flow was measured at several positions proximal and distal to the graft site before implantation and every week post-implantation for a total of 9 weeks (autograft n = 7 and allograft n = 10). Measurements of the ipsilateral leg with the graft were compared with those of the intact contralateral control leg. Both autografts and allografts exhibited an initial increase in blood flow followed by a gradual return to baseline levels. Blood flow elevation lasted up to 2 weeks in autografts, but this duration varied from 2 to 6 weeks in allografts depending on the spatial location of the measurement. Intact contralateral control leg blood flow remained at baseline levels throughout the 9 weeks in the autograft group; however, in the allograft group, blood flow followed a similar trend to the graft leg. Blood flow difference between the graft and contralateral legs (ΔrBF), a parameter defined to estimate graft-specific changes, was elevated at 1-2 weeks for the autograft group, and at 2-4 weeks for the allograft group at the proximal and the central locations. However, distal to the graft, the allograft group exhibited significantly greater ΔrBF than the autograft group at 3 weeks post-surgery (p < 0.05). These spatial and temporal differences in blood flow supports established trends of delayed healing in allografts versus autografts.
Han, Songfeng; Hoffman, Michael D.; Proctor, Ashley R.; Vella, Joseph B.; Mannoh, Emmanuel A.; Barber, Nathaniel E.; Kim, Hyun Jin; Jung, Ki Won; Benoit, Danielle S. W.; Choe, Regine
Vascular infiltration and associated alterations in microvascular blood flow are critical for complete bone graft healing. Therefore, real-time, longitudinal measurement of blood flow has the potential to successfully predict graft healing outcomes. Herein, we non-invasively measure longitudinal blood flow changes in bone autografts and allografts using diffuse correlation spectroscopy in a murine femoral segmental defect model. Blood flow was measured at several positions proximal and distal to the graft site before implantation and every week post-implantation for a total of 9 weeks (autograft n = 7 and allograft n = 10). Measurements of the ipsilateral leg with the graft were compared with those of the intact contralateral control leg. Both autografts and allografts exhibited an initial increase in blood flow followed by a gradual return to baseline levels. Blood flow elevation lasted up to 2 weeks in autografts, but this duration varied from 2 to 6 weeks in allografts depending on the spatial location of the measurement. Intact contralateral control leg blood flow remained at baseline levels throughout the 9 weeks in the autograft group; however, in the allograft group, blood flow followed a similar trend to the graft leg. Blood flow difference between the graft and contralateral legs (ΔrBF), a parameter defined to estimate graft-specific changes, was elevated at 1–2 weeks for the autograft group, and at 2–4 weeks for the allograft group at the proximal and the central locations. However, distal to the graft, the allograft group exhibited significantly greater ΔrBF than the autograft group at 3 weeks post-surgery (p < 0.05). These spatial and temporal differences in blood flow supports established trends of delayed healing in allografts versus autografts. PMID:26625352
Azorin, Jacques F; Bertin, Francois; Martinod, Emmanuel; Laskar, Marc
Tracheal replacement after extensive resection remains a challenge for the thoracic surgeon. We propose an innovative solution: the use of an aortic autograft. After an experimental work on animals with aortic autografts and allografts [Martinod E, Seguin A, Pfeuty K, Fornes P, Kambouchner M, Azorin JF, Carpentier AF. Long-term evaluation of the replacement of the trachea with an autologous aortic graft. Ann Thorac Surg 2003;75(5):1572-8; Martinod E, Seguin A, Holder-Espinasse M, Kambouchner M, Duterque-Coquillaud M, Azorin JF, Carpentier AF. Tracheal regeneration following tracheal replacement with an allogenic aorta. Ann Thorac Surg 2005;79(3):942-8], we present the first human case of long tracheal replacement with an aortic autograft. In this case we replaced 7 cm of a tumoral trachea using an aortic infra-renal autograft supported by a silicone stent. The early postoperative course was uneventful. The stent was removed at three months. The patient died at six months from an acute pulmonary infection without any sign of anastomosis leakage or graft rupture. A new field of clinical study has to be investigated.
Yamamoto, Yusuke; Enkhbaatar, Perenlei; Sakurai, Hiroyuki; Rehberg, Sebastian; Asmussen, Sven; Ito, Hiroshi; Sousse, Linda E; Cox, Robert A; Deyo, Donald J; Traber, Lillian D; Traber, Maret G; Herndon, David N; Traber, Daniel L
Smoke inhalation injury frequently increases the risk of pneumonia and mortality in burn patients. The pathophysiology of acute lung injury secondary to burn and smoke inhalation is well studied, but long-term pulmonary function, especially the process of lung tissue healing following burn and smoke inhalation, has not been fully investigated. By contrast, early burn excision has become the standard of care in the management of major burn injury. While many clinical studies and small-animal experiments support the concept of early burn wound excision, and show improved survival and infectious outcomes, we have developed a new chronic ovine model of burn and smoke inhalation injury with early excision and skin grafting that can be used to investigate lung pathophysiology over a period of 3 weeks. Eighteen female sheep were surgically prepared for this study under isoflurane anesthesia. The animals were divided into three groups: an Early Excision group (20% TBSA, third-degree cutaneous burn and 36 breaths of cotton smoke followed by early excision and skin autografting at 24h after injury, n=6), a Control group (20% TBSA, third-degree cutaneous burn and 36 breaths of cotton smoke without early excision, n=6) and a Sham group (no injury, no early excision, n=6). After induced injury, all sheep were placed on a ventilator and fluid-resuscitated with Lactated Ringers solution (4 mL/% TBS/kg). At 24h post-injury, early excision was carried out to fascia, and skin grafting with meshed autografts (20/1000 in., 1:4 ratio) was performed under isoflurane anesthesia. At 48 h post-injury, weaning from ventilator was begun if PaO(2)/FiO(2) was above 250 and sheep were monitored for 3 weeks. At 96 h post-injury, all animals were weaned from ventilator. There are no significant differences in PaO(2)/FiO(2) between Early Excision and Control groups at any points. All animals were survived for 3 weeks without infectious complication in Early Excision and Sham groups, whereas two
Yamamoto, Yusuke; Enkhbaatar, Perenlei; Sakurai, Hiroyuki; Rehberg, Sebastian; Asmussen, Sven; Ito, Hiroshi; Sousse, Linda E.; Cox, Robert A.; Deyo, Donald J.; Traber, Lillian D.; Traber, Maret G.; Herndon, David N.; Traber, Daniel L.
Smoke inhalation injury frequently increases the risk of pneumonia and mortality in burn patients. The pathophysiology of acute lung injury secondary to burn and smoke inhalation is well studied, but long-term pulmonary function, especially the process of lung tissue healing following burn and smoke inhalation, has not been fully investigated. By contrast, early burn excision has become the standard of care in the management of major burn injury. While many clinical studies and small-animal experiments support the concept of early burn wound excision, and show improved survival and infectious outcomes, we have developed a new chronic ovine model of burn and smoke inhalation injury with early excision and skin grafting that can be used to investigate lung pathophysiology over a period of 3 weeks. Materials and methods Eighteen female sheep were surgically prepared for this study under isoflurane anesthesia. The animals were divided into three groups: an Early Excision group (20% TBSA, third-degree cutaneous burn and 36 breaths of cotton smoke followed by early excision and skin autografting at 24 h after injury, n = 6), a Control group (20% TBSA, third-degree cutaneous burn and 36 breaths of cotton smoke without early excision, n = 6) and a Sham group (no injury, no early excision, n = 6). After induced injury, all sheep were placed on a ventilator and fluid-resuscitated with Lactated Ringers solution (4 mL/% TBS/kg). At 24 h post-injury, early excision was carried out to fascia, and skin grafting with meshed autografts (20/1000 in., 1:4 ratio) was performed under isoflurane anesthesia. At 48 h post-injury, weaning from ventilator was begun if PaO2/FiO2 was above 250 and sheep were monitored for 3 weeks. Results At 96 h post-injury, all animals were weaned from ventilator. There are no significant differences in PaO2/FiO2 between Early Excision and Control groups at any points. All animals were survived for 3 weeks without infectious complication in Early Excision
Jing, Wei; Smith, Andrew A; Liu, Bo; Li, Jingtao; Hunter, Daniel J; Dhamdhere, Girija; Salmon, Benjamin; Jiang, Jie; Cheng, Du; Johnson, Chelsey A; Chen, Serafine; Lee, Katherine; Singh, Gurpreet; Helms, Jill A
Autologous bone grafting represents the standard of care for treating bone defects but this biomaterial is unreliable in older patients. The efficacy of an autograft can be traced back to multipotent stem cells residing within the bone graft. Aging attenuates the viability and function of these stem cells, leading to inconsistent rates of bony union. We show that age-related changes in autograft efficacy are caused by a loss in endogenous Wnt signaling. Blocking this endogenous Wnt signal using Dkk1 abrogates autograft efficacy whereas providing a Wnt signal in the form of liposome-reconstituted WNT3A protein (L-WNT3A) restores bone forming potential to autografts from aged animals. The bioengineered autograft exhibits significantly better survival in the hosting site. Mesenchymal and skeletal stem cell populations in the autograft are activated by L-WNT3A and mitotic activity and osteogenic differentiation are significantly enhanced. In a spinal fusion model, aged autografts treated with L-WNT3A demonstrate superior bone forming capacity compared to the standard of care. Thus, a brief incubation in L-WNT3A reliably improves autologous bone grafting efficacy, which has the potential to significantly improve patient care in the elderly. Copyright © 2014 Elsevier Ltd. All rights reserved.
Brodke, Darrel S.; Youssef, Jim A.; Meisel, Hans-Jörg; Dettori, Joseph R.; Park, Jong-Beom; Yoon, S. Tim; Wang, Jeffrey C.
Study Design Systematic review. Objective To compare the effectiveness and safety between iliac crest bone graft (ICBG), non-ICBG autologous bone, and allograft in cervical spine fusion. To avoid problems at the donor site, various allograft materials have been used as a substitute for autograft. However, there are still questions as to the comparative effectiveness and safety of cadaver allograft compared with autologous ICBG. Methods A systematic search of multiple major medical reference databases was conducted to identify studies evaluating spinal fusion in patients with cervical degenerative disk disease using ICBG compared with non-ICBG autograft or allograft or non-ICBG autograft compared with allograft in the cervical spine. Radiographic fusion, patient-reported outcomes, and functional outcomes were the primary outcomes of interest. Adverse events were evaluated for safety. Results The search identified 13 comparative studies that met our inclusion criteria: 2 prospective cohort studies and 11 retrospective cohort studies. Twelve cohort studies compared allograft with ICBG autograft during anterior cervical fusion and demonstrated with a low evidence level of support that there are no differences in fusion percentages, pain scores, or functional results. There was insufficient evidence comparing patients receiving allograft with non-ICBG autograft for fusion, pain, revision, and functional and safety outcomes. No publications directly comparing non-ICBG autograft with ICBG were found. Conclusion Although the available literature suggests ICBG and allograft may have similar effectiveness in terms of fusion rates, pain scores, and functional outcomes following anterior cervical fusion, there are too many limitations in the available literature to draw any significant conclusions. No individual study provided greater than class III evidence, and when evaluating the overall body of literature, no conclusion had better than low evidence support. A prospective
Ho, Sean Wei Loong; Tan, Teong Jin Lester; Lee, Keng Thiam
To evaluate whether pre-operative anthropometric data can predict the optimal diameter and length of hamstring tendon autograft for anterior cruciate ligament (ACL) reconstruction. This was a cohort study that involved 169 patients who underwent single-bundle ACL reconstruction (single surgeon) with 4-stranded MM Gracilis and MM Semi-Tendinosus autografts. Height, weight, body mass index (BMI), gender, race, age and -smoking status were recorded pre-operatively. Intra-operatively, the diameter and functional length of the 4-stranded autograft was recorded. Multiple regression analysis was used to determine the relationship between the anthropometric measurements and the length and diameter of the implanted autografts. The strongest correlation between 4-stranded hamstring autograft diameter was height and weight. This correlation was stronger in females than males. BMI had a moderate correlation with the diameter of the graft in females. Females had a significantly smaller graft both in diameter and length when compared with males. Linear regression models did not show any significant correlation between hamstring autograft length with height and weight (p>0.05). Simple regression analysis demonstrated that height and weight can be used to predict hamstring graft diameter. The following regression equation was obtained for females: Graft diameter=0.012+0.034*Height+0.026*Weight (R2=0.358, p=0.004) The following regression equation was obtained for males: Graft diameter=5.130+0.012*Height+0.007*Weight (R2=0.086, p=0.002). Pre-operative anthropometric data has a positive correlation with the diameter of 4 stranded hamstring autografts but no significant correlation with the length. This data can be utilised to predict the autograft diameter and may be useful for pre-operative planning and patient counseling for graft selection.
Fredericks, Douglas C; Petersen, Emily B; Sahai, Nikhil; Corley, Katherine Gibson N; DeVries, Nicole; Grosland, Nicole M; Smucker, Joseph D
Randomized, controlled study in a laboratory setting. Blinded observations/assessment of study outcomes. The purpose of this study is to determine the performance characteristics of a novel silicate-substituted hydroxyapatite bone graft substitute (BGS), SiCaP EP (Baxter Healthcare/ ApaTech, Elstree, UK), in a stand-alone mode, a stand-alone with bone marrow aspirate (BMA) mode, and an extender mode with iliac crest autograft (ICBG) in a rabbit posterolateral spine fusion model. The investigational BGS is compared to a standard iliac crest autograft (ICBG) control. The rabbit posterolateral fusion model is an established environment for testing of fusion efficacy. It offers the opportunity to obtain radiographic, histological, and biomechanical data on novel bone graft substitutes. One hundred and twenty rabbits were entered into the study with 116 used for analysis. Bilateral posterolateral lumbar intertransverse fusions were performed at L5-L6. The lateral two thirds of the transverse processes were decorti cated and covered with graft material in the following five groups: ICBG, SiCaP EP stand-alone, SiCaP EP with BMA (1:0.5 by volume), and SiCaP EP with ICBG (1:3 by volume). Rabbits were necropsied at 4, 8, and 12-week time points and fusion rate, quantity, and quality was evaluated based on manual palpation, mechanical stiffness testing, pqCT, and histological assessment. SiCaP EP, ICBG+SiCaP EP (3:1), and SiCaP EP+BMA (1:0.5) compare favorably to iliac crest autologous bone by multiple metrics in this rabbit posterolateral fusion model. Fusion efficacy via manual palpation and mechanical stiffness testing metrics indicate that all SiCaP EP groups had similar group-to-group performance, and were not significantly different than the ICBG control at each time period evaluated. In this commonly used rabbit posterolateral fusion model, SiCaP EP utilized as a stand-alone, as a stand-alone with BMA, and as an autograft (ICBG) extender produces results that are
Kleiner, J.B.; Amiel, D.; Harwood, F.L.; Akeson, W.H.
A rabbit model for anterior cruciate ligament (ACL) reconstruction using autogenous patellar tendon was utilized to study the early events of autograft cellular dynamics. Biochemical, autoradiographic, histological, and vascular injection techniques demonstrated that the native autograft cell population rapidly necroses. This repopulation occurs without a vascular contribution; cells entering the autograft are reliant upon synovial fluid nutrition.
Ilharreborde, Brice; Morel, Etienne; Fitoussi, Franck; Presedo, Ana; Souchet, Philippe; Penneçot, Georges-François; Mazda, Keyvan
Iliac crest autograft is currently the gold standard material for spinal fusion. However, its use is limited by additional operative time, increased blood loss, and morbidity. Recently, a synthetic osteoconductive bone graft material composed of bioactive glass has been described, with high effectiveness in animal models. Its ability to achieve spinal fusion in human has never been reported. The aim of this study was to compare bioactive glass and iliac crest autograft as bone substitutes in the treatment thoracic adolescent idiopathic scoliosis (AIS). Eighty-eight consecutive patients underwent posterior spinal fusion for progressive thoracic AIS. There were 2 study groups based on the type of bone graft used: iliac crest autograft (n = 40) or bioglass (n = 48). A minimum 2-year follow-up was required. Medical data and radiographs were retrospectively analyzed and compared using unpaired t test and Mann-Whitney U test. Mean follow-up was 40 months in the autograft group and 38 months in the bioglass group. In the autograft group, there were 2 infections (5%) and 3 mechanical failures (7.5%). One infection (2%) and 1 early mechanical failure (2%) occurred in the bioglass group. Loss of correction of the main thoracic curve between immediate postoperative and latest follow-up averaged 15.5% for autograft group and 11% for the bioglass group (P = 0.025). The mean (+/-SD) gain of frontal balance between immediate postoperative latest follow-up was 0.8 (+/-9.3) mm in the autograft group and 8.1 (+/-12) mm for the bioglass group (P = 0.005). Results of this retrospective study suggest that bioglass is as effective as iliac crest graft to achieve fusion and maintain correction in AIS. Less complications were seen in the bioactive glass group, but the difference did not reach statistical significance. Bioactive glass can be proposed in the treatment of AIS, avoiding the morbidity of iliac crest harvesting. However, clinical and radiological outcomes need to be confirmed
Drew, S J; Fullarton, A C; Glasby, M A; Mountain, R E; Murray, J A
The hypoglossal nerve has been used both entirely and in part to repair the facial nerve. Using the partial technique it may be difficult to obtain sufficient length and a free interposed graft is then required to extend the hypoglossal element. In six sheep the facial nerve was excised between its emergence from the stylomastoid foramen and its bifurcation in the parotid gland. The hypoglossal nerve was exposed and split longitudinally producing a limb which was reflected towards the distal stump of the facial nerve. This left a gap of 4-5 cm which was bridged with a freeze-thawed coaxially aligned skeletal muscle autograft. The sheep were examined at 8 months. Laser doppler blood-flow studies showed the blood-flow distal to the graft to be about 25% of that at an equivalent site on the normal side. Peak nerve conduction velocities were also reduced on the repaired side but stimulation of the proximal hypoglossal nerve was nevertheless capable of causing adequate contraction of both facial and tongue muscles. Histological comparison of the repaired facial nerves with equivalent sites on the normal side showed a reduction in mean axon and fibre diameters with normal myelin sheath thickness for the regenerated axon sizes. All of these features are to be expected in a regenerated nerve and are consistent with a good level of recovery of function.
Thornton, G M; Boorman, R S; Shrive, N G; Frank, C B
Recent evidence has shown that 10-40% of knee joints reconstructed with soft-tissue autografts have a recurrence of abnormal joint laxity over time. One possible explanation is the "stretching out" (or unrecovered creep) of the graft tissue. To test in vitro creep and creep recovery of fresh anatomic ligament autografts in an extra-articular environment, 16 rabbits underwent an orthotopic medial collateral ligament (MCL) autograft procedure to one hindlimb. Three subgroups of animals had either unrestricted cage activity for 1 year (n = 5) or 2 years (n = 5) or pin-immobilization for the first 6 weeks followed by cage activity for the remainder of 1 year (n = 6). Following laxity measurements, to test their creep response, isolated MCL grafts were cyclically and then statically creep tested in vitro at 4.1 MPa, allowed to recover at zero load for 20 min, and finally elongated to failure. Due to differences in cross-sectional area between the grafts and normal MCLs, two normal control groups were tested: stress-matched tested at 4.1 MPa (16.2 N; n = 7) and force-matched tested at 29.1 N (7.1 MPa; n = 6). Ligament grafts had normal laxity but significantly increased creep and decreased creep recovery compared to normal MCLs after I and 2 years of healing (p < 0.0004). Graft failure stress was also significantly less than normal (p < 0.0001). Immobilized grafts had significantly greater creep compared to non-immobilized grafts at 1 year of healing (p < 0.05). These results support previous observations concerning material inferiority of fresh anatomic rabbit MCL autografts, but add the concept that such grafts also have increased potential to creep with either slower or incomplete recovery when subjected to low stresses in vitro. Joint and ligament laxities in situ were normal in this model, however, suggesting either that in vivo MCL graft stresses are lower than those used here in vitro or that these tissues have other mechanisms by which they can recover their
Abbasi, Kyomars; Shalileh, Keivan; Anvari, Maryam Sotudeh; Rabbani, Shahram; Mahdanian, Abolfazl; Ahmadi, Seyed Hosein; Moshtaghi, Naghmeh; Movahedi, Namvar; Karimi, Abbasali
Graft stenosis is a major complication of coronary artery bypass grafting with autologous saphenous vein grafts. Nitric oxide (NO) is believed to prevent this phenomenon. We studied the effect of perivascular application of an NO donor on the degree of stenosis of such grafts in an ovine model. Twenty white Iranian ewes were randomized to coronary artery bypass grafting using autologous saphenous vein grafts with application of an elastomer gel containing diethylenetriamine NO adduct in 0.9% sodium chloride solution around the grafted vessel (intervention group) or with the gel containing the saline solution alone (controls). Graft vessels were studied after 1 year using spot angiography and histological examination. The mean degree of stenosis was significantly lower in the intervention group than in the controls as found by histology (92.3 ± 5.5 vs. 80.9 ± 8.3%; p = 0.004). Although the difference in the angiographic score was not significant, the mean score was still lower in the intervention group (9.5 ± 11.3 vs. 12.0 ± 11.8). Perivascular application of an NO donor was, at least histologically, effective in reducing graft stenosis in our ovine model. This can be a step toward the development of drug-eluting coronary artery bypass grafts. Copyright © 2011 S. Karger AG, Basel.
Maletis, Gregory B; Chen, Jason; Inacio, Maria C S; Love, Rebecca M; Funahashi, Tadashi T
The use of allograft tissue for anterior cruciate ligament reconstruction (ACLR) remains controversial. To compare the risk of aseptic revision between bone-patellar tendon-bone (BPTB) autografts and BPTB allografts. Cohort study; Level of evidence, 2. A retrospective cohort study of prospectively collected data was conducted using the Kaiser Permanente ACLR Registry. A cohort of patients who underwent primary unilateral ACLR with BPTB autografts and BPTB allografts was identified. Aseptic revision was the endpoint. The type of graft and allograft processing method (nonprocessed, <1.8-Mrad, and ≥1.8-Mrad irradiation) were the exposures of interest evaluated. Age (≤21 and ≥22 years) was evaluated as an effect modifier. Analyses were adjusted for age, sex, and race. Kaplan-Meier curves and Cox proportional hazards models were employed. Hazard ratios (HRs) and 95% CIs are provided. The BPTB cohort consisted of 5586 patients: 3783 (67.7%) were male, 2359 (42.2%) were white, 1029 (18.4%) had allografts (nonprocessed: 155; <1.8 Mrad: 525; ≥1.8 Mrad: 288), and 4557 (81.6%) had autografts. The median age was 34.9 years (interquartile range [IQR], 25.4-44.0) for allograft cases and 22.0 years (IQR, 17.6-30.0) for autograft cases. The estimated cumulative revision rate at 2 years was 4.1% (95% CI, 2.9%-5.9%) for allografts and 1.7% (95% CI, 1.3%-2.2%) for autografts. BPTB allografts had a significantly higher adjusted risk of revision than BPTB autografts (HR, 4.54; 95% CI, 3.03-6.79; P < .001). This higher risk of revision was consistent with all allograft processing methods when compared with autografts and was also consistently higher in patients with allografts regardless of age. When BPTB allograft tissue was used for ACLR, an overall 4.54 times adjusted higher risk of revision was observed compared with surgery performed with a BPTB autograft. Whether the tissue was irradiated with either high- or low-dose radiation, chemically processed, or not processed at
Ziran, Navid M; Smith, Wade R
Reconstruction of critical-size bony defects remains a challenge to surgeons despite recent technological advances. Current treatments include distraction osteogenesis, cancellous autograft, induced membranes (Masquelet procedure), polymeric membranes, and titanium-mesh cages filled with bone graft. In this article, the authors presents two cases in which critical-sized defects were reconstructed using a meshed fascial autograft encasing reamer-irrigator-aspirator (RIA) autograft and cancellous allograft. This article will discuss the clinical outcomes of the technique, comparison to other current techniques, and technical insight into the potential biological mechanism.
Hsieh, Jeng-Long; Shen, Po-Chuan; Wu, Po-Ting; Jou, I-Ming; Wu, Chao-Liang; Shiau, Ai-Li; Wang, Chrong-Reen; Chong, Hao-Earn; Chuang, Shu-Han; Peng, Jia-Shiou; Chen, Shih-Yao
Non-union occurring in structural bone grafting is a major problem in allograft transplantation because of impaired interaction between the host and graft tissue. Activated toll-like receptor (TLR) induces inflammatory cytokines and chemokines and triggers cell-mediated immune responses. The TLR-mediated signal pathway is important for mediating allograft rejection. We evaluated the effects of local knockdown of the TLR4 signaling pathway in a mouse segmental femoral graft model. Allografts were coated with freeze-dried lentiviral vectors that encoded TLR4 and myeloid differentiation primary response gene 88 (MyD88) short-hairpin RNA (shRNA), which were individually transplanted into the mice. They were assessed morphologically, radiographically, and histologically for tissue remodeling. Union occurred in autografted but not in allografted mice at the graft and host junctions after 4 weeks. TLR4 and MyD88 expression was up-regulated in allografted mice. TLR4 and MyD88 shRNAs inhibited TLR4 and MyD88 expression, which led to better union in the grafted sites. More regulatory T-cells in the draining lymph nodes suggested inflammation suppression. Local inhibition of TLR4 and MyD88 might reduce immune responses and ameliorate allograft rejection. PMID:28393847
Tan, Richard P.; Michael, Praveesuda L.; Lee, Bob S. L.; Vanags, Laura Z.; Ng, Martin K. C.; Bursill, Christina A.; Wise, Steven G.
Current animal models for the evaluation of synthetic grafts are lacking many of the molecular tools and transgenic studies available to other branches of biology. A mouse model of vascular grafting would allow for the study of molecular mechanisms of graft failure, including in the context of clinically relevant disease states. In this study, we comprehensively characterise a sutureless grafting model which facilitates the evaluation of synthetic grafts in the mouse carotid artery. Using conduits electrospun from polycaprolactone (PCL) we show the gradual development of a significant neointima within 28 days, found to be greatest at the anastomoses. Histological analysis showed temporal increases in smooth muscle cell and collagen content within the neointima, demonstrating its maturation. Endothelialisation of the PCL grafts, assessed by scanning electron microscopy (SEM) analysis and CD31 staining, was near complete within 28 days, together replicating two critical aspects of graft performance. To further demonstrate the potential of this mouse model, we used longitudinal non-invasive tracking of bone-marrow mononuclear cells from a transgenic mouse strain with a dual reporter construct encoding both luciferase and green fluorescent protein (GFP). This enabled characterisation of mononuclear cell homing and engraftment to PCL using bioluminescence imaging and histological staining over time (7, 14 and 28 days). We observed peak luminescence at 7 days post-graft implantation that persisted until sacrifice at 28 days. Collectively, we have established and characterised a high-throughput model of grafting that allows for the evaluation of key clinical drivers of graft performance. PMID:28355300
Gorczynski, A; Trenkner, M; Anisimowicz, L; Gutkowski, R; Drapella, A; Kwiatkowska, E; Dobke, M
Pulmonary autograft valve replacement has been simulated by implanting the pulmonary valve into the aortic position of the same cadaver heart from both human and porcine sources. The forces acting on the pulmonary valve leaflets have been calculated on the basis of a triaxial ellipsoid mathematical model. These forces on the pulmonary autograft valve were shown to be essentially similar to those previously reported for aortic valve leaflets. Biomechanical measurements have been made on the simulated autograft valves and on the isolated pulmonary valve cusps. The tensile strengths of the pulmonary valve cusps in both circumferential and radial directions were roughly three times greater than those of aortic valve cusps. This indicated the ability of the pulmonary valves to accept, ab initio, aortic valve closing pressures. Pressure-induced changes in dimension, calculated on the basis of diameters of the simulated pulmonary autograft root, also indicated that the distensibility of the autograft valve was limited. It reached a maximum at 30 mm Hg (4 kPa) without any suggestion of further distension to the point of distortion and incompetence. The combination of the calculated forces acting on the valve and the biomechanical measurements have shown that pulmonary valves used as autograft aortic valve replacements are able to tolerate aortic pressures from the time of implantation. These experimental results from simulated autografts support the clinical use of this valve over the past 13 years. PMID:7135295
Qu-Knafo, Lise; Le Du, Brivael; Boumendil, Julien; Nordmann, Jean-Philippe
We report the first description of temporalis fascia autograft to repair a late leakage bleb with scleral defect that occurred long time after trabeculectomy with mitomycin C. A 65-year-old woman was referred to our hospital with chronic late bleb leakage on her right eye. She had previously undergone a trabeculectomy with mitomycin C 3 years ago for a pigmentary glaucoma. Bleb leakage occurred 1½ year after the initial surgery. She underwent 2 surgical revisions consisting of a conjunctival advancement then an autologous conjunctival with partial scleral grafts without success. The initial best-corrected visual acuity of the right eye was 20/50 (Snellen scale). Slit-lamp examination revealed an avascular filtering bleb with leakage (massive positive Seidel test) and a scleral defect. The anterior chamber was deep and intraocular pressure (IOP) was 9 mm Hg.Faced with the risk of blebitis, endophthalmitis, and with the failure of the previous surgeries announced earlier, a surgical revision with autologous superficial temporalis fascia graft was decided to repair the leaking bleb. After local anesthesia, a sample of superficial temporalis fascia was harvested. The necrotic avascular conjunctiva around the bleb was dissected to separate and excise it from the sclera. The autologous fascia graft was sutured on the scleral defect with 10-0 nylon. Subsequently healthy conjunctiva was sutured above the graft. No bleb leakage occurred postoperatively, best-corrected visual acuity improved to 20/25, and IOP remained within normal levels 6 months after surgery without IOP-lowering medication. Superficial temporalis fascia autograft seems to be an effective, safe, and easy technique for ophthalmologists. It is a new procedure in the management of late-onset bleb leakage.
Lim, Jit-Kheng; Hui, James; Li, Li; Thambyah, Ashvin; Goh, James; Lee, Eng-Hin
To study the effect of coating tendon grafts with mesenchymal stem cells (MSCs) on the rate and quality of graft osteointegration in anterior cruciate ligament (ACL) reconstruction. Animal model. Bilateral ACL reconstructions using hamstring tendon autografts were performed on 48 adult rabbits. Grafts were coated with MSCs in a fibrin glue carrier in one limb, and fibrin glue only in the other. Assessment was done at 2, 4, and 8 weeks. Histologic analysis was carried out using standard and immunohistochemical stains. Biomechanical testing of force and stiffness during loading to ultimate failure was performed. Control reconstructions showed mature scar tissue with some Sharpey's-like fibers spanning the tendon-bone interface at 8 weeks. The MSC-enhanced reconstructions had large areas of cartilage cells at the tendon-bone junction at 2 weeks. By 8 weeks, a mature zone of cartilage was seen gradually blending from bone into the tendon grafts. This zone stained strongly for type II collagen and showed histologic characteristics similar to normal rabbit ACL insertions. Biomechanically, there was no statistical difference between limbs at 2 and 4 weeks. At 8 weeks, the MSC-enhanced grafts had significantly higher failure load and stiffness. Coating of tendon grafts with MSCs results in healing by an intervening zone of cartilage resembling the chondral enthesis of normal ACL insertions rather than collagen fibers and scar tissue. MSC-enhanced ACL reconstructions perform significantly better than controls on biomechanical testing. Enhancement of tendon graft osteointegration with MSCs is a novel method offering the potential for more physiologic and biomechanically stronger ligament reconstructions.
Qiao, Jizeng; Philips, Erica; Teumer, Jeff
Follicular cell implantation (FCI) is an experimental cell therapy for the treatment of hair loss that uses cultured hair follicle cells to induce new hair formation. This treatment is based on the demonstration that adult dermal papilla cells (DPC) retain the hair inductive capacity they acquired during hair morphogenesis in the embryo. For FCI, hair inductive cells are isolated from scalp biopsies and then propagated in culture in order to provide enough cells to generate many new follicles from a few donor follicles. Following expansion in culture, the cells are implanted into the scalp where they induce the formation of new follicles. Because the process relies on the ability to retain the potential for hair induction during the expansion of DPC in culture, we sought a consistent, reliable and easily performed in vivo assay in which to test hair induction. In this study, we describe a simple graft model that supports hair morphogenesis. The assay combines dermal cells with embryonic mouse epidermis that provides the keratinocyte component of induced follicles. The grafts are placed under a protective skin flap in the host athymic mouse where the cells will form a skin graft with hair if the dermal cells are hair inductive DPC. Using the assay, freshly isolated and cultured mouse embryo dermal cells as well as cultured dermal papilla cells from other species all induced hair formation. The induced hairs were aesthetically indistinguishable from those of the epidermal donor in length, thickness, and pigmentation, and they were histologically normal.
Sandhu, Harvinder S; Toth, Jeffrey M; Diwan, Ashish D; Seim, H B; Kanim, Linda E A; Kabo, J Michael; Turner, A Simon
The sheep anterior lumbar spinal fusion model was used to study the efficacy of recombinant human bone morphogenetic protein-2 (rhBMP-2)-collagen composite in comparison with autograft to enhance spinal interbody fusion. Comparisons were drawn from temporal radiographic and end-point biomechanical and histologic data. To analyze histologically the ability of rhBMP-2 to achieve complete arthrodesis between vertebral bodies. Studies using rhBMP for enhancement of anterior interbody fusion have used numerous endpoints. However, systematic histologic evaluation of the fusion has not been conducted. Twelve sheep underwent single-level anterior lumbar interbody fusion performed with a cylindrical fenestrated titanium interbody fusion device (INTER FIX, Medtronic Sofamor Danek, Inc., Memphis, TN). The device was filled either with rhBMP-2-collagen (n = 6) or autogenous iliac crest bone graft (n = 6). Radiologic evaluation was carried out at 2-month intervals, and all sheep were killed 6 months after surgery. Nondestructive biomechanical testing for stiffness to flexion, extension, and lateral bending moments, un-decalcified histology, and qualitative and quantitative histologic evaluation were performed. Radiographs revealed a bony bridge anterior to the cage in five of six rhBMP-2-treated animals, whereas it was present only in one of five in the autogenous bone graft group. Segments treated with rhBMP-2 were 20% stiffer in flexion than autograft-treated segments at 6 months. Six of six in the rhBMP-2 group and two of six in the autograft group showed complete fusion. There was a significantly higher rate of bony continuity observed at the fenestrations of the rhBMP-2 group. Three times more number of cage fenestrations in the rhBMP-2 group demonstrated "all-bone" when compared with the autograft group (P < 0.001). Further, the scar tissue in and around the autograft-treated cages was 16-fold more (P < 0.01) than that seen for rhBMP-2-treated cages. The study
Segura-Sampedro, Juan José; Sampedro-Abascal, Consuelo; Parra-López, Loreto; Muñoz-Rodríguez, Juan Carlos
Radial graft is one of the optimal treatments for reconstruction after tongue cancer, but it is not free of side effects. Hypertrichosis over the graft, causing an intraoral paratrichosis, might downgrade the quality of life and even require further interventions. The case is presented of a 58 year-old man, who developed hypertrichosis after surgery for tongue carcinoma. The therapeutic options, from choosing a graft from less hairy areas to laser depilation or de-epithelisation of the graft are discussed. Intraoral paratrichosis is a serious complication that can produce dysphagia, nauseas, and vomiting, and can evolve into mal nutrition and produce an important decrease in life quality of our patients. Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.
Tuchman, Alexander; Brodke, Darrel S; Youssef, Jim A; Meisel, Hans-Jörg; Dettori, Joseph R; Park, Jong-Beom; Yoon, S Tim; Wang, Jeffrey C
Systematic review. To compare the effectiveness and safety between iliac crest bone graft (ICBG), non-ICBG autologous bone, and allograft in cervical spine fusion. To avoid problems at the donor site, various allograft materials have been used as a substitute for autograft. However, there are still questions as to the comparative effectiveness and safety of cadaver allograft compared with autologous ICBG. A systematic search of multiple major medical reference databases was conducted to identify studies evaluating spinal fusion in patients with cervical degenerative disk disease using ICBG compared with non-ICBG autograft or allograft or non-ICBG autograft compared with allograft in the cervical spine. Radiographic fusion, patient-reported outcomes, and functional outcomes were the primary outcomes of interest. Adverse events were evaluated for safety. The search identified 13 comparative studies that met our inclusion criteria: 2 prospective cohort studies and 11 retrospective cohort studies. Twelve cohort studies compared allograft with ICBG autograft during anterior cervical fusion and demonstrated with a low evidence level of support that there are no differences in fusion percentages, pain scores, or functional results. There was insufficient evidence comparing patients receiving allograft with non-ICBG autograft for fusion, pain, revision, and functional and safety outcomes. No publications directly comparing non-ICBG autograft with ICBG were found. Although the available literature suggests ICBG and allograft may have similar effectiveness in terms of fusion rates, pain scores, and functional outcomes following anterior cervical fusion, there are too many limitations in the available literature to draw any significant conclusions. No individual study provided greater than class III evidence, and when evaluating the overall body of literature, no conclusion had better than low evidence support. A prospective randomized trial with adequate sample size to
Song, Lei; Wang, Lai; Shah, Prediman K.; Chaux, Aurelio; Sharifi, Behrooz G.
Background We tested the hypothesis that the mouse peritoneum can function like a bioreactor to generate directed bio-engineered tissues such as those used for bypass grafting. Additionally, we reasoned that the mouse animal model would allow us to elucidate the underlying cellular and molecular mechanisms that are responsible for the generation of tissue in peritoneal cavity. Methods Plastic tubes (2 tubes/mouse) were implanted into the peritoneal cavity of 3 strains of mice (C57BL/6, BALB/c, and MRL). The tubes were harvested, tissue capsule surrounding the tubes was removed, and analyzed by immunostaining (5 capsules/5 mice/strain) and microarray (3 capsules/3 mice/strain). In addition, the tissue capsules that were harvested from MRL mice (n=21) were grafted into abdominal aorta of the same mice as autografts. The patency of all grafts was monitored by micro-ultrasound and their functionality was assessed by Laser Doppler Imaging of blood flow in femoral arteries. Venous (n=13) and arterial isografts (n=11) were used as positive controls. In a negative control group (5 mice/strain), the abdominal aorta was occluded by double ligation with 9-0 silk. Results The implanted plastic tubes required at least 8 weeks of incubation in the peritoneum of the 3 strains of mice in order to generate useful grafts. No vascular cells. were found in the tissue capsules. Microarray analysis of tissue capsules revealed that the capsular cells express a gene expression program that is vastly shared among the 3 strains of mice and the cells exhibit high degree of plasticity. The micro-ultrasound analysis of the grafts showed that 62% of autografts remained patent compared to 77% of venous isografts and 91% of arterial isografts. The Laser Doppler Imaging analysis showed that blood flow dropped by 40% and 35% in the autografts and vein isografts, respectively, one day after surgery. The flow, however, rebounded to the level of arterial isografts one month post surgery and remained
Darnley, James E.; Léger-St-Jean, Benjamin; Pedroza, Angela D.; Flanigan, David C.; Kaeding, Christopher C.; Magnussen, Robert A.
Background: Anterior cruciate ligament (ACL) reconstruction with hamstring autografts less than 8.5 mm in diameter is associated with worse patient-reported outcome scores and increased risk of revision surgery compared with reconstructions performed with larger grafts. One proposed solution to small autograft harvest is to create a hybrid graft by augmenting autografts with allograft tissue to increase graft diameter. Purpose: To compare hybrid autograft/allograft ACL reconstruction to autograft ACL reconstruction, specifically analyzing the patient-reported outcome scores and the risk of revision surgery at 2 years postoperative. Study Design: Cohort study; Level of evidence, 3. Methods: From the years 2002 to 2009, a total of 34 patients were identified from a prospectively collected database as having undergone hybrid ACL reconstruction. Twenty-seven of 34 (79.4%) patients had a 2-year follow-up. These 27 patients were matched by age (within 1 year) and sex to 27 patients who underwent hamstring autograft ACL reconstruction during the same period. At the 2-year mark, revision surgery risk and patient-reported outcome scores were compared between the 2 groups. Results: The mean age for the hybrid and matched groups (±SD) was 20.9 ± 7.0 years. Both the hybrid and control groups had 17 males and 10 females. There was no significant difference in preoperative patient-reported outcome scores, meniscus tears, or cartilage lesions between the 2 groups. Graft size was larger in the hybrid group (9.5 ± 0.6 mm) than in the autograft group (8.4 ± 0.9 mm) (P < .001). At 2 years postoperative, patient-reported outcome scores were similar between the hybrid and autograft groups. Revision surgery was required in 5 (18.5%) patients who underwent hybrid reconstruction compared with 2 (7.4%) of those who underwent autograft reconstruction (P = .26). Conclusion: Patients who undergo ACL reconstruction with hybrid hamstring grafts and hamstring autografts report similar
Lawrence, James P; Waked, Walid; Gillon, Thomas J; White, Andrew P; Spock, Christopher R; Biswas, Debdut; Rosenberger, Patricia; Troiano, Nancy; Albert, Todd J; Grauer, Jonathan N
The study design consisted of a New Zealand white rabbit model of pseudarthrosis repair. Study groups consisting of no graft, autograft, or recombinant human bone morphogenetic protein-2 (rhBMP-2) with absorbable collagen sponge (ACS) or compression resistant matrix (CRM) were evaluated. To evaluate the relative efficacy of bone graft materials (autograft, ACS, and CRM). rhBMP-2 has been shown to have a 100% fusion rate in a primary rabbit fusion model, even in the presence of nicotine, which is known to inhibit fusion. Seventy-two New Zealand white rabbits underwent posterolateral lumbar fusion with iliac crest autograft. To establish pseudarthroses, nicotine was administered to all animals. At 5 weeks, the spines were explored and all pseudarthroses were redecorticated and implanted with no graft, autograft, rhBMP-2/ACS, or rhBMP-2/CRM. At 10 weeks, fusions were assessed by manual palpation and histology. Eight rabbits (11%) were lost to complications. At 5 weeks, 66 (97%) had pseudarthroses. At 10 weeks, attempted pseudarthrosis repairs were fused in 1 of 16 of no graft rabbits (6%), 5 of 17 autograft rabbits (29%), and 31 of 31 rhBMP-2 rabbits (with ACS or CRM) (100%). Histologic analysis demonstrated more mature bone formation in the rhBMP-2 groups. The 2 rhBMP-2 formulations led to significantly higher fusion rates and histologic bone formation than no graft and autograft controls in this pseudarthrosis repair model.
Branski, Ludwik K; Mittermayr, Rainer; Herndon, David N; Jeschke, Marc G; Hofmann, Martina; Masters, Oscar E; Norbury, William B; Traber, Daniel L; Tangl, Stefan; Redl, Heinz
Autograft take and rapid wound closure is essential for the survival of severely burned patients. Loss of skin grafts typically occurs during the first few days after coverage, mainly due to shear forces and inadequate contact with the wound bed. Slow-clotting fibrin sealant, applied with a spray-on device, has been shown to improve healing of skin grafts in large wounds. However, its use in burn wounds has not been studied so far. To evaluate the effectiveness of sprayed fibrin sealant in excised and grafted full-thickness burns. Ten female Yorkshire pigs (30-45 kg) received a full-thickness contact burn of approximately 15% total body surface area. The burns were excised to the level of the muscular fascia after 24 h and covered with meshed skin autograft (mesh ratio 1:3). Wounds were randomized to either fibrin sealant (n=20) or standard skin staples (n=16) for graft fixation. Fibrin sealant was used as a slow-clotting spray (4 IU thrombin/ml). Outcome measurements included clinical scoring at days 2, 5, 9 and 14 postoperatively, planimetric analysis of wound closure, and histological examination of epidermal and dermal thickness 14 days after autografting. In the fibrin sealant group, graft adherence scores were significantly increased (p<0.02) and graft dislocation scores significantly decreased (p<0.01) at days 2 and 5 postoperatively, when compared to controls. Planimetric analysis of remaining open mesh interstices showed acceleration of wound closure in the fibrin sealant group but did not reach statistical significance (day 14 p=0.04 at significance level p<0.025). Wound contraction, occurrence of hematoma, and dermal as well as epidermal thickness were not different between the groups at 14 days postoperatively. The results indicate that the use of slow-clotting fibrin sealant spray for autograft fixation is advantageous over skin staples. Easy handling and reduced graft dislocation at early time points are key qualities of this method. Copyright © 2011
Egol, Kenneth A; Nauth, Aaron; Lee, Mark; Pape, Hans-Christoph; Watson, J Tracy; Borrelli, Joseph
Acute fractures, nonunions, and nonunions with bone defects or osteomyelitis often need bone graft to facilitate union. There are several factors to consider when it is determined that a bone graft is needed. These factors include the source of the bone graft (autograft vs. allograft), proper timing for placement of the bone graft, strategies to avoid further complications (particularly in the setting of osteomyelitis), and with the development of a variety of bone graft substitutes, whether alternatives to autograft are available and appropriate for the task at hand. Autograft bone has commonly been referred to as the "gold standard" of bone grafts, against which the efficacy of other grafts has been measured. The best timing for when to place a bone graft or substitute is also somewhat controversial, particularly after an open fracture or a potentially contaminated bed. The treatment of infected nonunions, particularly those that require a graft to facilitate healing, can be quite challenging. Typically, the infection is completely eradicated before placement of a bone graft, but achieving a sterile bed and the timing of a bone graft require strategic thinking and planning. This review outlines the benefits of autografts, the most suitable sites for harvesting bone grafts, the timing of bone graft procedures, the potential risks and benefits of grafting in the face of infection, and the currently available bone graft extenders.
Yadav, Amit R; Bhattad, Khushbu Ramesh; Sen, Pradhnya Alok; Jain, Elesh Budhendra; Sen, Alok; Jain, Budhendra K
Aim: To analyze surgical outcome of pterygium excision with conjunctival autografting in pediatric population ≤16 years. Settings and Design: Retrospective case series. Materials and Methods: A case sheet review of 145 patients (167 eyes) aged ≤16 years consecutively presented with pterygium from April 2008 to August 2014 in the single center was done. Twenty-six eyes of 25 children who underwent pterygium excision with conjunctival autograft were analyzed. Different techniques used to secure conjunctival autograft in a position were multiple interrupted 8-0 vicryl sutures, single 8-0 vicryl suture in the center of graft and sutureless glue free. Outcome measures were a failure of surgery and recurrence. Results: Of the total 167 eyes, 26 eyes of 25 children, mean age 13.07 ± 3.08 years (range 7–16 years) were managed surgically with pterygium excision and conjunctival autograft. The rest of the patients were managed conservatively. In 18 eyes, the graft was secured with multiple sutures, in 6 eyes with a single suture, whereas in 2 eyes, sutureless glue-free graft opposition was done. Mean follow-up was 8.03 months. No case of graft retraction, graft dehiscence or graft displacement was found. Recurrence occurred in 6 eyes and managed surgically. Conclusions: Occurrence of pterygium is not uncommon in the pediatric population. A single suture or sutureless glue-free technique may be good alternative for securing conjunctival autograft after pterygium excision in children. PMID:26265638
Miller, Christopher P; Chiodo, Christopher P
Bone graft is a common adjunct procedure in orthopedic surgery used for fusions, fracture repair, and the reconstruction of skeletal defects in the foot and ankle. Autologous graft, or autograft, involves the transport of bone from a donor site to another location in the same patient. It is considered by many to be the gold standard of bone grafting, as it is provides all biologic factors required for functional graft. Further, autograft is 100% histocompatible with no risk of disease transmission.
Young, Simon W.; Valladares, Roberto D.; Loi, Florence; Dragoo, Jason L.
Background: Loss of proprioceptive function occurs after anterior cruciate ligament (ACL) rupture. Clinical, motor, and proprioceptive function is known to improve after ACL reconstruction but does not return to normal. While histological studies of human ACL allografts have been unable to demonstrate mechanoreceptor reinnervation, animal data suggest that reinnervation may occur when an autograft is used. Purpose: To compare the presence or absence of mechanoreceptors between allograft versus autograft after ACL reconstruction in humans. Study Design: Cohort study; Level of evidence, 3. Methods: Ten patients with previous ACL reconstruction presenting for either revision ACL surgery or knee arthroscopy for other reasons were enrolled in a prospective, comparative study. Five patients had a previous autograft ACL and 5 patients had an allograft. Biopsies, either from intact or ruptured grafts, were taken from identical locations as close to the femoral and tibial insertions as possible. Specimens were stained with hematoxylin-eosin (H-E) and monoclonal antibodies against neurofilament protein (NFP), known to be present in mechanoreceptor tissue. Immunohistochemical examination was carried out, and the number of NFP+ neural tissue analogs was counted and compared with that of native ACL tissue. Results: The mean time between original graft and biopsy was 6.9 years (range, 0.5-15 years). Histological examination showed significantly less NFP+ neural analogs in allograft and autograft patients than control tissue (mean number of NFP+ analogs per high-power field, 0.7 ± 0.9 [allograft] and 0.5 ± 0.8 [autograft] vs 4.7 ± 0.9 [controls]; P < .0001). There was no significant difference in NFP analogs between autograft and allograft tissue. Conclusion: We found a reduced concentration of NFP+ neural analogs in ACL grafts compared with native ACL tissue. This deficit exists irrespective of whether allograft or autograft is used. These findings may explain the continued
Haifei, Shi; Xingang, Wang; Shoucheng, Wu; Zhengwei, Mao; Chuangang, You; Chunmao, Han
Dermal substitutes are used as dermal regeneration templates to reduce scar formation and improve wound healing. Unlike autografts, dermal substitutes lack normal vascular networks. The increased distance required for diffusion of oxygen and nutrients to the autograft following interpositioning of the substitute dramatically affects graft survival. To evaluate the effect of collagen-chitosan scaffold thickness on dermal regeneration, single-layer collagen-chitosan porous scaffolds of 0.5-, 1- and 2-mm thicknesses were fabricated and used to treat full-thickness wounds in a one-stage grafting procedure in a rat model. Skin-graft viability, wound contraction, histological changes, and wound tensile strength were evaluated. The results indicated that the distance for the diffusion of oxygen and nutrients to the autograft in the 2-mm-thick scaffold provided less support for graft take, which resulted in graft necrosis, extensive inflammatory reaction, marked foreign-body reaction (FBR), rapid scaffold degradation, and abnormal collagen deposition and remodeling. In contrast, the thinner scaffolds, especially of that 0.5-mm thickness, promoted earlier angiogenesis, ensuring skin-graft viability with a mild FBR, and ordered fibroblast infiltration and better collagen remodeling. It can be concluded that collagen-chitosan porous scaffolds with a thickness of <1mm are more suitable for dermal regeneration and can be used as dermal templates for treatment of dermal defects using a one-stage grafting procedure. © 2013 Elsevier Ltd. All rights reserved.
Buescu, Cristian Tudor; Onutu, Adela Hilda; Lucaciu, Dan Osvald; Todor, Adrian
The objective of this study was to compare the pain levels and analgesic consumption after single bundle ACL reconstruction with free quadriceps tendon autograft versus hamstring tendon autograft. A total of 48 patients scheduled for anatomic single-bundle ACL reconstruction were randomized into two groups: the free quadriceps tendon autograft group (24 patients) and the hamstring tendons autograft group (24 patients). A basic multimodal analgesic postoperative program was used for all patients and rescue analgesia was provided with tramadol, at pain scores over 30 on the Visual Analog Scale. The time to the first rescue analgesic, the number of doses of tramadol and pain scores were recorded. The results within the same group were compared with the Wilcoxon signed test. Supplementary analgesic drug administration proved significantly higher in the group of subjects with hamstring grafts, with a median (interquartile range) of 1 (1.3) dose, compared to the group of subjects treated with a quadriceps graft, median = 0.5 (0.1.25) (p = 0.009). A significantly higher number of subjects with a quadriceps graft did not require any supplementary analgesic drug (50%) as compared with subjects with hamstring graft (13%; Z-statistics = 3.01, p = 0.002). The percentage of subjects who required a supplementary analgesic drug was 38% higher in the HT group compared with the FQT group. The use of the free quadriceps tendon autograft for ACL reconstruction leads to less pain and analgesic consumption in the immediate postoperative period compared with the use of hamstrings autograft. Level I Therapeutic study. Copyright © 2017 Turkish Association of Orthopaedics and Traumatology. Production and hosting by Elsevier B.V. All rights reserved.
Zhu, Guochen; Lou, Weihua
Because of ease of harvest and low immunogenicity, xenogeneic acellular nerve graft (XANG) may be an alternative to autologous nerve to repair facial nerve defects. Facial nerve defects of Wistar rats were repaired by XANG, and nerve gap regeneration was investigated by electrophysiological test, horseradish peroxidase (HRP) retrograde tracing and histomorphometric analysis, as compared to autograft. Twenty weeks after the grafting, electrophysiology showed that whisker pad muscles responded to the electrical stimuli given at the site proximal to the transplantation in 2 groups. Some HRP-labeled facial motorneurons were located on the facial nucleus of the operated side, and an abundance of myelinated axons were found at the middle of the grafts and obvious motor endplates in the target muscles in 2 groups, although they were inferior to the contralateral side in numbers. XANG represents an alternative approach for the reconstruction of peripheral facial nerve defects. Copyright © 2013 Wiley Periodicals, Inc.
Capitán Guarnizo, A; Viviente Rodríguez, E; Osete Albaladejo, J M; Torregrosa Carrasquer, C; Díaz Manzano, J A; Pérez-Mateos Cachá, J A; Sprekelsen Gassó, C
We perform a subcutaneous autograft, in animals with preserved immunity (24 rabbits), of cartilage taken from the auricle, treated with tissue engineering thecnics and embeded in a reabsorbable polimer (Ethisorb) that acts as base. We observed a good quality cartilage with the expression of collagen type II and without graft rejection phenomenon.
Stensbirk, Frederik; Thorborg, Kristian; Konradsen, Lars; Jørgensen, Uffe; Hölmich, Per
The long-term results after using the iliotibial band autograft (ITB) in anterior cruciate ligament (ACL) reconstruction are not fully known. If equal in quality to conventional methods, the ITB graft could be a useful alternative as a primary graft, in revision surgery or multi-ligament reconstruction. The purpose is to assess whether the ITB autograft is a long-term reliable alternative to the bone-patella-tendon-bone (BPTB) autograft, using a prospective randomized controlled trial design. From 1995 to 1996, sixty patients scheduled for primary ACL reconstruction were included in a prospective randomized controlled trial. Three senior knee surgeons, experienced in both types of ACL surgery, performed all the operations. A standardized and supervised rehabilitation programme was used for both groups for 6 months. Thirty patients received the ITB reconstruction, and 30 received the BPTB reconstruction. Forty-nine participated at follow-up in 2010 (82%). Primary outcome was the failure rate after ACL reconstruction. Secondary outcomes were knee injury osteoarthritis outcome score (KOOS) [pain, symptoms, Sport/Rec, quality of life (QOL), daily living function], Tegner activity scale, anterior knee pain-score, Lysholm score, Rolimeter laxity, extension deficit, single hop and crossover hop for distance. At 15-year follow-up, no significant difference existed between the groups. Graft failure occurred in 4 ITB subjects (16%) and 3 BPTB subjects (13%). KOOS (Sport/Rec) for the ITB group was 75 and 73 for the BPTB group. The KOOS (QOL) was 72 and 68 for the ITB group and BPTB group, respectively. Similar graft failure rates and KOOS were found when comparing ITB- and BPTB-operated individuals, at 15-year follow-up. The ITB graft had equal long-term clinical results compared to the BPTB graft and is recommended as a reliable alternative autograft for ACL reconstruction. Therapeutic studies, Level I.
Chan, C.; Chew, P.; Alsagoff, Z.; Wong, J. S.; Tan, D.
AIMS—To characterise the vasculature of pterygium using indocyanine green (ICG) anterior segment angiography and to demonstrate the pattern of revascularisation following conjunctival autografting. METHODS—ICG anterior segment angiography was performed on nine patients with pterygium. Angiography was repeated at 1-2 weeks and 2 months following conjunctival autografting in these patients. RESULTS—Angiography showed a single feeder vessel originating from the anterior conjunctival circulation in six cases (66.7%). This vessel branched to form the radial vessels of the pterygium. Following conjunctival autografting, reperfusion of the vessels in the conjunctival autograft was demonstrable as early as 1 week postoperatively from the episcleral bed. At 2 months postoperatively, the graft appeared well perfused with mild leakage demonstrable at the edges of the graft. CONCLUSIONS—A single feeder vessel from the anterior conjunctival circulation branches to form the radial vessels in pterygium. Reperfusion of conjunctival autografts occurs as early as 1 week postoperatively from the episcleral bed. PMID:11222345
Müller, Sebastian A.; Barg, Alexej; Vavken, Patrick; Valderrabano, Victor; Müller, Andreas M.
Abstract Sterilized allografts may be less resistant to collapse and prone to nonunion leading to loss of correction in open wedge osteotomies. These adverse events usually occur at early time points (i.e., < 9 months postoperatively). The goal of this study was to compare sterilized allografts to autologous grafts in respect to secondary loss of hindfoot alignment and graft incorporation after lateral calcaneal lengthening osteotomies. Fifty patients (22 F/ 28 M, age: 16–69 years) who had undergone 50 lateral calcaneal lengthening osteotomies for adult flatfoot deformity were included in this retrospective study. Cortical sterilized allografts were used in 25 patients, autologous grafts in the remaining 25. Patients’ preoperative, 6 and 12 weeks, and 6 to 9 months follow-up weight-bearing radiographs of the affected foot were analyzed by 2 blinded radiologists: on each radiograph, graft incorporation, the talo-first metatarsal angle (TFMA), the talo-navicular coverage angle (TNCA), and the calcaneal pitch angle (CPA) were assessed. Loss of hindfoot alignment was defined as an increase of the TFMA or the TNCA or a decrease of the CPA, each by 5°. Inter- and intraclass correlation coefficients for TFMA, TNCA, and CPA measurements ranged from 0.93 to 0.99. At all follow-up visits, the ratio of patients with loss of hindfoot alignment and graft incorporation was not significantly different between the allograft and autograft group. However, loss of correction was associated with failure of graft incorporation. Compared with autografts, sterilized allografts do not increase the risk for loss of hindfoot alignment in lateral column lengthening of the calcaneus. With respect to mechanical resistance, allografts thus mean an equal and valid alternative without risk of donor site morbidities. PMID:27472719
Firat, Cemal; Gurlek, Ali; Aydin, Nasuhi Engin; Aydn, Nasuhi Engin
The viability of cartilage grafts, in many forms, has been researched since the using of cartilage grafts in surgical procedures. Cryopreservation period and viability of cartilage grafts have remained unclear. This study was performed to investigate the durability, viability, and behavior of fresh or cryopreserved cartilage grafts when used as autografts or allografts in various forms.Six cartilage grafts (1 of each preparation type; 3 blocks and 3 diced) were prepared by wrapping with Surgicel or autogenous fascia, or they were left bare. After the graft preparation stage, the cartilage grafts were inserted into pockets prepared on the dorsum of each rabbit. Groups 1, 2, 3, and 4 (6 rabbits in each group) received autogenous fresh grafts, allogenous fresh grafts, autogenous cryopreserved grafts, and allogenous cryopreserved grafts, respectively. All cartilage grafts were implanted for 2 months.At the end of the second month, specimens were harvested and analyzed. The bare grafts provided the most viable specimens. There was no significant difference between the frozen or fresh and allograft or autograft groups with respect to viability and resorption ratios. The bare block graft, in all groups, survived significantly more than the other graft types.Allografts (homografts), similar autografts, did not create major problems, and they had excellent host tolerance and low antigenicity, especially when the perichondrium was removed. Viability and durability of the bare grafts (diced and block) were better than fascia or Surgicel-wrapped cartilage graft forms.
Hammer, Peter E.; Chen, Peter C.; del Nido, Pedro J.; Howe, Robert D.
Aortic valve reconstruction using leaflet grafts made from autologous pericardium is an effective surgical treatment for some forms of aortic regurgitation. Despite favorable outcomes in the hands of skilled surgeons, the procedure is underutilized because of the difficulty of sizing grafts to effectively seal with the native leaflets. Difficulty is largely due to the complex geometry and function of the valve and the lower distensibility of the graft material relative to native leaflet tissue. We used a structural finite element model to explore how a pericardial leaflet graft of various sizes interacts with two native leaflets when the valve is closed and loaded. Native leaflets and pericardium are described by anisotropic, hyperelastic constitutive laws, and we model all three leaflets explicitly and resolve leaflet contact in order to simulate repair strategies that are asymmetrical with respect to valve geometry and leaflet properties. We ran simulations with pericardial leaflet grafts of various widths (increase of 0%, 7%, 14%, 21% and 27%) and heights (increase of 0%, 13%, 27% and 40%) relative to the native leaflets. Effectiveness of valve closure was quantified based on the overlap between coapting leaflets. Results showed that graft width and height must both be increased to achieve proper valve closure, and that a graft 21% wider and 27% higher than the native leaflet creates a seal similar to a valve with three normal leaflets. Experimental validation in excised porcine aortas (n=9) corroborates the results of simulations. PMID:22341628
Welder, Jeffrey D; Pandya, Hemang K; Nassiri, Nariman; Djalilian, Ali R
Conjunctival limbal autograft is the surgical treatment of choice for visually significant unilateral limbal stem cell deficiency. The use of fibrin glue, which has been reported extensively in pterygium and other conjunctival surgeries, has not been fully described in limbal stem cell transplantation. The authors reviewed 3 cases of conjunctival limbal autograft and 1 of living related conjunctival limbal allograft using only fibrin glue to secure the graft. Main outcome measures included ocular surface stability, visual acuity, and postoperative complications. At most recent follow-up, all 4 patients (100%) maintained a stable ocular surface. Mean epithelial healing time was 10 days. Mean visual acuity improved from 20/400 to 20/53. All grafts were successful with no postoperative dislocations or displacements. The findings demonstrate that fibrin glue can be used safely and effectively to secure conjunctival limbal grafts in limbal stem cell deficiency. This novel approach has the potential to decrease operative time, increase ease of technique, and improve patient comfort postoperatively. Copyright 2012, SLACK Incorporated.
Jacobs, Cale A; Burnham, Jeremy M; Makhni, Eric; Malempati, Chaitu S; Swart, Eric; Johnson, Darren L
Younger patients and those with smaller hamstring autograft diameters have been shown to be at significantly greater risk of graft failure after anterior cruciate ligament (ACL) reconstruction. To date, there is no information in the literature about the clinical success and/or cost-effectiveness of increasing graft diameter by augmenting with semitendinosus allograft tissue for younger patients. Hybrid hamstring grafts are a cost-effective treatment option because of a reduced rate of graft failure. Cohort study (economic and decision analysis); Level of evidence, 3. We retrospectively identified patients younger than 18 years who had undergone ACL reconstruction by a single surgeon between 2010 and 2015. During this period, the operating surgeon's graft selection algorithm included the use of bone-patellar tendon-bone (BTB) autografts for the majority of patients younger than 18 years. However, hamstring autografts (hamstring) or hybrid hamstring autografts with allograft augment (hybrid) were used in skeletally immature patients and in those whom the surgeon felt might have greater difficulty with postoperative rehabilitation after BTB graft harvest. Patient demographics, graft type, graft diameter, the time the patient was cleared to return to activity, and the need for secondary surgical procedures were compared between the hamstring and hybrid groups. The clinical results were then used to assess the potential cost-effectiveness of hybrid grafts in this select group of young patients with an ACL injury or reconstruction. This study comprised 88 patients (hamstring group, n = 46; hybrid group, n = 42). The 2 groups did not differ in terms of age, sex, timing of return to activity, or prevalence of skeletally immature patients. Graft diameters were significantly smaller in the hamstring group (7.8 vs 9.9 mm; P < .001), which corresponded with a significantly greater rate of graft failure (13 of 46 [28.3%] vs 5 of 42 [11.9%]; P = .049). As a result of the
Plante, Matthew J; Li, Xinning; Scully, Gail; Brown, Michael A; Busconi, Brian D; DeAngelis, Nicola A
Inadvertent contamination of the hamstring autograft during ACL reconstruction is infrequent, but can result in significant complications. The purpose of this study is to evaluate bacterial contamination of hamstring autografts dropped onto the operating room floor and methods of graft decontamination. Hamstring tendons were harvested from patients. Excess tendon not used in the ACL procedure was divided into 6 segments. Segments were assigned to 6 groups (A through F, N = 30 in each group): group A: uncontaminated graft immediately postharvest (control), group B: graft dropped onto the floor (5 s), group C: graft dropped onto the floor (15 s). grafts in groups D to F were dropped onto floor for 15 s then rinsed with saline (group D), bacitracin solution (group E) or chlorhexidine 4 % solution (group F) for 3 min. All grafts were sent to the microbiology laboratory for anaerobic and aerobic cultures. Cultures were positive in 23 % of graft segments from group A (7/30), 33 % of grafts from group B (10/30), 23 % from group C (7/30), 30 % from group D (9/30) and 3 % from both group E (1/30) and group F (1/30). Sixteen unique organisms were identified, with Staphylococcus aureus as the most common isolate. Grafts rinsed in either bacitracin solution or 4 % chlorhexidine solutions were significantly less likely to be culture positive when compared to control graft segments (p < 0.05). However, there was no significant difference between uncontaminated grafts retrieved in <5 versus 15 s from the floor. This study supports the practice of decontaminating a dropped ACL hamstring autograft using either 4 % chlorhexidine or bacitracin solution. Specimens should be retrieved sterilely and washed for at least 3 min. This study also demonstrates no advantage in retrieval time of less than 5 s as compared to 15 s for uncontaminated graft. Hamstring harvest in ACL reconstruction may result in positive cultures, thus routine soaking of the hamstring autograft
Neuhaus, R W; Shorr, N
A wide variety of materials have been used for reconstruction around the eyelids and orbit, including alloplastic materials, such as polyfilament surgical suture (Supramid), silicone, and Teflon, that have a tendency toward early infection or late extrusion. Preserved homografts, such as sclera or fascia lata, are unlikely to extrude but have variable absorption rates. Autografts have proved over the years to be the best, most reliable, and least reactive material for reconstruction. Our use of temporal fascia and muscule grafts has been quite successful.
Mittal, Kanhaiya; Gupta, Shikha; Khokhar, Sudarshan; Vanathi, Murugesan; Sharma, Namrata; Agarwal, Tushar; Vajpayee, Rasik Bihari
To compare graft outcomes following pterygium excision and conjunctival autograft fixation using patient's in situ autologous blood or standard fibrin glue-assisted conjunctival autograft adhesion. Outcomes of 23 consecutive eyes which underwent pterygium excision and conjunctival autograft with autologous in situ blood coagulum (group I) were compared with historical case controls (20 eyes) that had undergone fibrin glue-assisted conjunctival autograft (group II). Primary outcome measure was graft stability. Secondary outcome measure was severity of graft inflammation at day 1, day 7, 3 months, and 6 months. The two groups were similar regarding age, gender, uncorrected visual acuity (UCVA), best corrected visual acuity (BCVA), refractive error, tear function tests, and pterygium size. Mean surgical time was similar for the two groups (14.2±2.74 min, group I; 12.25±1.88 min, group II; P=0.1); with the mean difference in operative time being 1.95 min (95% CI, 0.48-3.42 min). Postoperatively, there was a statistically significant reduction in astigmatism and improvement in UCVA, BCVA, and spherical equivalent in all eyes. No difference was found in mean epithelial defect healing time, UCVA, BCVA, astigmatism, tear film break-up time, and Schirmer I and II at 6 months between the two groups. Initial graft stability was better for group II at 1 month (P=0.001) but was similar for both groups at 6 months. Median score of graft inflammation was significantly more for group II during the first week (P<0.05; Wilcoxon rank-sum test). Autologous blood may be used as an effective alternative with lesser postoperative inflammation in comparison to glue-assisted autograft fixation.
Nadarajah, Gaayathri; Ratnalingam, Vanitha Hema; Mohd Isa, Hazlita
To evaluate graft stability and recurrence rate between fibrin glue and autologous blood in pterygium conjunctival autograft surgery. A prospective, randomized, single-blinded clinical trial to assess the efficacy of autologous blood in place of fibrin glue in pterygium surgery. A total of 120 eyes of 111 patients were randomized according to pterygium morphology, to undergo pterygium surgery with autografting using either autologous blood or fibrin glue. All patients were operated by a single surgeon; 58 eyes were operated using fibrin glue and 62 eyes had a conjunctival autograft with autologous blood. Patients were seen on postoperative day 1, 1 week, 1 month, 6 months, and 1 year after surgery. Graft stability and pterygium recurrence were graded by an independent observer who was masked to the method of treatment. All 120 eyes completed the 1-year follow-up. Graft loss was seen only in the autologous blood group. Of the 62 eyes in this group, a total of 15 (24.2%) grafts dislodged. Recurrence was calculated after excluding grafts that were dislodged. Of the 105 patients, there were a total of 7 recurrences, 2 (3.4%) from the fibrin adhesive method and 5 (10.6%) from the autologous blood method. This was not statistically significant (P = 0.238). Autologous blood does not exhibit similar graft stability seen with fibrin glue. Although the recurrence rate may not be significant, careful patient selection and a standard method needs to be laid out before the use of this method is widely accepted.
Pakyari, Mohammadreza; Farokhi, Ali; Khosravi-Maharlooei, Mohsen; Kilani, Ruhangiz T; Ghahary, Aziz; Brown, Erin
Skin transplantation provides an excellent potential model to investigate the immunology of allograft rejection and tolerance induction. Despite the theoretical ease of performing skin transplantation, as well as the potential of directly observing the reaction to the transplanted tissue, the poor reliability of skin transplantation in the mouse has largely precluded the use of this model. Furthermore, there is controversy regarding the most appropriate skin graft donor site due to poor success of back skin transplantation, as compared with the thinner ear or tail skin. This study demonstrates a reliable method to successfully perform skin grafts in a mouse model, as well as the clinical and histologic outcome of syngeneic grafts. A total of 287 grafts were performed (in 126 mice) utilizing donor skin from the ear, tail or back. No graft failure or postoperative mortality was observed. Comparison of this technique with two previously established protocols of skin transplantation (5.0 absorbable Suture + tissue glue technique and no-suture technique) demonstrates the significant improvement in the engraftment success of the new technique. In summary, a new technique for murine skin grafting demonstrates improved reliability across donor site locations and strains, increasing the potential for investigating interventions to alter the rejection process. © 2016 by the Wound Healing Society.
Bailey, J Kevin; Blackstone, Britani N; DeBruler, Danielle M; Kim, Jayne Y; Baumann, Molly E; McFarland, Kevin L; Imeokparia, Folasade O; Supp, Dorothy M; Powell, Heather M
The use of pulsed dye laser (PDL) and fractional CO2 (FX CO2 ) laser therapy to treat and/or prevent scarring following burn injury is becoming more widespread with a number of studies reporting reduction in scar erythema and pruritus following treatment with lasers. While the majority of studies report positive outcomes following PDL or FX CO2 therapy, a number of studies have reported no benefit or worsening of the scar following treatment. The objective of this study was to directly compare the efficacy of PDL, FX CO2 , and PDL + FX CO2 laser therapy in reducing scarring post burn injury and autografting in a standardized animal model. Eight female red Duroc pigs (FRDP) received 4 standardized, 1 in. x 1 in. third degree burns that were excised and autografted. Wound sites were treated with PDL, FX CO2 , or both at 4, 8, and 12 weeks post grafting. Grafts receiving no laser therapy served as controls. Scar appearance, morphology, size, and erythema were assessed and punch biopsies collected at weeks 4, 8, 12, and 16. At week 16, additional tissue was collected for biomechanical analyses and markers for inflammatory cytokines, extracellular matrix (ECM) proteins, re-epithelialization, pigmentation, and angiogenesis were quantified at all time points using qRT-PCR. Treatment with PDL, FX CO2 , or PDL + FX CO2 resulted in significantly less contraction versus skin graft only controls with no statistically significant difference among laser therapy groups. Scars treated with both PDL and FX CO2 were visually more erythematous than other groups with a significant increase in redness between two and three standard deviations above normal skin redness. Scars treated with FX CO2 were visually smoother and contained significantly fewer wrinkles. In addition, hyperpigmentation was significantly reduced in scars treated with FX CO2 . The use of fractional carbon dioxide or pulsed dye laser therapy within 1 month of autografting significantly reduced scar
Papaziogas, B; Antoniadis, A; Lazaridis, Ch; Makris, J; Kotakidou, R; Paraskevas, G; Papaziogas, T
The aim of this study was to investigate the functional capacity of thyroid autografts after total thyroidectomy in a rabbit model. Thirty-eight rabbits underwent total thyroidetomy. One of the two thyroid lobes was cut into 1-mm pieces and was introduced intramuscularly into the right quadriceps muscle (group A, n = 10), the right rectus abdominalis muscle (group B, n = 10), and the right sacrodorsalis muscle (group C, n = 10). Another group of 8 rabbits underwent total thyroidectomy without autologous implantation and served as the control group (group D). The animals were observed for 8 weeks with weekly measurements of thyroid hormones. At the end of the 8th week, a scintigram was performed. The autografts were removed 2 days later. The thyroid hormone levels showed a gradual decrease until the 2nd-5th week after implantation, followed by a gradual increase and establishment of euthyroid levels between the 5th and 8th weeks. Respectively, an increase of thyreotropin hormone was noted with maximal values in the 4th week, followed by a gradual decrease until the end of the 8th week. The scintigram at the end of the 8th week revealed the presence of functional thyroid tissue in all cases. Functional thyroid follicles were found in all animals who survived. In 35.7% of the autografts, we noted the development of fibrous tissue and gigantocytic granulomas in the periphery, which could be interpretated as a "foreign body" reaction. Thyroid autografts can completely substitute thyroid function after total thyroidectomy.
Epstein, Nancy E.
Background: Grafting choices available for performing anterior cervical diskectomy/fusion (ACDF) procedures have become a major concern for spinal surgeons, and their institutions. The “gold standard”, iliac crest autograft, may still be the best and least expensive grafting option; it deserves to be reassessed along with the pros, cons, and costs for alternative grafts/spacers. Methods: Although single or multilevel ACDF have utilized iliac crest autograft for decades, the implant industry now offers multiple alternative grafting and spacer devices; (allografts, cages, polyether-etherketone (PEEK) amongst others). While most studies have focused on fusion rates and clinical outcomes following ACDF, few have analyzed the “value-added” of these various constructs (e.g. safety/efficacy, risks/complications, costs). Results: The majority of studies document 95%-100% fusion rates when iliac crest autograft is utilized to perform single level ACDF (X-ray or CT confirmed at 6-12 postoperative months). Although many allograft studies similarly quote 90%-100% fusion rates (X-ray alone confirmed at 6-12 postoperative months), a recent “post hoc analysis of data from a prospective multicenter trial” (Riew KD et. al., CSRS Abstract Dec. 2011; unpublished) revealed a much higher delayed fusion rate using allografts at one year 55.7%, 2 years 87%, and four years 92%. Conclusion: Iliac crest autograft utilized for single or multilevel ACDF is associated with the highest fusion, lowest complication rates, and significantly lower costs compared with allograft, cages, PEEK, or other grafts. As spinal surgeons and institutions become more cost conscious, we will have to account for the “value added” of these increasingly expensive graft constructs. PMID:22905321
Lin, Dan-Jae; Ju, Chien-Ping; Huang, Shu-Huei; Tien, Yin-Chun; Yin, Hsiang-Shu; Chen, Wen-Cheng; Chern Lin, Jiin-Huey
The purpose of this study was to evaluate the osteointegration of a titanium (Ti) implant with the calcium phosphate cement (CPC) and autograft prostheses by pull-out test and histological examination. Stems of sixty Ti cylinders were bilaterally inserted into femoral medullary canals in 30 rabbits at the 1st, 4th, 12th, 26th and 70th postoperative weeks. The bone autograft and CPC were filled into the pre-trimmed bone marrow cavity with a polymethyl methacrylate retarder in the distal end, and then a Ti cylinder was inserted into femurs. The CPC group was significantly (p<0.05) associated with a larger pull-out force at 4th (37%) and 12th (62%) weeks compared to the autograft group. The bone area and the bone-to-implant contact ratios of the CPC groups were significantly higher than that of the autograft groups at early healing stage. The histological exams suggest that the CPC enhanced the earlier bone formation around the implant at a period not longer than 12 weeks postoperation. We conclude that CPC graft has the higher ability to facilitate the osteointegration and stabilize the Ti implant at a relatively early stage than the autograft in vivo. Copyright © 2011. Published by Elsevier Ltd.
Cakmak, Attila; Cirpanli, Yasemin; Bilensoy, Erem; Yorganci, Kaya; Caliş, Sema; Saribaş, Zeynep; Kaynaroğlu, Volkan
The use of mesh in hernia repair has become common, because of lower recurrence rate and simple application. Data from the meta-analysis and the multi-central studies support the use of meshes in hernia repair. One of the complications due to the hernia repair with mesh is the infection. The incidence range is between 1 and 10%. Triclosan embedded commercial absorbable suture materials are used to reduce surgical site infection rate. This study was planned on mesh infection model, because of the low incidence rate. The agent isolated from mesh infections was mostly Staphylococcus aureus and thus it was used as the infecting agent in this research. To achieve a better therapeutic efficacy, triclosan was formulated in chitosan gels. Chitosan is an attractive biopolymer because of its biocompatible, biodegradable, bioadhesive properties. Gel formulations using chitosans (low, medium and high molecular weight) were prepared in 1% (v/v) acetic acid solution and in vitro release profiles were evaluated. Gel formulations showed release profile extended up to 7 days and high molecular weight chitosan gel formulation was released higher quantity drug than other formulations. Meshes coated with triclosan loaded chitosan gel were used to reduce bacterial count and to prevent mesh infection in the study. 24h and simultaneous bacteria inoculation was used to model mesh infection. The rats were observed for 8 days by means of surgical site infection. On the eighth day, the animals were sacrificed and the grafts were removed. Tissue squeezers were used to liberate bacterias from removed grafts. The isolated suspensions were cultured on blood agar plates and colony-forming units were counted overnight. Grafts coated with triclosan loaded chitosan gel presented satisfactory preventive effect against graft infection.
Shakked, Rachel; Weinberg, Maxwell; Capo, Jason; Jazrawi, Laith; Strauss, Eric
With the increasing incidence of anterior cruciate ligament (ACL) reconstruction in women and younger patients, the optimal graft choice in the young female patient has become the subject of much debate. This study aimed to evaluate patient-reported outcomes, objective knee stability, complication rates, and the incidence of failure after ACL reconstruction using bone-patellar tendon-bone (BPTB) autograft compared with hamstring (HS) autograft in young female patients. Female patients who underwent primary ACL reconstruction with BPTB or HS autograft between ages 15 and 25 years were identified. Medical records were reviewed for postoperative complications and subsequent procedures on the operative knee. Patients were evaluated with functional surveys, physical examination including Lachman and pivot-shift tests, and arthrometric testing with a KT-1000 arthrometer. There were 37 patients in the BPTB group and 28 patients in the HS group. For patients who did not undergo revision, significant differences were not found in visual analog score (p = 0.94), Lysholm score (p = 0.81), Kujala score (p = 0.85), or Tegner level (p = 0.81). No difference was detected in the rate of return to a level of activity at or above the same level prior to injury (p = 0.31). Significantly more patients in the BPTB group were graded 1a Lachman and negative pivot shift compared with the HS group (p < 0.001). There was a significant difference in mean side-to-side manual maximum arthrometric testing (p < 0.001). There were significantly fewer subsequent procedures and a lower rate of graft failures in the BPTB group. We detected no difference in subjective functional outcomes following ACL reconstruction. However, a higher failure rate in the HS reconstructions and greater laxity by arthrometric testing may indicate increased objective stability with the use of BPTB autograft in the young female patient population. The level of evidence for this article is
Chang, Spencer K Y; Egami, Darren K; Shaieb, Mark D; Kan, Darryl M; Richardson, Allen B
This study was performed to compare the minimal 2-year outcome of anterior cruciate ligament (ACL) reconstruction using bone-patellar tendon-bone (BPTB) allografts versus autografts, both augmented with an iliotibial band tenodesis. Retrospective review. Forty-six of 52 BPTB ACL reconstructions using allografts and 33 of 37 BPTB ACL reconstructions using autografts were followed up at a mean of 2.75 and 3.36 years, respectively. All patients had an iliotibial band tenodesis. Evaluations included the Lysholm II scale, a questionnaire, physical examination findings, and KT-1000 arthrometry. No statistically significant differences were seen between groups in Lysholm II scores or in any subjective category. Most patients (91% allograft; 97% autograft) had good to excellent Lysholm II scores. Sixty-five percent of allograft patients and 73% of autograft patients returned to their preinjury activity level. More allograft patients complained of retropatellar pain (16% v 9% for autograft patients). Fifty-three percent of allograft patients versus 23% of autograft patients had a flexion deficit of 5 degrees or more when compared with the normal contralateral side. When comparing KT-1000 side-to-side differences, we found no significant differences between groups. Ninety-one percent of both groups had maximum side-to-side differences less than 5 mm. Three allograft patients (6.5%) had traumatic ruptures at 12, 19, and 43 months postoperatively versus none in the autograft group. All three allograft patients who sustained postoperative traumatic ruptures had received fresh frozen, nonirradiated allografts. Results of ACL reconstruction using allografts or autografts augmented with an iliotibial band tenodesis were comparable. The BPTB autograft should remain the gold standard, although the BPTB allograft in ACL reconstruction is a reasonable alternative.
Truedsson, A; Hjalte, K; Sunzel, B; Warfvinge, G
To estimate and compare the costs of maxillary sinus augmentation performed with autologous bone graft either from the iliac crest or from local bone harvested from the mandibula. To evaluate post-operative health-related quality-of-life parameters for patients subjected to sinus augmentation and iliac bone surgery. The hospital records of 14 patients subjected to sinus augmentation with iliac autograft, and 14 patients treated with local autograft, were analysed with regard to costs related to surgery, hospitalization and sick leave. Post-operative health parameters were assessed with a questionnaire. Mean hospital costs, administration excluded, for sinus augmentation with iliac autograft was €3447. Policlinic treatment alternatives e.g. local bone autograft with or without bone substitutes, rendered costs of approximately 42% thereof. The loss of production for a worker was 41% of the total cost (€9285). With regard to health-related quality-of-life and post-operative morbidity, most of the patients had recovered 14 days after the iliac graft surgery. The cost for a sinus augmentation with iliac surgery exceeds that of a policlinic procedure manifold. Provided that a policlinic operation with local bone, with or without bone substitute, renders an adequate end result, the economic gain would be substantial and post-operative morbidity would be greatly reduced. © 2012 John Wiley & Sons A/S.
Boorman, R S; Shrive, N G; Frank, C B
Rehabilitation after soft-tissue autograft reconstructions is controversial because there is indirect evidence that some grafts fail by creeping over time. The vulnerability of soft-tissue grafts to creep over healing time and the effects of the load environment during healing on this vulnerability have never been studied specifically. We hypothesized that immobilization would decrease the magnitude of the vulnerability of ligament grafts to creep. Thirty-nine skeletally mature New Zealand White rabbits underwent a standardized medial collateral ligament autograft procedure to the right hindlimb, and 19 of the rabbits also had the limb rigidly pinned into flexion. Subgroups were killed at 3 or 8 weeks, and all isolated tibia/medial collateral ligament/femur complexes were tested for creep at 4.1 MPa under a standardized protocol. Eight normal medial collateral ligament controls were tested similarly. Results showed that all grafts were quantitatively more susceptible to cyclic and static creep than were normal medial collateral ligament controls (p < 0.05). By 3 weeks of healing, immobilization significantly increased the magnitude of the vulnerability of the grafts to cyclic, static, and total creep (all: p < 0.05). Furthermore, the grafts had more unrecovered creep strain than did the controls following a 20-minute recovery period. Contrary to our hypothesis, immobilization resulted in increased vulnerability of these ligament autografts to creep even with this relatively nonprovocative test of short duration and low stress. We postulate that following immobilization, this increase in the magnitude of susceptibility of the grafts to creep will result in functionally significant elongation of the graft if it is exposed to higher loads and over longer periods of time in vivo.
Numerous natural and industrial processes demand advances in our fundamental understanding of colloidal adsorption at liquid interfaces. Using dissipative particle dynamics (DPD), we model the interfacial adsorption of core-shell nanoparticles at the water-oil interface. The solid core of the nanoparticle encompasses beads arranged in an fcc lattice structure and its surface is uniformly grafted with polymer chains. The nanoparticles bind to the interface from either phase to minimize total surface energy. With a single nanoparticle, we demonstrate detailed kinetics of different stages in the adsorption process. Prominent effect of grafted polymer chains is characterized by varying molecular weight and polydispersity of the chains. We also preload nanoparticles straddling the interface to reveal the influence of nanoparticle surface density on further adsorption. Importantly, these studies show how surface-grafted polymer chains can alter the interfacial behavior of colloidal particles and provide guidelines for designing on-demand Pickering emulsion.
Leet, Arabella I.; Boyce, Alison M.; Ibrahim, Khalda A.; Wientroub, Shlomo; Kushner, Harvey; Collins, Michael T.
Background: Polyostotic fibrous dysplasia is a skeletal disease that results from somatic activating mutations in the gene GNAS in skeletal stem cells, leading to proliferation of immature osteogenic cells with replacement of normal marrow and bone with fibro-osseous tissue. Lesions may cause bone deformity or fracture. In the surgical care of polyostotic fibrous dysplasia, the role of grafting and the optimal grafting material are not clear. The purpose of this study was to evaluate the long-term survival of bone-grafting procedures in subjects with polyostotic fibrous dysplasia over time. Methods: The operative reports and radiographs of a cohort of subjects with polyostotic fibrous dysplasia followed in a natural history study were reviewed. Twenty-three subjects (mean age at the time of enrollment, thirteen years [range, two to forty years]) with fifty-two bone-grafting procedures had a mean follow-up time of 19.6 years (range, twenty-nine months to forty-seven years). Kaplan-Meier life table estimates, Cox proportional hazard models, and t tests comparing means were performed to assess various aspects of graft survival. Results: Kaplan-Meier curves showed a 50% estimate of survival of 14.5 years. Cox proportional hazards models showed no advantage comparing allograft with autograft or structural with nonstructural graft materials. The mean age of the patients was significantly greater (p < 0.001) in the subgroup of subjects in whom grafts were maintained over time (20.9 years) compared with the subgroup of patients whose grafts were resorbed over time (9.8 years). Conclusions: Bone-grafting, including both allograft and autograft, is of limited value in ablating the lesions of fibrous dysplasia. The expectations of patients and surgeons should include the high probability of graft resorption over time with return of bone characteristics of fibrous dysplasia, particularly in younger patients. This suggests the maintenance of normal bone mechanics with implant
Hashimoto, Takahiro; Sun, Yu-Long; An, Kai-Nan; Amadio, Peter C; Zhao, Chunfeng
For both tendon allografts and autografts, the surface, initially optimized for gliding, may not be ideal to facilitate tissue integration for graft healing to host tendon or bone. As a prelude to studying tendon-bone integration, we investigated the effect of surface treatments with trypsin or mechanical abrasion on cell attachment to the tendon surface in a canine ex vivo intrasynovial tendon tissue culture model. Intrasynovial tendon allograft surfaces were seeded with cells after the following treatments: (1) no treatment, (2) mechanical abrasion, (3) trypsin, and (4) abrasion and trypsin. The area covered by cells was determined using confocal laser microscopy at one and two weeks. Results were compared to untreated extrasynovial tendon. Additional tendons were characterized with scanning electron microscopy. Tendons with trypsin treatment had significantly more surface coverage with cells than the other groups, after both one and two weeks of culture. In terms of the cellular shape and size, cells on tendons with trypsin treatment spread more and were more polygonal in shape, whereas tendons with mechanical abrasion with/without trypsin treatment contained smaller, more spindle-like cells. Surface roughening can affect cell behavior with topographical stimulation. Trypsin surface digestion exposes a mesh-like structure on the tendon surface, which could enhance cell adherence and, possibly, tendon/bone healing.
Impact of bone morphogenetic proteins on frequency of revision surgery, use of autograft bone, and total hospital charges in surgery for lumbar degenerative disease: review of the Nationwide Inpatient Sample from 2002 to 2008.
Dagostino, Phillip R; Whitmore, Robert G; Smith, Gabriel A; Maltenfort, Mitchell G; Ratliff, John K
Bone morphogenetic proteins (BMPs) were developed with the goal of improving clinical outcomes through the promotion of bony healing and reducing morbidity from iliac crest bone graft harvest. To complete a population-based assessment of the impact of BMP on use of autograft, rates of operative treatment for lumbar pseudoarthrosis, and hospital charges. Nationwide Inpatient Sample (NIS) retrospective cohort assessment of 46,452 patients from 2002 to 2008. All patients who underwent lumbar arthrodesis procedures for degenerative spinal disease. Use of BMP, revision surgery status as a percentage of total procedures, and autograft harvest in lumbar fusion procedures completed for degenerative diagnoses. Demographic and geographic/practice data, hospital charges, and length of stay of all NIS patients with thoracolumbar and lumbosacral procedure codes for degenerative spinal diagnoses were recorded. Codes for autograft harvest, use of BMP, and revision surgery were included in multivariable regression analysis. The assessment found 46,452 patients from 2002 to 2008 undergoing thoracolumbar or lumbar arthrodesis procedures for degenerative disease. Assuming a representative sample, this cohort models more than 200,000 US patients. There was steady growth in lumbar spine fusion and in the use of BMP. The use of BMP increased from 2002 to 2008 (odds ratio [OR], 1.50; 95% confidence interval [CI], 1.48-1.52). Revision procedures decreased over the study period (OR, 0.94; 95% CI, 0.91-0.96). The use of autograft decreased substantially after introduction of BMP but then returned to baseline levels; there was no net change in autograft use from 2002 to 2008. The use of BMP correlated with significant increases in hospital charges ($13,362.39; standard deviation ± 596.28, p<.00001). The use of BMP in degenerative thoracolumbar procedures potentially added more than $900 million to hospital charges from 2002 to 2008. There was an overall decrease in rates of revision fusion
Lee, Yong-Ung; Yi, Tai; Tara, Shuhei; Lee, Avione Y.; Hibino, Narutoshi; Shinoka, Toshiharu; Breuer, Christopher K.
Biodegradable scaffolds seeded with bone marrow mononuclear cells (BMCs) are often used for reconstructive surgery to treat congenital cardiac anomalies. The long-term clinical results showed excellent patency rates, however, with significant incidence of stenosis. To investigate the cellular and molecular mechanisms of vascular neotissue formation and prevent stenosis development in tissue engineered vascular grafts (TEVGs), we developed a mouse model of the graft with approximately 1 mm internal diameter. First, the TEVGs were assembled from biodegradable tubular scaffolds fabricated from a polyglycolic acid nonwoven felt mesh coated with ε-caprolactone and L-lactide copolymer. The scaffolds were then placed in a lyophilizer, vacuumed for 24 hr, and stored in a desiccator until cell seeding. Second, bone marrow was collected from donor mice and mononuclear cells were isolated by density gradient centrifugation. Third, approximately one million cells were seeded on a scaffold and incubated O/N. Finally, the seeded scaffolds were then implanted as infrarenal vena cava interposition grafts in C57BL/6 mice. The implanted grafts demonstrated excellent patency (>90%) without evidence of thromboembolic complications or aneurysmal formation. This murine model will aid us in understanding and quantifying the cellular and molecular mechanisms of neotissue formation in the TEVG. PMID:24961688
Shih, Jessica; Podolsky, Dale; Binhammer, Paul
To determine the best fit of a hamate osteochondral graft to reconstruct a palmar defect of a middle phalanx articular fracture using three-dimensional remodelling. The proximal middle phalanx and distal hamate articular surfaces of 10 cadaveric right hands were scanned using a three-dimensional laser scanner. A defect was marked on the middle phalanx digital image to simulate a 50% palmar lip fracture. A hemihamate autograft surgical procedure was simulated by aligning the middle phalanx and hamate digital articular surfaces. In addition to the second digit measurements, the midpoint distances of the central ridge of proximal articular surface of the middle phalanx digital image for digits 3, 4 and 5 were recorded for reference value, as well as the offset distances for the long and small finger. The mean midpoint distance for the index finger was 2.96 mm (95% CI 2.71 mm to 3.21 mm). The mean angle of offset was 20.09° (95% CI 15.54° to 24.64°). The mean graft offset distance was prominent by 1.23 mm (95% CI 0.57 mm to 1.89 mm). The reference values for the third, fourth and fifth middle phalange midpoint distances were 3.26 mm (95% CI 3.09 mm to 3.43 mm), 3.13 mm (95% CI 2.93 mm to 3.33 mm) and 2.48 mm (95% CI 2.33 mm to 2.63 mm), respectively. The offset distances for digits 3 and 5 were 1.24 mm (95% CI 0.48 mm to 2.00 mm) and 1.08 mm (95% CI 0.48 mm to 1.68 mm), respectively. The present study provides information about best fit for placing a hamate autograft for the hemihamate arthroplasty procedure. In this model, the hamate graft must be offset to recreate the curvature of the middle phalanx.
Salle, Bruno; Demirci, Banu; Franck, Michel; Berthollet, Céline; Lornage, Jacqueline
To evaluate a 2-year follow-up of cryopreserved hemi-ovary autografts in ewes. Animal study. SERTTING: University fertility center, Hospices Civils de Lyon; Ecole Nationale Vétérinaire de Lyon, INSERM U 418 Hocaron;pital Debrousse, Lyon; and Hôpital Edouard Herriot, Lyon, France. Grivette ewes. Recently we reported four pregnancies and six live births after transplantation of frozen-thawed hemi-ovary in six different ewes. The four remaining ewes were monitored for 2 years. After the last birth, the autografted ovary was removed in each ewe during a final laparotomy. The entire grafted ovary was sliced to estimate the remaining primordial follicle population 2 years after grafting. Uterine ultrasound scanning was performed to diagnose pregnancy. Histological assessment of the grafted ovary was performed after delivery. The four remaining ewes began new gestations. For two of them, this was a second gestation obtained more than 2 years after the autograft. These two ewes delivered male lambs, which died immediately after delivery because of distocia. The lambs were both oversized for gestational age; autopsy found no malformation. A twin pregnancy of a healthy male and a healthy female occurred in May 2002, and a singleton male was born in February 2002. All grafted ovaries showed drastic reduction in follicle population. Frozen-thawed ovary autograft allowed recovery of fertility a very long time after the procedure despite a drastic reduction in the total number of follicles.
Yamazaki, Mutsuo; Sato, Shunichi; Saitoh, Daizo; Ishihara, Miya; Okada, Yoshiaki; Ashida, Hiroshi; Obara, Minoru
We previously proposed a new method for monitoring adhesion of skin graft by measuring photoacoustic (PA) signal originated from the neovascularities. In this study, immunohistochemical staining (IHC) with CD31 antibody was performed for grafted skin tissue to observe neovascularity, and the results were compared with PA signals. We also used a laser Doppler imaging (LDI) to observe blood flow in the grafted skin, and sensitivity of PA measurement and that of LDI were compared. In rat autograft models, PA signals were measured for the grafted skin at postgrafting times of 0-48 h. At 6 h postgrafting, PA signal was observed in the skin depth region of 500-600 mm, while the results of IHC showed that angiogenesis occurred at the depth of about 600 mm. Depths at which PA signal and angiogenesis were observed decreased with postgrafting time. These indicate that the PA signal observed at 6 h postgrafting originated from the neovascularities in the skin graft. Results of LDI showed no blood-originated signal before 48 h postgrafting. These findings suggest that PA measurement is effective in monitoring the adhesion of skin graft in early stage after transplantation.
Prim, David A; Zhou, Boran; Hartstone-Rose, Adam; Uline, Mark J; Shazly, Tarek; Eberth, John F
Coronary artery bypass grafting (CABG) acutely disturbs the homeostatic state of the transplanted vessel making retention of graft patency dependent on chronic remodeling processes. The time course and extent to which remodeling restores vessel homeostasis will depend, in part, on the nature and magnitude of the mechanical disturbances induced upon transplantation. In this investigation, biaxial mechanical testing and histology were performed on the porcine left anterior descending artery (LAD) and analogs of common autografts, including the internal thoracic artery (ITA), radial artery (RA), great saphenous vein (GSV) and lateral saphenous vein (LSV). Experimental data were used to quantify the parameters of a structure-based constitutive model enabling prediction of the acute vessel mechanical response pre-transplantation and under coronary loading conditions. A novel metric Ξ was developed to quantify mechanical differences between each graft vessel in situ and the LAD in situ, while a second metric Ω compares the graft vessels in situ to their state under coronary loading. The relative values of these metrics among candidate autograft sources are consistent with vessel-specific variations in CABG clinical success rates with the ITA as the superior and GSV the inferior graft choices based on mechanical performance. This approach can be used to evaluate other candidate tissues for grafting or to aid in the development of synthetic and tissue engineered alternatives.
Chen, Xu-Lin; Liang, Xun; Sun, Li; Wang, Fei; Liu, Sheng; Wang, Yong-Jie
Despite the fact that early excision and grafting have significantly improved burn outcomes, the management of severely burned patients whose burn size exceeds 70% total body surface area (TBSA) still represents a big challenge for burn surgeons all over the world. During the period of 1997-2010 at our centre, aggressive excision and microskin autografting were performed in 63 severely burned patients. Their burn sizes ranged from 70% to 98% TBSA with a mean of 84.9%. The average full-thickness burn was 66.3% (range, 29-94%). Thirty patients had concomitant inhalation injury. Two to 7 days after burn, these patients underwent aggressive excisions ranging from 25% to 60% TBSA and transplantation of microskin autograft overlaid with allograft. The ratios of donor-site to recipient-site surface area were between 1:6 and 1:18. Signs of epithelialization were shown within 35-55 days. The wound healing rate was 74.9% (176/235), with 51.1% of cases (120/235) healing completely and 23.8% (56/235) improving. Microskin autografting yielded an overall survival rate of 63.5%; only 23 patients died. Our clinical experience in using the microskin autografting for burn coverage suggests that the technique is very effective in covering extensive burns, and that it is particularly useful when graft donor sites are very limited due to its high utilization rate of donor site. The factors affecting the outcome of microskin autografting are discussed herein.
Allan, B D; Short, P; Crawford, G J; Barrett, G D; Constable, I J
The optimum mode of treatment for symptomatic pterygia would combine efficacy (a low recurrence rate) with safety (freedom from sight threatening complications), and would not affect visual acuity adversely. The efficacy of pterygium excision with conjunctival autografting in a sun exposed population in which pterygia are prevalent has previously been questioned. A cross sectional review of 93 eyes of 85 patients was carried out by slit-lamp examination a minimum of 6 months (range 6-76 months) after pterygium excision and free conjunctival autografting. Case notes were reviewed to obtain details of complications and visual acuity changes related to surgery. Of six recurrences (6.5%) four of these were asymptomatic with minor recurrences. Two patterns of recurrence were identified: cross graft recurrence (three cases) and outflanking (three cases). Complications (wound dehiscence, three cases; Tenon's granuloma one case; conjunctival cyst, one case) were all corrected by minor surgical revision without sequelae. Unaided acuities were unchanged or improved 3 months after surgery in 86 cases, with a minor diminution (1 Snellen line) in seven cases. This study demonstrates a low recurrence rate for a safe technique in an area in which ongoing ultraviolet light exposure levels are high and pterygia are prevalent. Images PMID:8280682
Genidy, Mahmoud M; Abdelghany, Ahmed A; Alio, Jorge L
To describe the outcomes of a novel technique for pterygium removal: tailored corneo-conjunctival autograft, which offers the advantages of better postoperative cosmetic outcomes and recurrence prevention. This retrospective interventional noncomparative study included 420 eyes in 370 patients (ages 25-60 years) (127 women, 243 men). We divided the patients into 2 groups. The first group included 348 primary pterygium; the second group included 72 recurrent pterygium. All underwent the same type of corneo-conjunctival autograft surgery from April 2009 to March 2014. The average follow-up period was 12 months. The main outcome measures were to assess pain after surgery, conjunctival healing, cosmetic appearance, and pterygium recurrence at the end of follow-up. In both groups, the graft donor site healed promptly without excessive scarring. No patient complained of pain during first week after surgery, except for mild discomfort. No major complications were observed such as infection or graft necrosis. In the first group, 2 patients had graft retraction towards the nasal side and were successfully managed conservatively. One patient had Tenon granuloma, which was removed surgically. Recurrence during the follow-up period was seen in one patient (0.2%). In the second group, no recurrent pterygium cases were observed. The proposed type of corneo-conjunctival autograft offers the advantage of better postoperative cosmetic outcomes. This new technique is effective for surgical management of both primary and recurrent pterygium and preventing its recurrences.
Ransford, A O; Morley, T; Edgar, M A; Webb, P; Passuti, N; Chopin, D; Morin, C; Michel, F; Garin, C; Pries, D
We have evaluated the use of a synthetic porous ceramic (Triosite) as a substitute for bone graft in posterior spinal fusion for idiopathic scoliosis. In a prospective, randomised study 341 patients at five hospitals in the UK and France were randomly allocated either to autograft from the iliac crest or rib segments (171) or to receive Triosite blocks (170). All patients were assessed after operation and at 3, 6, 12 and 18 months. The two groups were similar with regard to all demographic and baseline variables, but the 184 treated in France (54%) had Cotrel-Dubouset instrumentation and the 157 treated in the UK usually had Harrington-Luque implants. In the Triosite group the average Cobb angle of the upper curve was 56 degrees, corrected to 24 degrees (57%). At 18 months, the average was 26 degrees (3% loss). In the autograft group the average preoperative upper curve of 53 degrees was corrected to 21 degrees (60%). At 18 months the mean curve was 25 degrees (8% loss). Pain levels after operation were similar in the two groups, being mild in most cases. In the Triosite group only three patients had problems of wound healing, but in the autograft group, 14 patients had delayed healing, infection or haematoma in the spinal wound. In addition, 15 autograft patients had pain at the donor site at three months. Seven had infections, two had haematoma and four had delayed healing. The haematological and serum biochemistry results showed no abnormal trends and no significant differences between the groups. There were no adverse events related to the graft material and no evidence of allergenicity. Our results suggest that Triosite synthetic porous ceramic is a safe and effective substitute for autograft in these patients. Histological findings on biopsy indicate that Triosite provides a favourable scaffolding for the formation of new bone and is gradually incorporated into the fusion mass.
Elmasry, M; Steinvall, I; Thorfinn, J; Olofsson, P; Abbas, A H; Abdelrahman, I; Adly, O A; Sjoberg, F
During the 80s and 90s, early and total excision of full thickness burns followed by immediate autograft was the most common treatment, with repeated excision and grafting, mostly for failed grafts. It was hypothesized, therefore, that delayed coverage with an autograft preceded by a temporary xenograft after early and sequential smaller excisions would lead to a better wound bed with fewer failed grafts, a smaller donor site, and possibly also a shorter duration of stay in hospital. We carried out a case control study with retrospective analysis from our National Burn Centre registry for the period 1997-2011. Patients who had been managed with early total excision and autograft were compared with those who had had sequential smaller excisions covered with temporary xenografts until the burn was ready for the final autograft. The sequential excision and xenograft group (n=42) required one-third fewer autografts than patients in the total excision and autograft group (n=45), who needed more than one operation (p<0.001). We could not detect any differences in duration of stay in hospital / total body surface area burned% (duration of stay/TBSA%) (2.0 and 1.8) (p=0.83). The two groups showed no major differences in terms of adjusted duration of stay, but our findings suggest that doing early, smaller, sequential excisions using a xenograft for temporary cover can result in shorter operating times, saving us the trouble of making big excisions. However, costs tended to be higher when the burns were > 25% TBSA.
Elmasry, M.; Steinvall, I.; Thorfinn, J.; Olofsson, P.; Abbas, A.H.; Abdelrahman, I.; Adly, O.A.; Sjoberg, F.
Summary During the 80s and 90s, early and total excision of full thickness burns followed by immediate autograft was the most common treatment, with repeated excision and grafting, mostly for failed grafts. It was hypothesized, therefore, that delayed coverage with an autograft preceded by a temporary xenograft after early and sequential smaller excisions would lead to a better wound bed with fewer failed grafts, a smaller donor site, and possibly also a shorter duration of stay in hospital. We carried out a case control study with retrospective analysis from our National Burn Centre registry for the period 1997-2011. Patients who had been managed with early total excision and autograft were compared with those who had had sequential smaller excisions covered with temporary xenografts until the burn was ready for the final autograft. The sequential excision and xenograft group (n=42) required one-third fewer autografts than patients in the total excision and autograft group (n=45), who needed more than one operation (p<0.001). We could not detect any differences in duration of stay in hospital / total body surface area burned% (duration of stay/TBSA%) (2.0 and 1.8) (p=0.83). The two groups showed no major differences in terms of adjusted duration of stay, but our findings suggest that doing early, smaller, sequential excisions using a xenograft for temporary cover can result in shorter operating times, saving us the trouble of making big excisions. However, costs tended to be higher when the burns were > 25% TBSA. PMID:28149249
Grant, Sheila A; Smith, Sarah E; Schmidt, Hilary; Pfeiffer, Ferris; Kuroki, Kei; Sherman, Seth; White, Richard; Grant, David A
Acellular human gracilis tendons conjugated with gold nanoparticles (AuNP) and hydroxyapatite nanoparticles (nano-HAp) were used as a graft in an anterior cruciate ligament (ACL) reconstruction rabbit model. The ACLs of 11 New Zealand rabbits were reconstructed using grafts conjugated without nanoparticles, with AuNP only, and with both AuNP and nano-HAp. Semi-quantitative histological scoring of bone tunnel portion of grafts was performed after 14 weeks. Bone tunnels were scored for graft degeneration, graft remodeling, percentage of new host fibrous connective, collateral connection, head-to-head connection, graft collagen fiber organization, new host fibrous connective tissue organization, and graft and interface vascularity. All grafts were intact at 14 weeks. Results of bone tunnel scoring indicate remodeling in all graft types with new organized host fibrous connective tissue, head-to-head connection to bone and mild inflammation associated with remodeling. Components of the 20 nm AuNP grafts have significantly more graft degeneration, more new host fibrous connective tissue, and more vascularity compared to crosslinked grafts. Comparison between femoral and tibial tunnel scores indicate more degeneration in femoral tunnels compared to tibial tunnels. Overall results indicated potentially enhanced remodeling from the use of 20 nm AuNP grafts. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1071-1082, 2017.
Adiga, Shashishekar P.
Polymer chains undergo conformational transitions in response to a change in solvent quality of their environment, making them strong candidates to be used in smart nanometer-scale devices. In the present work molecular modeling is used to explore grafted polymer structures with various functionalities. The first part of this research focuses on two examples of selective transport through nanopores modified with polymer brush structures. The first is the investigation of solvent flow through nanopores grafted with linear chains. Molecular dynamics (MD) simulations are used to demonstrate how a stretch-collapse transition in grafted polymer chains can be used to control solvent flow rate through a nanopore in response to environmental stimuli. A continuum fluid dynamics method based on porous layer model for describing flow through the smart nanopore is described and its accuracy is analyzed by comparing with the results from MD simulations. The continuum method is then applied to determine regulation of water permeation in response to pH through a poly(L-glutamic acid) grafted nanoporous membrane. A second example is use of a rod-coil transition in "bottle brush" molecules that are grafted to the inside of a nanopore to size select macromolecules as they diffuse through the functionalized nanopores. These stimuli-responsive nanopores have a variety of potential applications including molecular sorting, smart drug delivery, and ultrafiltration, as well as controlled chemical release. Tethered polymers play an important role in biological structures as well. In the second part of the research, application of atomistic simulations to characterize the effect of phosphorylation on neurofilament structure is presented. Neurofilaments are intermediate filaments that regulate axonal diameter through their long, flexible side arms extending from the central core. Their functionality is imparted by polymer brush like structure that causes steric repulsion between the
Arriaza, Rafael; Gayoso, Raquel; López-Vidriero, Emilio; Aizpurúa, Jesús; Agrasar, Carlos
Chronic Achilles tendon tears could hinder patients and represent a challenge to surgeons. Although many different surgical techniques have been proposed for reconstruction of a neglected Achilles tendon rupture, there is no clear evidence to support one technique over the others, but the use of a technique that could allow for an "anatomical" reconstructions seems desirable. The present paper describes a new anatomic Achilles tendon reconstruction for chronic tears, using a quadriceps tendon autograft as graft source, with PRP injected into the graft and the neighbor tissue, and fixation in a bone trough with a simple small fragments screw. Autologous quadriceps tendon graft seems an excellent option, although -surprisingly- has received little attention until now. Autologous Quadriceps tendon graft (in bone-tendon configuration) is a simple technique that could allow surgeons to reconstruct tissue defects in the Achilles tendon with non-expensive hardware.
Logan, Martin; Williams, Andy; Myers, Peter
A 27-year-old man underwent anterior cruciate ligament (ACL) reconstruction using 4-strand hamstring autograft with femoral and tibial interference screw fixation. Four weeks after surgery, he developed a discharging hematoma through the graft harvest-tibial tunnel incision, which persisted. The patient required further surgical intervention 7 weeks after the initial surgery. The wound was debrided, the tibial interference screw was removed, and the tibial tunnel was completely cleared of graft remnants. Arthroscopy of the knee was performed, in which the ACL graft appeared healthy and viable. No evidence of intra-articular sepsis was found. Postoperatively, the rehabilitation program was uneventful and, at 36 months, the patient has unrestricted activity and no clinical evidence of excessive ACL laxity. This case supports the importance of marginal articular surface healing of the ACL graft, suggesting that tibial intratunnel healing becomes redundant.
López-Otero, A; Ruiz-Delgado, G J; Ruiz-Argüelles, G J
In a 14-year period in a single institution 31 autografts were performed in 26 patients with multiple myeloma (MM), using a simplified and affordable autografting procedure: conducting the grafts on an outpatient basis and avoiding stem cell freezing. Autografts were started on an outpatient basis in all instances, but four patients were admitted to the hospital. Median time to achieve more than 0.5 x 10(9)/l granulocytes was 27 days, whereas median time to recover above 20 x 10(9)/l plts was 37 days. CR was achieved in 19 cases and a very good partial response in 6 cases. The 100-day mortality was 9.6%. The overall median post-transplant survival has not been reached, being above 76 months, whereas the 76-month survival is 80%. The median cost of each procedure was US$ 15 000. Survival results were substantially better than those of historical control in a group of patients treated in the same institution with melphalan/prednisone. It is concluded that high-dose therapy rescued with a simplified autologous stem cell graft is a valid, useful and affordable therapeutic option for patients with MM, even with economical restraints.
Yazici, Cemal; Takahata, Masahiko; Reynolds, David G; Xie, Chao; Samulski, R Jude; Samulski, Jade; Beecham, E Jeffrey; Gertzman, Arthur A; Spilker, Mark; Zhang, Xinping; O'Keefe, Regis J; Awad, Hani A; Schwarz, Edward M
Structural allografts used for critical bone defects have limited osteogenic properties for biointegration. Although ex vivo tissue-engineered constructs expressing bone morphogenetic protein-2 (BMP2) have demonstrated efficacy in critical defect models, similar success has not been achieved with off-the-shelf acellular approaches, including allografts coated with freeze-dried single-stranded adeno-associated virus (ssAAV-BMP2). To see whether the self-complementary AAV serotype 2.5 vector (scAAV2.5-BMP2) could overcome this, we performed side-by-side comparisons in vitro and in the murine femoral allograft model. Although ssAAV-BMP2 was unable to induce BMP2 expression and differentiation of C3H10T1/2 cells in culture, scAAV2.5-BMP2 transduction led to dose-dependent BMP2 expression and alkaline phosphatase activity, and displayed a 25-fold increased transduction efficiency in vivo. After 6 weeks, the ssAAV-BMP2 coating failed to demonstrate any significant effects. However, all allografts coated with 1010 scAAV2.5-BMP2 formed a new cortical shell that was indistinguishable to that formed by live autografts. Additionally, coated allografts experienced reduced resorption resulting in a threefold increase in graft bone volume versus autograft. This led to biomechanical superiority versus both allografts and autografts, and equivalent torsional rigidity to unfractured femur. Collectively, these results demonstrate that scAAV2.5-BMP2 coating overcomes the major limitations of structural allografts, which can be used to heal critical defects of any size. PMID:21206485
Zadegan, Shayan Abdollah; Firouzi, Masoumeh; Nabian, Mohammad Hossein; Zanjani, Leila Oriady; Ashtiani, Ahmad Mohebbi; Kamrani, Reza Shahryar
Peripheral nerve repair outcomes are suboptimal in the presence of severe soft tissue injury and excessive scarring paralleling the process in tendon reconstruction of the hand. Inspired by the advantages of the two-stage technique in tendon grafting and with encouraging preliminary results, we aimed to investigate the two-stage nerve grafting technique as an alternative method of secondary nerve repair. Thirty female rats (~200 g) were randomly distributed into two groups (n=15). A 15 mm gap was created in the sciatic nerve of the animals and an excessive extraneural scar was induced using the "mincing" method. In this method, a thin strip of muscle was removed, minced in a petri dish and returned to the peripheral nerve. In the two-stage nerve graft group, a silicone tube was interposed in the first stage. After 4 weeks, in the second stage, the silicone tube was removed and a median nerve autograft was interposed through the newly formed vascularized sheath. In the conventional graft group, two nerve ends were protected with silicone caps in the first stage. After 4 weeks the caps were removed and the median graft was interposed. Behavioral assessments were performed at week 15 after surgery with the withdrawal reflex latency (WRL) and extensor postural thrust (EPT) and at the 3, 6 and 15-week time points with the TOA (toe out angle). Masson Trichrome staining method was used for histological assessments at week 15. According to the EPT and WRL, the two-stage nerve graft showed significant improvement (P=0.020 and P=0.017 respectively). The TOA showed no significant difference between the two groups. The total vascular index was significantly higher in the two-stage nerve graft group (P<0.001). Two-stage nerve graft using a silicone tube enhances vascularity of the graft and improves functional recovery.
Macaulay, Alec A.; Perfetti, Dean C.; Levine, William N.
Context: Reconstruction of the anterior cruciate ligament (ACL) is a common surgical procedure; however, there is no consensus to what the best graft option is to replace the injured ACL. The main options available consist of allografts and autografts, which include patellar tendon, hamstring tendon, and quadriceps tendon autografts. Evidence Acquisition: The PubMed database was searched in August 2010 for English-language articles pertaining to ACL grafts. Results: Postoperative outcome variables were analyzed to determine similarities and differences among the different graft options. These variables include stability, strength, function, return to sports, patient satisfaction, complications, and cost. Conclusions: Both allografts and the 3 main options for autografts can provide excellent results in ACL reconstruction and lead to a high percentage of satisfied patients. However, differences exist among the graft choices. Both the similarities and the differences are important to discuss with a patient who will be undergoing ACL reconstruction so that he or she has the best information available when making a choice of graft. PMID:23016071
It has not been known what drives revision anterior cruciate ligament (ACL) reconstruction graft choice in the past. We undertook this study to utilize the Multicenter ACL Revision Study (MARS) group and propensity score statistical analysis to determine the drivers of revision ACL reconstruction graft choice. We hypothesized that propensity analysis would demonstrate that individual surgeons still have significant impact on revision ACL reconstruction. Twelve hundred patients were enrolled in this longitudinal revision cohort by 83 surgeons at 52 sites. The median age was 26 years and 505 (42%) were females. One thousand forty-nine (87%) patients were undergoing their first ACL revision. Graft choice for revision ACL reconstruction for these patients was 48% autograft, 49% allograft, and 3% combination. The independent variables of this model included gender, age, ethnicity, body mass index, smoking status, sport, activity level, previous graft, revision number, surgeon, surgeon's opinion of failure, previous technical aspects, etc. Surgeons were defined as those who contributed more than 15 patients during the enrollment period. . We calculated a propensity score for graft type based on the predicted probability of receiving an allograft from a logistic regression model. Propensity scores demonstrated that surgeon, prior graft choice, and patient age each had significant influence on which graft type was chosen for the revision ACL reconstruction (p < 0.0001). The revising surgeon had the largest impact upon graft choice: ∼ 5 times that of the second-most important factor (prior graft). If the prior graft type was an autograft, then an allograft was 3.6 times more likely to be chosen for the revision. This current study demonstrates that the individual surgeon is ultimately the most important factor in revision ACL reconstruction graft choice. Additional statistically significant influences of graft choice included age, gender, previous graft choice, ACL
Marinello, Patrick G; Wagner, Timothy; Styron, Joseph; Maschke, Steven; Evans, Peter J
We present a modification and revisit of the Bell Tawse technique for annular ligament reconstruction with triceps autograft for chronic radial head instability. In patients with instability stemming from an incompetent annular ligament, this technique has proved successful to restore stability to the proximal radial capitellar joint as an augment after ensuring normal boney anatomy. Through a lateral Kocher approach, an approximately 10 cm × 4 mm strip of lateral triceps tendon is harvested as a free graft for the reconstruction. Following passing of the triceps autograft around the radial neck, it is sutured to a mini-Mitek suture anchor and is placed into a decorticated portion of the proximal ulna to recreate the annular ligament. Finally, we present 2 case illustrations where this technique was successfully used for chronic radial head instability.
Neen, Daniel; Noyes, David; Shaw, Matthew; Gwilym, Stephen; Fairlie, Neil; Birch, Nicholas
A prospective case controlled study to compare the clinical and radiographic performance of Healos soaked in bone marrow aspirate (BMA) to iliac crest autograft when used in lumbar spinal fusion. To evaluate the null hypothesis: Healos used with BMA is not an effective alternative to iliac crest autograft in lumbar spine fusions. Healos (a Type 1 collagen/hydroxyapatite matrix) is osteoconductive and when soaked for at least 20 minutes in BMA becomes osteoinductive. It is nontoxic and straightforward to use, avoiding the morbidity of autograft harvest. Animal studies and early clinical series in humans have suggested that Healos and BMA are an effective substitute for autograft in certain circumstances. From July 2000, Healos and BMA were used as the graft material, instead of autograft harvested from the iliac crest, in all patients undergoing lumbar spinal fusion. Clinical outcome measures used were the Low Back Outcome Score (LBOS), a Patient Satisfaction Score, and the Prolo Economic Score (after Schnee). Standing anteroposterior and lateral radiographs were taken at 12- and 24-month follow-up visits. The first 50 cases in this consecutive series were age, sex, and operative intervention matched to historical controls who underwent surgery between 1997 and 2000 and in whom autograft from the iliac crest had been used as the graft material. Surgical outcome data in these patients had also been gathered prospectively. An independent radiologist, blinded to the graft material, using standard plain radiograph criteria for fusion, examined all the radiographs. An independent surgeon assessed clinical outcomes. For posterolateral lumbar fusions, there were equivalent radiologic fusion rates for the 2 groups with no significant difference in the subjective and objective clinical outcomes. The radiologic fusions rate was significantly lower when Healos had been used for lumbar interbody fusions. Clinical outcomes for both groups were similar. There were no lasting
Denman et al. [P.K. Denman, D.L.S. McElwain, J. Norbury, Analysis of travelling waves associated with the modelling of aerosolised skin grafts, Bull. Math. Biol. 69 (2007) 495-523] proposed a novel model on the growth pattern of keratinocyte cell colonies that were sprayed on to a severe burn site to facilitate the healing process. They studied traveling wave solutions of the model by asymptotic analysis and obtained several qualitative properties. In this paper we establish the following result on the traveling waves: there exists a minimal speed c such that the model has a unique biologically meaningful travelling wave solution for each speed c≥c and has no such a solution for any c
Fujishiro, Takaaki; Bauer, Thomas W; Kobayashi, Naomi; Kobayashi, Hideo; Sunwoo, Moon Hae; Seim, Howard B; Turner, A Simon
Demineralized bone matrix (DBMs) preparations are a potential alternative or supplement to autogenous bone graft, but many DBMs have not been adequately tested in clinically relevant animal models. The aim of current study was to compare the efficacy of a new bone graft substitute composed of a combination of mineralized and demineralized allograft, along with hyaluronic acid (AFT Bone Void Filler) with several other bone graft materials in a sheep vertebral bone void model. A drilled defect in the sheep vertebral body was filled with either the new DBM preparation, calcium sulfate (OsteoSet), autologous bone graft, or left empty. The sheep were euthanized after 6 or 12 weeks, and the defects were examined by histology and quantitative histomorphometry. The morphometry data were analyzed by one-way analysis of variance with the post hoc Tukey-Kramer test or the Student's t-test. All of the bone defects in the AFT DBM preparation group showed good new bone formation with variable amounts of residual DBM and mineralized bone graft. The DBM preparation group at 12 weeks contained significantly more new bone than the defects treated with calcium sulfate or left empty (respectively, p < 0.05, p < 0.01). There was no significant difference between the DBM and autograft groups. No adverse inflammatory reactions were associated with any of the three graft materials. The AFT preparation of a mixture of mineralized and demineralized allograft appears to be an effective autograft substitute as tested in this sheep vertebral bone void model.
Thorogood, P V; Gray, J C
Osteogenesis in and around autografts has been studied in the hope of identifying the osteoblast precursor. Fresh autografts of cortical bone with its constituent bone marrow were implanted into intramuscular sites in rats. The grafts were removed at intervals over a four week period and examined by light and electron microscopy. A chronological sequence of degenerative, reparative and differentiative events was found and described. The relative contributions of the host and graft components to post-grafting osteogenesis are discussed and the problem of the origin of the osteoblast cells is examined, taking into account present views about the interrelationships between skeletal connective tissue cells and their precursors. It is concluded that, in the investigation described, the presence of host granulation tissue was necessary for osteogenesis and it is postulated that osteoblast progenitor cells can arise from this granulation tissue, their differentiation along the osteogenic line being stimulated in some way by the presence of the graft bone. Images Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 Fig. 13 Fig. 14 Fig. 15 PMID:1102503
Wang, Xingang; Zhang, Yuanhai; Han, Chunmao
The one-step surgical procedure for dermal substitutes combined with topical negative pressure (TNP) has proven effective for treating deep skin defects with improved graft take. The primary mechanism by which TNP improves autograft take is unknown. Some studies suggest that TNP promotes the rapid angiogenesis of dermal substitutes, improving graft take. However, at the early stage of one-step transplantation, the vascular system has not formed and imbibition is the main mode of nutrient supply. TNP can shorten the diffusion distance from the wound bed to the graft, leading to the timely renewal of the wound exudate via suction, removing any surplus exudate, and reducing tissue edema. In addition, TNP can regulate the local blood flow and inhibit bacterial colonization. Therefore, we hypothesized that TNP establishes a rapid balance between the nutrient supply to the wound bed and nutritional requirement of the graft via these pathways in the relatively closed, moist environment, improving autograft take. However, this balance could be affected by any negative pressure, intermittent or continuous. It is necessary to test this hypothesis in laboratory and clinical studies of the mode of nutrient supply in the imbibition phase and the change in exudate content.
Quiroga-Garza, Alejandro; Delgado-Brito, Miriam; Bazaldúa-Cruz, Juan José; Villarreal-Silva, Eliud; Velázquez-Gauna, Sergio E; Elizondo-Omaña, Rodrigo E; Guzmán-López, Santos
Animal models have been developed for the study of the intimal hyperplasia, a common cause of venous graft stenosis. To establish a venous graft animal model for the study of the morphologic adaptative response to the arterial circulation. A venous graft was placed in the arterial circulation of the caudal extremity from Wistar rats. In order to develop the model, it was carried out a morphologic study of the caudal extremity blood vessels. Three possible sites were evaluated for the obtaining of the venous graft. Graft permeability and viability were observed only in one segment, between the muscular branches and the origin of the saphenous vein. The portion of vein that was obtained from one extremity, was placed in the arterial circulation of the opposite extremity. A venous graft animal model was established, using a femoral vein segment, between the muscular branches and the origin of the saphenous vein, placing it in the homonyme artery of the opposite extremity.
Epstein, Nancy E.
Background: Patients with marked osteoporosis and/or obesity/morbid obesity and severe multilevel lumbar stenosis and other pathology often undergo multilevel laminectomies with non instrumented posterolateral fusions (PLF). The other pathology may include combinations of degenerative spondylolisthesis/lysis, foraminal/far lateral discs, and/or synovial cysts requiring more extensive facet resections. Presently, spine surgeons often use bone graft expanders to supplement the lamina autograft harvested in the course of laminectomy/decompressions for the PLF mass. Methods: In 59 patients, we prospectively analyzed the fusion rates following multilevel laminectomies/noninstrumented fusions using lamina autograft and the bone graft expander Nanoss (RTI Surgical Alachua, FL, and USA) with autogenous bone marrow aspirate (BMA). Patients averaged 66.1 years of age; many exhibited marked osteoporosis (48 patients) and obesity (13 of 27 morbidly obese). Magnetic resonance (MR) and computed tomography (CT) studies documented stenosis/ossified yellow ligament (OYL) and degenerative spondylolisthesis (51 patients)/lysis (2 patients), synovial cysts (32 patients), and disc herniations (10 of 21 far lateral). Patients were followed remove up for an average of 3.12 years. Results: Average 4.0 level laminectomies/1.2 level noninstrumented fusions utilized lamina autograft and Nanoss/BMA. Both X-ray/CT studies performed an average of 4.9 months postoperatively documented a 97% fusion rate (57 of 59 patients). Two patients with severe osteoporosis, morbid obesity, and smoking histories exhibited pseudarthroses; neither was sufficiently symptomatic to require secondary surgery. Conclusions: Fifty-nine patients with multilevel lumbar stenosis/OYL and other pathology underwent multilevel lumbar laminectomies/noninstrumented fusions using lamina autograft and Nanoss/BMA. Both dynamic X-ray/CT studies confirmed a 97% fusion rate an average of 4.9 months postoperatively. Nanoss
Costen, Robert C.; Su, Ji; Harrison, Joycelyn S.
Recently, it was reported that an electrostrictive graft elastomer exhibits large electric field-induced strain (4%). Combined with its high mechanical modulus, the elastomer can offer very promising electromechanical properties, in terms of output mechanical energy density, for an electroactive polymeric material. Therefore, it has been considered as one of the candidates that can be used in high performance, low mass actuation devices in many aerospace applications. Various bilayer- based bending actuators have been designed and fabricated. An analytic model based on beam theory in the strength of materials has been derived for the transverse deflection, or curvature, and the longitudinal strain of the bi-layer beam. The curvature and strain are functions of the applied voltage and the thickness, width, and Young s modulus of the active and passive layers. The model can be used to optimize the performance of electrostrictive graft elastomer-based actuators to meet the requirements of various applications. In this presentation, optimization and sensitivity studies are applied to the bending performance of such actuators.
Valencia Rivero, Karen Tatiana; Jaramillo Escobar, Juliana; Galvis Forero, Sergio David; Miranda Saldaña, Maria Clara; López Panqueva, Rocío Del Pilar; Sandoval Reyes, Néstor Fernando; Briceño Triana, Juan Carlos
The purpose of this study was to evaluate a suitable animal model for the in vivo evaluation of patency and vascular tissue regeneration in small intestinal submucosa (SIS) vascular grafts for hemodialysis access. First, a 4-mm U-shaped SIS vascular graft was implanted between the internal carotid artery (CA) and the external jugular vein (JV) in five sheep and six swine. The U-shape grafts remained functional for 53 ± 4 days in sheep and 32 ± 2 days in swine. The sheep model presented exaggerated inflammation, so the swine model was selected for the in vivo study. Based on these initial results, a 4-mm C-shape SIS vascular graft with SIS circumferential reinforcement was developed to mechanically improve the vascular graft and manage complications identified during surgery in both sheep and swine. The C-shape vascular graft was implanted in a swine model (n = 3) between the CA and JV. GORE-TEX® vascular grafts were used as controls in the contralateral side of the neck. C-shape grafts remained patent for 47 ± 4 days, whereas the GORE-TEX® grafts were patent for 30 ± 15 days. The C-shape vascular graft was easier to handle during surgery, and its circumferential reinforcement improved in vivo patency, avoiding kinks in the graft after implantation. Histological results showed neovascularization and some regeneration with the alignment of endothelial cells in the vascular wall of the grafts. The model developed may be helpful in other research involving in vivo studies of vascular grafts for hemodialysis access.
ATBAŞI, ZAFER; ERÇIN, ERSIN; ERDEM, YUSUF; EMRE, TULUHAN YUNUS; ATILLA, HALIS ATIL; PARLAK, ADEM
Purpose the aim of this study was to assess the relationship of patient weight, height and body mass index (BMI) with the size of the quadrupled hamstring tendon used in anterior cruciate ligament (ACL) reconstruction. Methods from patient records, we retrospectively assessed the weight, height, BMI and graft sizes of 126 patients who underwent ACL reconstruction using a quadrupled hamstring tendon autograft between January 2010 and January 2013 at our institution. The data obtained from perioperative measurements were studied using correlation analysis. Results statistically significant relationships were found between patient height and graft diameter (p = 0.033, r = 0.19) and between patient weight and graft diameter (p < 0.0001, r = 0.33). No statistically significant relationships were found between graft diameter and BMI or between graft length and patient height, weight and BMI (p > 0.05). Conclusions patient height and weight were found to be related to quadrupled hamstring graft diameter in our patient population. BMI was not related to the quadrupled hamstring graft size. The exact size of the graft cannot be predicted preoperatively on the basis of these variables. Level of evidence Level IV, retrospective case series. PMID:28217655
Vasudevan, Srikanth; Huang, Jiying; Botterman, Barry; Matloub, Hani S; Keefer, Edward; Cheng, Jonathan
Long-gap peripheral nerve defects arising from tumor, trauma, or birth-related injuries requiring nerve reconstruction are currently treated using nerve autografts and nerve allografts. Autografts are associated with limited supply and donor-site morbidity. Allografts require administration of transient immunosuppressants, which has substantial associated risks. To overcome these limitations, we investigated the use of detergent-free decellularized nerve grafts to reconstruct long-gap nerve defects in a rodent model and compared it with existing detergent processing techniques. Nerve grafts were harvested from the sciatic nerves of 9 donor rats. Twenty-four recipient rats were divided into 4 groups (6 animals per group): (1) nerve grafts (NG, positive control), (2) detergent-free decellularized (DFD) grafts, (3) detergent decellularized grafts, and (4) silicone tube conduits (negative control). Each recipient rat had a 3.5-cm graft or conduit sutured across a sciatic nerve transection injury. All animals were harvested at 12 weeks postimplantation for functional muscle analysis and nerve histomorphometry. Histomorphometry results indicated maximum growth in NG when compared with other groups. DFD and detergent decellularized groups showed comparable regeneration at 12 weeks. Silicone tube group showed no regeneration as expected. Muscle force data indicated functional recovery in NG and DFD groups only. This study describes a detergent-free nerve decellularization technique for reconstruction of long-gap nerve injuries. We compared DFD grafts with an established detergent processing technique and found that DFD nerve grafts are successful in promoting regeneration across long-gap peripheral nerve defects as an alternative to existing strategies.
Vasudevan, Srikanth; Huang, Jiying; Botterman, Barry; Matloub, Hani S.; Keefer, Edward
Background: Long-gap peripheral nerve defects arising from tumor, trauma, or birth-related injuries requiring nerve reconstruction are currently treated using nerve autografts and nerve allografts. Autografts are associated with limited supply and donor-site morbidity. Allografts require administration of transient immunosuppressants, which has substantial associated risks. To overcome these limitations, we investigated the use of detergent-free decellularized nerve grafts to reconstruct long-gap nerve defects in a rodent model and compared it with existing detergent processing techniques. Methods: Nerve grafts were harvested from the sciatic nerves of 9 donor rats. Twenty-four recipient rats were divided into 4 groups (6 animals per group): (1) nerve grafts (NG, positive control), (2) detergent-free decellularized (DFD) grafts, (3) detergent decellularized grafts, and (4) silicone tube conduits (negative control). Each recipient rat had a 3.5-cm graft or conduit sutured across a sciatic nerve transection injury. All animals were harvested at 12 weeks postimplantation for functional muscle analysis and nerve histomorphometry. Results: Histomorphometry results indicated maximum growth in NG when compared with other groups. DFD and detergent decellularized groups showed comparable regeneration at 12 weeks. Silicone tube group showed no regeneration as expected. Muscle force data indicated functional recovery in NG and DFD groups only. Conclusions: This study describes a detergent-free nerve decellularization technique for reconstruction of long-gap nerve injuries. We compared DFD grafts with an established detergent processing technique and found that DFD nerve grafts are successful in promoting regeneration across long-gap peripheral nerve defects as an alternative to existing strategies. PMID:25426384
Ohyama, Takashiro; Kubo, Yoshichika; Iwata, Hiroo; Taki, Waro
Beta-tricalcium phosphate (beta-TCP) combined with recombinant human bone morphogenetic protein-2 (BMP-2) was examined as a substitute for autograft for packing into interbody fusion cages in the canine lumbar spine model. Discectomy and interbody cage fusion were performed at three disc spaces in eight dogs. Examination of microradiographs and histological sections of the lumbar spine at 16 weeks postsurgery revealed three fusions in the autograft cages (Group A), three in the beta-TCP cages (Group B), and five in the beta-TCP-BMP-2 cages (Group C). The mean percentage of trabecular bone area in the cages was 51.9% in Group A, 48.8% in Group B, and 65.6% in Group C. Mean percentage of trabecular bone formation and mechanical stiffness were highest in the cages filled with beta-TCP and BMP-2. Combination of BMP to beta-TCP may act as an osteoconductive and osteoinductive bone graft substitute in clinical spine surgery.
Cheng, Lisheng; Cao, Dapeng
Brownian dynamics simulations are carried out to study the aggregation behavior of polymer-grafted nanoparticles (NPs) in good solvents by using the coarse-grained model derived from the all-atom force field, according to the hierarchical modeling strategy, and here PEG-grafted gold nanoparticles (GNPs) were taken as an example. Generally, grafting PEG to the surface of GNPs is to protect them from aggregation in the solution. However, our results reveal that PEG-grafted GNPs may also aggregate when concentration increases. Our simulations indicate that there exists a critical aggregating concentration (CAC), beyond which the PEG-grafted GNPs will aggregate. We further check the effects of grafting density and the length of grafted chains on the aggregation behavior of the grafted GNPs, and find that there exists an optimized length of grafted chain, at which the system has the maximal CAC. Furthermore, the aggregate size of self-assembled mesostructures formed by the grafted GNPs increases with the concentration. Interestingly, it is observed that the aggregation favors to form linear gold nanowires rather than compact gold nanoclusters, and the corresponding mechanism is also addressed. It is expected that this work would provide useful information for the fabrication of metal nanowires and the surface modification of metal nanoparticles.
Cheng, Lisheng; Cao, Dapeng
Brownian dynamics simulations are carried out to study the aggregation behavior of polymer-grafted nanoparticles (NPs) in good solvents by using the coarse-grained model derived from the all-atom force field, according to the hierarchical modeling strategy, and here PEG-grafted gold nanoparticles (GNPs) were taken as an example. Generally, grafting PEG to the surface of GNPs is to protect them from aggregation in the solution. However, our results reveal that PEG-grafted GNPs may also aggregate when concentration increases. Our simulations indicate that there exists a critical aggregating concentration (CAC), beyond which the PEG-grafted GNPs will aggregate. We further check the effects of grafting density and the length of grafted chains on the aggregation behavior of the grafted GNPs, and find that there exists an optimized length of grafted chain, at which the system has the maximal CAC. Furthermore, the aggregate size of self-assembled mesostructures formed by the grafted GNPs increases with the concentration. Interestingly, it is observed that the aggregation favors to form linear gold nanowires rather than compact gold nanoclusters, and the corresponding mechanism is also addressed. It is expected that this work would provide useful information for the fabrication of metal nanowires and the surface modification of metal nanoparticles. © 2011 American Institute of Physics
Wasserstein, David; Sheth, Ujash; Cabrera, Alison; Spindler, Kurt P.
Context: The advantages of allograft anterior cruciate ligament reconstruction (ACLR), which include shorter surgical time, less postoperative pain, and no donor site morbidity, may be offset by a higher risk of failure. Previous systematic reviews have inconsistently shown a difference in failure prevalence by graft type; however, such reviews have never been stratified for younger or more active patients. Objective: To determine whether there is a different ACLR failure prevalence of autograft compared with allograft in young, active patients. Data Sources: EMBASE, MEDLINE, Cochrane trials registry. Study Selection: Comparative studies of allograft versus autograft primary ACL reconstruction in patients <25 years of age or of high-activity level (military, Marx activity score >12 points, collegiate or semiprofessional athletes). Study Design: Systematic review with meta-analysis. Level of Evidence: Level 3. Data Extraction: Manual extraction of available data from eligible studies. Quantitative synthesis of failure prevalence and Lysholm score (outcomes in ≥3 studies) and I2 test for heterogeneity. Assessment of study quality using CLEAR NPT and Newcastle-Ottawa Scale (NOS). Results: Seven studies met inclusion criteria (1 level 1; 2 level 2, 4 level 3), including 788 patients treated with autograft tissue and 228 with various allografts. The mean age across studies was 21.7 years (64% male), and follow-up ranged between 24 and 51 months. The pooled failure prevalence was 9.6% (76/788) for autografts and 25.0% (57/228) for allografts (relative risk, 0.36; 95% CI, 0.24-0.53; P < 0.00001; I2 = 16%). The number needed to benefit to prevent 1 failure by using autograft was 7 patients (95% CI, 5-10). No difference between hamstrings autograft and patella tendon autograft was noted. Lysholm score was reported in 3 studies and did not differ between autograft and allograft. Conclusion: While systematic reviews comparing allograft and autograft ACLR have been equivocal
Won, Yougun; Lee, Gi Soo; Kim, Sang Bum; Kim, Sun Joong; Yang, Kyu Hyun
As anatomical reduction of the articular surface of femoral head fractures and restoration of damaged cartilage are essential for good long-term results, many treatment options have been suggested, including fixation of the fracture using various surgical exposures and implants, as well as arthroscopic irrigation and debridement, bone marrow stimulating techniques, osteochondral allograft, autograft, and autogenous chondrocyte implantation. We report a case of osteochondral autograft harvested from its own femoral articular surface through surgical hip dislocation. The osteochondral graft was harvested from the inferior non-weight-bearing articular surface and grafted to the osteochondral defect. One year later, the clinical and radiological results were good, without the collapse of the femoral head or arthritic change. This procedure introduced in our case is considered convenient and able to lessen surgical time without morbidity of the donor site associated with the harvest.
AD_________________ Award Number: DAMD17-03-1-0311 TITLE: Mechanisms of Graft-vs.- Leukemia ...against a Novel Murine Model of Chronic Myelogenous Leukemia PRINCIPAL INVESTIGATOR: Warren D. Shlomchik, M.D. CONTRACTING ORGANIZATION...5a. CONTRACT NUMBER Mechanisms of Graft-vs.- Leukemia against a Novel Murine Model of Chronic Myelogenous Leukemia 5b. GRANT NUMBER DAMD17
Kokai, Lauren E; Jones, Taraneh L; Silowash, Russell; Theisen, Brian; DiBernardo, Gabriella; Lu, Andrew; Yi, Bowen; Marra, Kacey G; Rubin, J Peter
Animal models are often used to assess interventions that might improve fat grafting outcomes, however, there is great variability in the models. We sought to determine the predictive value of the immunocompromised mouse model for fat grafting so that experiments could be standardized and optimized. Human lipoaspirate injections at different volumes and time points were assessed in a nude mouse model and compared with control injections of non-viable fat. Volume retention and explant histologic score were compared. In a separate study, inter-animal reproducibility was determined by implanting a highly consistent hydrogel and measuring variability in volume retention. Injection volume significantly affects adipose resorption kinetics at 6 and 12 weeks. Masson's trichrome revealed that macrophages were unable to infiltrate large (1 ml) grafts, and oil cysts were not absorbed by 18 weeks, which interfered with interpretation of volume retention data. Non-viable tissue was resorbed when grafts were of 0.3mL and quantification of graft histologic viability correlated well with graft retention at all study time points. Inter-animal variability was measured to be 8.44% of the mean retention volume for small graft volumes. Human fat graft retention in the immunodeficient mouse correlates with graft viability in small, 0.3mL volume grafts. However, centralized oil cysts in non-viable 1.0mL grafts were not resorbed by 18 weeks and thus volume measurements were confounded and not significantly different from viable samples. Additionally, tissue injury scores increased in initially healthy fat grafts at 18 weeks, possibly due to a delayed immune reaction.
Aubá, Cristina; Hontanilla, Bernardo; Arcocha, Juan; Gorría, Oscar
The clinical use of nerve allografts combined with immunosuppressant therapy has become a genuine possibility that could supersede the classic use of autografts. However, contradictory data have been reported on whether immunosuppressant therapy should be temporarily administered. The purpose of this study was to compare the nerve regeneration obtained using ulnar nerve allografts in nonhuman primates temporarily treated with FK506 (tacrolimus) with that obtained using nerve autografts. Four-centimeter nerve autografts or allografts were placed in the distal ulnar motor nerve of eight monkeys. The FK506 was temporarily administered to the animals of the allograft group for 2 months. At periods of 3, 5, and 8 months postsurgery, quantitative electrophysiological recordings were obtained to estimate muscle response. A quantitative analysis of ulnar motor neurons in the spinal cord was performed and axons were counted stereologically. No statistically significant differences were found in the neuronal and axonal counts between autograft and allograft groups at 8 months. The electrophysiological studies showed no differences relative to the amplitude, but the autograft group presented with a greater nerve conduction velocity (NCV). However, no statistically significant differences were found between the number of neurons and distal axonal counts in the two groups. Nerve regeneration through cold-preserved allografts in a primate model temporarily treated with FK506 was similar to that obtained using nerve autografts, in terms of neuronal and axonal counts. Nevertheless, temporary immunosuppression produced lower NCV when allografts were used, with less maturation of the myelinated fibers, which indicated that a partial rejection had taken place.
Zhang, Yongguang; Wang, Zhiqiang
To sum up the recent progress of common bone graft substitute and to forecast the possible directions for further research. Recent original articles about investigation and application for bone graft substitute were extensively reviewed. Several common bone graft substitutes were selected and expounded in different categories. Bone graft was an essential treatment in order to provide structural support, fill bone cavity and promote bone defect healing. The gold standard for bone graft was autograft which is subject to many restrictions. In recent years, the research and development of bone graft substitute have received public attention. A very great progress has been made in the research and application of allograft bones, synthetic bones and engineered bones, and some research results have been put into use for real products. There still exist many problems in present bone graft substitutes. Combining various biomaterials and using the specific processing technology to develop a biomaterial which has the similar mechanical and chemical properties and physical structures to autograft so as to promote bone defect healing is the direction for future research.
Dai, Li-Yang; Jiang, Lei-Sheng
A prospective, randomized clinical study comparing beta-tricalcium phosphate (beta-TCP) with autograft bone graft with follow-up of 3 years. To determine the efficacy of beta-TCP as a bone graft substitute combined with local autograft obtained from decompression compared with the use of autologous iliac crest bone graft in single-level instrumented posterolateral lumbar fusion. A variety of bone graft substitutes have been used in posterolateral lumbar fusion with different efficacy reported, but no controlled study was conducted on the clinical performance of beta-TCP in instrumented posterolateral lumbar fusion. Sixty-two patients with symptomatic degenerative lumbar spinal stenosis were treated with single-level instrumented posterolateral lumbar fusion. They were randomly assigned to fusion with beta-TCP combined with local bone obtained from the decompression (group A, n = 32) or autogenous iliac crest bone graft plus decompression bone (group B, n = 30). The patients were observed up for 3 years after surgery. The results were assessed clinically and radiographically. There were no significant differences in recovery rate of Japanese Orthopedic Association score and SF-36 score at all time intervals. Successful radiographic fusion was documented in all patients in both treatment groups. All patients in group B, however, complained bone graft donor site pain although significant improvement of pain was observed during the follow-up. Instrumented posterolateral fusion with beta-TCP combined with local autograft results in the same radiographic fusion rates and similar improvement of clinical outcomes and life quality compared with autograft alone. The authors therefore recommend the use of beta-TCP as bone graft substitute for instrumented posterolateral fusion of lumbar spine to eliminate the need of bone grafting harvesting from the ilium.
Glazebrook, Mark; Younger, Alastair; Wing, Kevin; Lalonde, Karl-Andre
To reduce fusion nonunion, autogenous bone graft is often incorporated into foot and ankle fusion procedures. B2A peptide-coated ceramic granules, with encouraging results in pilot studies of transforaminal lumbar interbody fusion, were here reformulated into Amplex with a coating concentration of 225 μg B2A/cm(3) ceramic granules (B2A-granule) with the goal of eliminating autogenous bone graft in foot and ankle arthrodesis. The purpose of this study was to perform a multicenter prospective randomized pilot clinical trial designed to compare the safety and effectiveness of B2A-granule to autogenous bone graft in patients undergoing foot and ankle arthrodesis surgery. This study was a multicenter, prospective, randomized, pilot clinical trial designed to compare safety and effectiveness of B2A-granule to autogenous bone graft in patients undergoing foot and ankle arthrodesis surgery. Twenty-four patients were enrolled and randomized (1:1) into 2 groups: autogenous bone graft control and B2A-granule. Primary outcome measures at 6 months (with follow-up at 9 and 12 months) included radiographic fusion assessed by computerized tomography and Ankle Osteoarthritis Scale scores for pain and disability. Radiographic fusion success rates were similar in both groups (100% in the B2A-granule group, 92% autograft). Both the B2A-granule group and the autograft group had improvements in the pain and disability scores over the course of the study. Graft harvest-site pain affected only autograft-treated patients. There were no adverse events attributed to the graft material in either the B2A-granule or autograft group. The results of this pilot study are supportive of a larger clinical trial to assess the safety and efficacy of B2A-granule as a bone graft substitute in foot and ankle fusions. Level II, prospective comparative study.
Lynch, Michael P; Chung, Michael T; Rinker, Brian D
The use of acellular dermal matrix (ADM) in tissue expander breast reconstruction has been touted to reduce capsular contracture rates and improve aesthetic outcomes. Autogenous dermal grafts have shown to be a safer and more cost-effective alternative to ADM. The purpose of this study was to compare the capsular contracture rates and long-term aesthetic outcomes of tissue expander breast reconstruction using dermal autografts with ADM-assisted reconstruction. Patients undergoing tissue expander breast reconstruction with either ADM or dermal autografts were enrolled. Autografts were harvested from the lower abdomen. The capsular contracture rate was assessed via physical examination using the Baker scale. Standardized patient photographs were scored for aesthetic appearance on a 7-point Likert scale by blinded female observers. The ADM and autograft groups were compared using Student t test. Significance was defined as P < 0.05. Forty-eight patients were enrolled (76 breasts). The average follow-up time for the ADM group was 9.6 months and 9.9 months for the dermal autograft group. Twenty-seven patients received ADM, and 21 patients received dermal autograft. Capsular contracture scores were identical between the 2 groups (mean Baker grade = 1.15, P = 0.55). The average long-term aesthetic outcome score for dermal autograft-assisted breast reconstruction was 3.85, compared to 3.79 for ADM-assisted reconstruction. This difference was not statistically significant (P = 0.87). In addition to an improved safety profile and lower cost, dermal autograft-assisted tissue expander breast reconstruction affords equivalent aesthetic results and capsular contracture rates, when compared to ADM.
Accioli De Vaconcellos, Z A; Duchossoy, Y; Kassar-Duchossoy, L; Mira, J C
The authors described the reconstruction of a terminal branch of the brachial plexus (the median nerve) by different kinds of peripheral nerve grafts, in rats. Fresh or frozen autografts from Sprague-Dawley rats and fresh or frozen xenografts from Beagle dogs were used. Three, six, nine and twelve months after grafting, rats underwent histological assessment (muscle, nerve and spinal cord) and simple functional assessment by the grasping test. The immune reaction was prevented by the freezing and thawing method that had rendered xenografts acellular. This process allowed a satisfactory reinnervation of the flexor carpi radialis muscle (FCR) and a function recovery about 75% of control value. Nevertheless, the force recovery in rats that received frozen grafts was slower than those received fresh autografts. Probably, the destruction of cellular elements by freezing produced a deficient environment for nerve regeneration. However, this gap was partially compensated at twelve months after surgery by the maturation and the secondary adaptation of regenerated nerve fibers. Theses results showed that the force recovery is directly correlated to the capability of the nerve fibers to reproduce, histologically, a next to normal nerve pattern.
Sun, Yuan-Xin; Sun, Cheng-Li; Tian, Ye; Xu, Wen-Xiao; Zhou, Chang-Long; Xi, Chun-Yang; Yan, Jing-Long; Wang, Xin-Tao
The osteogenic potential for bone grafts is based on numbers and activities of cells that survive transplantation. In this study, we compared the bioactivity of osteocytes in 300-500 μm fine particulate bone powder grafts to 2 mm larger bone grafts in a rat radial defect model. Expression levels of bone morphogenetic protein-2 (BMP-2), transforming growth factor-beta 1 (TGF-β1), alkaline phosphatase (ALP), and collagen I were semi-quantified by both immunohistochemistry and RT-PCR at days 1 and 4, as well as weeks 1, 2, 4, 6 and 10 post-transplantation. Within two weeks post-transplantation, more cells stained positively for BMP-2, TGF-β1, ALP, and collagen I within the bone grafts and in the surrounding tissues in the group transplanted with the fine particulate bone powder grafts than in those with larger bone grafts (P<0.05). The mRNA levels of all four markers in the group transplanted with fine particulate bone powder graft peaked earlier and were expressed more highly than in the larger bone graft group, suggesting that fine particulate bone powder grafts provide more viable and active osteocytes to accelerate bone defect healing than larger bone grafts. Copyright © 2014 Elsevier GmbH. All rights reserved.
Vereecken, P; Wautrecht, J C; De Dobbeleer, G; Heenen, M
Pyoderma gangrenosum is a chronic inflammatory ulcerative skin disease of unknown etiology, often associated with various systemic disorders such as inflammatory bowel disease, rheumatoid arthritis, chronic active hepatitis, diabetes mellitus and hematologic malignancies. The ulcers are characterized by their undermined violaceous borders. The disease remains a therapeutic challenge. Corticosteroids are the mainstay of therapy; however, side effects from this treatment and recalcitrant pyoderma gangrenosum require therapeutic alternatives. We report the case of a large subacute pyoderma gangrenosum stabilized with lymecycline, topical benzoyl peroxide and successfully treated by an autograft. This observation supports the opinion that the risk of pathergy of a graft can be avoided by the stabilization of the disease.
Ong, J C Y; Kennedy, M T; Mitra, A; Harty, J A
The goal of this study was to determine differences in fracture stability and functional outcome between synthetic bone graft and natural bone graft with internal fixation of tibia plateau metaphyseal defects. Hydroxyapatite calcium carbonate synthetic bone graft was utilised in 14 patients (six males and eight females). Allograft/autograft were utilised in the remaining 10 patients (six males and four females). All the 24 patients had clinical, radiological and subjective functional score assessments. There was no significant statistical difference between the groups for post-operative articular reduction, long-term subsidence, and WOMAC scores. The degree of subsidence was not related to age or fracture severity. Maintenance of knee flexion was found to be better in the allograft/autograft group (p = 0.048) when compared between the groups. Multivariate analysis compared graft type, fracture severity, post-operative reduction, subsidence rate, range of movement and WOMAC score. The only finding was a statistical significant association with the graft type related to the 6-month range of movement figures. Use of autologous or allogenic bone graft allows better recovery of long-term flexion, possibly due to reduced inflammatory response compared with synthetic bone composites. However, all other parameters, such as maintenance of joint reduction and subjective outcome measures were comparable with the use of hydroxyapatite calcium carbonate bone graft. This study shows that synthetic bone graft may be a suitable alternative in fixation of unstable tibia plateau fractures, avoiding risk of disease transmission with allograft and donor site morbidity associated with autograft.
Alomar, Abdulaziz Z; Somily, Ali Mohammed; Alraiyes, Thamer M; Bin Nasser, Ahmad S; Aljassir, Fawzi F
dropped specimens, the quantification of the autograft contamination level revealed a very low CFUs/g in both cases. The intraoperative autograft contamination level is very low. Hence, in cases of grafts with a known contamination incident, saving and reimplanting them after proper decontamination is recommended over discarding them or using an allograft. © 2016 The Author(s).
Lee, Nicolas; Daley, Roger A; Cooley, Brian C
Microvascular training models for vein grafting most often use the rat epigastric vein interpositioned to the femoral artery. We describe the rat posterior facial vein as an alternative vein graft model; it has at least a 2:1 diametric ratio to the femoral artery and a tougher connective tissue, making it more similar to clinical vein grafting for reconstructive microsurgery. A series of 24 grafts interpositioned to the femoral artery were done using 11-12 sutures per end-to-end anastomosis and yielded early patency rates of 96% at 20 min and 92% at 2 and 4 weeks for subsets of 12 grafts. As a training model the diametric disparity provides unique challenges with clinical relevance, for which a number of different techniques for matching arterial to venous circumferences can be done. © 2014 Wiley Periodicals, Inc.
Jamjoom, Amal; Cohen, Robert E.
Alveolar ridge bone resorption is a biologic phenomenon that occurs following tooth extraction and cannot be prevented. This paper reviews the vertical and horizontal ridge dimensional changes that are associated with tooth extraction. It also provides an overview of the advantages of ridge preservation as well as grafting materials. A Medline search among English language papers was performed in March 2015 using alveolar ridge preservation, ridge augmentation, and various graft types as search terms. Additional papers were considered following the preliminary review of the initial search that were relevant to alveolar ridge preservation. The literature suggests that ridge preservation methods and augmentation techniques are available to minimize and restore available bone. Numerous grafting materials, such as autografts, allografts, xenografts, and alloplasts, currently are used for ridge preservation. Other materials, such as growth factors, also can be used to enhance biologic outcome. PMID:26262646
Graves, Scott S; Rezvani, Andrew; Sale, George; Stone, Diane; Parker, Maura; Rosinski, Steven; Spector, Michele; Swearingen, Bruce; Kean, Leslie; Storb, Rainer
In long-term survivors of allogeneic hematopoietic cell transplantation (HCT), chronic graft-versus-host disease (GVHD) is the major cause of morbidity and mortality and a major determinant of quality of life. Chronic GVHD responds poorly to current immunosuppressive drugs, and while T cell depletion may be preventive, this gain is offset by increased relapse rates. A significant impediment to progress in treating chronic GVHD has been the limitations of existing animal models. The goal of this study was to develop a reproducible comprehensive model of chronic GVHD in the dog. Ten recipient dogs received 920 cGy total body irradiation, infusion of marrow, and an infusion of buffy coat cells from a dog leukocyte antigen (DLA)-mismatched unrelated donor. Postgrafting immunosuppression consisted of methotrexate (days 1, 3, 6, 11) and cyclosporine. The duration of cyclosporine administration was limited to 80 days instead of the clinically used 180 days. This was done to contain costs, as chronic GVHD was expected to develop at earlier time points. All recipients were given ursodiol for liver protection. One dog had graft failure and 9 dogs showed stable engraftment. Eight of the 9 developed de novo chronic GVHD. Dogs progressed with clinical signs of chronic GVHD over a period of 43 to 164 (median, 88) days after discontinuation of cyclosporine. Target organs showed the spectrum of chronic GVHD manifestations that are typically seen clinically. These included lichenoid changes of the skin, fasciitis, ocular involvement (xerophthalmia), conjunctivitis, bronchiolitis obliterans, salivary gland involvement, gingivitis, esophageal involvement, and hepatic involvement. Peripheral blood lymphocyte surface antigen expression of CD28 and inducible costimulator was elevated in dogs with GHVD compared with those in normal dogs, but not significantly so. Serum levels of IL-8 and monocyte chemotactic protein-1 in GVHD-affected dogs at time of euthanasia were elevated, whereas
Buchner, Alexander; Matiasek, Kaspar; Schlenker, Boris; Stief, Christian; Weidner, Norbert
ABSTRACT Dissection of the cavernous nerves during radical prostatectomy for prostate cancer eliminates spontaneous erections. Using the rat as an experimental model, we compared the regenerative capacity of autologous nerve grafts and Schwann-cell-seeded nerve guides. After bilateral excision of cavernous nerve segments, cavernous nerves were reconstructed using unseeded silicon tubes, nerve autografts and silicon tubes seeded with either Glial-cell-line-derived (GDNF)-overexpressing or green fluorescent protein (GFP)-expressing Schwann cells (SCs) (16 study nerves per group). Control groups underwent either a sham operation or bilateral excision of cavernous nerve segments without repair. After 12 weeks erectile function was assessed by neurostimulation and intracavernous pressure (ICP) measurement. The reconstructed nerve segments were excised and histologically analyzed. We demonstrated an intact erectile response upon neurostimulation in 25% (4/16) of autologous nerve grafts, in 50% (8/16) of unseeded tubes, in 75% (12/16) of the Schwann-cell–GFP group and in 93.75% (15/16) of the GDNF group. ICP was significantly increased when comparing the Schwann-cell–GFP group with nerve autografts, unseeded conduits and negative controls (P<0.005). In conclusion, Schwann-cell-seeded scaffolds combined with neurotrophic factors are superior to unseeded tubes and autologous nerve grafts. They present a promising therapeutic approach for the repair of erectile nerve gaps. PMID:27874834
Leiter, Jeff; Elkurbo, Mohamed; McRae, Sheila; Chiu, James; Froese, Warren; MacDonald, Peter
Large variation in tendon size between individuals makes hamstring graft diameter for anterior cruciate ligament (ACL) reconstruction unpredictable. Inadequate graft diameter may necessitate an alternative source of tissue requiring pre-operative planning. The purpose of this study was to determine whether magnetic resonance image (MRI) measurements and clinical anthropometric data are predictive of hamstring tendon graft diameter. Data from 109 patients having ACL reconstruction with semitendinosus-gracilis (STGT) autograft were retrospectively evaluated. Cross-sectional area (CSA) of the gracilis tendon (GT) and semitendinosus tendon (ST) were determined from pre-operative MRI scans. Variables included pre-operative height, weight, body mass index (BMI), age and gender; and intra-operative graft diameter. Correlations between anthropometric variables, hamstring tendons CSA and intra-operative graft diameter were calculated. Multiple stepwise regression was performed to assess the predictive value of these variables to graft diameter. Sensitivity and specificity were calculated to evaluate the utility of MRI CSA measurements in accurately identifying inadequate graft diameter (<8 mm). All anthropometric variables were positively correlated with intraoperative graft diameter (p < 0.01). Semitendinosus-gracilis tendon CSA (p < 0.001) and STGT CSA and weight (p < 0.001) were significantly predictive models of graft diameter. Sensitivity and specificity were 79 and 74 %, respectively. The strongest indicators of a four-stranded STGT graft for primary ACL reconstruction were STGT CSA on MRI plus weight. Measurement of graft diameter can be performed pre-operatively via MRI to identify tendons that may be of inadequate size for ACL reconstruction. This can assist with surgical planning to determine the most appropriate graft choice. III.
Ozgurhan, Engin Bilge; Kara, Necip; Bozkurt, Ercument; Gencer, Baran; Agca, Alper; Alkin, Zeynep; Demirok, Ahmet
To evaluate the effect of a fluorometholone/tetrahydrozoline fixed combination on conjunctival graft morphology after primary pterygium excision. The patients who underwent pterygium excision with conjunctival autograft transplantation were randomized into three groups based on postoperative medications as the fluorometholone/tetrahydrozoline group, fluorometholone group, and dexamethasone group. Conjunctival graft thickness was measured with anterior segment optical coherence tomography. The conjunctival graft hyperemia was evaluated using a high definition external camera. The mean graft thickness was significantly lower in the fluorometholone/tetrahydrozoline group compared with fluorometholone and dexamethasone groups at 2 weeks (P = 0.002 and P = 0.012, resp.) and at 1 month after surgery (P = 0.003 and P = 0.013, resp.). The conjunctival hyperemia score was significantly lower in the fluorometholone/tetrahydrozoline group compared with fluorometholone and dexamethasone groups at 2 weeks (P = 0.000 and P = 0.000, resp.) and at 1 month (P = 0.039 and P = 0.040, resp.). The graft thickness and conjunctival hyperemia score were similar among the groups at 1 week and 3 months (P > 0.05). The findings of the present study revealed that treatment with the fluorometholone/tetrahydrozoline fixed combination may be helpful to decrease graft edema and to achieve better cosmetic appearance at 2 weeks and 1 month after pterygium excision.
Ozgurhan, Engin Bilge; Kara, Necip; Bozkurt, Ercument; Gencer, Baran; Agca, Alper; Demirok, Ahmet
Purpose. To evaluate the effect of a fluorometholone/tetrahydrozoline fixed combination on conjunctival graft morphology after primary pterygium excision. Methods. The patients who underwent pterygium excision with conjunctival autograft transplantation were randomized into three groups based on postoperative medications as the fluorometholone/tetrahydrozoline group, fluorometholone group, and dexamethasone group. Conjunctival graft thickness was measured with anterior segment optical coherence tomography. The conjunctival graft hyperemia was evaluated using a high definition external camera. Results. The mean graft thickness was significantly lower in the fluorometholone/tetrahydrozoline group compared with fluorometholone and dexamethasone groups at 2 weeks (P = 0.002 and P = 0.012, resp.) and at 1 month after surgery (P = 0.003 and P = 0.013, resp.). The conjunctival hyperemia score was significantly lower in the fluorometholone/tetrahydrozoline group compared with fluorometholone and dexamethasone groups at 2 weeks (P = 0.000 and P = 0.000, resp.) and at 1 month (P = 0.039 and P = 0.040, resp.). The graft thickness and conjunctival hyperemia score were similar among the groups at 1 week and 3 months (P > 0.05). Conclusion. The findings of the present study revealed that treatment with the fluorometholone/tetrahydrozoline fixed combination may be helpful to decrease graft edema and to achieve better cosmetic appearance at 2 weeks and 1 month after pterygium excision. PMID:23865053
To, Nhat; Curtiss, Shane; Neu, Corey P; Salgado, Christopher J; Jamali, Amir A
Allografting and autografting of osteochondral tissues is a promising strategy to treat articular cartilage lesions in damaged joints. We developed a new model of fresh osteochondral allografting using the entire rabbit trochlea. The objective of the current study was to demonstrate that this model would achieve reproducible graft-host healing and maintain normal articular cartilage histologic, immunolocalization, and biochemical characteristics after transplantation under diverse storage and transplantation conditions. New Zealand white (n = 8) and Dutch belted (n = 8) rabbits underwent a 2-stage transplantation operation using osteochondral grafts that had been stored for 2 or 4 wk. Trochlear grafts harvested from the left knee were transplanted to the right knee as either autografts or allografts. Grafts were fixed with 22-gauge steel wire or 3-0 nylon suture. Rabbits were euthanized for evaluation at 1, 2, 4, 6, and 12 wk after transplantation. All grafts that remained in vivo for at least 4 wk demonstrated 100% interface healing by microCT. Trabecular bridging was present at the host-graft interface starting at 2 wk after transplantation, with no significant difference in cartilage histology between the various groups. The combined histology scores indicated minimal evidence of osteoarthritis. Immunostaining revealed that superficial zone protein was localized at the surface of all transplants. The rabbit trochlear model met our criteria for a successful model in regard to the ease of the procedure, low rate of surgical complications, relatively large articular cartilage surface area, and amount of host-graft bone interface available for analysis.
Background Expanded polytetrafluoroethylene (ePTFE) vascular grafts frequently develop occlusive neointimal hyperplasia as a result of myofibroblast over-growth, leading to graft failure. ePTFE exhibits higher ultrasound attenuation than native soft tissues. We modelled the selective absorption of ultrasound by ePTFE, and explored the feasibility of preventing hyperplasia in ePTFE grafts by ultrasound heating. Specifically, we simulated the temperature profiles of implanted grafts and nearby soft tissues and blood under ultrasound exposure. The goal was to determine whether ultrasound exposure of an ePTFE graft can generate temperatures sufficient to prevent cell growth on the graft without damaging nearby soft tissues and blood. Methods Ultrasound beams from two transducers (1.5 and 3.2 MHz) were simulated in two graft/tissue models, with and without an intra-graft cellular layer mimicking hyperplasia, using the finite-difference time-domain (FDTD) method. The resulting power deposition patterns were used as a heat source for the Pennes bioheat equation in a COMSOL® Multiphysics heat transfer model. 50°C is known to cause cell death and therefore the transducer powers were adjusted to produce a 13°C temperature rise from 37°C in the ePTFE. Results Simulations showed that both the frequency of the transducers and the presence of hyperplasia significantly affect the power deposition patterns and subsequent temperature profiles on the grafts and nearby tissues. While neither transducer significantly raised the temperature of the blood, the 1.5-MHz transducer was less focused and heated larger volumes of the graft and nearby soft tissues than the 3.2-MHz transducer. The presence of hyperplasia had little effect on the blood's temperature, but further increased the temperature of the graft and nearby soft tissues in response to either transducer. Skin cooling and blood flow play a significant role in preventing overheating of the native tissues. Conclusions
Bhora, Faiz Y; Lewis, Erik E; Rehmani, Sadiq S; Ayub, Adil; Raad, Wissam; Al-Ayoubi, Adnan M; Lebovics, Robert S
Methods for tracheal graft research have presented persistent challenges to investigators, and three-dimensional (3D)-printed biosynthetic grafts offer one potential development platform. We aimed to develop an efficient research platform for customizable circumferential 3D-printed tracheal grafts and evaluate feasibility and early structural integrity with a large-animal model. Virtual 3D models of porcine subject tracheas were generated using preoperative computed tomography scans. Two designs were used to test graft customizability and the limits of the construction process. Designs I and II used 270-degree and 360-degree external polycaprolactone scaffolds, respectively, both encompassing a circumferential extracellular matrix collagen layer. The polycaprolactone scaffolds were made in a fused-deposition modeling 3D printer and customized to the recipient's anatomy. Design I was implanted in 3 pigs and design II in 2 pigs, replacing 4-ring tracheal segments. Data collected included details of graft construction, clinical outcomes, bronchoscopy, and gross and histologic examination. The 3D-printed biosynthetic grafts were produced with high fidelity to the native organ. The fabrication process took 36 hours. Grafts were implanted without immediate complication. Bronchoscopy immediately postoperatively and at 1 week demonstrated patent grafts and appropriate healing. All animals lived beyond a predetermined 1-week survival period. Bronchoscopy at 2 weeks showed significant paraanastomotic granulation tissue, which, along with partial paraanastomotic epithelialization, was confirmed on pathology. Overall survival was 17 to 34 days. We propose a rapid, reproducible, resource efficient method to develop various anatomically precise grafts. Further graft refinement and strategies for granulation tissue management are needed to improve outcomes. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Kawajiri, Hidetake; Mizuno, Takeshi; Moriwaki, Takeshi; Iwai, Ryosuke; Ishibashi-Ueda, Hatsue; Yamanami, Masashi; Kanda, Keiichi; Yaku, Hitoshi; Nakayama, Yasuhide
The use of stent grafts for endovascular aortic repair has become an important treatment option for aortic aneurysms requiring surgery. This treatment has achieved excellent outcomes; however, problems like type 1 endoleaks and stent graft migration remain. Bio stent grafts (BSGs), which are self-expanding stents covered with connective tissue, were previously developed using "in-body tissue architecture" technology. We assessed their early adaptation to the aorta after transcatheter implantation in a beagle model. BSGs were prepared by subcutaneous embedding of acryl rods mounted with self-expanding nitinol stents in three beagles for 4 weeks (n = 3/dog). The BSGs were implanted as allografts into infrarenal abdominal aortas via the femoral artery of three other beagles. After 1 month of implantation, aortography revealed no stenosis or aneurysmal changes. The luminal surface of the BSGs was completely covered with neointimal tissue, including endothelialization, without any thrombus formation. The cover tissue could fuse the luminal surface of the native aorta with tight conjunctions even at both ends of the stents, resulting in complete impregnation of the strut into the reconstructed vascular wall, which is expected to prevent endoleaks and migration in clinical applications.
Nappi, Francesco; Spadaccio, Cristiano; Fraldi, Massimiliano; Montagnani, Stefania; Fouret, Pierre; Chachques, Juan Carlos; Acar, Christophe
Use of resorbable external reinforcement of the pulmonary autograft during the Ross operation has been suggested, but the differential regional potential for dilation of the aorta, mainly regarding the neo-root and the neo-Valsalva sinuses, represents an unresolved issue. Auxetic materials could be useful in preventing dilation given their favorable mechanical properties. We designed a composite semiresorbable armoured bioprosthesis constituted by polydioxanone and expanded polytetrafluoroethylene and evaluated its effectiveness as a pulmonary autograft reinforcement device in an animal model of the Ross procedure. An experimental model of the Ross procedure was performed in 20 three-month-old growing lambs. The pulmonary autograft was alternatively nonreinforced (control group n = 10) or reinforced with composite bioprosthesis (reinforced group n = 10). Animals were followed up during growth for 6 months by angiography and echocardiography. Specific stainings for extracellular matrix and immunohistochemistry for metalloproteinase-9 were performed. Reference aortic diameter increased from 14 ± 1 mm to 19 ± 2 mm over 6 months of growth. In the control group, pulmonary autograft distension (28 ± 2 mm) was immediately noted, followed by aneurysm development at 6 months (40 ± 2 mm, P < .001 vs reference). In the reinforced group, an initial dilation to 18 ± 1 mm was detected and the final diameter was 27 ± 2 mm (42% increase). Two deaths due to pulmonary autograft rupture occurred in the control group. On histology, the control group showed medial disruption with connective fibrous replacement, whereas in the reinforced group compensatory intimal hyperplasia was present in the absence of intimal tears. The bioprosthesis promoted a positive matrix rearrangement process favoring neoarterialization and elastic remodeling as demonstrated on specific staining for elastin collagen and metalloproteinase-9. The device adapted and functionally compensated for the
Ramachandra, Abhay B.; Sankaran, Sethuraman; Humphrey, Jay; Marsden, Alison
In coronary artery disease, surgical revascularization using venous bypass grafts is performed to relieve symptoms and prolong life. Coronary bypass graft surgery is performed on approximately 500,000 people every year in the United States, with graft failure rates as high as 50% within 5 years. When a vein graft is implanted in the arterial system it adapts to the high flow rate and high pressure of the arterial environment by changing composition and geometry, and thus stiffness. Hemodynamic loads, resulting in altered wall shear and intramural stresses, are major factors impacting vein graft remodeling. Here, a constrained mixture theory of growth and remodeling for arteries is extended to model the evolution of a vein graft subjected to arterial flow and pressure conditions. A derivative-free optimization method is used to estimate the optimal set of constitutive parameters that best match passive biaxial mouse inferior vena cava data from experiments. Optimization is performed using surrogate management framework, a pattern search method with established convergence theory. The resulting parameter set is used to predict optimal vein adaptation in an arterial environment for two illustrative cases: a) Step change b) Gradual change in loading. Results are compared against vein graft data from the literature and a possible set of mechanisms for sub-optimal vein graft remodeling is suggested.
Kim, Hyun Beom; Choi, Young Ho; So, Young Ho; Min, Seung-Kee; Kim, Hyo-Cheol; Kim, Young Il; Park, Jae Hyung
We investigated tissue responses to endoskeleton stent grafts for saccular abdominal aortic aneurysms (AAAs) in canines. Saccular AAAs were made with Dacron patch in 8 dogs, and were excluded by endoskeleton stent grafts composed of nitinol stent and expanded polytetrafluoroethylene graft. Animals were sacrificed at 2 months (Group 1; n = 3) or 6 months (Group 2; n = 5) after the placement, respectively. The aortas embedding stent grafts were excised en bloc for gross inspection and sliced at 5 to 8 mm intervals for histopathologic evaluation. Stent grafts were patent in all except a dog showing a thrombotic occlusion in Group 2. In the 7 dogs with patent lumen, the graft overhanging the saccular aneurysm was covered by thick or thin thrombi with no endothelial layer, and the graft over the aortic wall was completely covered by neointima with an endothelial layer. Transgraft cell migration was less active at an aneurysm than at adjacent normal aorta. In conclusion, endoskeleton stent grafts over saccular aneurysms show no endothelial coverage and poor transgraft cell migration in a canine model. PMID:23091313
Wang, Wei-Ming; Ma, Xiao-Jun; Huang, Shi-Bo; Ren, Liu-Bao; Liu, Yu-Peng
This study aimed to compare the effect of autograft or allograft anterior cruciate ligament (ACL) reconstruction on the expressions of LOXs and MMPs in a New Zealand white rabbit model. New Zealand white rabbits were divided randomly into control, sham, autograft and allograft groups At the 4th and 8th week after operation, biomechanical testing was performed to measure the primary length, cross-sectional area, maximum tensile load and stiffness of ACL, and HE staining was used to observe cell morphology and fibre alignment of ACL. At the 2nd, 4th and 8th week after operation, qRT-PCR, Western blotting and immunohistochemistry were applied to detect LOXs and MMPs expressions, and expressions of APC/Wnt signaling pathway-related proteins. At the 4th and 8th week after operation, the maximum tensile load and stiffness were higher in the autograft group than in the allograft group, and the values at the 8th week were higher than those at the 4th week after operation. The fibroblast proliferation in the allograft group was more significant than that in the autograft group. Compared with the control group, LOXs and MMPs expressions, and the positive expression rates of LOXs and MMPs proteins were elevated, and the values in the allograft group were higher than those in the autograft group at all time points. At 8th week after operation, compared with the autograft group, Wnt expression was higher and APC expression lower in the allograft group. Autograft and allograft ACL reconstruction can promote LOXs and MMPs expressions by activating the APC/Wnt signaling pathway.
Calvo Rodríguez, R; Figueroa Poblete, D; Anastasiadis Le Roy, Z; Etchegaray Bascur, F; Vaisman Burucker, A; Calvo Mena, R
The purpose of the study was to evaluate the functional results after medial patellofemoral ligament (MPFL) reconstruction in patients using auto- and allograft. A retrospective study was conducted on 28 patients with recurrent patellar dislocation, with 13 patients (13 knees) undergoing MPFL reconstruction with hamstring autograft, and 15 patients (16 knees) with reconstruction surgery with allograft. The total group included 13 males and 15 females, with an age range of 15 to 38 years. The graft-related morbidity was studied and a clinical assessment was performed using the pre- and postoperative Kujala score. Associated complications were reported for each group. All the patients had more than 12 months of follow up. No recurrent dislocations or graft related complications were reported in either group. The post-operative Kujala subjective knee score was 89.2 in the autograft group, and 92.6 in the allograft group (p >.05). One patient in the allograft group received a revision surgery due to poor positioning of anchors. Another patient in the allograft group had non-displaced patella fracture related to the bone tunnels and another patient had flexion deficit and needed mobilization under anesthesia. There were no significant differences between both groups, and the results were comparable. Copyright © 2014 SECOT. Published by Elsevier Espana. All rights reserved.
Purpose The aim of this study was to present new a model that allows the study of the bone healing process, with an emphasis on the biological behavior of different graft-to-host interfaces. A standardized “over-inlay” surgical technique combined with a differential histomorphometric analysis is presented in order to optimize the use of critical-size calvarial defects in pre-clinical testing. Methods Critical-size defects were created into the parietal bone of 8 male Wistar rats. Deproteinized bovine bone (DBBM) blocks were inserted into the defects, so that part of the block was included within the calvarial thickness and part exceeded the calvarial height (an “over-inlay” graft). All animals were sacrificed at 1 or 3 months. Histomorphometric and immunohistochemical evaluation was carried out within distinct regions of interest (ROIs): the areas adjacent to the native bone (BA), the periosteal area (PA) and the central area (CA). Results The animals healed without complications. Differential morphometry allowed the examination of the tissue composition within distinct regions: the BA presented consistent amounts of new bone formation (NB), which increased over time (24.53%±1.26% at 1 month; 37.73%±0.39% at 3 months), thus suggesting that this area makes a substantial contribution toward NB. The PA was mainly composed of fibrous tissue (71.16%±8.06% and 78.30%±2.67%, respectively), while the CA showed high amounts of DBBM at both time points (78.30%±2.67% and 74.68%±1.07%, respectively), demonstrating a slow remodeling process. Blood vessels revealed a progressive migration from the interface with native bone toward the central area of the graft. Osterix-positive cells observed at 1 month within the PA suggested that the periosteum was a source of osteoprogenitor elements. Alkaline phosphatase data on matrix deposition confirmed this observation. Conclusions The present model allowed for a standardized investigation of distinct graft
interposition grafts in a sheep (Ovis aries ) model." PRINCIPAL INVESTIGATOR (Pl) I TRAINING COORDINATOR (TC): Maj Lucas Neff DEPARTMENT: General...USAGE: Animal Species: Total# Approved # Used this FY Total# Used to Date Ovies aries 12 8 4 2. PROTOCOL TYPE I CHARACTERISTICS: (Check all applicable...and conclusions/applications.) Title: Study of the efficacy of extracellular matrix arterial interposition grafts in a sheep (Ovis aries ) model
Model water-soluble graft copolymers have been synthesized with acrylamide as the major grafting monomer and dextran as the substrate in order to define more clearly the structural parameters that are important in enhanced oil recovery applications. The structures of the model graft copolymer samples were studied by aqueous size exclusion chromatography, viscometry, elemental analysis, and selective hydrolysis of the graft copolymer backbone. The grafting systems with selected grafting monomers included Fe(II)/H/sub 2/O/sub 2/ with acrylamide, and Ce(IV)/HNO/sub 3/ with acrylamide, acrylamide/2-acrylamido-2-meth propane sulfonic acid, or acrylamide/diacetone acrylamide. The viscosity and pseudoplasticity of the resulting graft copolymers were affected by both total molecular weight and length of grafted chains; however, the latter was apparently more important when behavior was compared to linear counterparts.
Lenčová, Anna; Pokorná, Kateřina; Zajícová, Alena; Krulová, Magdaléna; Filipec, Martin; Holáň, Vladimír
Limbal transplantation or limbal stem cell (LSC) transfer represents the only way to treat severe ocular surface damage or LSC deficiency. However, limbal allografts are promptly rejected in spite of extensive immunosuppressive therapy. To characterize immune response after limbal transplantation, we established an experimental model of limbal transplantation in the mouse. Syngeneic, allogeneic and xenogeneic (rat) limbal grafts were grafted orthotopically in BALB/c mice and graft survival was evaluated. The presence of graft donor cells and the expression of IL-2, IL-4, IL-10, IFN-γ and inducible nitric oxide synthase (iNOS) mRNA in the grafts were detected by real-time PCR. While syngeneic grafts survived permanently, allografts were rejected in 9.0±1.8 days and xenografts in 6.5±1.1 days. The manifestation of clinical symptoms of rejection correlated with the disappearance of donor cells in the graft and in the recipient cornea. Intragraft expression of iNOS mRNA and distinct expression patterns of Th1 (IL-2, IFN-γ) and Th2 (IL-4, IL-10) cytokines were detected during rejection of limbal allografts and xenografts. The limbal graft rejection was prevented with anti-CD4, but not anti-CD8 monoclonal antibody therapy. The results indicate that limbal grafts do not enjoy immune privilege of the eye and are promptly rejected by Th1 (allografts) or by a combined Th1 and Th2 (xenografts) type of immune response involving CD4+ cells and iNOS expression. Targeting this pathway may be an effective way to prevent and treat limbal graft rejection. Copyright © 2010 Elsevier B.V. All rights reserved.
Sankaranarayanan, Meena; Chua, Leok Poh; Ghista, Dhanjoo N; Tan, Yong Seng
Background Coronary artery bypass grafting surgery is an effective treatment modality for patients with severe coronary artery disease. The conduits used during the surgery include both the arterial and venous conduits. Long- term graft patency rate for the internal mammary arterial graft is superior, but the same is not true for the saphenous vein grafts. At 10 years, more than 50% of the vein grafts would have occluded and many of them are diseased. Why do the saphenous vein grafts fail the test of time? Many causes have been proposed for saphenous graft failure. Some are non-modifiable and the rest are modifiable. Non-modifiable causes include different histological structure of the vein compared to artery, size disparity between coronary artery and saphenous vein. However, researches are more interested in the modifiable causes, such as graft flow dynamics and wall shear stress distribution at the anastomotic sites. Formation of intimal hyperplasia at the anastomotic junction has been implicated as the root cause of long- term graft failure. Many researchers have analyzed the complex flow patterns in the distal sapheno-coronary anastomotic region, using various simulated model in an attempt to explain the site of preferential intimal hyperplasia based on the flow disturbances and differential wall stress distribution. In this paper, the geometrical bypass models (aorto-left coronary bypass graft model and aorto-right coronary bypass graft model) are based on real-life situations. In our models, the dimensions of the aorta, saphenous vein and the coronary artery simulate the actual dimensions at surgery. Both the proximal and distal anastomoses are considered at the same time, and we also take into the consideration the cross-sectional shape change of the venous conduit from circular to elliptical. Contrary to previous works, we have carried out computational fluid dynamics (CFD) study in the entire aorta-graft-perfused artery domain. The results reported here
Kanamoto, Takashi; Tanaka, Yoshinari; Yonetani, Yasukazu; Kita, Keisuke; Amano, Hiroshi; Kusano, Masashi; Hirabayashi, Shinji; Horibe, Shuji
Anterior knee pain related to the donor site is a frequent complication of anterior cruciate ligament reconstruction (ACLR) with bone-patellar tendon-bone autograft tissue. Even when hamstring tendon (HT) grafts are used instead, symptoms such as mild pain and discomfort can still occur. The purpose of this study was to elucidate the pathophysiology of anterior knee symptoms after ACLR with HT autografts. Fifty-seven patients (22 men and 35 women; mean age, 24.7 years) who underwent anatomic double-bundle ACLR with HT autografts were examined 6 months post-operatively. The presence of anterior knee symptoms, anterior knee laxity, range of motion, and muscle strength were assessed. Changes in patellar tendon and infrapatellar fat pad (IFP) morphology and blood flow were also evaluated using ultrasound. Potential variables affecting the presence of anterior knee symptoms were subjected to univariate analysis and multivariate logistic regression analysis to identify independent risk factors. Six months post-operatively, the total incidence of anterior knee symptoms was 56.1 % (32/57). According to univariate analysis, age, quadriceps strength, and increased blood flow in the IFP were significantly associated with the presence of anterior knee symptoms. Multivariate logistic regression analysis revealed that increased blood flow in the IFP was an independent factor for the presence of anterior knee symptoms (odds ratio 5.0; 95 % confidence interval 1.3-19.9). There were no significant findings inside the patellar tendon. Increased blood flow in the IFP was identified as an independent factor for the presence of anterior knee symptoms 6 months after ACLR with HT autografts. The ultrasound evaluation can help to define precisely the origin of anterior knee symptoms after ACLR with HT autografts. Case series with no comparison groups, Level IV.
The lack of autograft donor sites with major burns provides the impetus to develop innovative solutions due to the difficulty of wound closure. Autograft donor sites are particularly limited in patients with burns involving over 50% total body surface area (TBSA). The introduction of cultured epithelial cell autografts offers a potential solution to assist in wound closure. The objective of this study was the assessment of clinical results after sprayed application of the cultured epithelial autograft (CEA, Keraheal™, Seoul, Korea, MCTT) suspension onto the wounds of extensively burned patients. This retrospective clinical audit of major burn patients (n=16) describes the use of CEA which was combined with 6:1 meshed expansion grafts in those with the burn over 40% TBSA in our hospital between the period of August 2007 and January 2010. The burn patients included 12 males and 4 females with a mean age 41.5 and a burn area of 51.3 ± 3.1% TBSA (30-70%; median: 50.5%) and a mean third burn area of 32.5 ± 3.0% TBSA (median 34.0%). The take rates were 37.6%, 68.0% and 90.0% on average at 2, 4 and 8 weeks after treatment with the suspension, respectively, and the transplantation of the cultured cells was applied to full-thickness burns, with the coverage of a skin area of 497.5 cm(2) per 1 ml of the cultured cells. For clinical follow-up, 12 patients were observed for 21.5 months on average, with a maximum follow-up period of 39 months. Six patients were excluded from the surveillance because two died during hospitalisation and the other four were impossible to trace. The use of a sprayed cultured epithelial cell autograft (Keraheal™) in treating a full-thickness skin wound in severely burned patients results in favourable quality of scars and also good potential to save lives by providing epidermal cover. Copyright © 2012 Elsevier Ltd and ISBI. All rights reserved.
Carlsson, Anders H; Rose, Lloyd F; Fletcher, John L; Wu, Jesse C; Leung, Kai P; Chan, Rodney K
Current standard of care for full-thickness burn is excision followed by autologous split-thickness skin graft placement. Skin grafts are also frequently used to cover surgical wounds not amenable to linear closure. While all grafts have potential to contract, clinical observation suggests that antecedent thermal injury worsens contraction and impairs functional and aesthetic outcomes. This study evaluates the impact of antecedent full-thickness burn on split-thickness skin graft scar outcomes and the potential mediating factors. Full-thickness contact burns (100°C, 30s) were created on the backs of anesthetized female Yorkshire Pigs. After seven days, burn eschar was tangentially excised and covered with 12/1000th inch (300μm) split-thickness skin graft. For comparison, unburned wounds were created by sharp excision to fat before graft application. From 7 to 120days post-grafting, planimetric measurements, digital imaging and biopsies for histology, immunohistochemistry and gene expression were obtained. At 120days post-grafting, the Observer Scar Assessment Scale, colorimetry, contour analysis and optical graft height assessments were performed. Twenty-nine porcine wounds were analyzed. All measured metrics of clinical skin quality were significantly worse (p<0.05) in burn injured wounds. Histological analysis supported objective clinical findings with marked scar-like collagen proliferation within the dermis, increased vascular density, and prolonged and increased cellular infiltration. Observed differences in contracture also correlated with earlier and more prominent myofibroblast differentiation as demonstrated by α-SMA staining. Antecedent thermal injury worsens split-thickness skin graft quality, likely by multiple mechanisms including burn-related inflammation, microscopically inadequate excision, and dysregulation of tissue remodeling. A valid, reliable, clinically relevant model of full-thickness burn, excision and skin replacement therapy has been
Ji, Qiang; Mei, Yunqing; Wang, Xisheng; Feng, Jing; Cai, Jianzhi; Sun, Yifeng; Dewei, Wusha; Wang, Chunping; Chi, Liangjie
Although the use of external vein graft support seems a promising approach to prevent neointimal hyperplasia and wall thickening in vein grafts, its extensive clinical application still has a long way to go. The aim of this study was to evaluate short-term effects of self-designed double-layer autologous saphenous vein graft on restraining excessive distension of vein graft and alleviating neointimal hyperplasia in a porcine model. Left and right hind femoral arteries of 24 white pigs were randomly divided into an experimental group (double-layer vein graft) and a control group (single-layer vein graft). After 1 h of implantation, then 1, 2, and 4 weeks later, the mean inner diameter of the vein grafts in the experimental group measured by Doppler-ultrasound was 2.7 ± 0.1, 2.8 ± 0.1, 2.9 ± 0.1, and 3.1 ± 0.1 mm, respectively; mean peak blood flow velocity measured by Doppler-ultrasound was 96.7 ± 12.8, 93.7 ± 11.5, 89.4 ± 9.6 and 84.6 ± 10.1 cm/s, respectively, while the mean neointimal thicknesses were 47.1 ± 7.7, 93.7 ± 15.1, and 177.4 ± 25.5 μm at 1, 2 and 4 weeks, respectively. As compared to the control group, inner diameter and neointimal thickness of vein grafts in the experimental group were significantly lower, while mean peak blood flow velocity was significantly higher at 1, 2, and 4 weeks after implantation. The proliferation index in the experimental group was also significantly lower within 4 weeks after implantation. The self-designed double-layer autologous saphenous vein graft restrains early excessive distension of vein graft and alleviates early neointimal hyperplasia.
Shimada, Kozo; Tanaka, Hiroyuki; Matsumoto, Taiichi; Miyake, Junichi; Higuchi, Haruhisa; Gamo, Kazushige; Fuji, Takeshi
Background: There is a need to clarify the usefulness of and problems associated with cylindrical costal osteochondral autograft for reconstruction of large defects of the capitellum due to osteochondritis dissecans. Methods: Twenty-six patients with advanced osteochondritis dissecans of the humeral capitellum were treated with use of cylindrical costal osteochondral autograft. All were males with elbow pain and full-thickness articular cartilage lesions of ≥15 mm in diameter. Clinical, radiographic, and magnetic resonance imaging outcomes were evaluated at a mean follow-up of thirty-six months (range, twenty-four to fifty-one months). Results: All patients had rapid functional improvement after treatment with costal osteochondral autograft and returned to their former activities, including sports. Five patients needed additional minor surgical procedures, including screw removal, loose body removal, and shaving of protruded articular cartilage. Mean elbow function, assessed with use of the clinical rating system of Timmerman and Andrews, was 111 points preoperatively and improved to 180 points at the time of follow-up and to 190 points after the five patients underwent the additional operations. Mean elbow motion was 126° of flexion with 16° of extension loss preoperatively and improved to 133° of flexion with 3° of extension loss at the time of follow-up. Osseous union of the graft on radiographs was obtained within three months in all patients. Revascularization of the graft depicted on T1-weighted magnetic resonance imaging and congruity of the reconstructed articular surface depicted on T2-weighted or short tau inversion recovery imaging were assessed at twelve and twenty-four months postoperatively. Functional recovery was good, and all patients were satisfied with the final outcomes. Conclusions: Cylindrical costal osteochondral autograft was useful for the treatment of advanced osteochondritis dissecans of the humeral capitellum. Functional recovery
Bone graft is widely used within orthopaedic surgery especially in revision joint arthroplasty and spine fusion. The early implant fixation in the revision situation of loose joint prostheses is important for the long-term survival. Bone autograft has been considered as gold standard in many orthopaedic procedures, whereas allograft is the gold standard by replacement of extensive bone loss. However, the use of autograft is associated with donor site morbidity, especially chronic pain. In addition, the limited supply is a significant clinical challenge. Limitations in the use of allograft include the risk of bacterial contamination and disease transmission as well as non-union and poor bone quality. Other bone graft and substitutes have been considered as alternative in order to improve implant fixation. Hydroxyapatite and collagen type I composite (HA/Collagen) have the potential in mimicking skeletal bones. The osteoconductive properties of the composite might be improved by adding bone marrow aspirate (BMA), which can be harvested during surgery. Other alternatives to bone graft are demineralised bone matrix (DBM) and human cancellous bone (CB). DBM is prepared by acid extraction of human bone and includes bone collagen, morphogenetic proteins and growth factors. The combination of DBM with CB and with allograft might improve the healing potential of these grafts around non-cemented orthopaedic implants and thereby the implant fixation. Study I investigates the effect of HA/Collagen composite alone and in combination with BMA on the early fixation of porous coated titanium implants. In addition, the study compares also the effect of autograft with the gold standard allograft. By using a sheep model, the implants were inserted in the trabecular bone of femoral condyles. The test biomaterials were placed in a well defined peri-implant gap. After the observation period, the bone-implant specimens were harvested and evaluated mechanically by a destructive push
Zdeblick, T A; Cooke, M E; Kunz, D N; Wilson, D; McCabe, R P
This study analyzed the use of a coral hydroxyapatite bone substitute for use in ACDF both with and without an anterior cervical plate. The healing of multilevel anterior cervical fusions was tested using a goat model. Comparisons were drawn with histologic, radiographic, and biomechanical test data. Forty-nine mature alpine goats had three-level anterior discectomies performed. Seven treatment groups of seven goats each were used; Group I with no fusion, Group IIa having tricortical iliac crest autograft, Group IIb having autograft plus an anterior plate, Group IIIa having tricortical iliac crest fresh-frozen allograft, Group IIIb having allograft plus an anterior plate, Group IVa having rectangular-shaped implants of porous hydroxyapatite, and Group IVb having ProOsteon 500 implants with an anterior cervical plate. Histologically, at 12 weeks 48% of the ProOsteon (Interpore, Irvine, CA) implants were rated as incorporated, 10% as possessing a fibrous gap, 29% as collapsed, and 14% as extruded. Anterior cervical plating improved the results with 71% of the implants showing good incorporation, 24% with collapse, and 5% with a fibrous gap. These histologic results compare favorably with autogenous bone and are improved over allograft bone. Fluorochrome analysis showed that none of the implants had complete turnover with host bone, but that all possessed peripheral creeping substitution with cutting cones of new bone formation at 12 weeks. Biomechanically, the spines using the ProOsteon implant were less stiff in torsion than autograft, but equal in stiffness to allograft. Flexion-extension neutral zone stiffness was lower in the ProOsteon implant group than either allograft or autograft. The use of a coral-based hydroxyapatite bone graft substitute for anterior cervical fusions led to significant rates of implant collapse at 12 weeks but showed excellent biologic compatibility with good early creeping substitution of the implant by host bone. The concomitant use of
Purpose To introduce a novel technique to treat necrotic scleral calcification caused by previous regional conjunctivectomy using conjunctival autografting and amniotic membrane inlay filling, and to evaluate the clinical outcome. Methods Ten patients (11 eyes, 12 regions) who had undergone regional conjunctivectomy with postoperative mitomycin C (MMC) for pterygia or pingueculae were included. Scleral calcification was removed using a bevel-down crescent knife. After the conjunctival donor tissue was harvested from the upper bulbar conjunctiva, the tissue was grafted to the scleral defect and secured with sutures. Amniotic membrane was inserted randomly into spaces between the conjunctival graft and the scleral bed. Protective amniotic membrane was transplanted over the graft, with stromal side up. Results Scleral calcification developed in ischaemic areas in 11 of the 12 regions; 50% of cases had a surface defect seen with a fluorescent dye. The grafted conjunctiva epithelialized successfully in all cases. In 10 regions, the epithelialization occurred in 1 or 2 weeks. In the remaining two regions, one region required another surgery because of graft failure, and epithelialization occurred in the last region in 9 weeks. Vascular growth into the graft from the surrounding tissue occurred in all cases in 1 to 10 weeks. The surgical wound stabilized 3 weeks postoperatively. Conclusion The combined technique had high success rates of graft survival and good revitalization of the necrotic area of scleral calcification, eliminated the need for invasive and time-consuming scleral autografting or allografting, and provided good cosmesis. Scleral ischaemia, which was caused by MMC, may induce scleral calcification. PMID:21869832
Ballarin, Francesco; Faggiano, Elena; Manzoni, Andrea; Quarteroni, Alfio; Rozza, Gianluigi; Ippolito, Sonia; Antona, Carlo; Scrofani, Roberto
A fast computational framework is devised to the study of several configurations of patient-specific coronary artery bypass grafts. This is especially useful to perform a sensitivity analysis of the hemodynamics for different flow conditions occurring in native coronary arteries and bypass grafts, the investigation of the progression of the coronary artery disease and the choice of the most appropriate surgical procedure. A complete pipeline, from the acquisition of patient-specific medical images to fast parameterized computational simulations, is proposed. Complex surgical configurations employed in the clinical practice, such as Y-grafts and sequential grafts, are studied. A virtual surgery platform based on model reduction of unsteady Navier-Stokes equations for blood dynamics is proposed to carry out sensitivity analyses in a very rapid and reliable way. A specialized geometrical parameterization is employed to compare the effect of stenosis and anastomosis variation on the outcome of the surgery in several relevant cases.
An, Vincent Vg; Scholes, Corey; Mhaskar, Vikram A; Hadden, William; Parker, David
Anterior cruciate ligament reconstruction (ACLR) is one of the most well studied and performed procedures in the world. Thus, it would be useful to develop a tool to predict patient outcomes post-operatively to allow clinicians to optimise management. To identify and summarise factors predictive of graft failure and patient-reported outcome (PROM) measures at minimum two years after ACLR with single-bundle quadruple hamstring autograft via the anteromedial portal technique. Studies reporting IKDC, KOOS, Lysholm and graft failure in ACLR were systematically reviewed. A methodological score was applied to these studies, with those above the mean analysed further. Only those reporting primary predictors of patient outcomes following ACLR were included. Twenty-six studies satisfied our inclusion criteria. Fourteen scored above the mean 20 Downs and Black score (18.4) and were considered higher level evidence. The higher quality papers reported that younger age, female sex, higher BMI, smoking history and activity levels predicted poorer outcomes. High-grade tears of the menisci or full-thickness cartilage defects were identified as predictors of poorer PROMs. None of the factors investigated by more than a single paper were unanimously significant in predicting the outcome of ACLR. The evidence surrounding predictors of outcome was inconsistent in design, methodology and reporting of results, hindering our ability to draw conclusions regarding the validity of the reported relationships. However, this systematic review identified several patient demographics, concomitant injuries, and surgical factors that could be investigated further in future prospective studies to create a definitive predictive model. Copyright © 2016 Elsevier B.V. All rights reserved.
Lombardero, Matilde; Quintanar-Stephano, Andres; Vidal, Sergio; Horvath, Eva; Kovacs, Kalman; Lloyd, Ricardo V; Scheithauer, Bernd W
Estrogens are known to cause pituitary enlargement and lactotroph proliferation. They also modulate pituitary angiogenesis and induce tumor formation. Pituitary grafts, due to the loss of hypothalamic dopamine, also show lactotroph hyperplasia. We investigated the role of estrogen on rat pituitary autograft vascularization by light and transmission electron microscopy, and assessed prolactin (PRL) blood levels, microvessel density (MVD) and cell proliferation using the BrdU labeling index. All adenohypophysial cell types were identified by immunohistochemistry (streptavidin-biotin-peroxidase complex method). The proangiogenic factors, vascular endothelial growth factor (VEGF), its receptor Flk-1, and hypoxia inducible factor-1α (HIF-1α) were similarly demonstrated. The prevalence of lactotrophs, as well as more intense staining for VEGF, Flk-1 and HIF-1α, was noted in those grafts exposed to estrogen, mainly in the area surrounding the central necrotic core. Immunostaining showed Flk-1 expression increased in endothelial cells of the estrogen-exposed grafts as compared with those unexposed. In contrast to the grafts not exposed to estrogen, in the estrogen-exposed grafts, only fenestrated endothelium could be demonstrated, suggesting that estrogen induces fenestration of newly formed capillaries. There was an increase in blood PRL levels in the estrogen-treated groups as compared with controls. Both MVD and BrdU labeling indices were higher in grafts exposed to estrogen, especially after 4 weeks. Our results suggest that estrogen administration not only enhances the expression of proangiogenic factors in the pituitary grafts but also induces their expression at earlier stages, leading to rapid neoformation of purely fenestrated capillaries. PMID:19207985
Benazzo, Franco; Cadossi, Matteo; Cavani, Francesco; Fini, Milena; Giavaresi, Gianluca; Setti, Stefania; Cadossi, Ruggero; Giardino, Roberto
The effect of pulsed electromagnetic fields (PEMFs) on the integration of osteochondral autografts was evaluated in sheep. After osteochondral grafts were performed, the animals were treated with PEMFs for 6 h/day or sham-treated. Six animals were sacrificed at 1 month. Fourteen animals were treated for 2 months and sacrificed at 6 months. At 1 month, the osteogenic activity at the transplant-host subchondral bone interface was increased in PEMF-treated animals compared to controls. Articular cartilage was healthy in controls and stimulated animals. At 6 months, complete resorption was observed in four control grafts only. Cyst-like resorption areas were more frequent within the graft of sham-treated animals versus PEMF-treated. The average volume of the cysts was not significantly different between the two groups; nevertheless, analysis of the variance of the volumes demonstrated a significant difference. The histological score showed no significant differences between controls and stimulated animals, but the percentage of surface covered by fibrous tissue was higher in the control group than in the stimulated one. Interleukin-1 and tumor necrosis factor-alpha concentration in the synovial fluid was significantly lower, and transforming growth factor-beta1 was significantly higher, in PEMF-treated animals compared to controls. One month after osteochondral graft implantation, we observed larger bone formation in PEMF-treated grafts which favors early graft stabilization. In the long term, PEMF exposure limited the bone resorption in subchondral bone; furthermore, the cytokine profile in the synovial fluid was indicative of a more favorable articular environment for the graft.
Voso, M T; Hohaus, S; Moos, M; Pförsich, M; Cremer, F W; Schlenk, R F; Martin, S; Hegenbart, U; Goldschmidt, H; Haas, R
The efficacy of an immunomagnetic purging method and the Isolex 300 devices were assessed for selecting CD34+ cells from leukapheresis products of 29 patients with non-Hodgkin's lymphoma (NHL), 39 with multiple myeloma and 34 with breast cancer. The mean purity of the CD34+ cell population was 93.6% and the mean recovery was 67.7%. Following enzymatic cleavage by chymopapain the expression of Thy-1 and Leu-8 was significantly reduced without affecting haematological recovery. The population of selected CD34+ cells of 4/8 patients with follicular lymphoma became PCR-negative. A 2.5 log reduction of tumour cells could be achieved in four patients with multiple myeloma as shown by a quantitative PCR assay. There were no tumour cells detectable in any of the 19 CD34+ cell preparations of patients with breast cancer. In 64 patients who received 94 cycles of high-dose therapy, a mean number of 4.7x 10(6) CD34+ cells/kg were autografted. The time needed for platelet reconstitution was different when a comparison was made with 156 patients, who had received unmanipulated leukapheresis products (10 v 12 d, P = 0.006). No significant differences with regard to neutrophil recovery were noted. Five patients had a graft failure. Two of them died (on day 78 and 88 following PBSCT), and three patients were rescued with unmanipulated back-up transplants. In conclusion, the immunomagnetic selection of CD34+ cells provides autografts with reduced tumour cell content and an engraftment ability similar to that of unmanipulated autografts.
Petrochenko, Peter; Narayan, Roger J
The disadvantages involving the use of a patient's own bone as graft material have led surgeons to search for alternative materials. In this review, several characteristics of a successful bone graft material are discussed. In addition, novel synthetic materials and natural bone graft materials are being considered. Various factors can determine the success of a bone graft substitute. For example, design considerations such as porosity, pore shape, and interconnection play significant roles in determining graft performance. The effective delivery of bone morphogenetic proteins and the ability to restore vascularization also play significant roles in determining the success of a bone graft material. Among current approaches, shorter bone morphogenetic protein sequences, more efficient delivery methods, and periosteal graft supplements have shown significant promise for use in autograft substitutes or autograft extenders.
Koenrades, Maaike A.; Struijs, Ella M.; Klein, Almar; Kuipers, Henny; Geelkerken, Robert H.; Slump, Cornelis H.
The application of endovascular aortic aneurysm repair has expanded over the last decade. However, the long-term performance of stent grafts, in particular durable fixation and sealing to the aortic wall, remains the main concern of this treatment. The sealing and fixation are challenged at every heartbeat due to downward and radial pulsatile forces. Yet knowledge on cardiac-induced dynamics of implanted stent grafts is sparse, as it is not measured in routine clinical follow-up. Such knowledge is particularly relevant to perform fatigue tests, to predict failure in the individual patient and to improve stent graft designs. Using a physical dynamic stent graft model in an anthropomorphic phantom, we have evaluated the performance of our previously proposed segmentation and registration algorithm to detect periodic motion of stent grafts on ECG-gated (3D+t) CT data. Abdominal aortic motion profiles were simulated in two series of Gaussian based patterns with different amplitudes and frequencies. Experiments were performed on a 64-slice CT scanner with a helical scan protocol and retrospective gating. Motion patterns as estimated by our algorithm were compared to motion patterns obtained from optical camera recordings of the physical stent graft model in motion. Absolute errors of the patterns' amplitude were smaller than 0.28 mm. Even the motion pattern with an amplitude of 0.23 mm was measured, although the amplitude of motion was overestimated by the algorithm with 43%. We conclude that the algorithm performs well for measurement of stent graft motion in the mm and sub-mm range. This ultimately is expected to aid in patient-specific risk assessment and improving stent graft designs.
Mancini, Derrick; Deshmukh, Sanket; Sankaranarayanan, Subramanian
We develop meso-scale models to explore the self-assembly behavior of polymer-grafted nanoparticles. Specifically, we study nanoparticles with grafts of the thermo-sensitive polymer poly(N-isopropylacrylamide) (PNIPAM), which undergoes a coil-to-globule transition across the LCST at around 305 K. The atomic-scale mechanism of the coil-to-globule transition of polymers grafted nanoparticles and their interactions (agglomeration, assembly behavior) with other particles that are in its vicinity is poorly understood, yet knowledge about these interactions would enable designing novel self-assembled materials with well-defined structural and dynamical properties. Additionally, the effects of chemical nature, geometry, and morphology of the nanoparticle surface on the conformational transition of thermo-sensitive polymers is also unknown. We report on 1) development of all-atom models of polymer-grafted nanoparticles to conduct MD simulations at atomic-levels and 2) perform mesoscopic scaling of the conformational dynamics resulting from the atomistic simulations with the aid of coarse-grained or meso-scale models of PNIPAM and its composites. Coarse-grained simulations allow modeling of larger assemblies of polymer-grafted nanoparticles over longer time scales. This research used resources of the Center for Nanoscale Materials and the Argonne Leadership Computing Facility at Argonne National Laboratory, which is supported by the Office of Science of the U.S. Department of Energy under Contract DE-AC02-06CH11357.
Jiang, Wenli; Wang, Yuexiang; Tang, Jie; Peng, Jiang; Wang, Yu; Guo, Quanyi; Guo, Zhiyuan; Li, Pan; Xiao, Bo; Zhang, Jinxing
Low intensity pulsed ultrasound (LIPUS) has been widely used in clinic for the treatment of repairing pseudarthrosis, bone fractures and of healing in various soft tissues. Some reports indicated that LIPUS accelerated peripheral nerve regeneration including Schwann cells (SCs) and injured nerves. But little is known about its appropriate intensities on autograft nerves. This study was to investigate which intensity of LIPUS improved the regeneration of gold standard postsurgical nerves in experimental rat model. Sprague-Dawley rats were made into 10 mm right side sciatic nerve reversed autologous nerve transplantation and randomly treated with 250 mW/cm2, 500 mW/cm2 or 750 mW/cm2 LIPUS for 2–12 weeks after operation. Functional and pathological results showed that LIPUS of 250 mW/cm2 significantly induced faster rate of axonal regeneration. This suggested that autograft nerve regeneration was improved. PMID:27102358
Dai, Longsheng; Gao, Mingxin; Gu, Chengxiong; Zhang, Fan; Yu, Yang
Effective therapies to prevent vein graft failure after coronary artery bypass grafting (CABG) are still lacking. α-Cyanoacrylate (α-CA, 99% n-octyl-α-cyanoacrylate + n-butyl-α-cyanoacrylate) has been increasingly used as a tissue sealant for wound closure because of its bacteriostatic, biodegradable and haemostatic properties. As a strong tissue adhesive, α-CA might prevent an arterial circulation-induced mechanical stretch on vein graft to attenuate intimal hyperplasia. Here, we investigated the effects of perivenous application of α-CA on the vein graft in a rabbit model of carotid artery bypass grafting. Healthy New Zealand white rabbits were randomized into no graft, graft or graft + α-CA group (n = 10 per group). Rabbit carotid artery was bypassed with the jugular vein. α-CA sealants were sprayed on the entire jugular graft including both anastomotic sites after completion of anastomoses. Blood flow parameters and histological characteristics of the vein grafts including vessel wall thickness, number of medial elastic lamina and proliferation index were evaluated 4 weeks after the surgery. The mRNA or protein levels of proinflammatory factors, chemokine (C-C motif) ligand-2 (CCL-2) and tumour necrosis factor-α (TNF-α) were measured 4 weeks after the operation by quantitative reverse transcription polymerase chain reaction or enzyme-linked immunosorbent assay. Compared with the untreated vein grafts at Week 4 after the operation, the α-CA spray significantly improved graft flow (39.4 ± 1.5 vs 27.8 ± 2.9 ml/min, P < 0.01), attenuated intimal and medial thickening (116.3 ± 1.0 vs 159.7 ± 0.9 μm, P < 0.01), reduced anti-proliferating cell nuclear antigen proliferation index of the vein grafts (15.0 ± 0.4 vs 23.6 ± 0.4%, P < 0.01), decreased the mRNA levels of plasminogen activator inhibitor-1 and CCL-2, and reduced the serum levels of TNF-α (92.9 ± 1.7 vs 102.7 ± 1.8 pg/ml, P < 0.01). Perivenous application of α-CA sealants exerts short
Gregory, Elaine K; Vercammen, Janet M; Flynn, Megan E; Kibbe, Melina R
Although the aortic interposition bypass model has been widely used to evaluate biomaterials for bypass grafting, there is no comprehensive description of the procedure or of the distribution of intimal hyperplasia that results. The objectives of this study were to (1) review and summarize approaches of aortic interposition grafting in animal models, (2) determine the pertinent anatomy for this procedure, (3) validate this model in the rat and guinea pig, and (4) compare the distribution of intimal hyperplasia that develops in each species. A literature search was performed in PubMed from 1980 to the present to analyze the use of anesthesia, anticoagulation, antiplatelet agents, graft material, suture, and anastomotic techniques. Using 10-week-old male Sprague-Dawley rats and Hartley guinea pigs, we established pertinent aortic anatomy, developed comparable models, and assessed complications for each model. At 30 days, the graft and associated aorta were explanted, intimal formation was assessed morphometrically, and cellularity was assessed via nuclear counting. We reviewed 30 articles and summarized the pertinent procedural findings. Upon establishing both animal models, key anatomic differences between the species that affect this model were noted. Guinea pigs have a much larger cecum, increased retroperitoneal fat, and lack the iliolumbar vessels compared with the rat. Surgical outcomes for the rat model included a 53% technical success rate and a 32% technical error rate. Surgical outcomes for the guinea pig model included a 69% technical success rate and a 31% technical error rate. These two species demonstrated unique distribution of intimal hyperplasia at 30 days. Intimal hyperplasia in the rat model was greatest at two areas, the proximal graft (5400 μm(2); P < .001) and distal graft (2800 μm(2); P < .04), whereas the guinea pig model developed similar intimal hyperplasia throughout the graft (4500-5100 μm(2); P < .01). In this report, we summarize
Johnson, Robert G
Prospective randomized study. To compare autologous bone marrow concentrate mixed with allograft cancellous bone to iliac crest autograft in lumbar fusions. Bone marrow has been shown to be a rich source of osteoprogenitor cells. Osteoprogenitor cells have been shown in animals, and some human studies, to have potential in use as a bone graft substitute. Twenty-five patients underwent from 1- to 3-level lumbar fusions. One patient was lost to follow-up. On one half of the spine, allograft plus autologous bone marrow concentrate was used, whereas on the other half, autologous iliac crest bone was used. Cellular analysis, consisting of nucleated cell count, mononuclear cell count, CD34+ count, and colony-forming-units-fibroblast count, was done on marrow aspirates and concentrates. At 1 year postoperation, computed tomographic scans of the fusions were evaluated on a blinded basis by 2 neuroradiologists independent of each other. Radiographical fusion was the primary outcome measure. There was no statistical difference in fusion scores between allograft and autograft in the lateral gutters, interbody cages, or facet joints. There was a positive trend between CD34+ counts and radiographical fusion. The study shows equivalence between cancellous allograft mixed with bone marrow concentrate and autologous iliac crest bone for lumbar fusions. 2.
Lee, Jae Hyup; Ryu, Hyun-Seung; Seo, Jun-Hyuk; Lee, Do-Yoon; Chang, Bong-Soon; Lee, Choon-Ki
Bioactive glass-ceramics have the ability to directly bind to bones and have been widely used as bone graft substitutes due to their high osteoconductivity and biocompatibility. CaO-SiO2-P2O5-B2O3 glass-ceramics are known to have good osteoconductivity and are used as bone graft extenders. This study aimed to evaluate the effects of the resorbing properties of glass-ceramics in bone fusion after producing and analyzing three types of CaO-SiO2-P2O5-B2O3 glass-ceramics with high osteoconductivity that had enhanced resorption by having an increased B2O3 content. The three types of CaO-SiO2-P2O5-B2O3 glass-ceramics with B2O3 contents of 8.0, 9.0, and 9.5 weight % were designated and grouped as P20B80, P10B90, and P5B95, respectively. Glass-ceramic types were tested for fusion rates and bone formation by employing the lumbar 5-6 intertransverse process fusion model in 51 New Zealand male rabbits. Bioactivity was assessed by soaking in simulated body fluid (SBF). In vitro study results showed sufficient hydroxycarbonate apatite layer formation occurred for P20B80 in1 day, for P10B90 in 3 days, and for P5B95 in 5 days after soaking in SBF. For the rabbit lumbar spine posterolateral fusion model, the autograft group recorded a 100% fusion rate with levels significantly higher than those of P20B80 (29.4%), P10B90 (0%), and P5B95 (14.3%), with high resorbing properties. Resorbing property differences among the three glass-ceramic groups were not significant. Histological results showed new bone formation confirming osteoconductivity in all three types of glass-ceramics. Radiomorphometric results also confirmed the resorbing properties of the three glass-ceramic types. The high resorbing properties and osteoconductivity of porous glass-ceramics can be advantageous as no glass-ceramics remain in the body. However, their relatively fast rate of resorption in the body negatively affects their role as an osteoconductive scaffold as glass-ceramics are resorbed before bony fusion.
Lee, Jae Hyup; Ryu, Hyun-Seung; Seo, Jun-Hyuk; Lee, Do-Yoon; Chang, Bong-Soon
Background Bioactive glass-ceramics have the ability to directly bind to bones and have been widely used as bone graft substitutes due to their high osteoconductivity and biocompatibility. CaO-SiO2-P2O5-B2O3 glass-ceramics are known to have good osteoconductivity and are used as bone graft extenders. Methods This study aimed to evaluate the effects of the resorbing properties of glass-ceramics in bone fusion after producing and analyzing three types of CaO-SiO2-P2O5-B2O3 glass-ceramics with high osteoconductivity that had enhanced resorption by having an increased B2O3 content. The three types of CaO-SiO2-P2O5-B2O3 glass-ceramics with B2O3 contents of 8.0, 9.0, and 9.5 weight % were designated and grouped as P20B80, P10B90, and P5B95, respectively. Glass-ceramic types were tested for fusion rates and bone formation by employing the lumbar 5-6 intertransverse process fusion model in 51 New Zealand male rabbits. Bioactivity was assessed by soaking in simulated body fluid (SBF). Results In vitro study results showed sufficient hydroxycarbonate apatite layer formation occurred for P20B80 in1 day, for P10B90 in 3 days, and for P5B95 in 5 days after soaking in SBF. For the rabbit lumbar spine posterolateral fusion model, the autograft group recorded a 100% fusion rate with levels significantly higher than those of P20B80 (29.4%), P10B90 (0%), and P5B95 (14.3%), with high resorbing properties. Resorbing property differences among the three glass-ceramic groups were not significant. Histological results showed new bone formation confirming osteoconductivity in all three types of glass-ceramics. Radiomorphometric results also confirmed the resorbing properties of the three glass-ceramic types. Conclusions The high resorbing properties and osteoconductivity of porous glass-ceramics can be advantageous as no glass-ceramics remain in the body. However, their relatively fast rate of resorption in the body negatively affects their role as an osteoconductive scaffold as glass
Bernad, Sandor I.; Totorean, Alin F.; Vekas, Ladislau
Bypass graft failures is a complex process starting with intimal hyperplasia development which involve many hemodynamic and biological factors. This work presents experimental results regarding the possibility to use magnetic drug delivery to prevent the development of the intimal hyperplasia using a simplified but intuitive model. The primary goal is to understand the magnetic particle deposition in the anastomosis region of the bypass graft taking into account the complex flow field created in this area which involves recirculation region, flow mixing and presence of particles with high residence time. The three-dimensional geometry model was used to simulate the motion and accumulation of the particles under the magnetic field influence in anastomotic region of the coronary bypass graft. The flow patterns are evaluated both numerically and experimentally and show a good correlation in term of flow parameters like vortex length and flow stagnation point positions. Particle depositions are strongly dependent on the magnet position and consequently of the magnetic field intensity and field gradient. Increased magnetic field controlled by the magnet position induces increased particle depositions in the bypass graft anastomosis. The result shows that particle depositions depend on the bypass graft angle, and the deposition shape and particle accumulation respectively, depend by the flow pattern in the anastomosis region.
Klein, Justin D; Turner, Christopher G B; Ahmed, Azra; Steigman, Shaun A; Zurakowski, David; Fauza, Dario O
We sought to compare the efficacy of engineered fetal bone grafts with acellular constructs in an autologous model of chest wall repair. Rabbits (n = 10) with a full-thickness sternal defect were equally divided in 2 groups based on how the defect was repaired, namely, either with an autologous bone construct engineered with amniotic mesenchymal stem cells on a nanofibrous scaffold or a size-matched identical scaffold with no cells. Animals were killed at comparable time-points 18 to 20 weeks postimplantation for multiple analyses. Gross evidence of nonunion confirmed by micro-computed tomography scanning was present in 3 (60%) of 5 of the acellular implants but in no engineered grafts. Histology confirmed the presence of bone in both types of repair, albeit seemingly less robust in the acellular grafts. Mineral density in vivo was significantly higher in engineered grafts than in acellular ones, with more variability among the latter. There was no difference in alkaline phosphatase activity between the groups. Chest wall repair with an autologous osseous graft engineered with amniotic mesenchymal stem cells leads to improved and more consistent outcomes in the midterm when compared with an equivalent acellular prosthetic repair in a leporine model. Amniotic fluid-derived engineered bone may become a practical alternative for perinatal chest wall reconstruction. Copyright 2010 Elsevier Inc. All rights reserved.
Millet, Eran; Haik, Josef; Ofir, Elad; Mardor, Yael; Winkler, Eyal; Harats, Moti; Tessone, Ariel
Although fat grafting is a common technique to repair defects after breast cancer reconstruction surgery and has a low complication rate, the relation between fat grafting and the risk of breast cancer is unknown. Clinical trials to investigate this connection can elucidate the benefits and potential risks of fat grafting in oncology patients. To establish an efficient experimental model, using magnetic resonance imaging (MRI) scans, for comparing different breast tumor study groups post-fat grafting. Breast tumor cells were injected into immunocompromised mice. After tumors formed they were removed. Liposuction was performed in a female human donor and fat was collected. Cells were extracted from the fat by enzymatic digestion. Immunocompromised mice were randomized into four groups: a preliminary experiment group and three equal groups according to the type of fat graft: (i) fresh fat enriched with adipose-derived mesenchymal stem cells (AdMSCs), (ii) fresh fat without cell enrichment, and (iii) no fat injected. Tumor volume was assessed by serial MRI scans. The rate of tumor growth was higher in the enriched fat group compared to the non-enriched fat group. This experimental model is an effective measurable method, allowing future investigation of the effect of autologous fat on breast cancer.
Sankaran, Sethuraman; Esmaily Moghadam, Mahdi; Kahn, Andrew M; Tseng, Elaine E; Guccione, Julius M; Marsden, Alison L
We present a computational framework for multiscale modeling and simulation of blood flow in coronary artery bypass graft (CABG) patients. Using this framework, only CT and non-invasive clinical measurements are required without the need to assume pressure and/or flow waveforms in the coronaries and we can capture global circulatory dynamics. We demonstrate this methodology in a case study of a patient with multiple CABGs. A patient-specific model of the blood vessels is constructed from CT image data to include the aorta, aortic branch vessels (brachiocephalic artery and carotids), the coronary arteries and multiple bypass grafts. The rest of the circulatory system is modeled using a lumped parameter network (LPN) 0 dimensional (0D) system comprised of resistances, capacitors (compliance), inductors (inertance), elastance and diodes (valves) that are tuned to match patient-specific clinical data. A finite element solver is used to compute blood flow and pressure in the 3D (3 dimensional) model, and this solver is implicitly coupled to the 0D LPN code at all inlets and outlets. By systematically parameterizing the graft geometry, we evaluate the influence of graft shape on the local hemodynamics, and global circulatory dynamics. Virtual manipulation of graft geometry is automated using Bezier splines and control points along the pathlines. Using this framework, we quantify wall shear stress, wall shear stress gradients and oscillatory shear index for different surgical geometries. We also compare pressures, flow rates and ventricular pressure-volume loops pre- and post-bypass graft surgery. We observe that PV loops do not change significantly after CABG but that both coronary perfusion and local hemodynamic parameters near the anastomosis region change substantially. Implications for future patient-specific optimization of CABG are discussed.
Weinfeld, Adam Bryce
In rhinoplasty, cartilage is often harvested from the nasal septum and meticulously carved into delicate grafts designed to reshape and strengthen the nasal osteocartilaginous framework. Proficiency at this task develops with experience in the clinical setting. The author offers a simulated educational model designed to provide rhinoplasty surgeons with increased preclinical experience in cartilage graft carving. This model relies on inexpensive, food-grade chickens, which may be purchased at any grocery store. Four whole chickens were dissected to expose and harvest the sternal (breast/keel) cartilage. A technique was developed for preparing the cartilage to approximate the shape and dimensions of human septal cartilage. Measurements were made to demonstrate similarities between the model material and the human septum. The average weight of the chickens was 4.27 lb. The average cartilage height, length, and thickness were 2.36 cm, 6.13 cm, and 3.4 mm, respectively. This size compared favorably with typical septal harvest pieces, which had both heights and lengths of 2.5 cm and thicknesses of 3.25 mm. The author found that one sternal cartilage piece could be employed to carve two spreader grafts, a columellar strut graft, a tip graft, and two alar rim cartilage grafts. The performance of the avian cartilage was subjectively very similar to that of septal cartilage. Furthermore, two pieces of the sternal cartilage could be glued together and fastened within a model of a human skull to replicate the cartilaginous septum in situ. This construct was employed for demonstrations of actual septal cartilage harvest. Carving septal cartilage into grafts is a difficult process. Precision and improved results increase with clinical experience on human patients, but this cadaveric avian (chicken) model provides an opportunity for simulated surgical training on a very similar tissue type at a very low cost. This model has the potential to improve human outcomes by providing
Jones, June E; Nelson, E Andrea; Al-Hity, Aws
Venous leg ulceration is a recurrent, chronic, disabling condition. It affects up to one in 100 people at some time in their lives. Standard treatments are simple dressings and compression bandages or stockings. Sometimes, despite treatment, ulcers remain open for months or years. Sometimes skin grafts are used to stimulate healing. These may be taken, or grown into a dressing, from the patient's own uninjured skin (autografts), or applied as a sheet of bioengineered skin grown from donor cells (allograft). Preserved skin from other animals, such as pigs, has also been used (xenografts). To assess the effect of skin grafts for treating venous leg ulcers. For this update we modified the search strategies and conducted searches of The Cochrane Wounds Group Specialised Register (searched 27 July 2012); The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 7); Ovid MEDLINE (2008 to July Week 3 2012); Ovid MEDLINE (In-Process & Other Non-Indexed Citations, July 26, 2012); Ovid EMBASE (2008 to 2012 Week 29); and EBSCO CINAHL (2008 to 26 July 2012). We did not apply date or language restrictions. Randomised controlled trials (RCTs) of skin grafts in the treatment of venous leg ulcers. Two review authors independently undertook data extraction and assessment of study quality. For this update of the review, we identified one new trial, bringing the total to 17 trials (1034 participants) - all of which were generally at moderate or high risk of bias. In 12 trials participants also received compression bandaging.Eleven trials compared a graft with standard care in which no graft was used. Two of these trials (102 participants) compared a dressing with an autograft; three trials (80 participants) compared frozen allografts with dressings, and two trials (45 participants) compared fresh allografts with dressings. Two trials (345 participants) compared tissue-engineered skin (bilayer artificial skin) with a dressing. In two trials (97
Chen, Guanyin; Zhang, Hongtao; Ma, Qiong; Zhao, Jian; Zhang, Yinglong; Fan, Qingyu; Ma, Baoan
Different clinical results have been reported in the repair of extensor mechanism disruption using fresh-frozen complete extensor mechanism (CEM) allograft, creating a need for a better understanding of fresh-frozen CME allograft reconstruction. Here, we perform histological and biomechanical analyses of fresh-frozen CEM allograft or autograft reconstruction in an in vivo rabbit model. Our histological results show complete incorporation of the quadriceps tendon into the host tissues, patellar survival and total integration of the allograft tibia, with relatively fewer osteocytes, into the host tibia. Vascularity and cellularity are reduced and delayed in the allograft but exhibit similar distributions to those in the autograft. The infrapatellar fat pad provides the main blood supply, and the lowest cellularity is observed in the patellar tendon close to the tibia in both the allograft and autograft. The biomechanical properties of the junction of quadriceps tendon and host tissues and those of the allograft patellar tendon are completely and considerably restored, respectively. Therefore, fresh-frozen CEM allograft reconstruction is viable, but the distal patellar tendon and the tibial block may be the weak links of the reconstruction. These findings provide new insight into the use of allograft in repairing disruption of the extensor mechanism. PMID:26911538
Chen, Da-Fu; Zhou, Zhi-Yu; Dai, Xue-Jun; Gao, Man-Man; Huang, Bao-Ding; Liang, Tang-Zhao; Shi, Rui; Zou, Li-Jin; Li, Hai-Sheng; Bünger, Cody; Tian, Wei; Zou, Xue-Nong
The precise mechanism of bone regeneration in different bone graft substitutes has been well studied in recent researches. However, miRNAs regulation of the bone formation has been always mysterious. We developed the anterior lumbar interbody fusion (ALIF) model in pigs using equine bone protein extract (BPE), recombinant human bone morphogenetic protein-2 (rhBMP-2) on an absorbable collagen sponge (ACS), and autograft as bone graft substitute, respectively. The miRNA and gene expression profiles of different bone graft materials were examined using microarray technology and data analysis, including self-organizing maps, KEGG pathway and Biological process GO analyses. We then jointly analyzed miRNA and mRNA profiles of the bone fusion tissue at different time points respectively. Results showed that miRNAs, including let-7, miR-129, miR-21, miR-133, miR-140, miR-146, miR-184, and miR-224, were involved in the regulation of the immune and inflammation response, which provided suitable inflammatory microenvironment for bone formation. At late stage, several miRNAs directly regulate SMAD4, Estrogen receptor 1 and 5-hydroxytryptamine (serotonin) receptor 2C for bone formation. It can be concluded that miRNAs play important roles in balancing the inflammation and bone formation.
extracellular matrix arterial interposition grafts in a sheep (Ovis aries) model." 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER...carotid arteries in sheep . Methods: Three crossbred sheep were anesthetized, instrumented, and had 10 cm interposition grafts placed in both carotid...was present by four weeks. Conclusion: In this pilot study, the Cormatrix extracellular matrix performed well in a sheep carotid interposition graft
Background Novel bone substitutes have challenged the notion of autologous bone grafting as the ‘gold standard’ for the surgical treatment of fracture nonunions. The present study was designed to test the hypothesis that autologous bone grafting is equivalent to other bone grafting modalities in the management of fracture nonunions of the long bones. Methods A retrospective review of patients with fracture nonunions included in two prospective databases was performed at two US level 1 trauma centers from January 1, 1998 (center 1) or January 1, 2004 (center 2), respectively, until December 31, 2010 (n = 574). Of these, 182 patients required adjunctive bone grafting and were stratified into the following cohorts: autograft (n = 105), allograft (n = 38), allograft and autograft combined (n = 16), and recombinant human bone morphogenetic protein-2 (rhBMP-2) with or without adjunctive bone grafting (n = 23). The primary outcome parameter was time to union. Secondary outcome parameters consisted of complication rates and the rate of revision procedures and revision bone grafting. Results The autograft cohort had a statistically significant shorter time to union (198 ± 172–225 days) compared to allograft (416 ± 290–543 days) and exhibited a trend towards earlier union when compared to allograft/autograft combined (389 ± 159–619 days) or rhBMP-2 (217 ± 158–277 days). Furthermore, the autograft cohort had the lowest rate of surgical revisions (17%) and revision bone grafting (9%), compared to allograft (47% and 32%), allograft/autograft combined (25% and 31%), or rhBMP-2 (27% and 17%). The overall new-onset postoperative infection rate was significantly lower in the autograft group (12.4%), compared to the allograft cohort (26.3%) (P < 0.05). Conclusion Autologous bone grafting appears to represent the bone grafting modality of choice with regard to safety and efficiency in the surgical management of long bone fracture nonunions. PMID:24016227
Gonzalez-Pinto, I M; Tryphonopoulos, P; Avison, D L; Nishida, S; Tekin, A; Santiago, S; Tzakis, A G
Uterine transplantation in the sheep model has been described as a partial or whole orthotopic graft from a living donor with vascular anastomoses. As an alternative to surrogate pregnancy or adoption uterus transplantation might be indicated for cases of infertility of uterine origin. The main complications might be rejection and thrombosis. The objective of this work was to develop a model of whole uterus transplantation that was applicable to the human setting, using grafts obtained from brain-dead donors, and suitable for immunologic and viability follow-up with a reduced risk of thrombosis. Two donors and 1 recipient were operated. The first graft was used for an anatomic study; the second was used for transplantation. The donor operation consisted of an en bloc harvest of the uterus, adnexa, and proximal vagina with the distal aorta and cava. After harvest the donor sheep was humanely killed. In the recipient ewe, heterotopic implantation was performed in the lower abdomen. An End-to-side anastomoses of aorta and cava were performed below the recipient's renal vessels. A cutaneous vaginal stoma was performed in the right lower quadrant. The recipient ewe was humanely killed for an autopsy study. The anatomy of uterine veins of the ewe differs from the human. The uterine and ovarian veins join, forming the utero-ovarian vein, which drains at the confluence of the common iliac to the cava. En bloc harvesting allows for rapid graft preparation, with vascular cuffs easily anastomosed with a low risk of thrombosis. The vaginal stoma seems appropriate to facilitate follow-up and graft biopsy. This approach can be a suitable experimental model applicable to humans using grafts from brain-dead donors.
Ye, Yuan; Liao, Yunjun; Lu, Feng; Gao, Jianhua
Fat grafting has variable and sometimes poor outcomes, and therefore new methods are needed. Multiple studies have demonstrated the excellent performance of external volume expansion and focused only on preexpansion with emphasis on the recipient. Two mouse models (a suction model and a fat-exchange transplantation model) were established to investigate changes in the origins and biological behaviors of regeneration-related cells in grafted fat under daily suction provided by external volume expansion. Blood supply increased from new host-derived capillaries or macrophage infiltration under suction. CD34-positive cells showed increased migration from the host into the grafts under suction. At week 12, nearly half of the mature adipocytes regenerated in the grafts in the suction group were derived from the host. Peroxisome proliferator-activated receptor γ expression of the suction group was significantly higher than that of controls at weeks 2 and 4 during adipogenesis. The normalized sample weight of the grafted fat was significantly greater than that of controls at 1 (0.081 ± 0.001 versus 0.072 ± 0.005; p < 0.001), 4 (0.060 ± 0.002 versus 0.048 ± 0.001; p = 0.002), 8 (0.060 ± 0.001 versus 0.046 ± 0.001; p < 0.001), and 12 weeks (0.060 ± 0.001 versus 0.046 ± 0.001; p = 0.002). The mechanical effect of daily suction provided by external volume expansion favors the regeneration of grafted fat and improves retention by promoting the migration of regeneration-related cells and the differentiation of adipocytes. Thus, more mature fat tissue with a well-organized structure was formed under suction.
Hattiangady, Bharathi; Shetty, Ashok K.
Neural stem cell (NSC) transplantation into the hippocampus could offer an alternative therapy to hippocampal resection in patients with drug-resistant chronic epilepsy, which afflicts ~30% of mesial temporal lobe epilepsy (TLE) cases. Multipotent, self-renewing NSCs could be expanded from multiple regions of the developing and adult brain, human embryonic stem cells (hESCs), induced pluripotent stem cells (iPSCs). However, to provide a comprehensive methodology involved in testing the efficacy of transplantation of NSCs in a rat model of chronic TLE, NSCs derived from the embryonic medial ganglionic eminence (MGE) are taken as an example in this article. The topics comprise description of the required materials, reagents and equipment, and protocols for expanding MGE-NSCs in culture, generating chronically epileptic rats, the intrahippocampal grafting, the post-grafting evaluation of the effects of NSC grafts on spontaneous recurrent seizures and cognitive impairments, analyses of the yield and the fate of graft-derived cells, and the effects of NSC grafts on the host hippocampus. PMID:21913169
Eskew, T D; Ollerenshaw, J D; Philpott, J M; Dennis, K; Dawson, P; Sun, Y S; Chitwood, W R; Lust, R M
Intimal hyperplasia (IH) limits the long-term success of veins as arterial grafts. IH occurs in veins partly as an adaptive process to arterial pressure conditions. The authors have previously reported early success with cryopreserved (CP) saphenous veins as aortocoronary bypass grafts, and they have hypothesized that CP arterial segments were already structurally adapted for arterial conditions. Six femoral arterial segments were harvested from three adult donor dogs, and cryopreserved. The segments were thawed and implanted into six recipient dogs, in end-to-end fashion, as interpositional grafts in the femoral artery. A similar length of native femoral artery was removed from the implant site and grafted in the contralateral femoral artery of the same animal to serve as native autograft-matched controls. Grafts were harvested bilaterally after 2 (n = 3) and 4 weeks (n = 3), perfusion fixed (80 mmHg, 15 min), and analyzed histologically. All grafts were patent at harvest, and flows distal to the grafted segments were not significantly different between grafts within an animal either at implant or subsequent harvest. Although CP arterial grafts still showed slight but significant dilation compared with native autograft, the dilation was much less than seen previously with either CP or native venous segments. No evidence of inflammation or IH was seen in CP arterial grafts. The absence of early IH or inflammation suggests that CP small diameter arteries may perform better than many currently available allograft tissues and synthetic prosthetics.
Cvetanovich, Gregory L; Mascarenhas, Randy; Saccomanno, Maristella F; Verma, Nikhil N; Cole, Brian J; Bush-Joseph, Charles A; Bach, Bernard R
To compare outcomes of anterior cruciate ligament (ACL) reconstruction with hamstring autograft versus soft-tissue allograft by systematic review and meta-analysis. A systematic review of randomized controlled studies comparing hamstring autograft with soft-tissue allograft in ACL reconstruction was performed. Studies were identified by strict inclusion and exclusion criteria. Descriptive statistics were reported. Where possible, the data were pooled and a meta-analysis was performed using RevMan software (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark). Dichotomous data were reported as risk ratios, whereas continuous data were reported as standardized mean differences and 95% confidence intervals. Heterogeneity was assessed by use of I(2) for each meta-analysis. Study methodologic quality was analyzed with the Modified Coleman Methodology Score and Jadad scale. Five studies with 504 combined patients (251 autograft and 253 allograft; 374 male and 130 female patients) with a mean age of 29.9 ± 2.2 years were included. The allografts used were fresh-frozen hamstring, irradiated hamstring, mixture of fresh-frozen and cryopreserved hamstring, fresh-frozen tibialis anterior, and fresh-frozen Achilles tendon grafts without bone blocks. The mean follow-up period was 47.4 ± 26.9 months, with a mean follow-up rate of 83.3% ± 8.6%. Two studies found a longer operative time with autograft than with allograft (77.1 ± 2.0 minutes v 59.9 ± 0.9 minutes, P = .008). Meta-analysis showed no statistically significant differences between autografts and allografts for any outcome measures (P > .05 for all tests). One study found significantly greater laxity for irradiated allograft than for autograft. The methodologic quality of the 5 studies was poor, with a mean Modified Coleman Methodology Score of 54.4 ± 6.9 and mean Jadad score of 1.6 ± 1.5. On the basis of this systematic review and meta-analysis of 5 randomized controlled trials, there is
Kienapfel, H; Sumner, D R; Turner, T M; Urban, R M; Galante, J O
Autogenous cancellous bone and freeze-dried allogeneic cancellous bone were tested in a total of 41 adult male mongrel dogs. In each humerus, an implant with a commercially pure titanium fiber metal porous coating was placed in an overreamed cavity so that a uniform 3-mm gap was present between the implant and host cancellous bone. Graft material was placed in the gap of one humerus while the gap of the other humerus was left empty and served as a paired negative control. Histologically, both autograft and allograft appeared to aid repair of the defect, but quantitatively only autograft enhanced new bone formation within the defect. Treatment with autograft significantly increased the amount of bone ingrowth within the implants by nearly three-fold at 4 weeks and eight-fold at 8 weeks. The enhancing effect was recognizable as early as 2 weeks. The strength of fixation was increased by nearly seven-fold at 4 weeks and two-fold at 8 weeks in the autograft group, but this was only statistically significant at 4 weeks. Treatment with allograft did not enhance bone ingrowth at any time period, but had a small positive effect on strength of fixation at 4 weeks.
Herscovici, D; Scaduto, J M
The use of autograft bone is the best option when undertaking a procedure that requires bone graft because it is osteogenic, osteoconductive and osseo-inductive. Pain, morbidity and complications associated with harvesting iliac or non-iliac sites occur in between 6% and 30% of cases. An alternative source of graft with possibly a lower morbidity is the intramedullary canal. In this study, 28 patients undergoing 30 arthrodesis procedures on the hindfoot had a mean of 48 cm(3) (43 to 50) of bone harvested locally from the hindfoot or the tibial shaft by antegrade or retrograde reaming. No patient sustained a fracture of the calcaneum, talus or tibia. There was no morbidity except for one complication when the reamer breached the medial tibial cortex. This healed uneventfully. This method of using the reamer-irrigator-aspirator system is an extension of the standard technique of intramedullary reaming of the lower limb: it produces good-quality bone graft with viable growth factors consistent with that of the iliac crest, and donor site morbidity is low. This is an efficient method of obtaining autologous bone for use in arthrodesis of the ankle or hindfoot.
Nappi, Francesco; Nenna, Antonio; Spadaccio, Cristiano; Chello, Massimo
The Ross operation provides several advantages compared to other valve substitutes to manage aortic valve disease, such as growth potential, excellent hemodynamics, freedom from oral anticoagulation and hemolysis, and better durability. However, progressive dilatation of the pulmonary autografts after Ross operation reflects the inadequate remodeling of the native pulmonary root in the systemic circulation, which results in impaired adaptability to systemic pressure and risk of reoperation after the first decade. A recently published article showed that remodeling increased wall thickness and decreased stiffness in the failed specimens after Ross operation, and the increased compliance might play a key role in determining the progressive long-term autograft root dilatation. Late dilatation can be counteracted by an external barrier which prevents failure. Therefore, an inclusion cylinder technique with a native aorta or a synthetic external support, such as Dacron, might stabilize the autograft root and improve long-term outcomes. In this article, we offer a prospective about the importance of biomechanical features in future developments of the Ross operation. Pre-clinical and clinical evaluations of the biomechanical properties of these reinforced pulmonary autografts might shed new light on the current debate about the long-term fate of the pulmonary autograft after Ross procedure.
Chapple, P; Prince, H M; Quinn, M; Bertoncello, I; Juneja, S; Wolf, M; Januszewicz, H; Brettell, M; Gardyn, J; Seymour, C; Venter, D
A reliable measure to predict peripheral blood progenitor cell (PBPC) autograft CD34+ cell content is required to optimize the timing of PBPC collection. We prospectively examined the peripheral blood (PB) CD34+ cell count in 59 consecutive patients with various malignancies and analyzed the correlation between the PB CD34+ cell count and various parameters in the PBPC autograft. Two hundred and thirty-five collections were performed with a median of 4.0 collections per patient (range, 2-10). The median PB CD34+ cell count at the time of collection was 39 x 10(6)/1 (range, 0.0-285.6). The PBPC autograft parameters measured were the CD34+ cell, colony-forming unit granulocyte-macrophage (CFU-GM) and mononuclear cell (MNC) content. There was a strong linear correlation between PB CD34+ cells/l and autograft CD34+ cells/kg (r = 0.8477). The correlation with CFU-GM/kg (r = 0.5512) was weaker. There was no correlation between autograft CD34+ cells/kg and PB WBC (r= 0.0684), PB MNC (r = 0.1518) or PB platelet count (r = 0.2010). At our institution we aim to obtain a minimum of 0.5 x 10(6) CD34+ cells/kg with each day of collection. We demonstrate that such a collection can be reliably obtained if the PB CD34+ cell count exceeds 5.0 x 10(6)/l.
Nenna, Antonio; Spadaccio, Cristiano; Chello, Massimo
The Ross operation provides several advantages compared to other valve substitutes to manage aortic valve disease, such as growth potential, excellent hemodynamics, freedom from oral anticoagulation and hemolysis, and better durability. However, progressive dilatation of the pulmonary autografts after Ross operation reflects the inadequate remodeling of the native pulmonary root in the systemic circulation, which results in impaired adaptability to systemic pressure and risk of reoperation after the first decade. A recently published article showed that remodeling increased wall thickness and decreased stiffness in the failed specimens after Ross operation, and the increased compliance might play a key role in determining the progressive long-term autograft root dilatation. Late dilatation can be counteracted by an external barrier which prevents failure. Therefore, an inclusion cylinder technique with a native aorta or a synthetic external support, such as Dacron, might stabilize the autograft root and improve long-term outcomes. In this article, we offer a prospective about the importance of biomechanical features in future developments of the Ross operation. Pre-clinical and clinical evaluations of the biomechanical properties of these reinforced pulmonary autografts might shed new light on the current debate about the long-term fate of the pulmonary autograft after Ross procedure. PMID:28164025
Iriuchishima, Takanori; Ryu, Keinosuke; Okano, Tatsumasa; Suruga, Makoto; Aizawa, Shin; Fu, Freddie H
The purpose of this study was to reveal the degree of muscle recovery and report the clinical results of anatomical single-bundle ACL reconstruction using a quadriceps autograft. Twenty subjects undergoing anatomical single-bundle ACL reconstruction using a quadriceps autograft were included in this study. A 5-mm-wide, 8-cm-long graft, involving the entire layer of the quadriceps tendon, was harvested without bone block. The average graft diameter was 8.1 ± 1.4 mm. An initial tension of 30 N was applied. The femoral tunnel was created from the far-medial portal. Each femoral and tibial tunnel was created close to the antero-medial bundle insertion site. For the evaluation of muscle recovery (quadriceps and hamstring), a handheld dynamometer was used. The evaluation of muscle recovery was performed pre-operatively, and at 3, 6, 9, and 12 months after surgery. Muscle recovery data were calculated as a percentage of leg strength in the non-operated leg. Anterior tibial translation (ATT), pivot shift test, and IKDC score were evaluated. The average quadriceps strength pre-operatively, and at 3, 6, 9, and 12 months after ACL reconstruction was 90.5 ± 19, 67.8 ± 21.4, 84 ± 17.5, and 85.1 ± 12.6 %, respectively. The average hamstring strength pre-operatively, and at 3, 6, 9, and 12 months after ACL reconstruction was 99.5 ± 13.7, 78.7 ± 11.4, 90.5 ± 19, and 96.7 ± 13.8 %, respectively. ATT pre-operatively and at 12 months after surgery was 5.4 ± 1.3 and 1.0 ± 0.8 mm, respectively. No subjects exhibited positive pivot shift after surgery. Within 6 months following surgery, quadriceps hypotrophy was observed in all subjects. However, the hypotrophy had recovered at 12 months following surgery. No subjects complained of donor site pain after surgery. Anatomical single-bundle ACL reconstruction using a quadriceps autograft resulted in equivalent level of muscle recovery and knee stability when compared with previously reported ACL
Background One major concern in the treatment of ACL lesions in children and adolescents with open physes is the risk of iatrogenic damage to the physes and a possibly resulting growth disturbance. Purpose The primary purpose of this article is to describe our technique of a transphyseal ACL reconstruction using quadriceps tendon-bone autograft in children and adolescents with open growth plates. The secondary aim is to report our early results in terms of postoperative growth disturbances which are considered to be a major concern in this challenging group of patients. It was our hypothesis that with our proposed technique no significant growth disturbances would occur. Methods From January 1997 to December 2007 49 consecutive children and adolescents with open growth plates were treated for a torn ACL using the aforementioned surgical technique. The patients (28 males and 21 females) with a median age at surgery of 13 (range 8-15) years were retrospectively evaluated. Outcome measures were follow-up radiographs (weight-bearing long leg radiographs of the injured and uninjured knee, anteroposterior and lateral views, a tangential view of the patella and a tunnel view of the injured knee) and follow-up notes (6 weeks, 3, 6, 12 months and until closing of physes) for occurrence of any tibial and/or femoral growth changes. Results: All of the 49 patients had a sufficient clinical and radiological follow-up (minimum 5 years, rate 100%). 48 cases did not show any clinical and radiological growth disturbance. One case of growth disturbance in a 10.5 years old girl was observed. She developed a progressive valgus-flexion deformity which was attributed to a malplacement of the autograft bone block within the femoral posterolateral epiphyseal plate leading to an early localized growth stop. None of the patients were reoperated due to ACL graft failure. Five of the patients underwent revision ACL surgery due to another adequate sports trauma after the growth-stop. The
Boronat-García, Alejandra; Palomero-Rivero, Marcela; Guerra-Crespo, Magdalena; Millán-Aldaco, Diana; Drucker-Colín, René
Cell replacement therapy in Parkinson's disease (PD) aims at re-establishing dopamine neurotransmission in the striatum by grafting dopamine-releasing cells. Chromaffin cell (CC) grafts produce some transitory improvements of functional motor deficits in PD animal models, and have the advantage of allowing autologous transplantation. However, CC grafts have exhibited low survival, poor functional effects and dopamine release compared to other cell types. Recently, chromaffin progenitor-like cells were isolated from bovine and human adult adrenal medulla. Under low-attachment conditions, these cells aggregate and grow as spheres, named chromospheres. Here, we found that bovine-derived chromosphere-cell cultures exhibit a greater fraction of cells with a dopaminergic phenotype and higher dopamine release than CC. Chromospheres grafted in a rat model of PD survived in 57% of the total grafted animals. Behavioral tests showed that surviving chromosphere cells induce a reduction in motor alterations for at least 3 months after grafting. Finally, we found that compared with CC, chromosphere grafts survive more and produce more robust and consistent motor improvements. However, further experiments would be necessary to determine whether the functional benefits induced by chromosphere grafts can be improved, and also to elucidate the mechanisms underlying the functional effects of the grafts.
Boronat-García, Alejandra; Palomero-Rivero, Marcela; Guerra-Crespo, Magdalena; Millán-Aldaco, Diana; Drucker-Colín, René
Cell replacement therapy in Parkinson’s disease (PD) aims at re-establishing dopamine neurotransmission in the striatum by grafting dopamine-releasing cells. Chromaffin cell (CC) grafts produce some transitory improvements of functional motor deficits in PD animal models, and have the advantage of allowing autologous transplantation. However, CC grafts have exhibited low survival, poor functional effects and dopamine release compared to other cell types. Recently, chromaffin progenitor-like cells were isolated from bovine and human adult adrenal medulla. Under low-attachment conditions, these cells aggregate and grow as spheres, named chromospheres. Here, we found that bovine-derived chromosphere-cell cultures exhibit a greater fraction of cells with a dopaminergic phenotype and higher dopamine release than CC. Chromospheres grafted in a rat model of PD survived in 57% of the total grafted animals. Behavioral tests showed that surviving chromosphere cells induce a reduction in motor alterations for at least 3 months after grafting. Finally, we found that compared with CC, chromosphere grafts survive more and produce more robust and consistent motor improvements. However, further experiments would be necessary to determine whether the functional benefits induced by chromosphere grafts can be improved, and also to elucidate the mechanisms underlying the functional effects of the grafts. PMID:27525967
Molnar, Amber O.; van Walraven, Carl; Fergusson, Dean; Garg, Amit X.; Knoll, Greg
Background: Acute kidney injury (AKI) is common in the kidney transplant population. Objective: To derive a multivariable survival model that predicts time to graft loss following AKI. Design: Retrospective cohort study using health care administrative and laboratory databases. Setting: Southwestern Ontario (1999-2013) and Ottawa, Ontario, Canada (1996-2013). Patients: We included first-time kidney only transplant recipients who had a hospitalization with AKI 6 months or greater following transplant. Measurements: AKI was defined using the Acute Kidney Injury Network criteria (stage 1 or greater). The first episode of AKI was included in the analysis. Graft loss was defined by return to dialysis or repeat kidney transplant. Methods: We performed a competing risk survival regression analysis using the Fine and Gray method and modified the model into a simple point system. Graft loss with death as a competing event was the primary outcome of interest. Results: A total of 315 kidney transplant recipients who had a hospitalization with AKI 6 months or greater following transplant were included. The median (interquartile range) follow-up time was 6.7 (3.3-10.3) years. Graft loss occurred in 27.6% of the cohort. The final model included 6 variables associated with an increased risk of graft loss: younger age, increased severity of AKI, failure to recover from AKI, lower baseline estimated glomerular filtration rate, increased time from kidney transplant to AKI admission, and receipt of a kidney from a deceased donor. The risk score had a concordance probability of 0.75 (95% confidence interval [CI], 0.69-0.82). The predicted 5-year risk of graft loss fell within the 95% CI of the observed risk more than 95% of the time. Limitations: The CIs of the estimates were wide, and model overfitting is possible due to the limited sample size; the risk score requires validation to determine its clinical utility. Conclusions: Our prognostic risk score uses commonly available
Molnar, Amber O; van Walraven, Carl; Fergusson, Dean; Garg, Amit X; Knoll, Greg
Acute kidney injury (AKI) is common in the kidney transplant population. To derive a multivariable survival model that predicts time to graft loss following AKI. Retrospective cohort study using health care administrative and laboratory databases. Southwestern Ontario (1999-2013) and Ottawa, Ontario, Canada (1996-2013). We included first-time kidney only transplant recipients who had a hospitalization with AKI 6 months or greater following transplant. AKI was defined using the Acute Kidney Injury Network criteria (stage 1 or greater). The first episode of AKI was included in the analysis. Graft loss was defined by return to dialysis or repeat kidney transplant. We performed a competing risk survival regression analysis using the Fine and Gray method and modified the model into a simple point system. Graft loss with death as a competing event was the primary outcome of interest. A total of 315 kidney transplant recipients who had a hospitalization with AKI 6 months or greater following transplant were included. The median (interquartile range) follow-up time was 6.7 (3.3-10.3) years. Graft loss occurred in 27.6% of the cohort. The final model included 6 variables associated with an increased risk of graft loss: younger age, increased severity of AKI, failure to recover from AKI, lower baseline estimated glomerular filtration rate, increased time from kidney transplant to AKI admission, and receipt of a kidney from a deceased donor. The risk score had a concordance probability of 0.75 (95% confidence interval [CI], 0.69-0.82). The predicted 5-year risk of graft loss fell within the 95% CI of the observed risk more than 95% of the time. The CIs of the estimates were wide, and model overfitting is possible due to the limited sample size; the risk score requires validation to determine its clinical utility. Our prognostic risk score uses commonly available information to predict the risk of graft loss in kidney transplant patients hospitalized with AKI. If validated
Friedrich, R E; Plambeck, K; Bartel-Friedrich, S; Hellner, D; Schmelzle, R
The objective of our investigation was to study the patency rates of anastomoses in arteries, damaged by a balloon dilatation, in a training model of microvascular surgery. In general anaesthesia, a balloon dilatation was repeated 5 times in 31 left common carotid arteries of female Wistar rats (body weight: 250 to 350 g). A common carotid artery autograft of 4 mm was harvested 1 minute after reflow, turned 180 degrees, and reinserted into the artery. The reflow of the vessels was investigated by micro-Doppler ultrasound equipment. Autografts without balloon dilatation or any other intended damage were performed in further 26 common carotid arteries. In addition, in further 14 common carotid arteries the balloon dilatation was the sole damage. The vessels were harvested and investigated postoperatively after perfusion with 3% glutaraldehyde at 1 day, 7 days, and 1 month. The balloon dilatation in no instance caused an occlusion of the vessel as judged by the micro-Doppler ultrasound. One vessel was found to be occluded after reflow was allowed following insertion of the autograft in the group without balloon dilatation. However, this vessel proved to be patent after explantation (patency rate: 100%). In the group with balloon dilatation preceding the autograft insertion, by micro-Doppler ultrasound, 16 vessels were occluded and 14 were patent. At different times of follow-up, in this group the summarized patency rates were 50%. The patency differences in both groups with autografts proved to be significant, both after micro-Doppler imaging and by histological evaluation (p < 0.001). For clinical use the balloon dilatation is recommended to remove a thrombus or to dilate a spastic vessel segment in anastomized vessels threatening the success of microvascular flaps. In this training model of microvascular surgery we demonstrated the thrombogenic effect of balloon dilatation.
Sun, Xiujiang; Zhang, Jianfeng; Qu, Xiaoyi
Introduction The aim of the study was to compare and analyze retrospectively the outcomes of arthroscopic posterior cruciate ligament reconstruction with autograft versus allograft. Material and methods Seventy-one patients who underwent arthroscopic posterior cruciate ligament reconstruction with an autograft or allograft met our inclusion criteria. There were 36 patients in the autograft group and 35 patients in the allograft group. All the patients were evaluated by physical examination and a functional ligament test. Comparative analysis was done in terms of operation time, incision length, fever time, postoperative infection rate, incidence of numbness and dysesthesia around the incision, as well as a routine blood test. Results The average follow-up of the autograft group was 3.2 ±0.2 years and that of the allograft group was 3.3 ±0.6 years; there was no significant difference (p > 0.05). No differences existed in knee range of motion, Lysholm scores, International Knee Documentation Committee standard evaluation form and Tegner activity score at final follow-up (p > 0.05), except that patients in the allograft group had a shorter operation time and incision length and a longer fever time (p < 0.05). We found a difference in posterior drawer test and KT-2000 arthrometer assessment (p < 0.05). The posterior tibia displacement averaged 3.8 ±1.5 mm in the autograft group and 4.8 ±1.7 mm in the allograft group (p < 0.05). The incidence of numbness and dysesthesia around the incision in the autograft group was higher than that in the allograft group (p < 0.05). There was no infection postoperatively. The white blood cells and neutrophils in the allograft group increased more than those in the autograft group postoperatively (p < 0.05). Conclusions Both groups of patients had satisfactory outcomes after the operation. However, in the instrumented posterior laxity test, the autograft gave better results than the allograft. No differences in functional scores
Wang, Yuzhuo; Wang, Joy X; Xue, Hui; Lin, Dong; Dong, Xin; Gout, Peter W; Gao, Xin; Pang, Jun
Patient-derived xenograft (PDX) cancer models with high fidelity are in great demand. While the majority of PDXs are grafted under the skin of immunodeficient mice, the Living Tumor Laboratory (LTL), using unique subrenal capsule grafting techniques, has successfully established more than 200 transplantable PDX models of various low to high grade human cancers. The LTL PDX models retain key biological properties of the original malignancies, including histopathological and molecular characteristics, tumor heterogeneity, metastatic ability, and response to treatment. The PDXs are stored frozen at early transplant generations in a resurrectable form, which eliminates continuous passaging in mice, thus ensuring maintenance of the high biologic and molecular fidelity and reproducibility of the models. The PDX models have been demonstrated to be powerful tools for (i) studies of cancer progression, metastasis and drug resistance, (ii) evidenced-based precision cancer therapy, (iii) preclinical drug efficacy testing and discovery of new anti-cancer drug candidates. To better provide resources for the research community, an LTL website (www.livingtumorlab.com) has been designed as a publicly accessible database which allows researchers to identify PDX models suitable for translational/preclinical cancer research. In summary, subrenal capsule grafting technology maximizes both tumor engraftment rate and retention of human cancer heterogeneity. Moreover, the method makes possible the recovery of PDXs from frozen stocks for further applications, thus providing a powerful platform for translational cancer research. Copyright © 2015 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.
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Langerhuus, S N; Tønnesen, E K; Jensen, K H; Damgaard, B M; Heegaard, P M H; Halekoh, U; Lauridsen, C
Aortic vascular prosthetic graft infection (AVPGI) with Staphylococcus aureus is a feared post-operative complication. This study was conducted to evaluate the clinical signs and potential biomarkers of infection in a porcine AVPGI model. The biomarkers evaluated were: C-reactive protein (CRP), fibrinogen, white blood cells (WBC), major histocompatibility complex II (MHC II) density, lymphocyte CD4:CD8 ratio and tumour necrosis factor-alpha (TNF-α) in vitro responsiveness. Sixteen pigs were included in the study, and randomly assigned into four groups (n = 4): "SHAM" pigs had their infra-renal aorta exposed by laparotomy; "CLEAN" pigs had an aortic graft inserted; "LOW" and "HIGH" pigs had an aortic graft inserted and, subsequently, S. aureus were inoculated on the graft material (5 × 10(4) colony-forming units [CFU] and 1 × 10(6) CFU, respectively). Biomarkers were evaluated prior to surgery and on day 2, 5, 7, and 14 post-operatively in blood samples. Of all biomarkers evaluated, CRP was superior for diagnosing S. aureus AVPGI in pigs, with a sensitivity of 0.86 and a specificity of 0.75.
Tønnesen, Jan; Parish, Clare L; Sørensen, Andreas T; Andersson, Angelica; Lundberg, Cecilia; Deisseroth, Karl; Arenas, Ernest; Lindvall, Olle; Kokaia, Merab
Intrastriatal grafts of stem cell-derived dopamine (DA) neurons induce behavioral recovery in animal models of Parkinson's disease (PD), but how they functionally integrate in host neural circuitries is poorly understood. Here, Wnt5a-overexpressing neural stem cells derived from embryonic ventral mesencephalon of tyrosine hydroxylase-GFP transgenic mice were expanded as neurospheres and transplanted into organotypic cultures of wild type mouse striatum. Differentiated GFP-labeled DA neurons in the grafts exhibited mature neuronal properties, including spontaneous firing of action potentials, presence of post-synaptic currents, and functional expression of DA D₂ autoreceptors. These properties resembled those recorded from identical cells in acute slices of intrastriatal grafts in the 6-hydroxy-DA-induced mouse PD model and from DA neurons in intact substantia nigra. Optogenetic activation or inhibition of grafted cells and host neurons using channelrhodopsin-2 (ChR2) and halorhodopsin (NpHR), respectively, revealed complex, bi-directional synaptic interactions between grafted cells and host neurons and extensive synaptic connectivity within the graft. Our data demonstrate for the first time using optogenetics that ectopically grafted stem cell-derived DA neurons become functionally integrated in the DA-denervated striatum. Further optogenetic dissection of the synaptic wiring between grafted and host neurons will be crucial to clarify the cellular and synaptic mechanisms underlying behavioral recovery as well as adverse effects following stem cell-based DA cell replacement strategies in PD.
Bilsel, Kerem; Demirhan, Mehmet; Atalar, Ata Can; Akkaya, Semih
A 17-year-old boy who was engaged in amateur weightlifting and body building presented with complaints of right elbow pain and limitation in elbow range of motion. Plain x-rays and magnetic resonance imaging showed an osteochondral defect in the medial third of the capitellum. At surgery, as a new technique, the lateral collateral ligament was detached from the humeral attachment to provide access to the capitellum with a clear and perpendicular exposure. Following removal of loose fragments within the joint, an osteochondral graft harvested from the lateral femoral condyle was implanted to the defect area of the capitellum. Postoperative radiologic controls showed that the defect was entirely filled by the graft with appropriate graft height. On follow-up examination at 12 months, the patient did not have any complaint about his elbow, and had no limitation of movement compared to the left elbow. Magnetic resonance imaging showed that the graft was successfully adapted to the recipient site without any sign of loosening. At final follow-up 40 months after surgery, the surface of the articular cartilage appeared normal. The range of elbow motion was preserved and the patient had no restriction in daily and sports activities. Considering technical difficulties posed by the narrow and complex structure of the elbow joint, this new technique involving detachment of the lateral collateral ligament facilitates perpendicular implantation of the graft. In our opinion, utilization of this new technique will improve functional and radiological results of osteochondral autograft transfer.
Darvish, Kurosh; Shafieian, Mehdi; Romanov, Vasily; Rotella, Vittorio; Salvatore, Michael D; Blebea, John
Endovascular stent grafts for the treatment of thoracic aortic aneurysms have become increasingly utilized and yet their locational stability in moderate chest trauma is unknown. A high speed impact system was developed to study the stability of aortic endovascular stent grafts in vitro. A straight segment of porcine descending aorta with stent graft was constrained in a custom-made transparent urethane casing. The specimen was tested in a novel impact system at an anterior inclination of 45 deg and an average deceleration of 55 G, which represented a frontal automobile crash. Due to the shock of the impact, which was shown to be below the threshold of aortic injury, the stent graft moved 0.6 mm longitudinally. This result was repeatable. The presented experimental model may be helpful in developing future grafts to withstand moderate shocks experienced in motor vehicle accidents or other dynamic loadings of the chest.
Transplantation of mesenchymal stem cells, recombinant human BMP-2,and their combination in accelerating the union after osteotomy and increasing, the mechanical strength of extracorporeally irradiated femoral autograft in rat models
Fauzi Kamal, Achmad; Hadisoebroto Dilogo, Ismail; Untung Hutagalung, Errol; Iskandriati, Diah; Susworo, R.; Chaerani Siregar, Nurjati; Aulia Yusuf, Achmad; Bachtiar, Adang
Background: Delayed union, nonunion, and mechanical failure is still problems encountered in limb salvage surgery (LSS) using extracorporeal irradiation (ECI). This study aimed to determine whether bone marrow mesenchymal stem cells (MSC) and recombinant human bone morphogenetic protein-2 (rhBMP-2) improve hostgraft union after osteotomy and also increase its mechanical strength. Methods: Thirty Sprague Dawley rats were randomly divided into five groups. Group I (control) underwent LSS using ECI method with 150 Gy single doses. Similar procedures were applied to other groups. Group II received hydroxyapatite (HA) scaffold. Group III received HA scaffold and MSC. Group IV received HA scaffold and rhBMP-2. Group V received HA scaffolds, MSC, and rhBMP-2. Radiograph were taken at week-2, 4, 6, and 8; serum alkaline phosphatase and osteocalcin were measured at week-2 and 4. Histopathological evaluation and biomechanical study was done at week-8. Results: The highest radiological score was found in group IV and V Similar result was obtained in histological score and ultimate bending force. These results were found to be statistically significant. There was no significant difference among groups in serum alkaline phosphatase and osteocalcin level. Conclusion: Combination of MSC and rhBMP-2 was proven to accelerate union and improve mechanical strength of ECI autograft. PMID:25679008
Brémard, C.; Girerd, J. J.; Merlin, J. C.; Moreau, S.
The degradation of hemoglobin by the intraerythrocytic Malaria parasite Plasmodium generates a pseudo crystalline dark product : the Malaria pigment. In a modeling effort to mimic the aggregation of the degradation products we have undertaken the synthesis of iron (III) protoporphyrin aggregates using grafted iron protoporphyrin on agarose gel. We demonstrate using Resonance Raman microspectrometry, EPR spectroscopy and magnetic measurements that the Malaria pigment is an aggregate of monomeric iron (III) protoporphyrin hydroxide compound.
Karsenty, G.; Petraglia, A.; Bourdeau, A.; Gambini, D.J.; Moreau, J.F.; Lecharpentier, Y.; Zingraff, J.; Bournerias, F.; Buisson, C.; Dubost, C.
The aim of our study was to evaluate the function and growth of parathyroid tissue autografted into the forearm of hemodialysis patients using several presently available methods. In a dynamic study, the secretory function of autografted tissue was evaluated in seven patients using either zero calcium dialysate or calcium infusion. In an additional prospective study, seven patients had repeated determinations of plasma immunoreactive parathyroid hormone (iPTH) concentration on samples from both forearms, a radionuclide evaluation of autograft function using thallium-201 chloride, and real time ultrasonography. Light microscopy analysis was performed in two patients. The dynamic study demonstrated that induction of hypocalcemia was followed by an increase, and induction of hypercalcemia by a decrease in circulating iPTH in both forearms using three different radioimmunoassays similar to what has been reported for normal parathyroid tissue. A significant gradient (ie, greater than 2.0) of plasma iPTH concentration in samples from both forearms was observed in only three out of the seven patients of the prospective study. Two of these patients disclosed an increased uptake of /sup 201/TI chloride at the site of autografted tissue and had an echographically detectable mass. In both, hyperplastic parathyroid tissue was removed. At present, the remaining third patient does not have other features of recurrent hyperparathyroidism. In conclusion, autotransplanted parathyroid tissue of hemodialysis patients shows an adequate response to physiologic stimuli such as hypo- and hypercalcemia. Dynamic tests, therefore, appear to be a useful tool in the assessment of its function. In addition, radionuclide and echographic studies may be reliable adjuncts in the detection of marked parathyroid autograft hyperplasia.
Lee, Simon; Wuerz, Thomas H; Shewman, Elizabeth; McCormick, Frank M; Salata, Michael J; Philippon, Marc J; Nho, Shane J
Labral reconstruction using iliotibial band (ITB) autografts and semitendinosus (Semi-T) allografts has recently been described in cases of labral deficiency. To characterize the joint biomechanics with a labrum-intact, labrum-deficient, and labrum-reconstructed acetabulum in a hip cadaveric model. The hypothesis was that labral resection would decrease contact area, increase contact pressure, and increase peak force, while subsequent labral reconstruction with ITB autografts or Semi-T allografts would restore these values toward the native intact labral state. Controlled laboratory study. Ten fresh-frozen human cadaveric hips were analyzed utilizing thin-film piezoresistive load sensors to measure contact area, contact pressure, and peak force (1) with the native intact labrum, (2) after segmental labral resection, and (3) after graft labral reconstruction with either ITB autografts or Semi-T allografts. Each specimen was examined at 20° of extension and 60° of flexion. Statistical analysis was conducted through 1-way analysis of variance with post hoc Games-Howell tests. For the ITB group, labral resection significantly decreased contact area (at 20°: 73.2%±5.38%, P=.0010; at 60°: 78.5%±6.93%, P=.0063) and increased contact pressure (at 20°: 106.7%±4.15%, P=.0387; at 60°: 103.9%±1.15%, P=.0428). In addition, ITB reconstruction improved contact area (at 20°: 87.2%±12.3%, P=.0130; at 60°: 90.5%±8.81%, P=.0079) and contact pressure (at 20°: 98.5%±5.71%, P=.0476; at 60°: 96.6%±1.13%, P=.0056) from the resected state. Contact pressure at 60° of flexion was significantly lower compared with the native labrum (P=.0420). For the Semi-T group, labral resection significantly decreased contact area (at 20°: 68.1%±12.57%, P=.0002; at 60°: 67.5%±6.70%, P=.0002) and increased contact pressure (at 20°: 105.3%±3.73%, P=.0304; at 60°: 106.8%±4.04%, P=.0231). Semi-T reconstruction improved contact area (at 20°: 87.9%±7.95%, P=.0087; at 60°: 92.9%±13
Alrobaiea, Saad M.; Ding, Jie; Ma, Zengshuan; Tredget, Edward E.
Objective: Hypertrophic scar (HTS) is a dermal form of fibroproliferative disorder that develops following deep skin injury. HTS can cause deformities, functional disabilities, and aesthetic disfigurements. The pathophysiology of HTS is not understood due to, in part, the lack of an ideal animal model. We hypothesize that human skin with deep dermal wounds grafted onto athymic nude mice will develop a scar similar to HTS. Our aim is to develop a representative animal model of human HTS. Approach: Thirty-six nude mice were grafted with full thickness human skin with deep dermal scratch wound before or 2 weeks after grafting or without scratch. The scratch on the human skin grafts was made using a specially designed jig that creates a wound >0.6 mm in depth. The xenografts were morphologically analyzed by digital photography. Mice were euthanized at 1, 2, and 3 months postoperatively for histology and immunohistochemistry analysis. Results: The mice developed raised and firm scars in the scratched xenografts with more contraction, increased infiltration of macrophage, and myofibroblasts compared to the xenografts without deep dermal scratch wound. Scar thickness and collagen bundle orientation and morphology resembled HTS. The fibrotic scars in the wounded human skin were morphologically and histologically similar to HTS, and human skin epithelial cells persisted in the remodeling tissues for 1 year postengraftment. Innovation and Conclusions: Deep dermal injury in human skin retains its profibrotic nature after transplantation, affording a novel model for the assessment of therapies for the treatment of human fibroproliferative disorders of the skin. PMID:27366591
Bernstein, Mark P.; Caldwell, Curtis B.; Antonyshyn, Oleh M.; Ma, Karen; Cooper, Perry W.; Ehrlich, Lisa E.
Bone autografts are routinely employed in the reconstruction of facial deformities resulting from trauma, tumor ablation or congenital malformations. The combined use of post- operative 3D CT and SPECT imaging provides a means for quantitative in vivo evaluation of bone graft volume and osteoblastic activity. The specific objectives of this study were: (1) Determine the reliability and accuracy of interactive computer-assisted analysis of bone graft volumes based on 3D CT scans; (2) Determine the error in CT/SPECT multimodality image registration; (3) Determine the error in SPECT/SPECT image registration; and (4) Determine the reliability and accuracy of CT-guided SPECT uptake measurements in cranial bone grafts. Five human cadaver heads served as anthropomorphic models for all experiments. Four cranial defects were created in each specimen with inlay and onlay split skull bone grafts and reconstructed to skull and malar recipient sites. To acquire all images, each specimen was CT scanned and coated with Technetium doped paint. For purposes of validation, skulls were landmarked with 1/16-inch ball-bearings and Indium. This study provides a new technique relating anatomy and physiology for the analysis of cranial bone graft survival.
Pan, Juan; Liu, Guo-Ming; Ning, Liang-Ju; Zhang, Yi; Luo, Jing-Cong; Huang, Fu-Guo; Qin, Ting-Wu
Although varieties of surgical repair techniques and materials have been used to repair rotator cuff defects, re-tearing frequently occurs. The purpose of this study is to evaluate the postoperative outcomes of rotator cuff repairs with a decellularized tendon slices (DTSs) graft in a rabbit model. Large defects in the infraspinatus tendons were created bilaterally in 21 rabbits. The graft group underwent reconstruction of the defects with the DTSs grafts, while the defect group did not undergo any treatment. The specimens underwent histological observation, biomechanical testing, and magnetic resonance imaging (MRI) detection at 4, 8, and 12 weeks after surgery. In addition, 2 rabbits that were not operated on were used for MRI detection as a normal reference. Histological analysis revealed that the graft promoted host cell ingrowth and tissue integration, and a tendon-like structure developed at 12 weeks. The ultimate tensile load had a significant difference between specimens at 4 and 12 weeks in the graft group, but there was no significant difference between the graft group and the defect group. In the graft group, the stiffness at 12 weeks was significantly greater than that at 4 or 8 weeks, and it was also greater than the stiffness in the defect group at 12 weeks. MRI demonstrated that the signal strength of the regenerative tissue from the graft group at 12 weeks was similar to that of normal infraspinatus tendon. The DTSs graft allowed for incorporation of host tendon and improved the biomechanical performance of the regenerative tendon. Therefore, the graft could be a promising bioscaffold to enhance the surgical repair of large rotator cuff defects and consequently improve the clinical outcome of rotator cuff tears.
Pepper, Victoria K; Clark, Elizabeth S; Best, Cameron A; Onwuka, Ekene A; Sugiura, Tadahisa; Heuer, Eric D; Moko, Lilamarie E; Miyamoto, Shinka; Miyachi, Hideki; Berman, Darren P; Cheatham, Sharon L; Chisolm, Joanne L; Shinoka, Toshiharu; Breuer, Christopher K; Cheatham, John P
Patients who undergo implantation of a tissue-engineered vascular graft (TEVG) for congenital cardiac anomalies are monitored with echocardiography, followed by magnetic resonance imaging or angiography when indicated. While these methods provide data regarding the lumen, minimal information regarding neotissue formation is obtained. Intravascular ultrasound (IVUS) has previously been used in a variety of conditions to evaluate the vessel wall. The purpose of this study was to evaluate the utility of IVUS for evaluation of TEVGs in our ovine model. Eight sheep underwent implantation of TEVGs either unseeded or seeded with bone marrow-derived mononuclear cells. Angiography, IVUS, and histology were directly compared. Endothelium, tunica media, and graft were identifiable on IVUS and histology at multiple time points. There was strong agreement between IVUS and angiography for evaluation of luminal diameter. IVUS offers a valuable tool to evaluate the changes within TEVGs, and clinical translation of this application is warranted.
Hashemi, H M; Parhiz, A; Ghafari, S
The aim of the present study was to compare the application of alloderm and mucosal graft for vestibuloplasty. This randomized controlled trial with split mouth design was carried out on 20 edentulous patients. Patients underwent vestibuloplasty surgery with the Clark technique. Half of the prepared bed in each patient was covered with alloderm and the other half with mucosal graft. Vestibule depth (width of fixed tissue) and relapse in the two sides immediately after surgery, and 1, 3 and 6 months after surgery were measured and compared. Statistical analysis was carried out using the Kolmogorov-Smirnov, Student's paired t and Friedman tests. The width of the fixed tissue in the alloderm graft at 1, 3 and 6 month intervals was significantly lower than that in the autograft (P<0.05). The difference in relapse between the two grafts was not statistically significant at any time. The results of the study suggest that alloderm is as effective as mucosal grafts in vestibuloplasty. Copyright Â© 2011 International Association of Oral and Maxillofacial Surgeons. All rights reserved.
Briggaman, R A
Human skin can be grown away from its donor for prolonged periods as grafts on congenitally athymic "nude" mice. This system has been used to analyze the defect in several skin diseases, specifically to localize the site of the defect to the skin itself or to the epidermal or dermal components of the skin. In order to validate the use of the nude mouse human skin graft system in the analysis of skin defects, we have demonstrated that a systemic metabolic defect which involves the skin, namely essential fatty acid deficiency, can be differentiated from a defect residing primarily in the skin itself. Skin-marker systems have been developed for use with the nude mouse-human skin graft model to document the identity of human skin grafts and epidermal and dermal components of the grafts after prolonged periods of growth on the nude athymic mice. Y-body, a small fluorescent segment of the Y-chromosome seen in interphase cells, is used as a sex marker and serves to distinguish sex differences between the graft and the mouse recipient or between skin components of the graft. The ABH "blood-group" antigens are present on differentiated epidermal cell surfaces and identify the grafted epidermis according to the blood groups of the donor. In previous studies, lamellar ichthyosis was shown to be well maintained after prolonged periods of growth on nude athymic mice, indicating that the defect in this disease resides in the skin itself. Recombinant grafts composed of normal and lamellar ichthyosis epidermis and dermis further localize the defect to lamellar ichthyosis epidermis. Psoriasis is well maintained on the nude mouse-skin graft model. The epidermal hyperplasia and hyperproliferative epidermal cell kinetics of psoriasis are manifested in the grafts of active psoriasis maintained for prolonged periods on the nude mice, but the inflammatory component of psoriasis is absent. Recombinant graft studies utilizing normal and psoriatic epidermis and dermis demonstrate psoriasis
Seiler, Stefanie; Di Santo, Stefano; Widmer, Hans Rudolf
Transplantation of fetal human ventral mesencephalic (VM) dopaminergic neurons into the striatum is a promising strategy to compensate for the characteristic dopamine deficit observed in Parkinson’s disease (PD). This therapeutic approach, however, is currently limited by the high number of fetuses needed for transplantation and the poor survival and functional integration of grafted dopaminergic neurons into the host brain. Accumulating evidence indicates that contrasting inhibitory signals endowed in the central nervous system (CNS) might support neuronal regeneration. Hence, in the present study we aimed at improving survival and integration of grafted cells in the host brain by neutralizing Nogo-A, one of the most potent neurite growth inhibitors in the CNS. For that purpose, VM tissue cultures were transplanted into rats with a partial 6-hydroxydopamine (6-OHDA) lesion causing a hemi-PD model and concomitantly treated for 2 weeks with intra-ventricular infusion of neutralizing anti-Nogo-A antibodies. Motor behavior using the cylinder test was assessed prior to and after transplantation as functional outcome. At the end of the experimental period the number of dopaminergic fibers growing into the host brain, the number of surviving dopaminergic neurons in the grafts as well as graft size was examined. We found that anti-Nogo-A antibody infusion significantly improved the asymmetrical forelimb use observed after lesions as compared to controls. Importantly, a significantly three-fold higher dopaminergic fiber outgrowth from the transplants was detected in the Nogo-A antibody treated group as compared to controls. Furthermore, Nogo-A neutralization showed a tendency for increased survival of dopaminergic neurons (by two-fold) in the grafts. No significant differences were observed for graft volume and the number of dopaminergic neurons co-expressing G-protein-coupled inward rectifier potassium channel subunit two between groups. In sum, our findings support the
Sankaran, Sethuraman; Esmaily Moghadam, Mahdi; Kahn, Andy; Marsden, Alison
We present a computational framework for modeling and simulation of blood flow in patients who undergo coronary artery bypass graft (CABG) surgeries. We evaluate the influence of shape on the homeostatic state, cardiac output, and other quantities of interest. We present a case study on a patient with multiple CABG. We build a patient-specific model of the blood vessels comprised of the aorta, vessels branching from the top of the aorta (brachiocephalic artery and carotids) and the coronary arteries, in addition to bypass grafts. The rest of the circulatory system is modeled using lumped parameter 0D models comprised of resistances, compliances, inertances and elastance. An algorithm is presented that computes these parameters automatically given constraints on the flow. A Finite element framework is used to compute blood flow and pressure in the 3D model to which the 0D code is coupled at the model inlets and outlets. An adaptive closed loop BC is used to capture the coupling of the various outlets of the model with inlets, and is compared with a model with fixed inlet BC. We compare and contrast the pressure, flowrate, coronary perfusion, and PV curves obtained in the different cases. Further, we compare and contrast quantities of interest such as wall shear stress, wall shear stress gradients and oscillatory shear index for different surgical geometries and discuss implications of patient-specific optimization. I would like to acknowlege AHA for funding this work.
Fang, Taolin; Lineaweaver, William C; Sailes, Frederick C; Kisner, Carson; Zhang, Feng
Achieving permanent replacement of skin in extensive full-thickness and deep partial-thickness burn injuries and chronic wounds remains one of the fundamental surgical problems. Presently, split-thickness skin grafts are still considered the best material for surgical repair of an excised burn wound. However, in burns that affect greater than 50% of total body surface area, the patient has insufficient areas of unaffected skin from which split-thickness skin grafts can be harvested. The use of cultured epithelial (or epidermal) autografts (CEAs) has achieved satisfactory results. But the take rate of CEAs is poor in full-thickness bed or in chronically infected area. Providing temporary cover with allograft skin, or a more permanent allodermis, may increase clinical take. This review aims to (1) describe the use of CEAs in the regeneration of the epidermis, (2) introduce the application of the acellular dermal matrices (ADMs) in the clinics, and (3) enhance understanding of the CEAs applied with ADM as an appropriate strategy to treat the extended burn injuries. The current evidence regarding the cultured epithelial cell or keratinocyte autograft and dermal grafts applied in the treatment of burn injuries was investigated with an extensive electronic and manual search (MEDLINE and EMBASE). The included literature (N=136 publications) was critically evaluated focusing on the efficacy and safety of this technique in improving the healing of the deep dermal and full-thickness burn injuries. This review concluded that the use of ADM with CEAs is becoming increasingly routine, particularly as a life-saving tool after acute thermal trauma.
Boyce, S T; Goretsky, M J; Greenhalgh, D G; Kagan, R J; Rieman, M T; Warden, G D
OBJECTIVE: Comparison of cultured skin substitutes (CSSs) and split-thickness autograft (STAG) was performed to assess whether the requirement for autologous skin grafts may be reduced in the treatment of massive burns. SUMMARY BACKGROUND DATA: Cultured skin substitutes consisting of collagen-glycosaminoglycan substrates populated with autologous fibroblasts and keratinocytes have been demonstrated to close full-thickness skin wounds in athymic mice and to express normal skin antigens after closure of excised wounds in burn patients. METHODS: Data were collected from 17 patients between days 2 and 14 to determine incidence of exudate, incidence of regrafting, coloration, keratinization, and percentage of site covered by graft (n = 17). Outcome was evaluated on an ordinal scale (0 = worst; 10 = best) beginning at day 14, with primary analyses at 28 days (n = 10) and 1 year (n = 4) for erythema, pigmentation, epithelial blistering, surface roughness, skin suppleness, and raised scar. RESULTS: Sites treated with CSSs had increased incidence of exudate (p = 0.06) and decreased percentage of engraftment (p < 0.05) compared with STAG. Outcome parameters during the first year showed no differences in erythema, blistering, or suppleness. Pigmentation was greater, scar was less raised, but regrafting was more frequent in CSS sites than STAG. No differences in qualitative outcomes were found after 1 year, and antibodies to bovine collagen were not detected in patient sera. CONCLUSIONS: These results suggest that outcome of engrafted CSSs is not different from STAG and that increased incidence of regrafting is related to decreased percentage of initial engraftment. Increased rates of engraftment of CSSs may lead to improved outcome for closure of burn wounds, allow greater availability of materials for grafting, and reduce requirements for donor skin autograft. Images Figure 1. Figure 2. PMID:8526581
McCall, Todd A; Brokaw, David S; Jelen, Bradley A; Scheid, D Kevin; Scharfenberger, Angela V; Maar, Dean C; Green, James M; Shipps, Melanie R; Stone, Marcus B; Musapatika, Dana; Weber, Timothy G
Treatment of large segmental defects using conventional autogenous iliac crest bone graft can be limited by volume of cancellous bone and donor site morbidity. The reamer-irrigator-aspirator (RIA) technique allows access to a large volume of cancellous bone graft containing growth factors with potency equal to or greater than autograft material from the iliac crest. The purpose of this study was to evaluate the effectiveness of RIA-harvested autogenous bone graft for treating large segmental defects of long bones.
Sun, Kang; Tian, Shao-qi; Zhang, Ji-hua; Xia, Chang-suo; Zhang, Cai-long; Yu, Teng-bo
Objective: To analyze the clinical outcomes of arthroscopic anterior cruciate ligament (ACL) reconstruction with irradiated bone-patellar tendon-bone (BPTB) allograft compared with non-irradiated allograft and autograft. Methods: All BPTB allografts were obtained from a single tissue bank and the irradiated allografts were sterilized with 2.5 mrad of irradiation prior to distribution. A total of 68 patients undergoing arthroscopic ACL reconstruction were prospectively randomized consecutively into one of the two groups (autograft and irradiated allograft groups). The same surgical technique was used in all operations done by the same senior surgeon. Before surgery and at the average of 31 months of follow-up (ranging from 24 to 47 months), patients were evaluated by the same observer according to objective and subjective clinical evaluations. Results: Of these patients, 65 (autograft 33, irradiated allograft 32) were available for full evaluation. When the irradiated allograft group was compared to the autograft group at the 31-month follow-up by the Lachman test, the anterior drawer test (ADT), the pivot shift test, and KT-2000 arthrometer test, statistically significant differences were found. Most importantly, 87.8% of patients in the autograft group and just only 31.3% in the irradiated allograft group had a side-to-side difference of less than 3 mm according to KT-2000. The failure rate of the ACL reconstruction with irradiated allograft (34.4%) was higher than that with autograft (6.1%). The anterior and rotational stabilities decreased significantly in the irradiated allograft group. According to the overall International Knee Documentation Committee (IKDC), functional and subjective evaluations, and activity level testing, no statistically significant differences were found between the two groups. Besides, patients in the irradiated allograft group had a shorter operation time and a longer duration of postoperative fever. When the patients had a fever, the
Singh, Charanpreet; Wang, Xungai
Stent-graft (SG) induced biomechanical mismatch at the aortic repair site forms the major reason behind postoperative hemodynamic complications. These complications arise from mismatched radial compliance and stiffness property of repair device relative to native aortic mechanics. The inability of an exoskeleton SG design (an externally stented rigid polyester graft) to achieve optimum balance between structural robustness and flexibility constrains its biomechanical performance limits. Therefore, a new SG design capable of dynamically controlling its stiffness and flexibility has been proposed in this study. The new design is adopted from the segmented hydroskeleton structure of a caterpillar cuticle and comprises of high performance polymeric filaments constructed in a segmented knit architecture. Initially, conceptual design models of caterpillar and SG were developed and later translated into an experimental SG prototype. The in-vitro biomechanical evaluation (compliance, bending moment, migration intensity, and viscoelasticity) revealed significantly better performance of hydroskeleton structure than a commercial SG device (Zenith(™) Flex SG) and woven Dacron(®) graft-prosthesis. Structural segmentation improved the biomechanical behaviour of new SG by inducing a three dimensional volumetric expansion property when the SG was subjected to hoop stresses. Interestingly, this behaviour matches the orthotropic elastic property of native aorta and hence proposes segmented hydroskeleton structures as promising design approach for future aortic repair devices.
Emery, S E; Brazinski, M S; Koka, A; Bensusan, J S; Stevenson, S
We evaluated the effects of irradiation on the healing of anterior vertebral strut grafts with use of a canine model. Through a left thoracotomy, a partial corpectomy of the seventh thoracic vertebra and autogenous iliac strut-grafting from the sixth to the eighth thoracic levels were performed in twenty-two adult beagles. Four groups were established: Group I (control) received no irradiation, Group II received preoperative irradiation, Group III received postoperative irradiation that began on the third postoperative day, and Group IV received postoperative irradiation that began on the twenty-first postoperative day. The irradiation protocol was five treatments of 500 centigray three times a week for a total of 2500 centigray. Fluorochromes were administered at regular intervals postoperatively. The beagles were killed three months postoperatively, and non-destructive biomechanical testing was done to evaluate the stiffness of the construct. The quality of healing at the junctions of the graft with the sixth and eighth thoracic vertebrae, the degree of revascularization of the graft, and the amount of new-bone formation were evaluated histologically. Statistical evaluation of the biomechanical data revealed no significant difference in the stiffness of the construct between Groups I, II, and IV. The specimens from Group III were significantly less stiff than those from Group I (the control group) in torsion (p = 0.03) and left lateral bending (p = 0.04) and than those from Group II in flexion (p = 0.02) and left lateral bending (p = 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)
Richter, J; Volz, R; Immendörfer, M; Schulz, M
Reconstruction of the anterior talofibular (ATFL) and calcaneofibular (CFL) ligament in patients with chronic lateral ankle instability. Symptomatic chronic lateral ankle instability. Bony malalignment, advanced arthritic changes of the ankle joint, diabetic foot syndrome. Reconstruction of the ATFL and CFL with a free gracilisor or semitendinosus tendon graft through a V-shaped tunnel at the insertion site of the ATFL on the talar neck as well as a transfibular tunnel directed anterior to posterior through the fibula tip to a blind ending tunnel in the calcaneus at the insertion site of the CFL. Insertion of the graft through the talar tunnel, passing both graft ends through the fibular tunnel to the calcaneus. Fixation with a bioabsorbable screw. Short leg cast for 10-14 days and partial weight-bearing. Afterwards ankle brace for 6 weeks and functional physical therapy. From December 2003 to August 2005, reconstruction of the ATFL and CFL with a hamstring tendon autograft was performed in 20 patients with chronic lateral instability of the ankle joint. All patients were evaluated after a mean follow-up time of 1.8 years (15-36 months). Clinical evaluation referred to the AOFAS score. Stress radiography was performed for objective assessment of lateral ankle stability. Postoperatively 19 of 20 patients reported good subjective stability with no further ankle sprains. The mean postoperative AOFAS score was 92 of 100 points (72-100). Stress radiography showed a significant reduction of both lateral ankle instability and talar tilt.
Imai, Yasuhiro; Urayama, Shin-ich; Uyama, Chikao; Inoue, Kanji; Ueno, Katsuya; Kuribayashi, Sachio; Takamiya, Makoto; Hamada, Seiki; Hirane, Yoshihisa
A three-dimensional model was constructed from helical CT images for abdominal aortic aneurysm (AAA) and thoracic aortic aneurysm (TAA). A stent-graft was designed and positioned endoluminally on the computer. One hundred and nine stent-grafts for 101 patients were designed by this method and deployed well in all patients. The design time was reduced from 4 to 0.5 hr.
Terry, Christi M.; Zhuplatov, Ilya; He, Yuxia; Wun, Tze-Chein; Kim, Seong-Eun; Cheung, Alfred K.
Background Hemodialysis arteriovenous synthetic grafts (AVG) provide high volumetric blood flow rates shortly after surgical placement. However, stenosis often develops at the vein-graft anastomosis contributing to thrombosis and early graft failure. Two novel fusion proteins, ANV-6L15 and TAP-ANV, inhibit the tissue factor/factor VIIa coagulation complex and the factor Xa/factor Va complex, respectively. Each inhibitor domain is fused to an annexin V domain that targets the inhibitor activity to sites of vascular injury to locally inhibit thrombosis. This study’s objective was to determine if these antithrombotic proteins are safe and effective in inhibiting AVG stenosis. Methods A bolus of either TAP-ANV or ANV-6L15 fusion protein was administered intravenously immediately prior to surgical placement of a synthetic graft between the external jugular vein and common carotid artery in a porcine model. At surgery, the vein and artery were irrigated with the anti-thrombotic fusion protein. Control animals received intravenous heparin. At 4 weeks, MRI was performed to evaluate graft patency, the pigs were then euthanized and grafts and attached vessels were explanted for histomorphometric assessment of neointimal hyperplasia at the vein-graft anastomosis. Blood was collected at surgery, immediately after surgery and at euthanasia for serum metabolic panels and coagulation chemistries. Results No acute thrombosis occurred in the control group or in either experimental group. No abnormal serum chemistries, activated clotting times or PT, PTT values were observed after treatment in experimental or control animals. However, at the vein-graft anastomosis, there was no difference between the control and experimental groups in cross-sectional lumen areas, as measured on MRI, and no difference in hyperplasia areas as determined by histomorphometry. These results suggest that local irrigation of TAP-ANV or ANV-6L15 intra-operatively was as effective in inhibiting acute graft
Greenhalgh, David G; Hinchcliff, Katharine; Sen, Soman; Palmieri, Tina L
The authors reviewed their 10-year experience of performing face grafts in children with burns. They sought to compare different methods for aesthetic outcome and need for reconstruction. In addition, they determined the efficacy of using allograft skin or Integra as temporary covers. They performed a review of 160 pediatric patients who underwent acute facial excision and grafting for burns between 2000 and 2010. Of the 160 patients with a mean age of 5.8 ± 4.8 years, 96 were males. The mean burn size was 39.4 ± 24.61%, of which 36.5 ± 25.4% was third degree. Overall length of stay was 72.1 days, intensive care unit length of stay was 44.2 days, and the mortality rate was 13.75%. Ninety patients had their entire face burned, 42 burned half, 15 burned their foreheads, and seven had other combinations. The interval between injury and grafting was 13.9 ± 13.19 days. Sixty-three percent patients required one face graft, 23% had two, 8% had three, and 6% four or more. For their initial procedure, 105 patients underwent autografting, 28 had allografting, and 23 received Integra. The authors performed a two-stage procedure in 20.4% and a 1-day procedure in 79.6%. Ten patients had a contiguous "U-shaped" graft wrapped around the face. At least partial regrafting was performed in 21.1%. Allograft and Integra were used for massive burns (69.9 ± 14.5%, 62.6 ± 18.3%, respectively). Of these, 39% died, 17% developed an Integra infection, and 43% required regrafting before autografting. Overall, 24.5% of patients underwent facial reconstruction during their first admission, and 57.1% during subsequent admissions. No difference in the rate of reconstructive surgery was noted between patients receiving Integra or autografting. Autografting face burns as an initial, one-stage procedure works well. The "wrap-around" autograft leads to excellent cosmetic results. When there is a shortage of autograft, allograft or Integra are good options but Integra does not reduce the need
Subhadrabandhu, Saran; Takeuchi, Akihiko; Yamamoto, Norio; Shirai, Toshiharu; Nishida, Hideji; Hayashi, Katsuhiro; Miwa, Shinji; Tsuchiya, Hiroyuki
Several methods are available using an endoprosthesis or biological reconstruction for malignant bone tumors. Methods that use allograft-prosthesis composites have shown promising results. In 1999, the authors developed a method of reconstruction that uses a tumor-bearing autograft treated with liquid nitrogen. This technique was modified to produce a pedicle frozen autograft to maintain anatomical continuity on one side. In this study, the results of bone reconstructions using frozen autograft-prosthesis composites were retrospectively evaluated. The demographic data, histological records, surgical procedures, functional scores, and complications of 22 patients who had bone sarcoma or metastasis and at least 2 years of follow-up were reviewed. There were 19 patients with primary bone sarcoma and 3 with bone metastasis. Average age was 36 years (range, 9-73 years), and mean follow-up was 63 months (range, 24-176 months). Reconstructions were performed on 10 proximal femurs, 5 distal femurs, 4 proximal tibias, 1 proximal humerus, 1 proximal radius, and 1 hemipelvis. There were 12 pedicle-freezing and 10 free-freezing procedures. Union rate was 90% (9/10), and average union time was 9.5 months. Average Musculoskeletal Tumor Society score was 89.3%. Complications included 1 fracture, 2 infections, 3 soft tissue recurrences, and 1 posterior interosseous nerve palsy. The authors concluded that the frozen autograft-prosthesis composite demonstrated excellent Musculoskeletal Tumor Society scores, a low complication rate, and a good union rate and was superior when used with the pedicle-freezing technique.
Ahn, Sanghyun; Lim, Gyuchang; Kim, Sooyong; Kim, Kyungsik
In this work, we graft the volatility clustering observed in empirical financial time series into the Equiluz and Zimmermann (EZ) model, which was introduced to reproduce the herding behaviors of a financial time series. The original EZ model failed to reproduce the empirically observed power-law exponents of real financial data. The EZ model ordinarily produces a more fat-tailed distribution compared to real data, and a long-range correlation of absolute returns that underlie the volatility clustering. As it is not appropriate to capture the empirically observed correlations in a modified EZ model, we apply a sorting method to incorporate the nonlinear correlation structure of a real financial time series into the generated returns. By doing so, we observe that the slow convergence of distribution of returns is well established for returns generated from the EZ model and its modified version. It is also found that the modified EZ model leads to a less fat-tailed distribution.
Bowland, Philippa; Ingham, E; Jennings, Louise; Fisher, John
A review of research undertaken to evaluate the biomechanical stability and biotribological behaviour of osteochondral grafts in the knee joint and a brief discussion of areas requiring further improvement in future studies are presented. The review takes into consideration osteochondral autografts, allografts, tissue engineered constructs and synthetic and biological scaffolds. PMID:26614801
Zinöcker, Severin; Dressel, Ralf; Wang, Xiao-Nong; Dickinson, Anne M.; Rolstad, Bent
Allogeneic hematopoietic cell transplantation (alloHCT) extends the lives of thousands of patients who would otherwise succumb to hematopoietic malignancies such as leukemias and lymphomas, aplastic anemia, and disorders of the immune system. In alloHCT, different immune cell types mediate beneficial graft-versus-tumor (GvT) effects, regulate detrimental graft-versus-host disease (GvHD), and are required for protection against infections. Today, the “good” (GvT effector cells and memory cells conferring protection) cannot be easily separated from the “bad” (GvHD-causing cells), and alloHCT remains a hazardous medical modality. The transplantation of hematopoietic stem cells into an immunosuppressed patient creates a delicate environment for the reconstitution of donor blood and immune cells in co-existence with host cells. Immunological reconstitution determines to a large extent the immune status of the allo-transplanted host against infections and the recurrence of cancer, and is critical for long-term protection and survival after clinical alloHCT. Animal models continue to be extremely valuable experimental tools that widen our understanding of, for example, the dynamics of post-transplant hematopoiesis and the complexity of immune reconstitution with multiple ways of interaction between host and donor cells. In this review, we discuss the rat as an experimental model of HCT between allogeneic individuals. We summarize our findings on lymphocyte reconstitution in transplanted rats and illustrate the disease pathology of this particular model. We also introduce the rat skin explant assay, a feasible alternative to in vivo transplantation studies. The skin explant assay can be used to elucidate the biology of graft-versus-host reactions, which are known to have a major impact on immune reconstitution, and to perform genome-wide gene expression studies using controlled combinations of minor and major histocompatibility between the donor and the recipient
El-Kurdi, Mohammed S; Soletti, Lorenzo; Nieponice, Alejandro; Abuin, Gustavo; Gross, Christina; Rousselle, Serge; Greisler, Howard; McGrath, Jonathan
Saphenous vein grafts (SVGs) are frequently used for multi-vessel coronary artery bypass grafting and peripheral arterial bypasses; however, the estimated 40% failure rate within the first 5 y due to intimal hyperplasia (IH) and the subsequent failure rate of 2%-4% per year pose a significant clinical problem. Here, we report a surgical model in sheep intended to study IH development in SVGs, which can also be used for the evaluation of potential alternative treatments. Autologous bilateral SVGs were implanted as femoral artery interposition grafts using end-to-side anastomoses in adult sheep (n = 23), which were survived for 30 (n = 6), 90 (n = 7), 180 (n = 7), or 365 (n = 3) days. Post-implant, mid-term, and pretermination angiograms were quantified, and harvested SVGs were evaluated using quantitative histomorphometry. We describe a peripheral arterial surgical technique that models the progression of SVG pathology. Angiographic analysis showed a progressive dilation of SVGs leading to worsening diametrical matching to the target artery and reduced blood flow; and histomorphometry data showed an increase in IH over time. Multivariable regression analysis suggested that statistically significant (P < 0.05) time-dependent relationships exist between SVG dilation and both reduction in blood flow and IH development. Bilateral SVGs implanted onto the femoral arteries of sheep produced, controlled and consistent angiographic and histomorphometric results for which direct correlations could be made. This preclinical investigation model can be used as a robust tool to evaluate therapies intended for cardiovascular pathologies such as occlusive IH in SVGs. Copyright © 2015 Elsevier Inc. All rights reserved.
Ruiz-Delgado, Guillermo J; Ruiz-Argüelles, Guillermo J
The widespread practice of stem cell grafting faces several problems in the world, derived mainly from the high costs of the procedure when conducted using traditional methods. In order to cope with this problem, we have implemented in México procedures to make stem cell grafting, both autologous and allogeneic, more affordable to patients living in our country and in other developing countries. The simplification of these procedures which have been done in our country are described; they have resulted in and increased number of patients both autografted and allografted in México. In the case of autografts, the changes have relied on the use of non-frozen autologous peripheral blood stem cells and short conditioning schedules delivered as outpatients, whereas in the case of allografts, changes have relied mainly in conducting the allografts fully on an outpatient basis and employing reduced-intensity conditioning preparative schedules.
García, Joanna; Carlsson, Thomas; Döbrössy, Máté; Nikkhah, Guido; Winkler, Christian
Graft-induced dyskinesia (GID), covering a range of dystonic and choreiform involuntary movements, has been observed in some patients with Parkinson's disease (PD) after intracerebral cell transplantation. These dyskinesias have been severe in a number of patients and represent one of the main obstacles for further development of the cell therapy in PD. Serotonin neurons, included into the dopaminergic cell suspension due to the nature of the dissection process, have been suggested as a key factor for the development of GID, since the administration of the serotonin (5-HT)(1A)-receptor agonist buspirone reduced dyskinesia in transplanted PD patients. In the present study, we characterized GID in the rat PD model after transplantation of dopaminergic grafts containing different amounts of serotonin neurons. The severity of GID was significantly correlated with the amount of grafted dopamine and serotonin neurons, but the r-values were low. However, neither the innervation density of dopamine and serotonin fibers in the grafted striatum nor the dopamine-to-serotonin cell ratio correlated significantly with the severity of GID. The results extend prior knowledge of the role of dopaminergic grafts in the development of GID and show that, in the animal model, serotonin neurons within the graft suspension might be involved, but given sufficient dopamine cells, their impact on GID may be minor.
Mohamed, Khalid M S; Fenelon, Christopher; Galbraith, John G; D'Souza, Lester G
Lateral column lengthening osteotomy is very useful surgical technique in treating stage II of pes planovalgus deformity of the foot. Either autograft from the iliac crest or allograft can be used for this purpose. In our technique we describe a novel method of obtaining bone graft locally from the calcaneus and therefore avoiding complications and morbidity associated with iliac crest graft. Copyright © 2016 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.
Willett, Emily S; Liu, Jingpeng; Berke, Molly; Giannini, Peter J; Schmid, Marian; Jia, Zhenshan; Wang, Xiaobei; Wang, Xiaoyan; Samson, Kaeli; Yu, Fang; Wang, Dong; Nawshad, Ali; Reinhardt, Richard A
Loss of alveolar ridge width and height after tooth extraction is well documented, but models to evaluate ridge preservation are neither standardized nor cost-effective. This rat model characterizes the pattern of bone turnover and inflammation after extraction and bone grafting with or without local simvastatin (SIM). Fifty retired-breeder rats underwent extraction of the maxillary right first molar and standard surgical defect creation under inhalation/local anesthesia. The left side of each animal served as unmanipulated control. Untreated groups (n = 8 to 9 per group) were compared (analysis of variance, t test) at days 0, 7, 14, and 28 for alveolar ridge height and width and for markers of inflammation and bone turnover by microcomputed tomography, histology, and enzyme-linked immunosorbent assay. Seventeen additional specimens had defects grafted with either bone mineralized matrix (BMM) or a BMM+SIM conjugate. Extraction-induced bone loss (BL) was noted on buccal, palatal, and interproximal height (P <0.05) and ridge width (P <0.01). Week 1 inflammation positively correlated with ridge height; thereafter, a more intense inflammatory reaction corresponded to reduction in alveolar bone height and density (r = 0.74; P <0.05; Spearman). BMM+SIM preserved the most interproximal bone height (P <0.01), increased ridge width and bone density (P <0.01), enhanced 7-day prostaglandin E2 (P <0.01), and reduced 28-day inflammation density (P <0.05). The standard defect used in the current study paralleled human postextraction alveolar BL. Defect grafting, especially BMM+SIM, reduced inflammation and preserved bone.
Agay, Diane; Scherthan, Harry; Forcheron, Fabien; Grenier, Nancy; Hérodin, Francis; Meineke, Viktor; Drouet, Michel
Cutaneous radiation syndrome (CRS) is the delayed consequence of localized skin exposure to high doses of ionizing radiation. Recent grafting of three ionizing radiation-burned patients has suggested the benefit of local bone marrow mesenchymal stem cell (MSC) injection in favor of wound healing and pain control. Here, we have developed a new minipig model of severe CRS to study underlying mechanisms of this cell therapy approach. Göttingen minipigs were locally irradiated using a (60)Co gamma source as follows: ungrafted 50 and 60 Gy (n = 4) and grafted 50 and 60 Gy (n = 3). Bone marrow MSCs were cultured in minimum essential medium with 10% fetal calf serum and basic fibroblast growth factor (2 ng.mL(-1)). Autologous MSCs were intradermally injected twice or three times from days 27 to 96 (range, 99-128.5 × 10(6) MSCs per injection). All animals exhibited a clinical evolution similar to humans after a latency phase of several weeks, including early erythema, hair loss, and dry/moist desquamation followed by necrosis during 81 to 222 days post-ionizing radiation. Skin damage in higher exposed animals appeared slightly earlier. Immunohistology revealed severe skin damage in all animals and rhabdomyolysis in the muscle tissue below the entry area, with the latter being more severe in controls. In grafted animals, MSCs led to local accumulation of lymphocytes at the dermis/subcutis border and improved vascularization. This study establishes a new minipig model that is close to human and allows development of stem cell therapy strategies that can be applied in treatment of human radiation burns. Copyright © 2010 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.
Donadoni, Francesca; Pichardo-Almarza, Cesar; Bartlett, Matthew; Dardik, Alan; Homer-Vanniasinkam, Shervanthi; Díaz-Zuccarini, Vanessa
Neointimal hyperplasia is amongst the major causes of failure of bypass grafts. The disease progression varies from patient to patient due to a range of different factors. In this paper, a mathematical model will be used to understand neointimal hyperplasia in individual patients, combining information from biological experiments and patient-specific data to analyze some aspects of the disease, particularly with regard to mechanical stimuli due to shear stresses on the vessel wall. By combining a biochemical model of cell growth and a patient-specific computational fluid dynamics analysis of blood flow in the lumen, remodeling of the blood vessel is studied by means of a novel computational framework. The framework was used to analyze two vein graft bypasses from one patient: a femoro-popliteal and a femoro-distal bypass. The remodeling of the vessel wall and analysis of the flow for each case was then compared to clinical data and discussed as a potential tool for a better understanding of the disease. Simulation results from this first computational approach showed an overall agreement on the locations of hyperplasia in these patients and demonstrated the potential of using new integrative modeling tools to understand disease progression. PMID:28458640
Zaccaria, R; Teti, G; Mecule, A; Torlone, N; Valeri, M; Adorno, D
Since 2013, the regional network of transplantation centers "LAZIO TRANSPLANT" have adopted a new, mixed system for the allocation of liver grafts. The organs from donors aged <65 are assigned to patients with higher Model for End-stage Liver Disease (MELD) scores on a common regional waiting list, whereas those from donors aged >65 are allocated to patients with higher MELD scores on a specific local waiting list (LWL) at each center, on a rotational basis. The new mixed allocation model grants a more rational allocation of the "standard" organs to the patients with the actual worst MELD score in the entire region, avoiding the possibility that a patient in relatively better clinical condition might be transplanted before a more severely ill patient on another center's waiting list. Nonstandard organs, presenting slightly increased transplant risks, are still allocated on a rotational basis among the different transplant centers, ensuring them the possibility to select, on the basis of a global clinical risk evaluation, those patients in their LWL whose MELD score would not grant any possibility to compete for the "standard" organ allocation. The application of the new model had no negative impact on the overall number of transplants performed or on the global list-satisfaction percentages, but has slightly improved the cumulative mortality of the patients in the waiting list, granting to the clinically worst patients a prompt graft allocation, independent of the local center belonging. Copyright © 2015 Elsevier Inc. All rights reserved.
Ryssel, H; Gazyakan, E; Germann, G; Ohlbauer, M
The application of dermal substitutes in deep partial and full-thickness burn wounds in a two-stage procedure prior to skin grafting has become increasingly popular. Synchronous application of dermal substitutes and skin graft has not yet been established as a standard procedure. In a consecutive study 20 wounds in 10 patients with severe burns (age 49.5+/-16.2 years; TBSA 45.6+/-14.5%) were treated with either simultaneous transplantation of Matriderm, a bovine based collagen I, III, V and elastin hydrolysate based dermal substitute and split-thickness skin grafting (STSG), or STSG alone after appropriate excision of the burn wound. The study was designed as a prospective intra-individual comparative study. After 1 week all wounds were assessed for the percentage of autograft survival. Autograft survival was not altered by simultaneous application of a dermal matrix (p=0.015). Skin elasticity was measured after 3-4 months with the Vancouver Burn Skin Score (VBSS). The VBSS demonstrated a significant increase of elasticity in the group with dermal substitutes (p=0.04) as compared with non-substituted wounds for sheet autograft, but not for meshed autograft (p=0.24). From this pilot study it can be concluded that simultaneous application of a dermal matrix is safe and feasible, yielding significantly better results with respect to skin elasticity. Skin elasticity was considerably improved by the collagen/elastin dermal substitute Matriderm in combination with sheet autograft.
Ohyama, Takashiro; Kubo, Yoshichika; Iwata, Hiroo; Taki, Waro
An interbody fusion cage has been introduced for cervical anterior interbody fusion. Autogenetic bone is packed into the cage to increase the rate of union between adjacent vertebral bodies. Thus, donor site-related complications can still occur. In this study a synthetic ceramic, beta-tricalcium phosphate (TCP), was examined as a substitute for autograft bone in a canine lumbar spine model. In 12 dogs L-1 to L-4 vertebrae were exposed via a posterolateral approach, and discectomy and placement of interbody fusion cages were performed at two intervertebral disc spaces. One cage was filled with autograft (Group A) and the other with TCP (Group B). The lumbar spine was excised at 16 weeks postsurgery, and biomechanical, microradiographic, and histological examinations were performed. Both the microradiographic and histological examinations revealed that fusion occurred in five (41.7%) of 12 operations performed in Group A and in six (50%) of 12 operations performed in Group B. The mean percentage of trabecular bone area in the cages was 54.6% in Group A and 53.8% in Group B. There were no significant intergroup differences in functional unit stiffness. Good histological and biomechanical results were obtained for TCP-filled interbody fusion cages. The results were comparable with those obtained using autograft-filled cages, suggesting that there is no need to harvest iliac bone or to use allo- or xenografts to increase the interlocking strength between the cage and vertebral bone to achieve anterior cervical interbody fusion.
Schackel, Stefanie; Pauly, Marie-Christin; Piroth, Tobias; Nikkhah, Guido; Döbrössy, Máté D
Neural cell replacement therapy using fetal striatal cells has provided evidence of disease modification in clinical trials in Huntington's disease (HD) patients, although the results have been inconsistent. One of the contributing factors to the variable outcome could be the different capacity of transplanted cells derived from the primordial striatum to proliferate and maturate into striatal projection neurons. Based on the rodent lesion model of HD, the current study investigated how intrastriatal-striatal grafts from variable aged donors develop in vivo and how they influence functional recovery. Young adult female Sprague-Dawley rats were lesioned unilaterally in the dorso-striatum with quinolinic acid (0.12 M) and transplanted 14 days later with single cell suspension grafts equivalent of one whole ganglionic eminence (WGE) from donors of embryonic developmental age E13, E14, or E15; animals with or without striatal lesion served as controls. All animals were tested on the Cylinder and the Corridor tests, as well as on apomorphine-induced rotation at baseline, post-lesion/pre-grafting, and at 6 and 10 weeks post-grafting. A week prior to perfusion, a sub-group in each grafted group received fluorogold injections into the ipsilateral globus pallidus to study graft efferent projections. In summary, the data demonstrates that the age of the embryonic donor tissue has an impact on both the graft mediated functional recovery, and on the in vivo cellular composition of the striatal transplant. E13 tissue grafts gave the best overall outcome indicating that WGE from different donor ages have different potential to promote functional recovery. Understanding the stages and process in rodent striatal development could improve tissue selection in clinical trials of cell therapy in HD. Copyright © 2013 Elsevier B.V. All rights reserved.
Cookson, Sarah Jane; Ollat, Nathalie
Grafting is widely used in the agriculture of fruit-bearing crops; rootstocks are known to confer differences in scion biomass in addition to improving other traits of agricultural interest. However, little is known about the effect of rootstocks on scion gene expression. The objective of this study was to determine whether hetero-grafting the grapevine variety Vitis vinifera cv. 'Cabernet Sauvignon N' with two different rootstocks alters gene expression in the shoot apex in comparison to the auto-grafted control. Cabernet Sauvignon was hetero-grafted with two commercial rootstock genotypes and auto-grafted with itself. Vigor was quantified by measurements of root, stem, leaf and trunk biomass. Gene expression profiling was done using a whole genome grapevine microarray; four pools of five shoot apex samples were harvested 4 months after grafting for each scion/rootstock combination. The rootstocks increased stem biomass or conferred increased vigor by the end of the first growth cycle. Globally hetero-grafting two different genotypes together triggered an increase in shoot apex gene expression; however no genes were differentially expressed between the two hetero-grafts. The functional categories related to DNA, chromatin structure, histones, flavonoids and leucine rich repeat containing receptor kinases were the most enriched in the up-regulated genes in the shoot apex of hetero-grafted plants. The choice of rootstock genotype had little effect on the gene expression in the shoot apex; this could suggest that auto- and hetero-grafting was the major factor regulating gene expression.
Loth, F; Jones, S A; Giddens, D P; Bassiouny, H S; Glagov, S; Zarins, C K
The flow field inside a model of a polytetrafluorethylene (PTFE) canine artery end-to-side bypass graft was studied under steady flow conditions using laser-Doppler anemometry. The anatomically realistic in vitro model was constructed to incorporate the major geometric features of the in vivo canine anastomosis geometry, most notably a larger graft than host artery diameter. The velocity measurements at Reynolds number 208, based on the host artery diameter, show the flow field to be three dimensional in nature. The wall shear stress distribution, computed from the near-wall velocity gradients, reveals a relatively low wall shear stress region on the wall opposite to the graft near the stagnation point approximately one artery diameter in axial length at the midplane. This low wall shear stress region extends to the sidewalls, suture lines, and along the PTFE graft where its axial length at the midplane is more than two artery diameters. The velocity distribution inside the graft model presented here provides a data set well suited for validation of numerical solutions on a model of this type.
Histological Evaluation of Hydroxyapatite Granules with and without Platelet-Rich Plasma versus an Autologous Bone Graft: Comparative study of biomaterials used for spinal fusion in a New Zealand white rabbit model.
Zakaria, Zamzuri; Seman, Che N Z C; Buyong, Zunariah; Sharifudin, Mohd A; Zulkifly, Ahmad H; Khalid, Kamarul A
Hydroxyapatite (HA) has osteoconductive properties and is widely used as a bone graft substitute. Platelet-rich plasma (PRP) is an autologous product with osteoinductive effects. Hypothetically, a combination of both would augment the bone formation effect of HA and widen its application in spinal fusion surgeries. This study aimed to compare new bone formation with HA granules alone and in combination with PRP versus an autologous bone graft during a lumbar intertransverse process spinal fusion. A total of 16 adult New Zealand white rabbits underwent single-level bilateral intertransverse process fusion at the L5-L6 vertebrae. One side of the spine received either HA granules alone or a combination of HA granules and PRP, while the contralateral side received an autologous bone graft. Four animals each from the HA group and the HA plus PRP group versus the autograft group were assessed either at six or 16 weeks by undecalcified histology and histomorphometry. The mean percentage of new bone areas over the corresponding fusion masses were compared between groups. No significant difference in new bone formation was observed between the HA and HA plus PRP groups at six or 16 weeks. The autograft group had significantly more new bone formation at six and 16 weeks (P = 0.004 and <0.001, respectively). An autologous bone graft remains superior to HA granules, with or without PRP. HA granules demonstrated an excellent osteoconductive scaffold but had poor biodegradability. While PRP enhances the properties of HA granules, these biomaterials do not have a synergistic effect.
Zhou, Xiang; He, Bo; Zhu, Zhaowei; He, Xinhua; Zheng, Canbin; Xu, Jian; Jiang, Li; Gu, Liqiang; Zhu, Jiakai; Zhu, Qingtang; Liu, Xiaolin
Acellular nerve grafts are good candidates for nerve repair, but the clinical outcome of grafting is not always satisfactory. We investigated whether etifoxine could enhance nerve regeneration. Seventy-two Sprague-Dawley rats were divided into 3 groups: (1) autograft; (2) acellular nerve graft; and (3) acellular nerve graft plus etifoxine. Histological and electrophysiological examinations were performed to evaluate the efficacy of nerve regeneration. Walking-track analysis was used to examine functional recovery. Quantitative polymerase chain reaction was used to evaluate changes in mRNA level. Etifoxine: (i) increased expression of neurofilaments in regenerated axons; (ii) improved sciatic nerve regeneration measured by histological examination; (iii) increased nerve conduction velocity; (iv) improved walking behavior as measured by footprint analysis; and (v) boosted expression of neurotrophins. These results show that etifoxine can enhance peripheral nerve regeneration across large nerve gaps repaired by acellular nerve grafts by increasing expression of neurotrophins. Copyright © 2013 Wiley Periodicals, Inc.
Huo, Yunlong; Luo, Tong; Guccione, Julius M.; Teague, Shawn D.; Tan, Wenchang; Navia, José A.; Kassab, Ghassan S.
It is well known that flow patterns at the anastomosis of coronary artery bypass graft (CABG) are complex and may affect the long-term patency. Various attempts at optimal designs of anastomosis have not improved long-term patency. Here, we hypothesize that mild anastomotic stenosis (area stenosis of about 40–60%) may be adaptive to enhance the hemodynamic conditions, which may contribute to slower progression of atherosclerosis. We further hypothesize that proximal/distal sites to the stenosis have converse changes that may be a risk factor for the diffuse expansion of atherosclerosis from the site of stenosis. Twelve (12) patient-specific models with various stenotic degrees were extracted from computed tomography images using a validated segmentation software package. A 3-D finite element model was used to compute flow patterns including wall shear stress (WSS) and its spatial and temporal gradients (WSS gradient, WSSG, and oscillatory shear index, OSI). The flow simulations showed that mild anastomotic stenosis significantly increased WSS (>15 dynes⋅cm−2) and decreased OSI (<0.02) to result in a more uniform distribution of hemodynamic parameters inside anastomosis albeit proximal/distal sites to the stenosis have a decrease of WSS (<4 dynes⋅cm−2). These findings have significant implications for graft adaptation and long-term patency. PMID:24058488
Huo, Yunlong; Luo, Tong; Guccione, Julius M; Teague, Shawn D; Tan, Wenchang; Navia, José A; Kassab, Ghassan S
It is well known that flow patterns at the anastomosis of coronary artery bypass graft (CABG) are complex and may affect the long-term patency. Various attempts at optimal designs of anastomosis have not improved long-term patency. Here, we hypothesize that mild anastomotic stenosis (area stenosis of about 40-60%) may be adaptive to enhance the hemodynamic conditions, which may contribute to slower progression of atherosclerosis. We further hypothesize that proximal/distal sites to the stenosis have converse changes that may be a risk factor for the diffuse expansion of atherosclerosis from the site of stenosis. Twelve (12) patient-specific models with various stenotic degrees were extracted from computed tomography images using a validated segmentation software package. A 3-D finite element model was used to compute flow patterns including wall shear stress (WSS) and its spatial and temporal gradients (WSS gradient, WSSG, and oscillatory shear index, OSI). The flow simulations showed that mild anastomotic stenosis significantly increased WSS (>15 dynes · cm(-2)) and decreased OSI (<0.02) to result in a more uniform distribution of hemodynamic parameters inside anastomosis albeit proximal/distal sites to the stenosis have a decrease of WSS (<4 dynes · cm(-2)). These findings have significant implications for graft adaptation and long-term patency.
Ito, M; Shizuru, J A
It is known that an important curative benefit of allogeneic bone marrow transplantation (BAMT) in the treatment of hematolymphoid malignancies is a graft-vs.-tumor (GVT) effect. GVT activity has been attributed to mature immune cells contained within the graft because T-cell depletion of bone marrow results in increased rates of disease relapse post-transplantation. We previously demonstrated successful engraftment of highly purified hematopoietic stem cells (HSCs) transplanted across major histocompatibility complex (MHC) barriers in mice. In the present study, we have developed a preclinical model of allogeneic HSC transplantation into lymphoma-inoculated mice, allowing us to directly test whether purified HSCs have measurable GVT activity. We then performed cotransfer studies of HSCs with purified immune cells to identify which population(s) confers tumor protection and the mechanism by which such cells suppress tumor growth. MHC-mismatched donor-recipient combinations were studied. All of the GVT activity was contained in the CD8+ cell fraction and, at the doses of CD8+ cells tested, tumor protection was separable from acute graft-vs.-host disease (aGVHD). Although there appears to be no functional difference between BM- and splenic-derived CDS8+ cells with regard to GVT activity without aGVHD, this was not the case for purified CD3+ cells. CD3+ cells derived from BM were tumor protective, whereas transplantation of equivalent doses of CD3+ cells purified from spleen resulted in lethal GVHD. The mechanism by which the GVT-conferring cells protect recipient mice from tumors was studied using immune defective mice as donors. We found that an intact pathway of perforin-dependent cytolysis, as well as an intact Fas-ligand pathway, is required in order to exert maximal anti-tumor activity.
Walters, Brian L.; Hobart, Sarah; Porter, David; Hogan, Daniel E.; McHugh, Malachy P.; Bedford, Benjamin B.; Nicholas, Stephen J.; Klein, Devon; Harousseau, Kendall
Objectives: Donor site morbidity in the form of anterior knee pain is a frequent complication after bone-patellar tendon-bone (BPTB) autograft ACL reconstruction. The purpose of this Level I study was to examine the effect of the intraoperative administration of platelet-rich plasma on post operative knee pain and patellar defect healing. Methods: Fifty-nine patients (29±12 y/o) undergoing BPTB ACL reconstruction and eligible to enter the study, were randomized to the treatment (PRP; n=31) or non treatment (sham n=28) arms of the study just prior to surgery. In either case, 10 cc of venous blood was drawn prior to the induction of anesthesia and either discarded (sham) or processed (PRP) for preparation of a PRP gel to be later mixed with donor site bone chips and inserted into the patellar defect. At 12 weeks and 6 months after surgery, patients completed IKDC forms and VAS pain scores for ADLs and kneeling (0-10 scale). Healing indices at the donor site were assessed by MRI at 6 months and included the following measurements taken from axial sequences: AP tendon dimensions at the level of the superior tibial cortex, roof of the intercondylar notch and width at the largest patella graft deficit. Mixed model ANOVA was used to assess the effect of PRP on patient symptoms and MRI indices of donor site healing. The primary dependent variable was VAS kneeling pain. It was estimated that with 25 patients per group there would be 80% power to detect a 1.5-point difference in kneeling pain between treatments at P<0.05. A between group difference of 1.5-points in VAS for kneeling pain was deemed to represent a clinically relevant difference. Results: VAS Kneeling Pain at 12 weeks tended to be lower in the PRP versus placebo group (4.5±3.6 vs. 6.2±2.4, P=0.051) but no difference was apparent at 6 months (3.7±3.2 vs. 4.4±2.9, P=0.41). Kneeling pain decreased from 12 weeks to 6 months (P<0.001) with a trend for a greater decrease in the placebo group (Time by Treatment P
ZHANG, YONG-GUANG; SHENG, QING-SONG; WANG, ZHI-JUN; LV, LI; ZHAO, WEI; CHEN, JIAN-MEI; XU, HAO
Despite the application of nerve grafts and considerable microsurgical innovations, the functional recovery across a long peripheral nerve gap is generally partial and unsatisfactory. Thus, additional strategies are required to improve nerve regeneration across long nerve gaps. Hydrogen possesses antioxidant and anti-apoptotic properties, which could be neuroprotective in the treatment of peripheral nerve injury; however, such a possibility has not been experimentally tested in vivo. The aim of the present study was to investigate the effectiveness of hydrogen-rich saline in promoting nerve regeneration after 10-mm sciatic nerve autografting in rats. The rats were randomly divided into two groups and intraperitoneally administered a daily regimen of 5 ml/kg hydrogen-rich or normal saline. Axonal regeneration and functional recovery were assessed through a combination of behavioral analyses, electrophysiological evaluations, Fluoro-Gold™ retrograde tracings and histomorphological observations. The data showed that rats receiving hydrogen-rich saline achieved better axonal regeneration and functional recovery than those receiving normal saline. These findings indicated that hydrogen-rich saline promotes nerve regeneration across long gaps, suggesting that hydrogen-rich saline could be used as a neuroprotective agent for peripheral nerve injury therapy. PMID:26622383
Hamed Kassem Abdelaal, Ahmed; Yamamoto, Norio; Hayashi, Katsuhiro; Takeuchi, Akihiko; Miwa, Shinji; Tsuchiya, Hiroyuki
Limb salvage surgery has become the standard treatment for malignant primary bone tumors in the extremities. Limb salvage represents a challenge in skeletally immature patients. Several treatment options are available for limb reconstruction after tumor resection in children. We report our results using the technique of epiphyseal sparing and reconstruction with frozen autograft bone in 18 children. The mean follow-up period for the all patients included in this study is 72 ± 26 m. Eight patients remained disease-free, seven patients lived with no evidence of disease, two were alive but with disease, and one patient died of the disease. Five- and ten-year rates of survival were 94.4%. Graft survival at 5 and 10 years was 94.4%. Functional outcome using the Enneking scale was excellent in 17 patients (94.4%) and poor in one patient (5.5%). Complications include 2 nonunions, 2 fractures, 2 deep infections, 1 soft tissue recurrence, and leg length discrepancy in 7 cases. This technique is a good reconstructive choice in a child with a nonosteolytic primary or secondary bone tumor, responsive to chemotherapy, without involvement of the articular cartilage. It is a straight forward, effective, and biological technique, which affords immediate mobilization of joints and possible cryoimmune effects, with excellent long term functional outcome and less complication. PMID:27034614
Levy, David M.; Vakhshori, Venus; DeWald, Christopher J.
This case report presents two patients who underwent fibular strut grafting for complex revisions of previous lumbar spine arthrodeses. A case review of the Electronic Medical Record at the index institution was performed to evaluate the timeline of events of the two patients who underwent fibular strut grafting for complex revisions of previous lumbar spine arthrodesis, including imaging studies, progress notes, and laboratory results. One patient had developed chronic L3 vertebral body osteomyelitis from a prior fibular allograft and instrumentation placed for a traumatic burst fracture. The second patient had a severe scoliosis recalcitrant to prior arthrodeses in the context of Marfan syndrome and a persistent L4-5 pseudarthrosis. Both patients underwent free vascularized fibular autograft revision arthrodeses. At most recent long-term follow-up, both patients had improved clinically and neither had required further revision. The use of free vascularized fibular grafting is an excellent option for a variety of spinal indications, and these two reports indicate that the technology may have an indication for use after multiple failed surgeries for osteomyelitis or correction of a multi-level large spinal deformity secondary to Marfan syndrome. PMID:26512280
Lempainen, Lasse; Sarimo, Janne; Orava, Sakari
Hamstring injuries are common, especially among athletes. A complete rupture of the proximal hamstring muscles requires surgical intervention. In this report we describe a reconstruction method for a complete proximal hamstring rupture using fascia lata autograft augmentation in addition to suture anchors. This method can be advocated in cases in which the primary repair has failed or in chronic injuries where a large defect between the distally retracted tendons and the ischial tuberosity prevents anatomic reinsertion. In our technique, a muscle-tendon flap is first created from the retracted tendon stump, turned proximally, and fixed to the ischial tuberosity by suture anchors. The fascia lata graft is then fixed from the midpart to the ischial tuberosity via the same sutures. The other sleeve of the graft is folded on the ventral side of the ruptured tendon stump and fixed by use of absorbable sutures. Then the other sleeve is folded on the dorsal side and fixed in the same manner. Finally, the fixation can still be reinforced with additional absorbable sutures passing through both sleeves of the graft, as well as the muscle-tendon bridge and the tendon stump.
Rodriguez-Pallares, Jannette; Rodriguez-Perez, Ana I; Muñoz, Ana; Parga, Juan A; Toledo-Aral, Juan J; Labandeira-Garcia, Jose L
In models of Parkinson's disease (PD), Rho kinase (ROCK) inhibitors have antiapoptotic and axon-stabilizing effects on damaged neurons, decrease the neuroinflammatory response, and protect against dopaminergic neuron death and axonal retraction. ROCK inhibitors have also shown protective effects against apoptosis induced by handling and dissociation of several types of stem cells. However, the effect of ROCK inhibitors on dopaminergic cell grafts has not been investigated. In the present study, treatment of dopaminergic cell suspension with ROCK inhibitors yielded significant decreases in the number of surviving dopaminergic neurons, in the density of graft-derived dopaminergic fibers, and in graft vascularization. Dopaminergic neuron death also markedly increased in primary mesencephalic cultures when the cell suspension was treated with ROCK inhibitors before plating, which suggests that decreased angiogenesis is not the only factor leading to cell death in grafts. Interestingly, treatment of the host 6-hydroxydopamine-lesioned rats with ROCK inhibitors induced a slight, nonsignificant increase in the number of surviving neurons, as well as marked increases in the density of graft-derived dopaminergic fibers and the size of the striatal reinnervated area. The study findings discourage treatment of cell suspensions before grafting. However, treatment of the host induces a marked increase in graft-derived striatal reinnervation. Because ROCK inhibitors have also exerted neuroprotective effects in several models of PD, treatment of the host with ROCK inhibitors, currently used against vascular diseases in clinical practice, before and after grafting may be a useful adjuvant to cell therapy in PD. Cell-replacement therapy is one promising therapy for Parkinson's disease (PD). However, many questions must be addressed before widespread application. Rho kinase (ROCK) inhibitors have been used in a variety of applications associated with stem cell research and may be an
Rodriguez-Pallares, Jannette; Rodriguez-Perez, Ana I.; Muñoz, Ana; Parga, Juan A.; Toledo-Aral, Juan J.
In models of Parkinson’s disease (PD), Rho kinase (ROCK) inhibitors have antiapoptotic and axon-stabilizing effects on damaged neurons, decrease the neuroinflammatory response, and protect against dopaminergic neuron death and axonal retraction. ROCK inhibitors have also shown protective effects against apoptosis induced by handling and dissociation of several types of stem cells. However, the effect of ROCK inhibitors on dopaminergic cell grafts has not been investigated. In the present study, treatment of dopaminergic cell suspension with ROCK inhibitors yielded significant decreases in the number of surviving dopaminergic neurons, in the density of graft-derived dopaminergic fibers, and in graft vascularization. Dopaminergic neuron death also markedly increased in primary mesencephalic cultures when the cell suspension was treated with ROCK inhibitors before plating, which suggests that decreased angiogenesis is not the only factor leading to cell death in grafts. Interestingly, treatment of the host 6-hydroxydopamine-lesioned rats with ROCK inhibitors induced a slight, nonsignificant increase in the number of surviving neurons, as well as marked increases in the density of graft-derived dopaminergic fibers and the size of the striatal reinnervated area. The study findings discourage treatment of cell suspensions before grafting. However, treatment of the host induces a marked increase in graft-derived striatal reinnervation. Because ROCK inhibitors have also exerted neuroprotective effects in several models of PD, treatment of the host with ROCK inhibitors, currently used against vascular diseases in clinical practice, before and after grafting may be a useful adjuvant to cell therapy in PD. Significance Cell-replacement therapy is one promising therapy for Parkinson's disease (PD). However, many questions must be addressed before widespread application. Rho kinase (ROCK) inhibitors have been used in a variety of applications associated with stem cell
Liu, Jiaming; Xiong, Xu; Long, Xinhua; Shu, Yong; Huang, Shanhu; Yang, Dong; Liu, Zhili
Study design: A prospective study and a technical note. Background: Autograft is considered to be the gold standard in achieving optimal fusion in anterior cervical discectomy and fusion (ACDF). In patients with combined postero-anterior cervical procedure, whether the cervical laminae harvested from laminectomy can be used as astructural bone graft in ACDF? Few studies have reported about this. Objective: To describe the clinical and radio graphic outcomes in patients undergoing combined postero-anterior cervical surgery using autologous laminae as bone graft in ACDF. Methods: Twenty-two patients (13 males, 9 females) with cervical spondylotic myelopathy underwent one-level combined postero-anterior procedure with anterior plate fixation from January 2010 to January 2014. All the patients received computed tomography scan before surgery and the heights of the target laminae and the middle intervertebral space were measured. Then, patients underwent combined postero-anterior surgery with laminectomy and ACDF. The structural laminae obtained from laminectomy were used as bone graft in ACDF. The clinical and radiographic outcomes of the patients were analyzed and the effectiveness and safety of the surgery was evaluated. Results: The average heights of the target laminae and the middle intervertebral space were 11.18±1.05 mm and 5.75±0.58 mm, respectively. Statistical significant difference was found between the heights of the laminae and the space (P<0.001). The mean operative time was 192±37 minutes with an average blood loss volume of 235±71 ml. All patients were followed up and the average follow-up period was 17.5±3.1 months. All patients had immediate postoperative resolution of symptoms and radiographic evidence of solid fusion 3 months later. Postoperatively, excellent results were reported in 62.5%, good results in 18.8%, and fair results in 18.8% of the patients according to Odom’s criteria. Visual analog scale score of the neck and extremities pain
Karim, Mohammed N; Reid, Christopher M; Cochrane, Andrew; Tran, Lavinia; Alramadan, Mohammed; Hossain, Mohammed N; Billah, Baki
Many risk prediction models are currently in use for predicting short-term mortality following coronary artery bypass graft (CABG) surgery. This review critically appraised the methods that were used for developing these models to assess their applicability in current practice setting as well as for the necessity of up-gradation. Medline via Ovid was searched for articles published between 1946 and 2016 and EMBASE via Ovid between 1974 and 2016 to identify risk prediction models for CABG. Article selection and data extraction was conducted using the CHARMS checklist for review of prediction model studies. Association between model development methods and model's discrimination was assessed using Kruskal-Wallis one-way analysis of variance and Mann-Whitney U-test. A total of 53 risk prediction models for short-term mortality following CABG were identified. The review found a wide variation in development methodology of risk prediction models in the field. Ambiguous predictor and outcome definition, sub-optimum sample size, inappropriate handling of missing data and inefficient predictor selection technique are major issues identified in the review. Quantitative synthesis in the review showed "missing value imputation" and "adopting machine learning algorithms" may result in better discrimination power of the models. There are aspects in current risk modeling, where there is room for improvement to reflect current clinical practice. Future risk modelling needs to adopt a standardized approach to defining both outcome and predictor variables, rational treatment of missing data and robust statistical techniques to enhance performance of the mortality risk prediction.
Matsumura, Hajime; Harunari, Nobuyuki; Ikeda, Hiroto
On June 27, 2015, a flammable starch-based powder exploded at Formosa Fun Coast in Taipei, Taiwan, injuring 499 people, and more than 200 people were in critical condition with severe burns. Although a cultured epidermal autograft (CEA) was not approved or used in clinical practice, the Taiwan Food and Drug Administration requested a Japanese CEA manufacturer to donate CEA for the burn victims as part of international medical assistance. The authors cooperated in this project and participated in the patient selection, wound bed management for CEA, and technical assistance for CEA use. Here, we provide an overview of the project. Nine patients were enrolled, and two patients were excluded from the skin biopsy; seven skin biopsies were collected approximately 1 month after the disaster. The average TBSA% burned was 81.0%, and the mean age was 20.1 years. CEA was grafted in five patients; wound closure had been obtained in one patient, and one patient was severely ill at the time of grafting. The CEA was combined with a wide split auto mesh graft or patch graft. The mean re-epithelization rate at 4 weeks after the grafting was 84.2% by patient, and all of the patients survived. Although this project had many obstacles to overcome, CEA grafting was successful and contributed to wound closure and survival.
Larrañaga, Aitor; Guay-Bégin, Andrée-Anne; Chevallier, Pascale; Sabbatier, Gad; Fernández, Jorge; Laroche, Gaétan; Sarasua, Jose-Ramon
Thermoplastic biodegradable polymers displaying elastomeric behavior and mechanical consistency are greatly appreciated for the regeneration of soft tissues and for various medical devices. However, while the selection of a suitable base material is determined by mechanical and biodegradation considerations, it is the surface properties of the biomaterial that are responsible for the biological response. In order to improve the interaction with cells and modulate their behavior, biologically active molecules can be incorporated onto the surface of the material. With this aim, the surface of a lactide and caprolactone based biodegradable elastomeric terpolymer was modified in two stages. First, the biodegradable polymer surface was aminated by atmospheric pressure plasma treatment and second a crosslinker was grafted in order to covalently bind the biomolecule. In this study, albumin was used as a model protein. According to X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM), albumin was efficiently immobilized on the surface of the terpolymer, the degree of albumin surface coverage (ΓBSA) reached ~35%. Moreover, gel permeation chromatography (GPC) studies showed that the hydrolytic degradation kinetic of the synthesized polymer was slightly delayed when albumin was grafted. However, the degradation process in the bulk of the material was unaffected, as demonstrated by Fourier transform infrared (FTIR) analyses. Furthermore, XPS analyses showed that the protein was still present on the surface after 28 days of degradation, meaning that the surface modification was stable, and that there had been enough time for the biological environment to interact with the modified material. PMID:24509417
Mbanga, Badel L.; Yashin, Victor V.; Holten-Andersen, Niels; Balazs, Anna C.
Inspired by the remarkable mechanical properties of such biological structures as mussel adhesive fibers, we use 3D computational modeling to study the behavior of heterogeneous polymer-grafted nanoparticle (PGN) networks under tensile deformation. The building block of a PGN network is a nanoparticle with grafted polymer chains whose free ends' reactive groups can form both permanent and labile bonds with the end chains on the nearby particles. The tunable behavior of cross-linked PGN networks makes them excellent candidates for designing novel materials with enhanced mechanical properties. Here, we consider the PGN networks having the core-shell structures, in which the type and strength of the inter-particle bonds in the outer shell differ from those in the core. Using the computer simulations, we obtain and compare the ultimate tensile properties (strength, toughness, ductility) and the strain recovery properties for the uniform samples and various core-shell structures. We demonstrate that the core-shell structures could be designed to obtain highly resilient self-healing materials
Stubbs, D; Deakin, M; Chapman-Sheath, P; Bruce, W; Debes, J; Gillies, R M; Walsh, W R
Calcium sulfate as a bone graft substitute is rapidly resorbed in vivo releasing calcium ions but fails to provide long-term three-dimensional framework to support osteoconduction. The setting properties of calcium sulfate however allow it to be applied in a slurry form making it easier to handle and apply in different situations. This study examines the in vivo response of calcium sulfate alone and as a carrier for a coralline hydroxyapatite in an established bilateral corticocancellous defect model in rabbits. Defects were filled flush to the anterior cortex with a resorbable porous ceramic alone and in combination with calcium sulfate slurry, calcium sulfate slurry alone or calcium sulfate pellets and examined at time points up to 52 weeks. Specimens where assessed using Faxitron X-ray, light and electron microscopy. Calcium sulfate in either slurry or pellet form does indeed support new bone formation alone however, complete filling of the bone defect is not observed. Calcium sulfate in slurry form does however improve the surgical handling of particulate bone graft substitutes such as Pro Osteon 200 R, which remained as an osteoconductive scaffold for up to 52 weeks and may have played an important role in the ultimate closure of the cortical windows.
Siemionow, Maria; Ulusal, Betul G; Ozmen, Selahattin; Ulusal, Ali E; Ozer, Kagan
In this study, we introduce a new model for vascularized skin and bone marrow transplantation. Twenty-five Lewis (RT1(1)) rats were studied. Anatomic dissection studies were performed in 5 animals. In the experimental group, 10 isograft transplantations were performed between Lewis rats. Combined groin skin and femoral bone flaps were transplanted based on the femoral artery and vein. Transplants were evaluated on a daily basis. All flaps survived without problems over 100 days posttransplant. The skin component remained pink and pliable, and grew new hair. Histological examination of the femoral bone (except the femoral head) revealed active hematopoiesis with a viable compact and cancellous bone components on day 100 posttransplant. This model can be applied to tolerance induction studies across the major Histocompatibility (MHC) barrier, where bone will serve as donor of stem and progenitor cells, and the skin flap will serve as a monitor of graft rejection.
Schellhammer, Frank; Haberstroh, Joerg; Wakhloo, Ajay K.; Gottschalk, Eva; Schumacher, Martin
Purpose: To evaluate different vein grafts for luminal coating of endovascular stents in normal canine arteries. Methods: Twenty-four tantalum Strecker stents were coated with either autologous (n= 10), denatured heterologous (n= 11), or denatured homologous vein grafts (n= 3). The carotid artery (n= 11) and the iliac artery (n= 13) were stented using a transfemoral approach. Angiograms were performed at days 0, 7, and 21, and months 3, 6, and 9. All grafts underwent histological examination. Results: Eight of 10 autologous vein grafts showed patency during the whole observation period of 9 months, without histological signs of inflammation. Denatured heterologous vein grafts revealed acute (n= 3), subacute (n= 5), or delayed (n= 3) vessel occlusion. Hyaloid transformation of the vein graft and lympho-plasmacellular formations were seen. Denatured homologous vein grafts showed acute vessel occlusion. Although significant inflammatory tissue response was seen, no host-versus-graft reaction was present. Conclusion: Autologous vein graft-coated stents showed good biocompatibility in canine arteries. Preparation was cumbersome and required surgical venae-sectio. Denatured vein grafts, however, were limited by inflammatory reactions.
Puschban, Zoe; Stefanova, Nadia; Nat, Roxana; Dechant, Georg; Wenning, Gregor K.
Evidence from carefully conducted open label clinical trials suggested that therapeutic benefit can be achieved by grafting fetal dopaminergic (DAergic) neurons derived from ventral mesencephalon (VM) into the denervated striatum of Parkinson's disease (PD) patients. However, two double-blind trials generated negative results reporting deleterious side effects such as prominent dyskinesias. Heterogeneous composition of VM grafts is likely to account for suboptimal clinical efficacy. We consider that gene expression patterns of the VM tissue needs to be better understood by comparing the genetic signature of the surviving and functioning grafts with the cell suspensions used for transplantation. In addition, it is crucial to assess whether the grafted cells exhibit the DAergic phenotype of adult substantia nigra pars compacta (SNpc). To investigate this further, we used a GFP reporter mouse as source of VM tissue that enabled the detection and dissection of the grafts 6 weeks post implantation. A comparative gene expression analysis of the VM cell suspension and grafts revealed that VM grafts continue to differentiate post-implantation. In addition, implanted grafts showed a mature SNpc-like molecular DAergic phenotype with similar expression levels of TH, Vmat2 and Dat. However, by comparing gene expression of the adult SNpc with dissected grafts we detected a higher expression of progenitor markers in the grafts. Finally, when compared to the VM cell suspension, post-grafting there was a higher expression of markers inherent to glia and other neuronal populations. In summary, our data highlight the dynamic development of distinctive DAergic and non-DAergic gene expression markers associated with the maturation of VM grafts in vivo. The molecular signature of VM grafts and its functional relevance should be further explored in future studies aimed at the optimization of DAergic cell therapy approaches in PD. PMID:23209667
De Cata, Angelo; Matarangolo, Angela; Inglese, Michele; Rubino, Rosa; Mazzoccoli, Gianluigi
Autoimmune diseases are characterized by an insufficiency of immune tolerance and, although treated with a number of useful drugs, may need more unconventional therapeutic strategies for their more severe presentations. Among such unconventional therapeutic approaches, stem cell autograft and allograft have been used, with the aim of stimulating disease remission by modifying the pathogenic mechanisms that induce anomalous responses against self-antigens. Autologous transplantation is performed with the purpose of retuning autoimmune cells, whereas allogeneic transplantation is performed with the purpose of replacing anomalous immune effectors and mediators. In this article, we comprehensively review up-to-date information on the autoimmune diseases for which the transplantation of stem cells is indicated.
Chahla, Jorge; Soares, Eduardo; Bhatia, Sanjeev; Mitchell, Justin J; Philippon, Marc J
The dynamic function of the acetabular labrum makes it an important structure for both hip stability and motion. Because of this, injuries to the labrum can cause significant dysfunction, leading to altered hip kinematics. Labral repair is the gold standard for symptomatic labral tears to keep as much labral tissue as possible; however, in cases where the labrum has been injured to such a degree that it is either deficient or repair is not possible, arthroscopic labral reconstruction is preferred. This article describes our preferred approach for reconstruction of the acetabular labrum using iliotibial band autograft.
Kitay, Alison; Waters, Peter M; Bae, Donald S
Post-traumatic osteonecrosis of the metacarpal head is a challenging problem, particularly in younger patients in whom arthroplasty may not be a durable option. Although several osteochondral reconstructive options have been proposed, some are associated with considerable donor site morbidity and/or require the use of internal fixation. We present an application of osteochondral autograft transplantation surgery as a treatment option for focal metacarpal head lesions. An osteochondral plug from the non-weight-bearing articular surface of the knee is transferred and press-fit to resurface a focal metacarpal head defect. The technical pearls and pitfalls are reviewed, and an illustrative case is presented.
Hong, Abigail L.; Newman, Benjamin T.; Khalid, Arbab; Teter, Olivia M.; Kobe, Elizabeth A.; Shukurova, Malika; Shinde, Rohit; Sipzner, Daniel; Pignolo, Robert J.; Udupa, Jayaram K.; Rajapakse, Chamith S.
Current methods of bone graft treatment for critical size bone defects can give way to several clinical complications such as limited available bone for autografts, non-matching bone structure, lack of strength which can compromise a patient's skeletal system, and sterilization processes that can prevent osteogenesis in the case of allografts. We intend to overcome these disadvantages by generating a patient-specific 3D printed bone graft guided by high-resolution medical imaging. Our synthetic model allows us to customize the graft for the patients' macro- and microstructure and correct any structural deficiencies in the re-meshing process. These 3D-printed models can presumptively serve as the scaffolding for human mesenchymal stem cell (hMSC) engraftment in order to facilitate bone growth. We performed highresolution CT imaging of a cadaveric human proximal femur at 0.030-mm isotropic voxels. We used these images to generate a 3D computer model that mimics bone geometry from micro to macro scale represented by STereoLithography (STL) format. These models were then reformatted to a format that can be interpreted by the 3D printer. To assess how much of the microstructure was replicated, 3D-printed models were re-imaged using micro-CT at 0.025-mm isotropic voxels and compared to original high-resolution CT images used to generate the 3D model in 32 sub-regions. We found a strong correlation between 3D-printed bone volume and volume of bone in the original images used for 3D printing (R2 = 0.97). We expect to further refine our approach with additional testing to create a viable synthetic bone graft with clinical functionality.
Chan, Queenie E; Harvey, John G; Graf, Nicole S; Godfrey, Craig; Holland, Andrew J A
One sequelae of burn injury remains the development of hypertrophic scarring. This appears more likely when the healing has been prolonged. Early excision of deep dermal burns and subsequent split skin grafting (SSG) may provide a more favorable result. The optimal timing of grafting for deeper dermal burns remains controversial. This study sought to establish evidence for the optimal grafting time using a porcine model. Five Large White female pigs were exposed to four contact burn injuries for duration of 20 seconds at 92°C. Each site was randomized to a treatment arm: dressing only as the control, SSG day 3, SSG day 14, and SSG day 21. Burn wound biopsies were obtained at days 0, 3, 14, 21, and 99 after the burn injury, together with microbiological swabs. Digital photographs were taken to assess scarring using the Vancouver scar scale. All biopsies were subject to histological and immunohistochemical analysis. Vancouver scar scale scores and histopathological analysis indicated that areas grafted on day 3 had the least fibrosis and scarring (P = 0.031). There was a strong correlation between the histological evaluation of the degree of fibrosis and α-smooth muscle actin levels (r = .60, P = .014). A greater degree of fibrosis was observed in the presence of infection (P = .028). Sites grafted on day 3 consistently exhibited the best clinical and histological scar outcome. The increased fibrosis observed in delayed grafting may have been be related to progression of burn depth and infection. These results suggest that early grafting of deep dermal burns may be preferential.
Zhou, S N; How, T V; Black, R A; Vallabhaneni, S R; McWilliams, R; Brennan, J A
The longitudinal haemodynamic force (LF) acting on a bifurcated stent graft for abdominal aortic aneurysm repair has been estimated previously using a simple one-dimensional analytical model based on the momentum equation which assumes steady flow of an inviscid fluid. Using an instrumented stent-graft model an experimental technique was developed to measure the LF under pulsatile flow conditions. The physical stent-graft model, with main trunk diameter of 30mm and limb diameters of 12 mm, was fabricated from aluminium. Strain gauges were bonded on to the main trunk to determine the longitudinal strain which is related to the LF. After calibration, the model was placed in a pulsatile flow system with 40 per cent aqueous glycerol solution as the circulating fluid. The LF was determined using a Wheatstone bridge signal-conditioning circuit. The signals were averaged over 590 cardiac cycles and saved to a personal computer for subsequent processing. The LF was strongly dependent on the pressure but less so on the flowrate. The measured forces were higher than those predicted by the simplified mathematical model by about 6-18 per cent during the cardiac cycle. The excess measured forces are due to the viscous drag and the effect of pulsatile flow. The peak measured LF in this model of 30 mm diameter may exceed the fixation force of some current clinical endovascular stent grafts.
Kreis, R W; Vloemans, A F; Hoekstra, M J; Mackie, D P; Hermans, R P
Allograft skin lyophilised in 98% glycerol is an effective overlay for widely expanded autografts. The technique was evaluated clinically on a total of 58 sandwich grafting procedures in a group of 39 patients with extensive third-degree burns. Forty-five grafting operations performed within 10 days postburn all resulted in an epithelialisation rate of at least 75% within 5 weeks. Thirty-three of these procedures achieved complete (more than 95%) wound closure. Of 13 operations performed after the 14th postburn day, ten resulted in a wound epithelialisation of at least 75%. Epithelial quality and cosmetic results were good. The mean length of hospitalisation was 56 days. One patient died from unassociated respiratory failure. The absence of allograft viability did not impair its function as an autograft overlay. The apparent attenuation of allograft antigenicity conferred by the action of 98% glycerol may have contributed to the results achieved. The process of cadaver skin preservation in 98% glycerol is simple and inexpensive.
Akashi, Yoshimasa; Oda, Tatsuya; Ohara, Yusuke; Miyamoto, Ryoichi; Hashimoto, Shinji; Enomoto, Tsuyoshi; Yamada, Keiichi; Kobayashi, Akihiko; Fukunaga, Kiyoshi; Ohkochi, Nobuhiro
Experimental data based on cell line-derived xenograft models (cell xenograft) seldom reproduce the clinical situation, and therefore we demonstrated here the superiority of a murine model involving transplantation of human pancreatic cancer tissue fragments (tumor graft), focusing on the histological features and drug delivery characteristics. Tumor pieces from 10 pancreatic cancer patients were transplanted into SCID (severe combined immunodeficient) mice. Histological characteristics of tumor grafts, including morphology, desmoplastic reaction, and vascularization, were compared with those of cell xenografts. Drug delivery was evaluated by quantifying the concentrations of injected drug, and the results were compared with its histological features. Eight of the 10 transplanted tumors successfully engrafted. Histological comparisons between tumor grafts and cell xenografts revealed the following: the amount of stroma was more (22.9% ± 11.8% vs 10.8% ± 5.4%; P < 0.05), vessel-cancer cell distance was longer (35.3 ± 39.0 vs 3.9 ± 3.1 μm; P < 0.001), and microvessel density was lower (6.8 ± 1.9 vs 10.8 ± 2.1 vessels/0.4 mm(2); P < 0.05) in tumor grafts. Drug concentrations in tumor grafts were lower than those in cell xenografts (3.3 ± 1.2 vs 6.0±0.2 μg/mL; P = 0.003), and the differences were correlated with the histological differences. Pancreatic tumor grafts better reproduce the histological nature of clinical cancer and thus provide a more realistic model that is applicable for pharmacokinetic studies.
Nezarati, Roya M.; Eifert, Michelle B.; Dempsey, David K.; Cosgriff-Hernandez, Elizabeth
Coronary artery bypass grafting (CABG) is one of the most commonly performed major surgeries in the United States. Autologous vessels such as the saphenous vein are the current gold standard for treatment; however, synthetic vascular prostheses made of expanded poly(tetrafluoroethylene) (ePTFE) or poly(ethylene terephthalate) (PET) are used when autologous vessels are unavailable. These synthetic grafts have a high failure rate in small diameter (<4 mm) applications due to rapid re-occlusion via intimal hyperplasia. Current strategies to improve clinical performance are focused on preventing intimal hyperplasia by fabricating grafts with compliance and burst pressure similar to native vessels. To this end, we have developed an electrospun vascular graft from segmented polyurethanes with tunable properties by altering material chemistry and graft microarchitecture. Relationships between polyurethane tensile properties and biomechanical properties were elucidated to select polymers with desirable properties. Graft thickness, fiber tortuosity, and fiber fusions were modulated to provide additional tools for controlling graft properties. Using a combination of these strategies, a vascular graft with compliance and burst pressure exceeding the saphenous vein autograft was fabricated (compliance = 6.0 ± 0.6 %/mmHg × 10−4, burst pressure = 2260 ± 160 mmHg). This graft is hypothesized to reduce intimal hyperplasia associated with low compliance in synthetic grafts and improve long term clinical success. Additionally, the fundamental relationships between electrospun mesh microarchitecture and mechanical properties identified in this work can be utilized in various biomedical applications. PMID:24846218
Hill, A; Estridge, T D; Maroney, M; Monnet, E; Egbert, B; Cruise, G; Coker, G T
CoSeal mark surgical sealant (CoSeal) was evaluated for inhibiting suture line bleeding using a canine iliac PTFE graft model. Both iliac arteries of 12 heparinized canines were grafted with PTFE. CoSeal was applied to the suture lines of one graft in each animal. The contra-lateral graft served as a control and bleeding was controlled with gauze and pressure (tamponade). The cross-clamps were removed 30 s following application of CoSeal. Times to hemostasis and volume of blood loss at each graft site were determined. Compared to tamponade control, CoSeal significantly reduced the time to hemostasis (average of 5 min vs. greater than 15 min, p < 0.05) and blood loss (19 g vs. 284 g, p < 0.05). Small amounts of CoSeal were visible grossly or histologically at day 7. Histology showed moderate to marked inflammation in CoSeal sites and moderate inflammation in control sites at day 7. At 30 and 60 days, no CoSeal was visible grossly or histologically. Histology showed moderate inflammation in both CoSeal treated sites and in control sites at day 30 and mild to moderate inflammation in both CoSeal and control sites at day 60. CoSeal significantly reduced the time to hemostasis and blood loss in comparison to tamponade. Copyright 2001 John Wiley & Sons, Inc.
Anterior cruciate ligament (ACL) reconstruction is one of the most commonly performed orthopedic procedures in the United States. Repair of the ACL often requires the use of autografts or allografts, and the RN first assistant (RNFA) often is the team member responsible for preparing the graft. Common grafts used in ACL repair include bone-patellar tendon-bone, hamstring, Achilles tendon, quadriceps tendon, and tibialis anterior tendon. The RNFA must be competent in preparing all of these grafts and in understanding the advantages and disadvantages of using each graft, such as the reasons for graft choice, and must ensure that all graft-related supplies and equipment are available and ready for use. The ability to prepare all graft types expands treatment options, reduces surgical time, and enhances the role of the RNFA.
Fine, A; Dunnett, S B; Björklund, A; Iversen, S D
The memory dysfunction of Alzheimer disease has been associated with a cortical cholinergic deficiency and loss of cholinergic neurons of the nucleus basalis of Meynert. This cholinergic component of Alzheimer disease can be modeled in the rat by ibotenic acid lesions of the cholinergic nucleus basalis magnocellularis. The memory impairment caused by such unilateral lesions, as reflected in passive avoidance behavior, is reversed by grafts into the deafferented neocortex of embryonic neurons of the cholinergic ventral forebrain, but not by grafts of noncholinergic hippocampal cells. Images PMID:3860857
Ellison, Philip; Mason, Lyndon William; Molloy, Andrew
Chronic rupture of the Achilles tendon (delayed diagnosis of more than 4 weeks) can result in retraction of the tendon and inadequate healing. Direct repair may not be possible and augmentation methods are challenging when the defect exceeds 5-6 cm, especially if the distal stump is grossly tendinopathic. We describe our method of Achilles tendon reconstruction with ipsilateral semitendinosis autograft and interference screw fixation in a patient with chronic rupture, a 9 cm defect and gross distal tendinopathy. Patient reported outcome measures consistently demonstrated improved health status at 12 months post surgery: MOXFQ-Index 38-25, EQ5D-5L 18-9, EQ VAS 70-90 and VISA-A 1-64. The patient was back to full daily function, could single leg heel raise and was gradually returning to sport. No complications or adverse events were recorded. Reconstruction of chronic tears of the Achilles tendon with large defects and gross tendinopathy using an ipsilateral semitendinosis autograft and interference screw fixation can achieve satisfactory improvements in patient reported outcomes up to 1 year post-surgery. Copyright © 2015 Elsevier Ltd. All rights reserved.
Bahçivan, Muzaffer; Elmali, Muzaffer; Kolbakir, Fersat; Göl, Kamil
The term "competitive flow" defines the flow from a partially stenosed native artery that "competes" with the flow from a graft to perfuse the distal tissues. The purpose of our study is to investigate the effects of competitive flow at different degrees of stenosis at common carotid artery, in a rabbit model by measuring both the flow volume and velocity in the venous graft. This prospective experimental study included 33 rabbits, which were divided into three groups: in Group 1, the common carotid arteries were ligated to form a total occlusion, in Group 2, the common carotid arteries were externally incompletely ligated to achieve 50% stenosis, and in Group 3, common carotid arteries were fully patent. The jugular vein was reversed and anastomosed to proximal and distal common carotid arteries using end to side anastomosis technique. Mean arterial pressure, the total flow and velocity were measured in native carotid arteries prior to surgery and in venous grafts 2 months after surgery using Doppler ultrasonography. Statistical analysis was performed using Chi-square test and Kruskal Wallis analysis of variances. There were no differences in graft mean velocity (Group 1--16.8+/- 6.7 cm/sec, Group 2--14.1+/- 6.1 cm/sec and Group 3--12.1+/- 6.7 cm/sec), and mean flow volume (Group 1--33.9+/- 11.5 mL/min, Group 2--29.0+/- 8.3 mL/min, and Group 3--24.4+/- 12.8 mL/min) between groups after surgery (p>0.05 for both). As it was the case in this rabbit model, the reduction of flow volume or velocity in lesser degrees of stenosis in the carotid artery venous bypass grafts is not significant in a statistical perspective. Although in short-term this effect did not create a difference for graft patencies between the groups, it may be important in long-term.
Torres, Bryan T; Chambers, Jonathan N; Budsberg, Steven C
To report repair of a periprosthetic acetabular fracture with concurrent component displacement after cementless total hip arthroplasty (THA). Clinical case report. Dog (n=1) with an acetabular fracture after THA. Acetabular repair was performed on a highly comminuted periprosthetic acetabular fracture after cementless THA. A bulk, structural corticocancellous autograft from the ipsilateral ilial wing was used for repair and reconstruction of the dorsal acetabular wall before reimplantation of a cementless acetabular component. Repair of a periprosthetic acetabular fracture with a bulk structural autograft was successful in reconstruction of the dorsal acetabular wall and in reestablishing a stable, functional cementless THA acetabular prosthesis. Structural corticocancellous autografts from the ilium can be successfully used in repair of periprosthetic acetabular fractures after THA. Structural corticocancellous grafting from the ilium can be considered as a treatment option for repair of periprosthetic acetabular fractures after THA.
Cavaignac, Etienne; Coulin, Benoit; Tscholl, Philippe; Nik Mohd Fatmy, Nik; Duthon, Victoria; Menetrey, Jacques
The quadriceps tendon (QT) autograft is known as an effective graft for anterior cruciate ligament (ACL) reconstruction and shows a similar functional outcome to the bone-patellar tendon-bone (BPTB) in randomized controlled trials, with a lesser incidence of complications. Up until now, only 2 studies have compared QT to hamstring tendon (HT) autograft. The functional outcomes of the QT technique are at least as good as those of the HT technique, with the same morbidity. Cohort study; Level of evidence, 3. Ninety-five patients underwent isolated ACL reconstruction between January 1 and December 31, 2012. Fifty underwent ACL reconstruction with the QT and 45 with the HT. The same surgical technique, fixation method, and postoperative protocol were used in both groups. The following parameters were evaluated: surgical revisions, functional outcome (Lysholm, Knee injury and Osteoarthritis Outcome Score [KOOS], Tegner, subjective International Knee Documentation Committee), joint stability (KT-1000, Lachman, pivot shift), anterior knee pain (Shelbourne-Trumper score), and isokinetic strength. Descriptive statistics are presented for these variables using the Student t test. Eighty-six patients (45 QT, 41 HT) were reviewed with a mean follow-up of 3.6 ± 0.4 years; minimum follow-up was 3 years. There were 4 reoperations in the QT group (including 1 ACL revision) and 3 in the HT group (including 2 ACL revisions) ( P > .05). The Lysholm (89 ± 6.9 vs 83.1 ± 5.3), KOOS Symptoms (90 ± 11.2 vs 81 ± 10.3), and KOOS Sport (82 ± 11.3 vs 67 ± 12.4) scores were significantly better in the QT group than in the HT group. In terms of stability, the mean side-to-side difference was 1.1 ± 0.9 mm for the QT group and 3.1 ± 1.3 mm for the HT group based on KT-1000 measurements ( P < .005). The negative Lachman component was higher in the QT group than in the HT group (90% vs 46%, P < .005). There was a trend for the negative pivot-shift component to be higher in the QT group
Kuribayashi, K.; Masuda, T.; Hanaoka, M.
We examined whether nude mice, which are deficient in T cell function, could be used as a model for induction of lethal graft-versus-host disease. Nude mice injected with MHC-disparate spleen cells exhibited only transient GVH reaction such as splenomegaly. Inoculation of B6 spleen cells into BALB/c nude mice produced high titers of alloantibodies to the donor cells. These alloantibodies eliminated host-MHC-reactive donor T cells from the host. After abolition by 400 rads irradiation of the capacity of nude mice to produce antibody, lethal GVHD could be induced by allogeneic spleen cell transfer and was mediated by donor T cells. This lethal GVHD was prevented by prior administration of antidonor alloantibody to the irradiated recipients at least 24 hr before donor-cell grafting. The role of alloantibody was substantiated in 2 other combinations in which little or no alloantibodies to donor spleen cells were produced. Engraftment of either MHC-identical but non-MHC disparate donor spleen cells into BALB/c nude mice or of parental spleen cells into F1 nude mice resulted in death mediated by T cells. In addition, irradiated BALB/c nude mice inoculated with non-MHC-incompatible B10.D2 spleen cells were much more sensitive to alloaggression by the donor cells than were nonirradiated hosts, indicating the presence of some radiation-sensitive component(s) acting in nude mice against GVHD induction by donor T cells. Thus the nude mouse is considered to be a useful recipient for clarifying the basic mechanisms involved in lethal GVHD.
Jenkins, E. D.; Melman, L.; Deeken, C. R.; Greco, S. C.; Frisella, M. M.; Matthews, B. D.
Introduction The purpose of this study is to compare the tissue incorporation of a novel fenestrated and non-fenestrated crosslinked porcine dermal matrix (CPDM) (CollaMend™, Davol Inc., Warwick, RI) in a porcine model of ventral hernia repair. Methods Bilateral abdominal wall defects were created in 12 Yucatan minipigs and repaired with a preperitoneal or intraperitoneal technique 21 days after hernia creation. Animals were randomized to fenestrated or non-fenestrated CPDM for n = 6 pieces of each graft in the preperitoneal or intraperitoneal location. All animals were sacrificed at 1 month. Adhesion characteristics and graft contraction/growth were measured by the Garrard adhesion grading scale and transparent grid overlay. Histological analysis of hematoxylin and eosin (H&E)-stained slides was performed to assess graft incorporation. Tissue incorporation strength was measured by a T-peel tensile test. The strength of explanted CPDM alone and de novo CPDM was measured by a uniaxial tensile test using a tensiometer (Instron, Norwood, MA) at a displacement rate of 0.42 mm/s. Statistical significance (P < 0.05) was determined for histological analysis using a Kruskal–Wallis non-parametric test with a Bonferroni correction, and for all other analyses using a two-way analysis of variance (ANOVA) with a Bonferroni post-test or a Kruskal–Wallis non-parametric test with a Dunn’s post-test. Results Intraperitoneal placement of fenestrated CPDM resulted in a significantly higher area of adhesions and adhesion score compared to the preperitoneal placement of fenestrated CPDM (P < 0.05). For both preperitoneal and intraperitoneal placement, histological findings demonstrated greater incorporation of the graft due to the fenestrations. No significant differences were detected in the uniaxial tensile strengths of the graft materials alone, either due to the graft type (non-fenestrated vs. fenestrated) or due to the placement location (preperitoneal vs. intraperitoneal
Graft selection remains the greatest challenge for surgeons performing rhinoplasty. The preferred choice thus far for nasal reconstruction would be autograft compared to allograft due to its lower rate of infection and extrusion as it does not induce an immune response. We have evaluated 26 patients who underwent open structured rhinoplasty at our center and compared our experience regarding the operative technique, graft availability, indications, and limitations. The racial distribution was 18 Indians, 5 Chinese, and 3 Malays with a mean age, hospitalization, and followup of 30.5 years, 16.9 months, and 4.4 days, respectively. Majority of the patients (57.6%) presented with twisted nose and 30.7% of the patients presented with history of nasal trauma. All the patients had deviated septum of varying severity. The most common graft used was quadrangular cartilage graft and the common complications noted were ala deformity and tip anaesthesia in 7.6% patients respectively. PMID:24078883
Seagrave, Richard A.; Sojka, John; Goodyear, Adam; Munns, Stephen W.
INTRODUCTION The lateral closing wedge high tibial osteotomy (HTO) was popularized by Coventry in the 1960s. In the 1990s the medial opening wedge osteotomy gained popularity because it could achieve greater valgus correction and it did not require dissociation of the fibula from the tibia, an important consideration when treating varus knees with lateral and posterolateral ligament deficiencies (Noyes’ double-varus and triple-varus knees). However, it has the disadvantage of requiring bone graft to fill bony defects. Recently, the reamer-irrigator-aspirator (RIA; Synthes, Paoli, PA) system was developed, and as a result of this procedure, a large amount of usable autogenous bone graft can be collected safely for use. To our knowledge, there is no published series combining opening wedge HTO with the use of RIA obtained autogenous bone graft. PRESENTATION OF CASE We present a novel technique in which a series of three patients underwent opening wedge HTO using ipsilateral, retrograde femur RIA graft to fill the bone defect. All patients had satisfactory clinical and radiologic outcomes following the new technique at latest follow up. DISCUSSION Opening wedge high tibial osteotomy is a well-documented and accepted orthopedic procedure, however, has the disadvantage of requiring varying amounts of bone graft. Traditionally, iliac crest or tricortical allograft have been the grafting modalities of choice, however both have inherent drawbacks to their use. In our series, the use of RIA autograft is a safe and reliable harvest technique for high tibial osteotomy, providing abundant and quality autogenous bone graft. CONCLUSION All three of our patients achieved radiographic union with high clinical patient satisfaction without any major complications. We feel this novel technique is a safe and acceptable operative solution grafting opening wedge osteotomies about the knee. PMID:24412805
Rutkowski, Gregory E; Heath, Carole A
A simple reaction-diffusion model has been developed to describe the mass transport of nutrients and nerve growth factor within a bioartificial nerve graft (BNG). The BNG consists of a porous polymer conduit that is preseeded with Schwann cells in its lumen. The Schwann cells produce growth factors to stimulate nerve regeneration within the lumen of the conduit. The model can predict the wall thickness, porosity, and Schwann cell seeding density needed to maximize the axon extension rate while ensuring that sufficient nutrients, especially oxygen, are made available to the neurons until the formation of the neovasculature. The model predicts a sixteen-fold increase in the levels of nerve growth factor by dropping the porosity from 95 to 55% but only at the expense of reducing the oxygen concentration. At higher porosities, increasing the wall thickness and increasing the Schwann cell seeding density both have the same effect of increasing the concentration of nerve growth factor within the lumen of the conduit. This model provides a simple tool for evaluating various conduit designs before continuing with experimental studies in vivo.
Schroeder, Mark A.; DiPersio, John F.
The limiting factor for successful hematopoietic stem cell transplantation (HSCT) is graft-versus-host disease (GvHD), a post-transplant disorder that results from immune-mediated attack of recipient tissue by donor T cells contained in the transplant. Mouse models of GvHD have provided important insights into the pathophysiology of this disease, which have helped to improve the success rate of HSCT in humans. The kinetics with which GvHD develops distinguishes acute from chronic GvHD, and it is clear from studies of mouse models of GvHD (and studies of human HSCT) that the pathophysiology of these two forms is also distinct. Mouse models also further the basic understanding of the immunological responses involved in GvHD pathology, such as antigen recognition and presentation, the involvement of the thymus and immune reconstitution after transplantation. In this Perspective, we provide an overview of currently available mouse models of acute and chronic GvHD, highlighting their benefits and limitations, and discuss research and clinical opportunities for the future. PMID:21558065
Tscherter, Anne; Heidemann, Martina; Kleinlogel, Sonja; Streit, Jürg
Presently there exists no cure for spinal cord injury (SCI). However, transplantation of embryonic tissue into spinal cord (SC) lesions resulted in axon outgrowth across the lesion site and some functional recovery, fostering hope for future stem cell therapies. Although in vivo evidence for functional recovery is given, the exact cellular mechanism of the graft support remains elusive: either the grafted cells provide a permissive environment for the host tissue to regenerate itself or the grafts actually integrate functionally into the host neuronal network reconnecting the separated SC circuits. We tested the two hypotheses in an in vitro SC lesion model that is based on propagation of activity between two rat organotypic SC slices in culture. Transplantation of dissociated cells from E14 rat SC or forebrain (FB) re-established the relay of activity over the lesion site and thus, provoked functional regeneration. Combining patch-clamp recordings from transplanted cells with network activity measurements from the host tissue on multi-electrode arrays (MEAs) we here show that neurons differentiate from the grafted cells and integrate into the host circuits. Optogenetic silencing of neurons developed from transplanted embryonic mouse FB cells provides clear evidence that they replace the lost neuronal connections to relay and synchronize activity between the separated SC circuits. In contrast, transplantation of neurospheres (NS) induced neither the differentiation of mature neurons from the grafts nor an improvement of functional regeneration. Together these findings suggest, that the formation of neuronal relays from grafted embryonic cells is essential to re-connect segregated SC circuits. PMID:27708562
Crooke, Philip S; Beavan, L Alan; Griffin, Charles D; Mazzitelli, Domenico; Rankin, J Scott
Available aortic root grafts generally flare outward in the sinus region, and this feature improves procedural ease. However, no current device is based on normal aortic root geometry, and a fully anatomic aortic root graft could further facilitate valve-sparing root operations. To develop a model of the normal human aortic root, high-resolution computed tomographic angiogram images from 11 normal human aortas generated high-density x, y, z coordinates of valve and root structures in Mathematica. Three-dimensional least-squares regression analyses assessed geometry of the aortic valve and root. Shapes and dimensions were quantified, and minor variations in geometry were simplified during graft design. Normal aortic valve and root geometry was represented as three leaflet-sinus general ellipsoids nested within a cylindrical aorta. Sinotubular junction diameter was 5 mm larger than the valve base-with a slight funnel-shaped outward commissural flare but cylindrical geometry above the midvalve. The valve base was elliptical, but the midvalve and the sinotubular junction were circular above the midvalve level. Commissural locations on the base circumference were equidistant. On the basis of average three-dimensional geometry, a root graft was designed for root remodeling procedures-to be used with an internal geometric annuloplasty ring of the same design. An aortic root graft was designed on the basis of mathematical analyses of computed tomographic angiogram images. The design incorporated three anatomic sinuses, commissural symmetry, and compatibility with geometric ring annuloplasty. The anatomic graft may prove useful for restoring aortic root geometry toward normal during aortic valve and root surgery.
Saygun, Oral; Agalar, Canan; Aydinuraz, Kuzey; Agalar, Fatih; Daphan, Cagatay; Saygun, Meral; Ceken, Sabahat; Akkus, Abdullah; Denkbas, Emir Baki
The use of non-absorbable mesh grafts in both abdominal wall defects and inguinal hernias are impossible in the presence of contamination. This study was conducted for evaluation of the efficiencies of polypropylene mesh grafts coated with gold and palladium-gold. Ten piece of 1 x 2 cm of polypropylene mesh grafts were used in each group of naïve, gold-coated, and palladium-gold-coated. The grafts were incubated in physiological saline buffered and 0.5 McFarland slime positive Staphylococcus epidermidis for 24 h. At intervals of 6, 12, 24, 48, 72 h grafts were washed with saline and vortexed for 2 min in 2 ml of physiological saline. There were 100 microl of samples of vortexed material incubated in blood agar and 24 h later, colony numbers were assessed. In the second part of study, the grafts were implanted below the musculoaponeurotic layer at inguinal region of rats following the same procedure of incubation and washing. On the 8th day, the rats were examined for infection rate and their wound cultures were obtained. The least amount of bacterial growth was detected in the samples obtained from gold-palladium coated grafts; whereas the highest rate of growth was found in samples of naive grafts. The superficial surgical site infection rate was 0% in gold-palladium coated, 30% in gold-coated and 100% in naïve polypropylene group. The bacterial growth rate from wound cultures confirmed the superficial surgical site infection rates in all groups. Prosthetic graft infection with S. epidermidis can be prevented by coating the graft with gold-palladium or gold.
Romanini, Emilio; D'Angelo, Franca; De Masi, Salvatore; Adriani, Ezio; Magaletti, Massimiliano; Lacorte, Eleonora; Laricchiuta, Paola; Sagliocca, Luciano; Morciano, Cristina; Mele, Alfonso
anterior cruciate ligament (ACL) surgical reconstruction is performed with the use of an autogenic, allogenic or synthetic graft. The document issued by the Italian National Guidelines System (SNLG, Sistema Nazionale Linee Guida) at the National Institute of Health aims to guide orthopaedic surgeons in selecting the optimal graft for ACL reconstruction using an evidence-based approach. A monodisciplinary panel was formed to define a restricted number of clinical questions, develop specific search strategies and critically appraise the literature using the grading of recommendations assessment, development, and evaluation (GRADE) method. The final draft was shared by the panel and then sent to four external referees to assess its readability and clarity, its clinical relevance and the feasibility of recommendations. autograft shows moderate superiority compared with allograft, in relation to the relevant outcomes and the quality of selected evidence, after an appropriate risk-benefit assessment. Allograft shows higher failure rate and higher risk of infection. The panel recommends use of autografts; patellar tendon should be the first choice, due to its higher stability, while use of hamstring is indicated for subjects for whom knee pain can represent a particular problem (e.g., some categories of workers). autograft shows better performance compared with allograft and no significant heterogeneity in relation to relevant outcomes. The GRADE method allowed collation of all the information needed to draw up the recommendations, and to highlight the core points for discussion.
Ahn, Jin Hwan; Jeong, Hwa Jae; Lee, Yong Seuk; Park, Jai Hyung; Lee, Jin Ho; Ko, Taeg Su
The purposes of this study were as follows: 1) to determine the correlation between the bending angle of the anterior cruciate ligament (ACL) graft at the femoral tunnel and the magnetic resonance imaging (MRI) signal intensity of the ACL graft and 2) to analyze the difference in the MRI signal intensity of the reconstructed ACL graft in different areas of the graft after single-bundle hamstring autograft ACL (SB ACL) reconstruction using an outside-in (OI) technique with bone-sparing retro-reaming. Thirty-eight patients who underwent SB ACL reconstruction with the hamstring tendon autograft using the OI technique were enrolled in this study. All patients were assessed using three-dimensional computed tomography (CT) to evaluate femoral tunnel factors, including tunnel placement, tunnel length, tunnel diameter, and femoral tunnel bending angle. At a mean of 6.3±0.8months after surgery, 3.0-T MRI was used to evaluate the graft signal intensity using signal/noise quotient for high-signal-intensity lesions. Among various femoral tunnel factors, only the femoral tunnel bending angle in the coronal plane was significantly (p=0.003) correlated with the signal/noise quotient of the femoral intraosseous graft. The femoral intraosseous graft had significantly (p=0.009) higher signal intensity than the other graft zone. Five cases (13.2%) showed high-signal-intensity zones around the femoral tunnel but not around the tibial tunnel. After ACL reconstruction using the OI technique, the graft bending angle was found to be significantly correlated with the femoral intraosseous graft signal intensity, indicating that increased signal intensity by acute graft bending might be related to the maturation of the graft. This was a retrospective comparative study with Level III evidence. Copyright © 2015 Elsevier B.V. All rights reserved.
Rachev, A; Manoach, E; Berry, J; Moore, J E
The mismatch between the elastic properties and initial geometry of a host artery and an implanted stent or graft cause significant stress concentration at the zones close to junctions. This may contribute to the often observed intimal hyperplasia, resulting in late lumen loss and eventual restenosis. This study proposes a mathematical model for stress-induced thickening of the arterial wall at the zones close to an implanted stent or graft. The host artery was considered initially as a cylindrical shell with constant thickness that was clamped to the stent or graft, which was assumed to be non-deformable in the circumferential direction. It was assumed that the abnormal circumferential and axial stresses due to the bending of the arterial wall cause wall thickening that tends to restore the stress state close to that existing far from the junction. The linear equations of a cylindrical shell with variable thickness were coupled to an evolution equation for the wall thickness. These equations were solved numerically and a parametric study was performed using finite difference method and explicit time step. The results show that the remodeling process is self-limiting and leads to local thickening that gradually decreases with distance from the edge of the stent/graft. Model predictions were tested against morphological findings existing in the literature. Recommendations on stent designs that reduce stress concentrations are discussed. Copyright 2000 Academic Press.
Sahin, S; Akoğlu, T F; Gürbüz, O; Ergun, T; Küllü, S; Sav, A; Ahiskali, R; Tüzüner, N; Doğusoy, G
An in vitro skin explant model has been proposed for prediction of graft versus host disease and reported to be highly sensitive and specific for this purpose. In this study we have re-evaluated this model in both HLA full-matched BMT recipient-donor sibling pairs and also in HLA one haplotype-matched parent-children pairs. All assessments were made blindly by 3 independent observers. The predictive value of the test for the occurrence of clinical GvHD in 14 BMT patients was found to be less sensitive than reported previously (correlation coefficients were +0.019, +0.067 and -0.061 between clinical GvHD and in vitro primed allogeneic, primed mixed and unprimed allogeneic settings, indicating "poor" correlation). False positive and false negative results were high and there were also significant discrepancies between three blind observations in the grading of skin changes. Weighted kappa analysis revealed that there were "fair" correlations between the 3 observers (K = 0.25). These results indicated that the skin explant model is an unpredictable test system and there are great problems in standardization of the method.
Conroy, Christine; Sethi, Paul; Macken, Craig; Wei, David; Kowalsky, Marc; Mirzayan, Raffy; Pauzenberger, Leo; Dyrna, Felix; Obopilwe, Elifho; Mazzocca, Augustus D
The majority of distal biceps tendon injuries can be repaired in a single procedure. In contrast, complete chronic tears with severe tendon substance deficiency and retraction often require tendon graft augmentation. In cases with extensive partial tears of the distal biceps, a human dermal allograft may be used as an alternative to restore tendon thickness and biomechanical integrity. Dermal graft augmentation will improve load to failure compared with nonaugmented repair in a tendon-deficient model. Controlled laboratory study. Thirty-six matched specimens were organized into 1 of 4 groups: native tendon, native tendon with dermal graft augmentation, tendon with an attritional defect, and tendon with an attritional defect repaired with a graft. To mimic a chronic attritional biceps lesion, a defect was created by a complete tear, leaving 30% of the tendon's width intact. The repair technique in all groups consisted of cortical button and interference screw fixation. All specimens underwent cyclical loading for 3000 cycles and were then tested to failure; gap formation and peak load at failure were documented. The mean (±SD) load to failure (320.9 ± 49.1 N vs 348.8 ± 77.6 N, respectively; P = .38) and gap formation (displacement) (1.8 ± 1.4 mm vs 1.6 ± 1.1 mm, respectively; P = .38) did not differ between the native tendon groups with and without graft augmentation. In the tendon-deficient model, the mean load to failure was significantly improved with graft augmentation compared with no graft augmentation (282.1 ± 83.8 N vs 199.7 ± 45.5 N, respectively; P = .04), while the mean gap formation was significantly reduced (1.2 ± 1.0 mm vs 2.7 ± 1.4 mm, respectively; P = .04). The mean load to failure of the deficient tendon with graft augmentation (282.1 N) compared with the native tendon (348.8 N) was not significantly different ( P = .12). This indicates that the native tendon did not perform differently from the grafted deficient tendon. In a tendon
Fanning, Stacey L; Zilberberg, Jenny; Stein, Johann; Vazzana, Kristin; Berger, Stephanie A; Korngold, Robert; Friedman, Thea M
The optimum use of allogeneic blood and marrow transplantation (BMT) as a curative therapy for hematological malignancies lies in the successful separation of mature donor T cells that are host reactive and induce graft-versus-host disease (GVHD) from those that are tumor reactive and mediate graft-versus-leukemia (GVL) effects. To study whether this separation was possible in an MHC-matched murine BMT model (B10.BR→CBA) with a CBA-derived myeloid leukemia line, MMC6, we used TCR Vβ CDR3-size spectratype analysis to first show that the Vβ13 family was highly skewed in the B10.BR anti-MMC6 CD8(+) T cell response but not in the alloresponse against recipient cells alone. Transplantation of CD8(+)Vβ13(+) T cells at the dose equivalent of their constituency in 1 × 10(7) CD8(+) T cells, a dose that had been shown to mediate lethal GVHD in recipient mice, induced a slight GVL response with no concomitant GVHD. Increasing doses of CD8(+)Vβ13(+) T cells led to more significant GVL responses but also increased GVHD symptoms and associated mortality. Subsequent spectratype analysis of GVHD target tissues revealed involvement of gut-infiltrating CD8(+)Vβ13(+) T cells accounting for the observed in vivo effects. When BMT recipients were given MMC6-presensitized CD8(+)Vβ13(+) T cells, they displayed a significant GVL response with minimal GVHD. Spectratype analysis of tumor-presensitized, gut-infiltrating CD8(+)Vβ13(+) T cells showed preferential usage of tumor-reactive CDR3-size lengths, and these cells expressed increased effector memory phenotype (CD44(+)CD62L(-/lo)). Thus, Vβ spectratyping can identify T cells involved in antihost and antitumor reactivity and tumor presensitization can aid in the separation of GVHD and GVL responses.
Cutiongco, Marie F. A.; Kukumberg, Marek; Peneyra, Jonnathan L.; Yeo, Matthew S.; Yao, Jia Y.; Rufaihah, Abdul Jalil; Le Visage, Catherine; Ho, Jackie Pei; Yim, Evelyn K. F.
Microvascular surgery is becoming a prevalent surgical practice. Replantation, hand reconstruction, orthopedic, and free tissue transfer procedures all rely on microvascular surgery for the repair of venous and arterial defects at the millimeter and submillimeter levels. Often, a vascular graft is required for the procedure as a means to bridge the gap between native arteries. While autologous vessels are desired for their bioactivity and non-thrombogenicity, the tedious harvest process, lack of availability, and caliber or mechanical mismatch contribute to graft failure. Thus, there is a need for an off-the-shelf artificial vascular graft that has low thrombogenic properties and mechanical properties matching those of submillimeter vessels. Poly(vinyl alcohol) hydrogel (PVA) has excellent prospects as a vascular graft due to its bioinertness, low thrombogenicity, high water content, and tunable mechanical properties. Here, we fabricated PVA grafts with submillimeter diameter and mechanical properties that closely approximated those of the rabbit femoral artery. In vitro platelet adhesion and microparticle release assay verified the low thrombogenicity of PVA. A stringent proof-of-concept in vivo test was performed by implanting PVA grafts in rabbit femoral artery with multilevel arterial occlusion. Laser Doppler measurements indicated the improved perfusion of the distal limb after implantation with PVA grafts. Moreover, ultrasound Doppler and angiography verified that the submillimeter diameter PVA vascular grafts remained patent for 2 weeks without the aid of anticoagulant or antithrombotics. Endothelial cells were observed in the luminal surface of one patent PVA graft. The advantageous non-thrombogenic and tunable mechanical properties of PVA that are retained even in the submillimeter diameter dimensions support the application of this biomaterial for vascular replacement in microvascular surgery. PMID:27376059
Bargar, W.L.; Paul, H.A.; Merritt, K.; Sharkey, N.
A canine model was developed to investigate the use of an autogeneic iliac bone graft to treat the calcar deficiency commonly found at the time of revision surgery for femoral component loosening. Five large male mixed-breed dogs had bilateral total hip arthroplasty staged at three-month intervals, and were sacrificed at six months. Prior to cementing the femoral component, an experimental calcar defect was made, and a bicortical iliac bone graft was fashioned to fill the defect. Serial roentgenograms showed the grafts had united with no resorption. Technetium-99 bone scans showed more uptake at three months than at six months in the graft region. Disulfine blue injection indicated all grafts were perfused at both three and six months. Thin section histology, fluorochromes, and microradiographs confirmed graft viability in all dogs. Semiquantitative grading of the fluorochromes indicated new bone deposition in 20%-50% of each graft at three months and 50%-80% at six months. Although the calcar bone graft was uniformly successful in this canine study, the clinical application of this technique should be evaluated by long-term results in humans.
Athanasiou, Thanos; Cherian, Ashok; Ross, Donald
The surgical management of mitral valve disease in women of childbearing age, young patients, and children with congenital mitral valve defects is made difficult by the prospect of lifelong anticoagulation. We suggest the use of a pulmonary autograft in the mitral position (Ross II procedure) as an alternative surgical technique. We present a review of the literature, historical perspectives, indications, selection criteria, and surgical technique for the Ross II procedure. Our literature search identified 14 studies that reported results from the Ross II operation. Performed in 103 patients, the overall in-hospital mortality was 7 (6.7%), with a late mortality of 10 (9%). Although further research is needed, current evidence suggests the Ross II operation is a valuable alternative in low-risk young patients where valve durability and the complication rate from other procedures is unsatisfactory and anticoagulation not ideal.
Ferrete-Barroso, A M; González-Díaz, R; Losada-Viñas, J I
To assess fusion rates and functional outcomes in patients undergoing anterior cervical discectomy and fusion by using a vertebral body autograft for interbody filling and anterior cervical plate fixation. The study included a total of 102 patients, 54 men and 48 women, who underwent surgery between 2006 and 2010 patients with degenerative disease, cervical disc herniation and radiculopathy, and who had failed standard conservative treatment (3 months). The study was limited to patients with fusion levels 1-3. The mean patient follow-up was 44 (24-96) months. Their mean age was 48.8 years. The clinical variables analyzed were: duration of symptoms (> 12 months), smoking (31% smokers), employment status (76% active), average days of hospitalization (2.2 days), operation time (62 min), etiology (100%, degenerative disease), notable comorbidities (28%), fusion levels (42% 1, 49% 2, 9% 3), symptoms (radiculalgia or axial pain). The functional variables analyzed (score pre-and post-operative scores) were: VAS (8.6-1.32), Neck Disability Index (37.7-5.8), and Odom criteria (76% reflected excellent results after surgery). Finally, radiological variables were also analyzed: anterior reactive osteophytosis (16%), significant collapse (0%), and fusion rate (98%). There were 4 cases of acute postoperative complications, and 4 chronic, none of them were related to the surgical technique. The use of autograft bone of the vertebral body itself reduces comorbidities associated with the use of the iliac crest of the patient. Our results using the technique described are comparable to those in the literature, with a fusion rate of 98% and a mean of 62 min duration of the procedure. Copyright © 2014 SECOT. Published by Elsevier Espana. All rights reserved.
Duran-Struuck, Raimon; Huang, Christene A; Orf, Katherine; Bronson, Roderick T; Sachs, David H; Spitzer, Thomas R
Miniature swine provide a preclinical model of hematopoietic cell transplantation (HCT) for studies of graft-versus-host disease. HCT between MHC-matched or ‑mismatched pigs can be performed to mimic clinical scenarios with outcomes that closely resemble those observed in human HCT recipients. With myeloablative conditioning, HCT across MHC barriers is typically fatal, with pigs developing severe (grade III or IV) GVHD involving the gastrointestinal tract, liver, and skin. Unlike rodent models, miniature swine provide an opportunity to perform extended longitudinal studies on individual animals, because multiple tissue biopsies can be harvested without the need for euthanasia. In addition, we have developed a swine GVHD scoring system that parallels that used in the human clinical setting. Given the similarities of GVHD in pigs and humans, we hope that the use of this scoring system facilitates clinical and scientific discourse between the laboratory and the clinic. We anticipate that results of swine studies will support the development of new strategies to improve the identification and treatment of GVHD in clinical HCT scenarios. PMID:26473348
Duran-Struuck, Raimon; Huang, Christene A; Orf, Katherine; Bronson, Roderick T; Sachs, David H; Spitzer, Thomas R
Miniature swine provide a preclinical model of hematopoietic cell transplantation (HCT) for studies of graft-versus-host disease. HCT between MHC-matched or -mismatched pigs can be performed to mimic clinical scenarios with outcomes that closely resemble those observed in human HCT recipients. With myeloablative conditioning, HCT across MHC barriers is typically fatal, with pigs developing severe (grade III or IV) GVHD involving the gastrointestinal tract, liver, and skin. Unlike rodent models, miniature swine provide an opportunity to perform extended longitudinal studies on individual animals, because multiple tissue biopsies can be harvested without the need for euthanasia. In addition, we have developed a swine GVHD scoring system that parallels that used in the human clinical setting. Given the similarities of GVHD in pigs and humans, we hope that the use of this scoring system facilitates clinical and scientific discourse between the laboratory and the clinic. We anticipate that results of swine studies will support the development of new strategies to improve the identification and treatment of GVHD in clinical HCT scenarios.
Zaza, Gianluigi; Ferraro, Pietro Manuel; Tessari, Gianpaolo; Sandrini, Silvio; Scolari, Maria Piera; Capelli, Irene; Minetti, Enrico; Gesualdo, Loreto; Girolomoni, Giampiero; Gambaro, Giovanni; Lupo, Antonio; Boschiero, Luigino
Identification of pre-transplant factors influencing delayed graft function (DGF) could have an important clinical impact. This could allow clinicians to early identify dialyzed chronic kidney disease (CKD) patients eligible for special transplant programs, preventive therapeutic strategies and specific post-transplant immunosuppressive treatments. To achieve these objectives, we retrospectively analyzed main demographic and clinical features, follow-up events and outcomes registered in a large dedicated dataset including 2,755 patients compiled collaboratively by four Italian renal/transplant units. The years of transplant ranged from 1984 to 2012. Statistical analysis clearly demonstrated that some recipients' characteristics at the time of transplantation (age and body weight) and dialysis-related variables (modality and duration) were significantly associated with DGF development (p ≤ 0.001). The area under the receiver-operating characteristic (ROC) curve of the final model based on the four identified variables predicting DGF was 0.63 (95 % CI 0.61, 0.65). Additionally, deciles of the score were significantly associated with the incidence of DGF (p value for trend <0.001). Therefore, in conclusion, in our study we identified a pre-operative predictive model for DGF, based on inexpensive and easily available variables, potentially useful in routine clinical practice in most of the Italian and European dialysis units.
Centola, M; Rainer, A; Spadaccio, C; De Porcellinis, S; Genovese, J A; Trombetta, M
Tissue engineering of blood vessels is a promising strategy in regenerative medicine with a broad spectrum of potential applications. However, many hurdles for tissue-engineered vascular grafts, such as poor mechanical properties, thrombogenicity and cell over-growth inside the construct, need to be overcome prior to the clinical application. To surmount these shortcomings, we developed a poly-L-lactide (PLLA)/poly-epsilon-caprolactone (PCL) scaffold releasing heparin by a combination of electrospinning and fused deposition modeling technique. PLLA/heparin scaffolds were produced by electrospinning in tubular shape and then fused deposition modeling was used to armor the tube with a single coil of PCL on the outer layer to improve mechanical properties. Scaffolds were then seeded with human mesenchymal stem cells (hMSCs) and assayed in terms of morphology, mechanical tensile strength, cell viability and differentiation. This particular scaffold design allowed the generation of both a drug delivery system amenable to surmount thrombogenic issues and a microenvironment able to induce endothelial differentiation. At the same time, the PCL external coiling improved mechanical resistance of the microfibrous scaffold. By the combination of two notable techniques in biofabrication--electrospinning and FDM--and exploiting the biological effects of heparin, we developed an ad hoc differentiating device for hMSCs seeding, able to induce differentiation into vascular endothelium.
Steinbeck, Julius A; Choi, Se Joon; Mrejeru, Ana; Ganat, Yosif; Deisseroth, Karl; Sulzer, David; Mosharov, Eugene V; Studer, Lorenz
Recent studies have shown evidence of behavioral recovery after transplantation of human pluripotent stem cell (PSC)-derived neural cells in animal models of neurological disease1–4. However, little is known about the mechanisms underlying graft function. Here we use optogenetics to modulate in real time electrophysiological and neurochemical properties of mesencephalic dopaminergic (mesDA) neurons derived from human embryonic stem cells (hESCs). In mice that had recovered from lesion-induced Parkinsonian motor deficits, light-induced selective silencing of graft activity rapidly and reversibly re-introduced the motor deficits. The re-introduction of motor deficits was prevented by the dopamine agonist apomorphine. These results suggest that functionality depends on graft neuronal activity and dopamine release. Combining optogenetics, slice electrophysiology and pharmacological approaches, we further show that mesDA-rich grafts modulate host glutamatergic synaptic transmission onto striatal medium spiny neurons in a manner reminiscent of endogenous mesDA neurons. Thus, application of optogenetics in cell therapy can link transplantation, animal behavior and postmortem analysis to enable the identification of mechanisms that drive recovery. PMID:25580598
Steinbeck, Julius A; Choi, Se Joon; Mrejeru, Ana; Ganat, Yosif; Deisseroth, Karl; Sulzer, David; Mosharov, Eugene V; Studer, Lorenz
Recent studies have shown evidence of behavioral recovery after transplantation of human pluripotent stem cell (PSC)-derived neural cells in animal models of neurological disease. However, little is known about the mechanisms underlying graft function. Here we use optogenetics to modulate in real time electrophysiological and neurochemical properties of mesencephalic dopaminergic (mesDA) neurons derived from human embryonic stem cells (hESCs). In mice that had recovered from lesion-induced Parkinsonian motor deficits, light-induced selective silencing of graft activity rapidly and reversibly re-introduced the motor deficits. The re-introduction of motor deficits was prevented by the dopamine agonist apomorphine. These results suggest that functionality depends on graft neuronal activity and dopamine release. Combining optogenetics, slice electrophysiology and pharmacological approaches, we further show that mesDA-rich grafts modulate host glutamatergic synaptic transmission onto striatal medium spiny neurons in a manner reminiscent of endogenous mesDA neurons. Thus, application of optogenetics in cell therapy can link transplantation, animal behavior and postmortem analysis to enable the identification of mechanisms that drive recovery.
Awad, Hani A.; O’Keefe, Regis J.; Guldberg, Robert E.; Schwarz, Edward M.
Autograft is superior to both allograft and synthetic bone graft in repair of large structural bone defect largely due to the presence of multipotent mesenchymal stem cells in periosteum. Recent studies have provided further evidence that activation, expansion and differentiation of the donor periosteal progenitor cells are essential for the initiation of osteogenesis and angiogenesis of donor bone graft healing. The formation of donor cell-derived periosteal callus enables efficient host-dependent graft repair and remodeling at the later stage of healing. Removal of periosteum from bone autograft markedly impairs healing whereas engraftment of multipotent mesenchymal stem cells on bone allograft improves healing and graft incorporation. These studies provide rationale for fabrication of a biomimetic periosteum substitute that could fit bone of any size and shape for enhanced allograft healing and repair. The success of such an approach will depend on further understanding of the molecular signals that control inflammation, cellular recruitment as well as mesenchymal stem cell differentiation and expansion during the early phase of the repair process. It will also depend on multidisciplinary collaborations between biologists, material scientists and bioengineers to address issues of material selection and modification, biological and biomechanical parameters for functional evaluation of bone allograft healing. PMID:18509709
Hulsey, Angela; Linneman, Paul
Introduction: Chronic wounds are a significant healthcare problem in the United States. Their costs approach 25 billion dollars in the United States. Current wound-care treatments of local wound care, moist dressings, and source control, while necessary for wound healing, are frequently not enough to ensure complete wound closure. The current surgical technique of split-thickness skin grafting is an operative procedure, painful, time-consuming, and leaves significant donor site wounds. A recently developed and marketed epidermal autograft harvester was tested at our university hospital wound center on 13 patients with wounds of various etiologies. Their clinical outcomes were evaluated, as were the costs associated with its usage compared with the potential costs of continued wound care without autograft placement. Methods: Thirteen patients whose wounds appeared to have "stalled" or reached a plateau in healing by measurement data and visual evidence were chosen to receive an epidermal autograft to accelerate wound closure. Wound-types included diabetic ulcers, venous or lymphedema-related ulcers, surgical site wounds, and traumatic wounds. Time-to-healing in days, when applicable, was captured. Wound center billing and charges were available and evaluated for nine of the 13 patients. Costs of standard care continuation compared with the cost of epidermal autograft technology usage were compared. Results: Healing rates were 62%; eight of the 13 patients had healed within four months, two were lost to follow-up, and three have wounds that remain open. Four of the patients healed in less than one month. The comparatively rapid closure of the open wound(s) post-epidermal autograft placement potentially reduced healthcare costs based on charges at an average of $1,153 per patient and yielded an average of $650 to the wound center, not applying the routine costs of dressings applied in the center. Conclusion: The epidermal autograft harvester
Habka, Dany; Mann, David; Landes, Ronald; Soto-Gutierrez, Alejandro
During the past 20 years liver transplantation has become the definitive treatment for most severe types of liver failure and hepatocellular carcinoma, in both children and adults. In the U.S., roughly 16,000 individuals are on the liver transplant waiting list. Only 38% of them will receive a transplant due to the organ shortage. This paper explores another option: bioengineering an autologous liver graft. We developed a 20-year model projecting future demand for liver transplants, along with costs based on current technology. We compared these cost projections against projected costs to bioengineer autologous liver grafts. The model was divided into: 1) the epidemiology model forecasting the number of wait-listed patients, operated patients and postoperative patients; and 2) the treatment model forecasting costs (pre-transplant-related costs; transplant (admission)-related costs; and 10-year post-transplant-related costs) during the simulation period. The patient population was categorized using the Model for End-Stage Liver Disease score. The number of patients on the waiting list was projected to increase 23% over 20 years while the weighted average treatment costs in the pre-liver transplantation phase were forecast to increase 83% in Year 20. Projected demand for livers will increase 10% in 10 years and 23% in 20 years. Total costs of liver transplantation are forecast to increase 33% in 10 years and 81% in 20 years. By comparison, the projected cost to bioengineer autologous liver grafts is $9.7M based on current catalog prices for iPS-derived liver cells. The model projects a persistent increase in need and cost of donor livers over the next 20 years that's constrained by a limited supply of donor livers. The number of patients who die while on the waiting list will reflect this ever-growing disparity. Currently, bioengineering autologous liver grafts is cost prohibitive. However, costs will decline rapidly with the introduction of new manufacturing
Friedrich, R E
To study the patency rates of anastomoses in damaged common carotid arteries in a training model of microvascular surgery (Wistar rats). Under general anaesthesia with xylazine (Rompun) and ketamine (Ketanest) balloon dilatation was repeated five times in 31 left common carotid arteries of female Wistar rats. One minute after reflow an autograft of 4 mm was harvested, turned 180 degrees, and reinserted into the artery. The flow through the vessels was investigated by micro-Doppler ultrasound (60 s after balloon dilatation and 30 min after insertion of the autograft). Autografts were fashioned in a further 26 common carotid arteries but left undamaged. A further 14 arteries were dilated, but no autografts were inserted. The vessels were harvested after perfusion with 3% glutaraldehyde after one day, seven days, and one month. The specimens were evaluated by light microscopy in longitudinal sections of 1.5 microm slides embedded in Epon. In addition, cross-sections were taken from arteries treated by balloon dilatation. In no instance did dilatation lead to occlusion of the vessel as judged by micro-Doppler ultrasound. In the group with autografts that were not dilated, one vessel was occluded after flow had restarted. However, this vessel proved to be patent after perfusion and examination. In this group, therefore, all arteries were patent after perfusion. In the group in which dilatation preceded the insertion 13 vessels were occluded and 13 were patent on micro-Doppler ultrasound. At different perfusion times, 14 vessels were patent, and 12 vessels were completely thrombosed. The differences in patency in both groups with autografts was significant, both after Doppler imaging and on histological evaluation (P < 0.001). Balloon dilatation is recommended for the removal of a thrombus or to dilate a spastic vessel segment in anastomosed vessels that threaten the success of microvascular flaps. For experimental research, balloon dilatation of the common carotid
Hubble, Matthew J W
Bone grafts are used in musculoskeletal surgery to restore structural integrity and enhance osteogenic potential. The demand for bone graft for skeletal reconstruction in bone tumor, revision arthroplasty, and trauma surgery, couple with recent advances in understanding and application of the biology of bone transplantation, has resulted in an exponential increase in the number of bone-grafting procedures performed over the last decade. It is estimated that 1.5 million bone-grafting procedures are currently performed worldwide each year, compared to a fraction of that number 20 years ago. Major developments also have resulted in the harvesting, storage, and use of bone grafts and production of graft derivatives, substitutes, and bone-inducing agents.
Smith, M M; Duncan, W J; Coates, D E
The aim of this pilot study was to characterize surface morphology and to evaluate resorption and osseous healing of two deproteinated bovine bone graft materials after sinus grafting in a large animal model. Surfaces of a novel particulate bovine bone graft, Moa-Bone(®) were compared with Bio-Oss(®) using scanning electron microscopy. Six sheep then had maxillary sinus grafting bilaterally, covered with BioGide(®) . Grafted maxillae were harvested after 4, 6 and 12 weeks. Healing was described for half of each site using resin-embedded ground sections. For the other half, paraffin-embedded sections were examined using tartrate resistant acid phosphatase staining for osteoclast activity, runt-related transcription factor2 immunohistochemistry for pre-osteoblasts and osteoblasts and proliferating cell nuclear antigen for proliferative cells. Moa-Bone(®) had a smoother, more porous fibrous structure with minimal globular particles compared with Bio-Oss(®) . After 4 weeks, woven bone formed on both grafts and the Moa-Bone(®) particles also showed signs of resorption. After 12 weeks, Moa-Bone(®) continued to be resorbed, however Bio-Oss(®) did not; both grafts were surrounded by maturing lamellar bone. Moa-Bone(®) was associated with earlier evidence of runt-related transcription factor 2-positive cells. Moa-Bone(®) but not Bio-Oss(®) was associated with strong tartrate resistant acid phosphatase-positive osteoclasts on the graft surface within resorption lacunae at both 4 and 6 weeks post-grafting. Both materials supported osseous healing and maturation without inflammation. Moa-Bone(®) showed marked osteoclast activity after 4 and 6 weeks and demonstrated positive attributes for grafting, if complete remodeling of the graft within the site is desired. Further optimization of Moa-Bone(®) for maxillofacial applications is warranted. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Strobel, Raymond J.; Liang, Qixing; Zhang, Min; Wu, Xiaoting; Rogers, Mary A. M.; Theurer, Patricia F.; Fishstrom, Astrid B.; Harrington, Steven D.; DeLucia, Alphonse; Paone, Gaetano; Patel, Himanshu J.; Prager, Richard L.; Likosky, Donald S.
Background Post-operative pneumonia is the most prevalent of all hospital-acquired infections following isolated coronary artery bypass grafting (CAB). Accurate prediction of a patient’s risk of this morbid complication is hindered by its low relative incidence. In an effort to support clinical decision-making and quality improvement, we developed a pre-operative prediction model for post-operative pneumonia following CAB. Methods We undertook an observational study of 16,084 patients undergoing CAB between Q3 2011 – Q2 2014 across 33 institutions participating in the Michigan Society of Thoracic and Cardiovascular Surgeons – Quality Collaborative. Variables related to patient demographics, medical history, admission status, comorbid disease, cardiac anatomy and the institution performing the procedure were investigated. Logistic regression via forwards stepwise selection (p < 0.05 threshold) was utilized to develop a risk prediction model for estimating the occurrence of pneumonia. Traditional methods were employed to assess the model’s performance. Results Post-operative pneumonia occurred in 3.30% of patients. Multivariable analysis identified 17 pre-operative factors, including: demographics, laboratory values, comorbid disease, pulmonary and cardiac function, and operative status. The final model significantly predicted the occurrence of pneumonia, and performed well (C-statistic: 0.74). These findings were confirmed via sensitivity analyses by center and clinically important sub-groups. Conclusions We identified 17 readily obtainable pre-operative variables associated with post-operative pneumonia. This model may be used to provide individualized risk estimation and to identify opportunities to reduce a patient’s pre-operative risk of pneumonia through pre-habilitation. PMID:27261082
Cocho, Lidia; Fernández, Itziar; Calonge, Margarita; Martínez, Verónica; González-García, María J; Caballero, Dolores; López-Corral, Lucía; García-Vázquez, Carmen; Vázquez, Lourdes; Stern, Michael E; Enríquez-de-Salamanca, Amalia
To develop a tear molecule level-based predictive model based on a panel of tear cytokines and their correlation with clinical features in ocular chronic graft versus host disease (cGVHD). Twenty-two ocular cGVHD patients and 21 healthy subjects were evaluated in a controlled environmental research laboratory (CERLab). Clinical parameters were recorded, and tears were collected. Levels of 15 molecules (epidermal growth factor [EGF], IL receptor antagonist [IL-1Ra], IL-1β, IL-2, IL-6, IL-8/CXCL8, IL-10, IL-12p70, IL-17A, interferon inducible protein [IP]-10/CXCL10, IFN-γ, VEGF, TNF-α, eotaxin 1, and regulated on activation normal T cell expressed and secreted [RANTES]) were measured by multiplex-bead assay and correlated with clinical parameters. Logistic regression was used to develop a predictive model. Leave-one-out cross-validation was applied. Classification capacity was evaluated in a cohort of individuals with dry eye (DE) of other etiologies different from GVHD. Epidermal growth factor and IP-10/CXCL10 levels were significantly decreased in ocular cGVHD, positively correlating with tear production and stability and negatively correlating with symptoms, hyperemia, and vital staining. Interleukin-1Ra, IL-8/CXCL8, and IL-10 were significantly increased in ocular cGVHD, and the first two correlated positively with symptoms, hyperemia, and ocular surface integrity while negatively correlating with tear production and stability. Predictive models were generated, and the best panel was based on IL-8/CXCL8 and IP-10/CXCL10 tear levels along with age and sex, with an area under the receiving operating curve of 0.9004, sensitivity of 86.36%, and specificity of 95.24%. A predictive model based on tear levels of IL-8/CXCL8 and IP-10/CXCL10 resulted in optimal sensitivity and specificity. These results add further knowledge to the search for potential biomarkers in this devastating ocular inflammatory disease.
Cho, Chan-Ho; Lee, Sang-Bumm
Scleromalacia, in the form of scleral thinning, melting, and necrosis, is a potentially serious complication of pterygium excision. This study introduces a new biodegradable material, Ologen™ collagen matrix (OCM), to repair scleral thinning as an alternative to preserved scleral tissue, and evaluates the long-term outcomes of OCM for ocular surface reconstruction surgery. Two cases of possibly mitomycin C (MMC)-associated marked scleral thinning after pterygium excision with 0.02 % topical MMC for 2-weeks were included in this study. An OCM graft at the scleral thinning area and conjunctival autograft (CAU) were performed on both patients. The scleral defect size was measured and its margin was marked with a biopsy punch. The margin of the scleral thinning area was trimmed by Vannas scissors and the OCM was cut using a circular-shape biopsy punch of the same size. The OCM was sutured with a recipient scleral wall using 10-0 nylon interrupted sutures. Free CAU was harvested from the superonasal bulbar conjunctiva with a punch biopsy 1-mm larger in diameter than that of the OCM. The previously sutured OCM bed was covered with CAU and the graft was secured with 10-0 nylon interrupted sutures. Both patients were examined periodically for over two years by assessing graft thickness and surface vascularization using a slit lamp biomicroscope. Reepithelialization of the ocular surface was observed within three to six days after surgery. Ocular discomfort and inflammation ceased in both patients as the ocular surface quickly stabilized. The entire graft site remained intact and provided a good healthy ocular surface with fluorescein stain negative intact epithelium and good vascularization of grafted conjunctiva. Epithelial defects and scleral thinning did not recur in either patient over the two year follow-up period. For treatment of a possibly MMC-associated scleral necrosis following the surgical excision of the pterygium, an OCM graft with CAU is highly recommended
Vázquez, Natalia; Chacón, Manuel; Rodríguez-Barrientos, Carlos A.; Merayo-Lloves, Jesús; Naveiras, Miguel; Baamonde, Begoña; Alfonso, Jose F.; Zambrano-Andazol, Iriana; Riestra, Ana C.; Meana, Álvaro
Corneal keratoplasty (penetrating or lamellar) using cadaveric human tissue, is nowadays the main treatment for corneal endotelial dysfunctions. However, there is a worldwide shortage of donor corneas available for transplantation and about 53% of the world’s population have no access to corneal transplantation. Generating a complete cornea by tissue engineering is still a tough goal, but an endothelial lamellar graft might be an easier task. In this study, we developed a tissue engineered corneal endothelium by culturing human corneal endothelial cells on a human purified type I collagen membrane. Human corneal endothelial cells were cultured from corneal rims after corneal penetrating keratoplasty and type I collagen was isolated from remnant cancellous bone chips. Isolated type I collagen was analyzed by western blot, liquid chromatography -mass spectrometry and quantified using the exponentially modified protein abundance index. Later on, collagen solution was casted at room temperature obtaining an optically transparent and mechanically manageable membrane that supports the growth of human and rabbit corneal endothelial cells which expressed characteristic markers of corneal endothelium: zonula ocluddens-1 and Na+/K+ ATPase. To evaluate the therapeutic efficiency of our artificial endothelial grafts, human purified type I collagen membranes cultured with rabbit corneal endothelial cells were transplanted in New Zealand white rabbits that were kept under a minimal immunosuppression regimen. Transplanted corneas maintained transparency for as long as 6 weeks without obvious edema or immune rejection and maintaining the same endothelial markers that in a healthy cornea. In conclusion, it is possible to develop an artificial human corneal endothelial graft using remnant tissues that are not employed in transplant procedures. This artificial endothelial graft can restore the integrality of corneal endothelium in an experimental model of endothelial dysfunction
Kim, Bum Soo; Kim, Hyun Tae; Kwon, Se Yun; Chun, So Young; Choi, Kyung Hee; Park, Min; Kim, Dae Hwan; Song, Phil Hyun; Kwon, Tae Gyun
To evaluate the efficacy and feasibility of nontransected ventral onlay-augmented urethroplasty using an autologous saphenous vein graft in a rabbit model of urethral stricture. Ten white male rabbits weighing 3.0-3.5 kg were selected, and a long tract urethral stricture was generated by excising an 0.8-cm wide and 2-cm long portion of the distal urethra. One month after the procedure, the rabbits were randomized into a urethral stricture group (n = 5) or urethroplasty with saphenous vein graft group (n = 5). Another 5 rabbits served as a normal control group. Retrograde urethrography was performed at 2, 4, 8, and 12 weeks after surgery in all groups, and the rabbits were killed at 12 weeks postoperatively for histopathologic and immunohistochemical evaluation. The mean operated urethral width of the normal, stricture, and vein graft group was 10.2 ± 0.84, 4.3 ± 0.97, and 10.04 ± 2.35 mm at 2 weeks postoperatively, respectively (P = .008). The 4-, 8-, and 12-week postoperative urethrograms revealed results similar to those of the 2-week postoperative urethrograms. Histologic analysis showed the neourethra was epithelialized with urothelium in the vein graft group. All the rabbits survived throughout the study period without fistula formation or infection. Nontransected ventral onlay-augmented urethroplasty using an autologous saphenous vein graft can be an effective and feasible procedure for the surgical management of long tract urethral stricture. Copyright © 2014 Elsevier Inc. All rights reserved.
Giraldo, Jaime A; Molano, R Damaris; Rengifo, Hernán R; Fotino, Carmen; Gattás-Asfura, Kerim M; Pileggi, Antonello; Stabler, Cherie L
Islet transplantation is a promising therapy for Type 1 diabetes mellitus; however, host inflammatory and immune responses lead to islet dysfunction and destruction, despite potent systemic immunosuppression. Grafting of poly(ethylene glycol) (PEG) to the periphery of cells or tissues can mitigate inflammation and immune recognition via generation of a steric barrier. Herein, we sought to evaluate the complementary impact of islet PEGylation with a short-course immunotherapy on the survival of fully-MHC mismatched islet allografts (DBA/2 islets into diabetic C57BL/6J recipients). Anti-Lymphocyte Function-associated Antigen 1 (LFA-1) antibody was selected as a complementary, transient, systemic immune monotherapy. Islets were PEGylated via an optimized protocol, with resulting islets exhibiting robust cell viability and function. Following transplantation, a significant subset of diabetic animals receiving PEGylated islets (60%) or anti-LFA-1 antibody (50%) exhibited long-term (>100d) normoglycemia. The combinatorial approach proved synergistic, with 78% of the grafts exhibiting euglycemia long-term. Additional studies examining graft cellular infiltrates at early time points characterized the local impact of the transplant protocol on graft survival. Results illustrate the capacity of a simple polymer grafting approach to impart significant immunoprotective effects via modulation of the local transplant environment, while short-term immunotherapy serves to complement this effect. We believe this study is important and of interest to the biomaterials and transplant community for several reasons: 1) it provides an optimized protocol for the PEGylation of islets, with minimal impact on the coated islets, which can be easily translated for clinical applications; 2) this optimized protocol demonstrates the benefits of islet PEGylation in providing modest immunosuppression in a murine model; 3) this work demonstrates the combinatory impact of PEGylation with short
Taraz-Jamshidi, Mohammad H; Gharadaghi, Mohammad; Mazloumi, Seyed Mahdi; Hallaj-Moghaddam, Mohammad; Ebrahimzadeh, Mohammad H
Background: Although giant cell tumor (GCT) is considered to be a primary benign bone tumor, its aggressive behavior makes its diagnosis and treatment, difficult and challenging. This is especially true in distal radius where GCT appears to be more aggressive and difficult to control locally. We report our clinical outcome of en-block resection and reconstruction with non-vascularized fibular autograft in 15 patients with distal radius GCT. Materials and Methods: We retrospectively reviewed 15 patients with GCT (Grade 2 and 3) of distal radius who were treated with en-block resection and non-vascularized fibular autograft. Five of 15 were recurrent GCT treated initially with extended curettage; local adjuvant therapy and filling the cavity with cement or bone graft. We followed the patients for mean 7.2 years post operation (range: 4-11 years). Patients were evaluated post operation with clinical examination, plain radiography of distal radius and chest X-ray and/or computed tomography scan. Furthermore pain, function, range of motion and grip strength of the affected limb were evaluated and mMayo wrist score was assessed. Results: A total of 11 patients were women and 4 were men. Mean age of patients was 29 years (range: 19-48). We had no lung metastasis and bony recurrence occurred in one patient (6.6%). Nearly 53.3% of patients had excellent or good functional wrist score, 80% of the patients were free of pain or had only occasional pain and 80% of patients returned to work. Mean range of motion of the wrist was 77° of flexion-extension and mean grip strength was 70% of the normal hand. Conclusion: En-block resection of distal radius GCT and reconstruction with non-vascularized fibular autograft is an effective technique for treatment in local control of the tumor and preserving function of the limb. PMID:24778664
Fiuza-Luces, Carmen; Soares-Miranda, Luisa; González-Murillo, Africa; Palacio, Jesús Martínez; Colmenero, Isabel; Casco, Fernando; Melén, Gustavo J; Delmiro, Aitor; Morán, María; Ramírez, Manuel; Lucia, Alejandro
Chronic graft versus host disease (cGVHD) is a life-threatening complication of allogeneic hematopoietic stem cell transplantation that generates considerable morbidity and compromises the physical capacity of patients. We determined the effects of an exercise training program performed after allogeneic hematopoietic stem cell transplantation on clinical and biological variables in a minor histocompatibility antigen-driven murine model of cGVHD treated with cyclosporine A. Recipient BALB/C female mice (age 8 wk) received bone marrow cells and splenocytes from donor B10.D2 male mice and were randomly assigned to an exercise (n = 11) or control group (n = 12). For approximately 11 wk after transplant, the exercise group completed a moderate-intensity treadmill program. Variables assessed were clinical severity scores, survival, physical fitness, cytokine profile, immune cell reconstitution, molecular markers of muscle exercise adaptations, and histological scores in affected tissues. Exercise training increased survival (P = 0.011), diminished total clinical severity scores (P = 0.002), improved physical fitness (P = 0.030), and reduced blood IL-4 and tumor necrosis factor α levels (P = 0.03), while increasing circulating B220 (P = 0.008) and CD4 lymphocytes (P = 0.043). A moderate-intensity exercise program that mimics widely accepted public health recommendations for physical activity in human adults was well tolerated and positive effects on survival as well as on clinical and biological indicators of cGVHD.
Gulick, Dawn T.; Yoder, Heather N.
An injury to the ACL can result in significant functional impairment. It has been estimated that more than 100,000 new ACL injuries occur each year. Surgeons employ numerous techniques for reconstruction of the ACL. Of critical importance is the source of the graft to replace the damaged ACL. The graft choices include autografts (the patient's own tissue), allografts (donor tendon), and synthetic/prosthetic ligaments. Tissue harvest sites for autografting include the middle third of the patella tendon, the quadriceps tendon, semitendinosus tendon, gracilis tendon, iliotibial band, tensor fascia lata, and the Achilles tendon. Selection of the type of graft material is predicated upon the tissue's ability to tolerate high levels of stress. Likewise, the clinical presentation and functional outcome is related to the graft material selected. This manuscript specifically examined the patella tendon and hamstring tendon grafts. Numerous manuscripts that studied the outcomes of these graft materials were compiled to help the clinician appreciate the advantages and disadvantages of each of the graft materials. Outcome measures such as thigh circumference, knee range of motion, isokinetic strength, knee stability, pain, and vertical jump/1-leg hop were incorporated. The purpose of this manuscript was to compare and contrast the clinical presentation of patients who underwent an ACL reconstruction using the patella tendon versus the hamstring tendons. This information can be valuable to the clinician when considering the rehabilitation protocol after ACL reconstruction. PMID:24701126
Kim, Young-Sung; Kim, Su-Hwan; Kim, Kyoung-Hwa; Jhin, Min-Ju; Kim, Won-Kyung; Lee, Young-Kyoo; Seol, Yang-Jo
Purpose This study was performed to establish an experimental rabbit model for single-stage maxillary sinus augmentation with simultaneous implant placement. Methods Twelve mature New Zealand white rabbits were used for the experiments. The rabbit maxillary sinuses were divided into 3 groups according to sinus augmentation materials: blood clot (BC), autogenous bone (AB), and bovine-derived hydroxyapatite (BHA). Small titanium implants were simultaneously placed in the animals during the sinus augmentation procedure. The rabbits were sacrificed 4 and 8 weeks after surgery and were observed histologically. Histomorphometric analyses using image analysis software were also performed to evaluate the parameters related to bone regeneration and implant-bone integration. Results The BC group showed an evident collapse of the sinus membrane and limited new bone formation around the original sinus floor at 4 and 8 weeks. In the AB group, the sinus membrane was well retained above the implant apex, and new bone formation was significant at both examination periods. The BHA group also showed retention of the elevated sinus membrane above the screw apex and evident new bone formation at both points in time. The total area of the mineral component (TMA) in the area of interest and the bone-to-implant contact did not show any significant differences among all the groups. In the AB group, the TMA had significantly decreased from 4 to 8 weeks. Conclusions Within the limits of this study, the rabbit sinus model showed satisfactory results in the comparison of different grafting conditions in single-stage sinus floor elevation with simultaneous implant placement. We found that the rabbit model was useful for maxillary sinus augmentation with simultaneous implant placement. PMID:23346463
Han, Songfeng; Proctor, Ashley R.; Vella, Joseph B.; Benoit, Danielle S. W.; Choe, Regine
Longitudinal blood flow during murine bone graft healing was monitored non-invasively using diffuse correlation tomography. The system utilized spatially dense data from a scanning set-up, non-linear reconstruction, and micro-CT anatomical information. Weekly in vivo measurements were performed. Blood flow changes in autografts, which heal successfully, were localized to graft regions and consistent across mice. Poor healing allografts showed heterogeneous blood flow elevation and high inter-subject variabilities. Allografts with tissue-engineered periosteum showed responses intermediate to both autografts and allografts, consistent with healing observed. These findings suggest that spatiotemporal blood flow changes can be utilized to differentiate the degree of bone graft healing. PMID:27699097
McDonald, Robert A.; White, Katie M.; Wu, Junxi; Cooley, Brian C.; Robertson, Keith E.; Halliday, Crawford A.; McClure, John D.; Francis, Sheila; Lu, Ruifaug; Kennedy, Simon; George, Sarah J.; Wan, Song; van Rooij, Eva; Baker, Andrew H.
Aims The long-term failure of autologous saphenous vein bypass grafts due to neointimal thickening is a major clinical burden. Identifying novel strategies to prevent neointimal thickening is important. Thus, this study aimed to identify microRNAs (miRNAs) that are dysregulated during neointimal formation and determine their pathophysiological relevance following miRNA manipulation. Methods and results We undertook a microarray approach to identify dysregulated miRNAs following engraftment in an interpositional porcine graft model. These profiling experiments identified a number of miRNAs which were dysregulated following engraftment. miR-21 levels were substantially elevated following engraftment and these results were confirmed by quantitative real-time PCR in mouse, pig, and human models of vein graft neointimal formation. Genetic ablation of miR-21 in mice or grafted veins dramatically reduced neointimal formation in a mouse model of vein grafting. Furthermore, pharmacological knockdown of miR-21 in human veins resulted in target gene de-repression and a significant reduction in neointimal formation. Conclusion This is the first report demonstrating that miR-21 plays a pathological role in vein graft failure. Furthermore, we also provided evidence that knockdown of miR-21 has therapeutic potential for the prevention of pathological vein graft remodelling. PMID:23530023
McDonald, Robert A; White, Katie M; Wu, Junxi; Cooley, Brian C; Robertson, Keith E; Halliday, Crawford A; McClure, John D; Francis, Sheila; Lu, Ruifaug; Kennedy, Simon; George, Sarah J; Wan, Song; van Rooij, Eva; Baker, Andrew H
The long-term failure of autologous saphenous vein bypass grafts due to neointimal thickening is a major clinical burden. Identifying novel strategies to prevent neointimal thickening is important. Thus, this study aimed to identify microRNAs (miRNAs) that are dysregulated during neointimal formation and determine their pathophysiological relevance following miRNA manipulation. We undertook a microarray approach to identify dysregulated miRNAs following engraftment in an interpositional porcine graft model. These profiling experiments identified a number of miRNAs which were dysregulated following engraftment. miR-21 levels were substantially elevated following engraftment and these results were confirmed by quantitative real-time PCR in mouse, pig, and human models of vein graft neointimal formation. Genetic ablation of miR-21 in mice or grafted veins dramatically reduced neointimal formation in a mouse model of vein grafting. Furthermore, pharmacological knockdown of miR-21 in human veins resulted in target gene de-repression and a significant reduction in neointimal formation. This is the first report demonstrating that miR-21 plays a pathological role in vein graft failure. Furthermore, we also provided evidence that knockdown of miR-21 has therapeutic potential for the prevention of pathological vein graft remodelling.
Bezinover, Dmitri; Ramamoorthy, Saravanan; Postula, Marek; Weller, Gregory; Mahmoud, Saifeldin; Mani, Haresh; Kadry, Zakiyah; Uemura, Tadahiro; Mets, Berend; Spiess, Bruce; Brucklacher, Robert; Freeman, Willard; Janicki, Piotr K
Effects of two perfluorocarbon (PFC) formulations (perfluorodecalin emulsion and perfluorodecalin liquid) on the quality of liver graft preservation, in a donation after cardiac death (DCD) rat model, were investigated. The significance of continuous graft perfusion during cold preservation was also explored. DCD model: 30 min after cardiopulmonary arrest was initiated, livers were excised and flushed with cold University of Wisconsin (UW) solution (± PFC) and preserved in the same solution for 8 h. The study groups were preserved as follows: group 1: no perfusion; group 2: perfusion with UW; group 3: PFC was administered before cardiac arrest and the liver was perfused with UW alone; and groups 4 and 5: perfused with UW + 1 of two PFCs. In a baseline group used only for comparison of gene expression, livers were quick-frozen after cardiac arrest. Microarrays were used to analyze liver messenger RNA transcripts. Histopathologic, immunohistochemical, and ADP/ATP ratio evaluations were performed to assess the quality of graft preservation. Significant decreases in downregulation and increases in upregulation of hepatic genes (relative to baseline) were demonstrated in all perfusion groups. This trend was most pronounced in the PFC groups. Lower fat content and ADP/ATP ratio and a reduction in Caspase 3 activation were found in all perfusion groups. Hypothermic perfusion of rat DCD liver grafts with oxygenated UW solution (± PFC) produced superior preservation compared with nonperfusion storage. The observed changes in expression of hepatic genes may represent a protective effect in the DCD model. Copyright © 2014 Elsevier Inc. All rights reserved.
Zhang, Y; Yang, M; Yang, Y; Zheng, S L; Cai, Y; Xia, P; Chen, W W; Chen, B C; Yang, Y R
The purpose of the current study was to evaluate the effects of thalidomide on graft arteriosclerosis. Male Lewis rats received abdominal aorta grafts from male Brown-Norway rats. The animals were divided into 4 groups: no treatment controls, a low-dose group that received thalidomide (50 mg/kg per day), a middle dose group that received thalidomide (100 mg/kg per day), and a high-dose group that received thalidomide (200 mg/kg per day) by daily intragastric administration. Rats were humanely killed at 60 days after surgery. The grafted aortas were analyzed by histology, immunohistochemistry, and Western blot analysis. The serum was analyzed by an enzyme-linked immunosorbent assay (ELISA). The neointimal thickness of the thalidomide treated aortas was significantly thinner compared with that of no treatment aortas (P < .05). Vascular endothelial growth factor (VEGF), platelet-derived growth factor, and intracellular adhesian molecule (ICAM-1) protein expression in the treatment group were significantly lower than those in the control group (P < .05). Moreover, thalidomide significantly inhibited the production of VEGF and ICAM-1 in serum (P < .05). Our data suggested that thalidomide can attenuate graft arteriosclerosis so as to protect aortic grafts. Copyright © 2011 Elsevier Inc. All rights reserved.
Background Scaffold-assisted autologous chondrocyte implantation is an effective clinical procedure for cartilage repair. From the regulatory point of view, the ovine model is one of the suggested large animal models for pre-clinical studies. The aim of our study was to evaluate the in vitro re-differentiation capacity of expanded ovine chondrocytes in biomechanically characterized polyglycolic acid (PGA)/fibrin biomaterials for scaffold-assisted cartilage repair. Methods Ovine chondrocytes harvested from adult articular cartilage were expanded in monolayer and re-assembled three-dimensionally in PGA-fibrin scaffolds. De- and re-differentiation of ovine chondrocytes in PGA-fibrin scaffolds was assessed by histological and immuno-histochemical staining as well as by real-time gene expression analysis of typical cartilage marker molecules and the matrix-remodelling enzymes matrix metalloproteinases (MMP) -1, -2 and −13 as well as their inhibitors. PGA scaffolds characteristics including degradation and stiffness were analysed by electron microscopy and biomechanical testing. Results Histological, immuno-histochemical and gene expression analysis showed that dedifferentiated chondrocytes re-differentiate in PGA-fibrin scaffolds and form a cartilaginous matrix. Re-differentiation was accompanied by the induction of type II collagen and aggrecan, while MMP expression decreased in prolonged tissue culture. Electron microscopy and biomechanical tests revealed that the non-woven PGA scaffold shows a textile structure with high tensile strength of 3.6 N/mm2 and a stiffness of up to 0.44 N/mm2, when combined with gel-like fibrin. Conclusion These data suggest that PGA-fibrin is suited as a mechanically stable support structure for scaffold-assisted chondrocyte grafts, initiating chondrogenic re-differentiation of expanded chondrocytes. PMID:23137017
AWARD NUMBER: W81XWH-13-2-0087 TITLE: Optimization of Soft Tissue Management, Spacer Design, and Grafting Strategies for Large Segmental Bone...Design, and Grafting Strategies for Large Segmental Bone Defects using the Chronic Caprine Tibial Defect Model 5a. CONTRACT NUMBER 5b. GRANT NUMBER...can be immediately translated into clinical practice. This study highlights the fact that the Chronic Caprine Tibial Defect Model is sufficiently
Ree, Jennifer J.; Baltzer, Wendy I.; Townsend, Katy L.
A technique for using free autogenous omental grafting with arthrodesis in dogs is described and radiographic osseous union and complications after surgery are evaluated. This retrospective study matched body weight and procedure type for 8 cases of pancarpal arthrodesis, 4 cases of pantarsal arthrodesis, and 2 cases of partial tarsal arthrodesis in dogs with omental and cancellous bone autograft (OBG group) and with cancellous bone autograft alone (BG group). Radiographs were reviewed 9 to 12 weeks after surgery to compare scores of radiographic osseous union and it was found that the OBG group had higher scores than the BG group. The BG group had significantly more major complications that required re-operation for implant removal or treatment of a deep infection compared to the OBG group. Overall, free autogenous omental grafts may be used to augment arthrodesis in dogs without significant morbidity and further investigation of its use to reduce major complications and speed bone healing are warranted. PMID:27493282
Pereira, G. C.T.; Kubiak, E. N.; Levine, B.; Chen, F. S.
The use of impacted morselized cancellous bone grafts in conjunction with cementless hemispherical acetabular cups for treatment of AAOS type II acetabular cavitary deficiencies was evaluated in a retrospective study of 23 primary and 24 revision total hip arthroplasties, at a mean follow-up of 7.9 and 8.1 years, respectively. All primary hips received autografts, while all revision hips received allografts. Modified Harris Hip Scores for primary and revision hip replacements increased from a pre-operative mean of 37 and 47 to a postoperative mean of 90 and 86, respectively. All 23 autografts and 23 out of 24 cancellous allografts were radiographically incorporated without evidence of resorption. There were no instances of infection, component migration, or cases requiring subsequent acetabular revision. We conclude that impacted morselized cancellous bone-graft augmentation of cementless cups is a viable surgical option for AAOS type II cavitary acetabular defects. PMID:16988799
Shetty, Ashok K.; Hattiangady, Bharathi
Degeneration of the CA3 pyramidal and dentate hilar neurons in the adult rat hippocampus after an intracerebroventricular kainic acid (KA) administration, a model of temporal lobe epilepsy, leads to permanent loss of the calcium binding protein calbindin in major fractions of dentate granule cells and CA1 pyramidal neurons. We hypothesize that the enduring loss of calbindin in the dentate gyrus and the CA1 subfield after CA3-lesion is due to disruption of the hippocampal circuitry leading to hyperexcitability in these regions; therefore, specific cell grafts that are capable of both reconstructing the disrupted circuitry and suppressing hyper-excitability in the injured hippocampus can restore calbindin. We compared the effects of fetal CA3 or CA1 cell grafting into the injured CA3 region of adult rats at 45 days after KA-induced injury on the hippocampal calbindin. The calbindin immunoreactivity in the dentate granule cells and the CA1 pyramidal neurons of grafted animals was evaluated at 6 months after injury (i.e. at 4.5 months post-grafting). Compared with the intact hippocampus, the calbindin in “lesion-only” hippocampus was dramatically reduced at 6 months post-lesion. However, calbindin expression was restored in the lesioned hippocampus receiving CA3 cell grafts. In contrast, in the lesioned hippocampus receiving CA1 cell grafts, calbindin expression remained less than the intact hippocampus. Thus, specific cell grafting restores the injury-induced loss of calbindin in the adult hippocampus, likely via restitution of the disrupted circuitry. Since loss of calbindin after hippocampal injury is linked to hyperexcitability, re-expression of calbindin in both dentate gyrus and CA1 subfield following CA3 cell grafting may suggest that specific cell grafting is efficacious for ameliorating injury-induced hyperexcitability in the adult hippocampus. However, electrophysiological studies of KA-lesioned hippocampus receiving CA3 cell grafts are required in future
Nabian, Mohammad Hosein; Nadji-Tehrani, Mehdi; Zanjani, Leila Oryadi; Kamrani, Reza Shahryar; Rahimi-Movaghar, Vafa; Firouzi, Masoumeh
Autologous nerve graft is still the treatment of choice in peripheral nerve injury when end-to-end nerve repair is not possible. The sciatic nerve is the most widely used nerve in rat experimental studies. To assess the possibility of using the rat median nerve as a delayed animal autologous nerve graft model in nerve regeneration studies, the effect of median nerve excision on the sciatic functional index (SFI) was evaluated. Thirty rats were distributed into three equal groups: in the sciatic and median nerve excision (SMNE) group, 10 mm of the right sciatic nerve was excised and 5 mm of both median nerves were excised a week later; in the median nerve excision (MNE) group, 5 mm of both median nerves were excised (both sciatic nerves remained intact); in the control group, no intervention was performed. SFI was calculated before and after each intervention. There was no significant difference between mean SFI values calculated before and after median nerve excision in SMNE (-86.8 versus -88.4, P = 0.61) and MNE groups (-3.9 versus -3.3, P = 0.93). Therefore, it may be suggested that median nerve excision does not affect SFI measurements in intact and/or completely injured sciatic nerve, which may propose the median nerve as an autologous donor nerve graft model in rats. © Thieme Medical Publishers.
Niu, Yuqing; Li, Linjing; Chen, Kevin C; Chen, Feiran; Liu, Xiangyu; Ye, Jianfu; Li, Wei; Xu, Kaitian
Nerve repair scaffolds from novel alternating block polyurethanes (PUCL-alt-PEG) based on PCL and PEG without additional growth factors or proteins were prepared by a particle leaching method. The scaffolds have pore size 10-20 µm and porosity 92%. Mechanical tests showed that the polyurethane scaffolds have maximum loads of 5.97 ± 0.35 N and maximal stresses of 8.84 ± 0.5 MPa. Histocompatiblity of the nerve repair scaffolds was tested in a SD rat model for peripheral nerve defect treatment. Two types of treatments including PUCL-alt-PEG scaffolds and autografts were compared in rat model. After 32 weeks, bridging of a 12 mm defect gap by the regenerated nerve was observed in all rats. The nerve regeneration was systematically characterized by sciatic function index (SFI), electrophysiology, histological assessment including HE staining, immunohistochemistry, ammonia sliver staining, Masson's trichrome staining and TEM observation. Results revealed that nerve repair scaffolds from PUCL-alt-PEG exhibit better regeneration effects compared to autografts. Electrophysiological recovery was seen in 90% and 87% of rats in PUCL-alt-PEG and autograft groups respectively. Biodegradation in vitro and in vivo shows good degradation match of PUCL-alt-PEG scaffolds with nerve regeneration. It demonstrates that plain nerve repair scaffolds from PUCL-alt-PEG biomaterials can achieve peripheral nerve regeneration satisfactorily.
Sankaran, Sethuraman; Marsden, Alison L.
It is well known that the fluid mechanics of bypass grafts impacts biomechanical responses and is linked to intimal thickening and plaque deposition on the vessel wall. In spite of this, quantitative information about the fluid mechanics is not currently incorporated into surgical planning and bypass graft design. In this work, we use a derivative-free optimization technique for performing systematic design of bypass grafts. The optimization method is coupled to a three-dimensional pulsatile Navier-Stokes solver. We systematically account for inevitable uncertainties that arise in cardiovascular simulations, owing to noise in medical image data, variable physiologic conditions, and surgical implementation. Uncertainties in the simulation input parameters as well as shape design variables are accounted for using the adaptive stochastic collocation technique. The derivative-free optimization framework is coupled with a stochastic response surface technique to make the problem computationally tractable. Two idealized numerical examples, an end-to-side anastomosis, and a bypass graft around a stenosis, demonstrate that accounting for uncertainty significantly changes the optimal graft design. Results show that small changes in the design variables from their optimal values should be accounted for in surgical planning. Changes in the downstream (distal) graft angle resulted in greater sensitivity of the wall-shear stress compared to changes in the upstream (proximal) angle. The impact of cost function choice on the optimal solution was explored. Additionally, this work represents the first use of the stochastic surrogate management framework method for robust shape optimization in a fully three-dimensional unsteady Navier-Stokes design problem.
Meng, Q-H; Irvine, S; Tagalakis, A D; McAnulty, R J; McEwan, J R; Hart, S L
Vein graft failure caused by neointimal hyperplasia (IH) after coronary artery bypass grafting with saphenous veins is a major clinical problem. The lack of safe and efficient vectors for vascular gene transfer has significantly hindered progress in this field. We have developed a Receptor-Targeted Nanocomplex (RTN) vector system for this purpose and assessed its therapeutic efficacy in a rabbit vein graft model of bypass grafting. Adventitial delivery of β-Galactosidase showed widespread transfection throughout the vein wall on day 7, estimated at about 10% of cells in the adventitia and media. Vein grafts were then transfected with a plasmid encoding inducible nitric oxide synthase (iNOS) and engrafted into the carotid artery. Fluorescent immunohistochemistry analysis of samples from rabbits killed at 7 days after surgery showed that mostly endothelial cells and macrophages were transfected. Morphometric analysis of vein graft samples from the 28-day groups showed approximately a 50% reduction of neointimal thickness and 64% reduction of neointimal area in the iNOS-treated group compared with the surgery control groups. This study demonstrates efficacy of iNOS gene delivery by the RTN formulation in reducing IH in the rabbit model of vein graft disease. PMID:23636244
Lei, M; Giddens, D P; Jones, S A; Loth, F; Bassiouny, H
Various hemodynamic factors have been implicated in vascular graft intimal hyperplasia, the major mechanism contributing to chronic failure of small-diameter grafts. However, a thorough knowledge of the graft flow field is needed in order to determine the role of hemodynamics and how these factors affect the underlying biological processes. Computational fluid dynamics offers much more versatility and resolution than in vitro or in vivo methods, yet computations must be validated by careful comparison with experimental data. Whereas numerous numerical and in vitro simulations of arterial geometries have been reported, direct point-by-point comparisons of the two techniques are rare in the literature. We have conducted finite element computational analyses for a model of an end-to-side vascular graft and compared the results with experimental data obtained using laser-Doppler velocimetry. Agreement for velocity profiles is found to be good, with some clear differences near the recirculation zones during the deceleration and reverse-flow segments of the flow waveform. Wall shear stresses are determined from velocity gradients, whether by computational or experimental methods, and hence the agreement for this quantity, while still good, is less consistent than for velocity itself from the wall shear stress numerical results, we computed four variables that have been cited in the development of intiimal hyperplasia-the time-averaged wall shear stress, an oscillating shear index, and spatial and temporal wall shear stress gradients in order to illustrate the versatility of numerical methods. We conclude that the computational approach is a valid alternative to the experimental approach for quantitative hemodynamic studies. Where differences in velocity were found by the two methods, it was generally attributed to the inability of the numerical method to model the fluid dynamics when flow conditions are destabilizing. Differences in wall shear, in the absence of
Tang, Bing; Zhu, Bin; Liang, Yue-Ying; Bi, Liang-Kuan; Chen, Bin; Hu, Zhi-Cheng; Zhang, Kai; Zhu, Jia-Yuan
Although escharectomy and full-thickness skin autografting have been widely used to treat deep facial burns, the clinical outcomes remain unacceptable. Composite razor-thin skin grafting over acellular dermal matrix scaffold has been used successfully in repairing burns of the trunk and limbs, but its use in covering deep facial burns has rarely been reported. In this study, the authors investigated the clinical outcomes of early escharectomy and concurrent composite razor-thin skin autografting and acellular dermal matrix scaffold for treating deep facial burns. Patients with deep facial burns (n = 16) involving 8 to 30 percent of the total body surface area received early escharectomy by postburn day 3 and concurrent, one-stage, large, razor-thin skin autografting on top of human acellular dermal matrix scaffold. Wound dressings were changed on postoperative days 7, 9, and 12 to examine the survival of skin autografts. Patients were followed up for 12 months to evaluate their facial profiles. The take rate of composite skin autografts was 97.3 percent at postoperative day 12. At the follow-up visit, the skin autografts appeared normal in color, with soft texture and good elasticity. The skin junctures showed little scarring. The patients exhibited a chubby facial appearance and abundant expression, except for one patient with microstomia and two patients with ectropion who required further plastic surgical interventions. Early escharectomy and concurrent composite razor-thin skin autografting on top of acellular dermal matrix scaffold constitute an effective and favorable option for covering deep facial burns, especially for patients with limited donor sites.
Schmid, Peter M; Bouazzaoui, Abdellatif; Schmid, Karin; Birner, Christoph; Schach, Christian; Maier, Lars S; Holler, Ernst; Endemann, Dierk H
Acute kidney injury (AKI) is a very common complication after allogeneic bone marrow transplantation (BMT) and associated with poor prognosis. Generally kidneys are assumed to be no direct target of Graft-versus-Host Disease (GvHD), and renal impairment is often attributed to several other factors occurring in the early phase after BMT. Our study aimed to prove the existence of renal GvHD in a fully MHC-mismatched model of BALB/c mice conditioned and transplanted according to two different intensity protocols. Syngeneically transplanted and untreated animals served as controls. 4 weeks after transplantation, allogeneic animals developed acute GvHD that was more pronounced in the high-intensity protocol (HIP) group than in the low-intensity protocol (LIP) group. Urea and creatinine as classic serum markers of renal function could not verify renal impairment 4 weeks after BMT. Creatinine levels were even reduced as a result of catabolic metabolism and loss of muscle mass due to acute GvHD. Proteinuria, albuminuria, and urinary N-acetyl-beta-Dglucosaminidase (NAG) levels were measured as additional renal markers before and after transplantation. Albuminuria and NAG were only significantly increased after allogeneic transplantation, correlating with disease severity between HIP and LIP animals. Histological investigations of the kidneys showed renal infiltration of T-cells and macrophages with endarteriitis, interstitial nephritis, tubulitis, and glomerulitis. T-cells consisted of CD4+, CD8+, and FoxP3+ cells. Renal expression analysis of allogeneic animals showed increases in indoleamine-2,3 dioxygenase (IDO), different cytokines (TNFα, IFN-γ, IL-1α, IL2, IL-6, and IL-10), and adhesion molecules (ICAM-1 and VCAM-1), resembling findings from other tissues in acute GvHD. In summary, our study supports the entity of renal GvHD with histological features suggestive of cell-mediated renal injury. Albuminuria and urinary NAG levels may serve as early markers of renal
Han, Songfeng; Johansson, Johannes; Mireles, Miguel; Proctor, Ashley R; Hoffman, Michael D; Vella, Joseph B; Benoit, Danielle S W; Durduran, Turgut; Choe, Regine
A non-contact galvanometer-based optical scanning system for diffuse correlation tomography was developed for monitoring bone graft healing in a murine femur model. A linear image reconstruction algorithm for diffuse correlation tomography was tested using finite-element method based simulated data and experimental data from a femur or a tube suspended in a homogeneous liquid phantom. Finally, the non-contact system was utilized to monitor in vivo blood flow changes prior to and one week after bone graft transplantation within murine femurs. Localized blood flow changes were observed in three mice, demonstrating a potential for quantification of longitudinal blood flow associated with bone graft healing.
Han, Songfeng; Johansson, Johannes; Mireles, Miguel; Proctor, Ashley R.; Hoffman, Michael D.; Vella, Joseph B.; Benoit, Danielle S. W.; Durduran, Turgut; Choe, Regine
A non-contact galvanometer-based optical scanning system for diffuse correlation tomography was developed for monitoring bone graft healing in a murine femur model. A linear image reconstruction algorithm for diffuse correlation tomography was tested using finite-element method based simulated data and experimental data from a femur or a tube suspended in a homogeneous liquid phantom. Finally, the non-contact system was utilized to monitor in vivo blood flow changes prior to and one week after bone graft transplantation within murine femurs. Localized blood flow changes were observed in three mice, demonstrating a potential for quantification of longitudinal blood flow associated with bone graft healing. PMID:26203392
Fowler, B L; DiStefano, V J
A problem that is frequently encountered during endoscopic anterior cruciate ligament reconstruction bone-patellar tendon-bone autograft is that the graft is often too long and protrudes from the tibial tunnel. If less than 20 mm of the bone plug remains in the tibial tunnel, interference screw fixation cannot safely be used, and an alternate form of fixation may have to be employed. A simple technique has been developed to deal with this problem. The technique involves bone-grafting the tibial tunnel with a cancellous core of bone that is removed while creating the tibial tunnel. This not only makes it possible to safely use interference screw fixation in all cases, but it also makes it possible to place the point of graft fixation very near the anatomic anterior cruciate ligament insertion site.
Saifzadeh, Siamak; Hobbenaghi, Rahim; Asadolahi, Aysan
Esophagotomy is commonly complicated by dehiscence and leakage. Recent studies provided evidence that omentopexy may reinforce the esophageal suture line and decrease the rate of postoperative complications. The use of nonvascularized omental autograft (NOA) to strengthen the linear esophagotomy wound is novel and this was derived from its successful use in other location by Saifzadeh et al. The goal of the current study was to examine the role of NOA on the healing quality of primary esophagotomy wound. Linear esophageal incisions of 8-10 mm were made at the cervical esophagus in 20 New Zealand white rabbits, which were assigned to two identical groups (10 rabbits in each group). The incisions were sutured in both groups but additionally covered by NOA in Group Pi. Twenty-eight days after the operations, the experimental animals were killed, and identical segments of the esophagus with the esophagotomy line at the center were removed. The intact specimens were evaluated for bursting pressure and histologic appearance. Bursting pressure was higher in Group Pi. Microscopic evaluation in Group Pi rabbits revealed the participation of NOA in esophagotomy healing, tough complete epithelial regeneration, marked neovascularization, and muscular regeneration and overgrowth. This study showed demonstrable benefit from the use of NOA in reinforcement of cervical esophagotomy. To the best of our knowledge, this is the first report of strengthening of the esophageal suture line with the transplantation of NOA.
Bagherifard, Abolfazl; Ghandhari, Hassan; Jabalameli, Mahmoud; Rahbar, Mohammad; Hadi, Hosseinali; Moayedfar, Mehdi; Sajadi, Mohammadreza Minatour; Karimpour, Alireza
There is no consensus regarding the use of filling agent in the re-elevation of depressed tibial plateau fracture (TPF). Although autograft is considered as the gold standard approach of such reconstructions, its limitation has led to a recent attraction toward allograft substitution. In this study, we compare the complications and outcome of autograft and allograft in TPF reconstruction, in order to address the existing controversy. A total of 81 patients with acute TPF were included in this study. Allograft and autograft were applied in 58 and 23 cases, respectively. The mean age of the patients was 40.26 years, and the mean follow-up period of patients was 19.1 months. Clinical and radiological assessment of the outcome was conducted, employing the modified Rasmussen clinical criteria. A total of three infections were observed in our patients, from which two infections occurred in allograft received patients. Articular surface collapse was seen in two cases, including one allograft and one autograft receiving patient. The mean clinical score was 18.65 and 18.55 in autograft and allograft received patients, respectively (p = 0.09). The mean radiological score was 15.65 and 15.68 in autograft and allograft received patients (p = 0.3). With respect to the comparable complication rate, clinical and radiological outcome of allogenic versus autologous reconstruction of TPF, freeze-dried allograft could be recommended as an appropriate substitute of autograft in this treatment. Nevertheless, the longer follow-up period of the patients could further extend our understanding of the clinical outcome of each component.
Huffaker, R Keith; Muir, Tristi W; Rao, Arundhati; Baumann, Shannon S; Kuehl, Thomas J; Pierce, Lisa M
The purpose of this study was to determine whether the host tissue response in the rabbit vagina differs for 2 synthetic graft materials that are used in pelvic reconstructive surgery. One strip of porcine collagen-coated or uncoated polypropylene mesh was implanted adjacent to a sham operative site into the posterior vagina of 10 New Zealand white rabbits and harvested 12 weeks later. Rabbits were assigned randomly to group 1 (coated; n = 5), group 2 (uncoated; n = 5), or group 3 (unoperated; n = 4). Full-thickness sagittal sections of posterior vaginal wall and rectum were scored for inflammation, neovascularization, and fibroblastic proliferation. Erosion of grafts did not occur in any animal. Coated and uncoated meshes induced a mild inflammatory response with minimal fibrosis and good host tissue incorporation within the grafts. Few apoptotic and proliferating cells were seen for both graft types. Both coated and uncoated polypropylene meshes elicit a mild foreign body reaction and minimal fibrotic response without evidence of vaginal epithelial erosion.
Chintawar, Satyan; Hourez, Raphael; Ravella, Ajay; Gall, David; Orduz, David; Rai, Myriam; Bishop, Don Patrick; Geuna, Stefano; Schiffmann, Serge N; Pandolfo, Massimo
The B05 transgenic SCA1 mice, expressing human ataxin-1 with an expanded polyglutamine tract in cerebellar Purkinje cells (PCs), recapitulate many pathological and behavioral characteristics of the neurodegenerative disease spinocerebellar ataxia type 1 (SCA1), including progressive ataxia and PC loss. We transplanted neural precursor cells (NPCs) derived from the subventricular zone of GFP-expressing adult mice into the cerebellar white matter of SCA1 mice when they showed absent (5 weeks), initial (13 weeks), and significant (24 weeks) PC loss. Only in mice with significant cell loss, grafted NPCs migrated into the cerebellar cortex. These animals showed improved motor skills compared with sham-treated controls. No grafted cell adopted the morphological and immunohistochemical characteristics of PCs, but the cerebellar cortex in NPC-grafted SCA1 mice had a significantly thicker molecular layer and more surviving PCs. Perforated patch-clamp recordings revealed a normalization of the PC basal membrane potential, which was abnormally depolarized in sham-treated animals. No significant increase in levels of several neurotrophic factors was observed, suggesting, along with morphological observation, that the neuroprotective effect of grafted NPCs was mediated by direct contact with the host PCs. We postulate that a similar neuroprotective effect of NPCs may be applicable to other cerebellar degenerative diseases.
Claro, Francisco; Moreira, Luciana R; Morari, Joseane; Sarian, Luis O Z; Pinto, Glauce A; Velloso, Licio A; Pinto-Neto, Aara O M
The results of experimental studies indicate that grafting of autologous adipose tissue may induce tumorigenesis at the recipient site, but clinical results do not support a carcinogenic effect of fat grafting to the breast. The authors assessed cancer risk following transplantation of autologous fat into murine mammary tissue. In this animal study, mammary tissues from 54 breasts of 9 female rats were either grafted with autologous subcutaneous fat, grafted with autologous omental fat, or unmanipulated. Tissues were harvested and processed for histologic and immunohistochemical analyses, and the mRNA expression levels of specific genes were determined. No atypia or changes in lobular structures were observed in lipofilled breasts compared with controls. The numbers of ductal cell layers and terminal ductal units were similar for lipofilled and control breasts. Macrophage concentrations also were similar for the 3 groups. The localization and magnitude of plasminogen activator inhibitor 1 were similar for lipofilled and unmanipulated breast tissue. The percentages of cells expressing Ki67 or estrogen receptor (ER) and the ER/Ki67 balance were similar for the 3 groups. Gene expression was not altered in lipofilled breasts, compared with controls. No theoretical risk of cancer was detected in the microenvironment of the lipofilled rat breast.
Perez, Julian; Eigenbrode, Sanford D; Hilje, Luko; Tripepi, Robert R; Aguilar, Maria E; Mesen, Francisco
The susceptible species Cedrela odorata and Swietenia macrophylla to attack by Hypsipyla grandella (Zeller) larvae were grafted onto the resistant species Khaya senegalensis and Toona ciliata. Six-month-old grafted plants were then compared to their reciprocal grafts and to both intact (non-grafted) and autografted plants for damage due to H. grandella larvae and for their effects on larval performance. Two experiments were conducted: one in which the apical bud of the main plant shoot was inoculated with H. grandella eggs, and the other in which the bud was inoculated with third instars. Damage in each experiment was assessed by the number of frass piles, number and length of tunnels, number of damaged leaves, and damage to the apical bud. Larval performance was evaluated in terms of time to reach pupation and pupal weight and length. In both experiments, plant damage differed significantly among treatments (P < 0.03). Resistant rootstocks conferred resistance to susceptible scions. In both experiments, grafting by itself, regardless of the rootstock and scion combination, also reduced damage caused by H. grandella larvae. Scions of autografted susceptible species had similar resistance to susceptible scions grafted on resistant rootstocks. Few larvae reached pupation, and their pupal weight and length were similar.
Perez-Basterrechea, Marcos; Esteban, Manuel Martinez; Alvarez-Viejo, Maria; Fontanil, Tania; Cal, Santiago; Sanchez Pitiot, Marta; Otero, Jesus; Obaya, Alvaro Jesus
Pancreatic islet transplantation has been considered for many years a promising therapy for beta-cell replacement in patients with type-1 diabetes despite that long-term clinical results are not as satisfactory. This fact points to the necessity of designing strategies to improve and accelerate islets engraftment, paying special attention to events assuring their revascularization. Fibroblasts constitute a cell population that collaborates on tissue homeostasis, keeping the equilibrium between production and degradation of structural components as well as maintaining the required amount of survival factors. Our group has developed a model for subcutaneous islet transplantation using a plasma-based scaffold containing fibroblasts as accessory cells that allowed achieving glycemic control in diabetic mice. Transplanted tissue engraftment is critical during the first days after transplantation, thus we have gone in depth into the graft-supporting role of fibroblasts during the first ten days after islet transplantation. All mice transplanted with islets embedded in the plasma-based scaffold reversed hyperglycemia, although long-term glycemic control was maintained only in the group transplanted with the fibroblasts-containing scaffold. By gene expression analysis and histology examination during the first days we could conclude that these differences might be explained by overexpression of genes involved in vessel development as well as in β-cell regeneration that were detected when fibroblasts were present in the graft. Furthermore, fibroblasts presence correlated with a faster graft re-vascularization, a higher insulin-positive area and a lower cell death. Therefore, this work underlines the importance of fibroblasts as accessory cells in islet transplantation, and suggests its possible use in other graft-supporting strategies.
Ohwada, Susumu; Sunose, Yutaka; Aiba, Masaaki; Tsutsumi, Hirofumi; Iwazaki, Shigeru; Totsuka, Osamu; Matsumoto, Koshi; Takeyoshi, Izumi; Morishita, Yasuo
The optimal method for preserving livers from non-heart-beating donors (NHBD) is still unknown. We compared the Celsior solution, a new extracellular-type, low-potassium, low-viscosity preservation solution, with the University of Wisconsin (UW) solution in a canine orthotopic liver transplantation from NHBD. Fourteen adult mongrel dogs, weighing 9 to 17 kg, were divided into two groups: the Celsior or the UW group (n = 7 each). The thoracic descending aorta and supradiaphragmatic inferior vena cava were cross-clamped for 20 min to induce warm ischemia as a NHBD model. The liver was flushed with the respective cold preservation solution and then stored at 4 degrees C for 4 h. The grafts were transplanted using the piggy-back technique under portal decompression by leaving the native right lobe as a temporary shunt. The duration of liver flushing out (min) was shorter (P < 0.05), and the serum glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, lactate dehydrogenase, lactate, and alpha-glutathione S-transferase concentrations 2 and 6 h after reperfusion of the graft (RPF) were lower (P < 0.05) in the Celsior group than in the UW group. Hepatic tissue blood flow (HTBF) did not deteriorate as much (P < 0.05) in the Celsior group. The serum endothelin-1 level was lower (P < 0.05) in the Celsior group 2 h after RPF. Histopathology of liver specimens revealed portal congestion and hepatocyte necrosis with neutrophil infiltration in the UW group, while these findings were mild in the Celsior group. The Celsior solution improves vascular endothelial injury in livers from NHBDs and may have advantages in graft flush and preservation of grafts from NHBDs. (c)2001 Elsevier Science.
Rockenstein, Edward; Desplats, Paula; Ubhi, Kiren; Mante, Michael; Florio, Jazmin; Adame, Anthony; Winter, Stefan; Brandstaetter, Hemma; Meier, Dieter; Masliah, Eliezer
Neural stem cells (NSCs) have been considered as potential therapy in Alzheimer's disease (AD) but their use is hampered by the poor survival of grafted cells. Supply of neurotrophic factors to the grafted cells has been proposed as a way to augment survival of the stem cells. In this context, we investigated the utility of Cerebrolysin (CBL), a peptidergic mixture with neurotrophic-like properties, as an adjunct to stem cell therapy in an APP transgenic (tg) model of AD. We grafted murine NSCs into the hippocampus of non-tg and APP tg that were treated systemically with CBL and analyzed after 1, 3, 6 and 9months post grafting. Compared to vehicle-treated non-tg mice, in the vehicle-treated APP tg mice there was considerable reduction in the survival of the grafted NSCs. Whereas, CBL treatment enhanced the survival of NSCs in both non-tg and APP tg with the majority of the surviving NSCs remaining as neuroblasts. The NSCs of the CBL treated mice displayed reduced numbers of caspase-3 and TUNEL positive cells and increased brain derived neurotrophic factor (BDNF) and furin immunoreactivity. These results suggest that CBL might protect grafted NSCs and as such be a potential adjuvant therapy when combined with grafting.
Aims/hypothesis There is evidence that plasma homocysteine augments vein graft failure and that it augments both micro- and macro-angiopathy in patients with diabetes mellitus. It is therefore suggested that homocysteine may augment vein graft thickening, a major cause of vein graft failure, in diabetic patients, as well as impairing adaptive growth of a new vasa vasorum, possibly through overproduction of superoxide. In order to test these proposals, the effect of folic acid administration, which lowers plasma homocysteine, on vein graft thickening and microvessel density was studied in pigs used as a model of diabetes. Methods Non-ketotic hyperglycaemia was induced in Landrace pigs by intravenous injection of streptozotocin, and folic acid was fed daily for 1 month. Vein grafts were excised and the thickness of the neointima and media and microvessel density were assessed by planimetry and superoxide formation. Results Plasma total homocysteine was significantly reduced by folic acid in both control and diabetic pigs, whereas glucose was unchanged. Compared with controls, diabetic pigs showed increased neointimal thickness and superoxide formation and decreased adventitial microvessel density. Folic acid reduced neointimal thickness and superoxide formation and augmented microvessel density in diabetic but not in control pigs. Conclusions Folic acid administration reduces neointimal thickening, augments vasa vasorum neoformation and reduces oxidative stress in saphenous vein grafts from diabetic pigs. Folic acid may therefore be particularly effective in reducing vein graft failure in diabetic patients. PMID:20182861
Ishii, Seigo; Sato, Morio Sonomura, Tetsuo; Yamada, Katsuyuki; Tanihata, Hirohiko; Ishikawa, Hime; Terada, Masaki; Sahara, Shinya; Kawai, Nobuyuki; Kimura, Masashi; Mori, Ichiro
Purpose. We evaluated the suitability of Dacron, polytetrafluoroethylene (PTFE), and small intestinal submucosa (SIS) as a covering material for stent-grafts placed in the portal vein as compared with a bare stent. Methods. Using 24 beagle dogs, either bare stents or stent-grafts covered with Dacron, PTFE, or SIS were placed in the main trunk of the portal vein in 6 animals each. Portography was performed immediately after stent placement, and at 2, 4, and 12 weeks thereafter. Next, the extracted stents or stent-grafts were examined histopathologically. Neointimal thickness adjacent to the stent wire and at the midportion between the stent wires was compared among the groups. Then, the neointimal thickness at the sub- and supragraft sites was compared between each stent-graft group. Serial changes in the histologic features of the thickened neointima were also investigated. Results. No significant difference was noted in the mean stenotic ratio of the portal vein diameter between the bare stent and PTFE groups, whereas it was significantly higher in the Dacron and SIS groups compared with the bare stent group. In neither of the studies on neointimal thickness adjacent to the stent wire and at the midportion between the stent wires were any significant differences noted between the neointimal thickness of the bare stent group and the sum of the neointimal thickness of the PTFE group, whereas the sum of the neointimal thickness of the Dacron and SIS groups was significantly greater than that of the bare stent group at both sites. In the comparison of the supragraft neointimal thickness, the SIS group showed significantly greater thickness than the PTFE group, while the difference between the Dacron and PTFE groups was not significant. In the comparison of the subgraft neointimal thickness, the Dacron and SIS groups showed significantly greater thickness than the PTFE group. Conclusion. The present results indicate that of the three covering materials examined here
Kouroupis, Dimitrios; Baboolal, Thomas G; Jones, Elena; Giannoudis, Peter V
Graft expanders are bone scaffolds used, in combination with autografts, to fill large bone defects in trauma surgery. This study investigates the graft expander potential of a natural bone substitute Orthoss by studying its ability to support attachment, growth and osteogenic differentiation of neighboring multipotential stromal cells (MSCs). Material consisting of bone marrow (BM) aspirate and reamer-irrigator-aspirator (RIA)-harvested autograft bone was co-cultured with commercially available Orthoss granules. Native MSCs attached to Orthoss were expanded and phenotypically characterized. MSCs egress from neighboring cancelous bone was assessed in 3D Matrigel co-cultures. MSC differentiation was evaluated using scanning electron microscopy and measuring alkaline phosphatase (ALP) activity per cell. CD45(+) hematopoietic lineage cells and highly proliferative CD90(+) CD73(+) CD105(+) MSCs preferentially colonized Orthoss granules, over RIA bone chips. MSC colonization was followed by their intrinsic osteogenic differentiation, assessed as mineral deposition and gradual rise in ALP activity, even in the absence of osteogenic stimuli. When in contact with mixed cell populations and RIA chips, Orthoss granules support the attachment, growth and osteogenic differentiation of neighboring MSCs. Therefore, natural bone substitutes similar to Orthoss can be used as void fillers and graft expanders for repairing large bone defects in conjunction with autologous BM aspirates and autografts.
Kim, Seong Joon
Objective Anterior cervical discectomy and fusion (ACDF) is often complicated by subsidence, pseudoarthrosis, kyphosis, and graft donor site morbidities. To decrease the occurrence of these complications, various types of cages have been developed. We designed this retrospective study to analyze and compare the efficacy and outcomes of ACDF using double cylindrical cages (DCC) (BK Medical, Seoul, Korea) versus an anterior cervical plating system with autogenous iliac crest grafts. Methods Forty-eight patients were treated with autograft and plating (plate group), and 48 with DCC group from October 2007 to October 2011. We analyzed construct length, cervical lordotic curvarture, the thickness of the prevertebral soft tissue, segmental instability, and clinical outcomes. Results There were no significant differences between the two groups with regard to the decrease in construct length or cervical lodortic curvature at the 3-, 6-, and 12-month follow-ups. The prevertebral soft tissue was thinner in the DCC group than the plate group immediately after surgery and at the 3-, 6-, and 12-month follow-ups. The difference in interspinous distance on flexion-extension was shorter in the plate group than the DCC group at the 3- and 6-month follow-ups. However, there was no significant difference in this distance between the two groups at the 12-month follow-up. Conclusion A double cylindrical cage is a good alternative for fusion in patients with cervical degenerative diseases; the surgical method is relatively simple, allows good synostosis, has less associated prevertebral soft tissue swelling, and complications associated with autografting can be avoided. PMID:24570812
Matsumura, Hajime; Matsushima, Asako; Ueyama, Masashi; Kumagai, Norio
In the 1970s, Green et al. developed a method that involved culturing keratinocyte sheets and used for treatment of burns. Since then, the take rate of cultured epidermal autograft (CEA) onto fascia, granulation tissue, or allografts has been extensively reported, while that on an artificial dermis in a large case series is not. Moreover, the contribution of CEA to patient survival has not been analyzed in a multicenter study. We conducted a 6-year multicenter surveillance on the application of the CEA "JACE(®") for treatment of burns >30% total body surface area (TBSA) across 118 Japanese hospitals. This surveillance included 216 patients and 718 graft sites for efficacy analysis. The CEA take rate at 4 weeks after grafting was evaluated, and safety was monitored until 52 weeks. In addition, the survival curve obtained in this study and the data obtained from the Tokyo Burn Unit Association (TBUA) were compared. The mean CEA take rates at week 4 were 66% (sites) and 68% (patients), and the rate on the artificial dermis was 65% for 226 sites. CEA application combined with wide split-thickness auto or patch autograft increased the CEA take rate. On comparison with the data obtained from the TBUA, which included data on individuals with burns of the same severity, CEA application was found to contribute to patient survival until 7 weeks after burn. We reported the take rate of CEA based on a 6-year multicenter surveillance. From our results, we found that the application of CEA is a useful treatment for the patients with extensive burns. Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.
Li, Li; Li, Huan; Zhuplatov, Ilya; Blumenthal, Donald K.; Kim, Seong-Eun; Owen, Shawn C.; Kholmovski, Eugene G.; Fowers, Kirk D.; Rathi, Ramesh; Cheung, Alfred K.
Synthetic arteriovenous (AV) hemodialysis grafts are plagued by hyperplasia resulting in occlusion and graft failure yet there are no clinically available preventative treatments. Here the delivery and degradation of a sirolimus-laden polymer gel was monitored in vivo by magnetic resonance imaging (MRI) and its efficacy for inhibiting hyperplasia was evaluated in a porcine model of AV graft stenosis. Synthetic grafts were placed between the carotid artery and ipsilateral jugular vein of swine. A biodegradable polymer gel loaded with sirolimus (2.5 mg/mL) was immediately applied perivascularly to the venous anastomosis, and reapplied by ultrasound-guided injections at one, two and three weeks. Control grafts received neither sirolimus nor polymer. The lumen cross-sectional area at the graft-vein anastomosis was assessed in vivo by non-invasive MRI. The explanted tissues also underwent histological analysis. A specifically developed MRI pulse sequence provided a high contrast-to-noise ratio (CNR) between the polymer and surrounding tissue that allowed confirmation of gel location after injection. Polymer signal decreased up to 80% at three to four weeks after injection, slightly faster than its degradation kinetics in vitro. The MR image of the polymer was confirmed by visual assessment at necropsy. On histological assessment, the mean hyperplasia surface area of the treated graft was 52% lower than that of the control grafts (0.43 mm2 vs. 0.89 mm2; p < 0.003), while the minimum cross-sectional lumen area, as measured on MRI, was doubled (5.3 mm2 vs 2.5 mm2; p < 0.05). In conclusion, customized MRI allowed non-invasive monitoring of the location and degradation of drug-delivery polymer gels in vivo. Perivascular application of sirolimus-laden polymer yielded a significant decrease in hyperplasia development and an increase in lumen area at the venous anastomosis of AV grafts. PMID:22465391
Habka, Dany; Mann, David; Landes, Ronald; Soto-Gutierrez, Alejandro
During the past 20 years liver transplantation has become the definitive treatment for most severe types of liver failure and hepatocellular carcinoma, in both children and adults. In the U.S., roughly 16,000 individuals are on the liver transplant waiting list. Only 38% of them will receive a transplant due to the organ shortage. This paper explores another option: bioengineering an autologous liver graft. We developed a 20-year model projecting future demand for liver transplants, along with costs based on current technology. We compared these cost projections against projected costs to bioengineer autologous liver grafts. The model was divided into: 1) the epidemiology model forecasting the number of wait-listed patients, operated patients and postoperative patients; and 2) the treatment model forecasting costs (pre-transplant-related costs; transplant (admission)-related costs; and 10-year post-transplant-related costs) during the simulation period. The patient population was categorized using the Model for End-Stage Liver Disease score. The number of patients on the waiting list was projected to increase 23% over 20 years while the weighted average treatment costs in the pre-liver transplantation phase were forecast to increase 83% in Year 20. Projected demand for livers will increase 10% in 10 years and 23% in 20 years. Total costs of liver transplantation are forecast to increase 33% in 10 years and 81% in 20 years. By comparison, the projected cost to bioengineer autologous liver grafts is $9.7M based on current catalog prices for iPS-derived liver cells. The model projects a persistent increase in need and cost of donor livers over the next 20 years that’s constrained by a limited supply of donor livers. The number of patients who die while on the waiting list will reflect this ever-growing disparity. Currently, bioengineering autologous liver grafts is cost prohibitive. However, costs will decline rapidly with the introduction of new manufacturing
Thong, Alan E; Zhao, Hongjuan; Ingels, Alexandre; Valta, Maija P; Nolley, Rosalie; Santos, Jennifer; Young, Sarah R; Peehl, Donna M
Discovery of curative therapies for renal cell carcinoma (RCC) is hampered by lack of authentic preclinical models. Tumorgrafts, generated by direct implantation of patient-derived tissues into mice, have demonstrated superior ability to predict therapeutic response. We evaluated "tissue slice grafts" (TSGs) as an improved tumorgraft model of RCC. Cores of fresh RCC were precision-cut at 300 µm and implanted under the renal capsule of RAG2(-/-)γC(-/-) mice. Engraftment rate, histology, biomarker expression, genetic fidelity, and metastatic potential were evaluated. Magnetic resonance imaging (MRI) was tested as a noninvasive method to measure tumor volume, and response to a targeted therapy was determined. All 13 cases of RCC engrafted and displayed characteristic histology and biomarkers. TSG volume quantified noninvasively by MRI highly correlated with graft weights, providing a unique tool for monitoring orthotopic growth. Moreover, in 2 cases, cancer cells from TSGs metastasized to clinically relevant sites, including bone. Microarray analysis and DNA sequencing demonstrated a high degree of correlation of global gene expression and von Hippel-Lindau (VHL) status between TSGs and parental tumors. Treatment of TSGs with sunitinib significantly decreased graft weight and mean vessel density compared with controls. The TSG model of RCC faithfully recapitulates tumor pathology, gene expression, genetic mutation, and drug response. The high engraftment rate and metastatic potential of this authentic model, in conjunction with the ability to generate large first-generation animal cohorts and to quantitate tumor volume at the orthotopic site by MRI, proffer significant advantages compared with other preclinical platforms. Copyright © 2014 Elsevier Inc. All rights reserved.
Madrazo, I; Drucker-Colín, R; Díaz, V; Martínez-Mata, J; Torres, C; Becerril, J J
Recent experimental studies and one clinical case have suggested that grafting tissue from the adrenal medulla into the brain may ameliorate the signs of Parkinson's disease. We describe the treatment of two young patients (35 and 39 years old) with intractable and incapacitating Parkinson's disease, in whom fragments of the adrenal medulla were autotransplanted to the right caudate nucleus. Clinical improvement was noted in both patients at 15 and 6 days (respectively) after implantation and has continued in both. Rigidity and akinesia had virtually disappeared in the first patient at 10 months after surgery, and his tremor was greatly reduced. A similar degree of improvement was present in the second patient at three months. We conclude that autografting of the adrenal medulla to the right caudate nucleus was associated with a marked improvement in the signs of Parkinson's disease in two patients, but our results are preliminary and further work is necessary to see whether this procedure will be applicable over the long term in other types of patients with Parkinson's disease.
Glas-Greenwalt, P; Dalton, B C; Astrup, T
Employing the histochemical fibrin slide technique, we studied the localization of fibrinolytically active sites in relation to morphologic changes in saphenous veins used as coronary artery bypass autografts. Of veins from 100 patients undergoing surgery for coronary heart disease, 63 samples revealed well-demarcated intimal fibrinolytic activity. Distinct foci of lysis were present in the media and adventitia of all vein samples corresponding to the distribution of the vasa vasorum. Graft specimens obtained by autopsy from 13 patients surviving from 30 minutes to 13 days revealed considerable intimal damage with loss of fibrinolytic activity. Medial fibrinolytic activity disappeared early concomitant with disorganization of the medial muscle fibers, followed by necrosis, atrophy and fibrous transformation of the muscular structures. Adventitial activity disappeared later. One reoperation sample obtained after 8 weeks in situ showed moderate proliferative intimal fibrosis without an apparent neo-intima and without fibrinolytic activity, and one section showed evidence of valve cusp fibrosis, while most of the media had been replaced by fibrous tissue. Numerous foci of "medial" -adventitial fibrinolytic activity indicated presence of vascular structures in the venous wall. The fibrin slide technique is a convenient tool for studying the process of revascularization. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. Figs. 5a-d. Fig. 6. Figs. 7a and b. Figs. 8a and b. PMID:1079445
Background Grafting is widely used in the agriculture of fruit-bearing crops; rootstocks are known to confer differences in scion biomass in addition to improving other traits of agricultural interest. However, little is known about the effect of rootstocks on scion gene expression. The objective of this study was to determine whether hetero-grafting the grapevine variety Vitis vinifera cv. 'Cabernet Sauvignon N’ with two different rootstocks alters gene expression in the shoot apex in comparison to the auto-grafted control. Cabernet Sauvignon was hetero-grafted with two commercial rootstock genotypes and auto-grafted with itself. Vigor was quantified by measurements of root, stem, leaf and trunk biomass. Gene expression profiling was done using a whole genome grapevine microarray; four pools of five shoot apex samples were harvested 4 months after grafting for each scion/rootstock combination. Results The rootstocks increased stem biomass or conferred increased vigor by the end of the first growth cycle. Globally hetero-grafting two different genotypes together triggered an increase in shoot apex gene expression; however no genes were differentially expressed between the two hetero-grafts. The functional categories related to DNA, chromatin structure, histones, flavonoids and leucine rich repeat containing receptor kinases were the most enriched in the up-regulated genes in the shoot apex of hetero-grafted plants. Conclusions The choice of rootstock genotype had little effect on the gene expression in the shoot apex; this could suggest that auto- and hetero-grafting was the major factor regulating gene expression. PMID:24083813
Moravvej, Hamideh; Hormozi, Abdoljalil Kalantar; Hosseini, Seyed Nejat; Sorouri, Rahim; Mozafari, Naser; Ghazisaidi, Mohammad Reza; Rad, Mahnaz Mahmoudi; Moghimi, Mohammad Hossein; Sadeghi, Shahin Mohammad; Mirzadeh, Hamid
Wound healing is a multipart process involving different cell types and growth factors. Third-degree burns are usually treated by early excision and skin grafting. Tissue engineering has been developed in this field in response to limitations associated with autografts. Allogeneic fibroblasts on meshed split thickness skin grafts (STSGs) are known to have useful properties in wound healing and can be used to construct a new model of living skin substitute. Fourteen patients were chosen from June 2009 until December 2010 as the sample for this study. After debridement and wound excision, meshed STSG was used to cover the entire wound. Alloskin (allofibroblasts cultured on a combination of silicone and glycosaminoglycan) was applied on one side and petroleum jelly-impregnated gauze (Iran Polymer and Petrochemical Institute) was applied on the other. The healing time, scar formation, and pigmentation score were assessed for the patients. All analyses were undertaken with SPSS 17 software. Alloskin demonstrated good properties compared to petroleum jelly-impregnated gauze. The average healing time and hypertrophic scar formation were significantly different between the two groups. In addition, the skin pigmentation score in the alloskin group was closer to normal. Alloskin grafting, including fibroblasts on meshed STSG, may be a useful method to reduce healing time and scar size and may require less autologous STSG in extensive burns where a high percentage of skin is burned and there is a lack of available donor sites.
El Shazly, Ossama; Abou El Soud, Maged M; El Mikkawy, Dalia M E; El Ganzoury, Ibrahim; Ibrahim, Ayman Mohamed
To evaluate the clinical and functional outcome of endoscopic-assisted reconstruction of chronic ruptures of the Achilles tendon using free hamstring tendon autograft. We present a case series of 15 patients who had chronic ruptures of the Achilles tendon (>6 weeks earlier) and underwent endoscopic-assisted reconstruction with a free hamstring autograft. The graft loop was passed through and fixed to the proximal stump of the tendon. The graft was then passed through suture to the distal stump and finally inserted into a tunnel in the anterior calcaneus to the Achilles tendon insertion and fixed with an bioabsorbable interference screw. The mean follow-up period was 27 months (SD, 3 months; range, 24 to 33 months). All patients underwent magnetic resonance imaging preoperatively, immediately postoperatively, and at follow-up 2 years postoperatively. All patients were functionally evaluated with the American Orthopaedic Foot & Ankle Society (AOFAS) score for the hindfoot preoperatively and postoperatively. Calf muscle power was evaluated by isokinetic strength testing at 2 years' follow-up. The mean size of the gap on preoperative magnetic resonance imaging was 49 mm (SD, 9 mm). The mean preoperative AOFAS score was 32.6 (SD, 7.5). There was a statistically significant improvement in the postoperative AOFAS score after 2 years to 90.8 (SD, 3.54) (P < .05). The mean time of return to all daily activities (except running and other sports) was 12.6 weeks (SD, 1.39 weeks). Isokinetic testing showed a nonsignificant deficit (<10%) between the involved and uninvolved plantar flexors and dorsiflexors with regard to peak torque, average power, and total work. Endoscopic-assisted Achilles tendon reconstruction with free hamstring tendon autograft for chronic ruptures of the Achilles tendon showed good to excellent results in all patients. Isokinetic testing showed a nonsignificant deficit between the involved and uninvolved sides at 2 years' follow-up. Level IV, therapeutic
Somja, Joan; Binsfeld, Marilène; Delvenne, Philippe; Drion, Pierre; Hannon, Muriel; Beguin, Yves; Ehx, Grégory; Baron, Frédéric
Background Sclerodermatous chronic Graft-versus-Host Disease (scl-cGVHD) is one of the most severe form of cGVHD. The Platelet-derived Grotwth Factor (PDGF) and the Transforming Growth Factor-β (TGF-β) play a significant role in the fibrosing process occurring in scl-cGVHD. This prompted us to assess the impact of the PDGF-r and c-Abl tyrosine kinase inhibitor imatinib on scl-cGVHD. Methods To assess the impact of imatinib on T cell subset proliferation in vivo, Balb/cJ recipient mice were lethally (7 Gy) irradiated and then injected with 10x106 bone marrow cells from B10.D2 mice on day 0. Fourteen days later, 70x106 carboxyfluorescein succinimidyl ester (CFSE)-labeled splenocytes from B10.D2 mice were infused and imatinib or sterile water was administered for 5 days. To induce severe scl-cGVHD, Balb/cJ mice were injected i.v. with 10.106 bone marrow cells and 70.106 splenocytes from B10.D2 donor mice after 7 Gy irradiation. Mice were then given sterile water or imatinib from day +7 after transplantation to the end of the experiment (day +52). Results Imatinib decreased the proliferation of total T cells (P = 0.02), CD8+ T cells (P = 0.01), and of regulatory T cells (Tregs) (P = 0.02) in the spleen. In the severe scl-cGVHD model, imatinib-treated mice had significantly lower levels of PDGF-r phosphorylation than control mice on day 29 after transplantation (P = 0.008). However, scl-cGVHD scores were similar between vehicle- and imatinib-treated mice during the whole experiment, while there was a suggestion for less weight loss in imatinib-treated mice that reached statistical significance at day +52 following transplantation (P = 0.02). Conclusions Imatinib had a limited impact in murine scl-cGVHD despite significant inhibition of PDGF-r. PMID:27942010
Deng, Mingge; Li, Xuejin; Liang, Haojun; Caswell, Bruce; Karniadakis, George Em
Fabrication of functionalized surfaces using polymer brushes is a relatively simple process and parallels the presence of glycocalyx filaments coating the luminal surface of our vasculature. In this paper, we perform atomistic-like simulations based on dissipative particle dynamics (DPD) to study both polymer brushes and glycocalyx filaments subject to shear flow, and we apply mean-field theory to extract useful scaling arguments on their response. For polymer brushes, a weak shear flow has no effect on the brush density profile or its height, while the slip length is independent of the shear rate and is of the order of the brush mesh size as a result of screening by hydrodynamic interactions. However, for strong shear flow, the polymer brush is penetrated deeper and is deformed, with a corresponding decrease of the brush height and an increase of the slip length. The transition from the weak to the strong shear regime can be described by a simple 'blob' argument, leading to the scaling γ̇0 ∝ σ(3/2), where γ̇0 is the critical transition shear rate and σ is the grafting density. Furthermore, in the strong shear regime, we observe a cyclic dynamic motion of individual polymers, causing a reversal in the direction of surface flow. To study the glycocalyx layer, we first assume a homogeneous flow that ignores the discrete effects of blood cells, and we simulate microchannel flows at different flow rates. Surprisingly, we find that, at low Reynolds number, the slip length decreases with the mean flow velocity, unlike the behaviour of polymer brushes, for which the slip length remains constant under similar conditions. (The slip length and brush height are measured with respect to polymer mesh size and polymer contour length, respectively.) We also performed additional DPD simulations of blood flow in a tube with walls having a glycocalyx layer and with the deformable red blood cells modelled accurately at the spectrin level. In this case, a plasma cell
Takeda, Ryuichiro; Ishida, Yasushi; Ebihara, Kosuke; Abe, Hiroshi; Matsuo, Hisae; Ikeda, Tetsuya; Koganemaru, Go; Kuramashi, Aki; Funahashi, Hideki; Magata, Yasuhiro; Kawai, Keiichi; Nishimori, Toshikazu
We previously reported that a unilateral 6-hydroxydopamine (6-OHDA) rat model of Parkinson's disease showed allodynia-like withdrawal response to mechanical stimulation of the ipsilateral side of the rat hindpaw. The goal of this study was to investigate the effect of intrastriatal grafts of fetal ventral mesencephalon (VM) on the withdrawal response in 6-OHDA rats. The withdrawal threshold in response to the mechanical stimulation of the rat hindpaw was measured using von Frey filaments. In the ipsilateral side of the 6-OHDA lesions, the withdrawal threshold in response to mechanical stimulation significantly increased in 6-OHDA rats with VM grafts compared with those with sham grafts, but did not change in the contralateral side at 5 weeks after transplantation. The present results suggest that the intrastriatal grafts of fetal VM may relieve pain sensation induced by mechanical stimulation in 6-OHDA rats. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
Aizawa, Kazuya; Sato, Shunichi; Terakawa, Mitsuhiro; Saitoh, Daizoh; Tsuda, Hitoshi; Ashida, Hiroshi; Obara, Minoru
Gene therapy using wound healing-associated growth factor gene has received much attention as a new strategy for improving the outcome of tissue transplantation. We delivered plasmid DNA coding for human hepatocyte growth factor (hHGF) to rat free skin grafts by the use of laser-induced stress waves (LISWs); autografting was performed with the grafts. Systematic analysis was conducted to evaluate the adhesion properties of the grafted tissue; angiogenesis, cell proliferation, and reepithelialization were assessed by immunohistochemistry, and reperfusion was measured by laser Doppler imaging as a function of time after grafting. Both the level of angiogenesis on day 3 after grafting and the increased ratio of blood flow on day 4 to that on day 3 were significantly higher than those in five control groups: grafting with hHGF gene injection alone, grafting with control plasmid vector injection alone, grafting with LISW application alone, grafting with LISW application after control plasmid vector injection, and normal grafting. Reepithelialization was almost completed on day 7 even at the center of the graft with LISW application after hHGF gene injection, while it was not for the grafts of the five control groups. These findings demonstrate the validity of our LISW-based HGF gene transfection to accelerate the adhesion of grafted skins.
Wolff, J.A.; Fisher, L.J.; Xu, L.; Jinnah, H.A.; Rosenberg, M.B.; Shimohama, S.; Gage, F.H. ); Langlais, P.J. School of Medicine and Veterans Administration Medical Center, La Jolla San Diego State Univ., CA ); Iuvone, P.M. ); O'Malley, K.L. )
Rat fibroblasts were infected with a retroviral vector containing the cDNA for rat tyrosine hydroxylase. A TH-positive clone was identified by biochemical assay and immunohistochemical staining. When supplemented in vitro with pterin cofactors required for TH activity, these cells produced L-dopa and released it into the cell cultured medium. Uninfected control cells and fibroblasts infected with the TH vector were grafted separately to the caudate of rats with unilateral 6-hydroxydopamine lesions of the nigrostriatal pathway. Only grafts containing TH-expressing fibroblasts were found to reduce rotational asymmetry. These results have general implications for the application of gene therapy to human neurological disease and specific implications for Parkinson disease.
Alexandre, Nuno; Amorim, Irina; Caseiro, Ana Rita; Pereira, Tiago; Alvites, Rui; Rêma, Alexandra; Gonçalves, Ana; Valadares, Guilherme; Costa, Elísio; Santos-Silva, Alice; Rodrigues, Miguel; Lopes, Maria Ascensão; Almeida, André; Santos, José Domingos; Maurício, Ana Colette; Luís, Ana Lúcia
The functional and structural performance of a 5cm synthetic small diameter vascular graft (SDVG) produced by the copolymerization of polyvinyl alcohol hydrogel with low molecular weight dextran (PVA/Dx graft) associated to mesenchymal stem cells (MSCs)-based therapies and anticoagulant treatment with heparin, clopidogrel and warfarin was tested using the ovine model during the healing period of 24 weeks. The results were compared to the ones obtained with standard expanded polyetetrafluoroethylene grafts (ePTFE graft). Blood flow, vessel and graft diameter measurements, graft appearance and patency rate (PR), thrombus, stenosis and collateral vessel formation were evaluated by B-mode ultrasound, audio and color flow Doppler. Graft and regenerated vessels morphologic evaluation was performed by scanning electronic microscopy (SEM), histopathological and immunohistochemical analysis. All PVA/Dx grafts could maintain a similar or higher PR and systolic/diastolic laminar blood flow velocities were similar to ePTFE grafts. CD14 (macrophages) and α-actin (smooth muscle) staining presented similar results in PVA/Dx/MSCs and ePTFE graft groups. Fibrosis layer was lower and endothelial cells were only detected at graft-artery transitions where it was added the MSCs. In conclusion, PVA/Dx graft can be an excellent scaffold candidate for vascular reconstruction, including clinic mechanically challenging applications, such as SDVGs, especially when associated to MSCs-based therapies to promote higher endothelialization and lower fibrosis of the vascular prosthesis, but also higher PR values.
Alexandre, Nuno; Amorim, Irina; Caseiro, Ana Rita; Pereira, Tiago; Alvites, Rui; Rêma, Alexandra; Gonçalves, Ana; Valadares, Guilherme; Costa, Elísio; Santos-Silva, Alice; Rodrigues, Miguel; Lopes, Maria Ascensão; Almeida, André; Santos, José Domingos; Maurício, Ana Colette; Luís, Ana Lúcia
The functional and structural performance of a 5cm synthetic small diameter vascular graft (SDVG) produced by the copolymerization of polyvinyl alcohol hydrogel with low molecular weight dextran (PVA/Dx graft) associated to mesenchymal stem cells (MSCs)-based therapies and anticoagulant treatment with heparin, clopidogrel and warfarin was tested using the ovine model during the healing period of 24 weeks. The results were compared to the ones obtained with standard expanded polyetetrafluoroethylene grafts (ePTFE graft). Blood flow, vessel and graft diameter measurements, graft appearance and patency rate (PR), thrombus, stenosis and collateral vessel formation were evaluated by B-mode ultrasound, audio and color flow Doppler. Graft and regenerated vessels morphologic evaluation was performed by scanning electronic microscopy (SEM), histopathological and immunohistochemical analysis. All PVA/Dx grafts could maintain a similar or higher PR and systolic/diastolic laminar blood flow velocities were similar to ePTFE grafts. CD14 (macrophages) and α-actin (smooth muscle) staining presented similar results in PVA/Dx/MSCs and ePTFE graft groups. Fibrosis layer was lower and endothelial cells were only detected at graft-artery transitions where it was added the MSCs. In conclusion, PVA/Dx graft can be an excellent scaffold candidate for vascular reconstruction, including clinic mechanically challenging applications, such as SDVGs, especially when associated to MSCs-based therapies to promote higher endothelialization and lower fibrosis of the vascular prosthesis, but also higher PR values.
Rajalaxmi Dash; Thomas Elder; Arthur Ragauskas
This study demonstrates regioselective oxidation of cellulose nanowhiskers using 2.80â10.02 mmols of sodium periodate per 5 g of whiskers followed by grafting with methyl and butyl amines through a Schiff base reaction to obtain their amine derivatives in 80â90 % yield. We found a corresponding increase in carbonyl content (0.06â0.14 mmols/g) of the dialdehyde...
Kraiss, L W; Raines, E W; Wilcox, J N; Seifert, R A; Barrett, T B; Kirkman, T R; Hart, C E; Bowen-Pope, D F; Ross, R; Clowes, A W
Healing baboon polytetrafluoroethylene grafts express PDGF mRNA in the neointima. Perfusates of graft segments also contain PDGF-like mitogenic activity. To extend these findings, we studied the expression and regional distribution of the PDGF protein isoforms and their receptors in this prosthetic graft model. By immunohistochemistry, as well as ELISA and Western blot analysis of tissue extracts, both PDGF-A and PDGF-B were identified in macrophages within the interstices of the synthetic material. In contrast, the neointima contained predominantly PDGF-A localized to the endothelial surface and the immediate subjacent smooth muscle cell layers. Tissue extracts of neointima and graft material were mitogenic for baboon aortic smooth muscle cells in culture; nearly all of this proliferative activity was blocked by a neutralizing anti-PDGF antibody. PDGF receptor beta-subunit mRNA and protein were easily detectable in the neointima and graft material. PDGF receptor alpha-subunit mRNA was also observed in the graft matrix and at lower levels in the neointima. This pattern of ligand and receptor expression further implicates locally produced PDGF as a regulator of neointimal smooth muscle cell growth in this model. The coexpression of ligand and receptor in the macrophage-rich matrix also suggests that PDGF may participate in the foreign body response. Images PMID:8326002
Kim, Sung-Jae; Chun, Yong-Min; Moon, Hong-Kyo; Jang, Jae-Won
Purpose The purpose of this study was to compare four graft-tunnel angles (GTA), the femoral GTA formed by three different femoral tunneling techniques (the outside-in, a modified inside-out technique in the posterior sag position with knee hyperflexion, and the conventional inside-out technique) and the tibia GTA in 3-dimensional (3D) knee flexion models, as well as to examine the influence of femoral tunneling techniques on the contact pressure between the intra-articular aperture of the femoral tunnel and the graft. Materials and Methods Twelve cadaveric knees were tested. Computed tomography scans were performed at different knee flexion angles (0°, 45°, 90°, and 120°). Femoral and tibial GTAs were measured at different knee flexion angles on the 3D knee models. Using pressure sensitive films, stress on the graft of the angulation of the femoral tunnel aperture was measured in posterior cruciate ligament reconstructed cadaveric knees. Results Between 45° and 120° of knee flexion, there were no significant differences between the outside-in and modified inside-out techniques. However, the femoral GTA for the conventional inside-out technique was significantly less than that for the other two techniques (p<0.001). In cadaveric experiments using pressure-sensitive film, the maximum contact pressure for the modified inside-out and outside-in technique was significantly lower than that for the conventional inside-out technique (p=0.024 and p=0.017). Conclusion The conventional inside-out technique results in a significantly lesser GTA and higher stress at the intra-articular aperture of the femoral tunnel than the outside-in technique. However, the results for the modified inside-out technique are similar to those for the outside-in technique. PMID:23709438
Obert, Laurent; Loisel, François; Gindraux, Florelle; Tropet, Yves; Lepage, Daniel
Introduction: Used routinely in maxillofacial reconstructive surgery, the chondrocostal graft is also used in hand surgery. The purpose of this overview was to analyze at long follow-up the radiological and histological evolution of this autograft, in the hand and wrist surgery. Materials and methods: Since 1992, 144 patients have benefitted from a chondrocostal autograft: 116 osteoarthritis of the thumb carpometacarpal joint, 18 radioscaphoid arthritis, six articular malunions of the distal radius, four kienbock, and four traumatic loss of cartilage of the PIP joint. Magnetic Resonance Imaging (MRI) was performed in 19 patients and histological study in 12 patients with a mean follow-up of 68 months (4–159). Results: Whatever the indication, the reconstruction by a chondrocostal or ostochondrocostal graft has allowed us to obtain satisfactory clinical results at long follow-up. The main question was the viability of the graft. The radiological study has shown the non-wear of the graft and a certain degree of ossification. The MRI confirmed a very small degree of osseous metaplasia but its viability. The biopsies showed a neo-vascularization of the cartilage. Conclusion: Despite the strong mechanical strain in the hand and wrist, the chondrocostal graft is a biological arthroplasty, trustworthy and secure at long time even if it can cause infrequent complications inherent to this type of surgery. Despite the inevitable histological modification, the cartilage remains alive and is of satisfactory quality at long term follow-up and fulfilling the requirements for interposition and reconstruction of an articular surface. PMID:27163069
Alam, N; McGrouther, D A; Wong, J K F
We investigated the cellular biology of tendon grafting in a mouse model using green fluorescent protein mismatch grafting and quantitative immunohistochemistry of molecular markers for inflammation, proliferation, collagen synthesis, cell death, and myofibroblast/pericyte expression. We provide a detailed analysis of the healing characteristics during the phases of inflammation, synthesis, and remodelling. Our findings indicated that survival of the cells in the grafted tendon was finite. Syngenic and autologous grafts provoked a similar cellular reaction and all grafts healed. Cells in the graft contributed significantly to collagen synthesis and do have a role in healing.
Anderson, John J; Boone, Joshua J; Hansen, Myron; Brady, Chad; Gough, Adam; Swayzee, Zflan
Ankle arthrodesis is commonly used in the treatment of ankle arthritis. The present study compared mesenchymal stem cell (MSC) bone allografts and proximal tibia autografts as adjuncts in performing ankle arthrodesis. A total of 109 consecutive ankle fusions performed from 2002 to 2008 were evaluated retrospectively. Of the 109 fusions, 24 were excluded from the present study, leaving 85 patients who had undergone ankle arthrodesis. Of the 85 patients, 41 had received a proximal tibia autograft and 44, an MSC bone allograft. These 2 groups were reviewed and compared retrospectively at least 2 years postoperatively for the overall fusion rate, interval to radiographic fusion, and interval to clinical fusion. A modified and adjusted American College of Foot and Ankle Surgeons ankle scale was used to measure patient satisfaction. The overall fusion rate was 84.1% in the MSC bone allograft group and 95.1% in the proximal tibia autograft group (p = .158). The corresponding mean intervals to radiographic fusion were 13.0 ± 2.5 weeks and 11.3 ± 2.8 weeks (p ≤ .001). The interval to clinical fusion was 13.1 ± 2.1 weeks and 11.0 ± 1.5 weeks (p ≤ .001) in the MSC bone allograft and proximal tibia autograft group, respectively. No statistically significant difference was found in the fusion rates between the MSC bone allograft and proximal tibia autograft groups. Also, no statistically significant difference was found between the preoperative and postoperative scores using a modified and adjusted American College of Foot and Ankle Surgeons ankle scale between the 2 groups (p = .41 and p = .44, respectively). A statistically significant delay to radiographic and clinical fusion was present in the MSC bone allograft group compared with the proximal tibia autograft group; however, no difference was found in patient satisfaction.
Coruh, Atilla; Yontar, Yalcin
Early tangential excision of nonviable burn tissue, followed by immediate skin grafting with autograft or allograft, has resulted in the improvement of burn patient survival. The aim of this study was to add split-thickness dermal grafts (STDGs) as a new source of auto-skin grafting tool to our reconstructive armamentarium in deep partial- and full-thickness burns and soft tissue defects. The authors successfully applied STDGs along with split-thickness skin grafts as a new source of auto-skin grafting in 11 deep partial- and full-thickness burns over a period of 1 year without any significant donor site morbidity. Dermal graft take was complete in all but one patient. There was no donor site healing problem, and donor site epithelization was completed generally 1 week later than split-thickness skin graft by semi-open technique. Autologous split-thickness skin grafting still remains the standard therapy for burn wound closure but may be in limited availability in severe burns. The authors conclude that STDGs may be a new source of auto-skin grafting tool in extensive deep partial- and full-thickness burns.
Gris, Oscar; Del Campo, Zoraida; Wolley-Dod, Charlotte; Güell, José L; Velasco, Fortino; Adán, Alfredo
To present a case of chemical injury associated with calcification and severe conjunctival and scleral ischemia, in which tissue regeneration was achieved using an amniotic membrane graft. A 65-year-old man presented to our department 8 weeks after suffering a chemical