Bovine Graft Research Articles

The Effects of Different Tensioning Strategies on Knee Laxity and Graft Tension after Double-Bundle Anterior Cruciate Ligament Reconstruction

Background Double-bundle anterior cruciate ligament reconstruction replicates the 2 functional bundles of the native ligament, the posterolateral and the anteromedial, to control anteroposterior and rotational laxity. Hypothesis Double-bundle anterior cruciate ligament reconstruction laxity should be affected by the way grafts are tensioned. Study Design Controlled laboratory study. Methods Fourteen intact cadaveric knees were instrumented in a 6 degree of freedom rig, and kinematics throughout flexion-extension were recorded with an electromagnetic system under a 90-N anterior force or a 5-N·m internal rotation torque. Anteromedial and posterolateral bundle bovine extensor tendon grafts were fixed to load cells on the tibia, and tension was adjusted to match the intact knee anteroposterior laxity with 3 different protocols: (1) anteromedial bundle first and then posterolateral bundle at 90° and 20° of flexion, respectively; (2) posterolateral bundle first and then anteromedial bundle at 20° and 90° of flexion, respectively; and (3) both bundles together at 20° of flexion. Finally, a single-bundle graft positioned at 10 o'clock was tensioned at 20° of flexion. Results Lower graft tensions were required to match intact knee laxity in double-bundle anterior cruciate ligament reconstruction. Tension patterns with knee flexion were independent from the tensioning protocol. Protocols 1 and 2 overconstrained anteroposterior laxity, whereas protocol 3 matched intact knee anteroposterior laxity throughout the range of motion. The single-bundle reconstructions had excess anteroposterior laxity in flexion. Rotations were better restored with double-bundle protocols 2 and 3. Conclusion Knee laxity after double-bundle anterior cruciate ligament reconstruction is affected by the sequence in which the grafts are tensioned. Clinical Relevance Double-bundle anterior cruciate ligament reconstruction ensures better laxity restoration than does single bundle when both bundles are fixed together.

8: Fetal Bovine Dermal Graft (Xenform Matrix) in Pelvic Floor Reconstruction

To evaluate the safety and efficacy of a bovine dermal graft (Xenform Soft Tissue Repair Matrix) in vaginal reconstructive surgery.

Leiomyosarcoma of the superior vena cava: Resection with vascular reconstruction - case report and review of the literature

The present report describes a case of pedunculated intraluminal leiomyosarcoma of the superior vena cava, extending to the right atrium, that was successfully resected surgically. Superior vena cava reconstruction was performed using bovine pericardial graft, saving the sinus node. The pathological variants of this neoplasm according to the anatomical site of the tumour are described.

Histological osseointegration of Tutobone®: first results in human

The aim of this study was to evaluate the histological and radiological osseointegration characteristics of implanted solvent-preserved cancellous bovine bone substitution material Tutobone after opening-wedge osteotomy and hip arthroplasty in human. The baseline hypothesis connected to the usage of bovine bone substitute materials is the assumption of temporary structural support, integration in the surrounding bone, bioresorption and replacement with vital bone. This hypothesis is based on numerous studies evaluating sintered bovine grafts showing good osseointegration and stability. Studies analyzing cancellous bovine grafts such as Tutobone hardly exist. The only rabbit defect model showed 100% remodeling of Tutobone after 26 weeks. However, no histological data are available on application of this xenograft in patients. In this study, nine patients biopsies were collected about 11 months after application of Tutobone. Unlike animal studies, the results showed incorporated avital graft remnants (47%) as well as new bone formation (53%) of the total mineralized area. Radiological evaluation confirmed increasing signs of osseointegration and an incomplete resorption. In conclusion, degradation and replacement of bovine graft seems to be less accelerated in patients than the animal study indicated. Nevertheless, Tutobone shows an excellent biocompatibility, good osteoconductive characteristics and may represent a useful alternative to autogenous graft.

Right Ventricular Outflow Tract Reconstruction With the Bovine Jugular Vein Graft: 5 Years’ Experience With 133 Patients

We analyzed the results in two centers of using bovine jugular vein graft for right ventricular outflow tract reconstruction. From April 1999 to July 2005, 133 children with a median age of 30.9 months (range, 4 days to 19 years) underwent graft implantation. Echocardiography was performed during follow-up and retrospectively reviewed. Nongraft-related early mortality occurred in 8 patients. Late mortality occurred in 11 patients, 2 late deaths were graft related (endocarditis). Median follow-up was 31.6 months (range, 1 to 73). Twelve patients received a new graft, because of endocarditis (3), distal pulmonary artery branch stenosis (4), graft obstruction caused by fibrosis (4), or thrombosis (1). Echocardiography Doppler studies showed good conduit function, with 92% of the patients having absent, trivial, or only mild valve regurgitation at last follow-up. A moderate degree of conduit stenosis due to external compression was observed in 2 patients. Twenty-five patients with otherwise intact conduits had hemodynamically significant distal stenosis. In most cases, the pulmonary branch stenosis was related to preoperative small pulmonary arteries and young age at operation. At 31.6 months, significant graft dilatation was observed in 4 grafts and was related to pulmonary artery branch obstruction or pulmonary hypertension. Calcification did not occur in 5 years time. Survival was 85.7%, freedom from conduit explantation was 91%, and freedom from intervention for pulmonary artery branch stenosis was 80% after 5 years. The bovine jugular vein graft is a valuable right ventricular outflow tract conduit, but younger age and small pulmonary arteries increase the risk of distal conduit stenosis.

Right Ventricular Outflow Tract Reconstruction: What Conduit to Use? Homograft or Contegra?

Both cryopreserved homografts and glutaraldehyde fixed bovine jugular vein grafts (Contegra) are used as conduits for right ventricular outflow tract (RVOT) reconstructions in children. Both types of conduits have their pros and cons vividly described in the literature, but so far only a few comparative studies have been presented. Between 1993 and 2005, 88 aortic homografts (54 blood-group compatible, iso, and 34 nonblood-group compatible, non-iso) and 50 Contegra conduits were implanted for RVOT reconstruction. Mean age was 4.9 +/- 3.6 years, ranging from 1 month to 15 years. The two important primary diagnoses were tetralogy of Fallot (61%), and double-outlet right ventricle with pulmonary stenosis (12%). There were no demographic differences between the groups. The mean graft diameter was 19 mm (homografts) and 15 mm (Contegra). There were no hospital deaths in the homograft group, whereas 1 patient died of graft unrelated causes in the Contegra group. Postoperative mean gradient was 14.5 +/- 11.2 mm Hg (homografts) and 19.8 +/- 11.5 mm Hg (Contegra). Freedom from graft dysfunction and reoperation at 2, 5, and 7 years was 88.9%, 87.6%, and 81.3% for all homografts; 100%, 97.4%, and 93.8% for homograft iso; 79.9%, 76.9%, and 66.6% for homograft non-iso; and 94.0%, 90.7%, and 90.7% for Contegra grafts. Moderate valvar regurgitation was seen in 3.4% (homografts) and 8.0% (Contegra). No supravalvar lesions were observed in either group. Blood-group compatible cryopreserved homografts and Contegra conduits for RVOT reconstruction have very similar performance as long as 7 years postoperatively, and are significantly superior to nonblood-group compatible homografts.

Qualitative Histological Evaluation of Photooxidized Bovine Osteochondral Grafts in Rabbits: A Pilot Study

Photooxidation is a treatment that can render tissue less immunogenic and resistant to enzymatic degradation, while maintaining the mechanical properties of the material. The purpose of this study was to histologically examine the biocompatibility of photooxidized bovine osteochondral grafts when implanted into the rabbit. Two holes were drilled into the patellar groove of the rabbit knee. Photooxidized bovine osteochondral grafts were implanted into the holes. As a control, 1 surgically created hole in each rabbit was left to heal naturally. The animals were killed after 12 weeks. Histological analysis of the control sites indicated that fibrocartilage had begun to regenerate in the defect. Analysis of the grafts revealed a chronic, nonspecific inflammatory reaction. Active remodeling was observed in the graft bone, with "bridging" between host and graft bone evident. The articulating surface and majority of the graft cartilage remained undamaged. In a few instances, however, there was an inflammatory response to the base of the graft cartilage, near the subchondral plate. The surface of the graft cartilage was covered by a thin layer of fibrous tissue, and no viable chondrocytes were present. In most cases, there was no fusion between host and graft cartilage. The results from this study suggest that, while a biological reaction to the grafts occurred, the bone portion of the graft appeared to be in the process of remodeling, and the majority of the graft cartilage, most significantly the articulating surface, remained intact. Photooxidized osteochondral grafts show promise for use in the repair of osteochondral defects.

Intraoperative Flow Measurements Are Helpful in the Treatment of High-Inflow Steal Syndrome on a Predialysis Patient with a Brachiocephalic Fistula: A Case Report

Distal revascularization and interval ligation (DRIL) is currently one of the mainstay treatments for severe steal syndrome. However, when high inflow is the underlying cause, this technique does not fully address the problem. Here, we describe the use of intraoperative flow measurements using transit time ultrasound technology to help identify the cause of steal syndrome in a predialysis patient (no transonic surveillance) with a brachiocephalic fistula, who then was treated successfully by inflow reduction surgery using a bovine ureter graft. We believe that inflow reduction might be superior to DRIL in treating steal syndrome caused by high inflow and that transit time ultrasound might be helpful when transonic treatment is not possible.

Effect of Preservation Methods on the Performance of Bovine Pericardium Graft in a Rat Model

This study investigates the effect of preservation methods on the performance of bovine parietal pericardium grafts in a rat model. Mid-ventral full thickness abdominal wall defects of 3 x 2.5 cm in size were created in 90 male Sprague-Dawley rats (300-400 g), which were divided into three groups of 30 rats each. The abdominal defects of group one and two were repaired with lyophilized and glycerolized bovine pericardium grafts, while the defects of group three were repaired with expanded polytetrafluoroethylene (ePTFE) Mycro Mesh as a positive control. Another group of 30 rats underwent sham operation and was used for comparison as negative control. Each group of rats (n = 30) was divided into five subgroups (n = 6) and killed at 1, 3, 6, 9 and 18 weeks post-surgery for gross and morphological evaluations. The rats tolerated the surgical procedure well with a total mortality of 0.05%. No serious post-operative clinical complications or signs of rejection were encountered. Adhesions between the grafts and the underlying visceral organs observed in the study were mostly results of post-surgical complications. Glycerol preservation delayed degradation and replacement of the grafts, whereas lyophilization caused early resorption and replacement of the grafts. The glycerolized grafts were replaced with thick dense fibrous tissue, and the lyophilized grafts were replaced with thin loose fibrous tissue. The healing characteristic of the bovine pericardium grafts was similar to those of the sham-operated group, and quite different from those of the ePTFE Mycro Mesh. The outcome of the present study confirmed the superiority of glycerolized bovine pericardium grafts over its lyophilized counter part.

Fixation of Vascular Grafts With Increased Glutaraldehyde Concentration Enhances Mechanical Properties Without Increasing Calcification

Our objective was to study the effect of glutaraldehyde (GLU) concentration, heat, and photooxidation on mechanical properties and calcification of bovine pericardium grafts in an in vivo model. Fresh pericardia were treated as follows: 0.625% GLU for 7 days (standard); 0.625%, 1%, and 3% GLU at 4 degrees C for 20 days and 50 degrees C for additional 20 days; irradiation in cross-linking medium with metilene blue at 0 degrees C for 8 hours. Tissues were subjected to tensile mechanical tests (n = 76). Fixed patches were subcutaneously implanted in mice for 50 days (n = 16 per treatment). Calcification was assessed by atomic absorption spectrophotometry (n = 55) and von Kossa staining (n = 28). Analysis of variance and Tukey's test were used for statistical analysis. The 3% GLU and 3% GLU + heat treatments showed an enhancement of the mechanical properties above standard treatment. No significant difference was found in calcification between treatments. The 3% GLU treatment enhances the mechanical properties of the tissue above standard treatment without increasing calcification and without applying heat; therefore it is recommended for high-strength applications. Supplementary treatments to decrease calcification could be combined with this methodology to obtain a high-strength-low-calcification biomaterial for manufacturing of long-term cardiovascular grafts.

Diagnostic Imaging of and Radiologic Intervention for Bovine Ureter Grafts Used as a Novel Conduit for Hemodialysis Fistulas

The objectives of our study were to review the appearances on diagnostic imaging and amenability to imaging-guided intervention of a novel bovine ureter graft (Syner-Graft 100 [SG 100]) for use as a conduit for hemodialysis fistulas. The SG 100 shows initial promise as a conduit for hemodialysis fistulas in patients with difficult vascular access. The SG 100 has characteristic appearances on diagnostic imaging and is prone to similar pathologic processes that affect autogenous venous and synthetic grafts. These grafts are readily amenable to imaging-guided percutaneous intervention, which plays a major role in prolonging graft function.

Analysis of Gene Expression in Bovine Testis Tissue Prior to Ectopic Testis Tissue Xenografting and During the Grafting Period1

The purpose of this study was to identify factors that contribute to bovine testis development and donor age-dependent differences in the abilities of bovine ectopic testis tissue grafts to produce elongated spermatids. We used real-time RT-PCR and microarrays to evaluate and to identify the expression of genes that are involved in Sertoli and germ cell development in bovine testis tissues. Testis tissues were obtained from 2-, 4-, and 8-wk-old bull calves and were grafted immediately. Grafted bovine testis tissue was removed from mice, RNA was isolated from the grafts, and real-time RT-PCR was used to evaluate gene expression during the grafting period. In addition, the gene expression in the donor tissue was analyzed using Affymetrix Bovine GeneChips, to identify differentially expressed genes. Examination of the testis tissue grafts indicated that Sertoli cell-specific gene expression was lower in 8-wk donor tissue grafts compared to the donors of other ages. Furthermore, the expression of KIT, which is a germ cell-specific gene, was low in testis tissue grafts. Microarray analysis of the donor tissue showed that several genes that are involved in angiogenesis or tissue growth were differentially expressed in 2-, 4-, and 8-wk-old bovine testes. The levels of expression of the genes for angiogenin, transgelin, thrombomodulin, early growth response 1, insulin-like growth factor 2, and insulin-like growth factor-binding protein 3 were lower in testis tissues from older animals. Using these data, it will be possible in the future to manipulate the testis xenograft microenvironment so as to improve the efficiency of sperm production within the graft.

Bovine Dural Graft: A Unique Cause of Unexplained Fever, Erythroderma and Eosinophilia

RATIONALE: We report the first case of eosinophilia from a bovine dural graft.METHODS: The patient's medical record was reviewed. The literature was reviewed for cases of eosinophilia related to a bovine dural graft.RESULTS: An 18 year old female with spina bifida presented with unexplained fever, erythroderma and eosinophilia. Ten weeks previously, she underwent surgical correction of a tethered spinal cord with bovine dural patch placement. Three weeks postoperatively she became febrile and methicillin resistant Staphylococcus aureus was cultured from the surgical site. Despite appropriate intravenous antibiotics, the patient remained febrile for several weeks. An erythematous, desquamating, pruritic erythroderma developed that was attributed to a possible drug reaction. All medications were stopped but the rash persisted. A peripheral eosinophilia to 6,300 x 10(9)/L developed as did transaminitis, hypoalbuminemia and anemia. Autoantibody and parasite serologies were negative and an indwelling central venous catheter was removed. On 2 separate occasions systemic corticosteroids successfully treated the fever and rash. Unfortunately, both returned whenever corticosteroids were stopped. Serum specific IgE was class 2 positive to beef (1.20 kU/L), and an intradermal injection of bovine collagen resulted in 5X3 mm area of induration at 24 hours. The bovine dural patch was removed, and pathology revealed moderate eosinophilic and chronic lymphocytic inflammation as well as a noncaseating granulomatous reaction. The fever, rash and eosinophilia resolved without postoperative corticosteroids. The 5 week postoperative eosinophil count was 800 x 10 (9)/L.CONCLUSIONS: Allergy to acellular bovine graft material should be considered in the differential diagnosis when evaluating fever, erythroderma and eosinophilia. RATIONALE: We report the first case of eosinophilia from a bovine dural graft. METHODS: The patient's medical record was reviewed. The literature was reviewed for cases of eosinophilia related to a bovine dural graft. RESULTS: An 18 year old female with spina bifida presented with unexplained fever, erythroderma and eosinophilia. Ten weeks previously, she underwent surgical correction of a tethered spinal cord with bovine dural patch placement. Three weeks postoperatively she became febrile and methicillin resistant Staphylococcus aureus was cultured from the surgical site. Despite appropriate intravenous antibiotics, the patient remained febrile for several weeks. An erythematous, desquamating, pruritic erythroderma developed that was attributed to a possible drug reaction. All medications were stopped but the rash persisted. A peripheral eosinophilia to 6,300 x 10(9)/L developed as did transaminitis, hypoalbuminemia and anemia. Autoantibody and parasite serologies were negative and an indwelling central venous catheter was removed. On 2 separate occasions systemic corticosteroids successfully treated the fever and rash. Unfortunately, both returned whenever corticosteroids were stopped. Serum specific IgE was class 2 positive to beef (1.20 kU/L), and an intradermal injection of bovine collagen resulted in 5X3 mm area of induration at 24 hours. The bovine dural patch was removed, and pathology revealed moderate eosinophilic and chronic lymphocytic inflammation as well as a noncaseating granulomatous reaction. The fever, rash and eosinophilia resolved without postoperative corticosteroids. The 5 week postoperative eosinophil count was 800 x 10 (9)/L. CONCLUSIONS: Allergy to acellular bovine graft material should be considered in the differential diagnosis when evaluating fever, erythroderma and eosinophilia.

In vivo repopulation of decellularized bovine jugular valved vein grafts with autologous cells occurs in sheep when implanted in pulmonary valve position

Introduction: Glutaraldehyd fixed bovine jugular valved vein grafts („Contegra“) used for reconstruction of the pulmonary outflow tract are unable to grow. The aim of this study was to investigate the performance of not fixed but decellularized bovine jugular valved vein grafts implanted in pulmonary position in respect to function, cellular repopulation – a prerequisite for potential growth –, and morphology in the sheep model.

Polytetrafluoroethylene and Bovine Mesenterial Vein Grafts for Hemodialysis Access: A Comparative Study

Purpose This study aimed to evaluate the safety and patency rate of bovine mesenterial vein grafts (BMVG) for vascular access (VA) in hemodialysis patients (HDP), compared to expanded polytetrafluorethylene (ePTFE grafts) over a mid- to long-term period. Methods Patency and complication rate of 23 consecutive HDP with BMVG for VA were compared to a control group consisting of 23 similar HDP with ePTFE grafts. In both groups, the graft was placed preferably in a forearm loop configuration. The same surgeon performed all procedures. All patients were followed over a period of 4 yrs. Results Graft placement was successful in all patients. Patency rates did not differ significantly in both groups. However, there were less severe complications in the BMVG group. Conclusion The BMVG is a viable alternative for HD access in patients where autologous construction is not possible, and should be given priority in patients with a failed ePTFE graft or high risk for infection.

Eletroacupuntura aplicada nas fases precoce e tardia da cicatrização do tendão calcanear comum de coelhos após reparo tardio com peritônio bovino conservado em solução supersaturada de sal: aspectos clínicos

Para avaliar o uso da eletroacupuntura (EA) sobre os aspectos clínicos e deambulatórios, 36 coelhos tiveram o tendão calcanear comum seccionado e, após 30 dias, receberam enxerto de peritônio bovino conservado em solução supersaturada de sal. Em seguida, os animais foram distribuídos aleatoriamente em três grupos de igual número: no primeiro grupo, os coelhos foram estimulados pela EA do segundo ao 11° dia de pós-operatório (PO) (E10); no segundo grupo do 11o ao 31o dia de PO (E20) e, no terceiro grupo, os animais não foram estimulados (C). Verificou-se, nos animais do E10, durante o PO, ausência de edema e hiperemia no membro tratado pela EA. Não se observou diferença significativa (P>0,05) entre os grupos quanto ao grau de deambulação dos animais. Todos os coelhos tiveram completa recuperação da deambulação até os 51 dias de PO. A utilização da eletroacupuntura na fase precoce da cicatrização do tendão calcanear comum de coelhos impediu a formação de edema e hiperemia. O tratamento com eletroacupuntura no PO não melhorou o desempenho da deambulação.

Resection of recurrent inferior vena cava tumor after radical nephrectomy for renal cell carcinoma

Management of recurrent tumor in the inferior vena cava (IVC) after radical nephrectomy is surgically challenging. We report 3 cases of recurrent renal cell carcinoma within the IVC managed by three different surgical techniques. One patient was treated with tumor thrombus removal and primary cavotomy closure. The second patient was treated with IVC ligation and removal without vascular reconstruction. A third patient was treated with IVC wall excision and placement of a bovine pericardium graft. Although technically difficult, repeat resection of IVC tumor recurrence after nephrectomy for renal cell carcinoma is an acceptable method of treatment.

Bovine ureter graft for haemodialysis access surgery**This article was presented as an oral presentation in the 54th International Congress of the European Society for Cardiovascular Surgery, Athens, Greece, May 19–22, Interactive Cardiovascular and Thoracic Surgery, Vol. 4 (Suppl 1), May 2005.

Bovine ureter SynerGraft (SG) (CryoLife, Inc.) has been recently introduced into haemodialysis access surgery. It is a non-glutaraldehyde fixed acellular collagen and elastin matrix conduit that may withstand arterial pressures. There has only been one published report in humans with this graft for vascular access, except for a canine model which Matsuura et al. reported [1]. In this study, we report the early and mid-term outcome of bovine ureter as a haemodialysis access graft in chronic haemodialysis. Four female patients with an average age of 44.5 years (range 25–67 years) underwent surgery in November 2004, using the bovine ureter SynerGraft (CryoLife, Inc.) as a conduit for haemodialysis access surgery. The operations were indicated in these patients, as they had no suitable superficial venous system to create an arteriovenous fistula; they also had previously failed arteriovenous fistulas and expanded polytetra flouroethylene (ePTFE) grafts in several different locations. The patients were evaluated with Doppler ultrasound which revealed normal deep venous system. All the patients were informed about the graft and written consents were taken prior to the operation. The operations were done under axillary block. The xenografts were implanted between the brachial artery and the axillary vein in two patients, and between the radial artery and the deep brachial vein in two patients. After systemic heparinization, the graft was anastomosed to the artery in an end-to-side fashion, using a running 6/0 polypropylene suture. The artery was declamped to fill the graft. The graft was passed through the tunnel and the venous anastomosis was done using the same suturing technique. Heparin was not neutralized after the anastomosis. All grafts were allowed for a 6-week maturation for the remodelling of the vascular prosthesis prior to haemodialysis. The grafts were accessed three times a week for haemodialysis. All grafts implanted were patent on the first postoperative day. One of the grafts between the brachial artery and the axillary vein failed at the end of the second month after four times of haemodialysis. A severe aneurysm and pseudoaneurysm formation occurred in the other graft after a fifth intervention for haemodialysis. This required total excision of the graft and saphenous vein interpositioning to the brachial artery. At the end of the third month, both of the grafts between the radial artery and the brachial vein were patent and the patients had had several haemodialysis sessions. However, these grafts also failed at the end of fifth and sixth months. A recently occluded graft was re-operated for thrombectomy, but it re-occluded in the first post-operative day. The patency rates of the grafts by means of graft location are seen in Table 1.

Effect of Vascular Endothelial Growth Factor and Testis Tissue Culture on Spermatogenesis in Bovine Ectopic Testis Tissue Xenografts

Bovine ectopic testis tissue grafting is a technique that can be used to study bovine spermatogenesis and for the production of germ cells for a variety of applications. Approximately 10% of seminiferous tubule cross sections in testis grafts contain spermatids, providing a unique tool to investigate what regulates germ cell differentiation. We hypothesized that manipulation of testis tissue grafts would increase the percentage of seminiferous tubule cross sections undergoing complete germ cell differentiation. To test this hypothesis, bovine testis tissue was treated with vascular endothelial growth factor (VEGF) at the time of grafting or explant cultured for 1 wk prior to grafting. For the VEGF experiment, 8-wk donor tissue and graft sites were treated with 1 microg of VEGF in order to increase angiogenesis at the graft site. For the testis tissue culture experiment, 4-wk-old donor testis was cultured for 1 wk prior to grafting to stimulate spermatogonial stem cell proliferation. Testis tissue grafts were removed from the mice 24 wk after grafting. VEGF treatment increased graft weight and the percentage of seminiferous tubule cross sections with elongating spermatids at the time of graft removal. Cultured testis tissue grafts were smaller and had fewer seminiferous tubules per graft. However, there was no difference in the percentage of seminiferous tubule cross sections that contained any germ cell type between groups. These data indicate for the first time that bovine testis tissue can be manipulated to better support germ cell differentiation in grafted tissue.

Immunogenicity of unprocessed and photooxidized bovine and human osteochondral grafts in collagen-sensitive mice

BackgroundAutologous and allogeneic osteochondral grafts have been used to repair damaged or diseased cartilage. There are drawbacks to both of these methods, however. Another possible source for osteochondral grafting is photooxidized xenograft scaffolds. The purpose of this study was to evaluate the adaptive immune response to unprocessed and photooxidized xenogeneic osteochondral grafts in a collagen-sensitive mouse model.MethodsUnprocessed and photooxidized bovine and human osteochondral grafts were used. The grafts were implanted subcutaneously in collagen-sensitive DBA/1LacJ mice for four or twelve weeks. ELISPOT assays were conducted with spleen cells to evaluate the number of collagen-specific T cells that produce IL-2, IL-4, IL-5 or IFN-γ. Serum was collected and ELISA assays were performed to determine the titers of collagen-specific and total IgG, IgG1, IgG2a, or IgM antibodies. Histology was conducted on the retrieved osteochondral grafts.ResultsResults indicated that, with respect to adaptive T cell immunity, the photooxidized bovine grafts, unprocessed human grafts and photooxidized human grafts did not induce a significant response to collagen. The unprocessed bovine grafts, however, were slightly more immunogenic, inducing a weak immune response. With respect to antibody production, the bovine grafts were less immunogenic than the human grafts. Bovine collagen-specific IgG antibodies were not induced by these grafts, but production of IgM after twelve weeks was observed with both the unprocessed and photooxidized bovine grafts. In contrast, photooxidized human osteochondral grafts induced IgG1 and IgG2a antibodies, while the unprocessed human grafts did not. Pre-existing human collagen-specific IgM antibodies were present in all mice, including sham-operated negative controls that did not receive an implant. Histological analysis revealed some degree of fibrous encapsulation and inflammatory infiltrations in both bovine and human implants, whether unprocessed or photooxidized.ConclusionBoth bovine and human cartilage grafts showed weak, but clear immunogenicity in the DBA/1LacJ mice, indicating that immunogenic collagen was still contained in the grafts, even after cleaning and photooxidation. The process of photooxidation is still important in osteochondral grafting, since it stabilizes the surface of the cartilage by cross-linking the collagen fibers, and allows for immediate load bearing and joint resurfacing.