A systematic review of inflammatory cells and markers in human tendinopathy.

BACKGROUND: This article systematically reviews the current evidence regarding inflammation in Tendinopathy with the aim to increase understanding of a potential common pathophysiology. METHODS: Following the PRISMA statements, the terms: (tendinopathy OR (tendons AND rupture)) AND (inflammation OR (inflammation AND cells) OR immune system OR inflammation mediators OR bacteria) were used. One thousand four hundred thirty-one articles were identified which was screened down to 53. RESULTS: 39/53 studies mentioned inflammatory cells but had contradicting conclusions. Macrophages were the most common cell type and inflammatory markers were detectable in all the articles which measure them. CONCLUSIONS: The included studies show different conclusions, but this heterogeneity is not unexpected since the clinical criteria of 'tendinopathy' encompass a huge clinical spectrum. Different 'tendinopathy' conditions may have different pathophysiology, and even the same clinical condition may be at different disease stages during sampling, which can alter the histological and biochemical picture. Control specimen sampling was suboptimal since the healthy areas of the pathological-tendon may actually be sub-clinically diseased, as could the contralateral tendon in the same subject. Detection of inflammatory cells is most sensitive using immunohistochemistry targeting the cluster of differentiation markers, especially when compared to the conventional haematoxylin and eosin staining methods. The identified inflammatory cell types favour a chronic inflammatory process; which suggests a persistent stimulus. This means NSAID and glucocorticoids may be useful since they suppress inflammation, but it is noted that they may hinder tendon healing and cause long term problems. This systematic review demonstrates a diversity of data and conclusions in regard to inflammation as part of the pathogenesis of Tendinopathy, ranging from ongoing or chronic inflammation to non-inflammatory degeneration and chronic infection. Whilst various inflammatory markers are present in two thirds of the reviewed articles, the heterogenicity of data and lack of comparable studies means we cannot conclude a common pathophysiology from this systematic review.

Irradiation sterilization used for allogenetic tendon: a literature review of current concept.

Tendon injury is a very common type of sports trauma, and its incidence has increased over the past decades. Surgical reconstruction with tendon allograft has been increasingly used to restore the motor function and stability of the injured site. However, the risk of disease transmission caused by allogeneic tendon transplantation has been a major problem for tissue bank researchers and clinicians. In order to eliminate the risk of disease transmission, a process of terminal sterilization is necessary. Ionizing irradiation, including gamma irradiation and electron beam irradiation is the most commonly used method for the terminal sterilization, which has been widely proved to be able to effectively inactivate the contained pathogens. Nevertheless, some accompanying damage to the mechanical and histological properties of collagen fibers in tendons will be caused. Therefore, more and more studies have begun to pay attention to the protective effect of radiation protection agents, including the radical scavengers and cross-linking agents, in the irradiation sterilization of allogeneic tendons.

Bacterial contamination rate and associated factors during bone and tendon allograft procurement from Spanish donors: exploring the contamination patterns.

BACKGROUND: Allograft contamination during extraction represents a major limiting factor for tissue bank availability. Contamination rates remain persistently high independent of the hospital, country or year considered. AIM: To analyse the factors associated with contamination of bone and tendon samples extracted from Spanish donors. METHODS: Data for 1162 bone and tendon samples extracted from 102 donors between 2014 and 2017 were collected retrospectively from the hospital database. Descriptive statistics, potentially associated factors and correlation of contamination between samples extracted from different anatomical locations of the same donor were analysed. FINDINGS: In total, 227 (19.54%) of the extracted samples [131 (18.49%) bone samples and 96 (20.92%) tendon samples] rendered positive cultures and were discarded. Male sex [odds ratio (OR) 2.023; P=0.019], extraction of >10 samples per donor (OR 1.997; P<0.001) and extraction time >240 min (OR 1.755; P=0.001) were factors independently associated with a higher contamination rate. Meanwhile, the tissue sample type 'bone-patellar tendon-bone' was associated with a significantly lower contamination rate (OR 0.446; P=0.001). Significant correlation between certain localization of contaminated samples and the concordance of bacterial species was also observed. CONCLUSION: Factors related to the extraction procedure, such as total extraction time, extraction sequence, number of samples extracted and anatomical location of extracted samples, play a major role in allograft contamination. Further optimization of procedures, guided by the contamination patterns analysed in this study, should help to increase tissue bank availability.

Biomechanical and microbiological effects of local vancomycin in anterior cruciate ligament (ACL) reconstruction: a porcine tendon model.

INTRODUCTION: Although there is increasing evidence for the successful use of local vancomycin applied by soaked compresses during ACL reconstruction, there are still little data on its microbiological and biomechanical effects. Furthermore, exact dosage of vancomycin with respect to tendon stability and microbiological effectivity is still unknown. MATERIALS AND METHODS: 63 porcine flexor digitorum profundus tendons were harvested under sterile conditions from fresh cadaver legs. After contamination with Staphylococcus epidermidis (S. epidermidis), tendons were wrapped into sterile compresses moistened with different concentrations of vancomycin for 10 or 20 min. Sterile sodium chloride was used for control. After treatment, tendons were rolled onto blood-agar plates to test for residual bacterial contamination and tested for maximum load and stiffness using a uniaxial testing device with cryo-clamps for tendon fixation. Agar plates were checked after 1 week of culture at 36 °C for signs of bacterial growth. RESULTS: When applying vancomycin for only 10 min, bacterial contamination was found in all dosage groups ranging from 28.6% contamination (n = 2 of 7 tendons) when using 10 mg/ml up to 85.7% (n = 6 of 7 tendons) when using 1 mg/ml. Applying vancomycin-soaked compresses for 20 min, bacterial contamination was still found in the groups using 1 mg/ml and 2.5 mg/ml (contamination rate 85.7 and 42.9% respectively). When using 5 mg/ml and 10 mg/ml, no bacterial contamination could be perceived after 7 days of culture. With regard to biomechanical properties, no differences were found regarding maximum load or Young's modulus between groups. CONCLUSIONS: This study showed no signs of biomechanical impairment of porcine flexor tendons after the use of vancomycin wraps with concentration ranging from 1 to 10 mg/ml for 10 or 20 min at a time zero testing. Contamination with S. epidermidis was cleansed in 100% of tendons when using at least 5 mg/ml of vancomycin for 20 min.

Musculosceletal tuberculosis with involvement of tendon sheaths and formation of synovial cyst.

Due to an increasing amount of patients on immunosuppressive treatment, the number of tuberculosis (TB) of atypical course and extrapulmonary tuberculosis cases increase. Locomotor system is a place of every fifth case of extrapulmonary TB. Because of lack of characteristic symptoms, as well as rare co-occurrence of active lung lesions in radiological imaging, proper diagnosis is hard to establish. We present a case of patient on immunosuppressive therapy due to myositis, in whom we diagnosed musculoskeletal tuberculosis in form of involvement of tendon sheath and formation of synovial cyst.

Quantification Analysis of the Intraoperative Bacterial Contamination Rate and Level in Osteochondral Autografts.

BACKGROUND: Inadvertent contamination of osteochondral (OC) autografts during harvesting and preparation can lead to significant complications and can cause the operating team to weigh the infection risk after reimplantation against discarding the OC fragment. The most commonly reported contamination mechanism is the accidental dropping of an OC fragment; however, associated contamination levels remain unclear. The rate and level of contamination during standard harvesting and preparation are also unknown. PURPOSE: To quantitatively evaluate the rate and level of bacterial contamination of OC autografts during harvesting and preparation compared with those of accidently dropped autografts. STUDY DESIGN: Controlled laboratory study. METHODS: Under sterile conditions, 138 fresh OC specimens were harvested and retrieved from 23 primary total knee arthroplasties (TKAs). Six OC fragments were retrieved from each TKA: 3 were used as controls, and 3 were dropped onto the operating room floor. Each specimen was incubated to allow for aerobic and anaerobic growth, and the number of colony-forming units (CFUs) per gram was calculated. RESULTS: Contamination rates (positive cultures) for the control and dropped groups were 29% (n = 20/69) and 42% (n = 29/69), respectively. The difference in the contamination rate between groups was not statistically significant (P = .109). The most common organisms identified were Staphylococcus aureus (40%) in the control group and Staphylococcus epidermidis (24.1%) and Bacillus species (20.7%) in the dropped group. The contamination level (CFUs/g) for both groups was low. The median (range) CFUs/g among the contaminated specimens in the dropped and control groups were 27 (1-120) and 3 (1-15), respectively (P < .0001). CONCLUSION: A relatively high rate of OC autograft contamination can be expected during harvesting and preparation (29%) or after accidentally dropping a specimen (42%). Although the types of organisms isolated differed between specimens contaminated during harvesting and preparation and dropped specimens, the quantification of the autograft contamination level revealed a very low CFUs/g in both cases. CLINICAL RELEVANCE: 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.

When the tendon autograft is dropped accidently on the floor: A study about bacterial contamination and antiseptic efficacy.

BACKGROUND: Inadvertent contamination of the autograft can occur during anterior cruciate ligament (ACL) reconstruction if the autograft is dropped on the floor during surgery. A study was undertaken to determine the incidence of contamination when a graft is dropped on the operating room floor and the efficacy of antimicrobial solutions to decontaminate it. METHODS: Samples from 25 patients undergoing ACL reconstruction with a hamstring tendon were sectioned and dropped onto the floor. Cultures were taken after immersion in antiseptic solutions (a chlorhexidine gluconate solution (group 1), a povidone-iodine solution (group 2), and a sodium hypochlorite solution (group 3)). A fourth piece (group 0) was cultured without being exposed to any solution. Cultures of a floor swab were taken at the same time. RESULTS: The floor swab cultures were positive in 96% of cases. The rate of contamination was 40% in group 0, 8% in group 1, 4% in group 2, and 16% in group 3. There was a significant difference between groups 1 and 2 and group 0 (p<0.05) but not between groups 3 and 0. CONCLUSIONS: Immersing a graft dropped on the floor during surgery in a chlorhexidine gluconate solution or povidone-iodine solution significantly reduces contamination of the graft. Soaking of the hamstring autograft in one of these solutions is recommended in the case of inadvertent contamination. CLINICAL RELEVANCE: Laboratory investigation (level 2).

Management of the contaminated anterior cruciate ligament graft.

PURPOSE: This systematic review explores management strategies for intraoperative anterior cruciate ligament (ACL) graft contamination. METHODS: Two databases (Medline and EMBASE) were screened for studies involving ACL graft contamination published between 1946 and April 2013. We included studies evaluating the management of a contaminated graft and excluded small case-series studies. We conducted a full-text review of eligible studies, and the references were searched for additional eligible studies. Inclusion and exclusion criteria were applied to the searched studies. RESULTS: Our search yielded 6 laboratory investigations with a total of 495 graft samples used. These samples were contaminated and cleansed by various methods. The most successful sterilization protocols used chlorhexidine or mechanical agitation with a polymyxin B-bacitracin solution to achieve sterility in 100% of their respective experimental graft tissues. A chlorhexidine soak and plain bacitracin soak were also effective, at 97.5% and 97%, respectively. Povidone-iodine and an antibiotic soak of polymyxin-bacitracin were the least effective, with sterility rates of 48% and 57%, respectively. CONCLUSIONS: The results of this review suggest that the optimal agent for sterilizing a dropped graft is chlorhexidine. A protocol of mechanical agitation and serial dilution with a polymyxin B-bacitracin solution was also highly effective; however, the sample size was too small to realistically recommend its use. Bacitracin alone was also found to be an effective sterilization agent, as was a combined solution of neomycin and polymyxin B. Pooled results showed that normal saline solution, povidone-iodine, and a polymyxin B-bacitracin solution all yielded suboptimal sterilization. The available evidence, however, is laboratory based and may not accurately reflect clinical conditions; moreover, there is a lack of biomechanical studies evaluating sterilized grafts. As a result, the findings should be interpreted with caution. LEVEL OF EVIDENCE: Level IV, systematic review of basic science studies.

Evaluation of sterilization methods following contamination of hamstring autograft during anterior cruciate ligament reconstruction.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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 in either bacitracin or 4 % chlorhexidine solution is recommended. In addition, dropped hamstring autograft can be effectively sterilized with bacitracin or 4 % chlorhexidine solution. LEVEL OF EVIDENCE: II.

A typically atypical tenosynovitis.

A 68-year-old woman developed tenosynovitis of the right second digit without a history of injury or animal bites. Apart from high titer anti-nuclear antibodies, serological studies were unremarkable. Tuberculin test and interferon gamma release assay were both negative. Several immunosuppressive therapies led only to partial relief of symptoms. Of note, clinical symptoms worsened significantly after introduction of adalimumab therapy. Tenosynovectomy was performed revealing a granulomatous inflammatory process. Seven weeks later, Mycobacterium malmoense could be cultured from the surgical specimen. A four drug antibiotic regimen was started and immunosuppressive therapy discontinued resulting in complete clinical remission. Our case highlights non-tuberculous mycobacterial (NTM) tenosynovitis as an important differential diagnosis of atypical arthritis. A negative tuberculin skin test as well as negative Ziehl-Neelsen stain does not argue against NTM infection. In fact, mycobacterial culture for extended periods remains the gold standard for diagnosis.

Tuberculosis of the entheses.

PURPOSE: Tuberculosis of the osteoarticular system usually manifests as joint arthritis. There is no available English literature on the tubercular involvement of the enthesis (tendon-bone junction). METHODS: We performed a retrospective analysis on 14 patients with tuberculosis of the tendon-bone junction. Patients presenting with a sinus with or without presence of radiological evidence of bone destruction around the enthesis, and pain unresponsive to a trial of analgesics and physical therapy, were evaluated by closed or open biopsy for tuberculosis. A staging system is proposed for biopsy-proven tuberculosis of the enthesis. RESULTS: Between 2006 and 2010, we treated 14 patients with tuberculosis of the tendon-bone junction. Biopsy-proven cases of tuberculosis of the enthesis were administered anti-tubercular drugs for a period of one year. Sequestrectomy was performed in advanced lesions. The tendon-bone junction was rested until the features of its healing were clinically evident. The patients aged between 18 and 52 years were followed up for an average of 1.7 years after cessation of anti-tubercular drug therapy. They responded favourably, and none had recurrence of the disease. CONCLUSIONS: This study describes the tubercular involvement of the entheses, which heretofore has not been described in the literature. The rarity of its occurrence and lack of suspicion of an infectious aetiology in these locations frequently results in late diagnosis and incorrect initial treatment. This study also supports the "microtrauma theory" in the genesis of osteoarticular tuberculosis.

Micro-organism colonization and intraoperative contamination in patients undergoing arthroscopic anterior cruciate ligament reconstruction.

PURPOSE: To investigate the status of preoperative micro-organism colonization and intraoperative contamination in patients undergoing anterior cruciate ligament (ACL) reconstruction. METHODS: Fifty patients who underwent scheduled ACL reconstruction were included in the study. At the preoperative checkup, swabs were taken from the skin at the surgical site and the nose. During surgery, swab samples were taken from the skin adjacent to the incision and the surface of the graft and examined for contamination. RESULTS: Preoperative examination for micro-organism colonization showed positive results in 23 of 50 samples (46%) taken from the skin and 45 of 50 samples (90%) taken from the nose. Intraoperative swab samples taken from the skin and the graft showed positive rates of 6% and 2%, respectively, which were significantly lower compared with the preoperative values (P < .05). The most frequently identified organism in both preoperative and postoperative examinations was coagulase-negative Staphylococcus (CNS), representing 93% of the positive results. Among those CNS strains, roughly one-third of the samples were shown to be methicillin resistant. During the study period, surgical-site infection with methicillin-resistant CNS occurred in 1 patient. In this patient the preoperative culture identified methicillin-sensitive CNS, whereas preoperative nasal culture and intraoperative examinations of the skin and the graft were negative. CONCLUSIONS: Preoperative examination of micro-organism colonization in patients undergoing ACL reconstruction showed positive results in 46% and 90% of the samples taken from the skin and the nose, respectively. In the intraoperative examination, 6% and 2% of the swabs taken from the adjacent skin and the graft, respectively, showed positive results. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Incidence of positive intraoperative allograft cultures used in knee ligament reconstruction.

Soft-tissue allografts are valuable options in knee ligament reconstructive surgery. The purpose of this study was to determine the risk of soft-tissue contamination before implantation and the occurrence of infection after implantation in patients who received soft-tissue allografts for knee reconstructive procedures. A retrospective review of medical records was performed for patients who had undergone knee ligament surgery with allograft tissues at one institution between 1993 and 2004. Cultures were positive in 6 (5.7%) of 105 cases. Coagulase-negative Staphylococcus was the most common organism. None of these patients developed postoperative infections. The culture-positive group had a longer period of joint effusion postoperatively, compared with the culture-negative group (14.2 weeks versus 9.6 weeks). Patients with positive cultures required no additional treatment other than close observation.

Intra-operative hamstring tendon graft contamination in anterior cruciate ligament reconstruction.

We aimed to evaluate the possibility of hamstring tendon contamination, the correlation with clinical infection and its association with C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) values in 89 anterior cruciate ligament reconstructions. Two tissue samples were obtained for culture from each graft: immediately after harvesting the graft and before implantation. The ESR and the CRP were evaluated preoperatively and on the 4th and 20th postoperative days. Nine patients (10%) had positive cultures but no patient had signs of postoperative infection. All patients had ESR and CRP values elevated at the 4th postoperative day. ESR and CRP values returned to normal levels at the 20th postoperative day. Higher mean values of CRP levels at the 4th day were observed in patients with contaminated grafts compared to those with uncontaminated. Both values reached normal levels at the 20th postoperative day.

High hydrostatic pressure, a novel approach in orthopedic surgical oncology to disinfect bone, tendons and cartilage.

High hydrostatic pressure (HHP) is widely used in the food processing industry, for example to inactivate vegetative microorganisms in meat products, milk and juice, thereby avoiding the addition of any chemical preservatives. Besides this, HHP is also an attractive novel approach to effectively kill vegetative microorganisms or tumor cells in bone, cartilage and tendon ex vivo while leaving the tissues' mechanical properties unimpaired, thus allowing reimplantation of the resected tissue explants. In contrast, sterilization by gamma irradiation and thermal or chemical inactivation of potentially infected autografts, allografts and other biomaterials considered for tissue regeneration and reconstruction is often associated with deterioration of the mechanical, physical and biological properties of the implant. HHP technology is now in preclinical testing with the aim of disinfecting/devitalizing grafts in order to inactivate both vegetative microorganisms and tumor cells in resected bone tissue segments, eventually allowing reimplantation of resected bone segments initially afflicted with osteomyelitis or tumors. The technical advantages, state-of-the-art, and potential application of HHP in orthopedic surgery are reviewed.

Flexor tendon synovitis of the hand as first manifestation of atypical tuberculosis.

We present the case of a 73-year old patient suffering from chronic flexor tendon synovitis of the wrist with carpal tunnel syndrome. He underwent synovectomy and median nerve release. Primary bacteriology was negative. Histology of the excised synovia revelead non-caseating granuloma as typical for sarcoidosis. Further screening for sarcoidosis was negative. Culture of a sample harvested from the poorly healing wound was finally positive for Mycobacterium tuberculosis. Tuberculostatic treatment was started and the wound gradually healed. To the best of our knowledge, this is the first reported case of atypical non-caseating and sarcoidosis-like granulomas of the flexor tendon synovia of the hand as first manifestation of tuberculosis.

Mycobacterium tuberculosis-induced carpal tunnel syndrome: management and follow-up evaluation.

PURPOSE: To determine the clinical characteristics of 12 patients with Mycobacterium tuberculosis-induced carpal tunnel syndrome. This article also presents our intraoperative findings and surgical treatment results. METHODS: Twelve patients with tuberculosis-induced carpal tunnel syndrome who had surgery during a 10-year period that began in March 1991 were reviewed. The entrance criterion was a positive histologic report of tuberculosis for surgical specimens. The preoperative evaluation leading to diagnosis was reviewed for all patients. Transection of the transverse carpal ligament and complete synovectomy were performed for all patients. After surgery the patients were given an antituberculosis regimen for 1 year and were followed up for an average of 6 years. RESULTS: Twelve cases from a total of 1,180 patients with carpal tunnel syndrome were traced to M tuberculosis involvement of synovial tissue of the flexor tendons. Ten patients had large rice bodies in thick synovial membranes, and in the other 2 patients thick synovial tissue with yellow exudates were observed during surgery. In contrast to tendon involvement with rupture, no direct median nerve involvement was noted. Histopathologic study results of surgical specimens were positive for tuberculosis in all patients. Eight of 10 initial smears showed acid-fast bacillus and all 10 cultures of the specimens were positive for tubercle bacilli. Surgery and antituberculosis therapy were associated with a desirable outcome and sensory disturbance in the median nerve distribution resolved in all patients. Anterior wrist swelling disappeared and there has been no clinical or laboratory evidence of recurrence in all treated patients. CONCLUSIONS: Early diagnosis and surgical treatment combined with antituberculosis medical treatment are important in treating this condition. All patients treated were relieved of symptoms of synovial proliferation at the wrist, with no recurrence of the condition during the follow-up period. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic, Level IV.

Clostridium infections associated with musculoskeletal-tissue allografts.

BACKGROUND: Allografts are commonly used in orthopedic reconstructive surgery. In 2001, approximately 875,000 musculoskeletal allografts were distributed by U.S. tissue banks. After the death from Clostridium sordellii sepsis of a 23-year-old man who had received a contaminated allograft from a tissue bank (Tissue Bank A), the Centers for Disease Control and Prevention initiated an investigation, including enhanced case finding, of the methods used for the recovery, processing, and testing of tissue. METHODS: A case of allograft-associated clostridium infection was defined as a culture-proven infection of a surgical site within one year after allograft implantation, from January 1998 to March 2002. We traced tissues to tissue banks that recovered and processed these tissues. We also estimated the rates of and risk ratios for clostridium infections for tissues processed by the implicated tissue bank and reviewed processing and testing methods used by various tissue banks. RESULTS: Fourteen patients were identified, all of whom had received allografts processed by Tissue Bank A. The rates of clostridium infection were 0.12 percent among patients who received sports-medicine tissues (i.e., tendons, femoral condyles, menisci) from Tissue Bank A and 0.36 percent among those who received femoral condyles in particular. The risk-ratio estimates for clostridium infections from tissues processed by Tissue Bank A, as compared with those from other tissue banks, were infinite (P<0.001) for musculoskeletal allografts, sports-medicine tissues, or tendons. Because Tissue Bank A cultured tissues only after treating them with a nonsporicidal antimicrobial solution, some test results were probably false negatives. Tissues from implicated donors were released despite the isolation of clostridium or bowel flora from other anatomical sites or reports of infections in other recipients. CONCLUSIONS: Clostridium infections were traced to allograft implantation. We provide interim recommendations to enhance tissue-transplantation safety. Tissue banks should validate processes and culture methods. Sterilization methods that do not adversely affect the functioning of transplanted tissue are needed to prevent allograft-related infections.