sterilization of allografts - purgo.co.krpurgo.co.kr/data/_24172 lifenet sterilization paper.pdf ·...

Advancing Allografts

®

An Advancing Allografts Brief • October 2004

Sterilization of Allografts

Tissue Safety — A Major Concern in TransplantationDisease transmission and bacterial infection in

musculoskeletal transplantation continue to raise significant

concerns despite efforts to reduce health risks to transplant

recipients. Nonetheless, allograft usage among orthopedic

surgeons and neurosurgeons has risen dramatically over the

past two decades, resulting in impressive life-enhancing

benefits. In 2002 alone, nearly 1 million allografts were

distributed in the United States.

Recently, an urgent concern about allograft safety was

raised when an implant contaminated with Clostridium

sordellii caused the death of a 21-year old man. The Food

and Drug Administration (FDA) responded by proposing

requirements for Good Tissue Practices (GTPs) covering

procedures, facilities, personnel, equipment, supplies,

reagents, process and labeling controls, process changes

and validation, storage, receipt and distribution, records,

tracking, and handling of complaints.1

Current preparation methods, including screening for disease,

bacterial testing and aseptic processing, substantially reduce

risk, but do not completely eliminate the possibility of

allograft-associated infections. A more certain way to

prevent infection and preserve function is needed.

Sterilization has been proposed as one definitive method

for eliminating microorganisms without adversely affecting

the structure of transplanted tissue1. This paper explores

the current state of tissue transplantation safety and offers

an in-depth look at such new sterilization methods as

included in Allowash XG™.

First, a brief exploration of the current risk of allograft-

related infection will be helpful to understanding the

challenges involved in safe tissue transplantation.

Estimated Rates of ViremiaDemonstrate Safety LimitationHepatitis B virus (HBV), hepatitis C virus (HCV),

human immunodeficiency virus (HIV), and human

T-lymphotropic virus (HTLV) have all been transmitted by

tissue transplantation.2,3,4 According to a recent study using

data from the various review and testing procedures of

tissue-banking organizations, the estimated incidence of

viremia at the time of donation is 1 in 55,000 for HBV,

1 in 34,000 for HCV, 1 in 42,000 for HIV, and 1 in

128,000 for HTLV.5 Actual incidence rates were estimated

to be 30.118, 18.325, 12.380, and 5.586, respectively.

Thus, prevalence rates of HBV, HCV, HIV, and HTLV

infections are lower among tissue donors than in the

general population.

This finding is not surprising, since tissue donors are

chosen carefully based on medical history, physical

examination and interviews with the next of kin. This

process, however, is not as effective as face-to-face interviews

conducted with blood donors. Not surprisingly, the estimated

probability of undetected viremia at the time of tissue

donation is higher among tissue donors than among first-

time blood donors. The fact that the probability of collecting

products from a viremic donor is low, but not negligible,

remains a primary safety concern in transplantation.

In blood donation, the implementation of nucleic acid-

amplification testing of “minipools” (pools of 16 to 24

Ensuring Safety in Tissue Transplantation: The Sterilization of Allografts

By Lloyd Wolfinbarger, Jr., PhD

1

STERILIZATION OF ALLOGRAFTS

blood donations) has markedly reduced the residual

risk of viremia and transfusion-transmitted infection.

Currently, efforts are underway to implement such

testing on cadaveric samples.

Allograft — Sustained Susceptibility to Contamination Utilizing allograft tissues can increase the inherent risk of

bacterial and fungal contamination. The surgical results of

contamination can be serious, but often go unreported.6

Thus, the FDA has recently increased inspection and

enforcement of tissue donation, including the implementa-

tion of a regulatory framework for tissues. Even so, it has

been widely proposed that more stringent, comprehensive

steps be taken to promote and enhance tissue safety.7

Current Tissue Bank Methods — Major Safety LimitationsThe goal of allograft tissue processing is to provide the

safest possible material to the surgeon while preserving

the inherent tissue characteristics of the graft. Even with

adequate donor screening, however, there remains a risk

of allograft contamination. Oversight of tissue-banking

practices has become more stringent to include monitoring

by the FDA, the American Association of Tissue Banks

(AATB) and individual state agencies.

The FDA now requires preparation, validation and

written procedures to reduce the probability of

contamination during processing. The AATB publishes

quality standards for procuring tissue, processing tissue

(including time limits for retrieval), and for screening

donors, as well as publishing strict recommendations for

preservation, sterilization, preparation, evaluation and

labeling of tissues. Individual tissue banks can apply for

voluntary accreditation by meeting AATB standards,

which include aseptic techniques, microbiologic testing

(i.e., aerobic, anaerobic, and fungal preprocessing and

postprocessing cultures) and adverse outcomes reporting.

Despite these safety guides, allograft preparation procedures

could be enhanced for safety. For instance, not all tissue

banks apply for AATB accreditation. In 2002, approximately

10% of musculoskeletal allografts were processed by non-

accredited banks.1 Further, a recent investigation by Kainer

and colleagues demonstrated that infections acquired

through bacterial contamination of allografts are

underreported and have the potential for resulting in

substantial complications or death.6 The study suggests that

the current standards for processing and testing allograft

tissue need to be enhanced to prevent such life-threatening

allograft-associated infections.

As a general rule, implanted tissues are not processed with

sporicidal methods. Moreover, current regulations do not

require tissue banks to eliminate bacteria present on tissues

at the time of recovery or to use processing methods that

guarantee tissue sterility.6 Most tissue banks process

musculoskeletal allografts aseptically by treating the tissue

using various chemical, mechanical and detergent steps.

Aseptic processing is defined by the AATB as the processing

of tissue using methods to prevent, restrict or minimize

contamination with microorganisms from the environment,

processing personnel or equipment. These methods reduce

the inherent microbial bioburden present in incoming

cadaveric tissue without entirely eradicating microorganisms

that sometimes remain after aseptic processing.

The specific problem with aseptic processing is that it only

minimizes bacteria without eradicating organisms and

spores, especially in tissue that is heavily contaminated at

the time of recovery.8 To reduce bacterial contaminants,

some tissue banks suspend tissue in antimicrobial solutions.

However, these solutions may not eradicate spores, as

demonstrated by in vitro studies.6 Two sterilization methods

that can be used to eliminate spores are gamma irradiation

and treatment with ethylene oxide. However, both methods

have the potential to create technical problems with

allografts, limiting their usefulness in tissue processing.8

Further, high doses of gamma irradiation may adversely

affect the biomechanical properties of allografts.9,10,11,12

Ethylene oxide has a limited ability to penetrate tissue

and has been associated with adverse outcomes such as

synovitis13 or damage to musculoskeletal tissue, resulting

in an unacceptably high rate of mechanical failure.14

2

To investigate true eradication of risk, several banks have

developed low-temperature sterilization approaches to kill

spores, while preserving allograft biomechanical integrity

and function. Notably, such a sterilization technique is

best served when it can be validated. Using allografts,

Moore and colleagues developed a viable adaptation of

sterilization for medical devices. Specifically, these

investigators adapted AAMI/ISO 1137 Method 2B terminal

sterilization validation to musculoskeletal grafts, both

soft tissue and bone grafts, using gamma radiation. This

sterilization method determines the minimum absorbed

dose of radiation necessary to achieve a sterility assurance

level (SAL) of 10-6 for products with consistently low levels

of microbial bioburden. By achieving a validated sterility

assurance level (SAL) of 10-6 for an allograft, the FDA

permits the product to be labeled sterile. Since the

destruction of microorganisms by gamma irradiation

follows an exponential rule, the probability of survival

is a function of the following:

• The number and species of microorganisms present

on the allograft

• The lethality of the gamma irradiation process

(i.e., radiosensitivity), and

• The environment the organisms are in during the

irradiation process

SAL can be mathematically derived to define the probability

of viable microorganism on an individual graft following a

specified gamma irradiation dose.

Gamma Irradiation Sterilization — A New Standard for Allograft SafetyGamma irradiation sterilization is the only method

available that has been proven to eliminate viruses, bacteria,

fungi and spores from tissue without affecting the structural

or biomechanical attributes of tissue grafts.15,16,17 The efficacy

of allograft sterilization is supported by the absence of

bacterial or viral allograft-associated infections in tissue

processed by this method.6 LifeNet offers a new technology,

Allowash XG™, which results in sterile tissue with no

residual processing agents left to complicate clinical use.

Allowash XG processed tissue does not produce

inflammation when implanted and the osteoconductive,

biomechanical or structural properties of such tissues are

not affected or altered.

Genuine Sterility — Confidence UsingAllowash XG™

LifeNet introduced Allowash® in 1995, when it was a

revolutionary process in cleaning and disinfection.

Allowash Solution is a combination of three detergents,

which have demonstrated superiority in solubilization of

bone marrow. These detergents include Brij 35, Nonoxynol

9, and Nonidet P40 for solubilizing bone marrow cells. In

addition, during the Allowash process, hydrogen peroxide

in a 3% solution is used as a “scrubber” and disinfectant,

and a 70% isopropanol alcohol solution is used as a

disinfectant and drying agent. In the traditional Allowash

process, bone marrow and other cellular elements associated

with bone are removed by detergents in “cleaning” steps.

The hydrogen peroxide and alcohol processing steps further

reduce potential bioburden by acting as disinfectants. See

Figure 1 for a schematic of the cut graft protocol design.

3


"Cut Graft" Protocol Design

Preprocessing/Debridement

DrySpin

DrySpin

Dry Spin

DrySpin

Dry Spin

AllowashSolution/

Ultrasonication

Ultrasonication inAntibiotic Solution

Ultrasonicationin H2O2

Ultrasonicationin H2O2

Ultrasonicationin IPA

Wet Spinwith H2O2

Soak inWater

Step in Protocol

Soak inWater

1

1110

2 3

456

7 8 9

Figure 1. Cut graft protocol design for Allowash Technology.

Allowash XG™ is LifeNet’s proprietary comprehensive and

validated process, which begins by controlling incoming

bioburden, reduces bioburden through a controlled (patent

protected) cleaning and disinfecting process, and ends with

terminally sterilized allograft tissue. Allowash XG-associated

terminal sterilization ensures that all allograft tissue is free

of bacteria and other viable and detectable organisms,

including mycobacteria, viruses, fungi and spores. It is

important to note that Allowash XG offers sterility without

compromising the biomechanical or biochemical properties

of allografts needed for surgical applications.

The following steps ensure sterilization:

Step 1: Bioburden Control

This meticulous and rigorous screening routine is

employed for all donors and tissue recovery samples.

Screening mirrors the requirements set forth by the

FDA and AATB. This first step allows for stringent

control of bioburden on incoming donor tissues

before entering LifeNet’s processing facilities.

Step 2: Bioburden Assessment

At the time of recovery, all tissue is sampled to assess for

microbiological contamination. Standard microbiological

methods, employing both aerobic and anaerobic culture

media, are employed to culture and identify bacteria and

fungi. Donor blood samples are also used for required

infectious disease testing and evaluated for acceptability

regarding the potential for hemodilution. This extensive

serological testing exceeds industry standards with the

latest NAT advanced testing techniques, allowing LifeNet

to control and virtually eliminate incoming bioburden

on tissues.

Step 3: Minimizing Contamination

This step utilizes state-of-the-art processing and serves to

further reduce any already-present low bioburden on

tissues, as they are prepared for cleaning and disinfection.

Due to the need for facilities designed for the processing

and preservation of both musculoskeletal and cardiovascular

tissue allografts, all tissue handling and processing areas

have been designed to allow for compliance with FDA,

state and federal requirements, including cGXP for

medical devices. LifeNet facilities maintain cleanliness

levels that minimize or eliminate environmentally

mediated graft contamination.

Step 4: Rigorous Cleaning, Blood and Marrow Removal

Through flushing, centrifugation, hypotonic processes and

ultrasonication, blood elements (i.e., marrow and lipids) are

solubilized and removed. Key solutions are forced into

and through the bone matrix and then directed to waste,

resulting in the lysis of cells and solubilization and removal

of greater than 99% of the cellular and humoral elements

of bone. A key advantage of this step in the Allowash®

process is the potential for an approximate 3-log removal

of disease elements associated with emerging (unknown)

infectious diseases. The Allowash process accomplishes

significant bioburden reduction through simple cleaning

of tissues and thus anticipates the need for reducing

problems associated with emerging infectious diseases.

Step 5: Disinfection and Rinsing Regimen

Freed from over 99% of marrow and lipids, the tissue is

then subjected to an intensive decontamination, disinfection

and scrubbing regimen designed to eliminate viruses and

bacteria. Failure to remove such tissue elements prior to

chemical or physical disinfection results in preferential

reaction of these processes with the tissue elements rather

than the contaminant microorganisms. However, Allowash

processed tissues are freed of these tissue elements; thus,

any residual contaminating micro-organisms are immediate-

ly accessible to the disinfecting reagents. As final steps in

the process, tissues undergo water soak mediation (rinsing)

to remove processing reagents, followed by centrifugation

and/or microabsorption to remove residual water.

4


Steps to Sterilization Description Summary

1. Bioburden Meticulous and rigorousControl screening routine; based on

FDA and AATB guidelines; strict donor exclusions.

2. Bioburden Extensive serologic testing forAssessment microbiological contamination,

including bacteria, fungi andinfectious diseases.

3. Minimizing State-of-the-art processing toContamination maintain or further reduce an

already low bioburden.

4. Rigorous Cleaning, Flushing, centrifugation, Blood and Marrow hypotonic processes and Removal ultrasonication to solubilize and

remove blood elements,(i.e., marrow and lipids).

5. Disinfection and Intensive decontamination, Rinsing Regimen disinfection and scrubbing

regimen to remove and eliminate viruses and bacteria,and centrifugation or microabsorption to removeresidual water.

6. Terminal Sterilization Low-level dose of gamma irradiation at low temperatures.

Table 1. Allowash XG sterilization steps.

Step 6: Terminal Sterilization

The Allowash XG™ process concludes with a controlled,

low-level dose of gamma irradiation, which is administered

at low temperatures after packaging. Due to extremely

low bioburden levels on tissues post-Allowash® processing,

gamma irradiation doses as low as 8.3 kGy (absorbed dose)

result in sterile tissue grafts. This final step produces

sterilization levels of 10-6 SAL without compromising

the biomechanical or biochemical properties needed

for surgical implementation. See Table 1 for summary.

Validation of Allowash XG and Gamma IrradiationThe AAMI/ISO 1137 Method 2B terminal sterilization

validation was undertaken in a study by LifeNet® R&D to

validate sterilization of musculoskeletal grafts, both soft

tissue and bone grafts, using gamma irradiation.18 Method

2B utilizes the incremental dosing approach, allowing the

calculation of a SAL of 1x10-2 to constitute the Verification

Dose, which is used to validate the sterilization process on

a regular (approximately quarterly) basis. According to this

method, the microbiological results from the Verification

Dose experiments are then used to calculate the sterilization

dose that provides a SAL of 1x10-6. Therefore, the probability

of a viable microorganism being present on an allograft

post-gamma irradiation is one in a million at the calculated

sterilization dose. Samples of bone and soft tissue allografts

were from donors for which research consent had been

granted. The allograft tissue was aseptically processed

utilizing LifeNet’s patent-protected Allowash Technology

in environmentally controlled suites.

Each incremental batch tested had 20 allografts exposed

to each dose of irradiation (1-5 kGy). Thus, each batch

contained 100 allografts that resulted in 200 samples for

sterility testing, since each graft was bisected for aerobic

and anaerobic microbiological testing. A total of three

batches of tissues were tested and resulted in 100% culture

negative test results. Because all tissue samples tested were

culture negative, the verification dose was, by standard

protocol, set to be 1 kGy. By Method 2B, the minimum

sterilization dose (absorbed dose) needed to achieve an

SAL of 10-6 was calculated to be 8.3 kGy.

5


Batch 1 kGy 2 kGy 3 kGy 4 kGy 5 kGy

1 ≤1.0 kGy 1.9 kGy 2.8 kGy 3.7 kGy 4.8 kGy



Verification ≤0.9 kGy N/A N/A N/A N/ADose

Table 2. Average absorbed dose of gamma irradiation for eachincremental dose experiment and verification dose experiment.

The investigators concluded that Method 2B terminal

sterilization validation can readily be transferred from the

medical device industry to tissue banking. Valid, reliable

results are produced when appropriate considerations are

taken into account.

Low–Dose Gamma Irradiation — No Impact on Biomechanical Tissue PropertiesGamma irradiation has been shown to provide complete

tissue sterilization when used in sufficiently high doses.19

However, using high dose irradiation (>40kGy) has a

negative impact on the biomechanical and biologic

properties of the tissue and cannot be recommended for

processing of allogenic tissue. Block and colleagues set

about to determine a recommended low irradiation

dose that achieves sterilization without compromising

biomechanical properties.20 These investigators found

that an irradiation dose in the range of 10 to 15 kGy

provides effective bactericidal coverage with minimal impact

on allograft integrity and function. The temperature at

which irradiation is used in allograft processing appears to

be crucial. Most studies show that administering irradiation

at room temperature in freeze-dried or hydrated samples is

particularly problematic, negatively affecting biomechanical

tissue properties.

Several studies have further demonstrated the safety of

low-dose gamma irradiation on allograft tissue. One

study performed on ovine by Wheeler and colleagues

was designed to evaluate the effects of irradiation dose

on the structural properties of the tendon-bone junction

(insertion site).21

The study investigators found that there were no statistical

differences between the 15 kGy treatment and the non-

irradiated controls for any biochemical properties tested.

However, the 25 kGy irradiated specimens were statistically

different from the non-irradiated controls in stiffness,

ultimate load and ultimate stress. Specifically, the 25 kGy

irradiated samples had reductions of 24% in stiffness, 27%

in ultimate strength, 29% in ultimate load compared to the

contralateral non-irradiated control. High-dose irradiation

significantly reduces structural and material properties of

patellar tendon, whereas low-dose irradiation has no

significant effect on tendon properties.

6


Soft SoftCortico- Tissue Tissue

Cortical cancellous Cancellous with withoutBone Bone Bone Bone Bone

B.SUBTILIS Pass Pass Pass Pass Pass

ATCC 6633

C.ALBICANS Pass Pass Pass Pass Pass

ATCC 10231

A.NIGER Pass Pass Pass Pass Pass

ATCC 16404

S.AUREUS Pass Pass Pass Pass Pass

ATCC 6538

C.SPOROGENES Pass Pass Pass Pass Pass

ATCC 11437

P.AERUGINOSA Pass Pass Pass Pass Pass

ATCC 9027

Batch 1 kGy 2 kGy 3 kGy 4 kGy 5 kGy

1 0/20 0/20 0/20 0/20 0/20grafts grafts grafts grafts grafts



Verification 0/100 N/A N/A N/A N/ADose grafts

Table 4. Positive (non-sterile) grafts per total grafts assessed at eachincremental irradiation dose and verification dose.

Table 3. Bacteriostasis/fungistasis (B/F) results for six families ofAllowash®-treated allografts.

LifeNet® Studies For the LifeNet Soft Tissue Study, data was collected from

15 Allowash® processed tibialis tendons, which served as

experimental controls, and 15 experimental tibialis

tendons, which received 18 kGy of irradiation at dry-ice

temperatures. The actual delivered dose for the tendons

was 20.2 - 22.4 kGy. Two methods were used to assess the

effects of irradiation on the tendons: biomechanical testing

to assess changes in the tensile strength or Young’s modulus,

a ratio of stress to strain; and enzyme susceptibility testing.

The two methods provide a macroscopic functional

assessment of the tendons and a microscopic molecular

assessment of the tendons, respectively.

The following three figures illustrate the results of the study:22 These data demonstrate that using 18 kGy of gamma

irradiation at dry-ice temperatures does not cause a

statistically significant decrease in the tensile strength,

elastic modulus or enzyme susceptibility of Allowash XG™

processed allograft tendon tissue.

Hard Tissue in Iliac Crest Wedges andCloward DowelsThe purpose of the LifeNet Hard Tissue Study was

to determine the effects of gamma irradiation on the

compressive strength of traditional weight-bearing cut

grafts (iliac crest wedges and Cloward dowels)23. It was

hypothesized that the gamma irradiation treatment would

not result in any statistically significant alteration in the

compressive strength of traditional cut grafts as assessed

by biomechanical testing.

The traditional cut grafts tested were 9 mm iliac crest

wedges and 14 mm Cloward dowels. The experimental

group was Allowash treated, freeze-dried, and then gamma

irradiated on dry ice with an absorbed dose of 15.2-16.4

kGy. The control group was Allowash treated, freeze-dried

and received no gamma irradiation treatment. Prior to

testing, the samples were measured and the cross-sectional

area was calculated. The samples were then loaded to failure

and the compressive strength was calculated.

The average compressive strength for the non-irradiated,

Allowash-treated iliac crest wedges was 21.6 ± 6.9 MPa. The

average compressive strength for the irradiated, Allowash-7


Figure 2. Tensile strength of gamma irradiated tendons compared tonon-gamma irradiated tendons.

140

120

100

80

60

40

20

0

Control 18 kGy

Str

ess

(MP

a)

Figure 3. Young’s Modulus for gamma irradiated tendons comparedto non-gamma irradiated tendons.

Figure 4. Chymotrypsin sensitivity of Allowash®-processed tendonscompared to Allowash-processed and gamma irradiated tendons.

600

500

400

300

200

100

0

Control 18 kGy

Ysuludo

M s'gnuo

Control 18 kGy 50 kGy ambient

120

100

80

60

40

20

0

-20% Hydroxyproline

in the Pellet% Hydroxyprolinein the Supernatant

treated iliac crest wedges was 22.2 ± 5.2 MPa. A T-test

performed comparing the results showed that the difference

between the two groups was not significant (p=0.74).

Figure 5 shows the compressive strength for all samples

tested. Each bar depicts each sample’s compressive strength

and is grouped with all samples from that same donor.

These LifeNet® studies show that when performed with

controlled conditions on temperature, doses and setting,

low-dose irradiation does not affect the biomechanical

properties of tissues needed for their intended clinical

applications.

The DePuy Spine StudyThree biomechanical tests were performed on three

VERTIGRAFT® allograft types at the DePuy Spine

(Raynham, MA) testing lab.24 VG2™ Cervical Allograft, VG2

PLIF Allograft and VG1™ ALIF Allograft, processed by

LifeNet, were tested in axial compression, compressive shear

and static torsion. Standard Allowash®-treated controls were

compared to those treated with Allowash XG™.

As shown in Figures 6-7, for all types (Cervical, PLIF

and ALIF) tested in axial compression, no statistical

differences were found between grafts that had been

treated with Allowash XG versus those that had been

treated with the Allowash XG without gamma irradiation

(Control) (P<0.05).

As shown in Figures 6-7, for all types (Cervical, PLIF and ALIF) tested in 45° compressive shear, no statistical differences were found between grafts that had been treatedwith Allowash XG versus those that had been treated withthe Allowash XG without gamma irradiation (Control)(P<0.05).

The average torsional strength of the VG2 Cervical graftwas 2.5 Newton-meters. (Figure 8) The lower torsionalstrength of the Allowash XG treated grafts compared to the control was statistically significant. However, Panjabi et al. reported that only 1.5 Newton-meters of torque wererequired to produce a full range of motion in the cervicalspine without damaging soft tissue structures.25 Therefore,the torsional strength of the VG2 Cervical graft is still 1.6times the torque required to produce a full range of motionin the cervical spine.

8


Figure 5. Compressive strength.

Non-Irradiated Irradiated

35

30

25

20

15

10

5

0IIiac Crest Wedges Cloward Dowels

)aP

M( htgnertS evisserp

moC

50000

45000

40000

35000

30000

25000

20000

15000

10000

5000

0

Control Allowash XG

Com

pres

sive

Str

engt

h (N

)

VG1 ALIF VG2 Cervical VG2 PLIF

Figure 6. Compressive strength.

VG2 Cervical

5500

4500

3500

2500

1500

500

0

Control Allowash XG

Com

pres

sive

She

ar (

N)

VG1 ALIF VG2 PLIF

Figure 7. Compressive shear.

9


These grafts received a higher dose of irradiation than willbe administered during normal Allowash XG™ processing.This safety factor also plays a part in the evaluation of thesegrafts and determination of their safety for use in theirintended spinal application.

CONCLUSION

By using a validated tissue cleaning process like AllowashXG, bioburden on allografts can be reduced to extremelylow levels. A key advantage of Allowash® XG steps 4 and 5is the potential for an approximate 3-log removal of diseasecausing elements associated with emerging (unknown) infectious diseases. Methods claiming disinfection throughchemical means would need to be validated for such disinfection and such validation studies would, of necessity,occur after disease transmission had occurred. TheAllowash process accomplishes significant bioburden reduction through simple cleaning of tissues and thus anticipates the need for reducing problems associated with emerging infectious diseases.

Using an ISO standard methodology, a very low dose ofgamma irradiation can be used to produce sterile allografts.The literature, animal testing and clinical data all indicatethat allografts processed by Allowash XG exhibit no measurable detrimental effects to the properties of the tissues. While other tissue banks may claim sterility at 10-3

SAL, LifeNet® and its Allowash XG deliver sterile tissue to the 10-6 SAL.

Allograft users now have more options than ever in thechoice of their tissue supplier. It is more than critical todaythat clinicians and hospital administrators rely on sterile tissue provided by well known, accredited tissue banks suchas LifeNet. To date, more than 500,000 Allowash-processedgrafts have been safely distributed and used without reportof bacterial or viral allograft-associated infection directlylinked to a graft screened and processed by LifeNet. Withthe introduction of Allowash XG, LifeNet® takes tissue safety to the next level.

Control Allowash XG

8

7

6

5

4

3

2

1

0VG2 Cervical VG2 PLIF

Tors

ion

(N-m

)

Figure 8. Torsion.

10


REFERENCES

1. Patel R and Trampuz A. Infections transmitted through musculoskeletal-tissue allografts. NEJM 350(25):2544-2546.

2. Joyce MJ, Greenwald AS, Rigney R, et al. Report on musculoskeletal allograft tissue safety. Presented at the American Academy ofOrthopaedic Surgeons 71st Annual Meeting, San Francisco, March 10-14, 2004.

3. Hepatitis C virus transmission from an antibody-negative organ and tissue donor -United States, 200-2002. MMWR Morb Mortal Wkly Rep 2004;53:273-4, 276.

4. Eastlund T, Strong DM. Infectious disease transmission through tissue transplantation. In: Phillips GO, Ed. Advances in TissueBanking. Vol 7, Singapore: World Scientific, 2004:51-131.

5. Zou S, Dodd RY, Stramer SL, et al. Probability of viremia with HBV, HCV, HIV, and HLV among tissue donors in the United States. NEJM 2004;251:751-9.

6. Kainer MA, Linden JV, Whaley DN, et al. Clostridium infections associated with musculoskeletal-tissue allografts. NEJM 2004;350:2564-71.

7. Goodman JL. The safety and availability of blood and tissues: progress and challenges. NEJM 351(8):819-822.

8. Septic arthritis following anterior cruciate ligament reconstruction using tendon allografts -Florida and Louisiana, 200. MMWR, Morb Mortal Wkly Rep 2001;50:1081-3.

9. Gibbons MJ, Butler DL, Grood ES, et al. Effects of gamma irradiation on the initial mechanical and material properties of goat bone-patellar tendon-bone grafts. J Orthop Res 1991;9:209-18.

10. Rasmussen TJ, Feder SM, Butler DL, et al. The effects of 4 Mrad gamma irradiation on the initial mechanical properties of bone-patellar tendon-bone grafts. Arthroscopy 1994;10:188-97.

11. Fideler BM, Vangsness CT Jr. Lu B, et al. Gamma irradiation: effects on biomechanical properties of human bone-patellar tendon-bone allografts. Am J Sports Med 1995;23:643-6.

12. Loty B, Courpried JP, Tomeno B, et al. Bone allografts sterilized by irradiation: biological properties, procurement and results of150 massive allografts. Int Orthop 1990;14:237-42.

13. Jackson DW, Windler GE, Simon TM. Intraarticular reaction associated with the use of freeze-dried, ethylene oxide-sterilized bone-patella tendon-bone allografts in the reconstruction of the anterior cruciate ligament. Am J Sports 1990;18:1-11.

14. Roberst TS, Drez D Jr., McCarthy W, et al. Anterior cruciate ligament reconstruction using freeze-dried, ethylene oxide-sterilized,bone-patellar tendon-bone allografts:two-year results in thirty-six patients. Am J Sports Med 1991;19:35-41.

15. Bianchi JR, Ross K, James E, et al. The effect of preservation/sterilization processes on the shear strength of cortical bone. In: Vol.42 of Proceedings of the 1999 Bioengineering Conference, Big Sky, Montana, June 16-20, 1999:407. Abstract.

16. Summit MC, Bianchi JR, Keesling JE, et al. Biomechanical testing of bone treated through a new tissue cleaning process. In: Proceedings of the 25th Annual Meeting of the American Association of Tissue Banks, Washington, D.C., August 25-29, 2001:55. Abstract.

17. Summit MC, Bianchi JR, Keesling JE, et al. Biomechanical testing of bone treated through a new tissue cleaning process. In: Proceedings of the 25th Annual Meeting of the American Association of Tissue Banks, Washington, D.C, August 25-29, 2001:54. Abstract.

18. Moore M, Jones AL, Gaskins B. Adaptation of ANSI/AAMI/ISO 1137 Method 2B sterilization validation for medical devices to tissue banking. In Press, 2004.

19. Bright RW, Smarsh JD, Gambill VM. Osteochondral Allografts: Biology, banking and clinical applications. Vol 1. 1st ed. Boston/Toronto:Little, Brown and Company; 1983.

20. Block JE. The impact of irradiation on microbiological safety, biomechanical properties and clinical performance of musculoskeletal allografts. In press, 2004.

21. Wheeler DL, Turner S, Kushner J. Effects of irradiation dose on the initial structural properties of ovine bone, patellar tendon, bone allografts. In press, 2004.

22. Data on File, LifeNet, 2004.



25. Panjabi MM, Oda T, Crisco JJ3rd, Dvorak J, Grob D. Posture affects motion coupling patterns of the upper cervical spine. J Orthop Res 1993;11:4,525-36.

®

LifeNet5809 Ward CourtVirginia Beach, VA 23455

TEL: 1-888-847-7831/757-464-4761FAX: 1-888-847-7832/757-363-2713

www.accesslifenet.org

LNPRO1264

VertiGraft is a registered trademark and VG1 and VG2 are trademarks of DePuy, Inc. LifeNet, Allowash and MatriGraft areregistered trademarks and Allowash XG is a trademark of LifeNet Inc., Virginia Beach, VA. ©2004 LifeNet. All rights reserved.

sterilization of allografts - purgo.co.krpurgo.co.kr/data/_24172 lifenet sterilization paper.pdf ·...

Documents