Tibial Delayed Healing Pivotal Clinical Trial

The purpose of this study is to evaluate the INFUSE/MASTERGRAFT™ Delayed Healing Device as
an alternative/replacement to autograft in the treatment of tibial delayed healing. A
subject will be considered to have tibial delayed healing when he/she is at least six months
from the date of the most recent surgical intervention and has shown no signs of
radiographic healing for at least three months. Radiographic signs of healing for this study
are defined as either the progressive disappearance of fracture lines or the development of
cortical continuity [bridging bone] at the site. All prospective patients must require
surgical treatment with rigid internal fixation [reamed IM nail or plate/screws] and bone
grafting.

Inclusion Criteria:

1. Has tibial delayed healing. A subject will be considered to have delayed healing
when he/she is at least six months from the date of the most recent surgical
intervention and has shown no signs of radiographic healing for at least three
months. (Radiographic signs of healing for this study are defined as either the
progressive disappearance of fracture lines or the development of cortical continuity
[bridging bone] at the site.)

2. Has delayed healing of the tibia that requires treatment with rigid internal fixation
and bone grafting. (Stable rigid internal fixation hardware may already be in place
prior to treatment. If required, the fixation hardware may be removed and replaced
along with the placement of the bone graft.)

3. Has adequate soft tissue coverage at the delayed healing site. All prior soft tissue
coverage procedures (e.g., skin grafts or flaps) should be sufficiently healed for
placement of a bone graft prior to enrollment in the study.

4. Has a sufficient amount of iliac crest autograft available for a bone grafting
procedure.

5. After walking 5 or 6 steps, has intensity of pain/discomfort at the injury site equal
to or greater than 4 (as reported on the preoperative Delayed Healing Site Pain
Questionnaire form; 0 being no pain and 10 being pain as bad as it could be).

6. Is at least 21 years of age and skeletally mature at the time of surgery.

7. If a female of child-bearing potential, patient is not pregnant or nursing and agrees
not to become pregnant for one year following surgery in the study.

8. Is willing and able to comply with the study plan and able to understand and sign the
Patient Informed Consent Form.

Exclusion Criteria:

1. Has a congenital pseudarthrosis or pathological fracture nonunion (not including
osteoporosis-related fractures).

2. Has a tibial delayed healing with articular involvement (e.g., intra-articular).
(The original fracture may have involved the joint, but the resulting delayed healing
site may not involve the joint.)

3. Has hypertrophic tibial delayed healing (e.g., observed on x-ray as having an
abundant callus or "horse hoof" appearance).

4. Has inadequate neurovascular status in the involved limb that may jeopardize healing.

5. Has an active or a known prior infection at the delayed healing site (e.g., the
presence of purulent drainage from the site, prior positive cultures from the site,
or evidence of active/prior osteomyelitis at the site). Enrolled subjects whose
intra-operative cultures test positive for bacteria may remain in the study.

6. Has existing stable hardware that will not be removed and does not meet the algorithm
requirements.

7. Has treatment planned for the delayed healing that does NOT include placement of a
bone graft and/or rigid internal fixation consisting of a reamed intramedullary nail
or plate/screws.

8. Has a tibial delayed healing injury site with a bony defect larger than 4 cm in
length.

9. Has another injury/condition that prevents ambulation or completion of any of the
study assessments.

10. Has a history of endocrine or metabolic disorder known to affect osteogenesis (e.g.,
Paget's disease, renal osteodystrophy, hyperthyroidism, parathyroid hormone disorder,
Ehler-Danlos syndrome, osteogenesis imperfecta, calcium imbalance).

11. Has a Vitamin D deficiency, defined as a 25-hydroxy Vitamin D serum concentration of
≤11ng/mL .

12. Has an active malignancy or prior history of malignancy (except for basal cell
carcinoma of the skin).

13. Has an overt or active systemic infection (e.g., HIV/AIDS, hepatitis, bacteremia).

14. Has been on oral or injectable steroids for six weeks or more at time of enrollment.
This does not include episodic steroid use; inhaled steroids; or steroid medication
(e.g., Epidural Steroid Injections, Medrol DosePaks) specifically for the
perioperative management of symptoms.

15. Has a condition requiring postoperative medications that could interfere with bone
healing of the implant, such as steroids. This does not include low dose aspirin for
prophylactic anticoagulation; routine perioperative anti-inflammatory drugs; episodic
steroid use; or inhaled steroids.

16. Has a history of certain autoimmune diseases. (Refer to the List of Autoimmune
Diseases in the CIP for further information.)

17. Has a history of exposure to injectable collagen or silicone implants.

18. Has any previous exposure to any recombinant BMPs of either human or animal
extraction.

19. Has a history of hypersensitivity to collagen or protein pharmaceuticals (e.g.,
monoclonal antibodies or gamma globulins).

20. Has a history of allergy to bovine collagen products.

21. Has a documented allergy or intolerance to metal or metal alloys, such as stainless
steel or titanium.

22. Has chronic or acute renal and/or hepatic failure or prior history of renal and/or
hepatic parenchymal disease.

23. Is mentally incompetent. If questionable, obtain psychiatric consult.

24. Is a prisoner.

25. Is an alcohol and/or drug abuser as defined by currently undergoing treatment for
alcohol and/or drug abuse.

26. Has received treatment with an investigational therapy (drug, device, and/or
biologic) within 28 days prior to implantation surgery or such treatment is planned
during the 12-month period following the study surgery