BIO4 Clinical Case Study: Cervical Spine

This is a prospective study with the intent to investigate the efficacy of BIO4 bone matrix
in patients undergoing 1 or 2-level Anterior Cervical Discectomy and Fusion (ACDF) spine
surgery. At the time a patient is scheduled for surgery, the patient's chart will be
evaluated for inclusion/exclusion criteria. If a patient meets the criteria for the study,
the study will be explained to the patient and consent obtained.

Investigators will utilize the BIO4 on label as a 361 HCT/P (human cell, tissue and cellular
and tissue-based product) for homologous use for the repair, replacement or reconstruction of
bone defects. Interbody fusion (1 or 2-level fusion) in conjunction with an allograft (hct/p)
interbody spacer (anterior approach in the cervical spine with hardware) will be utilized.

Investigators will also use the Aviator Anterior Cervical Plating System for anterior
intervertebral screw fixation of the cervical spine at levels C2-T1. The Aviator Anterior
Cervical Plating System is intended for use as an aid in cervical spinal fusion and is
intended for unilateral fixation. The Aviator plates are intended to be used with the Aviator
bone screws.

Study Outcomes:

- Radiological assessment (cervical spine x-ray and if needed, computed tomography (CT) at
1 year follow up)of fusion as the primary endpoint

- Arthrodesis rates assessed using CT (1 year follow up, if needed) and Anterior-Posterior
(AP), lateral and dynamic flexion-extension cervical spine x-rays pre-operative
(pre-op), post-operatively (post-op) 2~4 weeks (10~34 days post op), 3 months (83~97
days post-op), 6 months (173~187 days post-op) and 1 year post-op (351~379 days post op,
primary data point outcome)

- Revision rates

- Outcome scores: Visual Analog Scale (VAS) and Neck Disability Index (NDI) pre-op,
post-op 2~ 4weeks, 3 months, 6 months and 1 year.

The null hypothesis is that in ACDF model, the clinical and radiographic outcomes of
utilizing BIO4 bone matrix with Bio AVS Cervical Allograft are equivalent to historical high
level published data of similar product (Data reported in Meta-analysis ACDF obtained from
FDA disc arthroplasty trials).

Inclusion Criteria

1. Age>18 years

2. Scheduled 1 or 2-level ACDF spine surgery

3. The capacity to provide informed consent.

4. Subject has one or more of the following diagnoses:

1. Degenerative Disc Disease (as defined by neck pain of discogenic origin with
degeneration of the disc confirmed by patient history and radiographic studies)

2. Trauma (including fractures)

3. Tumors

4. Deformities or curvatures (including kyphosis, lordosis, or scoliosis)

5. Pseudoarthrosis

6. Failed previous fusion

7. Decompression of the spinal cord following total or partial cervical
vertebrectomy

8. Spondylolisthesis

9. Spinal stenosis

Exclusion Criteria Patients with any of the following conditions will be excluded, or if
enrolled and found to be ineligible and do not fit the inclusion criteria, will be
withdrawn from the study.

1. Patients with current or recent history of malignancy or infectious disease.

2. The inability to provide informed consent.

3. Subject has marked local inflammation

4. Subject has any mental or neuromuscular disorder which would create an unacceptable
risk of fixation failure or complications in postoperative care.

5. Subject has a bone stock compromised by disease, infection or prior implantation which
cannot provide adequate support and/or fixation to the devices.

6. Subject has bone abnormalities preventing safe screw fixation.

7. Subject has any open wounds.

8. Subject has rapid joint disease, bone absorption, osteopenia, osteomalacia, and/or
osteoporosis. Osteoporosis or osteopenia are relative contraindications, since this
condition may limit the degree of obtainable correction and/or the amount of
mechanical fixation.

9. Subject has a documented or suspected metal sensitivity.

10. Subject is pregnant.

11. Subject has anatomical structures or physiological performance that would interfere
with implant utilization.

12. Subject has inadequate tissue coverage over the operative site.

13. Subject has other medical or surgical conditions which would preclude the potential
benefit of surgery, such as congenital abnormalities, immunosuppressive disease,
elevation of sedimentation rate unexplained by other diseases, elevation of white
blood count (WBC), or marked left shift in the WBC differential count.

14. Note: The Aviator Anterior Cervical Plating System is not approved or intended for
screw attachment to the posterior elements (pedicles) of the cervical, thoracic, or
lumbar spine. The surgeon must consider the levels of implantation, patient weight,
patient activity level, and other patient conditions which may impact on the
performance of the system.