Healing Dynamics in Human Extraction Sockets Grafted With Bio-Oss Collagen®

Patients participating in this study are expected to return to the University of Iowa College
of Dentistry for a total of 12 visits. The estimated study length per subject will vary
between 42 to 48 months depending on group allocation.

VISIT 1: Screening Subjects in need of extraction of a single-rooted tooth, except for lower
incisors, that meet all the inclusion and none of the exclusion criteria will be eligible to
participate. The purpose of the study, the duration and the potential risks and benefits will
be explained in detailed to the patients. If the subject is interested in participating in
the study, copies of the study outline and consent forms will be given to them. Medical and
dental history form will be entered in patients' charts electronically, completed and signed
by the subjects.

VISIT 2: Tooth Extraction (TE) and Ridge Preservation via Socket Grafting Medical and dental
histories will be reviewed and possible changes will be recorded. Intra-oral photographs of
the sites of interest will be obtained. Clinical and radiographic examination of the sites
involved in the study will be performed. A cone-beam computed tomography (CBCT) scan will be
obtained and reviewed to prepare for the surgical approach and evaluate the tooth planned for
extraction as well as the adjacent sites for pathology and neighboring sensitive anatomic
structures that can alter the proposed treatment plan. Digital intra-oral scanning of the
area of interest will be performed using the Planmeca Emerald (TM) scanner. The subject will
sign the surgical consent form. After administration of local anesthesia, the tooth will be
extracted as less traumatically as possible, without flap reflection. Following tooth
extraction, the socket walls will be clinically evaluated for the existence of dehiscences or
fenestrations. Sites presenting a bony defect affecting >50% of the total wall height will be
excluded. Sockets will be grafted with Bio-Oss Collagen®, BioGide® will be utilized if
indicated for the treatment for a dehiscence and the coronal part will be covered with a
collagen matrix (Mucograft Seal®). Stabilizing sutures will be applied to maintain the
collagen matrix adequately in place. Written and verbal post-operative instructions will be
given to the patients. They will be instructed to avoid any mechanical disturbance in the
area for two weeks. Patients will be asked to use a mouthwash containing 0.12% of
chlorhexidine gluconate twice a day, thirty seconds at a time, avoiding any eating or
drinking for 30 minutes after rinsing, starting 48 hours after the baseline intervention.
Post-operative medication (antibiotics, analgesics, NSAIDs) will be prescribed on an
individual basis.

VISIT 3 (TE + 1 week) & VISIT 4 (TE + 2 weeks): Postops Medical and dental histories will be
reviewed and possible changes will be recorded. Intra-oral photographs of the sites of
interest will be obtained. Visual assessment of the healing status will be made using a WHI.
Patients will be asked to report their pain using a Visual Analog Scale (VAS). Sutures will
be removed at either of the two visits. Sites will be debrided, if necessary. and oral
hygiene instructions will be reviewed.

VISIT 5: Post-op (TE + 6 weeks) Medical and dental histories will be reviewed and possible
changes will be recorded. Intra-oral photographs of the sites of interest will be obtained.
Visual assessment of the healing status will be made using a WHI. Patients will be asked to
report their pain using a VAS. Gentle plaque debridement will be provided and oral hygiene
instructions will be reviewed.

VISIT 6: Follow-up and second CBCT scan Group 1 (TE + 10 weeks) Group 2 (TE + 22 weeks) Group
3 (TE + 34 weeks) Medical and dental histories will be reviewed and updated, if necessary.
Intra-oral pictures of the surgical sites will be obtained. At this visit, a second segmental
CBCT scan will be obtained for all patients, using the same settings employed at baseline.
Images will be used to analyze and compare the ridge dimensions to those obtained at baseline
as well as in terms of adequacy for dental implant placement.

VISIT 7: Implant Placement and Bone Core Biopsy Harvesting Group 1 (TE + 12 weeks) Group 2
(TE + 24 weeks) Group 3 (TE + 36 weeks) Medical and dental histories will be reviewed and
possible changes will be recorded. Intra-oral photographs of the sites of interest will be
obtained. Digital intra-oral scanning of the area of interest will be performed using the
Planmeca Emerald (TM) scanner. Implant placement will be done per standard procedure. A
trephine drill of 2.5 mm diameter, or wider, will be used to harvest a bone core for
histologic and µ-CT analyses. The bone core will be immediately submerged in a solution of
10% neutral buffered formalin (NBF). The selection of the implant system and dimensions will
depend on the surgical and restorative needs of each individual case. Osteotomies and implant
placement will be done following the manufacturer's recommendations. A final periapical
radiograph will be obtained to verify correct implant position and angulation. Depending on
the buccal bone and soft tissue thickness, ancillary soft tissue augmentation, bone
augmentation or a combination of both may be indicated. If adequate primary stability is
achieved and a one-stage approach is feasible, a healing abutment will be placed. If a
two-stage procedure is indicated, a cover screw will be placed and the implant will be
submerged. At the end of the appointment, written and verbal post-operative instructions will
be given to the patients.

VISIT 8: Post-op (Implant Placement + 2 weeks) Medical and dental histories will be reviewed
and possible changes will be recorded. Intra-oral photographs of the sites of interest will
be obtained. Sutures will be removed. Visual assessment of the healing status will be made
using a WHI. Patients will be asked to report their pain using a VAS. The sites will be
debrided and oral hygiene instructions will be reviewed. Upon completion of this visit, the
patient will be referred to the restorative dentist to complete the restorative part of the
treatment.

VISIT 9: Baseline Implant Follow-up (No more than 30 days after delivery of final
restoration) Medical and dental histories will be reviewed and possible changes will be
recorded. Intra-oral photographs of the sites of interest will be obtained. Digital
intra-oral scanning of the area of interest will be performed using the Planmeca Emerald (TM)
scanner. Patients will be asked to report their level of satisfaction in terms of function,
comfort and esthetics (PROMs). The sites will be inspected, deplaqued, if necessary, and oral
hygiene instructions will be reviewed. Clinical parameters will be recorded (i.e. probing
depth, recession respective to the incisal/occlusal plane, bleeding upon probing, keratinized
mucosa height, plaque and gingival index). A standardized periapical radiograph will be
obtained to assess marginal bone levels.

VISIT 10: Implant Follow-up #1 (1 year after delivery of final restoration) Medical and
dental histories will be reviewed and possible changes will be recorded. Intra-oral
photographs of the sites of interest will be obtained. Digital intra-oral scanning of the
area of interest will be performed using the Planmeca Emerald (TM) scanner. Patients will be
asked to report their level of satisfaction in terms of function, comfort and esthetics
(PROMs). The sites will be inspected, de-plaqued, if necessary, and oral hygiene instructions
will be reviewed. Clinical parameters will be recorded (i.e. probing depth, recession
respective to the incisal/occlusal plane, bleeding upon probing, keratinized mucosa height,
plaque and gingival index). A standardized periapical radiograph will be obtained to assess
marginal bone levels.

VISIT 11: Implant Follow-up #2 (2 years after delivery of final restoration) Medical and
dental histories will be reviewed and possible changes will be recorded. Intra-oral
photographs of the sites of interest will be obtained. Digital intra-oral scanning of the
area of interest will be performed using the Planmeca Emerald (TM) scanner. Patients will be
asked to report their level of satisfaction in terms of function, comfort and esthetics
(PROMs). The sites will be inspected, de-plaqued, if necessary, and oral hygiene instructions
will be reviewed. Clinical parameters will be recorded (i.e. probing depth, recession
respective to the incisal/occlusal plane, bleeding upon probing, keratinized mucosa height,
plaque and gingival index). A standardized periapical radiograph will be obtained to assess
marginal bone levels.

VISIT 12: Implant Follow-up #3 (3 years after delivery of final restoration) Medical and
dental histories will be reviewed and possible changes will be recorded. Intra-oral
photographs of the sites of interest will be obtained. Digital intra-oral scanning of the
area of interest will be performed using the Planmeca Emerald (TM) scanner. Patients will be
asked to report their level of satisfaction in terms of function, comfort and esthetics
(PROMs). The sites will be inspected, de-plaqued, if necessary, and oral hygiene instructions
will be reviewed. Clinical parameters will be recorded (i.e. probing depth, recession
respective to the incisal/occlusal plane, bleeding upon probing, keratinized mucosa height,
plaque and gingival index). A standardized periapical radiograph will be obtained to assess
marginal bone levels.

This is planned to be the final study visit.

Inclusion Criteria:

- May be either male or female

- Age: 18 years or older

- Subjects with a single-rooted tooth (except mandibular incisors) indicated for
extraction

- Extractions socket walls should either be intact or have no more than one bony wall
(buccal or lingual) dehiscence extending no more than 50% of the total bony wall
height

- Must be in adequate physical and mental health to undergo routine dental treatment
including the surgical procedures associated tooth extraction and implant placement

- Subjects' treatment plan must include replacement of the tooth to be extracted with
dental implant supported fixed restoration

- Subjects must have read, understood and signed an informed consent form

Exclusion Criteria:

- Mandibular incisors

- Acute infection associated with the tooth to be extracted or with adjacent teeth

- History of significant heart, stomach, liver, kidney, blood, immune system disease, or
other organ impairment or systemic diseases that would prevent undergoing the proposed
treatment or may result in compromised healing (e.g. poorly controlled diabetes,
active heavy tobacco use [>10 cigs/day])

- Subjects with uncontrolled and/or severe metabolic bone diseases or disorders, such as
osteoporosis, thyroid disorders or Paget's disease

- Subjects taking any medication or supplement known to largely influence bone
metabolism, such as IV bisphosphonates, long-term history of oral bisphosphonates or
chronic intake of glucocorticoids

- Pregnant women or nursing mothers

- Subjects that are unwilling or unable to sign the informed consent

- History of lack of compliance with dental visits

- Subjects unwilling to return for the required number of visits