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

Clinical, Radiographic and Histomorphotmetric Analysis of Healing Dynamics in Human Extraction Sockets Grafted With Bio-Oss Collagen®: A Prospective 3-year Post-loading Study

The purpose of this study is to clinically, radiographically and histologically evaluate the healing sequence of post-extraction sockets grafted with Bio-Oss Collagen® at 3, 6 and 9 months following tooth extraction in single-rooted tooth sites. Subjects with single rooted teeth planned for extraction and replacement with endosseous dental implants will be recruited for the study based on the eligibility criteria and will be divided in three groups (Groups 1, 2 and 3).A cone-beam computed tomography (CBCT) scan will be obtained and reviewed to prepare for the surgical approach and evaluate the ridge dimensions, the tooth planned for extraction as well as the adjacent sites. After tooth extraction, the socket will be grafted with Bio-Oss Collagen® and, depending on the morphology of the extraction sockets, a collagen matrix (Mucograft® seal) and/or a restorable collagen membrane (BioGide®)will be placed to cover and stabilize the graft. Patients will return at 2 and 6 weeks post-extraction to evaluate the healing. A second CBCT will be obtained 2 weeks prior to implant placement to evaluate the ridge dimensions and compare them to the baseline data. Implant placement will take place at 12, 24 and 36 after tooth extraction for Groups 1, 2 and 3 respectively. A bone core biopsy will be obtained at the time of implant placement and will be sent for histological analysis. Patients will return for a post-operative visit at two weeks. Clinical indices (probing depth, recession, bleeding upon probing, keratinized mucosa height, plaque and gingival index), patient reported outcomes and marginal bone levels via standardized periapical radiographs will be evaluated and recorded at baseline (no more than 30 days following delivery of final implant restoration) 1, 2 and 3 years post-loading.

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. Intra-oral scan will be obtained (multiple photos that comprise a 3-D impression) 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 and Intra-oral scan (multiple photos that comprise a 3-D impression) 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 and Intra-oral scan will be obtained (multiple photos that comprise a 3-D impression) 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. Intra-oral scan will be obtained (multiple photos that comprise a 3-D impression). 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.

Assessors collecting the data and conducting the appropriate statistical analyses for all outcomes in the study will be blinded.

Alveolar ridge preservation using xenograft (BioOss Collagen) and Implant placement 3 mo. after tooth ext.

Alveolar ridge preservation using xenograft (BioOss Collagen) and Implant placement 6 mo. after tooth ext.

Alveolar ridge preservation using xenograft (BioOss Collagen) and Implant placement 9 mo. after tooth ext.

Alveolar ridge preservation using xenograft (BioOss Collagen) and implant placement at 3 different time intervals (3, 6 and 9 months)

Linear Dimensional alterations of the alveolar ridge from the time of tooth extraction to the time of implant placement (3 months)

Clinical and radiographic (via CBCT) assessment. The buccal - lingual ridge width at the time of the extraction will be measured clinically using a periodontal probe (UNC-15) and prior to implant placement (3-months). The same measurements will be performed radiographically through the CBCTs taken prior to tooth extraction and prior to implant placement, utilizing a CBCT viewer software. The linear vertical alterations will be used utilizing the same methods, using fiduciary anatomical landmarks. Superimposition of the digital files obtained from the intra-oral scanner will be utilized to verify these changes clinically.

Linear dimensional alterations of the alveolar ridge from the time of tooth extraction to the time of implant placement (6 months)

Clinical and radiographic (via CBCT) assessment. The buccal - lingual ridge width at the time of the extraction will be measured clinically using a periodontal probe (UNC-15) and prior to implant placement (6-months). The same measurements will be performed radiographically through the CBCTs taken prior to tooth extraction and prior to implant placement, utilizing a CBCT viewer software. The linear vertical alterations will be used utilizing the same methods, using fiduciary anatomical landmarks. Superimposition of the digital files obtained from the intra-oral scanner will be utilized to verify these changes clinically.

Linear dimensional alterations of the alveolar ridge from the time of tooth extraction to the time of implant placement (9 months)

Clinical and radiographic (via CBCT) assessment. The buccal - lingual ridge width at the time of the extraction will be measured clinically using a periodontal probe (UNC-15) and prior to implant placement (9-months). The same measurements will be performed radiographically through the CBCTs taken prior to tooth extraction and prior to implant placement, utilizing a CBCT viewer software. The linear vertical alterations will be used utilizing the same methods, using fiduciary anatomical landmarks. Superimposition of the digital files obtained from the intra-oral scanner will be utilized to verify these changes clinically.

Assessment of the mucosal maturation of the extraction sites after the use of Mucograft Seal® @ 1 week, using a wound healing index (1-3 scale rating)

Wound Healing Index. 1-3 scale rating: 1) Uneventful Healing, 2) Normal healing with moderate soft tissue inflammation, erythema but no suppuration and 3) poor wound healing with significant signs of clinical inflammation and/or suppuration

Assessment of the mucosal maturation of the extraction sites after the use of Mucograft Seal® @ 2 weeks, using a wound healing index (1-3 scale rating)

Wound Healing Index.1-3 scale rating: 1) Uneventful Healing, 2) Normal healing with moderate soft tissue inflammation, erythema but no suppuration and 3) poor wound healing with significant signs of clinical inflammation and/or suppuration

Assessment of the mucosal maturation of the extraction sites after the use of Mucograft Seal® @ 6 weeks, using a wound healing index (1-3 scale rating)

Wound Healing Index. 1-3 scale rating: 1) Uneventful Healing, 2) Normal healing with moderate soft tissue inflammation, erythema but no suppuration and 3) poor wound healing with significant signs of clinical inflammation and/or suppuration

Assessment of the mucosal maturation following implant placement, using a wound healing index (1-3 scale rating)

Wound Healing Index. 1-3 scale rating: 1) Uneventful Healing, 2) Normal healing with moderate soft tissue inflammation, erythema but no suppuration and 3) poor wound healing with significant signs of clinical inflammation and/or suppuration

Patient reported outcomes (pain) 1 week following tooth extraction, using a Visual Analog Score for pain (0-100)

Visual Analog Score for pain (0-100, with 0 representing no pain, and 100 very severe pain, described as "worse pain imaginable").

Patient reported outcomes (pain) 2 weeks following tooth extraction, using a Visual Analog Score for pain (0-100)

Visual Analog Score for pain (0-100, with 0 representing no pain, and 100 very severe pain, described as "worse pain imaginable").

Patient reported outcomes (pain) 6 weeks following tooth extraction, using a Visual Analog Score for pain (0-100)

Visual Analog Score for pain (0-100, with 0 representing no pain, and 100 very severe pain, described as "worse pain imaginable").

Patient reported outcomes (pain) 2 weeks following implant placement, using a Visual Analog Score for pain (0-100)

Visual Analog Score for pain (0-100, with 0 representing no pain, and 100 very severe pain, described as "worse pain imaginable").

The patients will be asked to rate their satisfaction in terms of function, comfort and esthetics, using a Visual Analog Scale (0-100, with 0 meaning "not at satisfied at all" and 100 corresponding to "perfectly satisfied").

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

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