Utilization of d-PTFE Barriers for Post-Extraction Bone Regeneration in Preparation for Dental Implants

Dense polytetrafluoroethylene (d-PTFE) is a nonresorbable material that can be used as a cell occlusive barrier when performing guided bone (GBR) or guided tissue (GTR) regeneration procedures.¹ GBR is often employed to restore defective alveolar ridges post extractions prior to or in conjunction with dental implant insertion.² This technique usually involves inserting a bone graft and covering it with a barrier, which is either resorbable or nonresorbable. A barrier is used to prevent epithelium and connective tissue from migrating into the grafted site, thereby facilitating repopulation of the bone graft with progenitor cells from the adjacent bone.³

d-PTFE utilization avoids potential problems encountered with other types of barriers used during GBR procedures. For example, both resorbable and nonresorbable barriers (eg, expanded polytetrafluoroethylene [e-PTFE]) need to be completely submerged at the time of placement, because if they are left or become exposed, there may be negative consequences. If a resorbable barrier is not submerged or becomes exposed to oral fluids, it will not be fully intact in 7 days and will usually resorb quickly (approximately 2 weeks).⁴ This will not provide enough time for progenitor cells to repopulate the graft, and the progenitor cells will not have sufficient time to differentiate and create osteoid tissue (connective tissue that is the precursor of bone). Conversely, when a nonresorbable barrier—such as e-PTFE—is employed and becomes exposed due to a soft-tissue dehiscence, it is susceptible to becoming infected within 4 weeks.^5,6 These negative issues can be avoided if d-PTFE barriers are used. They do not have to be submerged, and they will not resorb prematurely. Furthermore, surgical sites treated with d-PTFE barriers do not become infected when they remain uncovered for 4 to 6 weeks.^7-9 d-PTFE barriers are marketed under various names by several companies (eg, Cytoplast™ [Osteogenics Biomedical, www.osteogenics.com], TefGen FD™ [Lifecore Biomedical, LLC, www.lifecore.com], Symbios OsteoShield® [DENTSPLY Implants, www.dentsplyimplants.us]). This article addresses the use of d-PTFE (Cytoplast) in GBR procedures and discusses the benefits of these barriers as well as data limitations. Since the larger studies in the literature addressing d-PTFE barriers have employed Cytoplast^7-10 and the authors’ cases were performed with this type of barrier, this article will focus on this brand of d-PTFE.

Historical Perspective

In 1976, Melcher¹¹ discussed the potential of the periodontal ligament (PDL) to provide progenitor cells to enhance regeneration of osseous defects. Subsequently, Nyman et al¹² used a Millipore filter (barrier) to exclude epithelium and connective tissue from human periodontal defects to help repopulate osseous defects with progenitor cells from the PDL. This was called guided tissue regeneration (GTR) and its goal was to regenerate bone, PDL, and cementum. Subsequently, the same principles were used by Dahlin et al in a rabbit model to augment a ridge, and this was labeled GBR.¹³

The main GBR principles are as follows: 1) exclude epithelium and connective tissue to allow progenitor cells to repopulate the treated site; 2) create a space under the barrier, which will fill in with bone (space maintenance)—the barrier is often held up with a bone graft or tenting screws; 3) the barrier protects the clot—this is referred to as “clot stabilization”; 4) attain angiogenesis; and 5) achieve primary closure by flap advancement.¹⁴

Primary closure often requires periosteal and vertical releasing incisions to facilitate flap advancement.¹⁵ If a periosteal releasing incision does not provide adequate flap advancement, then the tissue may need to be incised more deeply into the submucosa to attain primary closure.¹⁵ This will probably increase a patient’s morbidity (edema, ecchymosis, and discomfort). Thus, avoidance of this step would be advantageous if equivalent regenerative results could be attained without primary closure.

Characteristics of d-PTFE Barriers

Nonresorbable barriers (e-PTFE) first appeared as Gore-Tex®, and then TefGen became commercially available.¹ TefGen was considered a nano-porous barrier (n-PTFE), a term denoting that pores were extremely small.¹⁶ Characteristics of Cytoplast barriers, which were used in the four cases illustrated in this article (Figure 1 through Figure 25), are described as follows: The d-PTFE barriers have a 4-year shelf life.1 Cytoplast Regentex™ is textured on one side (Figure 3). The texture consists of small hexagonal dimples, which increase the barrier’s surface area by 250%.¹⁷ When inserting the barrier, the shiny, undimpled side is placed down onto the bone graft so that the dimpled side comes into contact with the overlying flap (Figure 6). Under the flap, fibroblasts migrate into the shallow dimples; this provides a grip for the soft tissue (adhesion). Available barrier sizes are 12 mm x 20 mm and 25 mm x 30 mm. The d-PTFE barrier is 0.13-mm to 0.25-mm thick. Other types of this brand of barriers are available (eg, titanium reinforced).

Barriers: d-PTFE vs e-PTFE

Barriers used for GBR procedures are referred to by a variety of names, including: membranes; barrier membranes; biologic barriers; occlusive membranes; bioresorbable (which need to be degraded by the body), bioabsorbable (which dissolve in body fluids without polymer chain cleavage), and biodegradable (which break down due to macromolecular degradation) barriers; and resorbable and nonresorbable barriers.¹⁸ Nonresorbable membranes can be divided into two categories: expanded (e-PTFE) and dense (d-PTFE) polytetrafluoroethylene. The material is the same for both barriers, but the e-PTFE has been stretched. The pore size for e-PTFE (trade name Gore-Tex) is 5 to 30 microns (µm), and d-PTFE (Cytoplast) pore size is 0.2 µm.¹ With regard to timing of removal of nonresorbable barriers, it has been suggested that they be removed in 4 to 6 weeks for GTR procedures and 6 to 9 months for GBR.¹⁸

When the efficacy of d-PFTE was compared to e-PTFE to achieve GTR in osseous defects, the studies demonstrated there were no statistically significant differences with respect to gaining bone.^19-21 In these three clinical trials the barriers were submerged, and alloplastic bone^20,21 or a xenograft was used.¹⁹ Barriers were left in place 6 to 8 weeks. No studies compared the regenerative efficacy of submerged versus exposed barriers.

Infections

The diameter of pathogenic bacteria is generally less than 10 µm.²² Stretching of e-PTFE increases its pore size (5 µm to 30 µm), which allows bacteria to penetrate the barrier. In contrast, d-PTFE (pore size 0.2 µm) is impervious to bacterial penetration. When d-PTFE barriers were experimentally challenged with Enterococcus faecalis, an organism commonly found intraorally (with a size of 0.5 µm to 1 µm), it was noted that the bacteria could not penetrate the barrier (data on file with Osteogenics).

As indicated, when e-PTFE barriers were used, if they became exposed, they had the potential to become infected by around 4 weeks, which could result in loss of part or all of the bone graft.^7-9 On the contrary, numerous articles noted that sites treated with d-PTFE barriers, despite exposure to the oral environment, did not become infected within 4 to 6 weeks.^1,7-9,23 No data is available with respect to exposure for longer treatment times.

Primary Closure

To attain bone regeneration when e-PTFE and resorbable barriers are used, primary closure is required. This precipitates two issues: 1) tissue contour usually will be altered as a result of primary closure; and 2) the position of the mucogingival junction is frequently changed.¹⁵ Thus, keratinized tissue may be translocated lingually, leaving the buccal aspect with only mucosa. In addition, there may be loss of vestibular depth when flaps are advanced. Pertinently, the size of the flap advancement is often related to the amount of patient morbidity. In summary, with d-PTFE barriers, there is no need for primary closure, the surgical procedure is easy, and a second surgery to remove the barrier is avoided.

Preservation of Keratinized Tissue

If a d-PTFE barrier is placed over a bone graft at an extraction socket, and primary closure is not performed, the linear amount of keratinized tissue will be maintained. When there is mid-buccal recession on a tooth and the tooth is removed, if a d-PTFE barrier is placed over a bone graft, the volume of keratinized tissue will be increased. When an extraction is done and no barrier is placed, the healed socket will develop keratinized gingiva, but its volume would be decreased due to partial collapse of the gingiva into the defect. In this regard, Barber et al²³ demonstrated that after maxillary anterior teeth were extracted and a d-PTFE barrier was used over a bone graft, the band of keratinized tissue was increased.

Epithelialization over the reddish colored connective tissue (osteoid) usually takes 14 to 21 days. Epithelial cells from the surfaces adjacent to the wound migrate across the connective tissue. They usually migrate 0.5 mm to 1 mm per day after a 12-hour lag period.²⁴

Time, Cost

When comparing the efficiency of using d-PTFE versus other barriers that must be submerged, the need to perform primary closure when utilizing other barriers will require additional time and, therefore, likely result in an increased cost for procedures.

Wound Healing

When a socket heals, the blood clot is replaced with granulation tissue (at around 96 hours),²⁵ which is subsequently converted to connective tissue (at around 21 to 28 days). The connective tissue, osteoid, is the precursor of bone. Osteoblasts initiate bone formation by secreting osteoid as several specific proteins. Osteoid is composed of fibers and ground substance.²⁶ The main fiber-type is Type I collagen, which accounts for 90% of the osteoid. The ground substance is mostly made up of chondroitin sulfate and osteocalcin.²⁶ The osteoid tissue organizes and mineralizes to become woven bone—it takes approximately 3 months for the socket to be filled with bone. Woven bone is immature bone and, with time, it mineralizes further and is referred to as lamellar bone.²⁷ It takes approximately 4 months to develop lamellar bone, and mineralization continues for a year.

Barrier Removal

The timing of barrier removal is a contentious issue, because the minimum amount of time the barrier needs to be in place to facilitate optimal maturation of the osteoid tissue is unknown. Barriers need to be left in place long enough for the osteoid tissue to become condensed and impervious to invasion by other tissues so that its mineralization and conversion to bone is not disturbed. Initially, some researchers suggested that after placement of e-PTFE barriers, they be left in place for a prolonged period of time (eg, 16 weeks) when doing GBR procedures.^28-30 Others suggested 4 to 6 weeks³¹ or 6 weeks^32,33 for GTR procedures.

With regard to Cytoplast d-PTFE barriers, investigators have removed them at various time intervals when they were left exposed after surgery (Table 1)^{7-10,23,34-41}: < 3 weeks¹⁰; 3 weeks^34,35,37; 3 to 4 weeks^8,36,38; 4 weeks^7,39,41; 4 to 6 weeks^9,23; and 6 weeks.⁴⁰ All authors reported successful results. However, there are several issues that require discussion. The manufacturer recommends that d-PTFE (Cytoplast) barriers be removed at about 4 weeks. Upon removal, there may be some slight bleeding, which reflects disturbance of the biological adherence between tissue and the d-PTFE membrane. In general, soft tissue will not grow over the membrane. After 4 to 6 weeks, the nonresorbable membrane is easily removed without local anesthesia, because the dense surface of the membrane does not allow deep fibrous ingrowth. If it is desired to leave the barrier in place for 8 weeks, when the barrier is removed it will leave an epithelialized pouch in the tissue, because the epithelium will have invaginated around the margin (observations of GG). To correct this issue, the current authors have used a diamond to remove the surface epithelium, which is around 0.3 mm thick.⁴² The walls of the pouch are then abraded, creating bleeding points, and the sites are sutured. Healing then occurs uneventfully.

Removal of the d-PTFE at 4 or 4 to 6 weeks does not appear to be detrimental to bone regeneration,^7,8,11,23,36 as is shown in the four cases presented (Figure 1 through Figure 25). Conceptually, the osteoid tissue is dense enough to preclude penetration of the epithelium or connective tissue that would inhibit healing. There are several possible explanations as to why barriers can be removed earlier than previously recommended:

• Several studies suggested that early barrier removal leads to poor results when performing a ridge augmentation.^29,30 However, this conclusion may be incorrect, because these investigations may have erroneously surmised that early barrier removal was associated with lack of regeneration, when in reality, failures were related to soft-tissue dehiscences and bacterial contamination, which resulted in early barrier removal.

• One study in dogs found early barrier removal of e-PTFE (4 weeks) resulted in poorer results than barriers left in place 16 weeks.²⁸ No clear explanation can be provided as to why these findings are not applicable to d-PTFE, but they are contrary to successful results obtained when barriers are removed at 4 weeks.

• There are no studies that sequentially examined healing at different time points to determine the minimum healing time at which osteoid is mature enough to proceed to mineralization.

• Factors that can affect healing are the relationship between the size of defects and the amount of time needed for maturation of the osteoid tissue, and the time for tissue maturation may be site- and patient-specific.

• The studies presented in this article all regenerated bone within the alveolar bony housing. Vertical augmentation was not attempted. Whether or not it is possible to achieve this with barrier removal after 4 weeks and no primary closure needs to be assessed. There have been no reports with respect to this endeavor.

Systematic Literature Review

Carbonell et al⁴³ recently conducted a literature review concerning the efficacy of high-density PTFE for regenerative purposes. The authors found 24 articles that addressed use of d-PTFE and n-PTFE barriers for regeneration around teeth and implants. These included two in-vitro studies, seven experimental studies, and 15 clinical studies. In general, the clinical studies were small or incomplete. They concluded that at present there is limited data supporting the use of n-PTFE membranes. It was mentioned that there may be some use for d-PTFE in GTR and GBR over immediate implants and fresh extraction sockets. However, just because numerous studies have not been conducted, it does not mean that the barriers are ineffective for certain procedures. For instance, clinicians have demonstrated the efficacy of d-PTFE as a barrier for socket preservations^7-10 and GBR to replace lost or defective buccal plates of bone.^7-9 In this regard, clinical practice is sometimes ahead of scientific evidence, since oftentimes there is insufficient funding to carry out expensive studies.

In Figure 1 through Figure 25 the authors present various case reports to demonstrate with radiographs or clinical re-entries that osseous regeneration was achieved with d-PTFE barriers and Puros® bone grafts (Zimmer Dental, www.zimmerdental.com) after extractions. (The technique is discussed after the literature review.)

Data Pertaining to d-PTFE Utilization

Socket preservation: four walls present—Several authors assessed socket preservation using d-PTFE without primary closure. Fotek et al¹⁰ evaluated Cytoplast barriers (N = 20) as a method to enhance socket preservation. After extractions, demineralized freeze-dried bone allograft (DFDBA) was placed into the sockets. The barriers were secured by elevating a small flap (3 mm on the buccal and lingual), and the barriers were tucked under the flap buccally and lingually without disturbing the mesial or distal papilla. Part of the barrier was left exposed, and barriers were removed after 4 weeks. They reported that the amount of bone loss was 0.3 mm horizontally and 0.25 mm vertically. Hoffman et al⁷ also evaluated socket preservation. They used barriers without bone grafts. The vertical amount of bone loss was between 0.5 mm and 1 mm; 14% of the sites in the middle of the socket lost 2 mm, because barriers collapsed due to lack of bone support. Yamashita et al⁹ employed bone grafts plus Emdogain® (Straumann, www.straumann.us) or plasma-rich protein (PRP) under d-PTFE barriers. They reported no bone loss during socket preservations, but noted that the original sockets were overbuilt by around 0.8 mm.

These were good results with respect to reducing horizontal and vertical bone loss after an extraction. In contrast, a recent systematic review reported that 6 months after tooth removal, which included flap elevation and no other therapy, the extraction sockets showed a mean 1.24-mm vertical bone loss (range 0.9 mm to 3.6 mm) and 3.79-mm horizontal bone decrease (range 2.46 mm to 4.56 mm).⁴⁴ Others who used a nonresorbable45 or a resorbable barrier⁴⁶ also found vertical bone loss to be around 1 mm and horizontal bone loss to be around 3 mm. When bone and a barrier were used, horizontal bone loss of around 1 mm was reported along with vertical bone gain of 1.3 mm.⁴⁷ Without flap elevation, typically there is vertical bone loss, but horizontal bone loss is diminished.^48,49

GBR when the buccal plate or part of the buccal plate(s) were resorbed—In several studies, d-PTFE barriers were employed and left exposed during treatment of defective buccal bony plates.^7-9 Barboza et al⁸ assessed the healing of 72 patients when a bone graft and a Cytoplast barrier were used to regenerate a resorbed buccal wall of the socket. The sizes of the defects were not reported. Bone grafts (lyophilized bone) were used to prevent collapse of the membrane. The barriers were removed between 21 and 28 days. No data was presented with respect to bone regeneration, but the authors indicated that all sites successfully received an implant.

Hoffman et al used d-PTFE barriers without adjunctive bone grafts at 276 sockets.⁷ Among those patients, 28 had defects in the buccal plate. In general, the defects were not greater than 50% of the buccal plate of bone. At these sites, there was a mean bone gain of 6 mm (range of 4 mm to 8 mm). There was no control group receiving any therapy, so it is unclear how much better the result was than osseous debridement. Nevertheless, even without bone grafts the data was encouraging with respect to bone regeneration at defective buccal plates.

Yamashita et al⁹ used d-PTFE to regenerate 86 sockets and 45 defective ridges in 111 patients. At the 45 ridges where the mean osseous defect was 5.5 mm, there was 5 mm of bone regenerated (95.8% fill). In conjunction with the alloplastic bone grafts, they used Emdogain and/or PRP. Therefore, it was impossible to know precisely which factor(s) accounted for the good results.

All three studies^7-9 addressing defective alveolar ridges reported a positive finding with respect to healing, which facilitated implant placement in all monitored patients. In addition, the four cases presented by the current authors (Figure 1 through Figure 25) attained excellent results with d-PTFE plus an alloplastic bone graft (Puros) when treating buccal wall defects.

Case Presentations

The four presented cases shown in Figure 1 through Figure 25 were all treated in a similar manner as outlined in detail in the captions for the first case (Figure 1 through Figure 11). In all four cases, teeth with pathosis were removed, buccal and lingual flaps were elevated, and sites were surgically debrided. A Cytoplast d-PTFE barrier was sized and inserted usually under the buccal flap, the bone graft was added, the barrier was then tucked under the lingual flap, and the flaps were sutured. Bone grafts were used in all of the cases, because buccal bony plates were resorbed and the bone graft helped support the barrier.

Summary and Conclusions

d-PTFE has many advantages. It is a biocompatible barrier that is as effective as e-PTFE for GTR procedures when they are both submerged and the barrier is left in place 4 to 6 weeks; however, no studies compared the efficacy of these barriers when the d-PTFE was left exposed and the e-PTFE was submerged. d-PTFE barriers are easy to remove. They allow cell adhesion without tissue in-growth into the barriers. The studies that assessed the efficacy of d-PTFE barriers when they were left exposed consistently reported good results with respect to socket preservation. Furthermore, it is advantageous to use a bone graft in conjunction with the d-PTFE to avoid the barrier collapsing into the defect.

There are a limited number of studies assessing the utilization of d-PTFE in conjunction with bone grafts when there are defective alveolar ridges.^7-9 However, these papers have consistently demonstrated that bone repair occurs despite the barrier being left exposed. In these reports, all bone repairs appear to be within the housing of the alveolar bone. No studies demonstrated horizontal or vertical augmentation beyond the existing alveolar boundaries. In this regard, it is advisable to overbuild bone-grafted sites, because the authors of this article have attained horizontal augmentation beyond the alveolar housing (Figure 18).

The amount of time that a barrier must be left in place remains controversial. However, it appears that a 4-week interval facilitated developing a dense osteoid tissue, which proceeds to mineralize and form bone with respect to sockets and ridge defects. It may be prudent to leave the barrier in longer for larger defects, but there are no data supporting this concept with d-PTFE barriers. If this is done, it will be necessary to remove the invaginated epithelium with a diamond bur after barrier removal, and the site will need to be sutured.

Despite a total lack of randomized clinical trials, the numerous cases presented demonstrate that this procedure is clinically beneficial with respect to restoring a defective buccal or lingual plate of bone. In conclusion, GBR procedures using d-PTFE are easy to perform and cause less morbidity when compared to procedures that require flap advancement to achieve primary closure.

Addendum: Histological Findings

A recent study by Borg and Mealey⁵⁰ evaluated the efficacy of socket preservation procedures when d-PTFE was employed in conjunction with a combination mineralized/demineralized allograft versus 100% mineralized FDBA (N = 42). After teeth were removed, a bone graft material was placed and a d-PTFE barrier was inserted as previously described and left exposed. Barriers were removed 4 weeks after placement. The data provided histological evidence that a bone allograft used in conjunction with a d-PTFE barrier resulted in increased vital bone formation. These findings validate that d-PTFE barriers in conjunction with an allograft or combination of allografts result in vital bone formation and help preserve the dimensions of the alveolar ridge. The data also corroborated that 4 weeks was sufficient time for barriers to be effective. Others also have histologically demonstrated that d-PTFE results in vital bone formation. Bartee37 reported vital bone formation after using d-PTFE and a “bone paste,” and Hoffman et al⁷ indicated that d-PTFE resulted in bone formation; however, bone grafts were not used.

Acknowledgment

The images for Figure 1 through Figure 11 were courtesy of Mehmet Dikmen, DMD, PhD. The images for Figure 12 through Figure 14 were courtesy of Siyan Lin, DDS.

Disclosure

The authors had no disclosures to report.

About the Authors

Gary Greenstein, DDS, MS
Clinical Professor
Department of Periodontology
College of Dental Medicine
Columbia University
Private Practice
Surgical Implantology and Periodontics
Freehold, New York

Joseph R. Carpentieri, DDS
Clinical Assistant Professor
College of Dental Medicine
Columbia University
Private Practice
Surgical Implantology and Prosthodontics
White Plains, New York

Queries to the author regarding this course may be submitted to authorqueries@aegiscomm.com.

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