Abstract
Background:
This clinical study aimed to overcome the difficulty of graft fixation and limited blood supply for dehiscence defects regeneration by using a cross-linked gelfoam matrix jointly with collagen membrane and xenograft.
Materials and Methods:
The study included twenty dehiscence-like defects in maxillary anterior teeth with ≥4 mm facial bone loss and ≥5 mm clinical attachment loss (CAL) in patients suffering from Stage III periodontitis. Sites were treated with regenerative surgery using a cross-linked gelfoam matrix with glutaraldehyde, xenograft, and collagen membrane. The recorded parameters were: CAL, probing pocket depth (PPD), and radiographic three-dimensional (3D) volume for dehiscence-like defects (3D volume of facial bone defects) and 3D volume of interproximal defects using cone-beam radiographs. Data of these parameters were collected at both baseline and 6 months postsurgery. “Paired t-test” was used to assess the two variables.”
Results:
Both CAL and PPD showed statistically significant reductions and there was a significant bone gain at 6 months postsurgery in comparison to baseline (P ≤ 0.05).
Conclusion:
Using a cross-linked gelfoam matrix with glutaraldehyde in combination with xenograft and collagen membrane could enhance the outcome of periodontal regeneration, especially in the treatment of challenging dehiscence defects.
Keywords: Cross-linked gel foam matrix, dehiscence defects, periodontal regeneration, three-dimensional volume
INTRODUCTION
Periodontitis is an inflammation of the soft tissue and bone supporting the tooth, which can cause tooth loss due to coronal bone and attachment loss. It features the creation of pockets and/or recession. One of the most prominent symptoms of periodontal disease is alveolar bone loss and it represents the anatomical sequel to the apical spread of periodontitis.[1]
Dehiscence and fenestration are the two common alveolar bone defects. A dehiscence in the alveolar region may show an absence of the facial or lingual cortical plate, which leaves the root surface denuded. The alveolar bone defect is diagnosed with dehiscence if there was a recession of cortical bone apical to the margin of interproximal bone by at least 4 mm. The exact reason for these issues is unknown. The predisposing factors include a thin bony plate combined with labial protrusion of the root malposition and prominent root contours.[2]
It is very difficult to treat bony cortical problems as it needs regenerative therapy. Regeneration of dehiscence defects faces many challenges as limited blood supply, graft fixation, gingival tissue problems, and frequent trauma to grafted sites.[3] While a variety of materials can be used in periodontal regeneration, an ideal graft material should be nonallergenic, biocompatible, nontoxic, and possess no potential for the transmission of disease. They ought to be durable enough to preserve space, and the rate at which they degrade should be reasonable.[4]
Deproteinized cancellous bone derived from different animals (such as bovine or porcine bone) can be used for xenografts. Once the organic components are extracted, the leftover inorganic structure offers a natural architectural matrix and a source that is rich in calcium. The inorganic remains also help with the retention of the augmentation physical dimension during the remodeling phases. Due to their porosity, bovine-derived hydroxyapatite grafts for bone replacement have the potential to increase the available surface area that can act as an osteoconductive scaffold, and they also possess a mineral composition similar to that of human bone.[5]
Gelatin sponge has been extensively applied during surgical procedures as an absorbent and adhesive pad as well as a wound dressing due to its hemostatic properties. The inexpensive gelatin matrix and high quantity production give it an advantage over the collagen matrix. Moreover, in distinction to collagen, gelatin does not exhibit any antigenicity in physiological settings.[6]
Gelatin scaffolds can be used as a matrix for bone regeneration and a delivery system for bone grafts. Since gelatin scaffolds can support osteoblast processes and promote cell proliferation and migration into the sponge porosities.[6]
Gelfoam is a gelatin-based sponge compiled from pure type A pork skin gelatin that has been broadly in use as a wound dressing and for bleeding control, during and after operative procedures.[6] Ponticiello et al. indicated that the formation of a cartilage-like extracellular matrix with cartilage markers like glycosaminoglycans and type-II collagen is possible using 21 days cultures of mesenchymal stem cells in gelfoam in a medium-containing transforming growth factors-beta 3.[7]
Collagen and gelatin sponges, as biomaterials, have a key drawback in that they break down rapidly owing to enzymatic digestion. A deficiency in the mechanical stability of protein-based scaffolds will cause high rates of breakdown of the newly formed bone and scaffold to become misaligned. Therefore, to set an ideal environment for bone formation, it is crucial that a proper balance between the formation of new bone and scaffold degradation in defective areas. Studies have attempted to solve this issue by cross-linking collagen and gelatin fibers using various chemical agents such as aldehydes (formaldehyde and glutaraldehyde); hexamethylene-diisocyanate, carbodiimides, and acyl acid. Cross-linked structures result in a slower rate of degradation, allowing for better durability of materials in the physiological environment.[6]
To provide three-dimensional (3D) images, cone-beam computed tomography (CBCT) has been seen as a useful tool for head-and-neck applications. It also provides arbitrary levels of data with higher resolution and lower radiation exposure than the alternative techniques. Zhao et al. using CBCT have highlighted the defects forms of alveolar bone in periodontitis, discovering that it was specific to both tooth site and type. Numerous publications have shown that CBCT can be used to identify alveolar bone loss in an accurate manner.[8]
Dehiscence defects can be accurately assessed by CBCT images. A sagittal, axial, and coronal image thoroughly presents the dehiscence size and morphology in each plane offering details regarding width, height, and depth of furcation involvement. The details might not be achievable with traditional radiographic techniques. Thus, the use of CBCT may provide new ways to evaluate periodontitis and develop treatment plans.[9]
The sensitivity and specificity of CBCT for the diagnosis of periodontal defects were tested and found to be, 100% for CBCT, whereas the conventional radiographs were 50%.[10] 3D volume assessment of CBCT gave accurate and promising results and can be used instead of linear measurement, which may be of value, especially for the reproducible assessment of bone defect topography for the research purposes.[11]
Owing to the difficulty of graft fixation and limited blood supply for dehiscence defects regeneration, this study was performed to evaluate the use of cross-linked gelfoam matrix for bone graft and clot fixation for guided tissue regeneration of dehiscence.
MATERIALS AND METHODS
This study was conducted on twenty dehiscence-like defects in maxillary anterior teeth in patients with Stage III periodontitis, their ages ranged between 39 and 65 years old. The patients were all made aware of the nature of the study and all patients filed an informed consent before starting procedures according to Helsinki ethical principles for medical research involving human subjects. Ethical approval for the study was taken.
The criteria for inclusion were as follows: The presence of dehiscence-like defects in maxillary anterior teeth with ≥4 mm facial bone loss,[10] facial bone loss was apical to interproximal bone loss. Clinical attachment loss (CAL) ≥5 mm, lack of any related medical issues that contraindicate periodontal surgery, optimum adherence as confirmed by a positive attitude toward oral hygiene, and successfully showing up for treatment appointments.
The general exclusion criteria were the use of antibiotics agents 6 months before the study, smokers, diabetics, and pregnant and lactating patients.
Study design
All patients underwent initial therapy, consisting of comprehensive oral hygiene instructions, scaling and root planing. Re-evaluation was conducted after 1 month. Patients who met all criteria for entry into the surgical phase were assessed clinically by the same periodontist. Probing pocket depth (PPD) and CAL were measured at baseline and 6 months following therapy. Customized acrylic stent was used for baseline and follow-up measurements to prevent angulation and positioning errors [Figure 1].
Figure 1.
Representative images of pre- and post-PPD measurement of the maxillary right central using customized acrylic stent. PPD – Probing pocket depth
Radiographical assessment by CBCT was performed using ITK-SNAP (Paul A. Yushkevich, Octavian Soldea, Baohua Wu, Michael Stauffer (University of Pennsylvania), Guido Gerig & Yang Gao (University of Utah), Supported by the U.S. National Institute of Biomedical Imaging and BioEngineering.) program as follows:
1.3D volume measurements of dehiscence-like defects in maxillary anterior teeth were measured from CEJ to the crest of the facial bone and from the mesial line angle to the distal line angle of the root. The width of the volume brush used by ITK-SNAP program is equal to the thickness of the remaining labial bone.
All pre- and post-surgery CBCT scans were performed by the same trained technician at baseline and 6-month posttreatment [Figure 2]. Each patient had exposed to the same voltage, current, exposure duration, and detection field during both times of exposure.
Figure 2.
CBCT at baseline and after 6 months – sagittal view. CBCT – Cone beam computed tomography
Surgical procedure
The surgical technique (regenerative surgical flap) followed a protocol similar to that described by Mengel et al.,[12] as follows:
Presurgical therapy consisted of Amoxicillin/clavulanate 375 mg tabs in addition to Metronidazole 250 mg tabs every three times per day. Systemic anti-inflammatory medications were prescribed to the patients the day before surgery. The area selected for surgery was anesthetized by infiltration technique. Buccal and lingual sulcular incisions with horizontal-releasing incisions were made around the tooth to be treated and at least one tooth mesial and one distal to elevate full-thickness mucoperiosteal flaps to facilitate instrumentation and accessibility care was taken into consideration to maintain as much interproximal soft tissue as possible. Complete debridement of the defect as scaling and root planing using a hand instrument, no osseous recontouring was performed. So as to eliminate the granulation tissue, the inner side of the flap was curetted and using sterile saline the surgical areas were cautiously rinsed and isolated with cotton rolls. Decortication of interproximal bone was done using small carbide round bur to improve blood supply and to increase the number of undifferentiated mesenchymal cells in the surgery field. Xenograft particles were prepared and mixed with pieces of crosslinked gel foam using small drops of sterile saline. After mixing, the graft material became sticky and putty in consistency that can be held easily and applied easily to the defect. After graft material application, cross-linked gelfoam rapidly absorbs blood and firmly holds in the selected grafted sites. The biomed collagen membrane was trimmed and prepared according to the grafted site [Figure 3]. Flaps were sutured coronally to the original levels to cover the treated sites with soft tissue. The areas were then packed by periodontal dressing for 2 weeks.
Figure 3.
(a) Alveolar defect after full-thickness flap reflection and complete debridement, (b) Graft filled in the defect, (c) Collagen membrane trimmed and prepared according to the grafted site, (d) Sticky and putty xenograft mixed with cross-linked gel foam using small drops of saline
All subjects received postoperative instructions, including rinsing with 0.1% chlorohexidine (twice daily for 2 weeks), and the combination of antibiotic therapy and anti-inflammatory systemic medications for 1 week was administered. Periodontal dressing and suture removal were performed after 14 days. Supportive periodontal therapy was performed monthly till the end of the study period which include, periodontal evaluation (except for PPD and CAL which were measured 6 months postoperative onward), reinforcement of plaque control, root planing and scaling were performed if required, and patient’s medical history was updated.
Collected data were analyzed using IBM SPSS software package version 20.0. (Armonk, NY, USA: IBM Corp). The normality of the distribution of variables was verified by Kolmogorov–Smirnov test. Paired t-test was assessed for the comparison between two periods for normally distributed quantitative variables. P < 0.05 was considered statistically significant.
The sample size was calculated using power analysis by the Epi-Info software package created by the World Health Organization and Center for Disease Control version 2007. The confidence limit was 95%, the power of the study was 80%, and the sample size was found to be n = 20.
RESULTS
The mean value of CAL was 6.5 ± 1 mm at baseline; this value was reduced to 3.6 ± 1 mm at 6 months posttreatment. Results showed a reduction in the mean value of PPD at all evaluation periods. At 6 months, the mean value was 3.1 ± 0.7 mm compared to the mean baseline value of 6.3 ± 0.8 mm. For both CAL and PPD, the reduction was statistically significant from baseline to 6 months as P < 0.05 [Figure 4 and Table 1].
Figure 4.
Comparison of CAL and PD mean values at baseline and 6 months’ post-surgery. PD – Pocket depth
Table 1.
Effect of studied treatment modality on the mean values of pocket depth, clinical attachment level and radiographic three dimensional volume measurements (n=20)
| Pre | Post | t | P | |
|---|---|---|---|---|
| CAL | ||||
| Mean±SD | 6.5±1 | 3.6±1 | 19.262* | <0.001* |
| Median (minimum-maximum) | 6.7 (4.7-8.3) | 3.3 (2.3-6.3) | ||
| PPD | ||||
| Mean±SD | 6.3±0.8 | 3.1±0.7 | 21.327* | <0.001* |
| Median (minimum-maximum) | 6.5 (5-7.7) | 3 (2.3-4.7) | ||
| 3D volume of facial bone defects | ||||
| Mean±SD | 75.2±20 | 36.8±11.7 | 12.813* | <0.001* |
| Median (minimum-maximum) | 72.2 (42.4-109.2) | 35 (20.2-60.2) | ||
| 3D volume of interproximal defects | ||||
| Mean±SD | 84.8±29 | 37.7±18.2 | 13.403* | <0.001* |
| Median (minimum-maximum) | 80 (49.9-150) | 37.6 (15.6-82.5) |
*Statistically significant at P≤0.05. P - P value for comparing between pre and post; t - Paired t-test; PD - Pocket depth; PPD - Probing pocket depth; CAL - Clinical attachment level; SD - Standard deviation; 3D - Three dimensional
Results showed a significant reduction in the mean value of the radiographic 3D volume of interproximal defects after 6 months posttherapy. At 6 months, the mean value was value 37.7 ± 18.2 mm3 compared to the mean baseline of 84.8 ± 29 mm3. This reduction was statistically significant as P < 0.05. It was found that the mean value of the radiographic 3D volume of facial bone loss was 75.2 ± 20 mm3 at baseline. At 6 months posttreatment, the mean values decreased to 36.8 ± 11.7 mm3. There was a statistically significant bone gain as P < 0.05 [Figure 5 and Table 1].
Figure 5.
Comparison between the two studied periods according to 3D volume of facial bone defects and 3D volume of interproximal defects. 3D – Three dimensional
DISCUSSION
Protein-derived biomaterials as a tissue scaffold possess a perfect affinity to and compatibility with other matrix proteins. Nevertheless, the practical use of these materials is limited because of their high rate of biodegradation after implantation which might result in mechanical weakness.[13] The present study examined the capability of cross-linked gelfoam matrix with glutaraldehyde in combination with xenograft and collagen membrane in the treatment of challenging dehiscence defects.
As gelfoam is generally effective at blocking cancellous bone replacement, it’s thought that this combination might have potential. Gelfoam packing would neither provide support for epithelial overgrowth nor promote the growth of fibroblast. This was evidenced by Singh et al.,[14] who argued the allegation that hemostatic agents can be used as bone graft substitutes.
Furthermore, Stanton et al. showed that a gelatin sponge is capable of playing the function of scaffold for sustaining chondrocyte and osteoblast cells in vitro.[15] After 25 days in culture, they observed cartilaginous matrix growth in the pores of gelatin sponges. A cross-linked gelatin scaffold constructed from tricalcium-phosphate contributed a notable porous structure, conducive to attachment and differentiation of osteoblast in an in vitro study by Yang et al.[16]
Xenograft was used in the current study since it has been extensively in use for bone reconstruction due to its safety and it is a well-grounded osteoconductive material with a low rate of resorption. Xenograft has demonstrated to be an effective scaffold for cell growth and consequently for bone regeneration because of its trabecular structure and chemical composition.[17]
Our study demonstrated favorable outcomes after 6 months. Cross-linked gelfoam matrix with glutraldehyde in combination with xenograft and collagen membrane significantly enhanced the mean PPD, CAL reduction after 6 months as compared to baseline. Furthermore, there was significant reduction in the area of the defect as evidenced radiographically by CBCT.
The improvement in clinical and radiographic parameters in our study may be due to the favorable properties of gelfoam as once it is in contact with blood, it expands and holds the clot and might also act as a scaffold allowing vessel in-growth. It also maintains the space until it resorbs. It can absorb 40–50 times its own weight of blood and might bring in more growth factors to the defect site leading to better regeneration outcomes.[18]
Furthermore, there was an additional benefit from a combination of gelfoam with xenograft and collagen membrane as evidenced recently by Toledano-Serrabona et al., who conducted a systematic review and meta-analysis and concluded that, in comparison to spontaneous healing, the xenograft and collagen membrane showed superior periodontal outcomes and less postoperative problems.[19]
On the other hand, in the current study, we used CBCT as a powerful tool for radiographic evaluation. 3D imaging with computed tomography, especially CBCT is a helpful tool to detect and diagnose obscure defects.[20]
The results of the current study were in correspondence with Rohanizadeh et al., who stated that: Gelatin sponge (Gelfoam) could be a candidate for a bone scaffold in low-load areas or as a drug delivery carrier to promote bone regeneration in defective areas.[6] As evidenced by Bains et al., who concluded that gelatin scaffolds demonstrated the ability to support osteoblast activities and allowed cell proliferation and cell migration into the sponge porosities.[21]
However, the results were inconsistent with Bodner,[22] who evaluated radiographically the alterations of jaw defects that appear after the enucleation of cysts. They compared demineralized freeze-dried bone allograft grafts (Group A) with packing with absorbable gelatine sponge (gelfoam) (Group B). The results were as follows: The density at 6 and 12 months postsurgery in Group A was significantly higher than in Group B. There was no significant difference at 24 months. Group A reached density levels at 6 months that were reached by Group B at 12 months. This discrepancy can be explained by the fact that: In our study, gelfoam was linked with glutaraldehyde in combination with xenograft and collagen membrane which gave additional effects as compared to using gelfoam as a solo treatment.
Throughout the study, there was no foreign-body reaction reported. This was in agreement with Ponticiello et al., who found that a gelatin sponge had excellent biocompatibility without the occurrence of any immune reaction.[7] Furthermore, Finn et al. in their study concluded that: The gelatin sponge residuals were placed into the new bone without any immune response taking place.[23]
Limitations and future study prospects
There were 20 defects in nine patients included in this study. A larger sample size and a comparative experimental design are necessary for future studies. The methods we used to evaluate the regenerative effect included clinical examination and CBCT. Although a good intra-examiner reproducibility was obtained, the re-entry measurement is still the “gold standard” to reflect the actual bone change. Furthermore, long-term results of 1 year or more are needed to build up stronger evidence to prove the role of gelfoam on periodontal regeneration. In the future, it is essential to create novel biomaterials and new delivery systems for the growing field of regenerative periodontal therapy, especially for challenging dehiscence defects.
CONCLUSION
The current study suggests that a cross-linked gelfoam matrix with glutaraldehyde can enhance wound healing and bone regeneration in dehiscence defects. When combined with xenograft and collagen membrane, it might be a superior scaffolding material.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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