Bone Regenerative Biomaterials in Periapical Surgery: A Systemic Review and Meta-Analysis.

INTRODUCTION: Successful treatment in the endodontics and periodontics depends on the periapical status. Hence, in the present meta-analysis, we evaluate the various bone regenerative materials in the periapical surgeries.
MATERIALS AND METHODS: Online data were collected from the search engines of EBSCO, PubMed, Google Scholar, and Scopus. The searched terms were bone regenerative, bone grafts, bio materials, periapical surgery, and endodontic surgery. Based on the PRISMA guidelines, the meta-analysis was performed. The studies for the past 10 years were considered that included at least 10 patients. The translatable articles were included that had the human studies that were clinical studies and/or trials and also had the bone regenerative materials used in the procedure.
RESULTS: A total of 475 articles were selected, of which 30 were selected based on the criteria. Of these, after the removal of the 21 duplicate articles, 9 articles were finalized. The meta-analysis showed that when the bone graft materials are used along with the barriers for the regeneration, there were observed higher success rates.
CONCLUSIONS: The bone regenerative materials can be used for the successful outcome for the periapical surgeries. The guided tissue regeneration along with the bone regenerative materials may aid in the good prognosis of the endodontic and periodontal cases. Copyright:

INTRODUCTION

One of the many modalities to save the decayed tooth is by endodontic treatment that relies on the removal of all the infectious agents from the periapical zone. However, the total elimination of the pathology from the periapical tissues is not easy. In the previous studies, the average time for the total elimination and the healing is seen to be an average of 5 years.[1] Even after thorough debridement, the pathogens may persist. Hence in severe and refractory cases, the periapical surgery is suggested to save the tooth as a last resort before the extraction.[23] The success of this periapical surgery includes the regeneration of the periodontium.[45] In the regeneration for the periodontium, the bone grafts, regenerative materials, barrier membranes are used.[67] There are studies related to the healing in the endodontic and periodontal surgeries by using the guided tissue regeneration (GTR), bone grafts, etc. However, there is less uniformity in these studies. The design and the criteria of the materials used in these studies are highly variable.[89101112131415] For performing the periapical surgery, there are few indications set by the periodontic and endodontic societies. These criteria are to be met for performing the periapical surgeries. When following these criteria and by the application of the GTR along with the bone regenerative materials, there have been successful results obtained previously.[1617181920] However, in these studies, the prognosis is inconsistent in these studies. Hence in the present meta-analysis, we evaluate the various bone regenerative materials and the barriers that are used for the periapical surgeries. Along with these, the prognostic factors that may aid in the success of the treatment are assessed.

MATERIALS AND METHODS

Online data were collected from the search engines of EBSCO, PubMed, Google Scholar, Scopus. The searched terms were bone regenerative, bone grafts, bio materials, periapical surgery, and endodontic surgery. Based on the PRISMA guidelines, the meta-analysis was performed. The studies for the past 10 years were considered that included at least 10 patients. The studies with the barrier membrane and/or the bone regenerative materials used in the procedure were included.

The following inclusion criteria were set

Application of the GTR

Application of the bone regenerative material

Minimum number of the subjects = 10

Languages are to be in English or any other translatable languages

Human studies only

Full text available.

The exclusion criterion was:

Poor design

Languages that required permission to translate

Animal studies

Only abstracts available without the full text.

Two reviewers were selected for the study. The entire text was evaluated after the title, and the abstracts were selected for the study. Any disputes were cleared by consensus. The most appropriate studies that fit in the inclusion and the exclusion criteria were considered for the study.

RESULTS

A total of 475 articles were selected. In these articles, 445 were excluded after the titles or the abstract didn't fit the study criteria. Thirty studies fit in the selection criteria. Of these, after the removal of the 21 duplicate articles, nine articles were finalized. The flowchart showing the article selection is shown in Figure 1.

Figure 1

Flowchart describing selection of articles

The meta-analysis showed that when the bone graft materials are used along with the barriers for the regeneration, there were observed higher success rates. These nine articles were selected for the preparation of the extraction data, and meta-analysis was done.[1114151617202122] The data contained the method of the surgery performed, the material used for the regeneration, the GTR, tooth, or the segment that was involved that was arranged in a tabular form.

Among these nine articles, one was a case report,[14] the remaining were clinical trials.[311151617202122] The arrangement of these studies was done based on the level of the evidence on the rank established based on the strength of recommendation taxonomy principles. In these nine studies, five were with level 2[314162122] and four had level one.[11151720] The demographics noted from these studies are depicted in Table 1.

Table 1

Demographics of the included studies

Authors	Goyal et al., 2011[3]	Dominiak et al., 2009[16]	Taschieri et al., 2008[21]	Taschieri et al., 2008	Taschieri et al., 2007[22]	Marín- Botero et al., 2006[20]	Dietrich et al., 2003[14]	Tobon et al., 2002[17]	Pecora et al., 2001[11]
Area
Maxillary	0	82	44	17	39	22	9	23	0
Mandiblular	0	24	25	14	20	8	14	7	0
Tooth type
Anterior	0	139	0	11/10	16/10	14	4/2	16	0
Premolar	0	18	0	4/3	14/6	16	3/1	14	0
Molar	0	10	0	2/1	9/4	2/11	0	0
Sex
Men	17	34	22	11	13	11	15	10	0
Women	13	72	31	16	28	19	7	18	0
Mean age	31	37.5	43 male/36 female	47 male/32 female	43 male/36 female	44.5	43.5	39.2	48

The studies were considered for the method of the surgery done, the type of the defect, the graft used, the material used, the subjects in the study and the success rate [Table 2].

Table 2

Comparison of the variables in the included studies

Author	Lesion types	GTR method and total subjects		Outcome			Evaluation done by clinical/radiographical/both	“SORT”
				Success	Uncertain	Fail
Pecora et al., 2001[11]	Through-and-through lesions	Surgiplaster®	10	77.7	22.2	0	Radiographical	One
		Control	10	33.3	55.5	11.1
Tobon et al., 2002[17]	Four-wall defects	OsteoGen® + Gore-Tex®	8	100	0	0	Both	One
		Gore-Tex®	9	66.66	33.33	0
		Control	9	44.44	44.44	11.11
Dietrich et al., 2003[14]	Apicomarginal defects	Bio-Oss® + Bio-Gide®	23	82.6	8.7	8.7	Both	Two
Marín- Botero et al., 2006[20]	Apicomarginal defects	Sliding periosteal grafts	15	60	40	0	Both	One
		Polyglactin-910 membrane	15	40	47	13
Taschieri et al., 2007[22]	Four-wall defects	Bio-Oss® + Bio-Gide®	16	87.5	12.5	0	Both	Two
		Control	22	81.8	13.6	4.5
	Through-and-through lesions	Bio-Oss® + Bio-Gide®	8	75	12.5	12.5
		Control	13	61.5	30.7	7.7
Taschieri et al., 2008[15]	Through-and-through lesions	Bio-Oss® + Bio-Gide®	17	88.2	5.9	5.9	Radiographical	One
		Control	14	57.1	35.7	7.1
Taschieri et al., 2008[21]	Four-wall defects	Bio-Oss® + Bio-Gide®	16	87.5	12.5	0	Both	Two
		Control	22	81.8	13.6	4.5
	Through-and-through lesions	Bio-Oss® + Bio-Gide®	17	88.2	5.9	5.9
		Control	14	64.3	28.6	7.1
Dominiak et al., 2009[16]	Four-wall defects	Bio-Gide®	26	80.77	18.86 Mean; not detailed	0.0094 Mean; not detailed	Both	Two
		Bio-Oss®	30	83.33
		Bio-Oss® + PRP	25	92
		Control	25	64
Goyal et al., 2011[3]	Apicomarginal defects	Healiguide®	10	70	30	0	Both	Two
		Healiguide® + PRP	9	77.78	22.22	0
		PRP	6	83.33	16.67	0

GTR: General time reversible, PRP: Platelet-rich plasma

We observed that five of the selected studies were dissimilar. The study of the remaining four was comparable. The five studies were without clear randomization protocol, there was no clear evaluation of the outcome, some studies were seen where the patients were not followed up, and also there were differences of the subjects between the case and the control groups. This made the statistical analysis difficult due to the heterogeneous nature of the previous studies included in the review.

DISCUSSION

In the study of von Arx and Cochran,[18] they proposed the membranes to be used for the various types of the lesions and defects. They set criteria to classify the lesion type that is based on the certain characteristics of the lesion-like area. They identified four types of the lesion. In the present study, we considered the periapical lesions based on these criteria.

In the present study, we observed that when the bone regenerative materials are used in the four-wall defects of the periapical surgeries, there was a nearly 100% success rate combining a synthetic bioactive resorbable hydroxylapatite than with only barriers.[17] This was clearly evident by the clinical and radiographic observations. When the Bio-Oss® that is xenograft (bovine bone) was used with the GTR, the success was higher than when the two were not applied for the periapical surgery in the through and through lesions. When the resorbable barrier membrane and the Bio-Oss® were used, the clinical and the radiographic signs significantly improved in the through and through periapical lesions.

For the endoperiodontal cases, only 50% of the success was seen with the application of the polyglactin alone, but with the platelet-rich plasma (PRP), the success rate significantly improved. However, the control group was not seen in this study. By performing the periapical surgery, the access to the region of the periapical tissues is attained easily. Sometimes the bone has to be removed in these procedures. The surgery also helps in healing. However, the previous tissue is not formed, but a new tissue regenerates. The regeneration of the tissue at the site of the periapical surgery is dependent on the native cells at the apex.[1591520] The epithelial cell migration in the wound area is the fastest. The GTR is based on the regeneration of the periodontium.[3456789101112] This method has been used in the implant surgeries, endodontics, periodontics for the regeneration. This procedure makes use of the barrier membranes that guide the cells for the periapical tissue regeneration.

On the other hand, the bone grafts help in the regeneration of the periapical bone. These may be of a variety of types like auto/allo/xenografts. They may be inductive or conductive.[101112] Usually, Ox bone is applied.[141516171819202122] Calcium phosphate silicate, β-tricalcium phosphate,[23] or calcium sulfate[5912] are synthetic materials.

The barrier is required to give time and base for the repopulation of the periapical cells that are bone and Periodontal Ligament cells. In the early cases, the nonresorbable membranes were used. However, due to the requirement of the second surgery, these were replaced by the resorbable membranes.

There are studies that show that periapical surgery alone has a good prognosis in the four-wall defects. The application of the GTR in these cases has been criticized with increasing cost. In the study of Dominiak et al.[16] they showed that in the four-wall defect, the maximum success was seen when the Bio-Oss® + PRP than in those where only periapical surgery is done. We also observed that the bone regenerative material when used along with the GTR the maximum success as seen in the through and through periapical defects.[18524] In the study of the Taschieri et al.[19] they stated that when in combination with the endodontic surgery, the barrier membranes may be successfully used for the through and through periapical defects. In a similar study Pecora et al.[11] stated that when the Ca2So4 is placed for these defects, they may act as a barrier and also sealing material. These barriers and the bioactive materials may aid in good prognosis, however, the studies done previously are inconclusive when compare with the control groups. One of the barriers is that the autogenous periosteal grafts may be used alternative to the routine barriers. The advantage of the above membrane is that it can promote the osteogenic cells that help in the bone formations in these lesions. The previous study done by Marín-Botero et al.[20] stated that superior results were obtained when the autogenous periosteal grafts were applied, than the regular barrier that was absorbable in the cases with the apicomarginal defect. However, in their study, they also stated that the success of their study might be influenced by periodontal status of the patients, the size, and the lesion shape. Furthermore, the reports were based on small sample size that could be a limitation in their study.

For the other materials that may help in the bone regeneration is the PRP. This PRP has the immune-modulatory effect that will help in the bone regeneration.[39] In the study of Dominiak et al.[16] they observed that the bone regenerative materials when used with the PRP the success was above 90% which was higher when compared to the bone grafts alone. Similarly, for the apicomarginal lesions, the PRP aided for the regenerative process that was evident in the successful outcomes. These were evident on the clinical assessment and radiographs.[93] In the four-wall defects, the bone regeneration was greater in the GTR + OsteoGen® group than when used alone. Similar observations for the Bio-Oss® + Bio-Gide® were registered for the through and through lesions, as shown in [Table 2].

These bone regenerative materials have aided in the correction of the defects that are generally a situation faced by the clinicians for these periapical surgeries.

From our study, it is evident that the Bio-Oss® combined with the barrier Bio-Gide® has shown superior outcome for the various defects. However, there has been a paucity of the research in the through-and-through defect.[3515122224] In the four-wall lesions the combinations OsteoGen® + Gore-Tex®[17] and Bio-Oss® + Bio-Gide®[2122] show comparable results.[25]

In the present study, the success was studied based on the clinical, histological, and radiographic evaluations. For the appreciation of the radiographic outcome, the average period suggested is 1 year. The follow-up for such long periods is seldom done in the previous studies. Furthermore, when the xenografts are used, the appearance of the radiograph has shown more opaque that may be misleading.[14151921] Furthermore, the interpretation of the radiograph is prone to bias as there is interobserver variability.

One study in the present analysis used the histological evaluation for the periapical status after the surgery. This is not often considered on the ethical grounds. However, it is the most reliable method.

Some authors have opined that the criteria put forward by von Arx and Kurt may help in calculating the success after the periapical surgery.

The following prognostic factors can be suggested from our study when the bone regenerative material and the barriers are used for the periapical surgery:

The location of the tooth

Amount of bone loss

Type of the defect

Periodontal status.

There were some limitations in our study. The included articles were highly heterogeneous. The sample size was small in almost all the included studies. Furthermore, the control groups were not uniform in few studies.

CONCLUSIONS

It can be concluded from our study that the combination of the bone regenerative biomaterials along with the barriers performs well in the periapical surgeries. Further, well-planned studies are suggested with larger samples.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.