The Journal of Contemporary Dental Practice
Volume 20 | Issue 8 | Year 2019

Role of Synthetic Hydroxyapatite—In Socket Preservation: A Systematic Review and Meta-analysis

Vivekanand S Kattimani1, Raja S Prathigudupu2, Abhishek Jairaj3, Mohasin A Khader4, Karthika Rajeev5, Anas A Khader6

1,2Department of Oral and Maxillofacial Surgery, Sibar Institute of Dental Sciences, Guntur, Andhra Pradesh, India
3Faculty of Dentistry, AIMST University, Bedong, Malaysia
4Department of Periodontics and Community Dental Sciences, College of Dentistry, King Khalid University, Abha, Kingdom of Saudi Arabia
5Department of Periodontics, Educare Institute of Dental Sciences, Malappuram, Kerala, India
6Department of Periodontics, Ar Rass College of Dentistry, University of Qassim, Kingdom of Saudi Arabia

Corresponding Author: Vivekanand S Kattimani, Department of Oral and Maxillofacial Surgery, Sibar Institute of Dental Sciences, Guntur, Andhra Pradesh, India, Phone: +91 9912400988, e-mail:

How to cite this article Kattimani VS, Prathigudupu RS, et al. Role of Synthetic Hydroxyapatite—In Socket Preservation: A Systematic Review and Meta-analysis. J Contemp Dent Pract 2019;20(8):987–993.

Source of support: Nil

Conflict of interest: None


Since a long time, the preservation of the socket is emphasized for various reasons. Many studies have suggested the ridge preservation through socket grafting using various bone graft substitute materials (GSMs). But none of the studies suggested the material of choice for the grafting. So, the systematic review was planned to analyze the outcomes of synthetic hydroxyapatite (SHA) graft material for socket preservation. The review was aimed to determine the existing evidence for the use of SHA GSM for grafting and its usefulness.

Materials and methods: The literature search was performed for the studies published in the English language independently by all four authors (search team) in the Medline database through the PubMed search engine for the past 5 years. The study involved predetermined inclusion and exclusion criteria for the search. The final lists of clinical trials were analyzed to determine the existing evidence and suggested the mechanism of action.

Review results: The search resulted in 117 titles. After application of inclusion and exclusion criteria, a total of seven studies were found eligible for this systematic review. Out of seven, two studies were found eligible for meta-analysis whereas remaining included for the systematic review.

Conclusion: The meta-analysis favors socket grafting compared to control in terms of preservation of existing bone height and width. The SHA grafting showed successful bone regeneration with less connective tissue component. The histomorphometric evaluation showed a good bone regeneration associated with SHA than xenograft. Within the limitations of this meta-analysis, the synthetic GSM can be used for socket grafting.

Clinical significance: In the wake of increasing graft materials in the market and different origin raw material sources for the preparation of graft materials, clinicians are in dilemma for selection and its use. The success of grafting depends on the selection of appropriate material with a suitable calcium/phosphate (Ca/P) ratio. The review provided available evidence for the use of SHA.

Keywords: Bone, Extraction, Healing, Implant, Regeneration, Restoration.


Extraction is the most common procedure performed in routine dental practice because of caries, periodontal disease, and so on. Bony defects secondary to extraction if left untreated may lead to further bone loss.13 Eventually, the fixed restoration of the missing tooth may be a nightmare for the patient and difficult for the clinician to restore without the sound alveolar bone using either implant-supported restoration or fixed partial denture using natural tooth as an abutment.47 The bone loss followed by extraction requires socket grafting to prevent bone resorption or enhance earlier bone formation.811 Various techniques have been demonstrated, developed, and published as successful means for the preservation of the alveolar bone.4,9,1225 But none of the techniques claimed the superiority over the other.5,20,2629

Many GSMs are available commercially for grafting and showed varying success rates. The published literature has shown the use of different origin synthetic substitute materials for grafting but none of them have advised single material as an ideal substitute.911,30 Many systematic reviews performed till date concluded with the uncertainty of recommendation because of heterogeneous study material, use of different origin GSMs, etc.5,2629,3144 Changing trends in the mechanism of action7,45 fascinated researchers to develop newer materials with the advent of production technology, and the clinicians to use it for enhancement ofbone regeneration.4649

In the light of changing the mechanism of action, synthetic GSMs are becoming more versatile, as these reduce the morbidity of the second surgery, time, and the skill required for harvesting autogenous graft.45,5053 Because of the disadvantages associated with autogenous grafting, the paradigm shift happened toward processed graft substitutes. The processed graft substitute of different origins requiresbone-banking facilities which are not economical and have a chance of disease transfer risk.54 This led to the pursuit of synthetic materials.

To the best of our knowledge, no systematic reviews are available till date exclusively assessed the use of synthetic graft substitute for socket preservation. So, this systematic review was planned to delineate the suggested mechanism of action and analyze critically the existing literature to discuss the level of evidence for the use of SHAGSM for socket grafting.


The literature search was performed for the studies published in the English language independently by all four authors (VSK, PSR, KR, and AAK) in the Medline database through the PubMed search engine for the past 5 years (January 2014–December 2018). The search for cross-reference articles was performed. The study involved predetermined inclusion and exclusion criteria for the search. The final lists of clinical trials were analyzed to determine the evidence and suggested the mechanism of action.

Search Strategy

The search was performed using MeSH keywords. Various Boolean operators were used and the search string was formed to focus the research question. The search words included “extraction” and “graft”, “extraction” and “synthetic graft”, “socket preservation”, “ridge augmentation” and “extraction”, “tooth extraction” and “hydroxyapatite” or “tooth extraction” and “bioceramic material” or “tooth extraction” and “post-extraction.” The search included title, abstract, and keywords fields. Various filters like year of publication, human, and clinical trials were applied as appropriate to derive the desired output. To broaden the understanding of the subject, the review articles were thoroughly screened for cross-reference studies. The review articles gave insights for the future directions and the lacunae noted by previous researchers were considered to deepen the understanding of the present review.

Inclusion and Exclusion Criteria

The randomized clinical trials (RCTs) which used asynthetic graft material for socket grafting have been considered with a minimum of 10 patients assessed for the nature of bone regeneration using histomorphometry and available in the Medline database (searched through PubMed). Case reports and case series of fewer than 10 patients and non-English language publications were excluded.

The Type of Patients

The patients requiring grafting after extraction for socket preservation followed by microscopic examination for bone characterization during implant placement were considered for review.

Type of Intervention and Outcome Measures

Synthetic hydroxyapatite from different origins compared with any of other graft substitutes or control (no intervention/natural healing) groups. The outcome variable considered was the bone level and the nature of bone formed irrespective of various methods opted for assessment.

Data Extraction and Analysis

The screening was performed individually by all authors (team 1—VSK and RSP; team 2—KR and AAK) along with cross-reference resources. Both groups of authors prepared the PRISMA flow diagram that was used for final screening (Flowchart 1). The bibliography was created using the Mendeley desktop app (version 1.19.3) and was used to check for duplicates. The Review Manager 5.3 (Version: 5.3.5) used to extract data from eligible studies (Tables 1 to 3). If there is any confusion in the inclusion and the exclusion of the studies, it was sorted out through discussion. The data extracted were validated by another team for accuracy and for any missing data from the studies (AJ and MAK). The corresponding authors of selected studies were consulted through e-mail for further clarification and the necessary data required for meta-analysis in case of missing observations in the published article. The studies included for meta-analysis were assessed for the quality using Maurits van Tulder et al.’s criteria for risk of bias55 (Tables 4 and 5).

Flowchart 1: PRISMA flow diagram for the review and meta-analysis


The search resulted in a total of 117 titles. After the application of inclusion and exclusion criteria, a total of 49 clinical trials were included for abstract review. The abstract review resulted in seven eligible studies for a full-length study assessment. Seven studies were found eligible for full-article review.5662 Only two studies (Mayer56 and Machtei57) were found eligible for a quantitative analysis among seven studies (Table 1 and Flowchart 1). Whereas remaining five studies were considered for systematic review; among them, three had (Mozzati,58 El-Chaar,61 and Canullo62) no control group and two studies (Oliveira59 and Cavdar60) used the radiographic analysis. So, only two studies were considered for meta-analysis56,57 (Tables 2 and 3).

The study by Mayer et al. used the biphasic calcium sulfate (BCS) with β tri-calcium phosphate (β-TCP) and hydroxyapatite (HA)compared with the control group.56 The study by Machtei et al. included 11 patients each in the test and the control group57 and compared BCS/HA with control and xenograft. Whereas Mozzati et al.58 used RegenOss [equine collagen I and magnesium (Mg)–hydroxyapatite (ratio: 40–60%)] and Canullo et al.62 used Mg-enriched nanohydroxyapatite powder in their study. All of them used synthetic GSM and performed the histomorphometric analysis. El-Chaar et al. study assessed less than 10 patients because of dropouts and had no control group.61 In Cavdar and Oliveira studies, only radiological assessment was performed.59,60 In both the studies, different synthetic GSMs were used.

Table 1: Sample size and intervention of included studies in the meta-analysis
S noAuthor nameStudy set up and region of study originSample size—controlSample size—test group/sInterventionType of studyInclusion/exclusion
1Mayer56Department of Dental School, Israel1514BCS with TCP and HARCTIncluded
2Machtei57Department of Dental School, Israel1111BCS/HARCTIncluded
Table 2: Characteristics of included studies in the systematic review with reasons for not considering in meta-analysis
S noAuthor nameStudy set up and region of study originSample size—control and test
InterventionType of studyReasons for not considering in meta-analysis
1Oliveira59University Department, Brazil26 patients divided into four groups, not mentioned the number of patients allotment to eachDeproteinized bovinebone mineral with 10% collagen (DBBM-C), poly(d,l-lactide-coglycolide) with hydroxyapatite/b-TCP scaffold (PLGA/HA), PLGA/HA/b-TCP with 2.0% simvastatin scaffold (PLGA/HA/S)RCTOnly radiographic study
2Cavdar60University Department, Turkey1141Demineralized bone matrix + collagen membrane (CM)(N = 14), hydroxyapatite bone substitute (HBS) + CM (N = 14), CM (N = 13), or left empty (N = 11)RCTOnly radiographic study
3Mozzati58University Department, Italy0032Equine collagen I and Mg–hydroxyapatiteSingle arm study no control groupNo control group
4El-Chaar61Private office, New York00815% hydroxyapatite, 85% b-TCP complexCase series, single arm study, no controlNo control group
5Luigi Canullo62Private office, Italy0020Mg-enriched hydroxy-apatite (MgHA)Case series, no controlNo control group


The use of SHA graft substitutes for bone formation has changed its mechanism of action from the scaffold6365 to osteo induction.6670 The synthetic graft material, in the beginning, was used as a scaffold. The clinicians still think that it acts as a scaffold and bone defect-filling material. With evolution, synthetic GSM acted as an osteoconductive material.30,54,71 The mechanism of osteoconduction depends on the nature of origin, particle size, porosity, resorption rate, etc.68,69,72 The published literature showed the structure of HA is an important factor for an osteoinductive property. A few studies have shown osteoinductivity of HA in heterotrophic sites.66,73 The nanotechnology-assisted production made the clinicians dream for an artificial bone. The dream has come to a part reality for bone reconstruction. A few case reports emphasized the bone formation using block grafts for larger bone defects reconstruction in both animal and humans.66,7375 The changing scenario has been well documented in the published literature.66,7375

Table 3: Quantity of bone formation in test groups among all the studies eligible for systematic review
S noAuthor nameTotal bone area in %Connective tissue/marrow space in %Residual graft in %
1Mayer5647.7 ± 10.636.3 ± 19.415.99 ± 11.4
2Machtei5744.15 ± 18.8NF* and NR**16.51 ± 16.2
4Luigi Canullo62 at 4th and 12th month31.85 ± 6.9927.33 ± 17.7240.82 ± 6.71
41.32 ± 9.3732.40 ± 9.8726.28 ± 11.49

* NF—not found in the article

** NR—no response from corresponding author

# NA—not applicable, radiological assessment only

$ NQ—no quantitative analysis performed

There are many clinical reports, case series, and few original research, and RCTsthat presented the benefits of synthetic GSM.5,29,30,54,56,57 But none of the systematic reviews nor the RCTs advised single material as an ideal graft substitute. This inconsistency in the conclusion might be due to a variety of commercially available GSMs and clinical scenarios which cannot be standardized like animal study defect models for conclusive remarks. The size and the nature of the lesion, along with patient factors, might be the reason for this inconclusiveness. So, this review addressed the focused question of SHAGSM use for socket grafting and emphasized on the histomorphometry of bone regeneration. The systematic review ascertained the objectives of the study. However, seven studies found eligible for systematic review; out of seven studies, four have discussed histomorphometry. One study exclusively described the effect of the synthetic graft substitute for bone regeneration pattern using various assays.76

Table 4: Internal quality assessment of included studies for meta-analysis
S noCharacteristics examined according to Maurits van Tulder et al.55*Mayer56Machtei57
AWas the method of randomization adequate?YesYes
BWas the treatment allocation concealed?NoYes
CWere the groups similar at baseline regarding the most important prognostic indicators?YesYes
DWas the patient blinded to the intervention?NoYes
EWas the care provider blinded to the intervention?NoYes
FWas the outcome assessor blinded to the intervention?NoYes
GWere co-interventions avoided or similar?NoYes
HWas the compliance acceptable in all groups?YesYes
IWas the drop-out rate described and acceptable?YesNo
JWas the timing of the outcome assessment in all groups similar?YesNo
KDid the analysis include an intention-to-treat analysis?Don’t knowYes

* It includes only the internal validity criteria (n = 11) that refer to characteristics of the study that might be related to selection bias (criteria a and b), performance bias (criteria d, e, g, and h), attrition bias (criteria i and k), and detection bias (criteria f and j)

A to K—scored as—yes/no/don’t know

Table 5: Risk of bias assessment in the included studies for meta-analysis
Type biasPoints to be consideredMayer56Machtei57
Selection biasCriteria a and bPartlyNo
Performance biasCriteria d, e, g, and hSignificantlyNo
Attrition biasCriteria i and kPartlyPartly
Detection biasCriteria f and jPartlyNo

Mayer et al. study included BCS with b-TCP and HA for grafting.56 The study assessed a combination of two alloplastic materials in comparison to natural socket healing in 40 extraction sites of 36 patients. The final assessment included 15 extraction sites in the control group and 14 in the test group.56 The study did not mention the tooth number, instead mentioned anterior and posterior teeth in the mandible and the maxilla. The study involved the premolar and the molar region in both controls (12/15 sockets) and graft (14/14 sockets).56 The graft group showed minimal bone loss compared to the control group. The histological evaluation revealed the mature lamellar bone in both groups.56 But, the study had not mentioned how many bony specimens were taken for assessment. The study showed more connective tissue in natural healing compared to the test group.56 The study used a combination of materials but not the individual material, so it is difficult to comment on the effect of each component as both materials have different resorption kinetics. The author claims that the combination improved the quality of the material.56

The study of Machtei et al. included 11 patients each in the test and the control group.57 The study compared BCS/HA with control and xenograft. The study group involved premolars, canine, and incisors evenly presented both in the mandible and the maxilla.57 The study showed a similar percentage of bone (44.15 ± 18.8%) as that of Mayer et al.’s study (47.7 ± 10.6%) but it was less compared with the control group. The study didnot reveal the connective tissue component as mentioned in Mayer et al.’s study for comparison. Both studies consist of a similar sample size of 10 in Mayer et al.56 and 11 in Machtei et al.57

Histomorphometric analysis showed more of bone in the control group (81.72 ± 4.3%) than that in the BCS/HA group (44.15 ± 18.8%) which, in turn, was greater than in the xenograft group (22.50 ± 24.72%)in Machtei et al.’s57 study. Residual scaffold material was significantly greater in the xenograft group (40.18%) than the BCS/HA group (16.51%). The BCS/HA group (44.15%) showed bone twice that of the xenograft group (22.50%).57

The meta-analysis favors the use of SHAGSM over the control/natural healing group in terms of clinical and radiological outcomes. The histomorphometric analysis favored the grafting procedure compared to control (Fig. 1). Even though meta-analysis involved only two studies, the quantitative analysis favors grafting of the socket for the preservation of bone (Fig. 2). Advances in tissue-engineering techniques might soon provide novel biomaterials which are currently evaluated worldwide and will soon be introduced into the clinical practice.77 The newer GSM falls into the category of biomimetic scaffolds, as they stimulate bone formation, not only chemically but also structurally through micropores which connect each other. The osteoinductivity of these materials has been shown by published literature.66,76,78 The changing scenario and improved production technology may make the dream of artificial bone formation for grafting in the near future. The recent systematic reviews showed that the SHAGSM improved the bone regeneration along with the preservation of resorption.33,37,38,71 Long-term follow-up data are mandatory to elucidate the presence of grafted particles which would eventually interfere with the longevity of implant function.

Fig. 1: Showing comparison of total bone formed among BCS/HA group and control. Comparison 1: BCS/HA vs control. Outcome changes 1.1 total bone area

Fig. 2: Showing comparison of vertical ridge changes among BCS/HA group and control. Comparison 1: BCS/HA vs control. Outcome changes 1. 2: vertical ridge


Socket preservation using synthetic HA showed beneficial results compared to control group within the limitation of available studies for meta analysis. The use of GSM prevented alveolar bone resorption. The histomorphometric evaluation showed less residual graft material associated with SHA. Ridge preservation should become the standard of care for every extraction, so that healthy bone can be retained for successful restoration. To derive more robust evidence, we may need more number of RCTs with similar methodology and the same material for grafting in an economical way.


VSK and PSR drafted the protocol; VSK, PSR and KR developed a search strategy; VSK, PSR, KR and AAK searched for trials; VSK, AJ, MAK and KR obtained copies of trials; VSK, PSR, AJ, MAK, KR and AAK selected trials to include; VSK, AJ, AAK and KR extracted data from trials; VSK, AJ and AAK entered data into RevMan; RK, Specialist-Cochrane South Asia carried out the analyses; VSK, KR and AAK interpreted the analysis; VSK, PSR, AJ, MAK, KR and AAK drafted the final review.


The authors thank Cochrane South Asia team, Christian Medical College, Vellore, Tamil Nadu, India, for their help and initiation of the idea during the training period and special thanks to Mr Richard Kirubakaran for the meta-analysis. The authors also thank Dean and Mentor Dr L Krishna Prasad for all the support rendered during the research period.


1. Van Der Weijden F, Dell’Acqua F, et al. Alveolar bone dimensional changes of post-extraction sockets in humans: A systematic review. J Clin Periodontol 2009;36(12):1048–1058. DOI: 10.1111/j.1600-051X.2009.01482.x.

2. Horváth A, Mardas N, et al. Alveolar ridge preservation. A systematic review. Clin Oral Investig 2013;17(2):341–363. DOI: 10.1007/s00784-012-0758-5.

3. Wang HL, Kiyonobu K, et al. Socket augmentation: Rationale and technique. Implant Dent 2004;13(4):286–296. DOI: 10.1097/

4. Artzi Z, Tal H, et al. Porous bovine bone mineral in healing of human extraction sockets. Part 1: histomorphometric evaluations at 9 months. J Periodonto 2000;71(6):1015–1023. DOI: 10.1902/jop.2000.71.6.1015.

5. Morjaria KR, Wilson R, et al. Bone healing after tooth extraction with or without an intervention: A systematic review of randomized controlled trials. Clin Implant Dent Relat Res 2014;16(1):1–20. DOI: 10.1111/j.1708-8208.2012.00450.x.

6. Araújo MG, Silva CO, et al. Alveolar socket healing: what can we learn? Periodontol 2000 2015;68(1):122–134. DOI: 10.1111/prd.12082.

7. Farina R, Trombelli L. Wound healing of extraction sockets. Endod Top 2011;25(1):16–43. DOI: 10.1111/etp.12016.

8. Pagni G, Pellegrini G, et al. Postextraction alveolar ridge preservation: Biological basis and treatments. Int J Dent 2012;2012: 151030. DOI: 10.1155/2012/151030.

9. Bartee BK. Extraction Site Reconstruction for Alveolar Ridge Preservation. Part 1: Rationale and Materials Selection. J Oral Implantol 2001;27(4):187–193. DOI: 10.1563/1548-1336(2001)027<0187:ESRFAR>2.3.CO;2.

10. Frost NA, Banjar AA, et al. The Decision-Making Process for Ridge Preservation Procedures After Tooth Extraction. Clin Adv Periodontics 2014;4(1):56–63. DOI: 10.1902/cap.2013.130013.

11. Fee L. Socket preservation. Br Dent J 2017;222(8):579–582. DOI: 10.1038/sj.bdj.2017.355.

12. Mangano C, Piattelli A, et al. Dense hydroxyapatite inserted into postextraction sockets: a histologic and histomorphometric 20-year case report. J Periodontol 2008;79(5):929–933. DOI: 10.1902/jop.2008.070245.

13. Caplanis N, Lozada JL, et al. Extraction Defect: Assessment, Classification and Management. J Calif Dent Assoc 2005 Nov;33(11):853–863.PMID: 16463907.

14. Ashman A, LoPinto J, et al. Ridge augmentation for immediate postextraction implants: eight year retrospective study. Pract Periodontics Aesthet Dent 1995;7(2):85–94,quiz 95.

15. Lekovic V, Kenney EB, et al. A bone regenerative approach to alveolar ridge maintenance following tooth extraction. Report of 10 cases. J Periodontol 1997;68(6):563–570. DOI: 10.1902/jop.1997.68.6.563.

16. Froum S, Orlowski W. Ridge preservation utilizing an alloplast prior to implant placement-clinical and histological case reports. Pract Periodontics Aesthet Dent 2000;12(4):393–402,;quiz 404.

17. Bolouri A, Haghighat N, et al. Evaluation of the effect of immediate grafting of mandibular postextraction sockets with synthetic bone. Compend Contin Educ Dent 2001;22(11):955.

18. Froum S, Cho S-C, et al. Extraction sockets and implantation of hydroxyapatites with membrane barriers a histologic study. Implant Dent 2004;13(2):153–164. DOI: 10.1097/01.ID.0000127524.98819.FF.

19. Gholami GA, Najafi B, et al. Clinical, histologic and histomorphometric evaluation of socket preservation using a synthetic nanocrystalline hydroxyapatite in comparison with a bovine xenograft: a randomized clinical trial. Clin Oral Implants Res 2012;23(10):1198–1204. DOI: 10.1111/j.1600-0501.2011.02288.x.

20. Esposito M, Grusovin MG, et al. Interventions for replacing missing teeth: horizontal and vertical bone augmentation techniques for dental implant treatment. Cochrane Database Syst Rev 2009(4):CD003607. DOI: 10.1002/14651858.CD003607.pub4.

21. Hong J-Y, Lee J-S, et al. Impact of different synthetic bone fillers on healing of extraction sockets: an experimental study in dogs. Clin Oral Implants Res 2014;25(2):e30–e37. DOI: 10.1111/clr.12041.

22. McCrea SJJ. “Sliding Full-Thickness Pedicle Flap” for Primary Wound Closure of the Socket Preservation Site. J Oral Implantol 2015;41(S1):372–376. DOI: 10.1563/AAID-JOI-D-13-00262.

23. Kim J-J, Schwarz F, et al. Ridge preservation of extraction sockets with chronic pathology using Bio-Oss® Collagen with or without collagen membrane: an experimental study in dogs. Clin Oral Implants Res 2017;28(6):727–733. DOI: 10.1111/clr.12870.

24. Caiazzo A, Brugnami F, et al. Buccal plate preservation with immediate implant placement and provisionalization: 5-year follow-up outcomes. J Maxillofac Oral Surg 2018;17(3):356–361. DOI: 10.1007/s12663-017-1054-3.

25. Jung RE, Ioannidis A, et al. Alveolar ridge preservation in the esthetic zone. Periodontol 2000 2018;77(1):165–175. DOI: 10.1111/prd.12209.

26. AkbarzadehBaghban A, Dehghani A, et al. Comparing alveolar bone regeneration using Bio-Oss and autogenous bone grafts in humans: a systematic review and meta-analysis. Iran Endod J 2009;4(4):125–130.

27. Atieh MA, Alsabeeha NHM, et al. Interventions for replacing missing teeth: alveolar ridge preservation techniques for dental implant site development. Cochrane Database Syst Rev 2015(5): CD010176. DOI: 10.1002/14651858.CD010176.pub2.

28. Barallat L, Ruíz-Magaz V, et al. Histomorphometric results in ridge preservation procedures comparing various graft materials in extraction sockets with nongrafted sockets in humans: a systematic review. Implant Dent 2014;23(5):539–554. DOI: 10.1097/ID.0000000000000124.

29. Jambhekar S, Kernen F, et al. Clinical and histologic outcomes of socket grafting after flapless tooth extraction: a systematic review of randomized controlled clinical trials. J Prosthet Dent 2015;113(5):371–382. DOI: 10.1016/j.prosdent.2014.12.009.

30. Kattimani VS, Kondaka S, et al. Hydroxyapatite-past, present, and future in bone regeneration. Bone Tissue Regen Insights 2016;7: BTRI.S36138. DOI: 10.4137/BTRI.S36138.

31. Avila-Ortiz G, Elangovan S, et al. Effect of alveolar ridge preservation after tooth extraction: a systematic review and meta-analysis. J Dent Res 2014;93(10):950–958. DOI: 10.1177/0022034514541127.

32. De Risi V, Clementini M, et al. Alveolar ridge preservation techniques: a systematic review and meta-analysis of histological and histomorphometrical data. Clin Oral Implants Res 2015;26(1):50–68. DOI: 10.1111/clr.12288.

33. Chan H-L, Lin G-H, et al. Alterations in bone quality after socket preservation with grafting materials: a systematic review. Int J Oral Maxillofac Implants 2013;28(3):710–720. DOI: 10.11607/jomi.2913.

34. Fiorellini JP, Nevins ML. Localized ridge augmentation/preservation. A systematic review. Ann Periodontol 2003;8(1):321–327. DOI: 10.1902/annals.2003.8.1.321.

35. Ten Heggeler JM, Slot DE, et al. Effect of socket preservation therapies following tooth extraction in non-molar regions in humans: a systematic review. Clin Oral Implants Res 2011;22(8):779–788. DOI: 10.1111/j.1600-0501.2010.02064.x.

36. VittoriniOrgeas G, Clementini M, et al. Surgical techniques for alveolar socket preservation: a systematic review. Int J Oral Maxillofac Implants 2013;28(4):1049–1061. DOI: 10.11607/jomi.2670.

37. Horváth A, Mardas N, et al. Alveolar ridge preservation. A systematic review. Clin Oral Investig 2013;17(2):341–363. DOI: 10.1007/s00784-012-0758-5.

38. Iocca O, Farcomeni A, et al. Alveolar ridge preservation after tooth extraction: a Bayesian Network meta-analysis of grafting materials efficacy on prevention of bone height and width reduction. J ClinPeriodontol 2017;44(1):104–114. DOI: 10.1111/jcpe.12633.

39. MacBeth N, Trullenque-Eriksson A, et al. Hard and soft tissue changes following alveolar ridge preservation: a systematic review. Clin Oral Implants Res 2017;28(8):982–1004. DOI: 10.1111/clr.12911.

40. Bassir SH, Alhareky M, et al. Systematic Review and Meta-Analysis of Hard Tissue Outcomes of Alveolar Ridge Preservation. Int J Oral Maxillofac Implants 2018;33(5):979–994. DOI: 10.11607/jomi.6399.

41. Lee J, Lee J-B, et al. Flap Management in Alveolar Ridge Preservation: A Systematic Review and Meta-Analysis. Int J Oral Maxillofac Implants 2018;33(3):613–621. DOI: 10.11607/jomi.6368.

42. Troiano G, Zhurakivska K, et al. Combination of bone graft and resorbable membrane for alveolar ridge preservation: A systematic review, meta-analysis, and trial sequential analysis. J Periodontol 2018;89(1):46–57. DOI: 10.1902/jop.2017.170241.

43. Avila-Ortiz G, Chambrone L, et al. Effect of Alveolar Ridge Preservation Interventions Following Tooth Extraction: A Systematic Review and Meta-Analysis. J Clin Periodontol Jun;46(Suppl 21):195–223. DOI: 10.1111/jcpe.13057.

44. Vignoletti F, Matesanz P, et al. Surgical protocols for ridge preservation after tooth extraction. A systematic review. Clin Oral Implants Res 2012;23(Suppl 5):22–38. DOI: 10.1111/j.1600-0501.2011.02331.x.

45. Oonishi H, Oonishi H, et al. 27—Clinical application of hydroxyapatite. In: ed. T. Kokubo ed.: Bioceramics and Their Clinical Applications. Woodhead Publishing Series in Biomaterials. Woodhead Publishing; 2008. pp. 606–687. DOI: 10.1533/9781845694227.3.606.

46. Kattimani VS, Lingamaneni KP. Natural bioceramics: our experience with changing perspectives in the reconstruction of maxillofacial skeleton. J Korean Assoc Oral Maxillofac Surg 2019;45(1):34–42. DOI: 10.5125/jkaoms.2019.45.1.34.

47. Kattimani V, Lingamaneni KP, et al. Eggshell-derived hydroxyapatite: A new era in bone regeneration. J Craniofac Surg 2016;27(1):112–117. DOI: 10.1097/SCS.0000000000002288.

48. Sampath Kumar TS. Value added bioceramics: A review of the developments and progress in India. Key Eng Mater 2016;696:3–8. DOI: 10.4028/

49. Kumar GS, Thamizhavel A, et al. Microwave conversion of eggshells into flower-like hydroxyapatite nanostructure for biomedical applications. Mater Lett 2012;76:198–200. DOI: 10.1016/j.matlet.2012.02.106.

50. Ashman A. Postextraction ridge preservation using a synthetic alloplast. Implant Dent 2000;9(2):168–176.

51. Damien CJ, Parsons JR. Bone graft and bone graft substitutes: a review of current technology and applications. J Appl Biomater Off J Soc Biomater 1991;2(3):187–208. DOI: 10.1002/jab.770020307.

52. Hench LL, Wilson J. An Introduction to Bioceramics. Singapore: World Scientific; 1993.

53. Habal MB, Reddi AH. Different forms of bone grafts. Bone Grafts and Bone Substitutes. Saunders; 1992. pp. 6–8.

54. Nasr HF, Aichelmann-Reidy ME, et al. Bone and bone substitutes. Periodontol 2000 1999;19(1):74–86. DOI: 10.1111/j.1600-0757.1999.tb00148.x.

55. Tulder MV, Furlan A, et al. Updated method guidelines for systematic reviews in the cochrane collaboration back review group. Spine 2003;28(12):1290–1299.

56. Mayer Y, Zigdon-Giladi H, et al. Ridge preservation using composite alloplastic materials: A randomized control clinical and histological study in humans. Clin Implant Dent Relat Res 2016;18(6):1163–1170. DOI: 10.1111/cid.12415.

57. Machtei EE, Mayer Y, et al. Prospective randomized controlled clinical trial to compare hard tissue changes following socket preservation using alloplasts, xenografts vs no grafting: Clinical and histological findings. Clin Implant Dent Relat Res 2019;21(1):14–20. DOI: 10.1111/cid.12707.

58. Mozzati M, Gallesio G, et al. Socket preservation using a biomimetic nanostructured matrix and atraumatic surgical extraction technique. J Craniofac Surg 2017;28(4):1042–1045. DOI: 10.1097/SCS.0000000000003496.

59. Noronha Oliveira M, Rau LH, et al. Ridge preservation after maxillary third molar extraction using 30% porosity PLGA/HA/β-TCP scaffolds with and without simvastatin: A pilot randomized controlled clinical trial. Implant Dent 2017;26(6):832–840. DOI: 10.1097/ID.0000000000000655.

60. Cavdar FH, Keceli HG, et al. Evaluation of Extraction Site Dimensions and Density Using Computed Tomography Treated with Different Graft Materials: A Preliminary Study. Implant Dent 2017;26(2):270–274. DOI: 10.1097/ID.0000000000000567.

61. El-Chaar ES. Clinical and histological evaluation of ceramic matrix in a collagen carrier for socket preservation in humans. Implant Dent 2016;25(1):149–154. DOI: 10.1097/ID.0000000000000362.

62. Canullo L, Wiel Marin G, et al. Histological and histomorphometrical evaluation of postextractive sites grafted with Mg-enriched nano-hydroxyapatite: A randomized controlled trial comparing 4 vs 12 months of healing. Clin Implant Dent Relat Res 2016;18(5):973–983. DOI: 10.1111/cid.12381.

63. Kentros GA, Filler SJ, et al. Six month evaluation of particulate Durapatite in extraction sockets for the preservation of the alveolar ridge. Implantologist 1985;3(2):53–62.

64. Bell DH.Jr Particles vs solid forms of hydroxyapatite as a treatment modality to preserve residual alveolar ridges. J Prosthet Dent 1986;56(3):322–326. DOI: 10.1016/0022-3913(86)90013-2.

65. Nemcovsky CE, Serfaty V. Alveolar ridge preservation following extraction of maxillary anterior teeth. Report on 23 consecutive cases. J Periodontol 1996;67(4):390–395. DOI: 10.1902/jop.1996.67.4.390.

66. Ripamonti U. Osteoinduction in porous hydroxyapatite implanted in heterotopic sites of different animal models. Biomaterials 1996;17(1):31–35.

67. Barba A, Diez-Escudero A, et al. Osteoinduction by Foamed and 3D-Printed Calcium Phosphate Scaffolds: Effect of Nanostructure and Pore Architecture. ACS Appl Mater Interfaces 2017;9(48):41722–41736. DOI: 10.1021/acsami.7b14175.

68. Götz W, Lenz S, et al. A preliminary study in osteoinduction by a nano-crystalline hydroxyapatite in the mini pig. Folia Histochem Cytobiol 2010;48(4):589–596. DOI: 10.2478/v10042-010-0096-x.

69. Habibovic P, Sees TM, et al. Osteoinduction by biomaterials–physicochemical and structural influences. J Biomed Mater Res A 2006;77(4):747–762. DOI: 10.1002/jbm.a.30712.

70. Hao Y, Yan H, et al. Evaluation of osteoinduction and proliferation on nano-Sr-HAP: a novel orthopedic biomaterial for bone tissue regeneration. J Nanosci Nanotechnol 2012;12(1):207–212.

71. Dewi AH, Ana ID. The use of hydroxyapatite bone substitute grafting for alveolar ridge preservation, sinus augmentation, and periodontal bone defect: A systematic review. Heliyon 2018;4(10): e00884. DOI: 10.1016/j.heliyon.2018.e00884.

72. Bruijn JDD, Shankar K, et al. 9—Osteoinduction and its evaluation. In: ed. T. Kokubo ed. Bioceramics and Their Clinical Applications. Woodhead Publishing Series in Biomaterials. Woodhead Publishing; 2008. pp. 199–219. DOI: 10.1533/9781845694227.1.199.

73. Gosain AK, Song L, et al. A 1-year study of osteoinduction in hydroxyapatite-derived biomaterials in an adult sheep model: part I. PlastReconstrSurg 2002;109(2):619–630.

74. Heliotis M, Lavery KM, et al. Transformation of a prefabricated hydroxyapatite/osteogenic protein-1 implant into a vascularisedpedicled bone flap in the human chest. Int J Oral MaxillofacSurg 2006;35(3):265–269. DOI: 10.1016/j.ijom.2005.07.013.

75. Kattimani VS, Chakravarthi PS, et al. Biograft Block Hydroxyapatite: A Ray of Hope in the Reconstruction of Maxillofacial Defects. J Craniofac Surg 2016;27(1):247–252. DOI: 10.1097/SCS.0000000000002252.

76. Canullo L, Pellegrini G, et al. Alveolar socket preservation technique: Effect of biomaterial on bone regenerative pattern. Ann Anat 2016;206:73–79. DOI: 10.1016/j.aanat.2015.05.007.

77. Pagni G, Pellegrini G, et al. Postextraction alveolar ridge preservation: biological basis and treatments. Int J Dent 2012;2012: 151030. DOI: 10.1155/2012/151030.

78. Kasaj A, Willershausen B, et al. Human periodontal ligament fibroblasts stimulated by nanocrystalline hydroxyapatite paste or enamel matrix derivative. An in vitro assessment of PDL attachment, migration, and proliferation. Clin Oral Investig 2012;16(3):745–754. DOI: 10.1007/s0-011-0570-7.

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