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   Table of Contents    
ORIGINAL ARTICLE
Year : 2019  |  Volume : 23  |  Issue : 5  |  Page : 448-460  

Comparison of microsurgical and macrosurgical technique using bioactive synthetic bone graft and collagen membrane for an implant site development: A randomized controlled clinical trial


Department of Periodontology, Teerthanker Mahaveer Dental College and Research Centre, Moradabad, Uttar Pradesh, India

Date of Submission12-Dec-2018
Date of Acceptance04-Jun-2019
Date of Web Publication29-Aug-2019

Correspondence Address:
Dr. Deepali Jain
Department of Periodontology, Teerthanker Mahaveer Dental College and Research Centre, Moradabad, Uttar Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jisp.jisp_738_18

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   Abstract 


Background: Implant site development can be effective in minimizing postextraction alveolar ridge resorption in the esthetic region. Microsurgical approach has demonstrated substantial improvement in soft-tissue architecture. Aim and Objectives: The aim of the present study was to evaluate and compare the efficacy of microsurgical technique with conventional one for implant site development utilizing biphasic hydroxyapatite/beta-tricalcium phosphate bone graft substitute and collagen membrane. Materials and Methods: Thirty extraction sites were planned for implant placement and randomly divided into control (macrosurgical/conventional) and test (microsurgery) sites. Clinical measurements were recorded at four different points of extraction socket, i.e., mesiobuccal, midbuccal, distobuccal, and midlingual/palatal at baseline, 3, 6, and 9 months. Postoperative neovascularization at control and test site was evaluated by ultrasound Doppler flowmetry at baseline, 10th day, and 1 month. Radiological assessment of bone density (Hounsfield units) was measured at control and test sites at baseline, 6 and 9 months by computed tomography. Data was subjected to statistical analysis. Results: Significant socket fill at all the four different sites was observed and found to be statistically significant at test as compared to control group with better tissue contour after 3, 6, and 9 months. Test group demonstrated better neovascularization (P < 0.05) with significantly higher bone density (P = 0.000) at different time intervals. Conclusions: The results indicate that the augmentation of extraction sockets, not only improved the quality of bone in both the techniques but the utilization of microsurgical instruments and microsutures under magnification definitely enhanced the quality of soft tissues which is imperative for successful implant placement and its survival.

Keywords: Beta-tricalcium phosphate, biphasic hydroxyapatite, collagen membrane, computed tomography, implant site development, magnification, microsurgery, microsutures, ultrasound Doppler flowmetry


How to cite this article:
Jain D, Mohan R, Singh VD. Comparison of microsurgical and macrosurgical technique using bioactive synthetic bone graft and collagen membrane for an implant site development: A randomized controlled clinical trial. J Indian Soc Periodontol 2019;23:448-60

How to cite this URL:
Jain D, Mohan R, Singh VD. Comparison of microsurgical and macrosurgical technique using bioactive synthetic bone graft and collagen membrane for an implant site development: A randomized controlled clinical trial. J Indian Soc Periodontol [serial online] 2019 [cited 2019 Nov 15];23:448-60. Available from: http://www.jisponline.com/text.asp?2019/23/5/448/265539




   Introduction Top


Implant site development refers to a variety of procedures aimed at augmenting the ridge to optimize implant positioning for excellent aesthetics and function. Periodontist has a better understanding of the dynamics and anatomical and biological concepts of the periodontium and peri-implant tissues. Adequate quality and quantity of bone at the implant site is a crucial factor for successful osseointegration of an implant. Post tooth extraction, the alveolar ridge inevitably undergoes remodeling with associated resorption and the diminished size of the ridge, which can result in compromised esthetic and functional outcomes of implant.[1] Augmentation of extraction socket has been proposed to preserve the bony contour along with the overlying soft tissues.[2]

Several therapeutic approaches have been attempted to preserve ridge dimensions including use of biomaterials, platelet-rich plasma, various bone graft materials, membranes, or combination techniques. An ideal graft material placed in alveolar sockets prevents the volume reduction that often occurs following tooth extraction and remains in situ until sufficient healing (bone formation) has occurred.[3] A plethora of bone grafts available today for the purpose of bone regeneration. Recently introduced biphasic formulation consists of sterile synthetic nanocrystalline hydroxyapatite and beta-tricalcium phosphate (β-TCP) composite bone graft and is claimed to be effective for ridge augmentation due to combined actions of its constituents. β-TCP resorbs rapidly helping in early bone mineralization, whereas the slower resorption of hydroxyapatite helps in bone ingrowth by providing a scaffold for calcification.[4],[5],[6] Barrier membranes can retain bone grafts during socket augmentation by excluding nonosteogenic cells from populating the healing area. Membranes made of resorbable material such as collagen are increasingly replacing e-PTFE membranes, their benefit being the avoidance of a second surgical procedure for removal.[7],[8]

The method of augmentation can also have implications on the final treatment outcome. Procedures that are less traumatic and minimally invasive have the potential for greater preservation of socket dimensions. Microsurgical techniques have been a recent advancement with a wide range of applications in periodontal surgery.[9],[10] Performing minimally invasive techniques under magnification with microsurgical instruments and fine suturing material results in lesser tissue trauma and precise wound closure which eventually leads to faster wound healing.[11]

Since there is limited literature comparing microsurgical with conventional techniques for an implant site development using bone graft and barrier membrane, the present study has been conducted to evaluate and compare the minimal intervention microsurgery with the conventional surgery for an implant site development in humans.


   Materials and Methods Top


Study design

A single centered, randomized controlled clinical trial was conducted in the department of periodontology. Ethical clearance was obtained before the commencement of the clinical trial from the Institutional Ethical Committee in accordance with Helsinki Declaration.[12] Informed consent was obtained from all the patients.

The study consisted of multiple fresh anterior extraction sockets either in maxilla or mandible having at least 7-mm residual alveolar bone height and intact socket walls. Patients with systemic diseases, history of drug allergy, smoking or tobacco chewing habits, and periapical pathology were excluded from the study.

After completion of initial therapy, 30 extraction sites from 9 patients (aged 30–55 years) were equally allotted to control group (conventional) and test group (microsurgery), 15 for each group. Allocations were performed utilizing randomization software.

Stent fabrication

A study cast of each patient was prepared with impressions obtained before the scheduled extraction at the surgical areas. The teeth to be extracted were removed from the cast, and an acrylic stent was fabricated on it with an opening aligned with the socket. Grooves were marked at four locations, i.e., mesiobuccal (MB), midbuccal (MidB), distobuccal (DB), and midlingual/palatal (MidL/P) on stent.

Surgical protocol

Intraoral photographs and computed tomography (CT) scans were obtained for each subject before the procedure [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]. Patients were instructed to rinse with chlorhexidine-digluconate 0.2% before surgical procedure. The surgical area was anesthetized with lidocaine 1: 80,000 (LIGNOX™). A flapless atraumatic extraction was carried out using periotomes (Uniti #UN633001, 002, 003) without any incisions [Figure 7]. All sockets were thoroughly curetted to remove infected tissue along with the debridement of pocket walls, followed by irrigation with saline [Figure 8], [Figure 9], [Figure 10]. Each socket was filled with commercially available bone graft, i.e., biphasic hydroxyapatite and β-TCP (Sybograf Plus™, Eucare Pharmaceuticals (P) Ltd., India), condensed till the coronal most point of the socket, and then covered with collagen membrane (Healiguide ®, Advanced Biotech, India) which helped contain the graft material [Figure 11], [Figure 12], [Figure 13]. At test sites, the procedure was performed under ×5.5 magnification by utilizing surgical microscope (LYZER™, India), microsurgical instruments (Obtura Spartan KIS kit, Germany), and microsuturing was performed using 6-0 braided silk (nonresorbable, Vicryl™, Johnson and Johnson), while at control sites, conventional surgical instruments (Hu-Friedy-USA) were used for the procedure without using any magnification device and suturing was done with 4-0 braided silk (nonresorbable, MERSILK™, Ethicon, Johnson and Johnson) [Figure 14], [Figure 15], [Figure 16]. Patients did not wear any prosthesis during postoperative healing period to avoid interference in the dimensions of augmented sockets. Patients were prescribed Amoxicillin 500 mg (Novamox, Cipla Limited, India) three times a day for 5 days and tablet Diclofenac sodium 50 mg thrice a day for 3 days and instructed to rinse with chlorhexidine gluconate 0.2% mouthwash two times daily for 15 days. All patients were reviewed at 3, 6, and 9 months.
Figure 1: Intraoral photograph of case 1

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Figure 2: Intraoral photograph of case 2

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Figure 3: Intraoral photograph of case 3

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Figure 4: Computed tomography scan of case 1 before extraction depicting alveolar bone height

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Figure 5: Computed tomography scan of case 2 before extraction depicting alveolar bone height

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Figure 6: Computed tomography scan of case 3 before extraction depicting alveolar bone height

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Figure 7: Atraumatic extraction of teeth at control (a) and test (b) sites by periotome

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Figure 8: Extraction sockets of control (white arrows) and test sites (black arrows) after debridement - case 1

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Figure 9: Extraction sockets of test (white arrow) and control group (black arrow) after debridement - case 2

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Figure 10: Extraction sockets of control (white arrow) and test group (black arrow) after debridement - case 3

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Figure 11: Bone graft placement till the crest of the alveolar bone and sites covered with collagen membrane at control site (a and b) and test site (c and d) of case 1

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Figure 12: Bone graft placement till the crest of the alveolar bone and sites covered with collagen membrane at test group (a and b) and control group (c and d) of case 2

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Figure 13: Bone graft placement till the crest of the alveolar bone and sites covered with collagen membrane at control group (a and b) and test group (c and d) of case 3

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Figure 14: Closure of the extraction socket by suturing. 4-0 suture at control site (a); and by 6-0 suture at test site (b) - case 1

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Figure 15: Closure of the extraction socket by Suturing. 6-0 suture at test site (a); and by 4-0 suture at control site (b) - case 2

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Figure 16: Closure of the extraction socket by Suturing. 4-0 suture at control site (a); and by 6-0 suture at test site (b) - case 3

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Clinical evaluation

Clinical measurements were recorded to evaluate the distance between alveolar crest at four different points, i.e., MB, MidB, DB, and MidL/P marked on individual surgical stent of all the patients with the help of UNC 15 probe (Hu-Friedy, USA). The probe tip was located on the crest of bone, and the angulation of probe was guided by markings on the stent and clinical assessment of soft-tissue healing, tissue architecture and contour were recorded immediately after surgery (baseline), 3, 6, and 9 months [Figure 17], [Figure 18], [Figure 19].
Figure 17: Clinical evaluation by the fabrication of surgical stent with the following markings: mesiobuccal, midbuccal, distobuccal, midlingual/palatal (a) Baseline measurements were recorded by UNC Probe at control site and at test site (b); 3 months evaluation of gingival contour at control site (c) (black arrow) and test site (d) (white arrow); 6 months evaluation at control site (e) (black arrow) and test site (f) (white arrow); 9 months gingival contour assessment at control site (g) (black arrow) and test site (h) (white arrow) - case 1

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Figure 18: Clinical evaluation by the fabrication of surgical stent with the following markings: mesiobuccal, midbuccal, distobuccal, midlingual/palatal (a) Baseline measurements were recorded by UNC Probe at test site and at control site (b); 3 months' evaluation of gingival contour at test site (c) (black arrow) and control site (d) (white arrow); 6 months' evaluation at test site (e) and control site (f); 9 months' gingival contour assessment at test site (g) (black arrow) and control site (h) (white arrow) - case 2

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Figure 19: Clinical evaluation by the fabrication of surgical stent with the following markings: mesiobuccal, midbuccal, distobuccal, midlingual/palatal (a) Baseline measurements were recorded by UNC Probe at control site and at test site (b); 3 months' evaluation of gingival contour at control site (c) (black arrow) and test site (d) (white arrow); 6 months' evaluation at control site (e) and test site (f); 9 months' gingival contour assessment at control site (g) (black arrow) and test site (h) (white arrow) - case 3

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Radiographic evaluation

CT scans of all control and test sites (Ingenuity Core128, Philips, India) were acquired immediately after the surgery (baseline). Height of the socket, buccolingual width at 1/4th, ½, and 3/4th [Figure 20], mesiodistal (MD) width were measured and density of the sockets in the Hounsfield units was recorded at apical, middle, and coronal 1/3rd of the socket as well as at mesial, distal, buccal, palatal, or lingual wall. Radiographic evaluation and interpretation were done at 6 and 9 months [Figure 21], [Figure 22], [Figure 23].
Figure 20: Diagrammatic representation of extraction socket for the evaluation of parameters

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Figure 21: Computed tomography scan image. Formation of bone at control site (a) (white arrow) and test site (b) (yellow arrow), after 6 months; 9 months' evaluation at control site (c) (white arrow) and test site (d) (yellow arrow) - case 1

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Figure 22: Computed tomography scan image. Formation of bone at test site (a) white arrow and control site (b) yellow arrow, after 6 months; 9 months' evaluation at test site (c) and control site (d) - case 2

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Figure 23: Computed tomography scan image. Formation of bone at control site (a) white arrow and test site (b) yellow arrow, after 6 months; 9 months' evaluation at control site (c) and test site (d) - case 3

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Assessment of vascularity using ultrasound Doppler flowmetry

To assess the neovascularization at control and test sites, ultrasound Doppler flowmetry was used. The ultrasound imaging was performed with an ACUSON X300™ (Siemens GE, USA), with four-dimensional transducer. Each patient underwent ultrasound Doppler flowmetry immediately after surgery (baseline), 10th day and 1 month [Figure 24], [Figure 25], [Figure 26].
Figure 24: Ultrasound Doppler flowmetry. Baseline evaluation shows no changes at both the sites control site (a) (white arrows) and test site (b) (yellow arrows); Evaluation at 10th day and 1 month depicts improved blood flow at test site (d and f) (yellow arrows) than control site (c and e) (white arrows) - case 1

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Figure 25: Ultrasound Doppler flowmetry. Baseline evaluation shows no changes at both the sites test site (a) white arrows and control site (b) yellow arrows; Evaluation at 10th day and 1 month depicts improved blood flow at test site (c and e) than control site (d and f) - case 2

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Figure 26: Ultrasound Doppler flowmetry. Baseline evaluation shows no changes at both the sites control site (a) white arrows and test site (b) yellow arrows; Evaluation at 10th day and 1 month depicts improved blood flow at test site (d and f) than control site (c and f) - case 3

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Statistical analysis

The obtained data was subjected to statistical analysis using Statistical Package for Social Sciences software program (SPSS version 20.0, IBM, Chicago, USA). The values were represented in mean ± standard deviation. A t-test, paired t-test, and bivariate correlation were used. P < 0.05 is considered statistically significant, with <0.001 considered highly significant and >0.05 considered as not statistically significant. The results were tabulated and plotted as graphs. Measurements were recorded by a single examiner, and surgical procedure was performed by the same operator.


   Results Top


A randomized controlled clinical trial was conducted to evaluate and compare the efficacy of microsurgery (test) with conventional (control) surgery for an implant site development using synthetic bone graft and collagen membrane. During the study, wound healing was uneventful in all the patients without any complication, and none of them dropped out before the termination of the study. Results of the study were statistically analyzed as follows.

Clinical measurements were recorded at baseline, 3, 6, and 9 months for control and test Group. The mean MB values of control and test groups at baseline were 10.07 ± 1.49 and 10.47 ± 1.41 which declined to 4.03 ± 0.88 and 2.30 ± 0.65, respectively, after 9 months. Similarly, they were recorded for MidB, DB, and MidL at the same intervals as MB [Table 1].
Table 1: Clinical measurements at different study intervals showing mean values and standard deviation of all the variables in (mm) for control and test groups

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The comparison of change in clinical measurements at different time intervals in two groups from baseline to 3, 6, and 9 months revealed that change in all the four variables were negative and statistically significant (P = 0.000) [Table 2] and [Graph 1].
Table 2: Mean change in clinical measurements in control and test groups at different time intervals with t and P values

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Intergroup comparison of mean changes in MB, MidB, DB, and MidL/P of control and test group at baseline, did not yield any significant difference between two groups (P > 0.05). When 3, 6, and 9 months results were compared to baseline, statistically significant higher reduction in Test group was observed as compared to control for MB, MidB, and MidL/P (MB, P= 0.00; MidB, P < 0.001, MidL) except DB (0.21, P > 0.05). No significant difference between the two groups was seen at DB; however, the mean value for DB measurement was lower in test as compared to the control group [Table 3].
Table 3: Intergroup comparison of clinical measurements at baseline, 3, 6 and 9 months for mesiobuccal, midbuccal, distobuccal and midlingual sites (mm) with mean and standard deviation

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Radiological evaluation was carried out for control and test groups at different time intervals [Table 4]. At baseline for socket height, buccolingual (BL) width at ¼, the mean value of test group was lower as compared to control group while for BL width at ½, BL width at ¾, and MD width the mean value of test was higher as compared to control group. For the assessment of density at apical, coronal, and distal wall, the mean value of test group was lower as compared to control group while the mean value for middle, mesial, buccal, and palatal variables were higher in test group as compared to control group. No statistically significant difference was seen between the two groups. At 6-month evaluation, mean radiographic measurements for all the variables were not statistically significant. In the control group, at 9 months, significant change was observed from baseline for all the variables except for MD width. In test group, all the changes were positive and statistically significant [Graph 2] and [Graph 3].
Table 4: Radiographic measurements at different study intervals showing socket height, buccolingual width, mesiodistal width (millimeter) and density (Hounsfield unit) for control and test groups with mean values and standard deviation

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The comparison of change in radiographic parameters at different time intervals in two groups from baseline to 6 and 9 months revealed that in control group, significant changes were seen from baseline for all the variables except for MD width (0.170, P > 0.05). In test group, for all the variables, the changes were positive and statistically significant (P > 0.05) [Table 5].
Table 5: Mean change in radiographic measurements at different study intervals showing socket height, buccolingual width, mesiodistal width (millimeter) and density (Hounsfield unit) for control and test groups with t and P values

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The significance of intergroup comparison has been discussed at different time intervals. At baseline, for all the variables, no statistically significant difference was seen between the two groups (P > 0.05). At 6 and 9 months' intervals, the mean value of all the parameters was not statistically significant except the mean value of MD width (0.009 and 0.001; P < 0.05) that demonstrated significantly higher in test group as compared to control [Table 6].
Table 6: Intergroup comparison of Radiographic measurements in Control and Test groups at different time intervals for socket height, buccolingual width, mesiodistal width (millimeter), density (Hounsfield unit) with t and P values

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Percentage changes of ultrasound Doppler flowmetry scores from 10th day to 1 month were 22.01% and 20.73% in control and test sites, respectively, and were statistically significant (P < 0.05) [Table 7] and [Graph 4].
Table 7: Comparison of ultrasound doppler flowmetry scores of control and test groups at baseline, 10th day and 1 month their differences from baseline with t and P value

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   Discussion Top


The success of osseointegrated implants requires an astute evaluation of the edentulous site. Alveolar ridge resorption following tooth removal is a physiologically undesirable and inevitable phenomenon with potential implications on the stability of implants.[3] Significant considerations begin with the preservation of the alveolar process that houses the roots to be extracted and decisions as to whether it is advantageous to preserve or augment these areas to protect the morphology of the proposed implant site.[13]

The shift in the paradigm from the fixed partial denture to the implant has placed new emphasis on the management of the extraction wound. Sound knowledge of the healing process of extraction wound and various histologic events is required for a clinician to make an implant site perfect, especially in the esthetic zone. The management of soft tissue by minimally invasive technique can have a significant effect on the wound healing process and subsequent integrity of the edentulous site.[1],[14]

The present study was conducted to evaluate and compare the efficacy of microsurgical over macrosurgical/traditional technique using biphasic hydroxyapatite and β-TCP bone graft and collagen membrane for an implant site development. Clinical and radiographic evaluation of control and test sites has revealed that for the changes in socket height, buccolingual width, MD width, and density, proved to be better at microsurgical sites than the conventional ones. These findings are supported by previously performed studies conducted by Burkhardt et al., Francetti et al., and Latha et al.[10],[15],[16]

Clinical measurements at MB, MidB, DB, and MidL aspects demonstrated that there was decrease in the socket height at both the surgical sites. Test sites clinically healed faster and better with lesser bone resorption than the control sites over a 9 months' period. Microsurgery offers certain benefits over conventional approach, in that the incisions can be accurately mapped, tissue manipulation could be done with minimal trauma, and wound can be closed without tension thus enhancing the healing potential of tissues. Approximation of incision edges is also more precise, enabling healing by primary intention although this was not followed in the present study as no effort was made to approximate wound edges over the surgical wound, the rationale being, any attempt at primary wound closure may cause compression of the socket walls thereby compromising the implant site dimensions.[17] Biphasic hydroxyapatite and β-TCP bone graft were used along with the collagen membrane at both control and test sites. Most graft material has been used as filling materials in fresh extraction sockets to avoid collapse of the membrane.[18] The graft serves as a supporting structure for the surrounding soft tissues in the extraction sockets preventing their collapse, whereas the membrane may aid in protecting the graft material in the extraction socket.

The comparison of radiological measurements of socket height, buccolingual width at ¼, ½, ¾ in both groups at 6 months were similar and not significant except for MD width was found to be higher in test group as compared to control group. The results obtained are comparable with those of previous studies conducted by Madan et al., and Loveless et al.[19],[20]

The increase in socket height was observed in test sockets at 9 months was significant as compared to control ones. The change in buccolingual width was positive for both the sites but the change was more significant in test sites as compared to control sites. Quality of bone is important for implant placement and is crucial for the overall success of the implant.[21] The most common failure observed due to collapse of the buccal wall of sockets in maxillary anterior region.[22]

Soft tissue architecture was found to be better at microsurgical site than the conventional site, which is important in terms of placing implants or prosthesis.[10] Issues regarding interimplant papilla while planning implant placement or prosthesis can also be solved by this technique as soft tissue deformity around the dental implant is a common finding in the esthetic zone.[23],[24]

Ultrasound Doppler flowmetry at 10th day and 1 month revealed a marked improvement in vascularization at microsurgically treated sites. This can be explained by the lesser tissue and blood vessel trauma and faster anastomosis of blood vessels resulting from a minimally invasive technique utilizing finer microsurgical instruments together with microsutures causing minimal surgical trauma.[25]

Present clinical trial support the wound healing studies conducted by Nobuto et al., Oliver et al. about revascularization of subepithelial connective tissue grafts starting shortly after the surgical procedure and lasting for about 10 days. It may be assumed that reduced vessel and tissue injury may facilitate the development of faster neovascularization.[26],[27],[28]

Minimal intervention periodontal surgeries with the use of magnification tools combined with microsurgical instruments could provide the best solutions while treating various periodontal conditions including ridge/socket augmentation and implant site development procedures. The potential benefits include reduction of healing time and pain with minimal postoperative inflammation optimizing the outcome. A minimal intervention approach for socket augmentation has been practiced for the first time in the present study with promising results.

Dental operating microscope guarantees an ergonomic working posture, optimal shadow-free illumination of the operation area, with a wide range of magnification. These advantages are countered by increased expense of the equipment, an extended learning phase, technique sensitivity, and prolonged operative period.


   Conclusions Top


Reconstruction of lost alveolar bone is still a challenge. Ridge preservation and/or augmentation techniques can minimize the resorption process and improve the quality of bone for successful implant placement and its long-term survival. Various innovative surgical techniques have been attempted. Recently, minimally invasive surgical techniques are being practiced for various periodontal and peri-implant conditions. The utilization of magnification with the selection of appropriate microsurgical instruments and microsutures has proved to be better over the conventional methods allowing delicate manipulation of tissues.

The success of an implant-supported rehabilitation is strictly influenced by both the density and volume of bone and the quality of soft tissues at the implant site. Although both microsurgical and macrosurgical/conventional techniques have demonstrated significant socket fill over the period of 9 months, microsurgical procedures for implant site development has been very effective in improving soft-tissue architecture due to minimal surgical trauma, precise tissue approximation, superior vascularization, and faster postoperative healing minimizing papilla-related issues with implants. Hence, a clinician should consider the surgical intervention, that is, minimally invasive and more predictable.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9], [Figure 10], [Figure 11], [Figure 12], [Figure 13], [Figure 14], [Figure 15], [Figure 16], [Figure 17], [Figure 18], [Figure 19], [Figure 20], [Figure 21], [Figure 22], [Figure 23], [Figure 24], [Figure 25], [Figure 26]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]



 

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