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. 2024 Oct 21;36(2):166–177. doi: 10.1111/clr.14372

Does Injectable Platelet‐Rich Fibrin Combined With Autogenous Demineralized Dentine Enhance Alveolar Ridge Preservation? A Randomized Controlled Trial

Odai Amer 1, Nesma Shemais 1, Karim Fawzy El‐Sayed 1,2,3,✉, Heba Ahmed Saleh 4, Mona Darhous 1
PMCID: PMC11810550  PMID: 39429193

ABSTRACT

Objective

The present trial evaluated the first‐time application of autogenous demineralized dentin graft with injectable platelet‐rich fibrin (ADDG + i‐PRF) versus autogenous demineralized dentin graft (ADDG), in alveolar ridge preservation (ARP) in the maxillary aesthetic zone.

Material and Methods

Twenty‐two maxillary (n = 22) non‐molar teeth indicated for extraction were randomized into two groups (n = 11/group). Extracted teeth were prepared into ADDG, implanted into extraction sockets with or without i‐PRF amalgamation and covered by collagen sponge. Cone‐beam computed tomography scans at baseline and 6 months were compared to assess ridge‐dimensional changes. Keratinized tissue width, patient satisfaction, pain score and chair time were recorded. In the course of dental implant placements at 6 months, bone core biopsies of engrafted sites were obtained and analysed histomorphometrically.

Results

Reduction in ridge width was 1.71 ± 1.08 and 1.8 ± 1.35 mm, while reduction in ridge height was 1.11 ± 0.76 and 1.8 ± 0.96 mm for ADDG + i‐PRF and ADDG, respectively (p > 0.05). Significant differences in keratinized tissue width reduction were notable between ADDG + i‐PRF and ADDG (0.12 ± 0.34 and 0.58 ± 0.34 mm respectively; p = 0.008). Postoperative pain scores were significantly lower in ADDG + i‐PRF (p = 0.012). All patients in the two groups were satisfied with no differences in chair time (p > 0.05). No differences in total percentage area of newly formed bone, soft tissue or graft particles were observed between the groups (p > 0.05).

Conclusions

ADDG alone or in combination with i‐PRF yields similar results regarding ARP clinically, quality of the formed osseous tissues, as well as patients' satisfaction. Yet, the addition of i‐PRF to ADDG tends to preserve the keratinized tissue and lessen postoperative pain.

Keywords: alveolar, autogenous, dentin, extraction, platelets, preservation

1. Introduction

With the thickness of the facial bone being < 1 mm in 90% of cases and < 0.5 mm in about 50% of cases in the anterior maxilla (Braut et al. 2011), exodontia, accompanied by the loss of bundle bone and its functions, is usually followed by significant dimensional changes of the alveolar ridge (Heimes et al. 2021; Van der Weijden, Dell'Acqua, and Slot 2009). Alveolar ridge preservation (ARP) techniques typically involve socket osseous grafting, possibly combined with a barrier membrane or soft tissue graft to seal the socket orifice (Horváth et al. 2013; Stumbras et al. 2019). The primary aim remains to lessen dimensional changes following exodontia along with optimizing the contour of the alveolar ridge, possibly for subsequent prosthetic rehabilitation (Mardas et al. 2023, 2015; Sanz et al. 2015).

Dentin and alveolar bone show comparable biochemical compositions, both consisting of organic and inorganic components (Kim et al. 2013), with related embryonic origins (Melek and Marwan 2016). Similar to alveolar bone, dentin harbours type I and III collagen as well as a variety of growth factors, including bone morphogenic protein (BMP), insulin‐like growth factor‐II (IGF‐II) and transforming growth factor‐β (TGF‐β) (Schmidt‐Schultz and Schultz 2005), and was thus suggested as an alternative grafting material with osteoconductive and osteoinductive properties (Park et al. 2015; Um, Kim, and Mitsugi 2017).

Platelets in turn encompass a variety of growth factors such as b‐fibroblast growth factor (b‐FGF), IGF, vascular endothelial growth factor (VEGF), platelet‐derived growth factor (PDGF) and TGF‐β (Boyapati and Wang 2006). Various platelet concentrates were studied in the field of periodontology, including platelet‐rich plasma (PRP) (Harnack et al. 2009), platelet‐rich fibrin (PRF) (Dohan et al. 2006; Elbehwashy et al. 2021), advanced platelet‐rich fibrin (A‐PRF) (Abdulrahman et al. 2022) and injectable platelet‐rich fibrin (i‐PRF) (Alshoiby et al. 2023; Miron and Zhang 2018; Yusri et al. 2024). A‐PRF and i‐PRF were developed through employment of the low‐speed centrifugation (LSCC) concepts (Choukroun and Ghanaati 2018), to retain increased levels of immune cells, growth factors and cytokines (Wend et al. 2017). When combined with bone grafts, they could provide various advantages, including graft stability and ease of handling for the resulting fibrin bone amalgamate “sticky graft” (Miron, Fujioka‐Kobayashi, Bishara, et al. 2017; Miron, Fujioka‐Kobayashi, Hernandez, et al. 2017; Miron et al. 2023).

The combination of i‐PRF and autogenous dentin graft in ARP was described in a case report (van Orten, Goetz, and Bilhan 2022), suggesting that this combination could be valuable in dimensional ridge preservation as well as obtaining vital and good quality bone structure. To the best of the authors' knowledge, no randomized clinical trials, evaluating the combination of i‐PRF to autogenous demineralized dentin graft (ADDG), are currently present in the literature. Hence, the aim of the present randomized controlled trial was to assess the buccolingual ridge width (primary outcome), as well as the height of buccal and lingual ridges of the socket, pain scores, patient satisfaction, chair time, keratinized tissue width and the quality of the newly formed osseous tissue histologically (secondary outcomes), following the application of i‐PRF with ADDG, in comparison to ADDG alone in ARP. The null hypothesis defined was that no differences would be observed between the two groups in term of buccolingual ridge width.

2. Materials and Methods

2.1. Study Design and Registration

The current study was designed as a double‐blind, randomized, parallel arms‐controlled clinical trial, with a 1:1 allocation ratio to compare i‐PRF and ADDG (test group) to ADDG alone (control group) in ARP of post‐extraction alveolar sockets of the aesthetic zone of the maxilla. The research protocol was registered on www.clinicaltrials.gov in June 2022 (ID:NCT05437172). Research protocol, informed consent templates and biological sample collection requests were approved by the Research Ethics Committee, Faculty of Dentistry, Cairo University, in April 2022 (IRB number: 6|04|22). The trial was conducted in compliance with the ethical principles of the Helsinki Declaration for medical research involving human subjects as revised in Seoul, 2008.

2.2. Recruitment of Participants

The study was conducted at the Faculty of Dentistry, Cairo University, Egypt. Participants were recruited from the outpatient clinic of the Department of Oral Medicine and Periodontology at Cairo University's Faculty of Dentistry, between September 2022 and July 2023. Recruitment of participants was conducted by screening patients who were admitted to the outpatient clinic, requiring tooth extractions for subsequent dental implants placement in the maxillary aesthetic zone, until the desired sample size was achieved.

Potential candidates requiring at least one single‐rooted tooth extraction, with periodontally healthy adjacent teeth in the maxillary aesthetic zone between the two the maxillary 2nd premolars (Stumbras et al. 2020), were screened for eligibility and voluntarily recruited. Teeth were extracted if they were non‐restorable due to tooth fracture, unfavourable crown‐to‐root ratio, and extensive caries (Avila et al. 2009; Elfana et al. 2021). Patients had to be systemically healthy, older than 18 years of age, with good oral hygiene and plaque index < 15%. Following extraction, sockets were checked to assure that they were inside the bony housing and having type 1 subdivision B sockets, with intact four walls and thin labial bone thickness (≤ 1 mm; Kim et al. 2021; Steigmann et al. 2022). Smokers, patients reporting any known allergies or systemic conditions that may compromise healing or bone metabolism (e.g., uncontrolled diabetes or hyperthyroidism), having a history of radiotherapy, chemotherapy or bisphosphonate therapy, females who were pregnant or lactating and patients with poor oral hygiene were excluded.

2.3. Sample Size

Sample size was determined based on a difference in buccopalatal alveolar ridge width (primary outcome) equivalent to 0.6 mm as the minimum clinically acceptable value and a standard deviation of 0.45 mm (Elfana et al. 2021). With a power β = 0.8 and α = 0.05, and based on independent samples t test, 10 sites per group were required to reject the null hypothesis, which was increased to 12 sites to account for a possible 20% dropout rate. Calculations were conducted using PS Power and Sample Size Calculations version 3.1.2.

2.4. Randomization

Participants were randomly assigned to receive either i‐PRF + ADDG (test group) or ADDG only (control group), following atraumatic teeth extraction with a 1:1 allocation ratio. A computer‐generated randomization list (www.randomizer.org) was performed by an investigator (MD) who was not involved in the recruitment for the purpose of concealment. Allocation was concealed in serially numbered, identical and opaque sealed envelopes. The investigator (MD), disclosed the allocation only after the atraumatic extraction step had been completed.

2.5. Blinding

Blinding was feasible for the outcome assessor (NS) and biostatistician (KK). However, it was not possible for the principal investigator to be blinded, given that the surgical procedures of the two groups were fundamentally distinct. Blinding of participants was not possible, as the test group participants were administered a distinct intervention, requiring venous blood withdrawal for the i‐PRF preparation.

2.6. Preoperative Phase

Following patients' inclusion, medical history was obtained, teeth of interest were clinically examined and a periapical radiograph was performed. Participants read and signed informed consents after detailed explanation of the aim of the study, benefits to participants, surgical procedures, harms and timeline. Professional mechanical plaque removal (PMPR) was performed and oral hygiene techniques were explained and emphasized.

2.7. Surgical Procedures

Patients were instructed to rinse with 0.12% chlorhexidine mouthwash (Hexitol, Adco Pharma Co., Egypt). Local anaesthesia was administered using 2% mepivacaine HCL, combined with 1:1000 levonordefrin (Alexandria Company for Pharmaceuticals). The removal of the non‐restorable tooth, using a minimally traumatic flapless extraction technique, was initiated by performing a supracrestal fiberotomy. Following tooth loosening via periotomes (Nordent Manufacturing Inc., IL, USA) and straight thin elevators (Nordent Manufacturing Inc., IL, USA), forceps (Nordent Manufacturing Inc., IL, USA) were used to extract it from its socket, followed by inspection of the integrity of the extraction socket using a periodontal probe.

For the ADDG group: The extracted tooth was thoroughly cleaned of any residual periodontal ligaments, cementum, soft tissue attachments, caries or restorations using a high‐speed fine finishing stone and irrigation by saline. Using sterile endodontic files, the pulp chamber was thoroughly cleaned. Subsequently, the tooth was ground using a bone rongeur and a hand bone mill (Gold Bone Mill, MCT Bio, Korea) to obtain chips powder (Kim 2015). To prepare ADDG particles, tooth graft particles were first demineralized by immersing them in 0.6 N hydrochloric acid for 30 min, followed by twice rinsing with saline and drying, using a sterile gauze (Elfana et al. 2021). Subsequently, the graft was placed into the socket and covered by a collagen sponge and a single crisscross 5‐0 polypropylene suture (Figure 1).

FIGURE 1.

FIGURE 1

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Clinical steps of graft harvesting, demineralization, placement, suturing and 6 months of follow‐up for the test and control groups. i‐PRF withdrawal, mixture of ADDG with i‐PRF in the test group. Biopsy harvesting steps using trephine bure and implant placement.

For the i‐PRF + ADDG group: Following the atraumatic extraction technique and the preparation of the dentin graft as previously described, 10 mm of venous blood was collected in a sterile vacutainer plastic tube. The blood was centrifuged at 700 rpm (60 g‐force) for 3 min (Miron, Fujioka‐Kobayashi, Bishara, et al. 2017; Miron, Fujioka‐Kobayashi, Hernandez, et al. 2017). The i‐PRF liquid layer was collected from the top of the tube and mixed with ADDG. The mixture was then allowed to set for 10 min to produce the sticky ADDG. Subsequently, the sticky ADDG was placed in the socket and covered with a collagen sponge and a crisscross 5‐0 polypropylene suture (Eldawlia Tibbi Atik Medical, Istanbul, Turkey; Figure 1).

2.8. Post‐Operative Care and Follow Up

Participants were instructed to avoid any trauma at the operative site, prevent any interference with the suture and abstain from consuming hot food or rinsing for a period of 24 h (Mani et al. 2021). It was recommended to avoid brushing of the surgical area and resume gentle brushing at the area of the operation after a period of 2 weeks (Alazzawi, Ghazi, and Jikia 2018; Bertoldi et al. 2021; Elfana et al. 2021). Participants were prescribed amoxicillin 500 mg (Misr Co. for Pharmaceutical Industries, Egypt) three times daily for a period of 10 days (Ben Amara et al. 2021; Corning and Mealey 2019) or doxycycline 100 mg (Doxymycin, Nile Co. for Pharmaceutical and Chemical Industries, Egypt) twice daily as an alternative to penicillin sensitivity (Corning and Mealey 2019), along with ibuprofen 600 mg (Brufen, Kahira Pharmaceuticals, Egypt) when necessary to alleviate severe pain (Santos et al. 2021). Additionally, a 0.12% chlorhexidine mouthwash was recommended for gentle rinsing, to be used twice daily for a period of 2 weeks (Demetter, Calahan, and Mealey 2017). On the second day postoperatively, baseline cone‐beam computed tomography (CBCT) was performed. The sutures were removed 2 weeks after surgery. Final follow‐up visits and CBCT scans were carried out 6 months postoperatively.

2.9. Outcomes

2.9.1. Radiographic Outcomes

At parameters of 0.2 mm voxel size, 90 KV and 8 mA, CBCT scans (Planmeca ProMax 3D Classic, Helsinki, Finland) were obtained at baseline and 6 months post‐operatively. Following exposure and image acquisition, these images were called “basis images” and transferred through a network for “Image reconstruction.” Scans were exported in DICOM format to the 3D viewer software (Ondemand 3D, Cybermed, 1.0.9, Seoul, South Korea). Preoperative images were fused to postoperative images using manual registration, followed by automatic registration through landmarks on the jaw (Fettouh et al. 2023). All measurements were first recorded on the primary image. Then the measurement on the primary image was left and the primary image itself was cancelled leaving the secondary image. New measurements were subsequently recorded on the secondary image on the same plane direction and cut of the primary image, ensuring standardization. Buccopalatal ridge width was measured from the outermost surface of the buccal and palatal ridges of the extraction socket at three levels (1, 3, and 5 mm below the most coronal aspect of the bone crest; Al Qabbani et al. 2017; dos Santos Canellas et al. 2020; Jung et al. 2013; Yang et al. 2023). For each image (baseline and six months of follow‐up) a colour code was assigned for identification. After the superimposition, measurements were recorded. The loss in alveolar ridge dimensions was reported by subtracting final values from baseline values and expressed in millimetres and percentages (Figure 2). For the buccal and palatal ridge heights, a tangential line was drawn at the most apical point of the socket depth, parallel to the horizontal plane (line A). This was followed by points marked at the most crestal parts of the buccal and lingual/palatal ridges (Point B). The line was then dropped from point B to line A to measure buccal and lingual/palatal ridge heights. The loss in alveolar ridge dimensions was reported by subtracting final values from baseline values and expressed in millimetres and percentages (Pohl, Binderman, and Tomac 2020; Figure 2).

FIGURE 2.

FIGURE 2

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CBCT images illustrating ridge width measurements (a–c) and ridge height measurements (d–f), (a) initial CBCT scan with ridge width measurements at 1, 3 and 5 mm below the most coronal aspect of the crest, (b) fusion superimposition of the initial and 6 months post‐operative scans, (c) 6 months postoperative scan, (d) initial CBCT scan showing a tangential line drawn at the most apical point of the socket depth parallel to the horizontal plane (*), points marked at the most crestal parts of the buccal and palatal ridges (+) and line dropped from (*) to (+) to measure buccal and palatal ridge heights, (e) fusion superimposition of the initial and 6 months post‐operative scans, (f) 6 months postoperative scan.

2.9.2. Clinical Outcomes

2.9.2.1. Post‐Operative Patient Satisfaction

Patient satisfaction was assessed on the same day of extraction after the completion of the surgical procedures by asking the patients whether they were satisfied about the treatment provided, if they would do it again and whether they would recommend the treatment to others (Shirley and Sanders 2013).

2.9.2.2. Chair Time

Chair time was measured using a timer starting from injection of the local anaesthesia and ending at the completion of sutures in both groups (Ribeiro et al. 2011).

2.9.2.3. Keratinized Tissue (KT) Width

The measurement of KT width was carried out at baseline and 6 months post‐operatively (Hong et al. 2019). Measurements were taken at the vertical distance from a line connecting the two adjacent teeth at the CEJs to the free gingival margin (FGM) using an UNC 15 probe (Nordent Manufacturing Inc., IL, USA).

2.9.2.4. Pain Score

Pain was assessed at the suture removal appointment (Machtei et al. 2019), where the patients reported any pain along the previous 2 weeks after the completion of surgical procedures using a 0–10 visual analogue scale (VAS) in which 0 means no pain while 10 represents the worst pain possible (Santos et al. 2021).

2.9.3. Histological Analysis

Microscopic examination and histomorphometric analysis were conducted on four core biopsies obtained from four patients during implant placement (two from the ADDG + i‐PRF group and two from the ADDG group). A trephine bur with an outer diameter of 3.3 mm and an inner diameter of 2.8 mm (Helmut, Zepf Medizintechnik, Seitingen‐Oberflacht, Germany) was used to obtain bone biopsies prior to implant placement (Figure 2). The collected samples were preserved in 10% formalin solution, decalcified in 10% formic acid for a period of 10–15 days to be prepared for embedding in paraffin blocks, which were then sliced longitudinally into thin histological 5 μm sections. This was followed by staining the prepared histological sections with haematoxylin and eosin (H&E) stain to detect area of newly formed bone and also to inspect any inflammatory changes. Also, Masson's trichromatic (MT) stain was used in other sections for histological inspection and histomorphometric analysis of the quality of the newly formed bone (Figure 3). A Leica Digital Microscope (Leica Digital Microscope, Leica Microsystems, Wetzlar, Germany) was used for the microscopic examination of all histologically stained sections and photomicrographs of some prepared slides were captured. Photomicrographs were taken by Leica Application Suite program (Leica Microsystems, Heerbrugg, Switzerland) for capturing the histological sections examined under the microscope (Leica Microsystems, Heerbrugg, Switzerland). Histomorphometric analysis for all the prepared MT‐stained sections was performed using image analyser software (Leica QWin 500 image analysis software, Leica Microsystems, Heerbrugg, Switzerland). Areas of newly formed bone (as unmineralized (osteoid) bone or mineralized (osseous) bone), along with the remaining graft particles and soft fibrous tissue in marrow spaces were measured using a measuring frame with a surface area of 24,790 μm2. Five fields were carefully selected for each sample in each group (Ersanli, Olgac, and Leblebicioglu 2004) and examined at magnification of ×100. The mean percentages for each group were measured, calculated and recorded (Elfana et al. 2021).

FIGURE 3.

FIGURE 3

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Qualitative histological examination. Representative microscopic images (100× magnification) with haematoxylin and eosin staining of histological sections of ADDG + i‐PRF (a) and ADDG (d) biopsies. Masson trichrome staining of histological sections of ADDG + i‐PRF (b, c) and ADDG (e, f) biopsies. B, newly formed bone; GP, graft particles; OSS, osseous tissue; OST, unmineralized osteoid tissue; ST, soft tissue.

2.10. Statistical Analysis

Data were explored for normality by checking the distribution of data and using tests of normality (Kolmogorov–Smirnov and Shapiro–Wilk tests). Age, buccolingual ridge width, ridge height and chair‐side time data showed normal (parametric) distribution while KTW, reduction in all parameters and pain scores data showed non‐normal (non‐parametric) distribution. Data were presented as mean, standard deviation (SD), median and range values. For parametric data, Student's t‐test was used to compare between mean age and chair‐side time values in the two groups. Two‐way repeated measures ANOVA test was used to compare between the two groups as well as to study the changes by time within each group. Bonferroni's post hoc test was used for pair‐wise comparisons when ANOVA test is significant. For non‐parametric data, Mann–Whitney U test was used to compare between the two groups. Wilcoxon‐signed rank test was used to study the changes by time within each group. Qualitative data were presented as frequencies and percentages. The significance level was set at p ≤ 0.05. Statistical analysis was performed with IBM SPSS Statistics for Windows, Version 23.0. Armonk, NY: IBM Corp.

After performing the histomorphometric analysis and recording the mean and standard deviation values for the area percentage for each histological structure in each study group, statistical analysis was done using an independent t‐test.

The trial was conducted and reported in compliance with the CONSORT guidelines/checklist.

3. Results

3.1. Baseline Characteristics

The present study included a total of 24 participants who were recruited and treated between September 2022 and July 2023, among them, 22 completed their follow‐up (Figure S1). No adverse effects were observed and all participants exhibited complete soft tissue healing at follow‐up. The ADDG + i‐PRF group included six males and five females with mean age of 36.5 ± 10.8 years, while the ADDG group included four males and seven females with mean age of 34.5 ± 4.9 years. The ADDG + i‐PRF group included five incisors, one canine and five premolars, while in the ADDG group, two incisors, two canines and seven premolars were included (Table 1).

TABLE 1.

Descriptive statistics and results of chi‐square, Fisher's exact test and Student's t‐test for comparisons between baseline characteristics in the two groups.

Baseline characteristics ADDG + i‐PRF (n = 11) ADDG (n = 11)
Gender (n, [%])
Male 6 (54.5%) 4 (36.4%)
Female 5 (45.5%) 7 (63.6%)
Age [Mean, SD] 36.5 (10.8) 34.5 (4.9)
Tooth (n, [%])
Incisors 5 (45.5%) 2 (18.2%)
Canine 1 (9.1%) 2 (18.2%)
Premolar 5 (45.5%) 7 (63.6%)
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Abbreviations: ADDG, autogenous demineralized dentin graft; i‐PRF, injectable platelet‐rich fibrin.

3.2. Radiographic Analysis

3.2.1. Bucco‐Palatal Ridge Width

A significant reduction in buccolingual ridge width and height between baseline and six months of follow‐up was notable up in both groups independently (p < 0.001). The mean buccolingual ridge width reduction at 1, 3 and 5 mm was 2.85 ± 2.12, 1.48 ± 0.92 and 0.81 ± 0.92 mm for the ADDG + i‐PRF group, respectively, while the ADDG group showed 2.88 ± 2.16, 1.76 ± 1.36 and 0.77 ± 0.81 mm respectively, with no differences between both groups (p > 0.05, Table 1). The overall width reduction was 1.71 ± 1.08 mm for the ADDG + i‐PRF group and 1.8 ± 1.35 mm for the ADDG group with no difference between the two groups (p > 0.05, Tables 2 and S1).

TABLE 2.

Descriptive statistics and results of Mann–Whitney U test for comparison between reductions in buccolingual ridge width and ridge height measurements (mm) in the two groups.

Level ADDG + i‐PRF (n = 11) ADDG (n = 11) p Effect size (d)
Median (IQR) Mean (SD) Median (IQR) Mean (SD)
1 mm 1.89 (1.07, 4.3) 2.85 (2.12) 2.79 (0.83, 4.26) 2.88 (2.16) 0.948 0.028
3 mm 1.29 (1.09, 1.58) 1.48 (0.92) 1.87 (0.29, 2.73) 1.76 (1.36) 0.532 0.268
5 mm 0.65 (0, 1.45) 0.81 (0.92) 0.93 (0, 1.27) 0.77 (0.81) 0.893 0.056
Overall 1.33 (0.84, 2.58) 1.71 (1.08) 2.03 (0.37, 3.06) 1.8 (1.35) 0.974 0.014
Side ADDG + i‐PRF (n = 11) ADDG (n = 11) p Effect size (d)
Median (IQR) Mean (SD) Median (IQR) Mean (SD)
Buccal 1.32 (0.81, 1.97) 1.33 (0.82) 2.17 (1.37, 2.43) 1.89 (0.89) 0.101 0.747
Lingual 0.71 (0, 1.41) 0.89 (0.98) 1.6 (0.53, 2.81) 1.7 (1.47) 0.137 0.664
Overall 1.14 (0.41, 1.37) 1.11 (0.67) 1.69 (1.08, 2.86) 1.8 (0.96) 0.140 0.664
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Abbreviations: ADDG, autogenous demineralized dentin graft; i‐PRF, injectable platelet‐rich fibrin.

3.2.2. Buccal and Palatal Ridge Height

Mean reduction in buccal and palatal ridge heights were 1.33 ± 0.82 and 0.89 ± 0.98 mm for in ADDG + i‐PRF group, and 1.89 ± 0.89 and 1.7 ± 0.47 mm in the ADDG group respectively, with no difference between both groups (p > 0.05, Table 2). The overall height reduction was 1.11 ± 0.76 mm for the ADDG + i‐PRF group and 1.8 ± 0.96 mm for the ADDG group with no difference between the two groups (p > 0.05, Tables 2 and S2).

3.3. Clinical Outcomes

3.3.1. KT Width

No significant reduction was notable in KT width between baseline and 6 months of follow‐up in the ADDG + i‐PRF group (p > 0.05), while for the ADDG group a significant reduction was evident (p = 0.005). A significant difference in the mean overall KT width after 6 months was further notable between ADDG + i‐PRF and ADDG groups (3.52 ± 1 and 2.33 ± 1.22 mm respectively, p = 0.017, Table 3). The mean overall reduction was significant between the two groups, with 0.12 ± 0.34 mm for the ADDG + i‐PRF and 0.58 ± 0.34 mm for the ADDG group (p = 0.008, Tables 3 and S3).

TABLE 3.

Descriptive statistics and results of Mann–Whitney U test for comparison between reductions in KTW measurements (mm) in the two groups.

Site ADDG + i‐PRF (n = 11) ADDG (n = 11) p Effect size (d)
Median (IQR) Mean (SD) Median (IQR) Mean (SD)
Mesial 0 (0, 0) 0.18 (0.4) 0 (0, 1) 0.45 (0.52) 0.180 0.475
Mid‐buccal 0 (0, 0) 0 (0.63) 1 (0, 1) 0.82 (0.6) 0.008* 1.211
Distal 0 (0, 0) 0.18 (0.4) 0 (0, 1) 0.45 (0.52) 0.180 0.475
Overall 0 (0, 0.33) 0.12 (0.34) 0.67 (0.33, 1) 0.58 (0.34) 0.008* 1.303
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Abbreviations: ADDG, autogenous demineralized dentin graft; i‐PRF, injectable platelet‐rich fibrin.

*

Significant at p ≤ 0.05.

3.3.2. Pain (VAS) Scores, Patient Satisfaction and Chair Time

Significantly lower pain scores were evident in the ADDG + i‐PRF compared to the ADDG group (p = 0.012, Table 4). All patients in the two groups were satisfied; thus, no statistical comparison was performed. Furthermore, no significant difference between chair times in the two groups was notable, with a mean of 68.6 ± 10.5 min and 66.4 ± 10.8 min for ADDG + i‐PRF and ADDG groups respectively (p > 0.05).

TABLE 4.

Descriptive statistics and results of Mann–Whitney U test for comparison between pain (VAS scores) in the two groups.

ADDG + i‐PRF (n = 11) ADDG (n = 11) p Effect size (d)
Median (IQR) Mean (SD) Median (IQR) Mean (SD)
2 (1, 3) 2.18 (1.17) 4 (3, 5) 3.82 (1.33) 0.012* 1.234
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Abbreviations: ADDG, autogenous demineralized dentin graft; i‐PRF, injectable platelet‐rich fibrin.

*

Significant at p ≤ 0.05.

3.4. Histological Evaluation and Histomorphometric Analysis

Regarding the H&E‐stained sections, areas of new bone formation without any inflammatory changes were observed surrounding the graft particles in both groups. On MT‐stained sections, soft unmineralized (osteoid) bone stained blue to green, while hard mineralized (osseous) bone was coloured pink to red. In the ADDG + i‐PRF group, the mean percentage area of mineralized osteoid tissue was 15.5%, mineralized osseous tissue was 33.8%, soft tissue part was 6.5%, and the remaining graft particles were 1.15%. While, for the ADDG group, the mean percentage area of unmineralized osteoid tissue was 10.7%, mineralized osseous tissue was 40.1%, soft tissue part was 14.4% and the remaining graft particles was 0.6%, with no significant differences between both groups (p > 0.05, Table 5).

TABLE 5.

Histomorphometric analysis of percentages of histological tissue for each group.

Newly formed bone Soft tissue part Remaining graft particles
Unmineralized osteoid tissue Mineralized osseous tissue
Mean (SD) Mean (SD) Mean (SD) Mean (SD)
ADDG + i‐PRF 15.5 (7.2) 33.8 (5.9) 6.5 (2.3) 1.15 (1.2)
ADDG 10.7 (9.2) 40.1 (3.9) 14.4 (7.6) 0.6 (0.04)
p‐value 0.5 0.2 0.2 0.5
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Abbreviations: ADDG, autogenous demineralized dentin graft; i‐PRF, injectable platelet‐rich fibrin.

4. Discussion

ARP aims at reducing post‐extraction alveolar bone resorption (Bassir et al. 2018; Stumbras et al. 2019; Tan et al. 2012), thus preserving the dimensions of the alveolar ridge (Mardas et al. 2015; Willenbacher et al. 2016). The maxillary aesthetic region is commonly linked to a greater degree of horizontal and vertical post‐extraction bone resorption, since it possesses mostly a thin labial plate of bone (Chappuis et al. 2013; Couso‐Queiruga et al. 2021). In a recent case report (van Orten, Goetz, and Bilhan 2022), the combination of i‐PRF with autogenous dentin graft was suggested as a valuable alternative for obtaining vital and good quality bone structure in post‐extraction ARP. The aim of the present randomized controlled trial was to compare for the first time the combination of ADDG with i‐PRF versus ADDG alone in ARP of extraction sockets in the maxillary aesthetic region.

Atraumatic tooth extraction was carefully conducted for maximal hard and soft tissue preservation (Singla and Sharma 2020). A collagen sponge sealed all extraction sockets to prevent possible graft displacement or soft tissue downgrowth (Kim et al. 2011). In the current investigation, ADDG was used as it is a non‐antigenic and chair‐side autologous grafting material (Hazballa et al. 2021) for ARP, with studies demonstrating equivalence in its radiologic and histologic outcomes to bone grafts (Cenicante et al. 2021). Earlier findings demonstrated that the ADDG compared to the mineralized dentin form showed better graft remodelling, integration and osteoinductive properties histologically (Elfana et al. 2021). The demineralization process could expose a variety of growth factors contained in the dentin matrix, including IGF‐II, BMP‐2 and TGF‐β (Strauss et al. 2019). Additionally, the combination of i‐PRF with osseous grafting materials (Kyyak et al. 2020, 2021; Nagrani et al. 2023) enhances their handling characteristics forming a “sticky graft” (Miron, Fujioka‐Kobayashi, Bishara, et al. 2017; Miron, Fujioka‐Kobayashi, Hernandez, et al. 2017), in the current trial the “sticky ADDG.”

In line with the current findings, earlier investigations demonstrated the potential of ADDG in ARP (Elfana et al. 2021; Jung et al. 2018). Similar to studies evaluating the effects of autogenous demineralized tooth matrix with PRF membrane (Ouyyamwongs, Leepong, and Suttapreyasri 2019), freeze‐dried bone allograft (FDBA) with PRF (Azangookhiavi et al. 2020), or mineralized dentin graft with chopped PRF (Pohl, Binderman, and Tomac 2020), the current amalgamation of ADDG with i‐PRF yielded comparable results regarding ARP. It is noteworthy to report that all implants subsequently placed, whether in the control or intervention groups, did not need any additional augmentation, similar to previous findings (van Orten, Goetz, and Bilhan 2022).

No significant differences were observed between the ADDG + i‐PRF and the ADDG group regarding alveolar ridge dimensions, with similar patient satisfaction between groups. Furthermore, the i‐PRF preparation process, consisting of venous blood withdrawal followed by a 3‐min centrifugation protocol did not result in a significant difference regarding chair time of both treatments. Yet, in accordance with earlier studies demonstrating the potential of PRF to improve soft tissue healing (Ali and Selim 2018; De Angelis et al. 2019; Kızıltoprak and Uslu 2020), significantly higher KT conservation potential was observed in the ADDG + i‐PRF compared to the ADDG group 6 months following ARP. This could be attributed to the ability of PRF to stimulate the proliferation of dermal gingival fibroblasts and keratinocytes, and its involvement in the production of extracellular matrix components and collagen 1 (Miron, Fujioka‐Kobayashi, Bishara, et al. 2017; Miron, Fujioka‐Kobayashi, Hernandez, et al. 2017). Furthermore, The use of i‐PRF produces higher and sustained release TGF‐β, platelet‐derived growth factors (PDGF), and collagen‐1 molecules and a protection against proteolytic degradation of endogenous fibrogenic factors that are important in wound healing (Choukroun, Aalam, and Miron 2017).

Similarly, in agreement with earlier investigations, demonstrating the ability of PRF to reduce postoperative pain (De Angelis et al. 2019; Marenzi et al. 2015; Pan et al. 2019), in the present study significantly lower pain scores were evident in the ADDG + i‐PRF. These effects could be attributed to the ability of i‐PRF to create a three‐dimensional fibrin scaffold, which in addition to forming a haemostatic plug, enriches the healing site with a variety of cytokines and growth/differentiation factors, endorsing cellular migration, proliferation, angiogenesis, laying down of fibronectin and collagen‐I, tissue formation and epithelization (Bahar, Karakan, and Vurmaz 2024; Choukroun, Aalam, and Miron 2017; Davis et al. 2014; Locatelli et al. 2021; Schär et al. 2015; van Orten, Goetz, and Bilhan 2022). Compared to higher speed centrifugation protocols as employed in L‐PRF, the LSSC of i‐PRF further heightens the levels of these cytokines and growth/differentiation factors (Wend et al. 2017), augmenting its soft and hard tissues healing potentials (Pall et al. 2023; Reda et al. 2021). Additionally, i‐PRF harbours leukocytes and exerts anti‐microbial properties (Kour et al. 2018; Moojen et al. 2008).

Histological evaluations provide an advantage for detecting the quality of newly formed bone (either unmineralized or mineralized) as well as early immune responses surrounding graft particles prior to the appearance of clinical or radiographic evidence. Two weeks following grafting, osteoid tissues are formed and could persist for up to 6 months prior to complete mineralization (Aludden et al. 2020; Wortmann et al. 2020). Qualitatively, similar to earlier findings histological sections of the ADDG + i‐PRF (Alrmali et al. 2023; Andrade et al. 2020) and the ADDG (Elfana et al. 2021) groups demonstrated new bone formation with no inflammatory infiltrates, with a tendency for thicker bone trabeculae in the ADDG + i‐PRF group. In both groups, the ADDG particles seemed to be resorbed and encircled by osteoid tissues with vascularized bone marrow spaces, suggesting the active stage of new bone formation (Forni et al. 2013).

Yet, the present findings should be carefully interpreted within the current trial's limitations. First, as the study involved blood withdrawal for i‐PRF preparation, some patients refused to participate. Furthermore, the blood withdrawal procedure might have influenced the patient's perception and reporting of any postoperative pain in the test group. Secondly, although particles were ground to the clinically most possible size via bone rongeurs and mills, no standardization of the ADDG particle size was possible. Yet due to the subsequent demineralization process differences in mineralized ADDG particle sizes may have been relativized. Thirdly, although the study involved one single‐rooted teeth extraction sites per patient, the use of ADDG in ARP of multiple extraction sockets would have been restricted by its limited availability, relying on the presence of teeth indicated for extraction to provide the allogenic grafting material. Fourthly, generalizability of the findings is not ensured as the current investigation was conducted on single‐rooted teeth and excluded multirooted ones. Fifth, histological sections of higher quality could have provided a more profound base for drawing conclusions of the biological healing events. Finally, chairside preparation of ADDG required considerable time and effort.

5. Conclusions

Both ADDG + i‐PRF or ADDG alone provide effective grafting materials for ARP, with ADDG + i‐PRF possibly associated with easier graft handling, lower patient‐reported pain and enhanced keratinized tissue preservation upon healing. Further randomized clinical trials are needed, standardizing and testing various dentin graft particle sizes as well as ARP effects in molar extraction sockets.

Author Contributions

Odai Amer: conceptualization, methodology, writing – review and editing, investigation. Nesma Shemais: supervision, formal analysis, writing – review and editing, data curation, investigation. Karim Fawzy El‐Sayed: formal analysis, writing – original draft, writing – review and editing, validation. Heba Ahmed Saleh: formal analysis, data curation, writing – review and editing. Mona Darhous: supervision, project administration, writing – review and editing.

Conflicts of Interest

The authors declare no conflicts of interest.

Supporting information

Appendix S1.

CLR-36-166-s001.doc (218.5KB, doc)

Appendix S2.

CLR-36-166-s002.docx (52.6KB, docx)

Acknowledgements

The authors would like to thank the members of Periodontology Department Cairo University for their cooperation and help along the research.

Funding: The authors received no specific funding for this work.

Odai Amer, Nesma Shemais, and Karim Fawzy El‐Sayed contributed equally to the manuscript.

Data Availability Statement

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Appendix S1.

CLR-36-166-s001.doc (218.5KB, doc)

Appendix S2.

CLR-36-166-s002.docx (52.6KB, docx)

Data Availability Statement

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

Articles from Clinical Oral Implants Research are provided here courtesy of Wiley

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