Hyaluronic acid versus microneedling with injectable platelet-rich fibrin in the treatment of partial loss of interdental papillae: A pilot randomized clinical trial

Abstract

Loss of the interdental papilla represents a frequent aesthetic and functional challenge in dentistry. Traditional surgical procedures can partially restore papillary form but are limited by technical sensitivity, donor-site morbidity, and unpredictable long-term results. Consequently, interest has shifted toward minimally invasive, biologically driven strategies for papilla reconstruction. Among non-surgical options, the injection of hyaluronic acid (HA) and the injectable form of platelet-rich fibrin (iPRF) have shown considerable promise. Combining microneedling (MN) enhances trans-mucosal delivery of the biologic agent and can boost regenerative outcomes. Despite promising results, direct comparisons between HA and MN + iPRF remain scarce. Therefore, the present study aims to compare the clinical outcomes of MN + iPRF versus HA gel injection in the reconstruction of Class I interdental papilla loss. This pilot study was conducted as a split-mouth, double-blind, randomized trial to compare the efficacy of MN + iPRF vs. HA injections in reconstructing interdental papillae. A total of seven adult patients (N = 7) were enrolled, contributing 20 interdental papillary sites based on individual clinical presentation. Each site was randomly assigned to one of two treatment groups: Group MN + iPRF (n = 10 sites), and Group HA (n = 10 sites). Clinical parameters measured at baseline, 6 weeks, and 12 weeks included papillary height and papillary width at three levels (base, middle, and tip), and Papillary thickness. Both techniques showed comparable improvements in papillae height and contour over the study period. Intergroup analysis showed no statistically significant difference in all parameters at any time point. This pilot study, with its small sample size, suggests comparable short-term outcomes, but larger studies are needed to determine definitive efficacy. The absence of statistical significance should therefore be interpreted cautiously and does not indicate equivalence between the two treatment approaches.

Introduction

Mucogingival deformities, including gingival recession and loss of interdental papillae, are frequent aesthetic and functional challenges in periodontology (Barakat 2024, Cortellini and Bissada 2018). These conditions are classified under periodontal and peri-implant diseases according to the 2018 World Workshop classification (Cortellini and Bissada 2018). They often result in root exposure, dentin hypersensitivity, plaque accumulation, and unaesthetic “black triangles” between teeth (Barakat 2024, Imber and Kasaj 2021). The interdental papilla represents a critical anatomical component of periodontal tissues occupying the gingival embrasure between adjacent teeth; its integrity supports periodontal health, prevents phonetic and food-impaction problems, and contributes to smile harmony (Joshi et al. 2017, Nordland and Tarnow 1998). When the papilla recedes or is lost, the resultant open gingival embrasure compromises both function and appearance. Kokich et al. (Kokich et al. 2006) demonstrated that black triangles larger than 3 mm are perceived as unattractive by both clinicians and patients, reflecting the strong psychosocial and esthetic impact of these defects.

Nordland and Tarnow introduced a simple classification system for papillary loss based on identifiable anatomical landmarks—the contact point, facial cemento-enamel junction (CEJ), and interproximal CEJ—which enables consistent clinical assessment and standardized outcome measurement. Traditional surgical procedures, including coronally advanced flaps, subepithelial connective-tissue grafts, and tunneling techniques, can partially restore papillary form but are limited by technical sensitivity, donor-site morbidity, and unpredictable long-term results (Dong et al. 2023, Shewale and Puri 2022). Consequently, interest has shifted toward minimally invasive, biologically driven strategies for papilla reconstruction.

Among non-surgical options, hyaluronic acid (HA) injections have shown considerable promise. HA is a glycosaminoglycan naturally abundant in the connective tissue and the extracellular matrix, with its strong hygroscopic and viscoelastic properties that allow volumization and hydration of soft tissue. It also promotes fibroblast proliferation, angiogenesis, and collagen synthesis, contributing to wound healing and tissue regeneration (Bhati et al. 2022, Ni et al. 2021, Sanchez-Perez et al. 2021). Several clinical studies have reported significant gains in papilla height, fill, and black-triangle area reduction after HA injection (Bal et al. 2023, Ficho et al. 2021, Marrelli and Tatullo 2013, Miron et al. 2024). Bal et al. (Bal et al. 2023) observed that combining HA with plasma rich in growth factors (PRGF) enhanced papillary regeneration more effectively than HA alone, emphasizing the potential of biologically active adjuncts to prolong HA’s regenerative effects.

Platelet-rich fibrin (PRF), a second-generation autologous platelet concentrate, provides a reservoir of growth factors such as PDGF, VEGF, and TGF-β, which accelerate neovascularization and extracellular-matrix formation. The injectable form (iPRF) serves as a bioactive scaffold and gradually releases these factors, enhancing soft tissue healing while minimizing immune reactions (Fujioka-Kobayashi et al. 2017, Patel et al. 2024).

Microneedling (MN), first introduced in dermatology as percutaneous collagen induction therapy, involves controlled micro-perforations that stimulate fibroblast activation, collagen deposition, and the release of endogenous growth factors (Iosifidis and Goutos 2019, Choukroun et al. 2001). The technique enhances trans-mucosal delivery of biologic agents and can synergize with materials like HA or PRF to boost regenerative outcomes. In a recent in-vivo study, Fan et al. 2023 demonstrated that combining MN with HA gel significantly improved the regeneration of periodontal soft-tissue when compared with HA alone. Similarly, clinical trials have shown that MN combined with platelet concentrates increases papillary height and gingival thickness, outperforming single-agent therapies (Chetana et al. 2024, Ozsagir et al. 2020, Żurek et al. 2024).

Despite these promising results, direct comparisons between HA and MN + iPRF remain scarce. The biological synergy between mechanical collagen induction and autologous growth-factor delivery may provide a more durable and natural restoration of interdental papilla than passive fillers alone. This approach could overcome the transient effect of HA by stimulating intrinsic tissue remodeling and angiogenesis.

Thus, this study seeks to assess and compare the clinical effectiveness of MN + iPRF and HA gel injection for the reconstruction of Class I interdental papilla loss.

This trial hypothesizes that MN + iPRF will yield greater papillary regeneration, offering a minimally invasive, biologically active alternative to traditional surgical approaches for soft-tissue esthetic rehabilitation.

Materials and methods

Study preparation

This pilot, split-mouth, double-blind, randomized study compares the efficacy of microneedling combined with injectable platelet-rich fibrin (iPRF) versus hyaluronic acid (HA) injections in the reconstruction of interdental papillae. The study was carried out at the post-graduate clinics at the Department of Periodontology, King Abdulaziz University, Faculty of Dentistry, Jeddah, Saudi Arabia, between September 2024 and September 2025. Ethical approval was granted by the King Abdulaziz University, Faculty of Dentistry, Research and Ethics Committee (Approval #117-10-24). Written informed consent was obtained from all participants prior to enrollment. The trial adhered to CONSORT (2010) guidelines (Fig. 1) and the Declaration of Helsinki (2013) (Schulz et al. 2010), and was registered at Clinicaltrials.gov (registration ID: NCT07280507. “Retrospectively registered”), with all primary and secondary outcomes predefined prior to participant recruitment and unchanged throughout the study.

Fig. 1.

CONSORT flow chart of the study. Enrollment, allocation to microneedling + iPRF or hyaluronic acid, follow-up, and analysis across baseline, 6 weeks, and 12 weeks. Notes: N = number of participants. n = number of sites

Given the exploratory nature, a convenience sample of 20 sites was recruited. The inclusion criteria were age between 18 and 45 years, Plaque index = 0 (Silness and Loe 1964), Gingival index = 0 (Loe and Silness 1963), Class I papillary loss (Nordland and Tarnow classification) (Nordland and Tarnow 1998), probing depth ≤ 4 mm at the test site, and interproximal bone crest distance ≤ 7 mm from the contact point. Patients with controlled systemic conditions, including well-controlled type 2 diabetes (HbA1c ≤ 6.5%), were eligible for inclusion. Exclusion criteria included: pregnancy, lactation, uncontrolled systemic diseases (e.g., uncontrolled diabetes), anticoagulant therapy, recent radiotherapy, orthodontic treatment, midline diastema, high frenum attachment, and Class II/III papillary loss.

A total of seven adult patients (N = 7) were enrolled, contributing 20 interdental papillary sites based on individual clinical presentation. Each site was randomly assigned to one of two treatment groups: Group MN + iPRF (n = 10 sites), which received microneedling with iPRF, and Group HA (n = 10 sites), which received hyaluronic acid injection (Juvéderm Ultra, Allergan). Randomization was achieved using computer-generated random numbers and a sealed opaque envelope method to allocate 10 right-side and 10 left-side designations. The surgeon drew one envelope to determine which treatment (MN+ iPRF or HA) would be applied to each site. The split-mouth design effectively controlled for intrasubject variability, improving internal validity, while double-blinding minimized experimenter and response biases.

Patients received standardized oral hygiene instruction and supragingival prophylaxis 1 week prior to the baseline measurement. The iPRF was prepared by drawing one tube of venous blood from the antecubital vein, placing it into anticoagulant-free Choukroun iPRF 13 ml tubes, and centrifuging at 700 rpm for 3 min using a Process for PRF centrifuge system (Choukroun PRF Duo Quattro Centrifuge). The freshly obtained iPRF (0.2 mL) was immediately injected into the papilla using a 0.25 mm x 6 mm sterile insulin syringe (BD Microfine Plus), followed by microneedling with a sterile blood lancet to create microchannels (ACCU-CHEK^®). This was performed at baseline and 3 weeks, with a standalone microneedling booster session (no iPRF) at 1 week. The control site received 0.2 mL of HA gel, split into 0.1 mL at baseline and 0.1 mL at 3 weeks. All procedures were performed under local anesthesia (2% Mepivacaine with 1:100,000 epinephrine). After the injection, patients were advised to avoid mechanical plaque control in the treated area for the first 24 h and to use a 0.2% chlorhexidine digluconate mouthwash twice daily. Following the initial 24 h, they were instructed to resume gentle brushing with a soft toothbrush in combination with the mouthwash.

A blinded, calibrated examiner performed all clinical assessments. Intra-examiner reliability for continuous clinical measurements was assessed using intraclass correlation coefficients (ICCs), which demonstrated excellent reproducibility (ICC > 0.90). All instruments were calibrated, and measurement procedures were standardized across all patients to ensure validity and reliability. At baseline, pocket depth, bone-to-contact distance, and gingival recession type were recorded. Clinical parameters measured at baseline, 6 weeks, and 12 weeks included papillary height, assessed by transgingival bone sounding under local anesthesia from the bone crest to the papilla tip; papillary width at three levels (base, middle, and tip) using a UNC-15 periodontal probe; and papillary thickness, which was measured using an endodontic K-file size 10 with a silicone stop inserted perpendicularly into the soft tissue 2 mm apical to the midbuccal region (Chetana et al. 2024). Standardized intraoral photographs were also taken using a camera with cheek retractors and occlusal mirrors under consistent lighting.

Statistical analysis

Descriptive statistics (mean ± standard deviation) summarized baseline and follow-up values (6 weeks and 12 weeks) within each group. Longitudinal and between-groups comparisons were analyzed using linear mixed-effects models. Linear mixed-effects models inherently accommodate missing observations under the missing-at-random assumption; therefore, all available data were included in the analyses without imputation. For each outcome, fixed effects were group (MN + iPRF vs. HA) and time (baseline, 6 weeks, 12 weeks), with their interaction; random effects were specified as sites nested within subjects. Pairwise contrasts (inter-group differences at each time point and intra-group change over time from baseline) were estimated from marginal means with false discovery rate (FDR) adjustment. Analyses were performed in R software version (4.5.1) within RStudio version (2025.05.1) (R Core Team 2025) using the packages lme4, lmerTest, and emmeans. The percent change from baseline to 6 and 12 weeks was calculated for each clinical parameter, with values expressed as percentages relative to baseline, where positive values indicate increases and negative values indicate decreases. In addition, correlations among clinical parameters for each group were assessed using the repeated-measures correlation (rmcorr) package, with results reported as the repeated-measures correlation coefficient (r_rm) (Bakdash 2017), P-values from (rmcorr) were corrected with FDR. A p-value < 0.05 was considered statistically significant.

Results

Study population

Seven participants met the inclusion criteria and were enrolled (N = 7). Participants’ mean age was 30.29 ± 6.78 years; the study population included 5 men (71%) and 2 women (29%). All participants were healthy except one individual with well-controlled diabetes. Some participants contributed to more than one site. The split-mouth design included 20 interdental papillae, with 10 sites randomly assigned to HA and 10 to MN + iPRF. All participants completed the baseline and 6 weeks visits; one participant was lost to follow-up at 12 weeks (Fig. 1). No adverse events were reported at any visit across the 12-week follow-up. Figure 2 illustrates representative clinical photographs of the upper anterior teeth of one patient included in our study at baseline, 6 weeks, and 12 weeks follow up. The interdental papilla between teeth #12 and 11 was treated with HA. While the papilla between teeth #21 and 22 was treated with MN + iPRF. The photographs demonstrate the clinical changes observed over the follow up period after administering both treatment modalities.

Fig. 2.

Clinical changes observed over the follow-up period after administering both treatment modalities. The photographs (a), (b), (c) show the interdental papilla between teeth #12 and 11, treated with HA, at: (a) baseline, (b) 6 weeks, and (c) 12 weeks. Photographs (d), (e), (f) show the interdental papilla between teeth #21 and 22, treated with MN + iPRF, at: (d) baseline, (e) 6 weeks, and (f) 12 weeks, respectively

Inter-groups clinical parameters comparisons across time

Between-group comparisons of clinical parameters for HA and MN + iPRF sites are summarized in Table 1.

Table 1.

Clinical parameters over time by treatment group

Parameter	Time	n (sites per group)	HA (Mean ± SD)	MN + iPRF (Mean ± SD)	P-Value†
Papilla Height (mm)	Baseline	10	7.4 ± 1.075	8.1 ± 1.37	0.125
	6 Weeks	10	8.1 ± 0.966	8.5 ± 1.08	0.375
	12 Weeks	9	8.167 ± 1.414*	8.722 ± 1.202	0.240
Papilla Thickness (mm)	Baseline	10	6.9 ± 1.838	6.95 ± 1.907	0.883
	6 Weeks	10	6.95 ± 1.423	7.3 ± 1.874	0.305
	12 Weeks	9	7.222 ± 0.667	7.222 ± 0.667	0.993
Average Papilla Width (mm)	Baseline	10	2.483 ± 0.611	2.667 ± 0.643	0.300
	6 Weeks	10	2.417 ± 0.345	2.367 ± 0.463	0.776
	12 Weeks	9	2 ± 0**	2.167 ± 0.333*	0.371
Papilla width at base (mm)	Baseline	10	3.85 ± 1.055	4.1 ± 0.994	0.406
	6 Weeks	10	4 ± 0.624	3.7 ± 0.823	0.320
	12 Weeks	9	3 ± 0**	3.389 ± 0.697	0.222
Papilla width at middle (mm)	Baseline	10	2.4 ± 0.516	2.5 ± 0.527	0.543
	6 Weeks	10	2.15 ± 0.337	2.3 ± 0.483	0.363
	12 Weeks	9	2 ± 0*	2.111 ± 0.333	0.528
Papilla width at tip (mm)	Baseline	10	1.2 ± 0.422	1.4 ± 0.459	0.117
	6 Weeks	10	1.1 ± 0.316	1.1 ± 0.211*	1.000
	12 Weeks	9	1 ± 0	1 ± 0**	1.000

†Inter-group comparisons p-values are from linear mixed-effects models with FDR adjustment; intra-group changes from baseline were assessed from the same models; asterisks denote statistical significance (*P < 0.05; **P < 0.01). Zero standard deviation values indicate identical recorded measurements among sites at the 12-week evaluation. Abbreviations: HA hyaluronic acid, MN + iPRF microneedling + iPRF

At baseline, bone-to-contact distance was similar between groups (MN + iPRF: 6.55 ± 1.343 mm; HA: 6.65 ± 1.564 mm; p = 0.969), and pocket depth was also comparable (MN + iPRF: 2.90 ± 0.394 mm; HA: 2.80 ± 0.587 mm; p = 0.538).

At baseline, papilla height was slightly higher in MN + iPRF than HA (8.1 ± 1.37 mm vs. 7.4 ± 1.075 mm; p = 0.125). Papilla thickness was comparable (MN + iPRF: 6.95 ± 1.907 vs. HA: 6.9 ± 1.838; p = 0.883). Average papilla width was also similar (MN + iPRF: 2.667 ± 0.643 mm vs. HA: 2.483 ± 0.611 mm; p = 0.300). At 6 weeks, papilla height increased in both groups (HA: 8.1 ± 0.966 mm; MN + iPRF: 8.5 ± 1.08 mm; p = 0.375). Papilla thickness and average width remained comparable in both groups with no significant difference.

At 12 weeks, papilla height remained slightly higher in MN + iPRF than HA without statistical significance (MN + iPRF: 8.722 ± 1.202 mm vs. HA: 8.167 ± 1.414 mm; p = 0.240). Average papilla width decreased in both groups, measuring 2.167 ± 0.333 mm in MN + iPRF and 2.00 ± 0.00 mm in HA (p = 0.371). Overall, HA and MN + iPRF showed no statistically significant between-group differences at any time point for papilla height, papilla thickness or papilla width across the 12-week follow-up. These findings do not necessarily indicate equivalence between the treatment groups and warrant cautious interpretation.

Intra-group changes over time in clinical parameters

Changes over time in papilla height, papilla width, and papilla thickness for each treatment group are shown in Fig. 3A–C and summarized in Table 2.

Fig. 3.

Changes Over Time in Clinical Parameters by Treatment Group. Box-and-whisker plots show site-level distributions for HA (blue) and MN + iPRF (orange) at Baseline, 6 weeks, and 12 weeks for: (A) Papilla Height (mm), (B) Papilla Width (mm), and (C) Papilla Thickness (mm). Points represent individual sites; boxes indicate median and interquartile range (IQR). Dashed lines represent group means across time. Sample sizes: baseline and 6 weeks n = 10 sites per group; 12 weeks n = 9 per group. Brackets with asterisks denote within-group significant change from baseline (p < 0.05 = *, p < 0.01 = **; FDR-adjusted). Abbreviation: HA, hyaluronic acid; MN + iPRF, microneedling + iPRF

Table 2.

Percent change in clinical parameters from baseline to 6 and 12 weeks by treatment group

Parameter	Week	n (sites per group)	Percent change in HA (%)†	Percent change in MN (%)†	Mean Difference (%)‡
Papilla height	6 weeks	10	10.786	6.369	4.417
	12 weeks	9	11.706	11.067	0.639
Papilla thickness	6 weeks	10	2.289	6.440	-4.151
	12 weeks	9	2.687	2.585	0.102
Average width	6 weeks	10	0.909	-5.726	6.635
	12 weeks	9	-16.873	-16.997	0.123
Width at base	6 weeks	10	9.333	-4.000	13.333
	12 weeks	9	-18.333	-15.000	-3.333
Width at middle	6 weeks	10	-8.333	-3.333	-5.000
	12 weeks	9	-14.815	-14.815	0.000
Width at tip	6 weeks	10	0.000	-11.667	11.667
	12 weeks	9	-11.111	-24.074	12.963

† Percent change from baseline was calculated as the relative change from baseline to follow-up, expressed as a percentage; positive values indicate an increase, and negative values indicate a reduction. ‡ Mean difference indicates the difference in percent change between the HA and MN groups. Abbreviations: HA hyaluronic acid, MN microneedling + iPRF

In the HA group, papilla height increased from 7.4 ± 1.075 mm at baseline to 8.167 ± 1.414 mm at 12 weeks, representing a statistically significant gain of + 11.7% (p = 0.025). In the MN + iPRF group, papilla height increased from 8.1 ± 1.37 mm to 8.722 ± 1.202 mm, an + 11.1% increase that did not reach statistical significance. Average papilla width decreased significantly from 2.483 ± 0.611 mm to 2 ± 0 mm in the HA group (p = 0.009; −16.9%) and from 2.667 ± 0.643 mm to 2.167 ± 0.333 mm in the MN+ iPRF group (p = 0.048; −17.0%). At 12 weeks, reductions were also observed in papilla width at the base (HA: −18.3%; MN: −15.0%), middle (both groups: −14.8%), and tip (HA: −11.1%; MN: −24.1%). Papilla thickness showed only small, non-significant increases over the 12-week follow-up in both groups (HA: +2.7%; MN: +2.6%).

Associations over time among clinical parameters

In the HA group, papilla height was inversely correlated with papilla thickness (r_rm = − 0.463; 95% CI, − 0.751 to − 0.026; p = 0.040). Papilla height was also inversely correlated with average papilla width but not statistically significant (r_rm = − 0.443; 95% CI, − 0.740 to − 0.001; p = 0.050). In contrast, average papilla width was positively correlated with papilla thickness (r_rm = 0.521; 95% CI, 0.102 to 0.783; p = 0.019).

In the MN + iPRF group, papilla height demonstrated a moderate, inverse but non-significant correlation with papilla thickness (r_rm = − 0.320; 95% CI, − 0.668 to 0.143; p = 0.170), and no other statistically significant correlations were observed in clinical parameters.

Discussion

Reconstruction of missing interdental papilla remains a challenging aspect of periodontal and restorative dentistry. Several surgical and non-surgical modalities have been proposed for papillary reconstruction. However, the esthetic outcomes and long-term stability of these techniques have varied across studies. This variability may be attributed to several factors. These include the complex anatomy of the papillary region, limited vascularity, and the influence of different local and restorative factors (Barakat 2024). The present study aimed to evaluate the efficacy of MN combined with iPRF compared to HA gel injection in reconstructing Class 1 interdental papilla defects, both of which represent minimally invasive modalities for papilla reconstructions.

The results of our study demonstrated favorable improvement in papillary height and reduction in width in both groups over the 12-week study period. However, no statistically significant differences in height and width gains were observed between the groups after 6 and 12 weeks of treatment. Additionally, changes in papilla thickness were not significant in either group from baseline to 12 weeks. Overall, the findings indicate that the two approaches yielded comparable short-term results. The intergroup comparison showed that papilla height remained slightly higher in MN + iPRF than in HA at 12 weeks. However, the difference was not statistically significant. This suggests that mechanical micro-injuries induced by microneedling may accelerate soft tissue regeneration. In contrast, HA primarily acts as a volumizing filler.

The controlled micro-injuries created by fine needles trigger a regenerative healing response. This response causes platelets to release cytokines (PDGF, FGF, TGF). These cytokines recruit fibroblasts and endothelial cells. As a result, collagen synthesis and angiogenesis are stimulated. Although microneedling was originally developed for dermatological use, it has recently been adopted in dentistry for gingival tissue regeneration. The Combination of iPRF with microneedling provides a synergistic effect. This enhances and accelerates the wound healing process (Vhanmane et al. 2025).

Contrary to expectations, no significant gain in gingival thickness was observed from baseline to 12 weeks. A recent meta-analysis of five randomized clinical trials examining the efficacy of iPRF in gingival biotype modification reported a significant increase in gingival thickness at three and six months. Furthermore, the combination of iPRF with microneedling yielded superior outcomes compared with iPRF alone (Idris et al. 2024). In agreement with our findings, Özsagir et al. also reported no statistically significant difference in gingival thickness at one and three months when iPRF combined with microneedling was compared to iPRF alone. A significant difference was observed only after six months, with gingival thickness increasing from 0.78 ± 0.12 mm to 1.00 ± 0.14 mm in the microneedling group, and from 0.77 ± 0.10 mm to 0.93 ± 0.12 mm in the iPRF group (Ozsagir et al. 2020).

It should be emphasized that most studies comparing MN + iPRF to HA gel injection that reported an increase in gingival thickness used these techniques to modify the gingival biotype. These studies did not report changes in papilla thickness and height.

Within-group analysis showed that the HA group exhibited a statistically significant increase in papilla height, while the MN + iPRF group showed a non-significant increase. This suggests the HA may cause an early volumizing effect. One case report evaluated iPRF injections for papilla reconstruction in 4 patients at 6 different sites. It showed a reduction in the distance from the tip of the papilla to the contact point. A complete papillary fill was observed in three sites after six months of injections, and the reduction in the black triangle surface area was correlated with the clinical exam (Puri et al. 2022).

On the other hand, a case series evaluating the use of different HA gel concentrations for papillary augmentation across 42 sites reported a significant improvement of about 18% at 6 months, with 39% in photographic analysis (Singh and Vandana 2019). Another prospective clinical trial applied HA gel using subperiosteal tunneling made apical to the base of the papilla in 17 patients. The trial demonstrated a significant reduction in the papillary defect height at 1, 3, and 6 months, with an overall reduction reaching 45% (Hamadeh et al. 2024). Ni et al. evaluated the effect of 1.6% HA gel on gingival papilla augmentation and reported modest increases in papillary height and volume at 6 and 12 months. Reductions of 13.6% and 23.6% were achieved in deficient areas at these respective time points (Ni et al. 2019). However, most studies indicate that HA gel outcomes remain inferior to those observed with PRGF-enhanced interventions. This suggests that biologically active materials may be more effective than passive fillers in promoting sustained tissue remodeling. A recent prospective clinical study by Adel et al. introduced a novel combined injectable approach consisting of hyper diluted calcium hydroxyapatite (CaHA) with hyaluronic acid for interdental papillae regeneration. Significant improvements in papillae height and width were observed. Peak results were obtained at three months and maintained at the six month follow up period. The results also showed high patient satisfaction with no reported complications. This study further supports minimally invasive techniques in the treatment of interdental papillae regeneration. It also shows that combining bioactive materials with volumizing fillers may enhance regenerative results (Adel et al. 2025).

Although a reduction in papilla width was observed, this finding may reflect contour adaptation or tissue contraction rather than true regenerative change. In the absence of a quantitative assessment of black triangle area or volumetric changes, its interpretation as definitive aesthetic improvement remains limited. The pattern of width reduction varied among the groups. The HA injection provides a homogeneous volumizing effect, which may explain the significant reduction in the base and middle parts. In contrast, the microneedling group showed a significant reduction at the tip of the papilla.

Surgical approaches for papilla reconstructions, such as the interproximal tunneling technique or advanced papillary flaps with subepithelial connective tissue grafts or acellular dermal matrix, continue to yield mixed outcomes. Their limitations include poor vascularization, technical sensitivity, and variable long-term predictability. A systematic review by Patel revealed that the use of connective tissue graft is the most effective method for papilla reconstruction compared to PRF. A study that compared the efficacy of semilunar coronally positioned flap with subepithelial connective tissue graft versus iPRF in class 1 and 2 black triangles showed significant improvement in both groups, but the esthetic outcome was superior in the connective tissue graft group. The study also reported faster healing and greater patient comfort with the iPRF group (Punse et al. 2025). Our findings support microneedling combined with iPRF as a simple, minimally invasive, and biologically potent alternative. It avoids donor site morbidity and offers more predictable soft tissue enhancement. This is particularly relevant for patients seeking a conservative approach. The study contributes to the emerging paradigm shift toward nonsurgical soft tissue regenerative therapies. As surgical modalities remain the gold standard for severe cases, approaches such as MN + iPRF may serve as effective adjuncts or alternatives for mild to moderate papillary defects.

The present investigation is subject to several limitations that must be considered when interpreting the results. The relatively small sample size may have reduced the statistical power of the analysis and restricted the generalizability of the results. Given the pilot design and limited number of participants and sites, the study was underpowered to detect intergroup differences. Therefore, the absence of statistically significant differences should not be interpreted as evidence of equivalence between treatments but rather as preliminary, hypothesis-generating findings with potential risk of Type II error. Although statistically significant improvements in papillary height were observed, the absolute magnitude of change was modest. Moreover, whether changes of this magnitude translate into clinically perceptible esthetic improvement cannot be determined from the present data. Additionally, variability in oral hygiene practices, compliance with postoperative instructions, and follow-up attendance contributed to heterogeneity within the sample. Another significant limitation is the absence of patient-reported outcome measures (PROMs), particularly given the esthetic nature of papilla reconstruction procedures. While clinical improvement in outcomes provides objective evidence of treatment efficacy, it does not capture patients perceived satisfaction or benefits. The lack of patient satisfaction questionnaires limits our ability to determine whether the measured outcomes are valuable for patients. Future studies should include standardized PROMs to ensure that clinical success aligns with patient satisfaction. Moreover, our findings report only short-term outcomes. The long-term stability and durability of our clinical results cannot be assessed during our current study period. Also, one important methodological consideration in the present study is the difference in treatment intensity between the two intervention arms. The MN + iPRF group received injection and microneedling at baseline and 3 weeks, in addition to a standalone microneedling session at 1 week, whereas the HA group received injection only at baseline and 3 weeks. Because microneedling itself is known to stimulate angiogenesis, fibroblast proliferation, and collagen remodeling through controlled mechanical microtrauma, the additional microneedling session in the MN + iPRF group may contribute to clinical improvements if done in larger studies. Moreover, one participant presented with controlled diabetes mellitus. Although glycemic levels were within acceptable clinical limits and no delayed healing was observed, systemic metabolic conditions may influence periodontal regenerative outcomes. Given the limited sample size, the potential impact of this variable cannot be fully excluded and should be controlled for in future studies. Despite those limitations, our study presented a predictable minimally invasive technique for reconstructing interdental papillae, a key esthetic and functional challenge, particularly in the anterior region. By demonstrating a biologically driven approach with favorable outcomes, this study contributes to the evolution of strategies in soft tissue management around natural teeth and implants.

Future research on minimally invasive techniques for papillary reconstruction and gingival biotype modification should aim to address limitations in the current literature by including a larger, more diverse study population. Additionally, the technique in the study’s protocol needs to be standardized to allow better comparison. This includes the follow-up duration, the number of iPRF injections required to achieve a significant result, and the outcome assessment methods. Importantly, future studies should incorporate patients’ reported outcomes, satisfaction with the results, and the treatment’s cost-effectiveness.

Conclusion

Considering our study’s limitations, the findings of this pilot, split-mouth, double-blind, randomized study indicate that the use of either HA or MN + iPRF with a booster session for the reconstruction of Class 1 papillae yields favorable short-term results. Both techniques demonstrate improvement in papillae height and contour over the 12-week study period. Inter-group parameters showed no statistically significant differences in papillae height, width, and thickness. Although intra-group analysis showed that the use of HA increased papillary height, most likely due to its early volumizing effect, the use of MN + iPRF resulted in higher papillary height gains at 12 weeks, possibly due to its regenerative effects. However, due to the limitations of our study, no evidence of superiority of one technique over the other can be concluded. Also, given the limited sample size and pilot nature of the study, the absence of statistical significance should be interpreted cautiously and cannot be considered evidence of equivalence between the two treatment protocols. Moreover, the lack of long-term data prevents the assessment of the stability and durability of clinical outcomes. In addition, the lack of PROMs is a significant limitation as patient satisfaction with clinical outcomes cannot be assessed.

Future research should aim to address our study’s limitations, such as using larger sample sizes and longer follow-up durations, incorporating more groups (e.g., iPRF alone, microneedling alone, and HA+ microneedling), and reporting patient satisfaction with minimally invasive papillary reconstructive procedures.

Author contributions

A.J. Conceptualized the idea. S.B Performed the Formal Analysis and Data Curation. A.B, A. A, A.B, R.A. M.A Wrote the manuscript. R. A, J.A., O.K., R.A., B.S., and M.A. Performed the investigation. B. O. and T. Z Performed the methodology. All authors reviewed the manuscript.

Data availability

The data supporting the findings of this study are subject to ethical restrictions and cannot be made publicly available. However, they may be accessed from the corresponding author upon request and with appropriate ethical approval.

Declarations

Competing interests

The authors declare no competing interests.