Monitorizarea prin CBCT a regenerării osoase potențate de PRP după chirurgia reconstructivă craniofacială pediatrică: studiu observațional prospectiv

Introduction

Craniofacial clefts represent some of the most complex congenital anomalies encountered in pediatric reconstructive surgery, affecting not only facial appearance but also feeding, speech development, dentofacial growth, psychosocial integration, and overall quality of life. Their management requires long-term multidisciplinary care involving pediatric surgeons, plastic surgeons, pediatric dentists, orthodontists, speech therapists, psychologists and imaging specialists. During childhood and adolescence, carefully planned stages of treatment are necessary to restore both facial harmony and function while minimizing long-term morbidity⁽¹⁾.

Among the numerous challenges associated with craniofacial clefts, restoration of alveolar and maxillary bone continuity remains particularly important. Adequate bone regeneration is essential for dental eruption, orthodontic treatment, stabilization of the maxillary arch, closure of residual fistulae and preparation for future reconstructive procedures. Although autologous bone grafting remains the standard approach for alveolar cleft reconstruction, variability in graft integration and postoperative bone remodeling continues to represent a significant clinical concern⁽²⁾.

In recent years, increasing attention has been directed toward biological strategies capable of enhancing tissue regeneration and improving surgical outcomes. Platelet-rich plasma (PRP) is an autologous blood-derived concentrate containing high concentrations of platelets and multiple growth factors involved in wound healing, angiogenesis, osteogenesis and soft tissue regeneration. Growth factors released by activated platelets – including platelet-derived growth factor (PDGF), transforming growth factor beta (TGF-b), vascular endothelial growth factor (VEGF) and insulin-like growth factor (IGF) – have been shown to promote cellular proliferation and tissue repair^(3-5).

The use of PRP in oral and maxillofacial surgery has become more common in the last twenty years. Studies conducted in the past have indicated advantages in promoting soft tissue healing, decreasing postoperative inflammation during surgery, increasing bone density and improving graft integration. Nevertheless, the evidence for its utilization in pediatric craniofacial reconstruction is still limited, particularly in terms of objective imaging evaluation of bone healing^(6-8).

Reliable evaluation of postoperative bone regeneration is fundamental for treatment planning and outcome assessment. While a thorough examination can reveal the mechanisms of wound healing and soft tissue evolution, clinical investigations offer only limited know­ledge about the internal architecture and maturation of newly formed bone. Conventional two-dimensional radiographic techniques may underestimate the complexity of postoperative changes and are often insufficient for accurate volumetric evaluation⁽⁹⁾.

The utilization of cone beam computed tomography (CBCT) is a significant advancement in imaging methods for dentomaxillofacial diagnostics, as it provides high-resolution three-dimensional visualization of craniofacial details with significantly lower radiation doses than conventional computed tomography. CBCT can accura­tely assess the morphology of defects, graft integration, cortical continuity, tramascular organization and postoperative bone remodeling in patients with craniofacial clefts. When used according to contemporary pediatric radiation protection principles, including ALARA and ALADA concepts, CBCT offers a valuable balance bet­ween diagnostic yield and radiation safety^(10-12).

The objective of the present prospective observational study was to evaluate the role of CBCT in monitoring bone regeneration following PRP-assisted pediatric craniofacial reconstructive surgery, as well as its contribution to assessment of graft integration and structural remodeling, and to evaluate treatment outcomes in children with craniofacial clefts.

Materials and method

A. Study design and patient population

This prospective observational study was conducted between March 2025 and June 2026 within the multidisciplinary craniofacial team of “Grigore Alexandrescu” Emergency Clinical Hospital for Children, Bucharest, Romania.

The study evaluated the role of cone beam computed tomography (CBCT) in monitoring bone regeneration following platelet-rich plasma (PRP)-assisted reconstructive surgery in pediatric patients with craniofacial clefts.

Approximately 50 children with various forms of craniofacial clefts were consecutively enrolled in a standardized multidisciplinary treatment protocol during the study period. The protocol included surgical reconstruction, regenerative therapy using PRP, clinical follow-up and imaging assessment when clinically indicated.

The imaging evaluation cohort included 20 patients who had completed the postoperative CBCT follow-up at the time of analysis. This subgroup consisted of 12 boys and eight girls, aged between 5 and 17 years old.

The study population included a broad spectrum of craniofacial cleft phenotypes, including unilateral cleft lip and palate, bilateral cleft lip and palate, isolated cleft palate and complete cleft deformities requiring staged reconstructive management.

The lower number of patients included in the CBCT analysis compared with the overall cohort reflects age-related limitations associated with three-dimensional imaging in pediatric patients. During infancy, the treatment is primarily focused on primary cheiloplasty, and routine CBCT imaging is not indicated. In addition, CBCT acquisition without sedation is frequently not feasible in children younger than 4-5 years old. As a result, postoperative CBCT examinations were exclusively conducted on patients whose imaging evaluation was both clinically and technically feasible.

This study followed the principles of Declaration of Helsinki. During imaging tests and treatment, parents or legal guardians gave written informed consent.

B. PRP protocol

PRP therapy was integrated into the reconstructive treatment pathway as a biological adjunct inten­ded to enhance angiogenesis, tissue healing and bone rege­ne­ra­tion.

The preparation of autologous platelet-rich plasma from peripheral venous blood took place immediately before the procedure. Centrifugation was used to purify blood samples, and the platelet-rich fraction was isolated and administered without any exogenous activating agents or additives.

The treatment protocol consisted of repeated PRP infiltration sessions performed at intervals of approximately three to five weeks. The initial treatment cycle included four infiltration sessions.

In patients requiring alveolar bone grafting, reconstructive surgery was generally scheduled following the third PRP session. A fourth PRP infiltration was performed at the completion of the surgical procedure. Additional platelet-rich plasma sessions were administered according to individual clinical needs and treatment stage.

The rationale for platelet-rich plasma administration was to promote vascularization, stimulate tissue regeneration, support bone healing and improve integration of reconstructed tissues.

C. Surgical reconstruction

All patients underwent reconstructive surgical procedures appropriate to their age, cleft phenotype and stage of treatment.

Surgical interventions included primary and secondary reconstructive procedures, as well as alveolar bone grafting when indicated. Treatment planning was performed within a multidisciplinary team involving pediatric surgeons, pediatric dentists, orthodontists, radiologists and other specialists involved in cleft care.

The main objectives of reconstruction were to restore anatomical stability, improve the quality of life, support dentofacial growth and optimize rehabilitation outcomes over time. The surgical protocol was modified to include PRP therapy as a complementary regenerative approach.

D. CBCT acquisition and imaging evaluation

Postoperative imaging assessment was performed using cone beam computed tomography (CBCT) examinations acquired in specialized dentomaxillofacial imaging centers.

CBCT scans were obtained selectively, and only when imaging findings were expected to influence therapeutic decision-making or provide clinically relevant information regarding bone regeneration and graft integration.

The examinations were generally performed approximately three months after reconstructive surgery, when postoperative healing allowed a meaningful assessment of bone remodeling and when patient cooperation permitted image acquisition without sedation.

In accordance with current radiation protection principles, such as ALARA (As Low As Reasonably Achievable) and ALADA (As Low As Diagnostically Acceptable), all scans were conducted in pediatric low-dose protocols and within restricted field-of-view settings whenever feasible.

Multiplanar reconstructions (axial, sagittal and coronal) together with three-dimensional renderings were analyzed to evaluate:

• reduction in cleft defect volume;
• cortical bone continuity;
• trabecular bone organization;
• integration and stability of bone grafts;
• spatial relationships between regenerated tissues and adjacent anatomical structures.

A standardized imaging evaluation protocol was applied to ensure the consistency of qualitative and semi-quantitative assessment across all patients.

E. Outcome measures

The main focus was on evaluating the postoperative bone growth in reconstructed craniofacial defects through CBCT.

Secondary outcome measures included:

• assessment of bone graft integration;
• evaluation of cortical continuity and trabecular remodeling;
• correlation between imaging findings and clinical healing;
• identification of postoperative complications;
• assessment of the usefulness of CBCT in multidisciplinary treatment planning and follow-up.

Imaging findings were interpreted alongside clinical examinations and the general development of each patient during reconstructive care.

Results

A. Patient characteristics

At the time of analysis, 20 pediatric patients had completed postoperative CBCT follow-up, and were included in the imaging evaluation cohort. The study group consisted of 12 boys and eight girls, aged between 5 and 17 years old.

The cohort included a broad spectrum of craniofacial cleft phenotypes requiring staged reconstructive management. Surgical procedures performed during the study period included alveolar bone grafting (n=11), palatal reconstruction (n=12) and secondary lip revision procedures (n=5). Some patients underwent multiple reconstructive procedures as part of their customized multidisciplinary treatment plan.

B. Clinical outcomes

Postoperative healing was favorable in all patients included in the CBCT evaluation cohort.

No cases of surgical site infection, graft loss, wound dehiscence or formation of postoperative fistula were found among 20 patients surveyed during the follow-up period. In addition, there were no negative outcomes directly linked to PRP implementation.

Two isolated events were documented during treatment. One patient experienced a transient headache episode following the first PRP infiltration session performed without sedation. The episode resolved spontaneously, and it was considered most likely related to procedural stress and anxiety. A second patient presented a transient pseudoseizure-like episode during follow-up. Comprehensive neurological assessment, including magnetic resonance imaging, revealed no pathological findings, and no causal relationship with PRP therapy could be established.

Overall, the PRP protocol demonstrated excellent tolerability, being successfully integrated into the multidisciplinary reconstructive treatment pathway.

C. CBCT findings

All twenty patients included in the imaging cohort underwent postoperative CBCT evaluation at a minimum follow-up interval of three months following reconstructive surgery.

Postoperative CBCT examinations demonstrated progressive bone regeneration in the majority of evaluated patients (Figure 1).

Three-dimensional reconstructions showed reduction of osseous defect dimensions and favorable integration of regenerated tissues within reconstructed anatomical regions. The examination revealed a gradual pattern of cortical continuity and trabecular organization that aligned with the physiological bone remodeling processes, using multiplanarity.

Among the 11 patients who underwent alveolar bone grafting, CBCT evaluation performed at least three months postoperatively demonstrated satisfactory graft positioning and integration within the maxillary arch (Figure 2). Bone graft stability was maintained throughout the observation period, with no radiological evidence of graft displacement, graft failure or clinically significant resorption.

Three-dimensional imaging proved particularly valuable for evaluating the spatial relationships between regenerated bone, adjacent teeth and surrounding maxil­lo­facial structures. CBCT findings facilitated objective postoperative monitoring and supported multidisciplinary treatment planning.

D. Imaging contribution to treatment as­ses­sment

CBCT provided detailed visualization of postoperative bone architecture that could not be reliably assessed through clinical examination alone.

By utilizing both multiplanar analysis and three-dimensional reconstruction, it became possible to assess cortical continuity, trabecular maturation and the interconnectivity between tissues and structural remodeling. These findings contributed to a more comprehensive understanding of postoperative healing and regenerative dynamics following PRP-assisted reconstructive surgery. 

Additionally, the imaging results were especially advantageous for patients undergoing alveolar reconstruction, where the incorporation of cells into the body and the closure of defects are critical aspects to treatment evaluation.

E. Safety profile

No local inflammatory complications, infectious events, allergic reactions, or procedure-related adverse effects attributable to PRP administration were observed within the imaging evaluation cohort.

The absence of clinically significant complications supports the feasibility and safety of incorporating autologous PRP into pediatric craniofacial reconstructive protocols.

Discussion

The management of craniofacial clefts remains one of the most challenging areas of pediatric reconstructive surgery. Successful treatment requires long-term multidisciplinary collaboration involving pediatric surgeons, orthodontists, maxillofacial surgeons, pediatric dentists, speech therapists and radiologists. Among the various treatment stages, the restoration of alveolar continuity and the achievement of stable bone regeneration are essential prerequisites for functional rehabilitation, dental eruption, orthodontic treatment and facial growth.

In recent years, increasing interest has been directed toward the use of autologous platelet-rich plasma (PRP) as a biological adjunct capable of enhancing tissue repair and bone regeneration. PRP represents a concentrated source of growth factors, including platelet-derived growth factor (PDGF), transforming growth factor-beta (TGF-b), vascular endothelial growth factor (VEGF) and insulin-like growth factor (IGF), all of which are known to participate in angiogenesis, osteogenesis and soft tissue healing. The rationale for incorporating PRP into craniofacial reconstruction protocols is therefore biologically plausible and supported by an expanding body of regenerative medicine literature.

The present study evaluated a prospective cohort of pediatric patients undergoing reconstructive surgery for craniofacial clefts in whom a standardized PRP protocol was integrated into the therapeutic approach. Although the study was not designed as a comparative trial, postoperative outcomes were encouraging. No cases of graft failure, postoperative infection, wound dehiscence or fistula formation were observed among the patients included in the CBCT follow-up cohort. Furthermore, the lack of direct adverse reactions to PRP administration suggests that it may be a safe and effective treatment option for children. 

One of the most relevant aspects of the present study is the use of cone-beam computed tomography as an objective monitoring tool for postoperative bone regeneration. The conventional clinical examination fails to provide comprehensive information on internal bone architecture, cortical continuity, graft incorporation and volumetric changes.  The use of CBCT allows the visualization of the reconstructed area on a three-dimensional basis and enables longitudinal assessment of healing processes that cannot be accurately measured through clinical examination.

The representative clinical case presented in Figures 1 and 2 illustrates the value of serial CBCT examinations in documenting the evolution of alveolar reconstruction. Progressive reduction of the osseous defect, maintenance of graft volume and restoration of maxillary continuity were observed following PRP-assisted alveolar bone grafting. The multiplanar CBCT examination revealed successful integration of the grafted region and satisfactory anatomical connections with adjacent developing teeth. The post-processing techniques used in CBCT provide additional diagnostic information, surpassing conventional multiplanar assessment. By utilizing three-dimensional segmentation and volumetric rendering, the craniofacial skeleton, dentition and spatial anatomical relationships can be graphically depicted (Figure 3). These reconstructions can facilitate communication among multidisciplinary team members and may aid in treatment planning, especially for complex craniofacial malformations.

The value of CBCT becomes even more evident in severe forms of cleft pathology. Figure 4 demonstrates a complex craniofacial cleft associated with additional craniofacial anomalies, in which advanced image reconstruction techniques provided information that would have been difficult to obtain using conventional two-dimensional imaging. The conclusions of these studies lend support to earlier reports that emphasize the significance of three-dimensional imaging in diagnosing, planning and monitoring craniofacial anomalies after surgery^(13,14). Furthermore, CBCT-based volumetric assessment has been shown to provide reliable information regarding the long-term stability and remodeling of alveolar bone grafts⁽¹⁵⁾.

An important consideration when using CBCT in children is radiation exposure. In order to justify the use of three-dimensional imaging, it is essential to adhere to current radiation protection principles like ALARA (As Low As Reasonably Achievable) and ALADAIP (As Low As Diagnostically Acceptable, being Indication-oriented and Patient-specific). The CBCT examinations in the current study were conducted only when clinically necessary and as part of the routine multidisciplinary management protocol. Consequently, imaging was not performed in younger children in whom the examination could not be justified or reliably obtained, explaining why only a subset of the overall treatment cohort underwent CBCT evaluation.

The present study has several limitations. Firstly, the number of patients available for postoperative CBCT evaluation remains relatively small. Secondly, the absence of a control group prevents definitive conclusions regarding the independent contribution of PRP to bone regeneration. Thirdly, quantitative volumetric analysis was not performed, and imaging assessment remained predominantly qualitative. Nevertheless, the prospective design, the standardized PRP protocol and the systematic use of CBCT follow-up represent important strengths of the study.

The use of PRP for craniofacial reconstruction could be further explored in future studies with larger patient cohorts, longer follow-up periods and quantitative three-dimensional measurements, which may help develop evidence-based approaches to regenerative pediatric surgery⁽¹⁵⁾.

Overall, the findings of this study suggest that PRP-assisted reconstructive surgery may represent a safe and promising adjunctive strategy in the management of pediatric craniofacial clefts. CBCT proved to be a valuable tool for monitoring bone regeneration and graft integration, providing objective information that supports clinical decision-making throughout the reconstructive process.

Conclusions

PRP-assisted reconstructive surgery appears to be a safe and promising alternative for treating pediatric craniofacial defects. The current prospective cohort demonstrated successful postoperative healing, minimal occurrence of significant issues and satisfactory graft integration during follow-up.

CBCT proved to be a valuable tool for the objective assessment of bone regeneration, graft incorporation and postoperative remodeling. The integration of multiplanar evaluation with advanced three-dimensional reconstruction techniques resulted in clinically important information that couldn’t be obtained through conventional examination methods.

Although larger controlled studies are required to establish the specific contribution of PRP to bone regeneration, the present findings support its feasibility in pediatric reconstructive protocols and highlight the important role of CBCT in the longitudinal monitoring of craniofacial reconstruction.

Future research should focus on larger patient cohorts, quantitative volumetric analyses and long-term evaluation of functional and anatomical outcomes.

Autor corespondent:  Diana-Monica Preda E-mail: diana_monica_preda@yahoo.com

CONFLICT OF INTEREST: none declared.

FINANCIAL SUPPORT: none declared.

This work is permanently accessible online free of charge and published under the CC-BY.