Recent research in secondary alveolar bone grafting for patients with cleft lip and palate has shown growing interest in xenogeneic graft materials, particularly those derived from bovine sources, as potential alternatives to autologous bone [4, 9, 10]. This shift is largely driven by the advantages of xenografts, including greater availability, ease of handling, and the elimination of donor site morbidity [8, 11]. However, autogenous bone remains the most widely used and well-established material for the reconstruction of bone defects. It is considered the gold standard due to its osteoinductive, osteoconductive, and osteogenic properties. With the development of alternative grafting materials, numerous comparative studies have emerged, evaluating the effectiveness of allografts and xenografts relative to autogenous bone in promoting bone healing and regeneration [9, 11,12,13]. Various grafting materials have been utilized for the reconstruction of alveolar cleft defects, including bioabsorbable hydroxyapatite, β-tricalcium phosphate, DMBM, and bone morphogenetic protein-2 (BMP-2). The identification and development of recombinant human BMP-2, in combination with a collagen sponge carrier, have facilitated the clinical use of alloplastic bone grafts even in SABG. A systematic review limited to randomized controlled trials further confirmed the effectiveness of alloplastic materials for SABG in patients with cleft lip and palate [11]. Among these, bovine-derived DMBM—a resorbable cortical xenograft composed primarily of type I collagen—has gained attention due to its osteoinductive properties, biocompatibility, and safety [5, 7]. Although xenograft material such as Bio-Oss® has been widely studied and applied in various clinical procedures—including periodontal bone defects, post-extraction sockets, dehiscence and fenestration defects, bone cavity filling, and sinus lift surgeries—its clinical use in cleft patients has been limited. This caution likely arises from concerns regarding potential complications specific to the cleft site. Despite its broader clinical utility, the application of bovine-derived xenograft materials in secondary alveolar bone grafting (SABG) remains relatively underexplored. Most existing studies, such as that by Francis et al., have reported outcomes over short-term periods ranging from 6 months to 1 year. However, there remains a notable lack of long-term prospective research evaluating critical parameters such as bone volume maintenance and graft resorption over time, as emphasized by Stasiak et al. and Kumar et al. [5, 6, 14]

These studies have investigated parameters such as bone volume augmentation, graft integration, periodontal outcomes, and long-term stability. Although high-level evidence remains limited, early findings suggest that bovine-derived xenografts may offer comparable outcomes to autologous grafts in secondary alveolar bone grafting [1,2,3, 8].

The five reviewed studies consistently reported no statistically significant differences between autogenous and xenogeneic grafts in terms of bone graft volume, density, or height in patients with cleft lip and palate. However, the limited number of direct comparative studies and the considerable methodological variability across the literature constrain definitive conclusions. Bahtiar et al. evaluated graft success using panoramic radiographs and the Bergland scale to quantify alveolar defect closure. Alnajjar et al. used CBCT to assess bone density, with two examiners evaluating grayscale values that were quantitatively converted into Hounsfield units (HU). The study compared autogenous bone chips with bovine bone particles combined with injectable platelet-rich fibrin (I-PRF). Benlidayi et al. utilized panoramic and occlusal radiographs alongside CBCT-based density measurements, applying a semiautomated method to outline and quantify the grafted region. Bezerra et al. measured graft area and volume using an automated navigation system and reported outcomes for xenografts mixed with platelet-rich plasma (PRP). Lastly, Kumar et al. assessed bone volume using the Cavalieri principle applied to CBCT volumetric data, reconstructed and sectioned into 1-mm isotropic slices in the axial plane. To evaluate the newly grafted site with greater precision, they extended the follow-up period, as this method of measurement was only applicable while new bone could still be clearly delineated. As a result, a long-term assessment was conducted, with a mean follow-up duration of 5.25 years (63 months). Despite diverse imaging modalities and evaluation protocols, none of the studies identified significant differences in bone regeneration outcomes between graft types.

While xenografts offer practical advantages such as reduced donor site morbidity and surgical time, their clinical use in SABG for cleft patients has been approached cautiously due to concerns over graft integration and complication risks. Postoperative follow-up periods varied considerably among the included studies, potentially affecting the reliability and comparability of their outcomes. Additionally, the nature of the cleft defect—whether complete or incomplete—was not consistently stratified in the outcome analyses, despite its likely influence on graft behavior. Among the five studies, only Kumar et al. provided long-term data on bone resorption and graft stability, underscoring a significant gap in longitudinal evidence. Evaluation of the methodological quality using the Cochrane risk-of-bias tool revealed that only two studies—Alnajjar et al. and Kumar et al.—were randomized controlled trials (RCTs). Kumar et al. demonstrated the strongest methodological rigor, incorporating clear randomization, allocation concealment, blinding of participants and assessors, and comprehensive long-term follow-up, indicating low risk of bias across most domains. In contrast, the retrospective or pilot nature of the remaining studies introduced several sources of bias, including lack of blinding, unclear outcome reporting, and small sample sizes, particularly in Bezerra et al., which further compromises internal validity.

Recent studies have explored the adjunctive use of platelet concentrates—namely PRP and PRF—with xenogeneic grafts to enhance bone regeneration. A commonly used xenograft material in this context is Bio-Oss® (Geistlich Pharma AG, Wolhusen, Switzerland), a deproteinized bovine mineral matrix with osteoconductive properties. Bio-Oss acts as a tridimensional scaffold supporting the ingrowth of host capillaries and osteoprogenitor cells, thus contributing to new bone formation. Its structure closely resembles human bone, with a natural porous architecture that facilitates revascularization, enhances blood clot stabilization, and promotes the adsorption of endogenous proteins and growth factors [7, 15,16,17]. It is available in various forms—including blocks and granules—and is biocompatible, with no reported induction of local or systemic immune responses.

The rationale behind combining platelet-rich plasma (PRP) with Bio-Oss® lies in its ability to release significant amounts of growth factors that may accelerate bone graft maturation and improve healing [18]. Alnajjar et al. evaluated injectable PRF (I-PRF) in combination with bovine xenografts and assessed postoperative bone density using CBCT. However, their 6-month follow-up revealed no statistically significant improvement compared to autogenous grafts. Likewise, Bezerra et al. mixed Bio-Oss® with PRP in a pilot study but found no significant differences in bone area or volume relative to controls. These findings suggest that while biologic adjuncts like PRP and PRF have theoretical and experimental support, their clinical effectiveness in the context of secondary alveolar bone grafting (SABG) remains inconclusive. The heterogeneity of preparation protocols, short follow-up periods, and limited sample sizes across current studies hinder definitive conclusions. Therefore, further well-designed clinical trials are warranted to better understand the potential synergistic effects of PRP and PRF in enhancing xenograft-based alveolar reconstruction.

Moreover, the nature of the cleft defect prior to grafting—whether complete or incomplete, or varying in size and volume—was not consistently classified or controlled. This lack of standardization may influence the interpretation of graft performance. Additionally, the literature is still limited in terms of randomized controlled trials and long-term outcome data assessing the safety, efficacy, and integration of xenografts.

Further research with larger sample sizes, standardized imaging protocols, and consistent classification of cleft morphology is essential to validate current findings and guide clinical decision-making. Longitudinal studies with well-defined outcome measures will be particularly important to evaluate the long-term stability and integration of xenogeneic grafts in alveolar cleft reconstruction.