This study compared the histological outcomes of DBBM with two different particle sizes during maxillary sinus floor elevation. It was concluded that there was no difference between the two DBBM preparations in histology and maxillary sinus floor lift by searching, screening and analyzing the previous literature. The two groups were similar in terms of percentage of connective tissue, the percentage of newly formed bone, and percentage of residual xenograft.

Multiple bone substitutes can be used in maxillary sinus elevation. According to the source of the materials, they can be divided into four categories: autografts, allografts, xenografts, and synthetic bone substitutes [16].

Autografts itself has osteogenic potential, and can be used as a scaffold for osteogenesis to play a role in osteoconduction and osteoinduction. The latter three types of bone substitutes lack osteoblastic cells, which mainly provide scaffolds for the formation of new bone and play the roles of osteoconduction and osteoinduction.

For maxillary sinus bone grafting with autogenous bone, a second surgical area needs to be opened to obtain sufficient autogenous bone. The opening of the second operative area not only increased the surgical trauma and operation time, but also the discomfort of the patients during and after the operation increased. Many patients have difficulty accepting autogenous bone grafting. Autogenous bone is rarely used in the treatment of maxillary sinus bone grafting [17, 18].

Allografts can be divided into three types: fresh/frozen bone, freeze-dried bone and demineralized freeze-dried bone. Among them, fresh/frozen bone had the greatest osteoinductive and osteoconductive potential. However, due to the risk of disease transmission, it is no longer in clinical application.

Synthetic bone substitutes refer to bioceramics or polymers made from natural materials or synthetic materials. Different synthetic bone substitutes have different physical and chemical properties and can be degraded in vivo or remain stable for a long time. However, as a scaffold material, it has no osteogenesis and osteoinducibility.

Xenogeneic bone refers to the bone graft substitutes derived from different species of biological individuals. The source is generally cattle, pigs, horses and other animals. The currently dominant product in the clinic is DBBM. DBBM is derived from natural calf bone and is a porous carbonate apatite crystal with bone conduction properties. Its physical and chemical properties are very similar to the structure of human bone tissue, and it retains the porous structure and trabecular bone of natural bone. It can provide a scaffold for the expansion of osteoblasts, and ensure the stability of blood clots and the regeneration of blood vessels. In the literature related to maxillary sinus elevation, DBBM as a bone augmentation material has involved the most clinical cases and the most complete data [19,20,21,22].

DBBM was a well-documented bone grafting material for maxillary sinus lift [23,24,25,26]. The most widely utilized commercial product in clinical practice was Bio-Oss with diameters ranging from 0.25 to 1 mm and 1–2 mm, respectively[27,28,29]. Bio-Oss was widely used because its characteristics, including its crystallinity and physicochemical properties, were very similar to those of human cancellous bone. DBBM acted as a scaffold and matrix to promote the migration of osteoblasts from the maxillary sinus wall to the graft material, and then increasing the ability of new bone formation [30,31,32]. There have been a number of studies using DBBM for maxillary sinus elevation and to evaluate the performance of bone healing from a histological perspective, but the application of DBBM with different particle sizes and maxillary sinus elevation has been limited and the results have been confusing. This is because maxillary sinus elevation with different sizes of DBBM results in completely different bone healing in only a few studies [33,34,35,36]. It was important to note that only four randomized controlled clinical trials have investigated the use of DBBM and maxillary fundus in different sizes.

A total of four literatures were included in this study. Chackartchi et al. [33] used large and small bovine bones separately in maxillary sinus floor lifting surgery. After a period of 6–9 months, they extracted bone samples from patients and found that both large and small bovine bones showed similar clinical and histological results. When comparing the application of large and small granular bovine bones in maxillary sinus floor elevation, Testori et al. [34] found that the large granular bovine bones produced more new bone than the small granular bovine bones in terms of histomorphometric results at 6–8 months after surgery. In addition, Molon et al. [35] conducted histomorphometric studies to stain the protein expression of osteocalcin, vascular endothelial growth factor and tartrate-resistant acid. The results showed no statistically significant difference between the large and the small, which suggesting that the size of DBBM did not affect the osteogenic effect during maxillary sinus elevation. Through a randomized controlled study, Kamolratanakul et al. [36] found that the application of large particles of DBBM in maxillary sinus floor elevation could induce more angiogenic expression and obtain more new bone. However, the clinical outcomes were similar in both groups. The reasons for their disagreement are multifaceted and the result of various factors, such as sample size, sample selection, population differences, differences in surgical techniques, and the way, location or time of collecting specimens.

In previous studies, bone specimens were obtained in different ways. Testori et al. [34] and Molon et al. [35] took bone specimens from the buccal side of the lateral wall of the maxillary sinus for analysis. On the contrary, Chackartchi et al. [33] and Kamolratanakul et al. [36] used a hollow bone drill to extract bone samples from the alveolar crest (the implant site) for analysis. The presence of partial autogenous cortical or cancellous bone in the bone specimens may affect the histological results, but this article believed that both methods of bone extraction were feasible, and the fact that autogenous bone may be included was unavoidable. Other limitations included the inability to control the size and morphology of the maxillary sinus itself and the size of its bulge. However, as the target of our evaluation was a complex multi-factor biological process, the experimental method and evaluation indicators were more important.

In modern medicine, immunohistochemical analysis can be independent of morphological observation, which can provide a broader overview of biological processes and directions of progress. In a previous report, ABB particles did not affect the expression of genes associated with bone remodeling and inflammation after a 6-month healing period. Histological evidence also suggested that DBBM particles were replaced by new bone formation and did not affect bone healing [37]. Similarly, Pereira et al. performed maxillary floor elevation 6 months after surgery using autogenous bone and DBBM, and they found similar histopathological and immunohistochemical evaluations of RUNX2 and vascular endothelial growth factor (VEGF) [38]. These data suggested that bone remodeling and neovascularization occur at least 6 months after surgery when DBBM was used for external maxillary sinus elevation, which explained why the experimental period of maxillary sinus lift was at least 6 months. Moreover, the use of DBBM did not inhibit the expression of genes related to bone remodeling induction. It is worth noting that the four studies included in this paper also had an observation period of more than 6 months, which revealed the reliability of DBBM in clinical application.

Although both large and small particles used for grafting maxillary sinus lifting after surgery have similar histological results, they have significant advantages and disadvantages from the perspective of clinical application. For large particles, it can safely reduce the amount of biomaterial filling the maxillary sinus without affecting the graft volume, so more space could be obtained for implantation. Another important aspect was that the surgical time can also be shortened due to the reduction in the size of the graft. Conversely, the use of large particles also increased the amount of void space in the whole area, thus in turn increased the risk of infection. For small particles, its application allowed for a better grasp of the space and volume of bone graft, based on the size of the maxillary sinus, the number of implants needed, the anatomy of the maxillary sinus and other factors. On the other hand, the application of DBBM with small particles for suitable patients can not only reduce the use of materials, but also reduce the consumption of patients while achieving the same results as the large particles.

When it comes to implant success rates, even in cases of perfect bone condition, objective factors such as general health must be considered, not to mention the complexities involved in maxillary sinus elevation. The implant stability is regarded as a crucial factor for successful osseointegration and serves as one of the most commonly employed indicators to predict implant stability. There are numerous factors that impact the stability of implants, including but not limited to overall physical health, bone density and quantity, implant surface design, among others. There is little evidence suggests that the utilization of various bone substitutes has impact on implant stability [39,40,41,42].

Even if the stability of the implant is not significantly affected by the bone graft material, it does not imply that the bone substitutes are insignificant. No matter which type of bone graft material is used to support the maxillary sinus mucosa, it can effectively maintain the stability of the osteogenic space, particularly when utilizing a small diameter implant tip. Additionally, the bone graft material can disperse pressure on the maxillary sinus mucosa, preventing secondary infections caused by maxillary sinus perforation or collapse of the maxillary sinus mucosa that could reduce osteogenic space.

In conclusion, this study systematically reviewed the previous literature and found that both large-particle DBBM and small-particle DBBM could achieve similar histological results in the following three aspects during maxillary sinus elevation: connective tissue, newly formed bone, and residual xenograft. It can draw a conclusion from the above that the large granular bovine bone and the small granular bovine bone were equally effective in maxillary sinus elevation, which provided a valuable reference for clinical application.It is difficult to make conclusion from limited evidence from four studies. More clinical evidence was needed.