https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8910217/#B63-ijms-23-02539

Marija Čandrlić, Matej Tomas, Matej Karl, Lucija Malešić, Aleksandar Včev, Željka Perić Kačarević and Marko Matijević

Original title: Comparison of Injectable Biphasic Calcium Phosphate and a Bovine Xenograft in Socket Preservation: Qualitative and Quantitative Histologic Study in Humans. Int J Mol Sci. 2022 Mar; 23(5): 2539.

The demand for Synthetic (alloplastic) bone grafting materials

Even though the risk of disease transmission from bovine bone grafts is neglectable, some people reject the use of xenografts, also because of ethical and religious reasons.
An alternative are alloplastic biomaterials, that are developed based on the understanding of the nanostructure of bone and the organic-inorganic interactions of the bone matrix. The ultimate goal is to achieve the ultrastructure and morphology of natural biominerals.
Alloplastic grafts for dental purposes are usually based on hydroxyapatite (HA), beta-tricalcium phosphate (β-TCP) and alpha-tricalcium phosphate (α-TCP) and combinations thereof. Biphasic calcium phosphate (BCP) is formed by the fusion of HA and β-TCP in various ratios, such as 60:40 in maxresorb® inject.

Aim of the Study

Since no randomization clinical trial to date has evaluated the use of IBCP, the aim of the presented randomized clinical trial was to evaluate and compare the safety and efficacy of the above-mentioned IBCP and a BX in alveolar ridge preservation using qualitative and quantitative histologic analysis.

Surgical Procedure

After extraction, the surgeon performed curettage of the alveolus to remove granulation tissue.
In both groups (see flow charts of the randomization process in Figure 1), the graft material was gently pressed into the socket and covered with a resorbable membrane made of porcine collagen (collprotect® membrane, botiss biomaterials, Zossen, Germany) (Figure 2 and Figure 3).
After six months, bone biopsy was taken from the central part of the preexisting defect using a 2.5 mm trephine drill and implants were placed using a standardized implant set.

Fig.1 Flow charts of the randomization process

Fig.2 Surgical Procedure of the application of maxresorb® inject (test group)

Fig.3 Surgical Procedure of the application of cerabone® (control group)

Results

Clinical Observations

• The IBCP was easy to handle and insert into the extraction socket.
• The healing phase was uneventful.
• No membrane exposure was noted during early postoperative checks.
• On the 90th postoperative day, wound healing was observed as complete closure of the oral mucosa at the extraction site in all participants.

Qualitative Histologic Analysis

New Bone (NB):

•  Successful bone growth from the apical to the coronal segment of both groups.
• NB and non-mineralized tissue surrounding the residual biomaterials.
• Bone growth began in both groups at the boundaries where the biomaterial and pristine bone were in direct contact.
• Regular lamellar structure with osteocytes enclosed within.
• Osteoblasts were detected at the contact between biomaterial and NB.

Safety:

• No detection of foreign body reaction.
• No inflammatory tissue reaction.

Quantitative Histologic Analysis

• Comparable results in terms of the percentage of NB and residual BM in both groups
• No significant difference was observed between the test and control groups in the percentage of NB and residual BM
• Socket preservation with maxresorb® inject resulted in an average percentage of 26.47 ± 14.71% of NB and 13.1 ± 14.07% of residual BM (representable specimen of biopsy with maxresorb® inject in Figure 4)
• Socket preservation with cerabone® resulted in an average percentage of 30.47 ± 16.39% and 17.89 ± 11.81% (representable specimen of biopsy with maxresorb® inject in Figure 5)

Fig.4 Representative specimen of a bone biopsy taken six months after augmentation with maxresorb® inject.

Fig.5 Representative specimen of a bone biopsy taken six months after augmentation with cerabone®.

Discussion

At the time of the study, according to the authors, this is the first published human histologic study on the use of injectable biphasic calcium phosphate (maxresorb inject®), composed of a water-based gel with nano-hydroxyapatite particles and biphasic calcium phosphate granules (60% HA and 40% β–TCP) in socket preservation, and its comparison with BX (cerabone®).

Comparison of the study results to studies on biphasic calcium phosphate in maxillary sinus model

Previous comparative histologic studies of BX and BCP were mostly based on the maxillary sinus model. All in all, the results regarding the comparison of new bone formation between BCP and BX are in agreement with the author’s findings 6 months after socket preservation.

IBCP composition and its effect on bone formation

A comparative histological evaluation of BCPs with different ratios of HA and β-TCP in socket preservation showed that BCP composed of HA (60.28%) and β-TCP (39.72%) had the highest percentage of NB after 6 months of healing. The IBCP used in this study has granules with almost the same HA and β-TCP ratio. During bone healing, β-TCP is rapidly resorbed, and volume stability of the graft until it is replaced by new bone is provided by a high proportion of HA, which is a more stable and less resorbable component of BCP. These observations are consistent with the here presented qualitative and quantitative histologic findings that 6 months after socket preservation residual particles of biomaterial (IBCP: 13.1 ± 14.07%, BX: 17.89 ± 11.81%, p = 0.121, Mann—Whitney U Test) were integrated into the NB in both groups.

Effect of injectability of ICBP on handling and application

Due to its viscosity, the biomaterial was easily applied into the extraction sockets and filled them completely. In addition, the investigated biomaterial in this study was also pre-filled in a sterilized plastic syringe, which expedited the surgical procedure and reduced the treatment burden.

Conclusion

To summarize, both IBCP and BX provide comparable histomorphometric results for newly formed bone. Based on qualitative histologic findings one can conclude that both biomaterials have good osteoconductive properties and biocompatibility. The higher percentage of soft tissue in the IBCP group and its clinical relevance should be the focus of future research, as well as the regenerative potential of IBCP in larger alveolar defects.

Study summarized by Dr. Fabian Langenbach