Influence of physicochemical characteristics of calcium phosphate-based biomaterials in cranio-maxillofacial bone regeneration. A systematic literature review and meta-analysis of preclinical models.

Objectives: Calcium phosphate-based biomaterials (CaP) are the most widely used biomaterials to enhance bone regeneration in the treatment of alveolar bone deficiencies, cranio-maxillofacial and periodontal infrabony defects, with positive preclinical and clinical results reported. This systematic review aimed to assess the influence of the physicochemical properties of CaP biomaterials on the performance of bone regeneration in preclinical animal models. Methods: The PubMed, EMBASE and Web of Science databases were searched to retrieve the preclinical studies investigating physicochemical characteristics of CaP biomaterials. The studies were screened for inclusion based on intervention (physicochemical characterization and in vivo evaluation) and reported measurable outcomes. Results: A total of 1532 articles were retrieved and 58 studies were ultimately included in the systematic review. A wide range of physicochemical characteristics of CaP biomaterials was found to be assessed in the included studies. Despite a high degree of heterogeneity, the meta-analysis was performed on 39 studies and evidenced significant effects of biomaterial characteristics on their bone regeneration outcomes. The study specifically showed that macropore size, Ca/P ratio, and compressive strength exerted significant influence on the formation of newly regenerated bone. Moreover, factors such as particle size, Ca/P ratio, and surface area were found to impact bone-to-material contact during the regeneration process. In terms of biodegradability, the amount of residual graft was determined by macropore size, particle size, and compressive strength. Conclusion: The systematic review showed that the physicochemical characteristics of CaP biomaterials are highly determining for scaffold's performance, emphasizing its usefulness in designing the next generation of bone scaffolds to target higher rates of regeneration.

Model-Based Design to Enhance Neotissue Formation in Additively Manufactured Calcium-Phosphate-Based Scaffolds.

In biomaterial-based bone tissue engineering, optimizing scaffold structure and composition remains an active field of research. Additive manufacturing has enabled the production of custom designs in a variety of materials. This study aims to improve the design of calcium-phosphate-based additively manufactured scaffolds, the material of choice in oral bone regeneration, by using a combination of in silico and in vitro tools. Computer models are increasingly used to assist in design optimization by providing a rational way of merging different requirements into a single design. The starting point for this study was an in-house developed in silico model describing the in vitro formation of neotissue, i.e., cells and the extracellular matrix they produced. The level set method was applied to simulate the interface between the neotissue and the void space inside the scaffold pores. In order to calibrate the model, a custom disk-shaped scaffold was produced with prismatic canals of different geometries (circle, hexagon, square, triangle) and inner diameters (0.5 mm, 0.7 mm, 1 mm, 2 mm). The disks were produced with three biomaterials (hydroxyapatite, tricalcium phosphate, and a blend of both). After seeding with skeletal progenitor cells and a cell culture for up to 21 days, the extent of neotissue growth in the disks' canals was analyzed using fluorescence microscopy. The results clearly demonstrated that in the presence of calcium-phosphate-based materials, the curvature-based growth principle was maintained. Bayesian optimization was used to determine the model parameters for the different biomaterials used. Subsequently, the calibrated model was used to predict neotissue growth in a 3D gyroid structure. The predicted results were in line with the experimentally obtained ones, demonstrating the potential of the calibrated model to be used as a tool in the design and optimization of 3D-printed calcium-phosphate-based biomaterials for bone regeneration.

An Empirical Model Linking Physico-Chemical Biomaterial Characteristics to Intra-Oral Bone Formation.

Facial trauma, bone resection due to cancer, periodontal diseases, and bone atrophy following tooth extraction often leads to alveolar bone defects that require bone regeneration in order to restore dental function. Guided bone regeneration using synthetic biomaterials has been suggested as an alternative approach to autologous bone grafts. The efficiency of bone substitute materials seems to be influenced by their physico-chemical characteristics; however, the debate is still ongoing on what constitutes optimal biomaterial characteristics. The purpose of this study was to develop an empirical model allowing the assessment of the bone regeneration potential of new biomaterials on the basis of their physico-chemical characteristics, potentially giving directions for the design of a new generation of dental biomaterials. A quantitative data set was built composed of physico-chemical characteristics of seven commercially available intra-oral bone biomaterials and their in vivo response. This empirical model allowed the identification of the construct parameters driving optimized bone formation. The presented model provides a better understanding of the influence of driving biomaterial properties in the bone healing process and can be used as a tool to design bone biomaterials with a more controlled and custom-made composition and structure, thereby facilitating and improving the clinical translation.