Bioactivity Evaluation of Biphasic Hydroxyapatite Bone Substitutes Immersed and Grown with Supersaturated Calcium Phosphate Solution

Recently, the frequency of use of bone substitute materials for the purpose of bone augmentation has increased in implant treatment, but bone formation with bone substitute materials alone is limited. Calcification of bone in the body progresses as Ca2+, H2PO4-, and HPO42- in the body form hydroxyapatite (HA) crystals. In this study, therefore, we prepared a biphasic bone substitute with biological activity to promote bone formation by inducing precipitation and growth of HA crystals on the surface of a bone substitute and evaluated it. Biphasic bone substitute granules were prepared by immersing HA granules in a supersaturated calcium phosphate solution prepared by mixing five medical infusion solutions, the precipitate was analyzed, and the biological activities of biphasic HA granules were evaluated in vitro and in vivo. As a result, the precipitated calcium phosphate crystals were identified as low crystalline HA. On the surface of the HA granules, low-crystalline HA grew markedly as needle-shaped crystals and significantly promoted cell proliferation and bone differentiation. In animal experiments, biphasic HA granules had a significantly higher bone mineral density, new bone volume ratio, and new bone area ratio. Therefore, it suggests that biphasic hydroxyapatite is a useful bone substitute for bone augmentation in dental implant treatment.

Chitosan Based Biocomposites for Hard Tissue Engineering

Bone is the second most transplanted organ, just after blood. It provides structural support, protection for organs and soft tissues. It holds some critical biological processes such as the bone marrow blood forming system. It is responsible for storing and supplying minerals such calcium and phosphate. Bone is a connective tissue formed by two predominant phases: an inorganic phase containing mainly apatitic calcium and phosphate and an organic phase made of fibrous type I collagen. This natural biocomposite has many biological features such osteoconductivity, osteoinductivity, osteogenicity and is subject to a continuous remodeling process through osteoclastic and osteoblastic activities. In biomedical engineering, the restoration of damaged hard tissue with autologous bone is not always possible or even the best option. The development of some safe and low-cost alternatives such as biocomposites that mimic organic and calcified bone materials have shown very good results and offer an alternative to autologous bone implants. However, the mechanical properties of biocomposites still present a big challenge as a hard tissue substitute. This chapter reviews the properties of bone substitute materials chitosan and calcium phosphates, discusses strategies used in the treatment of calcified hard tissues as well as new approaches developed in this field.

The Influence of Hyaluronic Acid Biofunctionalization of a Bovine Bone Substitute on Osteoblast Activity In Vitro

Bovine bone substitute materials (BSMs) are used for oral bone regeneration. The objective was to analyze the influence of BSM biofunctionalization via hyaluronic acid (HA) on human osteoblasts (HOBs). BSMs with ± HA were incubated with HOBs including HOBs alone as a negative control. On days 3, 7 and 10, cell viability, migration and proliferation were analyzed by fluorescence staining, scratch wound assay and MTT assay. On days 3, 7 and 10, an increased cell viability was demonstrated for BSM+ compared with BSM− and the control (each p ≤ 0.05). The cell migration was enhanced for BSM+ compared with BSM− and the control after day 3 and day 7 (each p ≤ 0.05). At day 10, an accelerated wound closure was found for the control compared with BSM+/− (each p < 0.05). The highest proliferation rate was observed for BSM+ on day 3 (p ≤ 0.05) followed by BSM− and the control (each p ≤ 0.05). At day 7, a non-significantly increased proliferation was shown for BSM+ while the control was higher than BSM− (each p < 0.05). The least proliferation activity was observed for BSM− (p < 0.05) at day 10. HA biofunctionalization of the BSMs caused an increased HOB activity and might represent a promising alternative to BSM− in oral bone regeneration.

Mg,Sr-Cosubstituted Hydroxyapatite with Improved Structural Properties

Bone substitute materials require specific properties to make them suitable for implantation, such as biocompatibility and resistance to mechanical loads. Mg,Sr-cosubstituted hydroxyapatite (MgSr-HA) is a promising bone scaffold candidate because its structure is similar to the native bone matrix. However, MgSr-HA materials do not typically withstand thermal treatments over 800 °C, because Mg promotes HA degradation to less stable tricalcium phosphate, a compound that, albeit biocompatible, is not found in bone. We, therefore, designed an ion-exchange process to enrich sintered Sr-HA with Mg and obtain MgSr-HA porous constructs. These materials contained a 0.04–0.08 Mg/Ca molar ratio and a 0.12–0.13 Sr/Ca molar ratio, and had up to 20 MPa of compressive strength, suitable for use as bone fillers or scaffolds. Unlike previous synthetic Mg,Sr-substituted apatite powders, the proposed process did not degrade HA and thus preserved its similarity to bone structure. The obtained material thus combines the presence of bioactive Mg and Sr ions in the HA lattice with a 3D morphological/structural organization that can be customized in pore size and distribution, as well as in mechanical strength, thus potentially covering a wide range of clinical applications.

Bone Grafts and Substitutes in Dentistry: A Review of Current Trends and Developments

After tooth loss, bone resorption is irreversible, leaving the area without adequate bone volume for successful implant treatment. Bone grafting is the only solution to reverse dental bone loss and is a well-accepted procedure required in one in every four dental implants. Research and development in materials, design and fabrication technologies have expanded over the years to achieve successful and long-lasting dental implants for tooth substitution. This review will critically present the various dental bone graft and substitute materials that have been used to achieve a successful dental implant. The article also reviews the properties of dental bone grafts and various dental bone substitutes that have been studied or are currently available commercially. The various classifications of bone grafts and substitutes, including natural and synthetic materials, are critically presented, and available commercial products in each category are discussed. Different bone substitute materials, including metals, ceramics, polymers, or their combinations, and their chemical, physical, and biocompatibility properties are explored. Limitations of the available materials are presented, and areas which require further research and development are highlighted. Tissue engineering hybrid constructions with enhanced bone regeneration ability, such as cell-based or growth factor-based bone substitutes, are discussed as an emerging area of development.

Development and Characterization of 3D Printed Multifunctional Bioscaffolds Based on PLA/PCL/HAp/BaTiO3 Composites

Bone substitute materials are placed in bone defects and play an important role in bone regeneration and fracture healing. The main objective of the present research is fabrication through the technique of 3D printing and the characterization of innovative composite bone scaffolds composed of polylactic acid (PLA), poly (ε-caprolactone) (PCL) while hydroxyapatite (HAp), and/or barium titanate (BaTiO3—BT) used as fillers. Composite filaments were prepared using a single screw melt extruder, and finally, 3D composite scaffolds were fabricated using the fused deposition modeling (FDM) technique. Scanning electron microscopy (SEM) images showed a satisfactory distribution of the fillers into the filaments and the printed objects. Furthermore, differential scanning calorimetry (DSC) measurements revealed that PLA/PCL filaments exhibit lower glass transition and melting point temperatures than the pure PLA filaments. Finally, piezoelectric and dielectric measurements of the 3D objects showed that composite PLA/PCL scaffolds containing HAp and BT exhibited piezoelectric coefficient (d33) values close to the human bone and high dielectric permittivity values.

Application of Bovine Acellular Cancellous Bone Matrix in Alveolar Ridge Preservation Following Tooth Extraction

Objective: In this article, we explored the microscopic structure and composition of the decellular-ized cancellous bone matrix of the calf, and established the animal model of Beagle dog extraction. By applying different bone substitute materials in the extraction of teeth, we observed the new collagen-rich in the preservation of the site after tooth extraction. The protein bone matrix maintained the three-dimensional shape of the alveolar ridge compared to other biological materials. Methods: The microstructure of the new collagen-rich bone matrix was observed by scanning electron microscopy. The porous structure, porosity and distribution of collagen fibers were observed. XRD and infrared spectroscopy were used to further detect the inorganic and organic components in the new collagen-rich bone matrix. The premolar extraction and site preservation model of Beagle dogs were constructed. The changes of collagen-rich bone matrix, Bio-oss bone powder, CGF filling and blank control alveolar ridge volume were compared by CBCT. HE staining was used to observe and compare new bone formation, bone remodeling and bone resorption between groups, and to observe the formation of blood vessels, osteogenic mineralization, trabecular bone formation and inflammatory response in different periods. Results: (1) The acellular bone matrix of bovine cancellous bone completely removes the immunogenicity of the cells and has good histocompat-ibility; the pore diameter and porosity closest to the physiological structure, the main component is hydroxyapatite and collagen. (2) Site preservation can reduce the absorption of alveolar ridge following tooth extraction, preserve sufficient bone mass for alveolar fossa, and retain a good width of attachment, which provides further protection for implant surgery. (3) In the post-extraction site preservation, the CGF group has better bone composition than the BABM group and Bio-oss bone powder. Conclusion: Bovine Acellular Cancellous Bone Matrix is a new type of biological bone matrix. The main components are collagen and hydroxyapatite, which can promote bone formation in the extraction socket.

Exploring the Biomaterial-Induced Secretome: Physical Bone Substitute Characteristics Influence the Cytokine Expression of Macrophages

In addition to their chemical composition various physical properties of synthetic bone substitute materials have been shown to influence their regenerative potential and to influence the expression of cytokines produced by monocytes, the key cell-type responsible for tissue reaction to biomaterials in vivo. In the present study both the regenerative potential and the inflammatory response to five bone substitute materials all based on β-tricalcium phosphate (β-TCP), but which differed in their physical characteristics (i.e., granule size, granule shape and porosity) were analyzed for their effects on monocyte cytokine expression. To determine the effects of the physical characteristics of the different materials, the proliferation of primary human osteoblasts growing on the materials was analyzed. To determine the immunogenic effects of the different materials on human peripheral blood monocytes, cells cultured on the materials were evaluated for the expression of 14 pro- and anti-inflammatory cytokines, i.e., IL-6, IL-10, IL-1β, VEGF, RANTES, IL-12p40, I-CAM, IL-4, V-CAM, TNF-α, GM-CSF, MIP-1α, Il-8 and MCP-1 using a Bio-Plex® Multiplex System. The granular shape of bone substitutes showed a significant influence on the osteoblast proliferation. Moreover, smaller pore sizes, round granular shape and larger granule size increased the expression of GM-CSF, RANTES, IL-10 and IL-12 by monocytes, while polygonal shape and the larger pore sizes increased the expression of V-CAM. The physical characteristics of a bone biomaterial can influence the proliferation rate of osteoblasts and has an influence on the cytokine gene expression of monocytes in vitro. These results indicate that the physical structure of a biomaterial has a significant effect of how cells interact with the material. Thus, specific characteristics of a material may strongly affect the regenerative potential in vivo.