Optimized Bone Regeneration in Calvarial Bone Defect Based on Biodegradation-Tailoring Dual-shell Biphasic Bioactive Ceramic Microspheres

Abstract

Bioceramic particulates capable of filling bone defects have gained considerable interest over the last decade. Herein, dual-shell bioceramic microspheres (CaP@CaSi@CaP, CaSi@CaP@CaSi) with adjustable beta-tricalcium phosphate (CaP) and beta-calcium silicate (CaSi) distribution were fabricated using a co-concentric capillary system enabling bone repair via a tailorable biodegradation process. The in vitro results showed the optimal concentration (1/16 of 200 mg/ml) of extracts of dual-shell microspheres could promote bone marrow mesenchymal cell (BMSC) proliferation and enhance the level of ALP activity and Alizarin Red staining. The in vivo bone repair and microsphere biodegradation in calvarial bone defects were compared using micro-computed tomography and histological evaluations. The results indicated the pure CaP microspheres were minimally resorbed at 18 weeks post-operatively and new bone tissue was limited; however, the dual-shell microspheres were appreciably biodegraded with time in accordance with the priority from CaSi to CaP in specific layers. The CaSi@CaP@CaSi group showed a significantly higher ability to promote bone regeneration than the CaP@CaSi@CaP group. This study indicates that the biphasic microspheres with adjustable composition distribution are promising for tailoring material degradation and bone regeneration rate, and such versatile design strategy is thought to fabricate various advanced biomaterials with tailorable biological performances for bone reconstruction.

The Impact of Bioceramic Scaffolds on Bone Regeneration in Preclinical In Vivo Studies: A Systematic Review

“…Only qualitative data extracted from each study were synthesized in analytic tables. In seven of the 13 included studies, New Zealand rabbits were used [16,[115][116][117][118][119][120], while six studies were conducted in rats, of which three used the Sprague-Dawley strain [17,121,122], two the Wistar strain [123,124] and one the Lewis strain [125]. The calvarial critical-sized defect was the most used model for assessing new bone formation (Table 3).…”

“…A variety of production methods were reported, leading to the manufacturing of scaffolds with different compositions and morphologies, from 3D bone structures to particles of smaller dimensions, such as the microspheres employed in Xu et al [117]. The definition of bone scaffold was not limited to 3D bone structures, but it was here used to describe a matrix allowing and stimulating cell attachment and proliferation on its surfaces.…”

“…In two studies the same calvaria bone defect model was used to assess the osteoconductive properties of different calcium phosphate and silica-based bioceramics [116,117]. In Shao et al, the in vivo behaviors of 3D-printed pure calcium silicate (CaSi) and dilute Mg-doped CaSi (CaSi-Mg6) scaffolds, characterized by different side-wall pore architectures depending on the deposition mode, were investigated [116].…”

Effect of chitosan and Dysphania ambrosioides on the bone regeneration process: A randomized controlled trial in an animal model

“…Although autogenous bone grafting is the gold standard treatment for these cases, the collection procedure at the donor site can generate complications including hemorrhage, nerve, and vascular lesions, postoperative pain, and affect the quantity and quality of the tissues collected (Behnia, Khojasteh, Soleimani, Tehranchi, & Atashi, 2012;Kumar, Vinitha, & Fathima, 2013). Therefore, the development of natural or synthetic materials that are capable of replacing or accelerating the repair process of this tissue has been the target of research (Li et al, 2018;Xu et al, 2018).…”

“…Bone substitutes may be obtained from biomaterials such as chitosan (Moraes et al, 2017;Shinohara, Nakamura, Shirakata, & Noguchi, 2016;Toskas et al, 2013) that has presented osteoconductive properties (Pogorelov, Sikora, & Bumeyster, 2011), a polysaccharide derived from chitin (Dash, Chiellini, Ottenbriteb, & Chiellini, 2011) that has been tested with other materials such as hormones, growth factors, vegetable extracts, and drugs for use in bone grafting (Martin & Bettencourt, 2018;Xu et al, 2018). However, authors have suggested the application of chitosan spheres combined with herbal extracts that have osteoinductive action (Medeiros et al, 2016) to increase the capacity of repair.…”