Bioactive glass scaffold architectures regulate patterning of bone regeneration in vivo

Abstract

The architecture of bone scaffolds, such as pore dimensions, connectivity and orientation can regulate osteogenic defect repair, as can their rate of degradation. Synthetic bone grafts have historically been developed with a foam structures to mimic trabecular bone. Now, Additive Manufacturing techniques enable production of open and regular pore architectures with improved compressive strengths. Here, we compare two types of bioactive glass scaffolds, made of the highly degradable ICIE16 composition, with distinctively different architectures but matched interconnect sizes (~150 µm), produced via two different techniques: gel-cast foaming and direct ink writing. A rabbit lateral femoral defect model was used to compare the effect of their architecture on in vivo bone regeneration, relative to a defect only control group, after 4 and 10 weeks of implantation. 3D X-ray microcomputed tomography (micro-CT), correlated to histology and back-scatter electron microscopy (BS-SEM) permitted quantitative evaluation of new bone ingrowth and degradation of the scaffolds. Both foam and printed scaffolds showed equal or higher bone ingrowth compared to the control group. After 4 weeks, the foam group showed the highest osteogenesis, with 51% more bone ingrowth than the defect only controls, but after 10 weeks the defect treated with the printed scaffold had the most bone ingrowth (40% more than the empty defect). Energy dispersive X-ray (EDS) mapping revealed degradation of the glass and calcium-phosphate deposition. The foam group showed more rapid degradation than the printed group, due to higher total porosity (even though interconnected pore size was equivalent). The foam scaffold appeared to allow rapid bone ingrowth and cancellous bone formation, whereas the printed scaffold seemed to provoke corticallike bone formation, while remaining in place for longer than the 10 week study. While concave architectures promote initial bone ingrowth, the higher strength open pore channels of the printed scaffolds are beneficial for scaffolds made of highly degradable bioactive glasses.

Tissue Engineering Through 3D Bioprinting to Recreate and Study Bone Disease

“…Recently, bio-glasses were tested in 3D bone manufacturing and showed a high bioactivity, osteogenesis, and angiogenesis of bone cells in orthopedics implants [ 41 ]. Another 3D-bioprinted nanocomposite material consisting of copper-loaded-ZIF-8 nanoparticles (PLGA/Cu(I)@ZIF-8) was prepared as an antibacterial and osteoconductive scaffold and suggested as a construct for bone infection repair [ 21 ].…”

“…Its prevalence is expected to increase as more than 50% of the population over the age of 50 will have, or be at risk of developing, osteoporosis by 2025. Fractures caused by osteoporosis were estimated at 9 million in the year 2000 globally, and mainly affects the elderly population aged 60 and over [ 40 , 41 ]. With the aging world population, osteoporosis will have substantial individual, societal, and economic consequences in the US and internationally.…”

Toward Biomimetic Scaffolds for Tissue Engineering: 3D Printing Techniques in Regenerative Medicine

“…Constrained by temperature and complex multi-layer fabrication is challenging for bioprinting Sachlos and Czernuszka, 2003;Wang et al, 2006;Lee et al, 2009Lee et al, , 2014bLee et al, , 2019Haberstroh et al, 2010;Ragaert et al, 2010;Fu et al, 2011;Wu et al, 2011;Hockaday et al, 2012;Bose et al, 2013;Gao et al, 2013;Luo et al, 2013;Mannoor et al, 2013;Duan et al, 2014;Inzana et al, 2014;Murphy and Atala, 2014;Markstedt et al, 2015;Kim et al, 2018;Nommeots-Nomm et al, 2018;Tallia et al, 2018;Li et al, 2020;Shi et al, 2020 Inkjet Precise and controlled placement printing for small volume biological materials Difficult to print viscose materials/cells. Large volume construct fabrication is challenging Boland et al, 2006;Cui and Boland, 2009;Koch et al, 2010;Xu et al, 2013 LOM Ideal for fabricating large 3D objects Lamination coatings can be toxic and vulnerable when fabricating small constructs Park et al, 2000;Yang et al, 2002;Murr(ed.…”

“…Although bioactive glasses are not commercially successful as bioceramics, they are known to be more bioactive, and 45S5 composition (Bioglass R ) was the first artificial material that formed a chemical bond to bone (Hench, 2006;Jones, 2013;Cai et al, 2018). Various compositions of bioactive glasses were also 3D printed to biomimic the porous structure of bone (Fu et al, 2011;Nommeots-Nomm et al, 2018;Shi et al, 2020). However, inorganic scaffolds (i.e., bioceramics and bioactive glasses) are too brittle for repairing defect sites that are exposed to constant loading.…”

In Vitro Study on the Piezodynamic Therapy with a BaTiO3-Coating Titanium Scaffold under Low-Intensity Pulsed Ultrasound Stimulation

“…In general, bioactive materials are the first choice to induce bone regeneration. For example, a three-dimensional (3D)-printed bioactive glass (ICIE16) scaffold can induce new bone ingrowth and cortical bone formation . Also, physical therapy can promote bone healing.…”