Improved Bone Regeneration in Rabbit Bone Defects Using 3D Printed Composite Scaffolds Functionalized with Osteoinductive Factors

Abstract

Large critical size bone defects are complicated to treat and in many cases autografts become a challenge due to size and availability. In such situations, a synthetic bone implant that can be patient specifically designed and fabricated with control over parameters such as: porosity, rigidity and osteogenic cues, can act as a potential synthetic bone substitute. In this study we produced photocuring composite resins with poly(trimethylene carbonate) containing high ratios of bioactive ceramics and printed porous 3D composite scaffolds to be used as bone grafts. To enhance the overall surface area available for cell infiltration the scaffolds were also filled with a macroporous cryogel. Furthermore, the scaffolds were functionalized with osteoactive factors: bone morphogenetic protein (BMP) and zoledronic acid (ZA). The scaffolds were evaluated in vitro for biocompatibility and for functionality in vivo in critical bone defects (~8 mm) in two clinically relevant rabbit models. These studies included a smaller study in rabbit tibia and a larger study in the rabbit cranium. It was observed that the bioactive molecule functionalized 3D printed porous composite scaffolds provide an excellent conductive surface inducing higher bone formation and improved defect healing in both critical size long bone and cranial defects. Our findings provide strong evidence in favour of these composites as next generation synthetic bone substitutes.

Regulating Macrophage Polarization in High Glucose Microenvironment Using Lithium‐Modified Bioglass‐Hydrogel for Diabetic Bone Regeneration

“…It is of vital importance whether the hydrogels could induce osteogenesis at the defect in situ. [ 21 ] Thus, we investigate the potential osteogenesis ability of these hydrogel. Initially, BMSCs cells were cultured using 3D cell system and hydrogel extracts from different groups to evaluate the alkaline phosphatase (ALP) activity, which was represented as a marker of early osteogenic differentiation.…”

Periosteum-Mimicking Tissue-Engineered Composite for Treating Periosteum Damage in Critical-Sized Bone Defects

“…We have been working on different types of critical-sized bone defect models, including bone infection models, where we have previously used a nanohydroxyapatite-based bone substitute as an antibiotic carrier to promote bone healing in infectious fractures. , Moreover, we have developed a polymeric cryogel and a calcium-sulfate–nanohydroxyapatite (CS-HAP) bone cement-based bilayered model for critical-sized cranial defects . Additionally, we have observed enhancement in bone infiltration into the porous polymeric matrix in the presence of a guiding membrane in critical-sized cranial defects in rabbits …”

“…21 Additionally, we have observed enhancement in bone infiltration into the porous polymeric matrix in the presence of a guiding membrane in critical-sized cranial defects in rabbits. 45…”

Exosome-Functionalized Ceramic Bone Substitute Promotes Critical-Sized Bone Defect Repair in Rats

“…Hematoxylin and eosin (H&E) and Masson's trichrome staining was performed on the sections as described elsewhere. 39,42 Statistical Analysis. All the in vitro experiments were carried out in triplicate with the minimum sample size of n = 3.…”

“…The decalcified bones were longitudinally cut into two from the center of the defect, paraffin-embedded, and sectioned at a 5 μm thickness. Hematoxylin and eosin (H&E) and Masson’s trichrome staining was performed on the sections as described elsewhere. , …”