Ginger and Garlic Extracts Enhance Osteogenesis in 3D Printed Calcium Phosphate Bone Scaffolds with Bimodal Pore Distribution

Abstract

Natural medicines have long been used to treat physiological ailments where both ginger (gingerol) and garlic (allicin) are key players in immune system promotion, reduction in blood pressure, and lowering inflammation response. With their efficacy in bone healing, these compounds have great value as medicinal additives in bone scaffolds for localized treatment to support tissue formation, along with providing their natural therapeutic benefits. Utilization of 3D-printed (3DP) bone tissue engineering scaffolds as drug delivery vehicles for ginger and garlic extracts enables patient specificity in bone defect applications with enhanced osseointegration. Our objective is to understand their combined efficacy on osteogenesis when released from 3DP calcium phosphate bone scaffolds designed with a bimodal pore distribution. With a porous core and dense exterior, the resulting scaffolds have good mechanical integrity with 10 ± 1 MPa compressive strengths. Results show that ginger + garlic extracts released from bone scaffolds enhance their osteogenic potential through on site drug delivery. Both compounds exhibit exponential drug release profiles which fit Weibull distribution equations. The release of ginger extract also increases osteoblast proliferation by 59%. Both compounds show decreased osteoclast resorption activity, with a greater than 20% reduction in pit area on sample surfaces. Ginger + garlic extract induces a twofold increase in early osteoid tissue formation in vivo at week 4, in addition to a 30% increase in total bone area and a 90% increase in osteocytes with respect to control 3DP tricalcium phosphate scaffolds. Late-stage bone healing at week 10 reveals healthy angiogenic tissue, a twofold higher bone mineralization, and significant enhancement of type I collagen formation in the presence of ginger and garlic extracts. Naturally sourced ginger and garlic extracts provide osteogenic promotion and improved bone tissue in-growth in a patient-specific 3DP scaffold biomedical device for low load-bearing bone tissue engineering and dental applications.

In vivoandIn vitroproperties evaluation of curcumin loaded MgO doped 3D printed TCP scaffolds

“…TRAP enzyme is secreted by the osteoclast cells during bone resorption, and it is a marker to quantify osteoclastic activity. 70 Our results show a significant decrease in TRAP expression in presence of Mg 2+ and curcumin. This behavior is possible because of two reasons (a) there are fewer viable cells on the treatment samples (b) the cells are not attached well to the scaffold surface, and they are unable to resorb the TCP, followed by releasing TRAP.…”

“…The growth of new blood vessels results in nutrient supply to the newly grown bone segment. 70 Our quantification results (Fig. 8) reveal that the presence of MgO helps to significantly enhance blood vessel formation as compared to the control.…”

Dietary organosulfur compounds: Emerging players in the regulation of bone homeostasis by plant-derived molecules

“…However, MG-63 cells are osteoblasts derived from osteosarcoma, a malignant bone tumors, thus are not fully representative of physiological osteoblasts (122). Increased cells proliferation by Allium genus was also shown by ginger and garlic extracts released by 3D-printed calcium phosphate scaffolds on human fetal osteoblast cells (82); increased osteogenesis by Allium fistulosum was also shown in the mouse C57BL/6 osteoblastic calvaria cell line (MC3T3-E1) (80). Up to date no studies on primary cultures of human MSCs have been performed with extracts derived from Alliaceae or Brassicaceae.…”

“…Using human THP1 monocytes, Bose et al. showed that ginger and garlic extracts reduce the frequency and the size of resorption pits carved by osteoclasts ( 82 ); inhibition of osteoclast number was found also by onion and commercial onion extracts in rat and rabbit osteoclasts ( 81 ). Notably, Wetli et al.…”

“…Other receptors involved in osteoclastogenesis are calcitonin receptor (CTR), ITAM bearing Fc receptor standard g chain (FcRγ), osteoclasts-specific activating receptor (OSCAR) ( 126 , 130 ); key signaling is mediated by mitogen-activated protein kinases (MAPK), and includes extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 activation. Moreover, critical to osteoclast differentiation and function are: intracellular reactive oxygen species (ROS) generation, which act as key signaling molecules ( 82 , 88 , 94 ); osteoclast fusion mediated among other factors, by the fusogenic molecules osteoclasts-stimulatory transmembrane protein (OC-STAMP) and dendritic cell-specific transmembrane protein (DC-STAMP) ( 126 , 131 , 132 ); and expression of specific enzymes such as tartrate-resistant acid phosphatase (TRAP), cathepsin K (CTSK) ( 126 , 130 ), tartrate-resistant acid phosphatase 5b (TRAP5b) ( 83 ) and matrix metallopeptidase 9 (MMP-9).…”