Bioactive PLGA/tricalcium phosphate scaffolds incorporating phytomolecule icaritin developed for calvarial defect repair in rat model.

Published on Jun 7, 2020in Journal of orthopaedic translation3.986
· DOI :10.1016/J.JOT.2020.05.008
Guang-Sen Shi1
Estimated H-index: 1
(SJTU: Shanghai Jiao Tong University),
Ying-Ying Li1
Estimated H-index: 1
(SJTU: Shanghai Jiao Tong University)
+ 8 AuthorsShihui Chen11
Estimated H-index: 11
(CUHK: The Chinese University of Hong Kong)
Abstract Background/objectives For treatment of large bone defects challenging in orthopaedic clinics, bone graft substitutes are commonly used for the majority of surgeons. It would be proposed in the current study that our bioactive scaffolds could additionally serve as a local delivery system for therapeutic small molecule agents capable of providing support to enhance biological bone repair. Methods In this study, composite scaffolds made of poly (lactic-co-glycolic acid) (PLGA) and tricalcium phosphate (TCP) named by P/T was fabricated by a low-temperature rapid prototyping technique. For optimizing the scaffolds, the phytomolecule icaritin (ICT) was incorporated into P/T scaffolds called P/T/ICT. The osteogenic efficacies of the two groups of scaffolds were compared in a successfully established calvarial defect model in rats. Bone regeneration was evaluated by X-ray, micro-computerised tomography (micro-CT), and histology at weeks 4 and/or 8 post-implantation. In vitro induction of osteogenesis and osteoclastogenesis was established for identification of differentiation potentials evoked by icaritin in primary cultured precursor cells. Results The results of radiographies and decalcified histology demonstrated more area and volume fractions of newly formed bone within bone defect sites implanted with P/T/ICT scaffold than that with P/T scaffold. Undecalcified histological results presented more osteoid and mineralized bone tissues, and also more active bone remodeling in P/T/ICT group than that in P/T group. The results of histological staining in osteoclast-like cells and newly formed vessels indicated favorable biocompatibility, rapid bioresorption and more new vessel growth in P/T/ICT scaffolds in contrast to P/T scaffolds. Based on in vitro induction, the results presented that icaritin could significantly facilitate osteogenic differentiation, while suppressed adipogenic differentiation. Meanwhile, icaritin demonstrated remarkable inhibition of osteoclastogenic differentiation. Conclusion The finding that P/T/ICT composite scaffold can enhance bone regeneration in calvarial bone defects through facilitating effective bone formation and restraining excessive bone resorption. The translational potential of this article The osteogenic bioactivity of icaritin facilitated PLGA/TCP/icartin composite scaffold to exert significant bone regeneration in calvarial defects in rat model. It might form an optimized foundation for potential clinical validation in bone defects application.
📖 Papers frequently viewed together
40 Citations
9 Authors (Ying Yang, ..., Tingting Tang)
45 Citations
276 Citations
#1Katherine M. Powell (IUPUI: Indiana University – Purdue University Indianapolis)H-Index: 2
#2Cayla G. Skaggs (IUPUI: Indiana University – Purdue University Indianapolis)H-Index: 3
Last. Joseph M. Wallace (IUPUI: Indiana University – Purdue University Indianapolis)H-Index: 23
view all 6 authors...
Abstract Current interventions to reduce skeletal fragility are insufficient at enhancing both the quantity and quality of bone when attempting to improve overall mechanical integrity. Bisphosphonates, such as Zoledronate (ZOL), are used to treat a variety of bone disorders by increasing bone mass to decrease fracture risk, but long-term use has been shown in some settings to compromise bone quality. Alternatively, Raloxifene (RAL) has recently been demonstrated to improve tissue quality and ove...
5 CitationsSource
#1Dominic Simon (FAU: University of Erlangen-Nuremberg)H-Index: 1
#2Anja Derer (FAU: University of Erlangen-Nuremberg)H-Index: 13
Last. Ulrike Harre (FAU: University of Erlangen-Nuremberg)H-Index: 14
view all 8 authors...
Abstract Bone tissue undergoes permanent and lifelong remodeling with a concerted action of bone-building osteoblasts and bone-resorbing osteoclasts. A precise cooperation between those two cell types is critical in the complex process of bone renewal. Galectin-3 is a member of the β-galactoside-binding lectin family playing multiple roles in cell growth, differentiation and aggregation. As it has been described to be expressed in bone, galectin-3 might influence bone homeostasis by regulating t...
23 CitationsSource
#1Shihui Chen (HMU: Harbin Medical University)H-Index: 11
#2Poying Lau (CUHK: The Chinese University of Hong Kong)H-Index: 2
Last. Shekhar M. Kumta (CUHK: The Chinese University of Hong Kong)H-Index: 28
view all 8 authors...
A functional biomaterial with a therapeutic effect is desirable as an adjuvant therapy to enhance bone formation and prevent local recurrence of bone tumours, especially when the resection margins are not identifiable. In this study, novel composite materials were developed with dual properties of osteopromotion and bone resorption to mimic the tumour inhibition effect, including water-soluble phosphorylated chitosan (P-chitosan) for increasing osteoblasts activity and disodium (1 4)-2-deoxy-2-s...
5 CitationsSource
#1Koichi Ichikawa (OCU: Osaka City University)H-Index: 2
#2Yoichi Ohta (OCU: Osaka City University)H-Index: 9
Last. Hiroaki Nakamura (OCU: Osaka City University)H-Index: 32
view all 8 authors...
Abstract Bone Morphogenetic Proteins (BMPs) strongly induce the recruitment and differentiation of mesenchymal progenitor cells into mature osteoblasts, but also directly and indirectly stimulate differentiation of osteoclast progenitor cells and acceleration of mature osteoclasts function leading excessive bone resorption. Bisphosphonates, such as zoledronate (ZOL), inhibit osteoclasts function and osteoclasts mediated bone resorption. The short or middle term effect of BMPs and bisphosphonates...
8 CitationsSource
#1Sarah M. Almubarak (UCSF: University of California, San Francisco)H-Index: 3
#2Hubert Nethercott (UCSF: University of California, San Francisco)H-Index: 1
Last. Chelsea S. Bahney (University of California, Berkeley)H-Index: 14
view all 10 authors...
This review focuses on current tissue engineering strategies for promoting vascularized bone regeneration. We review the role of angiogenic growth factors in promoting vascularized bone regeneration and discuss the different therapeutic strategies for controlled/sustained growth factor delivery. Next, we address the therapeutic uses of stem cells in vascularized bone regeneration. Specifically, this review addresses the concept of co-culture using osteogenic and vasculogenic stem cells, and how ...
83 CitationsSource
#1Xinhui Xie (Soochow University (Suzhou))H-Index: 21
#2Xinluan Wang (CAS: Chinese Academy of Sciences)H-Index: 25
Last. Ling Qin (CAS: Chinese Academy of Sciences)H-Index: 58
view all 8 authors...
A phytomolecule, icaritin, has been identified and shown to be osteopromotive for the prevention of osteoporosis and osteonecrosis. This study aimed to produce a bioactive poly (l-lactide-co-glycolide)–tricalcium phosphate (PLGA–TCP)-based porous scaffold incorporating the osteopromotive phytomolecule icaritin, using a fine spinning technology. Both the structure and the composition of icaritin-releasing PLGA–TCP-based scaffolds were evaluated by scanning electron microscopy (SEM). The porosity ...
20 CitationsSource
#1Huijuan Cao (CAS: Chinese Academy of Sciences)H-Index: 8
#2Lizhen Zheng (CUHK: The Chinese University of Hong Kong)H-Index: 17
Last. Ling Qin (CAS: Chinese Academy of Sciences)H-Index: 58
view all 9 authors...
Abstract Introduction Destructive repair is the pathological feature of ONFH characterized with the elevated vascular permeability and persistent bone resorption, which is associated with higher VEGF expression, activated c-Src, and vascular leakage. Activated c-Src also participates in mediating endothelial permeability and osteoclasts activity. However, the molecular mechanism of the VEGF and c-Src contributing to the destructive repair process remains unknown. The purpose of this study is to ...
16 CitationsSource
#1Zhang MH-Index: 1
#2James FgH-Index: 1
Last. Zheng LzH-Index: 1
view all 11 authors...
6 Citations
#1Yifei Gu (Tongji University)H-Index: 8
#2Wenhai Huang (Tongji University)H-Index: 27
Last. Delbert E. Day (Missouri University of Science and Technology)H-Index: 62
view all 4 authors...
Previous studies have evaluated the capacity of porous scaffolds composed of a single bioactive glass to regenerate bone. In the present study, scaffolds composed of a mixture of two different bioactive glasses (silicate 13-93 and borate 13-93B3) were created and evaluated for their response to osteogenic MLO-A5 cells in vitro and their capacity to regenerate bone in rat calvarial defects in vivo. The scaffolds, which have similar microstructures (porosity = 5867%) and contain 0, 25, 50 and 100 ...
49 CitationsSource
#1Ling Qin (CUHK: The Chinese University of Hong Kong)H-Index: 58
11 CitationsSource
Cited By1
#1Qi Pan (CUHK: The Chinese University of Hong Kong)H-Index: 6
#2Yucong Li (CUHK: The Chinese University of Hong Kong)H-Index: 1
Last. Gang Li (CUHK: The Chinese University of Hong Kong)H-Index: 48
view all 9 authors...
Summary Background Long duration of bone consolidation in distraction osteogenesis (DO) has been regarded as a major disadvantage. Porous bone substitutes have been long used in aiding bone formation. However the effects of geometric tubular structure of the porous scaffolds on bone formation in DO remains unknown. This study investigated the effects of porous scaffolds with three different geometric structures on bone regeneration in a rabbit DO model. Methods β-tricalcium phosphate (β-TCP) was...