OBJECTIVESTo improve the biocompatibility and osteogenic activity of demineralized dentin matrix (DDM) by grafting peptides on its surface.METHODSDDM was obtained by pulverizing extracted human teeth that had been systematically demineralized and dried. Four groups of materials were evaluated: DDM, DDM/carboxymethyl chitosan (CMC), DDM/CMC/bone forming peptide-1 (BFP-1), and blank. X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FT-IR) and fluorescence localization were used to characterize the surface of the DDM materials. Cell viability was assessed using a CCK8 assay, scanning electron microscopy (SEM) and in vitro osteogenesis was analyzed using real-time RT-PCR (RT-qPCR) and Alizarin red and alkaline phosphatase staining. Three different materials were implanted into mandibular bone defects in rats. After 8 weeks, bone regeneration was assessed by histomorphometry of HE-stained slides.RESULTSFT-IR, XPS, and fluorescence microscopy demonstrated that the DDM surfaces were successfully modified with BFP-1. The CCK8 assay indicated that the proliferation of cells is higher on the DDM/CMC/BFP-1 material than on DDM or DDM/CMC (P < 0.05). Cells were more likely to adhere to DDM/CMC/BFP-1, as observed by SEM. Greater in vitro osteogenesis was observed in the DDM/CMC/BFP-1 group which displayed stronger alkaline phosphatase activity, more alizarin red-stained nodules, and higher target gene expression, as detected by RT-qPCR (P＜0.05). HE staining of in vivo explants indicated that greater quantities of new bone had formed in the DDM/CMC/BFP-1 group.SIGNIFICANCECompared with DDM, DDM/CMC/BFP-1 exhibited superior biocompatibility and osteogenesis, using a method of surface modification that has great potential for future clinical use.

09 Mar 2020·ACS Biomaterials Science & EngineeringQ3 · ENGINEERING & TECHNOLOGY

Dual-Functionalized Apatite Nanocomposites with Enhanced Cytocompatibility and Osteogenesis for Periodontal Bone Regeneration

Q3 · ENGINEERING & TECHNOLOGY

Article

Author: Gao, Xiang ; Xiang, MingLi ; Yang, Zun ; Wei, Jingjing ; He, Ping ; Zhu, Mengyuan ; Song, Jinlin

The development of biomimetic bone graft materials for periodontal tissue engineering is a field of topical interest. In this study, we designed a dual-functionalized apatite nanocomposite, which could integrate multiple molecular cues for manipulating the fate of periodontal ligament stem cells (PDLSCs). Briefly, inspired by mussels, a biomimetic nanohydroxyapatite was fabricated using a polydopamine structure as a template (named as tHA) and then surface-modified with bone-forming peptide-1 (BFP-1) and vascular endothelial growth factor-mimicking peptide (QK) via a single step of catechol chemistry. Our study showed that the biofunctions of tethered peptides were not compromised on the surface of apatite nanoparticles. Because of the synergistic effect of BFP-1 and QK peptides, the dual-functionalized apatite nanocomposite showed improved cytocompatibility compared to controls. Moreover, it can boost the proliferation and osteogenic differentiation of PDLSCs, indicating excellent bioactivity of tHA-BFP/QK nanoparticles on cell fate decision. More importantly, animal experiments showed that dual-functionalized apatite nanocomposites could dramatically promote the regeneration of periodontal bone. It is concluded that our work provides an instructive insight into the design of biomimetic apatite nanocomposites, which holds a great potential for applications in periodontal bone repair.

01 May 2018·BiomaterialsQ1 · ENGINEERING & TECHNOLOGY

Time-responsive osteogenic niche of stem cells: A sequentially triggered, dual-peptide loaded, alginate hybrid system for promoting cell activity and osteo-differentiation

Q1 · ENGINEERING & TECHNOLOGY

Article

Author: Lyu, Yalin ; Shi, Rui ; Luo, En ; Wei, Shicheng ; Yang, Yue ; Li, Yan ; Han, Xiao ; Luo, Zuyuan ; Xu, Zhixiu ; Sui, Yi ; Liu, Hao ; Zhang, Yuanyuan ; Zhang, Siqi ; Pan, Jijia

The efficacy of stem cell-based bone tissue engineering has been hampered by cell death and limited fate control. A smart cell culture system with the capability of sequentially delivering multiple factors in specific growth stages, like the mechanism of the natural extracellular matrix modulating tissue formation, is attractive for enhancing cell activity and controlling cell fate. Here, a bone forming peptide-1 (BFP-1)-laden mesoporous silica nanoparticles (pep@MSNs) incorporated adhesion peptide, containing the arginine-glycine-aspartic acid (RGD) domain, modified alginate hydrogel (RA) system (pep@MSNs-RA) was developed to promote the activity and stimulate osteo-differentiation of human mesenchymal stem cells (hMSCs) in sequence. The survivability and proliferation of hMSCs were enhanced in the adhesion peptide modified hydrogel. Next, BFP-1 released from pep@MSNs induced hMSCs osteo-differentiation after the proliferation stage. Moreover, BFP-1 near the cells was self-captured by the additional cell-peptide cross-linked networks formed by the ligands (RGD) binding to receptors on the cell surface, leading to long-term sustained osteo-stimulation of hMSCs. The results suggest that independent and sequential stimulation in proliferation and osteo-differentiation stages could synergistically enhance the survivability, expansion, and osteogenesis of hMSCs, as compared to stimulating alone or simultaneously. Overall, this study provided a new and valid strategy for stem cell expansion and osteo-differentiation in 2D or 3D culture systems, possessing potential applications in 3D bio-printing and tissue regeneration.

100 Deals associated with BFP-001

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Indication	Highest Phase	Country/Location	Organization	Date
Bone and joint infections	Discovery	France	Biofilm PharmaStartup	-
Diabetic Foot	Discovery	France	Biofilm PharmaStartup	-
Staphylococcal Infections	Discovery	France	Biofilm PharmaStartup	-

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