title: Enhanced bone tissue regeneration by antibacterial and osteoinductive silica-HACC-zein composite scaffolds loaded with rhBMP-2.
abstract: Next-generation orthopedic implants with both osteoinductivity and antibacterial ability are greatly needed. In the present study, biodegradable rhBMP-2 loaded zein-based scaffolds with a macroporous structure were synthesized, and SBA-15 nanoparticles and hydroxypropyltrimethyl ammonium chloride chitosan (HACC) were incorporated into the scaffolds to produce an anti-infective composite scaffold for delivery of osteogenic factors that facilitate the functional repair of bone defects. The silica/HACC/zein scaffolds developed here showed bioactivity, biocompatibility, and effective antibacterial activity. Confocal laser scanning microscopy (CLSM) was used to quantitatively measure the bactericidal efficacy with respect to bacterial adhesion. Results showed that the sample zein-HACC-S20 exhibited long-lasting antibacterial activity against Escherichia coli and Staphylococcus aureus up to 5 d. At a low dosage of rhBMP-2 (ca. 80 μg), the scaffolds released rhBMP-2 protein efficiently at a relatively slow rate, even after 27 d. An ALP activity and ECM mineralization assay showed that the zein-HACC-S20 scaffolds exhibited significant early osteogenic differentiation by generating enhanced ALP product on day 14 and ECM mineralization on day 21. In a mouse model of thigh muscle pouches, zein-S20 and zein-HACC-S20 groups resulted in obvious bone formation and gave more extensive mineralization to the implants than silica free groups, indicating effective bone induction in vivo. In a rabbit model of critical-sized radius bone defects (20 mm in length and 5 mm in diameter), the bone defects were almost fully repaired and bone marrow cavity recanalization was detectable by 3D micro-CT technique and histological analysis after 12 weeks. In this way, the zein-HACC-S20 scaffolds were proven to significantly promote the bone repair. They also demonstrated considerable promise for tissue engineering. Silica/HACC/zein scaffolds with both antibacterial activity and the ability to induce osteogenesis have immense potential in orthopedics and other biomedical applications.
authors.affiliation: Department of Emergency, Changhai Hospital, Second Military Medical University, Shanghai, China; Department of Orthopedics, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Panyu
authors.initials: P
authors.lastname: Zhou
authors.affiliation: Department of Emergency, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xia
authors.affiliation: Department of Emergency, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Xiaosong
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Department of Emergency, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Panfeng
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Department of Emergency, Changhai Hospital, Second Military Medical University, Shanghai, China; Department of Orthopedics, Changhai Hospital, Second Military Medical University, Shanghai, China. Electronic address: shuogui126@126.com.
authors.forename: Shuogui
authors.initials: S
authors.lastname: Xu
mesh_terms: D000643:Ammonium Chloride / Q000008:administration & dosage* / Q000737:chemistry; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage; D018407:Bacterial Physiological Phenomena / Q000187:drug effects*; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage* / Q000737:chemistry; D001861:Bone Regeneration / Q000187:drug effects*; D018786:Bone Substitutes / Q000008:administration & dosage; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry; D004343:Drug Implants / Q000008:administration & dosage / Q000737:chemistry; D019544:Equipment Failure Analysis; D006801:Humans; D051379:Mice; D053761:Nanocomposites / Q000008:administration & dosage* / Q000737:chemistry; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology; D011474:Prosthesis Design; D011817:Rabbits; D011885:Radius Fractures / Q000473:pathology / Q000628:therapy*; D011994:Recombinant Proteins / Q000008:administration & dosage; D012822:Silicon Dioxide / Q000737:chemistry; D054457:Tissue Scaffolds; D016896:Treatment Outcome; D015028:Zein / Q000737:chemistry
chemical_list: D000900:Anti-Bacterial Agents; C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D018786:Bone Substitutes; D004343:Drug Implants; D011994:Recombinant Proteins; C509969:SBA-15; D000643:Ammonium Chloride; D012822:Silicon Dioxide; D015028:Zein; D048271:Chitosan
keywords: Antibacterial; Bone tissue engineering; Osteoinductive; Silica-HACC-zein; rhBMP-2