title: Design strategies and applications of nacre-based biomaterials.
abstract: The field of tissue engineering and regenerative medicine relies heavily on materials capable of implantation without significant foreign body reactions and with the ability to promote tissue differentiation and regeneration. The field of bone tissue engineering in particular requires materials capable of providing enhanced mechanical properties and promoting osteogenic cell lineage commitment. While bone repair has long relied almost exclusively on inorganic, calcium phosphate ceramics such as hydroxyapatite and their composites or on non-degradable metals, the organically derived shell and pearl nacre generated by mollusks has emerged as a promising alternative. Nacre is a naturally occurring composite material composed of inorganic, calcium carbonate plates connected by a framework of organic molecules. Similar to mammalian bone, the highly organized microstructure of nacre endows the composite with superior mechanical properties while the organic phase contributes to significant bioactivity. Studies, both in vitro and in vivo, have demonstrated nacre's biocompatibility, biodegradability, and osteogenic potential, which are superior to pure inorganic minerals such as hydroxyapatite or non-degradable metals. Nacre can be used directly as a bulk implant or as part of a composite material when combined with polymers or other ceramics. While nacre has demonstrated its effectiveness in multiple cell culture and animal models, it remains a relatively underexplored biomaterial. This review introduces the formation, structure, and characteristics of nacre, and discusses the present and future uses of this biologically-derived material as a novel biomaterial for orthopedic and other tissue engineering applications.
  
  
  
  Mussel derived nacre, a biological composite composed of mineralized calcium carbonate platelets and interplatelet protein components, has recently gained interest as a potential alternative ceramic material in orthopedic biomaterials, combining the integration and mechanical capabilities of calcium phosphates with increased bioactivity derived from proteins and biomolecules; however, there is limited awareness of this material's potential. Herein, we present, to our knowledge, the first comprehensive review of nacre as a biomaterial. Nacre is a highly promising yet overlooked biomaterial for orthopedic tissue engineering with great potential in a wide variety of material systems. It is our hope that publication of this article will lead to increased community awareness of the potential of nacre as a versatile, bioactive ceramic capable of improving bone tissue regeneration and will elicit increased research effort and innovation utilizing nacre.
authors.affiliation: Department of Biomedical Engineering, Materials Research Institute, The Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Ethan Michael
authors.initials: EM
authors.lastname: Gerhard
authors.affiliation: Zhejiang Provincial Top Key Discipline of Bioengineering, College of Biological and Environmental Sciences, Zhejiang Wanli University, South Qianhu Road 8, Ningbo 315100, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Zhejiang Provincial Top Key Discipline of Bioengineering, College of Biological and Environmental Sciences, Zhejiang Wanli University, South Qianhu Road 8, Ningbo 315100, China.
authors.forename: Caiyan
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Biomedical Engineering, Materials Research Institute, The Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Jinshan
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Biomedical Engineering, Materials Research Institute, The Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA 16802, USA; Engineering Science and Mechanics Department, Materials Research Institute, The Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Ibrahim Tarik
authors.initials: IT
authors.lastname: Ozbolat
authors.affiliation: Department of Biomedical Engineering, Materials Research Institute, The Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Kevin Michael
authors.initials: KM
authors.lastname: Rahn
authors.affiliation: Department of Orthopaedics and Rehabilitation, College of Medicine, The Pennsylvania State University, Hershey, PA 17033, USA.
authors.forename: April Dawn
authors.initials: AD
authors.lastname: Armstrong
authors.affiliation: Zhejiang Provincial Top Key Discipline of Bioengineering, College of Biological and Environmental Sciences, Zhejiang Wanli University, South Qianhu Road 8, Ningbo 315100, China.
authors.forename: Jingfen
authors.initials: J
authors.lastname: Xia
authors.affiliation: Zhejiang Provincial Top Key Discipline of Bioengineering, College of Biological and Environmental Sciences, Zhejiang Wanli University, South Qianhu Road 8, Ningbo 315100, China. Electronic address: qiangy@zwu.edu.cn.
authors.forename: Guoying
authors.initials: G
authors.lastname: Qian
authors.affiliation: Department of Biomedical Engineering, Materials Research Institute, The Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA 16802, USA. Electronic address: jxy30@psu.edu.
authors.forename: Jian
authors.initials: J
authors.lastname: Yang
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry* / Q000494:pharmacology; D018786:Bone Substitutes / Q000737:chemistry* / Q000494:pharmacology; D001842:Bone and Bones / Q000378:metabolism; D017886:Durapatite / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008422:Materials Testing / Q000379:methods*; D060734:Nacre / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D001672:Biocompatible Materials; D018786:Bone Substitutes; D060734:Nacre; D017886:Durapatite
keywords: Biomaterials; Bone; Nacre; Orthopedic; Pearl; Pearl powder; Tissue engineering