title: Synthesis and characterization of biomimetic citrate-based biodegradable composites.
abstract: Natural bone apatite crystals, which mediate the development and regulate the load-bearing function of bone, have recently been associated with strongly bound citrate molecules. However, such understanding has not been translated into bone biomaterial design and osteoblast cell culture. In this work, we have developed a new class of biodegradable, mechanically strong, and biocompatible citrate-based polymer blends (CBPBs), which offer enhanced hydroxyapatite binding to produce more biomimetic composites (CBPBHAs) for orthopedic applications. CBPBHAs consist of the newly developed osteoconductive citrate-presenting biodegradable polymers, crosslinked urethane-doped polyester and poly (octanediol citrate), which can be composited with up to 65 wt % hydroxyapatite. CBPBHA networks produced materials with a compressive strength of 116.23 ± 5.37 MPa comparable to human cortical bone (100-230 MPa), and increased C2C12 osterix gene and alkaline phosphatase gene expression in vitro. The promising results above prompted an investigation on the role of citrate supplementation in culture medium for osteoblast culture, which showed that exogenous citrate supplemented into media accelerated the in vitro phenotype progression of MG-63 osteoblasts. After 6 weeks of implantation in a rabbit lateral femoral condyle defect model, CBPBHA composites elicited minimal fibrous tissue encapsulation and were well integrated with the surrounding bone tissues. The development of citrate-presenting CBPBHA biomaterials and preliminary studies revealing the effects of free exogenous citrate on osteoblast culture shows the potential of citrate biomaterials to bridge the gap in orthopedic biomaterial design and osteoblast cell culture in that the role of citrate molecules has previously been overlooked.
authors.affiliation: Department of Bioengineering, Materials Research Institute, The Huck Institutes of The Life Sciences, The Pennsylvania State University, University Park, Pennsylvania, 16802.
authors.forename: Richard T
authors.initials: RT
authors.lastname: Tran
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.forename: Chang
authors.initials: C
authors.lastname: Zhang
authors.forename: Minjun
authors.initials: M
authors.lastname: Huang
authors.forename: Wanjin
authors.initials: W
authors.lastname: Tang
authors.forename: Chi
authors.initials: C
authors.lastname: Zhang
authors.forename: Zhongmin
authors.initials: Z
authors.lastname: Zhang
authors.forename: Dadi
authors.initials: D
authors.lastname: Jin
authors.forename: Brittany
authors.initials: B
authors.lastname: Banik
authors.forename: Justin L
authors.initials: JL
authors.lastname: Brown
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Xie
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Bai
authors.forename: Jian
authors.initials: J
authors.lastname: Yang
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001672:Biocompatible Materials / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D040761:Biomimetic Materials / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D019343:Citric Acid / Q000737:chemistry*; D017886:Durapatite / Q000737:chemistry; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D008422:Materials Testing / Q000379:methods*; D051379:Mice; D016348:Osseointegration / Q000187:drug effects; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry; D011817:Rabbits; D055114:X-Ray Microtomography; D000097382:CD68 Molecule
chemical_list: D000469:Alkaline Phosphatase; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D001672:Biocompatible Materials; D019343:Citric Acid; D017886:Durapatite; D016326:Extracellular Matrix Proteins; D018960:Hyaluronan Receptors; D011108:Polymers; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C098946:hyaluronan-mediated motility receptor
keywords: biodegradable composites; bone tissue engineering; citric acid; osterix