title: Selective cell affinity of biomimetic micro-nano-hybrid structured TiO2 overcomes the biological dilemma of osteoblasts.
abstract: OBJECTIVE
  There is a great demand for dental implant surfaces to accelerate the process of peri-implant bone generation to reduce its healing time and enable early loading. To this end, an inverse correlation between the proliferation and functional maturation (differentiation) in osteoblasts presents a challenge for the rapid generation of greater amounts of bone. For instance, osteoblasts exhibit faster differentiation but slower proliferation on micro-roughened titanium surfaces. Using a unique micro-nano-hierarchical topography of TiO(2) that mimics biomineralized matrices, this study demonstrates that this challenge can be overcome without the use of biological agents.
  
  
  METHODS
  Titanium disks of grade 2 commercially pure titanium were prepared by machining (smooth surface). To create a microtexture with peaks and valleys (micropit surface), titanium disks were acid-etched. To create 200-nm TiO(2) nanonodules within the micropits (nanonodule-in-micropit surface), TiO(2) was sputter-deposited onto the acid-etched surface. Rat bone marrow-derived osteoblasts and NIH3T3 fibroblasts were cultured on machined smooth, micropit, and nanonodule-in-micropit surfaces.
  
  
  RESULTS
  Despite the substantially increased surface roughness, the addition of 200-nm nanonodules to micropits increased osteoblast proliferation while enhancing their functional differentiation. In contrast, this nanonodule-in-micropit surface decreased proliferation and function in fibroblasts.
  
  
  CONCLUSIONS
  The data suggest the establishment of cell-selectively functionalized nano-in-micro smart titanium surfaces that involve a regulatory effect on osteoblast proliferation, abrogating the inhibitory mechanism on the micropitted surface, while enhancing their functional differentiation. Biomimetic and controllable nature of this nanonodules-in-micropits surface may offer a novel micro-to-nanoscale hierarchical platform to biologically optimize nanofeatures of biomaterials. Particularly, this micro-nano-hybrid surface may be an effective approach to improve current dental implant surfaces for accelerated bone integration.
authors.affiliation: The Jane and Jerry Weintraub Center for Reconstructive Biotechnology, Division of Advanced Prosthodontics, Biomaterials and Hospital Dentistry, UCLA School of Dentistry, 10833 Le Conte Avenue, Los Angeles, CA 90095-1668, USA.
authors.forename: Norio
authors.initials: N
authors.lastname: Hori
authors.forename: Fuminori
authors.initials: F
authors.lastname: Iwasa
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ueno
authors.forename: Kazuo
authors.initials: K
authors.lastname: Takeuchi
authors.forename: Naoki
authors.initials: N
authors.lastname: Tsukimura
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yamada
authors.forename: Masami
authors.initials: M
authors.lastname: Hattori
authors.forename: Akiko
authors.initials: A
authors.lastname: Yamamoto
authors.forename: Takahiro
authors.initials: T
authors.lastname: Ogawa
mesh_terms: D016475:3T3 Cells; D000134:Acid Etching, Dental; D000818:Animals; D040761:Biomimetic Materials / Q000737:chemistry*; D002448:Cell Adhesion; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis; D005347:Fibroblasts / Q000166:cytology; D051379:Mice; D049329:Nanostructures; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism / Q000502:physiology*; D015675:Osteocalcin / Q000096:biosynthesis; D053495:Osteopontin / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013499:Surface Properties; D014025:Titanium / Q000737:chemistry*
chemical_list: D015675:Osteocalcin; D053495:Osteopontin; C009495:titanium dioxide; D003094:Collagen; D014025:Titanium