title: Rescuing failed oral implants via Wnt activation.
abstract: OBJECTIVE
  Implant osseointegration is not always guaranteed and once fibrous encapsulation occurs clinicians have few options other than implant removal. Our goal was to test whether a WNT protein therapeutic could rescue such failed implants.
  
  
  METHODS
  Titanium implants were placed in over-sized murine oral osteotomies. A lack of primary stability was verified by mechanical testing. Interfacial strains were estimated by finite element modelling and histology coupled with histomorphometry confirmed the lack of peri-implant bone. After fibrous encapsulation was established peri-implant injections of a liposomal formulation of WNT3A protein (L-WNT3A) or liposomal PBS (L-PBS) were then initiated. Quantitative assays were employed to analyse the effects of L-WNT3A treatment.
  
  
  RESULTS
  Implants in gap-type interfaces exhibited high interfacial strains and no primary stability. After verification of implant failure, L-WNT3A or L-PBS injections were initiated. L-WNT3A induced a rapid, significant increase in Wnt responsiveness in the peri-implant environment, cell proliferation and osteogenic protein expression. The amount of peri-implant bone and bone in contact with the implant were significantly higher in L-WNT3A cases.
  
  
  CONCLUSIONS
  These data demonstrate L-WNT3A can induce peri-implant bone formation even in cases where fibrous encapsulation predominates.
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.|Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford School of Medicine, Stanford, CA, USA.
authors.forename: Xing
authors.initials: X
authors.lastname: Yin
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.|Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford School of Medicine, Stanford, CA, USA.
authors.forename: Jingtao
authors.initials: J
authors.lastname: Li
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.|Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford School of Medicine, Stanford, CA, USA.
authors.forename: Tao
authors.initials: T
authors.lastname: Chen
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford School of Medicine, Stanford, CA, USA.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Mouraret
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford School of Medicine, Stanford, CA, USA.
authors.forename: Girija
authors.initials: G
authors.lastname: Dhamdhere
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford School of Medicine, Stanford, CA, USA.
authors.forename: John B
authors.initials: JB
authors.lastname: Brunski
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
authors.forename: Shujuan
authors.initials: S
authors.lastname: Zou
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford School of Medicine, Stanford, CA, USA.
authors.forename: Jill A
authors.initials: JA
authors.lastname: Helms
mesh_terms: D000818:Animals; D015921:Dental Implants; D008297:Male; D051379:Mice; D016348:Osseointegration; D010012:Osteogenesis; D013499:Surface Properties; D014025:Titanium; D051153:Wnt Proteins
chemical_list: D015921:Dental Implants; D051153:Wnt Proteins; D014025:Titanium
keywords: biomechanics; fibrosis; finite element analysis; osseointegration; osteogenesis