title: Emerging ideas: Engineering the periosteum: revitalizing allografts by mimicking autograft healing.
abstract: BACKGROUND
  To fulfill the need for large volumes, devitalized allografts are used to treat massive bone defects despite a 60%, 10-year postimplantation fracture rate. Allograft healing is inferior to autografts where the periosteum orchestrates remodeling.
  
  
  OBJECTIVE
  By augmenting allografts with a tissue engineered periosteum consisting of tunable and degradable, poly(ethylene glycol) (PEG) hydrogels for mesenchymal stem cell (MSC) transplantation, the functions critical for periosteum-mediated healing will be identified and emulated.
  
  
  METHODS
  PEG hydrogels will be designed to emulate periosteum-mediated autograft healing to revitalize allografts. We will exploit murine femoral defect models for these approaches. Critical-sized, 5-mm segmental defects will be created and filled with decellularized allograft controls or live autograft controls. Alternatively, defects will be treated with our experimental approaches: decellularized allografts coated with MSCs transplanted via degradable PEG hydrogels to mimic progenitor cell densities and persistence during autograft healing. Healing will be evaluated for 9 weeks using microcomputed tomography, mechanical testing, and histologic analysis. If promising, MSC densities, hydrogel compositions, and genetic methods will be used to isolate critical aspects of engineered periosteum that modulate healing. Finally, hydrogel biochemical characteristics will be altered to initiate MSC and/or host-material interactions to further promote remodeling of allografts.
  
  
  CONCLUSIONS
  This approach represents a novel tissue engineering strategy whereby degradable, synthetic hydrogels will be exploited to emulate the periosteum. The microenvironment, which will mediate MSC transplantation, will use tunable PEG hydrogels for isolation of critical allograft revitalization factors. In addition, hydrogels will be modified with biochemical cues to further augment allografts to reduce or eliminate revision surgeries associated with allograft failures.
authors.affiliation: Department of Biomedical Engineering, University of Rochester, Rochester, NY 14627-0168, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Hoffman
authors.forename: Danielle S W
authors.initials: DS
authors.lastname: Benoit
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D016025:Bone Transplantation / Q000379:methods*; D004195:Disease Models, Animal; D005264:Femoral Fractures / Q000000981:diagnostic imaging / Q000473:pathology / Q000601:surgery*; D020100:Hydrogels; D045164:Mesenchymal Stem Cell Transplantation; D051379:Mice; D008810:Mice, Inbred C57BL; D009985:Orthopedics / Q000379:methods*; D016348:Osseointegration; D010521:Periosteum / Q000000981:diagnostic imaging / Q000637:transplantation*; D011092:Polyethylene Glycols / Q000737:chemistry*; D013997:Time Factors; D023822:Tissue Engineering; D054457:Tissue Scaffolds; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous; D055114:X-Ray Microtomography
chemical_list: D020100:Hydrogels; D011092:Polyethylene Glycols