title: Histologic characterization of human ear ossicles for the development of tissue-engineered replacements.
abstract: OBJECTIVE
  Precise knowledge of the expression and distribution of extracellular matrix (ECM) molecules and osteochondrogenic markers helps target the proper in vitro regeneration of novel ossicular chain (OC) replacements via tissue engineering (TE).
  
  
  BACKGROUND
  We performed an extensive histologic analysis of human ear ossicles in healthy adults. A variety of OC prostheses are currently available, but extrusion of synthetic devices still represents an important clinical phenomenon. TE is a novel discipline combining stem cells, bioresorbable biomaterials, and stimulatory factors for the development of new living tissues in vitro, which might offer forefront opportunities to otologic surgery. However, to drive stem cell differentiation correctly, the final tissue target must be accurately known.
  
  
  METHODS
  Malleus, incus, and stapes were collected from cadaveric temporal bones. TE PORPs were obtained via osteodifferentiation of human mesenchymal stromal cells on polymeric scaffolds. Histochemical and immunohistochemical analyses were performed to detect ECM molecules and osteochondrogenic markers.
  
  
  RESULTS
  Malleus and incus showed the same histologic tissue type, with similar levels of expression and distributions for both ECM molecules and osteochondrogenic markers, whereas the stapes showed self-standing histologic patterns. In TE PORPs, mesenchymal ECM synthesis and early stage development of ossification sites could be observed, highlighting good cellular integration with the scaffold biomaterial.
  
  
  CONCLUSIONS
  Detailed morphologic study of the ossicles provides data related to tissue dynamics involved in their development, defining features of tissue differentiation and maturation. Such findings underpin the future development of biomimetic ossicular replacement, data that can guide tissue-engineered ossiculoplasty.
authors.affiliation: Department of Neurosciences, University of Pisa, Pisa, Italy.
authors.forename: Delfo
authors.initials: D
authors.lastname: D'Alessandro
authors.forename: Serena
authors.initials: S
authors.lastname: Danti
authors.forename: Andrea
authors.initials: A
authors.lastname: De Vito
authors.forename: Francesca
authors.initials: F
authors.lastname: Forli
authors.forename: Luca
authors.initials: L
authors.lastname: Bruschini
authors.forename: Stefano
authors.initials: S
authors.lastname: Berrettini
mesh_terms: D015415:Biomarkers; D002102:Cadaver; D003094:Collagen / Q000378:metabolism; D004429:Ear Ossicles / Q000033:anatomy & histology*; D005109:Extracellular Matrix / Q000648:ultrastructure; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005557:Formaldehyde; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008855:Microscopy, Electron, Scanning; D009998:Ossicular Prosthesis; D019933:Ossicular Replacement / Q000379:methods*; D011474:Prosthesis Design; D012038:Regeneration; D023822:Tissue Engineering / Q000379:methods*; D016707:Tissue Fixation; D054457:Tissue Scaffolds
chemical_list: D015415:Biomarkers; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D005557:Formaldehyde; D003094:Collagen