title: Shape retaining injectable hydrogels for minimally invasive bulking.
abstract: OBJECTIVE
  Particle migration, poor shape definition and/or rapid resorption limit the success of current urethral bulking agents. We propose that shape defining porous scaffolds that allow cell infiltration and anchoring, and may be delivered in a minimally invasive manner may provide many advantageous features.
  
  
  METHODS
  Alginate hydrogels were prepared with varying degrees of covalent cross-linking and different pore characteristics. Dehydrated scaffolds were compressed into smaller, temporary forms, introduced into the dorsal subcutaneous space of CD-1 mice by minimally invasive delivery through a 10 gauge angiocatheter and rehydrated in situ with a saline solution delivered through the same catheter. Ionically cross-linked calcium alginate gel served as a control. Specimens were harvested at 2, 6, 12 and 24 weeks to evaluate implant shape retention and volume, cell infiltration and calcification, and the presence of an inflammatory response.
  
  
  RESULTS
  A total of 90 scaffolds were implanted and 95% were recovered at the site of injection. All of these scaffolds successfully rehydrated and 80% recovered and maintained their original 3-dimensional shape for 6 months. Scaffold volume and tissue infiltration varied depending on the degree of alginate cross-linking. Highly cross-linked materials (20% and 35%) demonstrated the best volume maintenance with the latter facilitating the most tissue infiltration. The inflammatory response was minimal except with the 80% cross-linked material. Calcification was not observed in covalently cross-linked scaffolds. In contrast, 98% of calcium alginate implants were calcified.
  
  
  CONCLUSIONS
  Shape retaining porous hydrogels meet many of the requirements necessary for a successful injectable bulking agent and offer advantages over currently used agents.
authors.affiliation: Department of Biologic and Material Sciences, University of Michigan, Ann Arbor, 48109, USA.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Thornton
authors.forename: Eben
authors.initials: E
authors.lastname: Alsberg
authors.forename: Elliot E
authors.initials: EE
authors.lastname: Hill
authors.forename: David J
authors.initials: DJ
authors.lastname: Mooney
mesh_terms: D000464:Alginates; D000818:Animals; D003432:Cross-Linking Reagents; D005782:Gels; D020100:Hydrogels / Q000627:therapeutic use*; D020007:Implants, Experimental; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D014521:Urethra / Q000601:surgery*
chemical_list: D000464:Alginates; D003432:Cross-Linking Reagents; D005782:Gels; D020100:Hydrogels