title: Comparison of hydrogels in the in vivo formation of tissue-engineered bone using mesenchymal stem cells and beta-tricalcium phosphate.
abstract: Availability of grafts and morbidity at the donor site limit autologous transplantation in patients requiring bone reconstruction. A tissue-engineering approach can overcome these limitations by producing bone-like tissue of custom shape and size from isolated cells. Several hydrogels facilitate osteogenesis on porous scaffolds; however, the relative suitability of various hydrogels has not been rigorously assessed. Fibrin glue, alginate, and collagen I hydrogels were mixed with swine bone marrow-derived differentiated mesenchymal stem cells (MSCs), applied to 3-dimensionally printed porous beta-tricalcium phosphate (beta-TCP) scaffolds and implanted subcutaneously in nude mice. Although noninvasive assessment of osteogenesis in 3 dimensions is desirable for monitoring new bone formation in vivo, correlations with traditional histological and mechanical testing need to be established. High-resolution volumetric computed tomography (VCT) scanning, histological examination, biomechanical compression testing, and osteonectin (ON) expression were performed on excised scaffolds after 1, 2, 4, and 6 weeks of subcutaneous implantation in mice. Statistical correlation analyses were performed between radiological density, stiffness, and ON expression. Use of collagen I as a hydrogel carrier produced superior bone formation at 6 weeks, as demonstrated using VCT scanning with densities similar to native bone and the highest compression values. Continued contribution of the seeded MSCs was demonstrated using swine-specific messenger ribonucleic acid probes. Radiological density values correlated closely with the results of histological and biomechanical testing and ON expression. High-resolution VCT is a promising method for monitoring osteogenesis.
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Harvard, Medical School, Boston, Massachusetts 02114, USA.
authors.forename: Christian
authors.initials: C
authors.lastname: Weinand
authors.forename: Rajiv
authors.initials: R
authors.lastname: Gupta
authors.forename: Albert Y
authors.initials: AY
authors.lastname: Huang
authors.forename: Eli
authors.initials: E
authors.lastname: Weinberg
authors.forename: Ijad
authors.initials: I
authors.lastname: Madisch
authors.forename: Rameez A
authors.initials: RA
authors.lastname: Qudsi
authors.forename: Craig M
authors.initials: CM
authors.lastname: Neville
authors.forename: Irina
authors.initials: I
authors.lastname: Pomerantseva
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Vacanti
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D018786:Bone Substitutes; D002130:Calcium Phosphates / Q000737:chemistry*; D002454:Cell Differentiation; D002478:Cells, Cultured; D020100:Hydrogels / Q000737:chemistry*; D008422:Materials Testing / Q000379:methods; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology*; D051379:Mice; D010012:Osteogenesis / Q000502:physiology; D013552:Swine; D013556:Swine, Miniature; D023822:Tissue Engineering / Q000379:methods*; D014057:Tomography, X-Ray Computed / Q000379:methods*
chemical_list: D001672:Biocompatible Materials; D018786:Bone Substitutes; D002130:Calcium Phosphates; D020100:Hydrogels; C485817:beta-tricalcium phosphate