Comparison of hydrogels in the in vivo formation of tissue-engineered bone using mesenchymal stem cells and beta-tricalcium phosphate.
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.
Weinand
Christian
C
Department of Surgery, Massachusetts General Hospital, Harvard, Medical School, Boston, Massachusetts 02114, USA.
Gupta
Rajiv
R
Huang
Albert Y
AY
Weinberg
Eli
E
Madisch
Ijad
I
Qudsi
Rameez A
RA
Neville
Craig M
CM
Pomerantseva
Irina
I
Vacanti
Joseph P
JP
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*
D001672:Biocompatible Materials; D018786:Bone Substitutes; D002130:Calcium Phosphates; D020100:Hydrogels; C485817:beta-tricalcium phosphate