Injectable dual-gelling cell-laden composite hydrogels for bone tissue engineering

• Published in: Biomaterials Vol. 83; pp. 1 - 11
• Main Authors: Vo, T.N, Shah, S.R, Lu, S, Tatara, A.M, Lee, E.J, Roh, T.T, Tabata, Y, Mikos, A.G
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01-03-2016
• Subjects: Advanced Basic Science; Alkaline Phosphatase - metabolism; Animals; Biological Assay; Biomedical materials; Bone and Bones - diagnostic imaging; Bone and Bones - drug effects; Bone and Bones - physiology; Bones; Cells, Immobilized - cytology; Cells, Immobilized - drug effects; Cells, Immobilized - metabolism; Critical size cranial defect; Defects; Dentistry; Encapsulation; Gelatin - pharmacology; Gelatin microparticles; Hydrogels; Hydrogels - pharmacology; In vitro testing; Injections; Mesenchymal stem cells; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - drug effects; Microspheres; Mineralization; N-isopropylacrylamide; Rats, Inbred F344; Tissue engineering; Tissue Engineering - methods; X-Ray Microtomography; MicroCT; DBA; ALP; Phosphate buffered saline; Mineralization; FBS; GMA; Mesenchymal stem cells; Weight average molecular weight; AA; Mesenchymal stem cell; PBS; Volume of interest; 1H NMR; GMP; Fetal bovine serum; PAMAM; High Performance Liquid Chromatography; VOI; Azobisisobutyronitrile; N-isopropylacrylamide; Glycidyl methacrylate; TGM; Microcomputed tomography; Alkaline phosphatase; Acrylic acid; Polyamidoamine; Proton Nuclear Magnetic Spectroscopy; MBA; Number average molecular weight; Thermogelling macromer; PDI; Piperazine; PiP; Extracellular matrix; M n; MSC; HPLC; NiPAAm; Three dimensional; COM; Methylene Bisacrylamide; Dimethyl-γ-butyrolactone acrylate; Gelatin microparticles; M w; AIBN; Polydispersity index; ECM; 3D; Complete osteogenic media; Critical size cranial defect; Gelatin microparticle; Mn; Mw
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2015.12.026

Abstract The present work investigated the osteogenic potential of injectable, dual thermally and chemically gelable composite hydrogels for mesenchymal stem cell (MSC) delivery in vitro and in vivo . Composite hydrogels comprising copolymer macromers of N -isopropylacrylamide were fabricated through the incorporation of gelatin microparticles (GMPs) as enzymatically digestible porogens and sites for cellular attachment. High and low polymer content hydrogels with and without GMP loading were shown to successfully encapsulate viable MSCs and maintain their survival over 28 days in vitro . GMP incorporation was also shown to modulate alkaline phosphatase production, but enhanced hydrogel mineralization along with higher polymer content even in the absence of cells. Moreover, the regenerative capacity of 2 mm thick hydrogels with GMPs only, MSCs only, or GMPs and MSCs was evaluated in vivo in an 8 mm rat critical size cranial defect for 4 and 12 weeks. GMP incorporation led to enhanced bony bridging and mineralization within the defect at each timepoint, and direct bone-implant contact as determined by microcomputed tomography and histological scoring, respectively. Encapsulation of both GMPs and MSCs enabled hydrogel degradation leading to significant tissue infiltration and osteoid formation. The results suggest that these injectable, dual-gelling cell-laden composite hydrogels can facilitate bone ingrowth and integration, warranting further investigation for bone tissue engineering.