Browsing by Author "Vo, Tiffany N."

Now showing 1 - 8 of 8
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    Biodegradable, phosphate-containing, dual-gelling macromers for cellular delivery in bone tissue engineering
    (Elsevier, 2015) Watson, Brendan M.; Vo, Tiffany N.; Tatara, Alexander M.; Shah, Sarita R.; Scott, David W.; Engel, Paul S.; Mikos, Antonios G.
    Injectable, biodegradable, dual-gelling macromer solutions were used to encapsulate mesenchymal stem cells (MSCs) within stable hydrogels when elevated to physiologic temperature. Pendant phosphate groups were incorporated in the N-isopropyl acrylamide-based macromers to improve biointegration and facilitate hydrogel degradation. The MSCs were shown to survive the encapsulation process, and live cells were detected within the hydrogels for up to 28 days inﾠvitro. Cell-laden hydrogels were shown to undergo significant mineralization in osteogenic medium. Cell-laden and acellular hydrogels were implanted into a critical-size rat cranial defect for 4 and 12 weeks. Both cell-laden and acellular hydrogels were shown to degrade inﾠvivo and help to facilitate bone growth into the defect. Improved bone bridging of the defect was seen with the incorporation of cells, as well as with higher phosphate content of the macromer. Furthermore, direct bone-to-hydrogel contact was observed in the majority of implants, which is not commonly seen in this model. The ability of these macromers to deliver stem cells while forming in situ and subsequently degrade while facilitating bone ingrowth into the defect makes this class of macromers a promising material for craniofacial bone tissue engineering.
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    Effects of cellular parameters on the in vitro osteogenic potential of dual-gelling mesenchymal stem cell-laden hydrogels
    (Taylor & Francis, 2016) Vo, Tiffany N.; Tabata, Yasuhiko; Mikos, Antonios G.
    This work investigated the effects of cellular encapsulation density and differentiation stage on the osteogenic capacity of injectable, dual physically and chemically gelling hydrogels comprised of thermogelling macromers and polyamidoamine crosslinkers. Undifferentiated and osteogenically predifferentiated mesenchymal stem cells (MSCs) were encapsulated within 20 wt% composite hydrogels with gelatin microparticles at densities of six or 15 million cells/mL. We hypothesized that a high encapsulation density and predifferentiation would promote increased cellular interaction and accelerate osteogenesis, leading to enhanced osteogenic potential in vitro. Hydrogels were able to maintain the viability of the encapsulated cells over a period of 28 days, with the high encapsulation density and predifferentiation group possessing the highest DNA content at all time points. Early alkaline phosphatase activity and mineralization were promoted by encapsulation density, whereas this effect by predifferentiation was only observed in the low seeding density groups. Both parameters only demonstrated short-lived effects when examined independently, but jointly led to greater levels of alkaline phosphatase activity and mineralization. The combined effects suggest that there may be optimal encapsulation densities and differentiation periods that need to be investigated to improve MSCs for biomaterial-based therapeutics in bone tissue engineering.
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    In vitroﾠandﾠin vivoﾠevaluation of self-mineralization and biocompatibility of injectable, dual-gelling hydrogels for bone tissue engineering
    (Elsevier, 2015) Vo, Tiffany N.; Ekenseair, Adam K.; Spicer, Patrick P.; Watson, Brendan M.; Tzouanas, Stephanie N.; Roh, Terrence T.; Mikos, Antonios G.
    In this study, we investigated the mineralization capacity and biocompatibility of injectable, dual-gelling hydrogels in a rat cranial defect as a function of hydrogel hydrophobicity from either the copolymerization of a hydrolyzable lactone ring or the hydrogel polymer content. The hydrogel system comprised a poly(N-isopropylacrylamide)-based thermogelling macromer (TGM) and a polyamidoamine crosslinker. The thermogelling macromer was copolymerized with (TGM/DBA) or without (TGM) a dimethyl-γ-butyrolactone acrylate (DBA)-containing lactone ring that modulated the lower critical solution temperature and thus, the hydrogel hydrophobicity, over time. Three hydrogel groups were examined: (1) 15wt.% TGM, (2) 15wt.% TGM/DBA, and (3) 20wt.% TGM/DBA. The hydrogels were implanted within an 8mm critical size rat cranial defect for 4 and 12weeks. Implants were harvested at each timepoint and analyzed for bone formation, hydrogel mineralization and tissue response using microcomputed tomography (microCT). Histology and fibrous capsule scoring showed a light inflammatory response at 4weeks that was mitigated by 12weeks for all groups. MicroCT scoring and bone volume quantification demonstrated a similar bone formation at 4weeks that was significantly increased for the more hydrophobic hydrogel formulations - 15wt.% TGM and 20wt.% TGM/DBA - from 4weeks to 12weeks. A complementary in vitro acellular mineralization study revealed that the hydrogels exhibited calcium binding properties in the presence of serum-containing media, which was modulated by the hydrogel hydrophobicity. The tailored mineralization capacity of these injectable, dual-gelling hydrogels with hydrolysis-dependent hydrophobicity presents an exciting property for their use in bone tissue engineering applications.
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    Injectable hydrogels
    (2016-03-15) Mikos, Antonios G.; Kasper, Kurtis F.; Ekenseair, Adam K.; Vo, Tiffany N.; Boere, Kristel W.M.; Touchet, Tyler J.; Rice University; United States Patent and Trademark Office
    The present disclosure generally relates to injectable compositions. More particularly, the present disclosure relates to injectable, thermogelling hydrogels and associated methods. In one embodiment, the present disclosure provides for a composition comprising a poly(N-isopropylacrylamide)-based macromer and a polyamidoamine-based macromer.
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    Pre-clinical Characterization of Tissue Engineering Constructs for Bone and Cartilage Regeneration
    (Springer, 2015) Trachtenberg, Jordan E.; Vo, Tiffany N.; Mikos, Antonios G.
    Pre-clinical animal models play a crucial role in the translation of biomedical technologies from the bench top to the bedside. However, there is a need for improved techniques to evaluate implanted biomaterials within the host, including consideration of the care and ethics associated with animal studies, as well as the evaluation of host tissue repair in a clinically relevant manner. This review discusses non-invasive, quantitative, and real-time techniques for evaluating host-materials interactions, quality and rate of neotissue formation, and functional outcomes of implanted biomaterials for bone and cartilage tissue engineering. Specifically, a comparison will be presented for pre-clinical animal models, histological scoring systems, and non-invasive imaging modalities. Additionally, novel technologies to track delivered cells and growth factors will be discussed, including methods to directly correlate their release with tissue growth.
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    Structure-Property Evaluation of Thermally and Chemically Gelling Injectable Hydrogels for Tissue Engineering
    (American Chemical Society, 2012) Ekenseair, Adam K.; Boere, Kristel W.M.; Tzouanas, Stephanie N.; Vo, Tiffany N.; Kasper, F. Kurtis; Mikos, Antonios G.
    The impact of synthesis and solution formulation parameters on the swelling and mechanical properties of a novel class of thermally and chemically gelling hydrogels combining poly(N-isopropylacrylamide)-based thermogelling macromers containing pendant epoxy rings with polyamidoamine-based hydrophilic and degradable diamine cross-linking macromers was evaluated. Through variation of network hydrophilicity and capacity for chain rearrangement, the often problematic tendency of thermogelling hydrogels to undergo significant syneresis was addressed. The demonstrated ability to tune postformation dimensional stability easily at both the synthesis and formulation stages represents a significant novel contribution toward efforts to utilize poly(N-isopropylacrylamide)-based polymers as injectable biomaterials. Furthermore, the cytocompatibility of the hydrogel system under relevant conditions was established while demonstrating time- and dose-dependent cytotoxicity at high solution osmolality. Such injectable in situ forming degradable hydrogels with tunable water content are promising candidates for many tissue-engineering applications, particularly for cell delivery to promote rapid tissue regeneration in non-load-bearing defects.
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    Synthesis and Characterization of Thermally and Chemically Gelling Injectable Hydrogels for Tissue Engineering
    (American Chemical Society, 2012) Ekenseair, Adam K.; Boere, Kristel W.M.; Tzouanas, Stephanie N.; Vo, Tiffany N.; Kasper, F. Kurtis; Mikos, Antonios G.
    Novel, injectable hydrogels were developed that solidify through a dual-gelation, physical and chemical, mechanism upon preparation and elevation of temperature to 37°C. A thermogelling, poly(N-isopropylacrylamide)-based macromer with pendant epoxy rings and a hydrolyticallydegradable polyamidoamine-based diamine crosslinker were synthesized, characterized, and combined to produce in situ forming hydrogel constructs. Network formation through the epoxyamine reaction was shown to be rapid and facile, and the progressive incorporation of the hydrophilic polyamidoamine crosslinker into the hydrogel was shown to mitigate the often problematic tendency of thermogelling materials to undergo significant post-formation gel syneresis. The results suggest that this novel class of injectable hydrogels may be attractive substrates for tissue engineering applications due to the synthetic versatility of the component materials and beneficial hydrogel gelation kinetics and stability.
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    Synthesis, Physicochemical Characterization, and Cytocompatibility of Bioresorbable, Dual-Gelling Injectable Hydrogels
    (American Chemical Society, 2014) Vo, Tiffany N.; Ekenseair, Adam K.; Kasper, F. Kurtis; Mikos, Antonios G.
    Injectable, dual-gelling hydrogels were successfully developed through the combination of physical thermogellation at 37 °C and favorable amine:epoxy chemical cross-linking. Poly(N-isopropylacrylamide)-based thermogelling macromers with a hydrolyzable lactone ring and epoxy pendant groups and a biodegradable diamine-functionalized polyamidoamine cross-linker were synthesized, characterized, and combined to produce nonsyneresing and bioresorbable hydrogels. Differential scanning calorimetry and oscillatory rheometry demonstrated the rapid and dual-gelling nature of the hydrogel formation. The postgelation dimensional stability, swelling, and mechanical behavior of the hydrogel system were shown to be easily tuned in the synthesis and formulation stages. The leachable products were found to be cytocompatible under all conditions, while the degradation products demonstrated a dose- and time-dependent response due to solution osmolality. Preliminary encapsulation studies showed mesenchymal stem cell viability could be maintained for 7 days. The results suggest that injectable and thermally and chemically cross-linkable hydrogels are promising alternatives to prefabricated biomaterials for tissue engineering applications, particularly for cell delivery.