Soft tissue reconstruction often requires multiple surgical procedures that can
result in scars and disfiguration. Facial soft tissue reconstruction represents a clinical
challenge because even subtle deformities can severely affect an individual’s
social and psychological function. We therefore developed a biosynthetic soft tissue
replacement composed of poly(ethylene glycol) (PEG) and hyaluronic acid (HA) that can be
injected and photocrosslinked in situ with transdermal light exposure. Modulating the
ratio of synthetic to biological polymer allowed us to tune implant elasticity and volume
persistence. In a small-animal model, implanted photocrosslinked PEG-HA showed a
dose-dependent relationship between increasing PEG concentration and enhanced implant
volume persistence. In direct comparison with commercial HA injections, the PEG-HA
implants maintained significantly greater average volumes and heights. Reversibility of
the implant volume was achieved with hyaluronidase injection. Pilot clinical testing in
human patients confirmed the feasibility of the transdermal photocrosslinking approach for
implantation in abdomen soft tissue, although an inflammatory response was observed
surrounding some of the materials.
Three-dimensional (3D) tumor spheroid models have gained increased recognition as important tools in cancer research and anti-cancer drug development. However, currently available imaging approaches employed in high-throughput screening drug discovery platforms e.g. bright field, phase contrast, and fluorescence microscopies, are unable to resolve 3D structures deep inside (>50 µm) tumor spheroids. In this study, we established a label-free, non-invasive optical coherence tomography (OCT) imaging platform to characterize 3D morphological and physiological information of multicellular tumor spheroids (MCTS) growing from ~250 µm up to ~600 µm in height over 21 days. In particular, tumor spheroids of two cell lines glioblastoma (U-87 MG) and colorectal carcinoma (HCT 116) exhibited distinctive evolutions in their geometric shapes at late growth stages. Volumes of MCTS were accurately quantified using a voxel-based approach without presumptions of their geometries. In contrast, conventional diameter-based volume calculations assuming perfect spherical shape resulted in large quantification errors. Furthermore, we successfully detected necrotic regions within these tumor spheroids based on increased intrinsic optical attenuation, suggesting a promising alternative of label-free viability tests in tumor spheroids. Therefore, OCT can serve as a promising imaging modality to characterize morphological and physiological features of MCTS, showing great potential for high-throughput drug screening.
Collagen-rich tissues in the cornea exhibit unique and highly organized extracellular matrix ultrastructures, which contribute to its high load-bearing capacity and light transmittance. Corneal collagen fibrils are controlled during development by small leucine-rich proteoglycans (SLRPs) that regulate the fibril diameter and spacing in order to achieve the unique optical transparency. Cyclodextrins (CDs) of varying size and chemical functionality for their ability to regulate collagen assembly during vitrification process are screened in order to create biosynthetic materials that mimic the native cornea structure. Addition of βCD to collagen vitrigels produces materials with aligned fibers and lamellae similar to native cornea, resulting in mechanically robust and transparent materials. Biochemistry analysis revealed that CD interacts with hydrophobic amino acids in collagen to influence assembly and fibril organization. To translate the self-assembled collagen materials for cornea reconstruction, custom molds for gelation and vitrification are engineered to create βCD/Col implants with curvature matching that of the cornea. Acellular βCD/Col materials are implanted in a rabbit partial keratoplasty model with interrupted sutures. The implants demonstrate tissue integration and support re-epithelialization. Therefore, the addition of CD molecules regulates collagen self-assembly and provides a simple process to engineer corneal mimetic substitutes with advanced structural and functional properties.
Triggering shape-memory functionality under clinical hyperthermia temperatures could enable the control and actuation of shape-memory systems in clinical practice. For this purpose, we developed light-inducible shape-memory microparticles composed of a poly(d,l-lactic acid) (PDLLA) matrix encapsulating gold nanoparticles (Au@PDLLA hybrid microparticles). This shape-memory polymeric system for the first time demonstrates the capability of maintaining an anisotropic shape at body temperature with triggered shape-memory effect back to a spherical shape at a narrow temperature range above body temperature with a proper shape recovery speed (37 < T < 45 °C). We applied a modified film-stretching processing method with carefully controlled stretching temperature to enable shape memory and anisotropy in these micron-sized particles. Accordingly, we achieved purely entanglement-based shape-memory response without chemical cross-links in the miniaturized shape-memory system. Furthermore, these shape-memory microparticles exhibited light-induced spatiotemporal control of their shape recovery using a laser to trigger the photothermal heating of doped gold nanoparticles. This shape-memory system is composed of biocompatible components and exhibits spatiotemporal controllability of its properties, demonstrating a potential for various biomedical applications, such as tuning macrophage phagocytosis as demonstrated in this study.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.