Three-dimensional (3D) printing is becoming an increasingly common technique to fabricate scaffolds and devices for tissue engineering applications. This is due to the potential of 3D printing to provide patient-specific designs, high structural complexity, rapid on-demand fabrication at a low-cost. One of the major bottlenecks that limits the widespread acceptance of 3D printing in biomanufacturing is the lack of diversity in “biomaterial inks”. Printability of a biomaterial is determined by the printing technique. Although a wide range of biomaterial inks including polymers, ceramics, hydrogels and composites have been developed, the field is still struggling with processing of these materials into self-supporting devices with tunable mechanics, degradation, and bioactivity. This review aims to highlight the past and recent advances in biomaterial ink development and design considerations moving forward. A brief overview of 3D printing technologies focusing on ink design parameters is also included.
Stem cells that adopt distinct lineages cannot be distinguished based on traditional cell shape. This study reports that higher-order variations in cell shape and cytoskeletal organization that occur within hours of stimulation forecast the lineage commitment fates of human mesenchymal stem cells (hMSCs). The unique approach captures numerous early (24 h), quantitative features of actin fluororeporter shapes, intensities, textures, and spatial distributions (collectively termed morphometric descriptors). The large number of descriptors are reduced into "combinations" through which distinct subpopulations of cells featuring unique combinations are identified. We demonstrate that hMSCs cultured on fibronectin-treated glass substrates under environments permissive to bone lineage induction could be readily discerned within the first 24 h from those cultured in basal-or fat-inductive conditions by such cytoskeletal feature groupings. We extend the utility of this approach to forecast osteogenic stem cell lineage fates across a series of synthetic polymeric materials of diverse physicochemical properties. Within the first 24 h following stem cell seeding, we could successfully "profile" the substrate responsiveness prospectively in terms of the degree of bone versus nonbone predisposition. The morphometric methodology also provided insights into how substrates may modulate the pace of osteogenic lineage specification. Cells on glass substrates deficient in fibronectin showed a similar divergence of lineage fates, but delayed beyond 48 h. In summary, this high-content imaging and single cell modeling approach offers a framework to elucidate and manipulate determinants of stem cell behaviors, as well as to screen stem cell lineage modulating materials and environments.biomaterials | differentiation | imaging and modeling | stem cells | actin organization
The design of polymers for specialty applications such as medical implants, 1,2 piezoelectric 3 and photonic materials, 4 or self-assembling systems 5 is challenging since such materials must meet multifaceted requirements. For example, the field of tissue engineering hinges on developing degradable scaffolds that promote cell proliferation and expression of desired physiologic behaviors through careful control of the polymer surface properties. 6 Here we report the concept of permutationally designed monomer systems to create libraries of structurally related polymers. To obtain libraries in which material properties vary in a predictable and systematic fashion, it is necessary to use carefully designed monomers and polymerization strategies. This can be achieved in strictly alternating A-B type copolymers in which the first monomer (A) contains a reactive group for the attachment of a series of pendent chains, while the second monomer (B) allows for systematic variations in the polymer backbone structure. The copolymerization of n different monomers A with m different monomers B gives rise to an array of n×m structurally related copolymers. Such libraries can be used to (1) increase the number of available polymeric candidate materials for any specific application and (2) systematize the study of correlations between polymer structure, material properties, and performance. As a first implementation of this concept, a library of 112 polyarylates 3 was prepared from 14 distinct tyrosine-derived diphenols 1 and eight aliphatic diacids 2 ( Figure 1). These polymers are based on natural metabolites and are biodegradable and potentially useful as medical implant materials. 7 In the set of tyrosine-derived diphenols 1, the pendent group R and the number of methylene groups (n ) 0, 1) were varied, while in the set of diacids 2, the polymer backbone was varied via structural changes at Y. In combination, variations at R and Y provided incremental differences in polymer free volume, bulkiness, flexibility, and hydrophobicity. We found that the library of 112 polymers exhibited predictable changes in glass transition temperature (T g ), surface wettability (as measured by the air-water contact angle), and cellular response (as measured by in vitro cell proliferation studies). On the other hand, since all polymers were derived from very similar monomers, they could be prepared under identical reaction conditions and shared important material properties such as solubility in organic solvents, thermal processibility, and amorphous morphology.Up to 32 simultaneous reactions on a 0.2 g scale (based on the amount of diphenol 1) were conducted in separate reaction vessels set up in a water shaker bath. Since the monomers used had almost identical reactivities at their respective functional groups, the same reaction conditions were employed and each polymerization was conducted and worked up in the same reaction vessel. About 0.1-0.2 g of each polymer was obtained after two precipitations from methanol. This methodology can be...
This review provides the first comprehensive overview of the use of both nanoparticles and nanofibers for topical drug delivery. Researchers have explored the use of nanotechnology, specifically nanoparticles and nanofibers, as drug delivery systems for topical and transdermal applications. This approach employs increased drug concentration in the carrier, in order to increase drug flux into and through the skin. Both nanoparticles and nanofibers can be used to deliver hydrophobic and hydrophilic drugs and are capable of controlled release for a prolonged period of time. The examples presented provide significant evidence that this area of research has—and will continue to have — a profound impact on both clinical outcomes and the development of new products.
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