Softness and firmness are seemingly incompatible traits that synergize to create the unique soft-yet-firm tactility of living tissues pursued in soft robotics, wearable electronics, and plastic surgery. This dichotomy is particularly pronounced in tissues such as fat that are known to be both ultrasoft and ultrafirm. However, synthetically replicating this mechanical response remains elusive since ubiquitously employed soft gels are unable to concurrently reproduce tissue firmness. We have addressed the tissue challenge through the self-assembly of linear–bottlebrush–linear (LBL) block copolymers into thermoplastic elastomers. This hybrid molecular architecture delivers a hierarchical network organization with a cascade of deformation mechanisms responsible for initially low moduli followed by intense strain-stiffening. By bridging the firmness gap between gels and tissues, we have replicated the mechanics of fat, fetal membrane, spinal cord, and brain tissues. These solvent-free, nonleachable, and tissue-mimetic elastomers also show enhanced biocompatibility as demonstrated by cell proliferation studies, all of which are vital for the safety and longevity of future biomedical devices.

The use of solvent‐free microfluidics to fine‐tune the physical and chemical properties of chitosan nanoparticles for drug delivery is demonstrated. Nanoparticle self‐assembly is driven by pH changes in a water environment, which increases biocompatibility by avoiding organic solvent contamination common with traditional techniques. Controlling the time of mixing (2.5–75 ms) during nanoparticle self‐assembly enables us to adjust nanoparticle size and surface potential in order to maximize cellular uptake, which in turn dramatically increases drug effectiveness. The compact nanostructure of these nanoparticles preserves drug potency better than previous nanoparticles, and is more stable during long‐term circulation at physiological pH. However, when the nanoparticles encounter a tumor cell and the associated drop in pH, the drug contents are released. Moreover, the loading efficiency of hydrophobic drugs into the nanoparticles increases significantly from previous work to over 95%. The microfluidic techniques used here have applications not just for drug‐carrying nanoparticle fabrication, but also for the better control of virtually any self‐assembly process.

While chain branching generally promotes swelling of polymer networks, it also leads to nonlinear modulus increase with network expansion. To understand the effect of branched architecture on swelling, we study comb-like and bottlebrush networks using a combination of theoretical analysis, computer simulations, and experiments. The equilibrium swelling ratio of such networks is shown to be larger than that of conventional linear chain networks as a result of two effects: architectural disentanglement of network strands and amplification of polymer–solvent interactions by side chains. For networks of brush-like strands with poly­(dimethylsiloxane) side chains in toluene, we achieve a swelling ratio of Q = 30, which is larger than that of linear chain networks with the same strand length. All of the studied systems, including linear chain, comb, and bottlebrush networks, follow a universal scaling relation, G(Q) ∝ Q –δ, between the deformation-dependent shear modulus G(Q) and swelling ratio Q with scaling exponents δ = 2.6 ± 0.08 (simulations) and δ = 2.6 ± 0.12 (experiments). These values agree with the theoretically predicted exponent δ = 8/3, confirming dominant contribution of three-body interactions to the osmotic pressure which drives network swelling. The established correlations between network strand architecture, nonlinear elastic modulus, and equilibrium swelling ratio provide a general framework for architectural control of swelling capacity and the design of superabsorbent materials.

Porous scaffolds were 3D-printed using poly lactic-co-glycolic acid (PLGA)/TiO 2 composite (10:1 weight ratio) for bone tissue engineering applications. Addition of TiO 2 nanoparticles improved the compressive modulus of scaffolds. Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) revealed an increase in both glass transition temperature and thermal decomposition onset of the composite compared to pure PLGA. Furthermore, addition of TiO 2 was found to enhance the wettability of the surface evidenced by reducing the contact angle from 90.5 ± 3.2 to 79.8 ± 2.4 which in favor of cellular attachment and activity. The obtained results revealed that PLGA/TiO 2 scaffolds significantly improved osteoblast proliferation compared to pure PLGA (P < 0.05). Furthermore, osteoblasts cultured on PLGA/TiO 2 nanocomposite represented significantly higher ALP activity and improved calcium secretion compared to pure PLGA scaffolds (p < 0.05).

Vascularization is a critical process during bone regeneration/repair and the lack of tissue vascularization is recognized as a major challenge in applying bone tissue engineering methods for cranial and maxillofacial surgeries. The aim of our study is to fabricate a vascular endothelial growth factor (VEGF)-loaded gelatin/alginate/β-TCP composite scaffold by 3D printing method using a computer-assisted design (CAD) model. Rheological characterization of various gelatin/alginate/β-TCP formulations led to an optimized paste as a printable bioink at room temperature. VEGF-loaded PLGA microspheres were then incorporated into the paste prior to printing to ensure sustained release of the growth factor. The in vitro release kinetics of the loaded VEGF revealed that the designed scaffolds fulfill the bioavailability of VEGF required for vascularization in the early stages of tissue regeneration. The results were confirmed by two times increment of proliferation of human umbilical vein endothelial cells (HUVECs) seeded on the scaffolds after 10 days. The compressive modulus of the scaffolds, 98 ± 11 MPa, was found to be in the range of cancellous bone suggesting their potential application for craniofacial tissue engineering. Osteoblast culture on the scaffolds showed that the construct supports cell viability, adhesion and proliferation. It was found that the ALP activity increased over 50% using VEGF-loaded scaffolds after 2 weeks of culture. In conclusion, the 3D printed gelatin/alginate/β-TCP scaffold with slow releasing of VEGF can be considered as a potential candidate for regeneration of craniofacial defects.

Injectable hydrogels are desired in many biomedical applications due to their minimally invasive deployment to the body and their ability to introduce drugs. However, current injectables suffer from mechanical mismatch with tissue, fragility, water expulsion, and high viscosity. To address these issues, we design brush-like macromolecules that concurrently provide softness, firmness, strength, fluidity, and swellability. The synthesized linear-bottlebrush-linear (LBL) copolymers facilitate improved injectability as the compact conformation of bottlebrush blocks results in low solution viscosity, while the thermoresponsive linear blocks permit prompt gelation at 37°C. The resulting hydrogels mimic the deformation response of supersoft tissues such as adipose and brain while withstanding deformations of 700% and precluding water expulsion upon gelation. Given their low cytotoxicity and mild inflammation in vivo, the developed materials will have vital implications for reconstructive surgery, tissue engineering, and drug delivery applications.

We present a microfluidic platform for the synthesis of monodisperse chitosan based nanoparticles via self-assembly at physiological pH. The resultant nanoparticles are shown to encapsulate hydrophobic anticancer drugs while providing a sustainable release profile with high tunability.

Alginate is a biopolymer with favorable pH-sensitive properties for oral delivery of peptides and proteins. However, conventional alginate nanogels have limitations such as low encapsulation efficiency because of drug leaching during bead preparation and burst release in high pH values. These shortcomings originate from large pore size of the nanogels. In this work, we proposed an on-chip hydrodynamic flow focusing approach for synthesis of alginate nanogels with adjustable pore size to achieve fine-tunable release profile of the encapsulated bioactive agents. It is demonstrated that the microstructure of nanogels can be controlled through adjusting flow ratio and mixing time directed on microfluidic platforms consisting of cross-junction microchannels. In this study, the average pore size of alginate nanogels (i.e., average molecular weight between cross-links, Mc) was related to synthesis parameters. Mc was calculated from equations based on equilibrium swelling theory and proposed methods to modify the theory for pH-sensitive nanogels. In the equations we derived, size and compactness of nanogels are key factors, which can be adjusted by controlling the flow ratio. It was found that increase in flow ratio increases the size of nanogels and decreases their compactness. The size of on-chip generated nanogels for flow ratio of 0.02-0.2 was measured to be in the range of 68-138 nm. Moreover, a method based on the Mie theory was implemented to estimate the aggregation number (Nagg) of polymer chains inside the nanogels as an indicator of compactness. According to the size and compactness results along with equations of modified swelling theory, Mc obtained to be in the range of 0.5-0.8 kDa. The proposed method could be considered as a promising approach for efficient polypeptides encapsulation and their sustained release.