Electrospun Photocrosslinkable Hydrogel Fibrous Scaffolds for Rapid In Vivo Vascularized Skin Flap Regeneration

Distal necrosis of random skin flap is always clinical problematic in plastic surgery. The development of 3D functional vascular networks is fundamental for the survival of a local random skin flap. Herein, an effective technique on constructing 3D fibrous scaffolds for accelerated vascularization is demonstrated using a photocrosslinkable natural hydrogel based on gelatin methacryloyl (GelMA) by electrospinning. It is found that the ultraviolet (UV) photocrosslinkable gelatin electrospun hydrogel fibrous membranes exhibit soft adjustable mechanical properties and controllable degradation properties. Furthermore, it is observed that the optimized hydrogel scaffolds can support endothelial cells and dermal fibroblasts adhesion, proliferation, and migration into the scaffolds, which facilitates vascularization. Importantly, a rapid formation of tubes is observed after 3 d seeding of endothelial cells. After GelMA fibrous scaffold implantation below the skin flap in a rat model, it is found that the flap survival rate is higher than the control group, and there is more microvascular formation, which is potentially beneficial for the flap tissue vascularization. These data suggest that GelMA hydrogels can be used for biomedical applications that require the formation of microvascular networks, including the development of complex engineered tissues.     

Combining 3D Printing with Electrospinning for Rapid Response and Enhanced Designability of Hydrogel Actuators

Porous structures have emerged as a breakthrough of shape‐morphing hydrogels to achieve a rapid response. However, these porous actuators generally suffer from a lack of complexity and diversity in obtained 3D shapes. Herein, a simple yet versatile strategy is developed to generate shape‐morphing hydrogels with both fast deformation and enhanced designability in 3D shapes by combining two promising technologies: electrospinning and 3D printing. Elaborate patterns are printed on mesostructured stimuli‐responsive electrospun membranes, modulating in‐plane and interlayer internal stresses induced by swelling/shrinkage mismatch, and thus guiding morphing behaviors of electrospun membranes to adapt to changes of the environment. With this strategy, a series of fast deformed hydrogel actuators are constructed with various distinctive responsive behaviors, including reversible/irreversible formations of 3D structures, folding of 3D tubes, and formations of 3D structures with multi low‐energy states. It is worth noting that although poly(N‐isopropyl acrylamide) is chosen as the model system in the present research, our strategy is applicable to other stimuli‐responsive hydrogels, which enriches designs of rapid deformed hydrogel actuators.     

Nanofibrillar Decellularized Wharton's Jelly Matrix for Segmental Tracheal Repair

Wharton's jelly (WJ) is considered a potential scaffold in tissue‐engineered trachea for its similar composition and function to cartilage tissue. However, the feasibility of using WJ to construct engineered neocartilage tissue has not been reported, let alone tubular tracheal cartilage regeneration and segmental tracheal lesion repair. Here, electrospun nanofibrous membranes composed of three different decellularized WJ matrix (DWJM)/poly(ε‐caprolactone) (PCL) ratios (8:2, 5:5, and 2:8) are fabricated. The results demonstrate improved degradation speed, absorption, and cell adhesion capacity but weakened mechanical properties with increased DWJM content, but satisfactory homogeneous cartilage regeneration is only achieved in the DWJM/PCL (8:2) group after 12 weeks in vivo culture. Furthermore, homogeneous, 3D, tubular, trachea‐shaped cartilage is constructed with a controllable lumen diameter and wall thickness based on the 2D nanofibrous membrane using a modified sandwich model, in which the chondrocyte‐membrane construct is rolled around a silicon tube. Most importantly, by combining the above schemes with previously established vascularization and epithelialization techniques, chondrification, vascularization, and epithelialization are achieved simultaneously thus realizing long‐term (6 months) circumferential tracheal lesion repair in a rabbit model with a biological structure and function similar to that of native trachea, representing a promising approach for the clinical application of tracheal tissue engineering.     

Nanofibrous Patches for Spinal Cord Regeneration

The difficulty in spinal cord regeneration is related to the inhibitory factors for axon growth and the lack of appropriate axon guidance in the lesion region. Here scaffolds are developed with aligned nanofibers for nerve guidance and drug delivery in the spinal cord. Blended polymers including poly(L ‐lactic acid) (PLLA) and poly(lactide‐co‐glycolide) (PLGA) are used to electrospin nanofibrous scaffolds with a two‐layer structure: aligned nanofibers in the inner layer and random nanofibers in the outer layer. Rolipram, a small molecule that can enhance cAMP (cyclic adenosine monophosphate) activity in neurons and suppress inflammatory responses, is immobilized onto nanofibers. To test the therapeutic effects of nanofibrous scaffolds, the nanofibrous scaffolds loaded with rolipram are used to bridge the hemisection lesion in 8‐week old athymic rats. The scaffolds with rolipram increase axon growth through the scaffolds and in the lesion, promote angiogenesis through the scaffold, and decrease the population of astrocytes and chondroitin sulfate proteoglycans in the lesion. Locomotor scale rating analysis shows that the scaffolds with rolipram significantly improved hindlimb function after 3 weeks. This study demonstrates that nanofibrous scaffolds offer a valuable platform for drug delivery for spinal cord regeneration.     

Bioinspired Hydrogel Electrospun Fibers for Spinal Cord Regeneration

Fully simulating the components and microstructures of soft tissue is a challenge for its functional regeneration. A new aligned hydrogel microfiber scaffold for spinal cord regeneration is constructed with photocrosslinked gelatin methacryloyl (GelMA) and electrospinning technology. The directional porous hydrogel fibrous scaffold consistent with nerve axons is vital to guide cell migration and axon extension. The GelMA hydrogel electrospun fibers soak up water more than six times their weight, with a lower Young's modulus, providing a favorable survival and metabolic environment for neuronal cells. GelMA fibers further demonstrate higher antinestin, anti‐Tuj‐1, antisynaptophysin, and anti‐CD31 gene expression in neural stem cells, neuronal cells, synapses, and vascular endothelial cells, respectively. In contrast, anti‐GFAP and anti‐CS56 labeled astrocytes and glial scars of GelMA fibers are shown to be present in a lesser extent compared with gelatin fibers. The soft bionic scaffold constructed with electrospun GelMA hydrogel fibers not only facilitates the migration of neural stem cells and induces their differentiation into neuronal cells, but also inhibits the glial scar formation and promotes angiogenesis. Moreover, the scaffold with a high degree of elasticity can resist deformation without the protection of a bony spinal canal. The bioinspired aligned hydrogel microfiber proves to be efficient and versatile in triggering functional regeneration of the spinal cord.     

Polymer Scaffolds for Small‐Diameter Vascular Tissue Engineering

To better engineer small‐diameter blood vessels, a few types of novel scaffolds are fabricated from biodegradable poly(L ‐lactic acid) (PLLA) by means of thermally induced phase‐separation (TIPS) techniques. By utilizing the differences in thermal conductivities of the mold materials and using benzene as the solvent scaffolds with oriented gradient microtubular structures in the axial or radial direction can be created. The porosity, tubular size, and the orientational direction of the microtubules can be controlled by the polymer concentration, the TIPS temperature, and by utilizing materials of different thermal conductivities. These gradient microtubular structures facilitate cell seeding and mass transfer for cell growth and function. Nanofibrous scaffolds with an oriented and interconnected microtubular pore network are also developed by a one‐step TIPS method using a benzene/tetrahydrofuran mixture as the solvent without the need for porogen materials. The structural features of such scaffolds can be conveniently adjusted by varying the solvent ratio, phase‐separation temperature, and polymer concentration to mimic the nanofibrous features of an extracellular matrix. These scaffolds were fabricated for the tissue engineering of small‐diameter blood vessels by utilizing their advantageous structural features to facilitate blood‐vessel regeneration.     

Heterotypic Scaffold Design Orchestrates Primary Cell Organization and Phenotypes in Cocultured Small Diameter Vascular Grafts

To facilitate true regeneration, a vascular graft should direct the evolution of a neovessel to obtain the function of a native vessel. For this, scaffolds have to permit the formation of an intraluminal endothelial cell monolayer, mimicking the tunica intima. In addition, when attempting to mimic a tunica media‐like outer layer, the stacking and orientation of vascular smooth muscle cells (vSMCs) should be recapitulated. An integral scaffold design that facilitates this has so far remained a challenge. A hybrid fabrication approach is introduced by combining solution electrospinning and melt electrowriting. This allows a tissue‐structure mimetic, hierarchically bilayered tubular scaffold, comprising an inner layer of randomly oriented dense fiber mesh and an outer layer of microfibers with controlled orientation. The scaffold supports the organization of a continuous luminal endothelial monolayer and oriented layers of vSM‐like cells in the media, thus facilitating control over specific and tissue‐mimetic cellular differentiation and support of the phenotypic morphology in the respective layers. Neither soluble factors nor a surface bioactivation of the scaffold is needed with this approach, demonstrating that heterotypic scaffold design can direct physiological tissue‐like cell organization and differentiation.     

Functional Human Vascular Network Generated in Photocrosslinkable Gelatin Methacrylate Hydrogels

The generation of functional, 3D vascular networks is a fundamental prerequisite for the development of many future tissue engineering-based therapies. Current approaches in vascular network bioengineering are largely carried out using natural hydrogels as embedding scaffolds. However, most natural hydrogels present a poor mechanical stability and a suboptimal durability, which are critical limitations that hamper their widespread applicability. The search for improved hydrogels has become a priority in tissue engineering research. Here, the suitability of a photopolymerizable gelatin methacrylate (GelMA) hydrogel to support human progenitor cell-based formation of vascular networks is demonstrated. Using GelMA as the embedding scaffold, it is shown that 3D constructs containing human blood-derived endothelial colony-forming cells (ECFCs) and bone marrow-derived mesenchymal stem cells (MSCs) generate extensive capillary-like networks in vitro. These vascular structures contain distinct lumens that are formed by the fusion of ECFC intracellular vacuoles in a process of vascular morphogenesis. The process of vascular network formation is dependent on the presence of MSCs, which differentiate into perivascular cells occupying abluminal positions within the network. Importantly, it is shown that implantation of cell-laden GelMA hydrogels into immunodeficient mice results in a rapid formation of functional anastomoses between the bioengineered human vascular network and the mouse vasculature. Furthermore, it is shown that the degree of methacrylation of the GelMA can be used to modulate the cellular behavior and the extent of vascular network formation both in vitro and in vivo. These data suggest that GelMA hydrogels can be used for biomedical applications that require the formation of microvascular networks, including the development of complex engineered tissues.     

Matrix‐Bound VEGF Mimetic Peptides: Design and Endothelial‐Cell Activation in Collagen Scaffolds

Long‐term survival and success of artificial tissue constructs depend greatly on vascularization. Endothelial‐cell (EC) differentiation and vasculature formation are dependent on spatiotemporal cues in the extracellular matrix that dynamically interact with cells; a process that is difficult to reproduce in artificial systems. Here, a novel bifunctional peptide is presented that mimics matrix‐bound vascular endothelial growth factor (VEGF) which can be used to encode spatially controlled angiogenic signals in collagen scaffolds. The peptide is comprised of a collagen mimetic domain that was previously reported to bind to type I collagen by a unique hybridization mechanism, and a VEGF‐mimetic domain with pro‐angiogenic activity. Circular dichroism and collagen‐binding studies confirm the triple‐helical structure and the collagen binding affinity of the collagen‐mimetic domain, and EC‐culture studies demonstrate the peptide's ability to induce endothelial cell morphogenesis and network formation as a matrix‐bound factor in 2D and 3D collagen scaffolds. Spatial modification of collagen substrates is also shown with this peptide, which allows localized EC activation and network formation. These results demonstrate that the peptide can be used to present spatially directed angiogenic cues in collagen scaffolds, which may be useful for engineering organized microvasculature.     

Biomimetic Elastomeric Bioactive Siloxane‐Based Hybrid Nanofibrous Scaffolds with miRNA Activation: A Joint Physico‐Chemical‐Biological Strategy for Promoting Bone Regeneration

Rapid and efficient disease‐induced or critical‐size bone regeneration remains a challenge in tissue engineering due to the lack of highly bioactive biomaterial scaffolds. Physical structures such as nanostructures, chemical components such as silicon elements, and biological factors such as genes have shown positive effects on bone regeneration. Herein, a bioactive photoluminescent elastomeric silicate‐based nanofibrous scaffold with sustained miRNA release is reported for promoting bone regeneration based on a joint physico‐chemical‐biological strategy. Bioactive nanofibrous scaffolds are fabricated by cospinning poly (ε‐caprolactone) (PCL), elastomeric poly (citrates‐siloxane) (PCS), and bioactive osteogenic miRNA nanocomplexes (denoted PPM nanofibrous scaffolds). The PPM scaffolds possess uniform nanostructures, significantly enhanced tensile stress (≈15 MPa) and modulus (≈32 MPa), improved hydrophilicity (30–60°), controlled biodegradation, and strong blue fluorescence. Bioactive miRNA complexes are efficiently loaded into the nanofibrous matrix and exhibit long‐term release for up to 70 h. The PPM scaffolds significantly promote the adhesion, proliferation, and osteoblast differentiation of bone marrow stem cells in vitro and enhanced rat cranial defect restoration (12 weeks) in vivo. This work reports an attractive joint physico‐chemical‐biological strategy for the design of novel cell/protein‐free bioactive scaffolds for synergistic tissue regeneration.     

Fabrication of Nanofiber Microarchitectures Localized within Hydrogel Microparticles and Their Application to Protein Delivery and Cell Encapsulation

A simple method to generate well‐defined microscopic architectures composed of electrospun nanofibers is reported and their potential application to biomedical fields are described. The photopatterning of polyethylene glycol (PEG) hydrogel on electrospun polycarprolactone (PCL) nanofibers leads to the formation of two different microdomains in nanofibrous mats: a bare nanofiber region and a hydrogel‐entrapped nanofiber region. The selective dissolution of bare nanofibers with an organic solvent that cannot penetrate the PEG hydrogel enables the localization of PCL nanofibers within the hydrogel microstructures, thus generating microarchitectured nanofibers. The resultant microarchitectures are easily detached from the substrate by the water‐induced swelling of the PEG hydrogel. Microparticles are ultimately obtained, the size and shape of which can be easily controlled with proper photomask designs. In proof of concept experiments, bovine serum albumin(BSA)‐loaded PCL nanofibers that are entrapped within the hydrogel microparticles are prepared and the sustained release of BSA from micropatterned nanofibers is successfully demonstrated, indicating the potential application of the proposed microarchitectured nanofibers to drug delivery systems. For another possible application, the capability of the nanofiber‐incorporated hydrogel to encapsulate mammalian cells is investigated and the incorporation of nanofibers within the PEG hydrogel promoted cell adhesion and spreading when compared with bare PEG hydrogel is confirmed.     

Light‐Coded Digital Crystallinity Patterns Toward Bioinspired 4D Transformation of Shape‐Memory Polymers

Spatially heterogeneous distribution of active components is key to the diverse shape‐morphing behaviors of biological species and their associated functions. Artificial morphing materials employing similar strategies have widened the design space for advanced functional devices. Typically, the spatial heterogeneity is introduced during the material synthesis/fabrication step and cannot be altered afterward. An approach that allows spatio‐selective programming of crystallinity in a shape‐memory polymer (SMP) by a digital photothermal effect is reported. The light‐patternable crystallinity affects greatly the shape morphing behavior. Consequently, a pre‐stretched 2D film with spatial heterogeneity in crystallinity can morph with time into designable 3D permanent shapes, achieving the 4D transformation. This approach utilizes a reprocessible thermoplastic SMP (polylactide) and the programming relies on a physical phase transformation (crystallization) instead of chemical heterogeneity. This allows repeated erasing and reprogramming using the same material, suggesting a versatile and sustainable means for manufacturing advanced morphing devices.     

Layered Gradient Nonwovens of In Situ Crosslinked Electrospun Collagenous Nanofibers Used as Modular Scaffold Systems for Soft Tissue Regeneration

In a versatile modular scaffold system, gradient nonwovens of in situ crosslinked gelatin nanofibers (CGN), fabricated by reactive electrospinning, are laminated with perforated layers and nonwovens of thermoplastic non‐crosslinked biodegradable polyesters. The addition of glyoxal to a gelatin solution in a non‐toxic solvent mixture consisting of acetic acid, ethyl acetate, and water (5:3:2 w/w/w) enables the in situ crosslinking of gelatin nanofibers during electrospinning. The use of this fluorine‐free crosslinking system eliminates the need of post‐treatment crosslinking and purification steps typical for conventional CGN scaffolds. The slowly progressing crosslinking of the dissolved gelatin in the presence of glyoxal increases the viscosity of the gelatin solution during electrospinning so that the average diameter of the crosslinked gelatin nanofibers gradually increases from 90 to 680 nm. During the subsequent lamination process, alternating layers of CGN and polycaprolactone (PCL) nonwovens, produced by 3D microextrusion of micrometer‐sized PCL fibers, are bonded together upon heating above the PCL melting temperature. In contrast to the water‐soluble gelatin nanofibers and the comparatively weak CGN, the CGN/PCL/CGN layered biocomposites are water‐resistant and very robust. In such modular scaffold systems, strength, biodegradation rate, and biological functions can be controlled by varying the type, composition, fiber diameter, porosity, number, and sequence of the individual layers. The CGN/PCL multilayer biocomposites can be cut into any desired scaffold shape and attached to tissue by surgical sutures in order to suit the needs of individual patients.     

Void‐Free 3D Bioprinting for In Situ Endothelialization and Microfluidic Perfusion

Two major challenges of 3D bioprinting are the retention of structural fidelity and efficient endothelialization for tissue vascularization. Both of these issues are addressed by introducing a versatile 3D bioprinting strategy, in which a templating bioink is deposited layer‐by‐layer alongside a matrix bioink to establish void‐free multimaterial structures. After crosslinking the matrix phase, the templating phase is sacrificed to create a well‐defined 3D network of interconnected tubular channels. This void‐free 3D printing (VF‐3DP) approach circumvents the traditional concerns of structural collapse, deformation, and oxygen inhibition, moreover, it can be readily used to print materials that are widely considered “unprintable.” By preloading endothelial cells into the templating bioink, the inner surface of the channels can be efficiently cellularized with a confluent endothelial layer. This in situ endothelialization method can be used to produce endothelium with a far greater cell seeding uniformity than can be achieved using the conventional postseeding approach. This VF‐3DP approach can also be extended beyond tissue fabrication and toward customized hydrogel‐based microfluidics and self‐supported perfusable hydrogel constructs.     

Bi‐Layered Tubular Microfiber Scaffolds as Functional Templates for Engineering Human Intestinal Smooth Muscle Tissue

Designing biomimetic scaffolds with in vivo–like microenvironments using biomaterials is an essential component of successful tissue engineering approaches. The intestinal smooth muscle layers exhibit a complex tubular structure consisting of two concentric muscle layers in which the inner circular layer is orthogonally oriented to the outer longitudinal layer. Here, a 3D bi‐layered tubular scaffold is presented based on flexible, mechanically robust, and well aligned silk protein microfibers to mimic the native human intestinal smooth muscle structure. The scaffolds are seeded with primary human intestinal smooth muscle cells to replicate intestinal muscle tissues in vitro. Characterization of the tissue constructs reveals good biocompatibility and support for cell alignment and elongation in the different scaffold layers to enhance cell differentiation and functions. Furthermore, the engineered smooth muscle constructs support oriented neurite outgrowth, a requisite step to achieve functional innervation. These results suggest these microfiber scaffolds as functional templates for in vitro regeneration of human intestinal smooth muscle systems. The scaffolding provides a crucial step toward engineering functional human intestinal tissue in vitro, as well as engineering other types of smooth muscles in terms of their similar phenotypes. Such utility may lead to a better understanding of smooth muscle associated diseases and treatments.     

3D Superelastic Scaffolds Constructed from Flexible Inorganic Nanofibers with Self‐Fitting Capability and Tailorable Gradient for Bone Regeneration

Repair of bone defects with irregular shapes or at soft tissue insertion sites faces a huge challenge. Scaffolds capable of adapting to bone cavities, generating stiffness gradients, and inducing osteogenesis are necessary. Herein, a superelastic 3D ceramic fibrous scaffold is developed by assembly of intrinsically rigid, structurally flexible electrospun SiO₂ nanofibers with chitosan as bonding sites (SiO₂ NF‐CS) via a lyophilization technique. SiO₂ NF‐CS scaffolds exhibit excellent elasticity (full recovery from 80% compression), fast recovery rate (>500 mm min^?1), and good fatigue resistance (>10 000 cycles of compression) in an aqueous medium. SiO₂ NF‐CS scaffolds induce human mesenchymal stem cell (hMSC) elongation and differentiation into osteoblasts. In vivo self‐fitting capability is demonstrated by implanting compressed SiO₂ NF‐CS scaffolds into different shaped mandibular defects in rabbits, with a spontaneous recovery and full filling of defects. Rat calvarial defect repair validates enhanced bone formation and vascularization by cell (hMSC) histomorphology analysis. Further, subchondral bone scaffolds with gradations in SiO₂ nanofibers are developed, leading to a stiffness gradient and spatially chondrogenic and osteogenic differentiation of hMSCs. This work presents a type of 3D ceramic fibrous scaffold, which can closely match bone defects with irregular shapes or at different implant sites, and is promising for clinical translation.     

3D Molecularly Functionalized Cell‐Free Biomimetic Scaffolds for Osteochondral Regeneration

Clinically, cartilage damage is frequently accompanied with subchondral bone injuries caused by disease or trauma. However, the construction of biomimetic scaffolds to support both cartilage and subchondral bone regeneration remains a great challenge. Herein, a novel strategy is adopted to realize the simultaneous repair of osteochondral defects by employing a self‐assembling peptide hydrogel (SAPH) FEFEFKFK (F, phenylalanine; E, glutamic acid; K, lysine) to coat onto 3D‐printed polycaprolactone (PCL) scaffolds. Results show that the SAPH‐coated PCL scaffolds exhibit highly improved hydrophilicity and biomimetic extracellular matrix (ECM) structures compared to PCL scaffolds. In vitro experiments demonstrate that the SAPH‐coated PCL scaffolds promote the proliferation and osteogenic differentiation of rabbit bone mesenchymal stem cells (rBMSCs) and maintain the chondrocyte phenotypes. Furthermore, 3% SAPH‐coated PCL scaffolds significantly induce simultaneous regeneration of cartilage and subchondral bone after 8‐ and 12‐week implantation in vivo, respectively. Mechanistically, by virtue of the enhanced deposition of ECM in SAPH‐coated PCL scaffolds, SAPH with increased stiffness facilitates and remodels the microenvironment around osteochondral defects, which may favor simultaneous dual tissue regeneration. These findings indicate that the 3% SAPH provides efficient and reliable modification on PCL scaffolds and SAPH‐coated PCL scaffolds appear to be a promising biomaterial for osteochondral defect repair.     

High‐Throughput Scaffold System for Studying the Effect of Local Geometry and Topology on the Development and Orientation of Sprouting Blood Vessels

Live tissues require vascular networks for cell nourishing. Mimicking the complex structure of native vascular networks in vitro requires understanding the governing factors of early tubulogenesis. Current vascularization protocols allow for spontaneous formation of vascular networks; however, there is still a need to provide control over the defined network structure. Moreover, there is little understanding on sprouting decision and migration, especially within 3D environments. Here, tessellated polymer scaffolds with various compartment geometries and a novel two‐step seeding protocol are used to study vessel sprouting decisions. Endothelial cells first organize into hollow vessels tracing the shape contour with high fidelity. Subsequent sprouts emerge in specific directions, responding to compartment geometry. Time‐lapse imaging is used to track vessel migration, evidencing that sprouts frequently emerge from the side centers, mainly migrating toward opposing corners, where the density of support cells (SCs) is the highest, providing the highest levels of angiogenic factors. SCs distribution is quantified by smooth muscle actin expression, confirming the cells preference for curved compartment surfaces and corners. Displacements within the hydrogel correlate with SCs distribution during the initial tubulogenesis phase. This work provides new insight regarding vessel sprouting decisions that should be considered when designing scaffolds for vascularized engineered tissues.     

Molecularly‐Engineered, 4D‐Printed Liquid Crystal Elastomer Actuators

Three‐dimensional structures that undergo reversible shape changes in response to mild stimuli enable a wide range of smart devices, such as soft robots or implantable medical devices. Herein, a dual thiol‐ene reaction scheme is used to synthesize a class of liquid crystal (LC) elastomers that can be 3D printed into complex shapes and subsequently undergo controlled shape change. Through controlling the phase transition temperature of polymerizable LC inks, morphing 3D structures with tunable actuation temperature (28 ± 2 to 105 ± 1 °C) are fabricated. Finally, multiple LC inks are 3D printed into single structures to allow for the production of untethered, thermo‐responsive structures that sequentially and reversibly undergo multiple shape changes.     

Supramolecular Antifouling Additives for Robust and Efficient Functionalization of Elastomeric Materials: Molecular Design Matters

The ultimate functionality of elastomeric materials can be largely influenced by the molecular design of antifouling additives that interact through directed hydrogen bonding bisurea motifs. Herein, three additives, composed of matching bisurea groups and antifouling oligo(ethylene glycol) (OEG) functionalities, are judiciously designed. The first additive is composed of one bisurea and one OEG, the second additive of one bisurea and two OEGs, and the third additive of two bisurea and one OEG. On solution‐cast films, non‐cell adhesive properties are dependent on the amount of incorporated OEG irrespective of the bisurea design; however, on 3D electrospun scaffolds only the additive that consists of two bisurea moieties connected via an OEG functionality ensures proper non‐cell adhesive properties. Interestingly, robust non‐cell adhesive properties are maintained, both with repeated cell seeding and after partial enzymatic degradation of the scaffold. These results highlight the importance of additive design in supramolecular functionalization and show that translation from simple 2D solution‐cast films to 3D electrospun scaffolds is not trivial with respect to additive presentation and functionality.