Tissue Engineering Applications Research Articles

Poly(norepinephrine)-Mediated Universal Surface Modification for Patterning Human Pluripotent Stem Cell Culture and Differentiation.

Maintaining undifferentiated states of human pluripotent stem cells (hPSCs) is key to accomplishing successful hPSC research. Specific culture conditions, including hPSC-compatible substrates, are required for the hPSC culture. Over the past two decades, substrates supporting hPSC self-renewal have evolved from undefined and xenogeneic protein components to chemically defined and xenogeneic-free materials. However, these synthetic substrates are often costly and complex to use, leading many laboratories to continue using simpler undefined extracellular matrix (ECM) protein mixtures. In this study, we present a method using poly(norepinephrine) (pNE) for surface modification to enhance the immobilization of ECM proteins on various substrates, including polydimethylsiloxane (PDMS) and ultralow attachment (ULA) hydrogels, thereby supporting hPSC culture and maintenance of pluripotency. The pNE-mediated surface modification enables spatial patterning of ECM proteins on nonadhesive ULA surfaces, facilitating tunable macroscopic cell patterning. This approach improves hPSC attachment and growth and allows for cell patterning to study the effects of anisotropic environments on the hPSC fate. Our findings demonstrate the versatility and simplicity of pNE-mediated surface modification for improving hPSC culture and spatially controlled differentiation into endothelial cells and cardiomyocytes on previously nonamenable substrates, providing a valuable tool for tissue engineering and regenerative medicine applications.

Multi‐Material Gradient Printing Using Meniscus‐enabled Projection Stereolithography (MAPS)

AbstractLight‐based additive manufacturing methods are widely used to print high‐resolution 3D structures for applications in tissue engineering, soft robotics, photonics, and microfluidics, among others. Despite this progress, multi‐material printing with these methods remains challenging due to constraints associated with hardware modifications, control systems, cross‐contamination, waste, and resin properties. Here, a new printing platform coined Meniscus‐enabled Projection Stereolithography (MAPS) is reported, a vat‐free method that relies on generating and maintaining a resin meniscus between a crosslinked structure and bottom window to print lateral, vertical, discrete, or gradient multi‐material 3D structures with no waste and user‐defined mixing between layers. MAPS is compatible with a wide range of resins shown and can print complex multi‐material 3D structures without requiring specialized hardware, software, or complex washing protocols. MAPS's ability to print structures with microscale variations in mechanical stiffness, opacity, surface energy, cell densities, and magnetic properties provides a generic method to make advanced materials for a broad range of applications.

Biocomposite Scaffolds for Tissue Engineering: Materials, Fabrication Techniques and Future Directions

Tissue engineering is an interdisciplinary field that combines materials, methods, and biological molecules to engineer newly formed tissues to replace or restore functional organs. Biomaterials-based scaffolds play a crucial role in developing new tissue by interacting with human cells. Tissue engineering scaffolds with ideal characteristics, namely, nontoxicity, biodegradability, and appropriate mechanical and surface properties, are vital for tissue regeneration applications. However, current biocomposite scaffolds face significant limitations, particularly in achieving structural durability, controlled degradation rates, and effective cellular integration. These qualities are essential for maintaining long-term functionality in vivo. Although commonly utilized biomaterials can provide physical and chemical properties needed for tissue regeneration, inadequate biomimetic properties, as well as insufficient interactions of cells-scaffolds interaction, still need to be improved for the application of tissue engineering in vivo. It is impossible to achieve some essential features using a single material, so combining two or more materials may accomplish the requirements. In order to achieve a proper scaffold design, a suitable fabrication technique and combination of biomaterials with controlled micro or nanostructures are needed to achieve the proper biological responses. This review emphasizes advancements in scaffold durability, biocompatibility, and cellular responsiveness. It focuses on natural and synthetic polymer combinations and innovative fabrication techniques. Developing stimulus-responsive 3D scaffolds is critical, as these scaffolds enhance cell adhesion and promote functional tissue formation while maintaining structural integrity over time. This review also highlights the natural polymers, smart materials, and recent advanced techniques currently used to create emerging scaffolds for tissue regeneration applications.

Silk Nanofibers/Carbon Nanotube Conductive Aerogel.

Natural silk nanofibers (SNF) are attractive conductive substrates due to their high aspect ratio, outstanding mechanical strength, excellent biocompatibility, and controllable degradability. However, the inherently non-conductivity severely restricts the potential sensor application of SNF-based aerogels. In this work, the conductive nanofibrous aerogels with low-density achieved through freeze-drying by dispersing carbon nanotubes (CNT) into SNF suspension. The addition of CNT significantly increases the conductivity with improved mechanical properties of composite aerogels. SEM results reveal that the distinct hierarchical structure comprising micropores and nanofibrous networks within the pores is formed when CNT content reached 30%. Furthermore, increased cell viability suggested the excellent biocompatibility of SNF-CNT-based conductive aerogel for tissue-engineering applications. Subsequently, the elastic water-borne polyurethane (WPU) is incorporated to SNF-CNT system to construct aerogel with good sensing properties. The introduction of WPU demonstrates enhanced compressive performances and an exceptionally high elastic recovery ratio of 99.8%, thereby exhibiting a stable and lossless strain-sensing signal output at 5% strain. This study provides a feasible choice and strategy for exploring the potential application of SNF in functional aerogels.

Cysteine Conjugation: An Approach to Obtain Polymers with Enhanced Muco- and Tissue Adhesion

The modification of polymers towards increasing their biocompatibility gathers the attention of scientists worldwide. Several strategies are used in this field, among which chemical post-polymerization modification has recently been the most explored. Particular attention revolves around polymer-L-cysteine (Cys) conjugates. Cys, a natural amino acid, contains reactive thiol, amine, and carboxyl moieties, allowing hydrogen bond formation and improved tissue adhesion when conjugated to polymers. Conjugation of Cys and its derivatives to polymers has been examined mostly for hyaluronic acid, chitosan, alginate, polyesters, polyurethanes, poly(ethylene glycol), poly(acrylic acid), polycarbophil, and carboxymethyl cellulose. It was shown that the conjugation of Cys and its derivatives to polymers significantly increased their tissue adhesion, particularly mucoadhesion, stability at physiological pH, drug encapsulation efficiency, drug release, and drug permeation. Conjugates were also non-toxic toward various cell lines. These properties make Cys conjugation a promising strategy for advancing polymer applications in drug delivery systems and tissue engineering. This review aims to provide an overview of these features and to present the conjugation of Cys and its derivatives as a modern and promising approach for enhancing polymer tissue adhesion and its application in the medical field.

Implantable 3D printed hydrogels with intrinsic channels for liver tissue engineering

This study presents the design, fabrication, and evaluation of a general platform for the creation of three-dimensional printed devices (3DPDs) for tissue engineering applications. As a demonstration, we modeled the liver with 3DPDs consisting of a pair of parallel millifluidic channels that function as portal-venous (PV) and hepatobiliary (HB) structures. Perfusion of medium or whole blood through the PV channel supports the hepatocyte-containing HB channel. Device computer-aided design was optimized for structural stability, after which 3DPDs were 3D printed in a polyethylene(glycol) diacrylate photoink by digital light processing and evaluated in vitro. The HB channels were subsequently seeded with hepatic cells suspended in a collagen hydrogel. Perfusion of 3DPDs in bioreactors enhanced the viability and function of rat hepatoma cells and were maintained over time, along with improved liver-specific functions. Similar results were observed with primary rat hepatocytes, including significant upregulation of cytochrome p450 activity. Additionally, coculture experiments involving primary rat hepatocytes, endothelial cells, and mesenchymal stem cells in 3DPDs showed enhanced viability, broad liver-specific gene expression, and histological features indicative of liver tissue architecture. In vivo implantation of 3DPDs in a rat renal shunt model demonstrated successful blood flow through the devices without clot formation and maintenance of cell viability. 3D printed designs can be scaled in 3D space, allowing for larger devices with increased cell mass. Overall, these findings highlight the potential of 3DPDs for clinical translation in hepatic support applications.

Synthesis methods of Mg-based scaffolds and their applications in tissue engineering: A review.

Repair and regeneration of damaged tissues due to disease and accidents have become a severe challenge to tissue engineers and researchers. In recent years, biocompatible metal materials such as stainless steels, cobalt alloys, titanium alloys, tantalum alloys, nitinol, and Mg alloys have been studied for tissue engineering applications; as suitable candidates in orthopedic and dentistry implants. These materials and their alloys are used for load-bearing and physiological roles in biological applications. Due to the suitable conditions provided by a porous material, many studies have been performed on the porous implants, including Mg-based scaffolds. Mg alloy scaffolds are attractive due to some outstanding features and susceptibilities, such as providing a cell matrix for cell proliferation, migration, and regeneration, providing metabolic substances for bone tissue growth, biocompatibility, good biodegradability, elastic modulus comparable to the natural bone, etc. Accordingly, in the present study, a general classification of all the production methods of Mg-based scaffolds is provided. Strengths and weaknesses, the effect of the production approach on the final properties of scaffolds, including mechanical and biological capabilities, and the impact of alloying elements and process parameters have been reviewed, and discussed. Finally, the manufacturing methods have been compared and the upcoming challenges have been stated.

Enhanced Bioactivity of Chitosan-Alginate-Riboflavin Liquid-Exfoliated Molybdenum Disulfide Nanosheets for Bone Tissue Engineering Applications

Enhanced Bioactivity of Chitosan-Alginate-Riboflavin Liquid-Exfoliated Molybdenum Disulfide Nanosheets for Bone Tissue Engineering Applications

Bioactive Peptide Hydrogel Scaffold with High Fluidity, Thermosensitivity, and Neurotropism in 3D Spatial Structure for Promoted Repair of Spinal Cord Injury.

Spinal cord injury (SCI) has been considered a clinically challenging disease that is characterized by local disturbance of the microenvironment, which inhibits post-injury neural regeneration. The simulation of a microenvironment conducive to the regeneration of spinal cord is beneficial for SCI repair. In this study, bioactive composite hydrogels are developed that mimic the regenerative microenvironment of spinal cord for enhanced SCI repair. The fabricated composite hydrogels (CRP) based on chitosan (CS), RADA16 nanofibers, and nerve-promoted peptide (PPFLMLLKGSTR) exhibit excellent injectability, superior biodegradability and biocompatibility. In addition, the CRP hydrogels can formquickly (a few minutes) by mixing three components at human body temperature, showing high potential as a biomimetic matrix for in situ repair of SCI. The in vitro studies demonstrate that the CRP hydrogels can not only promote the proliferation and migration of bone marrow mesenchymal stem cells but also induce the proliferation and differentiation of neural stem cells (NSCs) into neurons. Meanwhile, the hydrogels reveal the efficiency of protecting neurons and promoting axonal growth. Furthermore, the in vivo tests prove that the CRP hydrogels can reduce post-SCI inflammatory responses, inhibit reactive astrocyte over-proliferation, and promote the migration, proliferation, and differentiation of endogenous NSCs, which agree well with the in vitro results. The pre-clinical test demonstrates that the CRP hydrogels restore the motor function in completely transected spinal cord rats, and the SCI repair mechanism may involve the activation of the PI3K/AKT/mTOR pathway. It is believed that the strategies shown in this work will be valuable for the design and synthesis of novel hydrogels for biomedical and tissue engineering applications.

Influence of the PAN:PEO Ratio on the Morphology of Needleless Electrospun Nanofiber Mats Before and After Carbonization

Nanofiber mats with a high surface-to-volume ratio can be prepared by electrospinning. The Porosity is sometimes reported to be tunable by blending different materials, e.g., water-soluble poly(ethylene oxide) (PEO) with not water-soluble poly(acrylonitrile) (PAN). Here, nanofiber mats were electrospun from different PAN:PEO ratios, using a wire-based electrospinning machine “Nanospider Lab”. Investigations of the as-spun nanofiber mats as well as of membranes after washing off the water-soluble PEO by scanning electron microscopy (SEM) revealed severe differences in the nanofiber mat morphologies, such as varying fiber diameters and especially non-fibrous areas in the carbonized nanofiber mats, depending on the amount of PEO in the nanofiber mat as well as the molecular weight of the PEO. Similarly, the ratio and molecular weight of PEO influenced the results of stabilization and carbonization. This paper discusses the possibility of tailoring nanofiber porosity for the potential use of PAN nanofiber mats in tissue engineering, filtration, and other applications.

Mechanical Behavior of 3D-Printed Schwarz Diamond-Structured Scaffolds for Tissue Engineering Applications

Mechanical Behavior of 3D-Printed Schwarz Diamond-Structured Scaffolds for Tissue Engineering Applications

Design of cellulose nanocrystal‐integrated poly(vinyl alcohol)/polyethylene glycol electrospun nanofiber scaffolds for biomedical applications

AbstractThe present study aims to fabricate cellulose nanocrystals (CNCs) doped poly(vinyl alcohol) polyethylene glycol (PVA/PEG) nanocomposite films for biomedical applications. The nanocomposite films were prepared by using electrospinning techniques with varying percentages of CNCs (10% and 20%) mixed with PVA and PEG (50:50). The properties of the produced nanocomposites were evaluated using a battery of tests. The results of surface morphology and structural miscibility obtained from field emission‐scanning electron microscopy (FE‐SEM), atomic force microscopy, and Fourier transformer infra‐red studies revealed appreciable compatibility among the three components (CNCs, PVA, and PEG). FE‐SEM micrographs revealed that the nanomaterials underwent a dramatic transition from discontinuous to continuous fibers, with interconnected or network‐like fibers. The constructed scaffold material's stability went up from three to four phases, according to thermal and degradation experiments. In addition, research on biodegradation and water absorption found that CNCs outperformed pure PVA and PVA/PEG in terms of swelling percentage time and enzyme degradation rate. The hemolysis assay of the PVA/PEG/CNC scaffold showed good compatibility (below 5%) and according to the MTT assay, both NIH 3T3 and L929 cells survived well, indicating that the CNCs could serve as a useful scaffold for tissue engineering applications such skin tissue regeneration. In sum, the findings proved that biological domains including tissue engineering and wound healing can benefit from produced nanofiber scaffolds.

L-DOPA Promotes Functional Proliferation Through GPR143, Specific L-DOPA Receptor of Astrocytes.

l-3,4-Dihydroxyphenylalanine (levodopa and L-DOPA in this text), alongside dopamine, boasts high biocompatibility, prompting industrial demand for its use as a coating material. Indeed, the effectiveness of L-DOPA is steadily rising as it serves as an oral therapeutic agent for neurodegenerative brain diseases, particularly Parkinson's disease (PD). However, the effects of L-DOPA on the growth and function of astrocytes, the main glial cells, and the most numerous glial cells in the brain, are unknown. Here, we investigated whether L-DOPA is possible as a coating material on cover glass and polystyrene for rat primary astrocytes. The coating state of L-DOPA on the cover glass and polystyrene was characterized by X-ray photoelectron spectroscopy (XPS) and static water contact angle (WCA). Interestingly, L-DOPA coated on the cover glass promoted the proliferation of astrocytes but not neurons. Furthermore, L-DOPA coated on the cover glass, as opposed to polystyrene, facilitated the proliferation of the astrocytes. The astrocytes grown on L-DOPA-coated cover glasses exhibited functional receptor-activated Ca2+ transients through the activation of protease-activated receptor subtype 1 (PAR-1), recognized as an astrocytic functional marker. However, cover glass coated with 0, 500, 1000, 2000, and 4000 μg/mL L-DOPA maintained astrocyte viability, while supplementation with 500 and 1000 μM L-DOPA significantly decreased astrocyte viability. This suggests that treatments with free 500 and 1000 μM L-DOPA significantly reduced the number of astrocytes. Both Pimozide, an inhibitor of G protein-coupled receptor 143 (GPR143), also known as Ocular albinism type 1 (OA1), and CCG2046, an inhibitor of regulator of G protein signaling 4 (RGS4), reduced the viability of astrocytes on cover glass coated with L-DOPA compared to astrocytes on cover glass coated with poly-d-lysine (PDL). This suggests that L-DOPA promotes astrocyte proliferation through activation of the GPR143 signaling pathway. These findings imply that L-DOPA proliferates functional astrocytes through the activation of GPR143. These results are the first report that L-DOPA coating cover glass proliferates rat primary astrocytes with the activation of GPR143. The discovery that levodopa enhances cell adhesion can significantly influence research in multiple ways. It provides insights into cell behavior, disease mechanisms, and potential therapeutic applications in tissue engineering and regenerative medicine. Additionally, it offers opportunities to explore novel approaches for improving cell-based therapies and tissue regeneration. Overall, this finding opens up new avenues for research, with broad implications across various scientific fields.

Human acellular amniotic membrane/polycaprolactone vascular grafts prepared by electrospinning enable vascular remodeling in vivo

BackgroundVascular transplantation is an effective treatment for severe vascular lesions. The design of the bioactive and mechanical properties of small-caliber vascular grafts is critical for their application in tissue engineering. In this study, we sought to develope a small-caliber vascular graft by electrospinning a mixture of a human acellular amniotic membrane (HAAM) and polycaprolactone (PCL).ResultsMechanical tests showed that the vascular grafts were strong enough to endure stress from adjacent blood vessels and blood pressure. The biocompatibility of the HAAM/PCL vascular grafts was evaluated based on cell proliferation in vitro. The tubular formation test demonstrated that vascular grafts containing HAAM could improve human umbilical vein endothelial cell function, and in vivo implantation was performed by replacing the rat abdominal aorta. The HAAM/PCL vascular graft was found to promote attachment and endothelial cell retention. The regenerated smooth muscle layer was similar to native arteries' smooth muscle layer and the endothelium coverage was complete.ConclusionsThese results suggest that our constructs may be promising vascular graft candidates and can potentially be used to develop vascular grafts that can endothelialize rapidly in vivo.

Transformative Biomaterials in Burn Care: Utilizing Scaffolds, Hydrogels, and Chitosan for Optimized Healing and Scar Reduction

With over a million patients per year in the USA alone, burns are among the most common injuries in the world. In addition to preventing difficulties during burn injuries, the growing impact of scaffolds, hydrogels, cell scaffolds, and cell sheets with healing boosting elements expedite triggers and strengthens re-epithelialization and wound healing, which limits the creation of scars. While superficial partial-thickness and superficial burns typically heal without surgery, severe burns require special care, including topical antimicrobial surgery or bandages. Usually composed of polymeric biomaterials, scaffolds offer the structural support needed for cell adhesion and the subsequent formation of tissue. The term "tissue engineering triad" often refers to cells, scaffolds, and growth-stimulating signals. This may be accomplished in several ways by combining different polymers. Simple (planar) 3D structures may be produced using conventional and rapid prototyping techniques, but complicated structures have been successfully produced by carefully controlling the Molds and processing parameters. For biomedical and tissue engineering applications, chitosan has been widely employed (skin, bone, cartilage, and vascular grafts to substrates for mammalian cell culture). Additionally, it is renewable, biocompatible, biodegradable, nonantigenic, bioactive, and nontoxic.

Mechanical Properties of Cocoon Silk Derivatives for Biomedical Application: A Systematic Review

Background: Despite cocoon silk’s well-known strength, biocompatibility, and hypoallergenic properties, its potential medical applications remain largely unexplored. This review, therefore, is of significance as it evaluates the mechanical properties and clinical potential of cocoon silk, a material with promising applications in biomaterials and tissue engineering. Methods: We conducted a comprehensive systematic review adhering to PRISMA guidelines. Our focus was on the primary outcomes of tensile strength and elongation at break, and the secondary outcomes included other mechanical properties, applications, and complications. Results: Out of the 192 silk-related studies, 9 met the criteria. These studies revealed that cocoon silk derivatives exhibit a wide range of tensile strength, from 0.464 to 483.9 MPa (with a median of 4.27 MPa), and elongation at break, from 2.56% to 946.5% (with a median of 60.0%). Biomedical applications of cocoon silk derivatives span from tissue regeneration (n = 6) to energy harvesting (n = 4). Complications often arose from material fragility in non-optimized derivative components. Conclusions: While cocoon silk shows expansive promise due to its suitable mechanical properties and low complication risk, plenty remains to be discovered. Future research is crucial to fully realizing its vast surgical and biomedical potential.

Hyaluronic Acid-Based 3D Bioprinted Hydrogel Structure for Directed Axonal Guidance and Modeling Innervation In Vitro.

Neurons form predefined connections and innervate target tissues through elongating axons, which are crucial for the development, maturation, and function of these tissues. However, innervation is often overlooked in tissue engineering (TE) applications. Here, multimaterial 3D bioprinting is used to develop a novel 3D axonal guidance structure in vitro. The approach uses the stiffness difference of acellular hyaluronic acid-based bioink printed as two alternating, parallel-aligned filaments. The structure has soft passages incorporated with guidance cues for axonal elongation while the stiff bioink acts as a structural support and contact guidance. The mechanical properties and viscosity differences of the bioinks are confirmed. Additionally, human pluripotent stem cell (hPSC) -derived neurons form a 3D neuronal network in the softer bioink supplemented with guidance cues whereas the stiffer restricts the network formation. Successful 3D multimaterial bioprinting of the axonal structure enables complete innervation by peripheral neurons via soft passages within 14 days of culture. This model provides a novel, stable, and long-term platform for studies of 3D innervation and axonal dynamics in health and disease.

Foreign Body Immune Response to Zwitterionic and Hyaluronic Acid Granular Hydrogels Made with Mechanical Fragmentation.

Granular hydrogels have recently attracted the attention for diverse tissue engineering applications due to their versatility and modularity. Despite previous studies showing enhanced viability and metabolism of cells encapsulated in these hydrogels, the in vitro immune response and long-term fibrotic response of these scaffolds have not been well characterized. Here, bulk and granular hydrogels are studied based on synthetic zwitterionic (ZI) and natural polysaccharide hyaluronic acid (HA) made with mechanical fragmentation. In vitro, immunomodulatory studies show an increased stimulatory effect of HA granular hydrogels compared to bulk, while both bulk and granular ZI hydrogels do not induce an inflammatory response. Subcutaneous implantation in mice shows that both ZI and HA granular hydrogels resulted in less collagen capsule deposition around implants compared to bulk HA hydrogels 10 weeks after implantation. Moreover, the HA granular hydrogels are infiltrated by host cells, including macrophages and mature blood vessels, in a porosity-dependent manner. However, a large number of cells, including multinucleated giant cells as well as blood vessels, surround bulk and granular ZI hydrogels and are not able to infiltrate. Overall, this study provides new insights on the long-term stability and fibrotic response of granular hydrogels, paving the way for future studies and applications.

Comprehensive Review of Hydrogel Synthesis, Characterization, and Emerging Applications

Hydrogels play a crucial role due to their high-water content and 3D structure, which make them ideal for various applications in biomedicine, sensing, and beyond. They can be prepared from a variety of biomaterials, polymers, and their combinations, allowing for versatility in properties and applications. Hydrogels include natural types derived from collagen, gelatin, alginate, and hyaluronic acid, as well as synthetic types based on polyethylene glycol (PEG), polyvinyl alcohol (PVA), and polyacrylamide (PAAm). Each type possesses distinct properties, such as mechanical strength, biodegradability, and biocompatibility, which can be tailored for applications such as wound healing, contact lenses, 3D bioprinting, and tissue engineering. The high-water content of hydrogels mimics natural tissue environments, promoting cell growth and allowing nutrient and waste exchange, which supports the development of functional tissues. They serve as scaffolds in tissue engineering applications, including wound healing, cartilage and bone regeneration, vascular tissue engineering, and organ-on-a-chip systems. Additionally, hydrogels can encapsulate and deliver therapeutic agents, such as growth factors or drugs, to specific target sites in the body. Hydrogels can be prepared through three primary methods: physical crosslinking, which relies on non-covalent interactions such as physical entanglements or hydrogen bonding; chemical crosslinking, which forms covalent bonds between polymer chains to create a stable structure; and irradiation-based crosslinking, where UV irradiation induces rapid hydrogel formation. The choice of crosslinking method depends on the desired properties and applications of the hydrogel. By providing a biomimetic environment, hydrogels facilitate cell growth and differentiation, support tissue formation, and aid in the regeneration of damaged or diseased tissues while delivering therapeutic agents. This review focuses on the critical advancements in processing routes for hydrogel development, summarizing the characterization and application of hydrogels. It also details key applications, including wound healing and cartilage and bone regeneration, as well as the challenges and future perspectives in the field.

Hierarchical Structures of Amino Acid Derived Polyhydroxyurethanes: Promising Candidates as Drug Carriers and Cell Adhesive Scaffolds.

In this study, we examined the self-assembly of a series of biodegradable and biocompatible amino acid-based polyhydroxyurethanes (PHUs), investigating the structural influence of these polymers on their self-assembly and the resulting morphological features. The presence of hydrophilic and hydrophobic segments, along with carbonyl urethane, ester, and hydroxyl groups in the PHU backbone, facilitates intermolecular hydrogen bonding, enabling the formation of self-assemblies with hierarchical nanodimensional morphologies. We determined the critical aggregation concentration (CAC) and found that it largely depends on the PHU's structure. In-depth morphological studies demonstrated that the evolution of morphology proceeds in four steps: (1) the initial formation of micelles, which act as seeds at very low concentrations, (2) the elongation of these micelles into nanorod or nanopalette shapes below the CAC range, (3) the epitaxial growth of nanofibers at the CAC, and (4) the complete formation of fibrous mats above the CAC. Additionally, these hierarchical structures were utilized for the encapsulation and release of the drug doxorubicin (DOX). We observed that 75% of the encapsulated DOX was readily released in a mildly acidic environment, similar to the physiological conditions of cancer cells. Cellular uptake studies confirmed the effective uptake of the drug-loaded nanoassemblies into the cytoplasm of cells. Our studies also confirmed that these self-assembled structures can serve as effective cell adhesive scaffolds for tissue engineering applications.