skip to main content


Title: Soft, Strong, Tough, and Durable Bio‐Hydrogels Via Maximizing Elastic Entropy
Abstract

Load‐bearing soft tissues are soft but strong, strong yet tough. These properties can only be replicated in synthetic hydrogels, which do not have the biocomplexity required by many biomedical applications. By contrast, natural hydrogels, although retaining the native complexity, are weak and fragile. Here a thermomechanical casting method is presented to achieve the mechanical capabilities of synthetic materials in biopolymer hydrogels. The thermomechanical cast and chemically crosslinked biopolymer chains form a short‐range disordered but long‐range ordered structure in water. Upon stretch, the disordered structure transforms to a hierarchically ordered structure. This disorder‐order transformation resembles the synergy of the disordered elastin and ordered collagen in load‐bearing soft tissues. As entropy drives a reverse order‐disorder transformation, the hydrogels can resist repeated cycles of loads without deterioration in mechanical properties. Gelatin hydrogels produced by this method combine tissue‐like tunable mechanical properties that outperform the gelatin prepared by synthetic approaches, and in vivo biocomplexity beyond current natural systems. Unlike polymer engineering approaches, which rely on specific crosslinks provided by special polymers, this strategy utilizes the entropy of swollen chains and is generalizable to many other biopolymers. It could thus significantly accelerate translational success of biomaterials.

 
more » « less
Award ID(s):
1719875
NSF-PAR ID:
10418944
Author(s) / Creator(s):
 ;  ;  ;  ;  ;  ;  ;  
Publisher / Repository:
Wiley Blackwell (John Wiley & Sons)
Date Published:
Journal Name:
Advanced Functional Materials
Volume:
33
Issue:
28
ISSN:
1616-301X
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. Load-bearing soft tissues normally show J-shaped stress–strain behaviors with high compliance at low strains yet high strength at high strains. They have high water content but are still tough and durable. By contrast, naturally derived hydrogels are weak and brittle. Although hydrogels prepared from synthetic polymers can be strong and tough, they do not have the desired bioactivity for emerging biomedical applications. Here, we present a thermomechanical approach to replicate the combinational properties of soft tissues in protein-based photocrosslinkable hydrogels. As a demonstration, we create a gelatin methacryloyl fiber hydrogel with soft tissue-like mechanical properties, such as low Young’s modulus (0.1 to 0.3 MPa), high strength (1.1 ± 0.2 MPa), high toughness (9,100 ± 2,200 J/m 3 ), and high fatigue resistance (2,300 ± 500 J/m 2 ). This hydrogel also resembles the biochemical and architectural properties of native extracellular matrix, which enables a fast formation of 3D interconnected cell meshwork inside hydrogels. The fiber architecture also regulates cellular mechanoresponse and supports cell remodeling inside hydrogels. The integration of tissue-like mechanical properties and bioactivity is highly desirable for the next-generation biomaterials and could advance emerging fields such as tissue engineering and regenerative medicine. 
    more » « less
  2. Skeletal muscles possess the combinational properties of high fatigue resistance (1,000 J/m 2 ), high strength (1 MPa), low Young’s modulus (100 kPa), and high water content (70 to 80 wt %), which have not been achieved in synthetic hydrogels. The muscle-like properties are highly desirable for hydrogels’ nascent applications in load-bearing artificial tissues and soft devices. Here, we propose a strategy of mechanical training to achieve the aligned nanofibrillar architectures of skeletal muscles in synthetic hydrogels, resulting in the combinational muscle-like properties. These properties are obtained through the training-induced alignment of nanofibrils, without additional chemical modifications or additives. In situ confocal microscopy of the hydrogels’ fracturing processes reveals that the fatigue resistance results from the crack pinning by the aligned nanofibrils, which require much higher energy to fracture than the corresponding amorphous polymer chains. This strategy is particularly applicable for 3D-printed microstructures of hydrogels, in which we can achieve isotropically fatigue-resistant, strong yet compliant properties. 
    more » « less
  3. Abstract

    Load‐bearing soft tissues, e.g., cartilage, ligaments, and blood vessels, are made predominantly from water (65–90%) which is essential for nutrient transport to cells. Yet, they display amazing stiffness, toughness, strength, and deformability attributed to the reconfigurable 3D network from stiff collagen nanofibers and flexible proteoglycans. Existing hydrogels and composites partially achieve some of the mechanical properties of natural soft tissues, but at the expense of water content. Concurrently, water‐rich biomedical polymers are elastic but weak. Here, biomimetic composites from aramid nanofibers interlaced with poly(vinyl alcohol), with water contents of as high as 70–92%, are reported. With tensile moduli of ≈9.1 MPa, ultimate tensile strains of ≈325%, compressive strengths of ≈26 MPa, and fracture toughness of as high as ≈9200 J m−2, their mechanical properties match or exceed those of prototype tissues, e.g., cartilage. Furthermore, with reconfigurable, noncovalent interactions at nanomaterial interfaces, the composite nanofiber network can adapt itself under stress, enabling abiotic soft tissue with multiscale self‐organization for effective load bearing and energy dissipation.

     
    more » « less
  4. Hydrogels are a class of soft, highly deformable materials formed by swelling a network of polymer chains in water. With mechanical properties that mimic biological materials, hydrogels are often proposed for load bearing biomedical or other applications in which their deformation and failure properties will be important. To study the failure of such materials a means for the measurement of deformation fields beyond simple uniaxial tension tests is required. As a non-contact, full-field deformation measurement method, Digital Image Correlation (DIC) is a good candidate for such studies. The application of DIC to hydrogels is studied here with the goal of establishing the accuracy of DIC when applied to hydrogels in the presence of large strains and large strain gradients. Experimental details such as how to form a durable speckle pattern on a material that is 90% water are discussed. DIC is used to measure the strain field in tension loaded samples containing a central hole, a circular edge notch and a sharp crack. Using a nonlinear, large deformation constitutive model, these experiments are modeled using the finite element method (FEM). Excellent agreement between FEM and DIC results for all three geometries shows that the DIC measurements are accurate up to strains of over 10, even in the presence of very high strain gradients near a crack tip. The method is then applied to verify a theoretical prediction that the deformation field in a cracked sample under relaxation loading, i.e. constant applied boundary displacement, is stationary in time even as the stress relaxes by a factor of three. 
    more » « less
  5. Abstract

    Effective tendon regeneration following injury is contingent on appropriate differentiation of recruited cells and deposition of mature, aligned, collagenous extracellular matrix that can withstand the extreme mechanical demands placed on the tissue. As such, myriad biomaterial approaches have been explored to provide biochemical and physical cues that encourage tenogenesis and template aligned matrix deposition in lieu of dysfunctional scar tissue formation. Fiber‐reinforced hydrogels present an ideal biomaterial system toward this end given their transdermal injectability, tunable stiffness over a range amenable to tenogenic differentiation of progenitors, and capacity for modular inclusion of biochemical cues. Here, tunable and modular, fiber‐reinforced, synthetic hydrogels are employed to elucidate salient microenvironmental determinants of tenogenesis and aligned collagen deposition by tendon progenitor cells. Transforming growth factor β3 drives a cell fate switch toward pro‐regenerative or pro‐fibrotic phenotypes, which can be biased toward the former by culture in softer microenvironments or inhibition of the RhoA/ROCK activity. Furthermore, studies demonstrate that topographical anisotropy in fiber‐reinforced hydrogels critically mediates the alignment ofde novocollagen fibrils, reflecting native tendon architecture. These findings inform the design of cell‐free, injectable, synthetic hydrogels for tendon tissue regeneration and, likely, that of a range of load‐bearing connective tissues.

     
    more » « less