Temporal and spatial control over fiber alignment within hyaluronic acid hydrogels using magnetic fields.

Wound healing is tightly regulated in both space and time. To mimic this behavior, we designed magnetically-responsive, fiber-hydrogel composites. When covalently crosslinked hydrogels were combined with layer-by-layer stacking, we demonstrated precise spatial control over fiber orientation.

Development and Characterization of Hyaluronic Acid Microgels for Neural Regeneration Applications.

Delivery of therapeutic compounds via biomaterial systems has shown promise for tissue regeneration following central nervous system (CNS) injuries. Stromal cell-derived factor-1a (SDF-1a) modulates progenitor cell recruitment to neural injury sites and may contribute to neural repair. However, SDF-1a has a short half-life and requires a delivery system to both protect and sustain its release.

Exponentially Decreasing Antigen Release Reduces Inflammatory Markers in an Antigen-Specific Manner.

Vaccine development requires innovative approaches to improve immune responses while reducing the number of immunizations. In this study, we explore the impact of controlled antigen release on immune activation and regulation using programmable infusion pumps and biodegradable biomaterials in OT-II and wild-type mice to understand the adaptive immune response through controlled antigen delivery in the absence of adjuvant. Ovalbumin (OVA) was delivered via an exponentially decreasing profile, mimicking clearance of infection, and an exponentially increasing profile, mimicking induction of infection.

Crystallinity of covalent organic frameworks controls immune responses.

Biomaterials can act as pro- or anti-inflammatory agents. However, effects of biomaterials crystallinity on immune responses are poorly understood. We demonstrate that the adjuvant-like behaviour of covalent organic framework (COF) biomaterial is dependent on its crystallinity.

Using dynamic biomaterials to study the temporal role of bioactive peptides during osteogenesis.

The extracellular matrix is a highly dynamic environment, and the precise temporal presentation of biochemical signals is critical for regulating cell behavior during development, healing, and disease progression. To mimic this behavior, we developed a modular DNA-based hydrogel platform to enable independent and reversible control over the immobilization of multiple biomolecules during in vitro cell culture. We combined reversible DNA handles with a norbornene-modified hyaluronic acid hydrogel to orthogonally add and remove multiple biomolecule-DNA conjugates at user-defined timepoints.

Using dynamic biomaterials to study the temporal role of osteogenic growth peptide during osteogenesis.

The extracellular matrix is a highly dynamic environment, and the precise temporal presentation of biochemical signals is critical for regulating cell behavior during development, healing, and disease progression. To mimic this behavior, we developed a modular DNA-based hydrogel platform to enable independent and reversible control over the immobilization of multiple biomolecules during in vitro cell culture. We combined reversible DNA handles with a norbornene-modified hyaluronic acid hydrogel to orthogonally add and remove multiple biomolecule-DNA conjugates at user-defined timepoints.

Magnetic fields enable precise spatial control over electrospun fiber alignment for fabricating complex gradient materials.

Musculoskeletal interfacial tissues consist of complex gradients in structure, cell phenotype, and biochemical signaling that are important for function. Designing tissue engineering strategies to mimic these types of gradients is an ongoing challenge. In particular, new fabrication techniques that enable precise spatial control over fiber alignment are needed to better mimic the structural gradients present in interfacial tissues, such as the tendon-bone interface.

Trilayered Hydrogel Scaffold for Vocal Fold Tissue Engineering.

The lamina propria within the vocal fold (VF) is a complex multilayered tissue that increases in stiffness from the superficial to deep layer, where this characteristic is crucial for VF sound production. Tissue-engineered scaffolds designed for VF repair must mimic the biophysical nature of the native vocal fold and promote cell viability, cell spreading, and vibration with air flow. In this study, we present a unique trilayered, partially degradable hydrogel scaffold that mimics the multilayered structure of the VF lamina propria.

Reversible control of biomaterial properties for dynamically tuning cell behavior.

In the past decade, significant advances in chemistry and manufacturing have enabled the development of increasingly complex and controllable biomaterials. A key innovation is the design of dynamic biomaterials that allow for user-specified, reversible, temporal control over material properties. In this review, we provide an overview of recent advancements in reversible biomaterials, including control of stiffness, chemistry, ligand presentation, and topography.

Comparative Analysis of Fiber Alignment Methods in Electrospinning.

Fabrication of anisotropic materials is highly desirable in designing biomaterials and tissue engineered constructs. Electrospinning has been broadly adopted due to its versatility in producing non-woven fibrous meshes with tunable fiber diameters (from 10 nanometers to 10 microns), microarchitectures, and construct geometries. A myriad of approaches have been utilized to control fiber alignment of electrospun materials to achieve complex microarchitectures, improve mechanical properties, and provide topographical cellular cues.

Hyaluronic Acid Biomaterials for Central Nervous System Regenerative Medicine.

Hyaluronic acid (HA) is a primary component of the brain extracellular matrix and functions through cellular receptors to regulate cell behavior within the central nervous system (CNS). These behaviors, such as migration, proliferation, differentiation, and inflammation contribute to maintenance and homeostasis of the CNS. However, such equilibrium is disrupted following injury or disease leading to significantly altered extracellular matrix milieu and cell functions.

Stepping into the Next Dimension of Biomaterial Design.

Recapitulating the dynamic spatiotemporal behavior of the extracellular matrix using biomaterials is an ongoing challenge. A recent breakthrough by Shadish et al. demonstrates the use of sortase-mediated transpeptidation to site-specifically modify proteins with a range of chemical motifs.

Programmed biomolecule delivery to enable and direct cell migration for connective tissue repair.

Dense connective tissue injuries have limited repair, due to the paucity of cells at the wound site. We hypothesize that decreasing the density of the local extracellular matrix (ECM) in conjunction with releasing chemoattractive signals increases cellularity and tissue formation after injury. Using the knee meniscus as a model system, we query interstitial cell migration in the context of migratory barriers using a novel tissue Boyden chamber and show that a gradient of platelet-derived growth factor-AB (PDGF-AB) expedites migration through native tissue.

Synergistic Effects of SDF-1α and BMP-2 Delivery from Proteolytically Degradable Hyaluronic Acid Hydrogels for Bone Repair.

In order to achieve bone repair, bone morphogenetic protein-2 (BMP-2) is typically delivered in non-physiological doses and can result in significant adverse side effects. To reduce the amount of BMP-2 necessary for bone formation, we delivered a known chemokine (stromal cell derived factor-1α, SDF-1α) in combination with BMP-2 using proteolytically degradable hydrogels. A critical-sized calvarial defect was used to determine the effect of biomolecule delivery on bone formation in vivo.

Modulating hydrogel crosslink density and degradation to control bone morphogenetic protein delivery and in vivo bone formation.

Bone morphogenetic proteins (BMPs) show promise in therapies for improving bone formation after injury; however, the high supraphysiological concentrations required for desired osteoinductive effects, off-target concerns, costs, and patient variability have limited the use of BMP-based therapeutics. To better understand the role of biomaterial design in BMP delivery, a matrix metalloprotease (MMP)-sensitive hyaluronic acid (HA)-based hydrogel was used for BMP-2 delivery to evaluate the influence of hydrogel degradation rate on bone repair in vivo. Specifically, maleimide-modified HA (MaHA) macromers were crosslinked with difunctional MMP-sensitive peptides to permit protease-mediated hydrogel degradation and growth factor release.

Interfacial optimization of fiber-reinforced hydrogel composites for soft fibrous tissue applications.

Meniscal tears are the most common orthopedic injuries to the human body, yet the current treatment of choice is a partial meniscectomy, which is known to lead to joint degeneration and osteoarthritis. As a result, there is a significant clinical need to develop materials capable of restoring function to the meniscus following an injury. Fiber-reinforced hydrogel composites are particularly suited for replicating the mechanical function of native fibrous tissues due to their ability to mimic the native anisotropic property distribution present.

Transdermal gelation of methacrylated macromers with near-infrared light and gold nanorods.

Injectable hydrogels provide locally controlled tissue bulking and a means to deliver drugs and cells to the body. The formation of hydrogels in vivo may involve the delivery of two solutions that spontaneously crosslink when mixed, with pH or temperature changes, or with light (e.g.

Aging behavior of PVA hydrogels for soft tissue applications after in vitro swelling using osmotic pressure solutions.

The osmotic pressure of the medium used for in vitro swelling evaluation has been shown to have a significant effect on the swelling behavior of a material. In this study, the effect of osmotic pressure during swelling on poly(vinyl alcohol) hydrogel material properties was evaluated in vitro. Osmotic pressure solutions are necessary in order to mimic the swelling pressure observed in vivo for soft tissues present in load-bearing joints.

A novel method for the direct fabrication of growth factor-loaded microspheres within porous nondegradable hydrogels: controlled release for cartilage tissue engineering.

Because of similar mechanical properties to native cartilage, synthetic hydrogels based on poly(vinyl alcohol) (PVA) have been proposed for replacement of damaged articular cartilage, but they suffer from a complete lack of integration with surrounding tissue. In this study, insulin-like growth factor-1 (IGF-1), an important growth factor in cartilage regeneration, was encapsulated in degradable poly(lactic-co-glycolic acid) (PLGA) microparticles embedded in the PVA hydrogels in a single step based on a double emulsion. The release of IGF-1 from these hydrogels was sustained over 6 weeks in vitro.

Design of semi-degradable hydrogels based on poly(vinyl alcohol) and poly(lactic-co-glycolic acid) for cartilage tissue engineering.

Articular cartilage damage is a persistent challenge in biomaterials and tissue engineering. Poly(vinyl alcohol) (PVA) hydrogels have shown promise as implants, but their lack of integration with surrounding cartilage prevents their utility. We sought to combine the advantages of PVA hydrogels with poly(lactic-co-glycolic acid) (PLGA) scaffolds, which have been successful in facilitating the integration of neocartilage with surrounding tissue.

Analysis of the in vitro swelling behavior of poly(vinyl alcohol) hydrogels in osmotic pressure solution for soft tissue replacement.

An osmotic solution was used to evaluate poly(vinyl alcohol) (PVA) hydrogels as potential non-degradable soft tissue replacements in vitro. Osmotic solutions are necessary in order to mimic the swelling pressure observed in vivo for soft tissues present in load-bearing joints. In vitro studies indicated that PVA hydrogels experience minimal changes in swelling with a polymer concentration of 20 wt.

Mechanical evaluation of poly(vinyl alcohol)-based fibrous composites as biomaterials for meniscal tissue replacement.

In this study, poly(vinyl alcohol) (PVA) hydrogels were reinforced with ultrahigh molecular weight polyethylene (UHMWPE) and PP fibers and evaluated as potential nondegradable meniscal replacements. An investigation of hydrogel and composite mechanical properties indicates that fiber-reinforced PVA hydrogels could replicate the unique anisotropic modulus distribution present in the native meniscus; the most commonly damaged orthopedic tissue. More specifically, fibrous reinforcement successfully increased the tensile modulus of the biomaterial from 0.