Interface Performance Enhancement in 3D-Printed Biphasic Scaffolds with Interlocking Hourglass Geometry.

The cartilaginous surfaces in ginglymus (hinge) joints such as the knee, elbow, and the ginglymoarthrodial temporomandibular joint (TMJ) primarily function under unidirectional shear and orthogonal compression. Regenerative medicine approaches to treat injured or arthritic joints include biphasic scaffolds, which must withstand the joint's biomechanical demands. In the current study, we leveraged computational modeling to design a 3D-printed biphasic scaffold with enhanced biomechanical performance for ginglymus joints.

Comparison of the chondrogenic potential of eBMSCs and eUCMSCs in response to selected peptides and compounds.

Background: Cartilage injuries pose significant challenges in horses and often lead to post-traumatic osteoarthritis (PTOA). Despite the advances in surgical and regenerative techniques, the result in most cases is the formation of a fibrocartilage repair tissue. Cell-based cartilage therapies are mainly focused on equine bone marrow-derived mesenchymal stem cells (eBMSCs) as they are easily accessible, and multipotent.

Improved Mesenchymal Stem Cell Viability in High-Stiffness, Translational Cartilage Matrix Hydrogels.

Scaffolds made from cartilage extracellular matrix are promising materials for articular cartilage repair, attributed to their intrinsic bioactivity that may promote chondrogenesis. While several cartilage matrix-based scaffolds have supported chondrogenesis and/or , it remains a challenge to balance the biological response (e.g.

Osteochondral Regeneration With Anatomical Scaffold 3D-Printing-Design Considerations for Interface Integration.

There is a clinical need for osteochondral scaffolds with complex geometries for restoring articulating joint surfaces. To address that need, 3D-printing has enabled scaffolds to be created with anatomically shaped geometries and interconnected internal architectures, going beyond simple plug-shaped scaffolds that are limited to small, cylindrical, focal defects. A key challenge for restoring articulating joint surfaces with 3D-printed constructs is the mechanical loading environment, particularly to withstand delamination or mechanical failure.

Regenerative Engineering of a Biphasic Patient-Fitted Temporomandibular Joint Condylar Prosthesis.

Regenerative medicine approaches to restore the mandibular condyle of the temporomandibular joint (TMJ) may fill an unmet patient need. In this study, a method to implant an acellular regenerative TMJ prosthesis was developed for orthotopic implantation in a pilot goat study. The scaffold incorporated a porous, polycaprolactone-hydroxyapatite (PCL-HAp, 20wt% HAp) 3D printed condyle with a cartilage-matrix-containing hydrogel.

Modulation of Smooth Muscle Cell Phenotype for Translation of Tissue-Engineered Vascular Grafts.

Translation of small-diameter tissue-engineered vascular grafts (TEVGs) for the treatment of coronary artery disease (CAD) remains an unfulfilled promise. This is largely due to the limited integration of TEVGs into the native vascular wall-a process hampered by the insufficient smooth muscle cell (SMC) infiltration and extracellular matrix deposition, and low vasoactivity. These processes can be promoted through the judicious modulation of the SMC toward a synthetic phenotype to promote remodeling and vascular integration; however, the expression of synthetic markers is often accompanied by a decrease in the expression of contractile proteins.

The Ogden model for hydrogels in tissue engineering: Modulus determination with compression to failure.

Hydrogel mechanical properties for tissue engineering are often reported in terms of a compressive elastic modulus derived from a linear regression of a typically non-linear stress-strain plot. There is a need for an alternative model to fit the full strain range of tissue engineering hydrogels. Fortunately, the Ogden model provides a shear modulus, μ, and a nonlinear parameter, α, for routine analysis of compression to failure.

High-stiffness, fast-crosslinking, cartilage matrix bioinks.

Scaffolds derived from cartilage extracellular matrix may contain intrinsic chondroinductivity and have promise for cartilage regeneration. Cartilage is typically ground into devitalized particles (DVC) and several groups have pioneered innovative methods to rebuild the DVC into a new scaffold. However, challenges remain regarding the fluid and solid biomechanics of cartilage-based scaffolds in achieving 1) high mechanical performance akin to native cartilage and 2) easy surgical delivery/retention.

Comparison of a Thiolated Demineralized Bone Matrix Hydrogel to a Clinical Product Control for Regeneration of Large Sheep Cranial Defects.

Regeneration of calvarial bone remains a major challenge in the clinic as available options do not sufficiently regenerate bone in larger defect sizes. Calvarial bone regeneration cases involving secondary medical conditions, such as brain herniation during traumatic brain injury (TBI) treatment, further exacerbate treatment options. Hydrogels are well-positioned for severe TBI treatment, given their innate flexibility and potential for bone regeneration to treat TBI in a single-stage surgery.

Independent control of molecular weight, concentration, and stiffness of hyaluronic acid hydrogels.

Hyaluronic acid (HA) hydrogels have been used for a multitude of applications, perhaps most notably for tissue engineering and regenerative medicine, owing to the versatility of the polymer and its tunable nature. Various groups have investigated the impact of hydrogel parameters (e.g.

The Rheology and Printability of Cartilage Matrix-Only Biomaterials.

The potential chondroinductivity from cartilage matrix makes it promising for cartilage repair; however, cartilage matrix-based hydrogels developed thus far have failed to match the mechanical performance of native cartilage or be bioprinted without adding polymers for reinforcement. There is a need for cartilage matrix-based hydrogels with robust mechanical performance and paste-like precursor rheology for bioprinting/enhanced surgical placement. In the current study, our goals were to increase hydrogel stiffness and develop the paste-like precursor/printability of our methacryl-modified solubilized and devitalized cartilage (MeSDVC) hydrogels.

Automated Decellularization of Musculoskeletal Tissues with High Extracellular Matrix Retention.

Manual tissue decellularization is an onerous process that requires the application of many sequential treatments by an operator and can be prone to user error and result variability. While automated decellularization devices have been previously reported, with advances being made in recent years toward open-source platforms, previous automated decellularization devices have been reliant on hardware or software components that are closed-source and proprietary. The aim of the current work was to develop and validate a full open-source automated decellularization system to be available for others to adopt.

Conductive and injectable hyaluronic acid/gelatin/gold nanorod hydrogels for enhanced surgical translation and bioprinting.

There is growing evidence indicating the need to combine the rehabilitation and regenerative medicine fields to maximize functional recovery after spinal cord injury (SCI), but there are limited methods to synergistically combine the fields. Conductive biomaterials may enable synergistic combination of biomaterials with electric stimulation (ES), which may enable direct ES of neurons to enhance axon regeneration and reorganization for better functional recovery; however, there are three major challenges in developing conductive biomaterials: (1) low conductivity of conductive composites, (2) many conductive components are cytotoxic, and (3) many conductive biomaterials are pre-formed scaffolds and are not injectable. Pre-formed, noninjectable scaffolds may hinder clinical translation in a surgical context for the most common contusion-type of SCI.

Chondroinductive Peptides for Cartilage Regeneration.

Inducing and maintaining a hyaline cartilage phenotype are the greatest challenge for cartilage regeneration. Synthetic chondroinductive biomaterials might be the answer to the unmet clinical need for a safe, stable, and cost-effective material capable of inducing true hyaline cartilage formation. The past decade witnessed an emergence of peptides to achieve chondrogenesis, as peptides have the advantages of versatility, high target specificity, minimized toxicity and immunogenicity, and ease of synthesis.

Regenerative rehabilitation with conductive biomaterials for spinal cord injury.

The individual approaches of regenerative medicine efforts alone and rehabilitation efforts alone have not yet fully restored function after severe spinal cord injury (SCI). Regenerative rehabilitation may be leveraged to promote regeneration of the spinal cord tissue, and promote reorganization of the regenerated neural pathways and intact spinal circuits for better functional recovery for SCI. Conductive biomaterials may be a linchpin that empowers the synergy between regenerative medicine and rehabilitation approaches, as electrical stimulation applied to the spinal cord could facilitate neural reorganization.

Standardization of Microcomputed Tomography for Tracheal Tissue Engineering Analysis.

Tracheal tissue engineering has become an active area of interest among clinical and scientific communities; however, methods to evaluate success of tissue-engineered solutions remain primarily qualitative. These evaluation methods have generally relied on the use of photographs to qualitatively demonstrate tracheal patency, endoscopy to image healing over time, and histology to determine the quality of the regenerated extracellular matrix. Although those generally qualitative methods are valuable, they alone may be insufficient.

Assessing nanoparticle colloidal stability with single-particle inductively coupled plasma mass spectrometry (SP-ICP-MS).

Biological interactions, toxicity, and environmental fate of engineered nanoparticles are affected by colloidal stability and aggregation. To assess nanoparticle aggregation, analytical methods are needed that allow quantification of individual nanoparticle aggregates. However, most techniques used for nanoparticle aggregation analysis are limited to ensemble measurements or require harsh sample preparation that may introduce artifacts.

Thiolated bone and tendon tissue particles covalently bound in hydrogels for in vivo calvarial bone regeneration.

Bone regeneration of large cranial defects, potentially including traumatic brain injury (TBI) treatment, presents a major problem with non-crosslinking, clinically available products due to material migration outside the defect. Commercial products such as bone cements are permanent and thus not conducive to bone regeneration, and typical commercial bioactive materials for bone regeneration do not crosslink. Our previous work demonstrated that non-crosslinking materials may be prone to material migration following surgical placement, and the current study attempted to address these problems by introducing a new hydrogel system where tissue particles are themselves the crosslinker.

Biodegradable electrospun patch containing cell adhesion or antimicrobial compounds for trachea repair in vivo.

Difficulty breathing due to tracheal stenosis (i.e. narrowed airway) diminishes the quality of life and can potentially be life-threatening.

Flow Behavior Prior to Crosslinking: The Need for Precursor Rheology for Placement of Hydrogels in Medical Applications and for 3D Bioprinting.

Hydrogels - water swollen cross-linked networks - have demonstrated considerable promise in tissue engineering and regenerative medicine applications. However, ambiguity over which rheological properties are needed to characterize these gels before crosslinking still exists. Most hydrogel research focuses on the performance of the hydrogel construct after implantation, but for clinical practice, and for related applications such as bioinks for 3D bioprinting, the behavior of the pre-gelled state is also critical.

Temporomandibular Joint Bioengineering Conference: Working Together Toward Improving Clinical Outcomes.

The sixth temporomandibular joint (TMJ) Bioengineering Conference (TMJBC) was held on June 14-15 2018, in Redondo Beach, California, 12 years after the first TMJBC. Speakers gave 30 presentations and came from the United States, Europe, Asia, and Australia. The goal of the conference has remained to foster a continuing forum for bioengineers, scientists, and surgeons and veterinarians to advance technology related to TMJ disorders.

Effects of a Bioactive SPPEPS Peptide on Chondrogenic Differentiation of Mesenchymal Stem Cells.

A synthetic 'chondroinductive' biomaterial that could induce chondrogenesis without the need for growth factors, extracellular matrix, or pre-seeded cells could revolutionize orthopedic regenerative medicine. The objective of the current study was thus to introduce a synthetic SPPEPS peptide and evaluate its ability to induce chondrogenic differentiation. In the current study, dissolving a synthetic chondroinductive peptide candidate (100 ng/mL SPPEPS) in the culture medium of rat bone marrow-derived mesenchymal stem cells (rBMSCs) elevated collagen type II gene expression compared to the negative control (no growth factor or peptide in the cell culture medium) after 3 days.

Development and quantitative characterization of the precursor rheology of hyaluronic acid hydrogels for bioprinting.

Bioprinting technologies have tremendous potential for advancing regenerative medicine due to the precise spatial control over depositing a printable biomaterial, or bioink. Despite the growing interest in bioprinting, the field is challenged with developing biomaterials for extrusion-based bioprinting. The paradigm of contemporary bioink studies relies on trial-and-error methods for discovering printable biomaterials, which has little practical use for others who endeavor to develop bioinks.

Fabrication of a Double-Cross-Linked Interpenetrating Polymeric Network (IPN) Hydrogel Surface Modified with Polydopamine to Modulate the Osteogenic Differentiation of Adipose-Derived Stem Cells.

Hydrogel surface properties can be modified to form bioactive interfaces to modulate the osteogenic differentiation of stem cells. In this work, a hydrogel made of gelatin methacrylamide (GelMA) and alginate was designed and tested as a scaffold to control stem-cell osteogenic differentiation. The hydrogel's surface was treated with polydopamine (pDA) to create an adhesive layer for the adsorption of the osteoinductive drug dexamethasone (Dex).