TyroFill-Titanium Implant Constructs for the Coordinated Repair of Rabbit Mandible and Tooth Defects.

Currently used methods to repair craniomaxillofacial (CMF) bone and tooth defects require a multi-staged surgical approach for bone repair followed by dental implant placement. Our previously published results demonstrated significant bioengineered bone formation using human dental pulp stem cell (hDPSC)-seeded tyrosine-derived polycarbonate scaffolds (E1001(1K)-bTCP). Here, we improved upon this approach using a modified TyroFill (E1001(1K)/dicalcium phosphate dihydrate (DCPD)) scaffold-supported titanium dental implant model for simultaneous bone-dental implant repair.

Asymmetrical interactions between nanoparticles and proteins arising from deformation upon adsorption to surfaces.

Drug release from polymeric nanoparticles (NPs) is governed by their adsorption onto cell membranes and transmigration across cell walls. These steps are influenced by their interactions with proteins near the cells. These interactions were investigated by studying the sequential adsorption of plasma proteins, albumin (Alb) and fibrinogen (Fg), and micellar NPs using quartz crystal microbalance with dissipation (QCMD), X-ray photoelectron spectroscopy (XPS), and small-angle X-ray scattering (SAXS).

Rational design of poly(peptide-ester) block copolymers for enzyme-specific surface resorption.

Tissue resorption and remodeling are pivotal steps in successful healing and regeneration, and it is important to design biomaterials that are responsive to regenerative processes in native tissue. The cell types responsible for remodeling, such as macrophages in the soft tissue wound environment and osteoclasts in the bone environment, utilize a class of enzymes called proteases to degrade the organic matrix. Many hydrophobic thermoplastics used in tissue regeneration are designed to degrade and resorb passively through hydrolytic mechanisms, leaving the potential of proteolytic-guided degradation underutilized.

Tyrosine-derived polymeric surfactant nanospheres insert cholesterol in cell membranes.

Hypothesis: The design of biodegradable tyrosine-derived polymeric surfactants (TyPS) through the use of calculated thermodynamic parameters could lead to phospholipid membrane surface modifiers capable of controlling cellular properties such as viability. Delivery of cholesterol by TyPS nanospheres into membrane phospholipid domains could provide further controlled modulation of membrane physical and biological properties.

Experiment: Calculated Hansen solubility parameters (∂) and hydrophile:lipophile balances (HLB) were applied to design and synthesize a small family of diblock and triblock TyPS with different hydrophobic blocks and PEG hydrophilic blocks.

Iodination of PEGylated Polymers Counteracts the Inhibition of Fibrinogen Adsorption by PEG.

Poly(ethylene glycol), PEG, known to inhibit protein adsorption, is widely used on the surfaces of biomedical devices when biofilm formation is undesirable. Poly(desaminotyrosyl-tyrosine ethyl ester carbonate), PDTEC, PC for short, has been a promising coating polymer for insertion devices, and it has been anticipated that PEG plays a similar role if it is copolymerized with PC. Earlier studies show that no fibrinogen (Fg) is adsorbed onto PC polymers with PEG beyond the threshold weight percentage.

Self-Assembled Hydrogel Microparticle-Based Tooth-Germ Organoids.

Here, we describe the characterization of tooth-germ organoids, three-dimensional (3D) constructs cultured in vitro with the potential to develop into living teeth. To date, the methods used to successfully create tooth organoids capable of forming functional teeth have been quite limited. Recently, hydrogel microparticles (HMP) have demonstrated utility in tissue repair and regeneration based on their useful characteristics, including their scaffolding ability, effective cell and drug delivery, their ability to mimic the natural tissue extracellular matrix, and their injectability.

Nanosphere size control by varying the ratio of poly(ester amide) block copolymer blends.

Hypothesis: Blending amphiphilic triblock (A-B-A) and diblock (A-B) copolymers comprised of the same hydrophobic tyrosine-derived oligomeric B-block and hydrophilic poly(ethylene glycol) methyl ether (mPEG) A-block can provide highly tunable self-assembled nanosphere particle sizes suitable for biomedical applications.

Experiment: Triblock and diblock copolymers were synthesized via carbodiimide chemistry and were characterized by nuclear magnetic resonance (NMR) and gel permeation chromatography (GPC). The amount of free PEG present in the purified copolymers was determined using a standard addition calibration curve and GPC peak deconvolution methods.

Local FK506 implants in non-human primates to prevent early acute rejection in vascularized composite allografts.

Background: Previous vascularized composite allograft (VCA) studies from our laboratory have shown that topical FK506 delivery in non-human primates (NHPs) was limited by inadequate dermal penetration and rejection persisted. Herein, we report the first utilization of FK506 via subcutaneously implanted discs to mitigate VCA rejection in NHPs.

Methods: Full major histocompatibility complex (MHC)-mismatched NHP pairs underwent partial-face VCA and FK506 disc implantation along the suture line.

Thermal Processing of a Degradable Carboxylic Acid-Functionalized Polycarbonate into Scaffolds for Tissue Engineering.

Degradable polymers are often desirable for the fabrication of medical implants, but thermal processing of these polymers is a challenge. We describe here how these problems can be addressed by discussing the extrusion of fibers and injection molding of bone pins from a hydrolytically degradable tyrosine-derived polycarbonate. Our initial attempts produced fibers and pins with bubbles, voids, and discoloration, and resulted in the formation of large polymer plugs that seized screws and blocked extruder dies.

Tyrosol-Derived Biodegradable Inks with Tunable Properties for 3D Printing.

Three-dimensional (3D) printing has emerged as a valuable tool in medicine over the past few decades. With a growing number of applications using this advanced processing technique, new polymer libraries with varied properties are required. Herein, we investigate tyrosol-based poly(ester-arylate)s as biodegradable inks in fused deposition modeling (FDM).

Tyrosol Derived Poly(ester-arylate)s for Sustained Drug Delivery from Microparticles.

New biodegradable polymers are needed for use in drug delivery systems to overcome the high burst release, lack of sustained drug release, and acidic degradation products frequently observed in current formulations. Commercially available poly(lactide--glycolide) (PLGA) is often used for particle drug release formulations; however, it is often limited by its large burst release and acidic degradation products. Therefore, a biocompatible and biodegradable tyrosol-derived poly(ester-arylate) library has been used to prepare a microparticle drug delivery system which shows sustained delivery of hydrophobic drugs.

Synergistic Combination of Bioactive Hydroxyapatite Nanoparticles and the Chemotherapeutic Doxorubicin to Overcome Tumor Multidrug Resistance.

Multidrug resistance (MDR) is one of the biggest obstacles in cancer chemotherapy. Here, a remarkable reversal of MDR in breast cancer through the synergistic effects of bioactive hydroxyapatite nanoparticles (HAPNs) and doxorubicin (DOX) is shown. DOX loaded HAPNs (DHAPNs) exhibit a 150-fold reduction in IC compared with free DOX for human MDR breast cancer MCF-7/ADR cells, and lead to almost complete inhibition of tumor growth in vivo without obvious side effects of free DOX.

Exosomes Secreted from Amniotic Membrane Contribute to Its Anti-Fibrotic Activity.

Amniotic membranes (AM) have anti-fibrotic activity. Exosomes (nano-sized vesicles) function as conduits for intercellular transfer and contain all the necessary components to induce the resolution of fibrosis. In this study, we tested the hypothesis that the anti-fibrotic activity of AM is mediated by exosomes.

Tag-Free Site-Specific BMP-2 Immobilization with Long-Acting Bioactivities via a Simple Sugar-Lectin Interaction.

The construction of a biomaterial matrix with biological properties is of great importance to developing functional materials for clinical use. However, the site-specific immobilization of growth factors to endow materials with bioactivities has been a challenge to date. Considering the wide existence of glycosylation in mammalian proteins or recombinant proteins, we establish a bioaffinity-based protein immobilization strategy (bioanchoring method) utilizing the native sugar-lectin interaction between concanavalin A (Con A) and the oligosaccharide chain on glycosylated bone morphogenetic protein-2 (GBMP-2).

Corrigendum: Use of Human Dental Pulp and Endothelial Cell Seeded Tyrosine-Derived Polycarbonate Scaffolds for Robust Alveolar Jaw Bone Regeneration.

[This corrects the article DOI: 10.3389/fbioe.2020.

Engineering Silk Fibroin-Based Nerve Conduit with Neurotrophic Factors for Proximal Protection after Peripheral Nerve Injury.

Artificial nerve conduits capable of adequately releasing neurotrophic factors are extensively studied to bridge nerve defects. However, the lack of neurotrophic factors in the proximal area and their visible effects in axonal retrograde transport following nerve injury is one of the factors causing an incomplete nerve regeneration. Herein, an advanced conduit made of silk fibroin is produced, which can incorporate growth factors and promote an effective regeneration after injury.

Optical Biosensors for Virus Detection: Prospects for SARS-CoV-2/COVID-19.

The recent pandemic of the novel coronavirus disease 2019 (COVID-19) has caused huge worldwide disruption due to the lack of available testing locations and equipment. The use of optical techniques for viral detection has flourished in the past 15 years, providing more reliable, inexpensive, and accurate detection methods. In the current minireview, optical phenomena including fluorescence, surface plasmons, surface-enhanced Raman scattering (SERS), and colorimetry are discussed in the context of detecting virus pathogens.

Tyrosine-derived polycarbonate nerve guidance tubes elicit proregenerative extracellular matrix deposition when used to bridge segmental nerve defects in swine.

Promising biomaterials should be tested in appropriate large animal models that recapitulate human inflammatory and regenerative responses. Previous studies have shown tyrosine-derived polycarbonates (TyrPC) are versatile biomaterials with a wide range of applications across multiple disciplines. The library of TyrPC has been well studied and consists of thousands of polymer compositions with tunable mechanical characteristics and degradation and resorption rates that are useful for nerve guidance tubes (NGTs).

Calcium phosphate enriched synthetic tyrosine-derived polycarbonate - dicalcium phosphate dihydrate polymer scaffolds for enhanced bone regeneration.

Optimal repair of large craniomaxillofacial (CMF) defects caused by trauma or disease requires the development of new, synthetic osteoconductive materials in combination with cell-based therapies, to overcome the limitations of traditionally used bone graft substitutes. In this study, tyrosine-derived polycarbonate, E1001(1k) scaffolds were fabricated to incorporate the osteoinductive coating, Dicalcium phosphate dihydrate (DCPD). The biocompatibility of E1001(1k)-DCPD, E1001(1k)-βTCP and E1001(1k) scaffolds was compared using culture with human dental pulp stem cells (hDPSCs).

Use of Human Dental Pulp and Endothelial Cell Seeded Tyrosine-Derived Polycarbonate Scaffolds for Robust Alveolar Jaw Bone Regeneration.

The ability to effectively repair craniomaxillofacial (CMF) bone defects in a fully functional and aesthetically pleasing manner is essential to maintain physical and psychological health. Current challenges for CMF repair therapies include the facts that craniofacial bones exhibit highly distinct properties as compared to axial and appendicular bones, including their unique sizes, shapes and contours, and mechanical properties that enable the ability to support teeth and withstand the strong forces of mastication. The study described here examined the ability for tyrosine-derived polycarbonate, E1001(1K)/β-TCP scaffolds seeded with human dental pulp stem cells (hDPSCs) and human umbilical vein endothelial cells (HUVECs) to repair critical sized alveolar bone defects in an rabbit mandible defect model.

Opportunities for biomaterials to address the challenges of COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic has revealed major shortcomings in our ability to mitigate transmission of infectious viral disease and provide treatment to patients, resulting in a public health crisis. Within months of the first reported case in China, the virus has spread worldwide at an unprecedented rate. COVID-19 illustrates that the biomaterials community was engaged in significant research efforts against bacteria and fungi with relatively little effort devoted to viruses.

A multilayered scaffold for regeneration of smooth muscle and connective tissue layers.

Tissue regeneration often requires recruitment of different cell types and rebuilding of two or more tissue layers to restore function. Here, we describe the creation of a novel multilayered scaffold with distinct fiber organizations-aligned to unaligned and dense to porous-to template common architectures found in adjacent tissue layers. Electrospun scaffolds were fabricated using a biodegradable, tyrosine-derived terpolymer, yielding densely-packed, aligned fibers that transition into randomly-oriented fibers of increasing diameter and porosity.

Porphyrin-Loaded TyroSpheres for the Intracellular Delivery of Drugs and Photoinduced Oxidant Species.

In order to understand the intracellular delivery of drugs and to improve the cell killing efficiency of photosensitizers (PSs) used in photodynamic therapy (PDT), we prepared TyroSphere nanoparticles, which are triblock polymer [poly(ethylene glycol)--oligo(desaminotyrosyltyrosine octyl ester suberate)--poly(ethylene glycol)] aggregates, loaded with amphiphilic porphyrins with either positive (CisDiMPyP) or negative (TPPS) charges. Their physicochemical and photochemical properties were investigated, as well as the efficiency and mechanism of PDT death in a cervical cancer cell line (HeLa). The photophysical properties of both PSs were improved when loaded in the nanocarrier, with a decrease in aggregation as well as an increase in the yield of singlet oxygen generation.

Tissue Engineered Axon Tracts Serve as Living Scaffolds to Accelerate Axonal Regeneration and Functional Recovery Following Peripheral Nerve Injury in Rats.

Strategies to accelerate the rate of axon regeneration would improve functional recovery following peripheral nerve injury, in particular for cases involving segmental nerve defects. We are advancing tissue engineered nerve grafts (TENGs) comprised of long, aligned, centimeter-scale axon tracts developed by the controlled process of axon "stretch-growth" in custom mechanobioreactors. The current study used a rat sciatic nerve model to investigate the mechanisms of axon regeneration across nerve gaps bridged by TENGs as well as the extent of functional recovery compared to nerve guidance tubes (NGT) or autografts.

Local Immunosuppression for Vascularized Composite Allografts: Application of Topical FK506-TyroSpheres in a Nonhuman Primate Model.

Transplantation of vascularized composite allografts (VCAs) provides a means of restoring complex anatomical and functional units following burns and other disfigurement otherwise not amenable to conventional autologous reconstructive surgery. While short- to intermediate-term VCA survival is largely dependent on patient compliance with medication, the myriad of side effects resulting from lifelong systemic immunosuppression continue to pose a significant challenge. Topical immunosuppression is therefore a logical and attractive alternative for VCA.