Assessment of Linear and Cyclic Peptides' Immobilization onto Cross-Linked, Poly(vinyl alcohol)/Cellulose Nanocrystal Nanofibers Electrospun over Quartz Crystal Microbalances with Dissipation Sensors.

Immobilization of peptides onto nanofiber dressings holds significant potential for chronic wound treatment. However, it is necessary to understand the adsorptive capacity of the produced substrates and the binding affinity of the peptides to determine the interface success. This study aims at exploring for the first time the influence of electrospun poly(vinyl alcohol)-based nanofibers on the adsorption of a cyclic peptide, Tiger 17, and of a linear peptide, Pexiganan, using quartz crystal microbalance with dissipation monitoring (QCM-D).

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.

Axonal Tract Reconstruction Using a Tissue-Engineered Nigrostriatal Pathway in a Rat Model of Parkinson's Disease.

Parkinson's disease (PD) affects 1-2% of people over 65, causing significant morbidity across a progressive disease course. The classic PD motor deficits are caused by the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc), resulting in the loss of their long-distance axonal projections that modulate striatal output. While contemporary treatments temporarily alleviate symptoms of this disconnection, there is no approach able to replace the nigrostriatal pathway.

A sciatic nerve gap-injury model in the rabbit.

There has been an increased number of studies of nerve transection injuries with the sciatic nerve gap-injury model in the rabbit in the past 2 years. We wanted to define in greater detail what is needed to test artificial nerve guides in a sciatic nerve gap-injury model in the rabbit. We hope that this will help investigators to fully exploit the robust translational potential of the rabbit sciatic nerve gap-injury model in its capacity to test devices whose diameter and length are in the range of those commonly applied in hand and wrist surgery (diameter ranging between 2 and 4 mm; length up to 30 mm).

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.

Recent Advances in Polymer-Based Vaginal Drug Delivery Systems.

The vagina has been considered a potential drug administration route for centuries. Most of the currently marketed and investigated vaginal formulations are composed with the use of natural or synthetic polymers having different functions in the product. The vaginal route is usually investigated as an administration site for topically acting active ingredients; however, the anatomical and physiological features of the vagina make it suitable also for drug systemic absorption.

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.

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.

Tissue engineered axon-based "living scaffolds" promote survival of spinal cord motor neurons following peripheral nerve repair.

Peripheral nerve injury (PNI) impacts millions annually, often leaving debilitated patients with minimal repair options to improve functional recovery. Our group has previously developed tissue engineered nerve grafts (TENGs) featuring long, aligned axonal tracts from dorsal root ganglia (DRG) neurons that are fabricated in custom bioreactors using the process of axon "stretch-growth." We have shown that TENGs effectively serve as "living scaffolds" to promote regeneration across segmental nerve defects by exploiting the newfound mechanism of axon-facilitated axon regeneration, or "AFAR," by simultaneously providing haptic and neurotrophic support.

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).

Retracted: Exploring the microbiome and mindfulness connection.

Mental health and its impact on overall well-being is a topic that is at the forefront of consideration in most industrialized countries. Ironically in the expansive world of the microbiome, gut microbes are most affected by modern, fast paced, westernized lifestyles, indicating a significant correlation based on geography, and physical and mental habits. The gut–brain axis is an established axis demonstrating the effect of the gut microbiota on the biochemical processes in the brain.

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).

Hydrogel-based local drug delivery strategies for spinal cord repair.

Spinal cord injury results in significant loss of motor, sensory, and autonomic functions. Although a wide range of therapeutic agents have been shown to attenuate secondary injury or promote regeneration/repair in animal models of spinal cord injury, clinical translation of these strategies has been limited, in part due to difficulty in safely and effectively achieving therapeutic concentrations in the injured spinal cord tissue. Hydrogel-based drug delivery systems offer unique opportunities to locally deliver drugs to the injured spinal cord with sufficient dose and duration, while avoiding deleterious side effects associated with systemic drug administration.

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.

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.

A Porcine Model of Peripheral Nerve Injury Enabling Ultra-Long Regenerative Distances: Surgical Approach, Recovery Kinetics, and Clinical Relevance.

Background: Millions of Americans experience residual deficits from traumatic peripheral nerve injury (PNI). Despite advancements in surgical technique, repair typically results in poor functional outcomes due to prolonged periods of denervation resulting from long regenerative distances coupled with slow rates of axonal regeneration. Novel surgical solutions require valid preclinical models that adequately replicate the key challenges of clinical PNI.

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.

Architectured helically coiled scaffolds from elastomeric poly(butylene succinate) (PBS) copolyester via wet electrospinning.

Electrospinning is one of the most investigated methods used to produce polymeric fiber scaffolds that mimic the morphology of native extracellular matrix. These structures have been extensively studied in the context of scaffolds for tissue regeneration. However, the compactness of materials obtained by traditional electrospinning, collected as two-dimensional non-woven scaffolds, can limit cell infiltration and tissue ingrowth.

A Dual Wavelength Polymerization and Bioconjugation Strategy for High Throughput Synthesis of Multivalent Ligands.

Structure-function relationships for multivalent polymer scaffolds are highly complex due to the wide diversity of architectures offered by such macromolecules. Evaluation of this landscape has traditionally been accomplished case-by-case due to the experimental difficulty associated with making these complex conjugates. Here, we introduce a simple dual-wavelength, two-step polymerize and click approach for making combinatorial conjugate libraries.

A step toward engineering thick tissues: Distributing microfibers within 3D printed frames.

Microfiber mats for tissue engineering scaffolds support cell growth, but are limited by poor cell infiltration and nutrient transport. Three-dimensional printing, specifically fused deposition modeling (FDM), can rapidly produce customized constructs, but macroscopic porosity resulting from low resolution reduces cell seeding efficiency and prevents the formation of continuous cell networks. Here we describe the fabrication of hierarchical scaffolds that integrate a fibrous microenvironment with the open macropore structure of FDM.